Sample records for ocular choroidal neovascularization

  1. Apatinib, an Inhibitor of Vascular Endothelial Growth Factor Receptor 2, Suppresses Pathologic Ocular Neovascularization in Mice.

    PubMed

    Kim, Koung Li; Suh, Wonhee

    2017-07-01

    Vascular endothelial growth factor (VEGF) signaling via VEGF receptor 2 (VEGFR2) plays a crucial role in pathologic ocular neovascularization. In this study, we investigated the antiangiogenic effect of apatinib, a pharmacologic inhibitor of VEGFR2 tyrosine kinase, against oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) in mice. Western blotting and in vitro angiogenesis assays were performed using human retinal microvascular endothelial cells (HRMECs). OIR was induced in neonatal mice by exposure to 75% oxygen from postnatal day (P) 7 to P12 and to room air from P12 to P17. Experimental CNV was induced in mice using laser photocoagulation. Apatinib was intravitreally and orally administered to mice. Neovascularization and phosphorylation of VEGFR2 were evaluated by immunofluorescence staining. Apatinib inhibited VEGF-mediated activation of VEGFR2 signaling and substantially reduced VEGF-induced proliferation, migration, and cord formation in HRMECs. A single intravitreal injection of apatinib significantly attenuated retinal or choroidal neovascularization in mice with OIR or laser injury-induced CNV, respectively. Retinal or choroidal tissues of the eyes treated with apatinib exhibited substantially lower phosphorylation of VEGFR2 than those of controls injected with vehicle. Intravitreal injection of apatinib did not cause noticeable ocular toxicity. Moreover, oral administration of apatinib significantly reduced laser-induced CNV in mice. Our study demonstrates that apatinib inhibits pathologic ocular neovascularization in mice with OIR or laser-induced CNV. Apatinib may, therefore, be a promising drug for the prevention and treatment of ischemia-induced proliferative retinopathy and neovascular age-related macular degeneration.

  2. Critical role of caveolin-1 in ocular neovascularization and multitargeted antiangiogenic effects of cavtratin via JNK

    PubMed Central

    Jiang, Yida; Lin, Xianchai; Tang, Zhongshu; Lee, Chunsik; Tian, Geng; Du, Yuxiang; Yin, Xiangke; Ren, Xiangrong; Huang, Lijuan; Ye, Zhimin; Chen, Wei; Zhang, Fan; Mi, Jia; Gao, Zhiqin; Wang, Shasha; Chen, Qishan; Xing, Liying; Wang, Bin; Cao, Yihai; Sessa, William C.; Ju, Rong; Liu, Yizhi; Li, Xuri

    2017-01-01

    Ocular neovascularization is a devastating pathology of numerous ocular diseases and is a major cause of blindness. Caveolin-1 (Cav-1) plays important roles in the vascular system. However, little is known regarding its function and mechanisms in ocular neovascularization. Here, using comprehensive model systems and a cell permeable peptide of Cav-1, cavtratin, we show that Cav-1 is a critical player in ocular neovascularization. The genetic deletion of Cav-1 exacerbated and cavtratin administration inhibited choroidal and retinal neovascularization. Importantly, combined administration of cavtratin and anti–VEGF-A inhibited neovascularization more effectively than monotherapy, suggesting the existence of other pathways inhibited by cavtratin in addition to VEGF-A. Indeed, we found that cavtratin suppressed multiple critical components of pathological angiogenesis, including inflammation, permeability, PDGF-B and endothelial nitric oxide synthase expression (eNOS). Mechanistically, we show that cavtratin inhibits CNV and the survival and migration of microglia and macrophages via JNK. Together, our data demonstrate the unique advantages of cavtratin in antiangiogenic therapy to treat neovascular diseases. PMID:28923916

  3. Indirect choroidal ruptures: aetiological factors, patterns of ocular damage, and final visual outcome.

    PubMed Central

    Wood, C M; Richardson, J

    1990-01-01

    Indirect choroidal ruptures result from blunt ocular trauma and have a pathognomonic fundal appearance. We analysed a group of 30 patients with indirect choroidal ruptures with specific reference to the circumstances of the injury, the pattern of ocular damage, the cause of any visual loss, and the final visual outcome. Using this analysis we deduce a pathogenetic explanation for the characteristic fundus signs in patients with indirect choroidal ruptures. The majority of cases were young males injured during sport or by an assault, a minority were injured at work. Diffuse nonfocal impact injuries due to punches were associated with ruptures concentric with and adjacent to the optic disc. Focal impact injuries, due to projectiles, showed more extensive ocular damage. Seventeen of 30 patients regained 6/12 vision after injury. Injuries due to projectiles and temporally situated ruptures were associated with a poorer visual outcome than others. Macular damage was the commonest cause of visual loss, principally due to pigmentary maculopathy, traumatic inner retinal damage, and choroidal neovascular membranes rather than direct focal damage by the rupture. Images PMID:2337545

  4. Detection of new-onset choroidal neovascularization.

    PubMed

    Do, Diana V

    2013-05-01

    To highlight the most common methods that are used to detect new-onset choroidal neovascularization (CNV) as a result of age-related macular degeneration (AMD). Numerous modalities are available to try to detect CNV. Amsler grid testing, preferential hyperacuity perimetry (PHP), optical coherence tomography (OCT), and fluorescein angiography are tools that may be used to detect CNV. The Age-Related Macular Degeneration: Detection of Onset of new Choroidal neovascularization Study (AMD DOC Study) evaluated the sensitivity of time domain OCT, relative to fluorescein angiography, in detecting new-onset neovascular AMD within a 2-year period. The sensitivity of each modality for detecting CNV was OCT 0.40 [(95% confidence interval (95% CI) (0.16-0.68), supervised Amsler grid 0.42 (95% CI 0.15-0.72), and PHP 0.50 (95% CI 0.23-0.77)]. Numerous modalities are available to try to detect CNV. The prospective AMD DOC Study demonstrated that fluorescein angiography still remains the best method to detect new-onset CNV.

  5. POLYPOIDAL CHOROIDAL VASCULOPATHY SECONDARY TO A STABLE CHOROIDAL NEVUS.

    PubMed

    Wong, James G; Lai, Xin Jie; Sarafian, Richard Y; Wong, Hon Seng; Smith, Jeremy B

    2016-01-01

    Choroidal nevus is the most common ocular fundus tumor in adults. Previous studies have widely discussed the features of choroidal neovascularization secondary to nevus and its treatment options. Polypoidal choroidal vasculopathy (PCV) is an exudative chorioretinopathy that is often underdiagnosed. Clinical features, natural history, and treatment response of PCV are distinct from occult choroidal neovascularization. Polypoidal choroidal vasculopathy secondary to choroidal nevus has not been previously documented. We report a patient with a history of stable choroidal nevus who developed a polypoidal lesion at the edge of the nevus lesion. A white woman who presented with a choroidal nevus and clinical features of PCV was examined using fundoscopy, optical coherence tomography, fluorescein angiography, and indocyanine green angiography. A polypoidal lesion with an associated branching vascular network adjacent to the nevus was demonstrated by optical coherence tomography, fluorescein angiography, and indocyanine green angiography. The patient was asymptomatic and was managed conservatively. Our case showed that PCV developing in association with a stable choroidal nevus. Pathogenic mechanisms of this condition may include chronic degenerative or inflammatory changes at the level of the retinal pigment epithelium resulting in vascular changes. Unlike treatment of occult choroidal neovascularization secondary to nevus, optimal management of PCV secondary to nevus may vary. Indocyanine green angiography is the gold standard for the diagnosis of PCV and is a useful investigation in atypical choroidal neovascularization.

  6. Bilateral midperipheral large drusen and retinal pigment epithelial detachments associated with multifocal areas of choroidal neovascularization: a histopathologic study.

    PubMed

    Tabandeh, Homayoun; Dubovy, Sander; Green, W Richard

    2006-01-01

    The ocular histopathologic features of a patient with bilateral multiple midperipheral areas of choroidal vascularization, large drusen, and detachments of the retinal pigment epithelium (RPE) are presented. The eyes were obtained at autopsy and fixed in 4% buffered formaldehyde. Serial sections through the macula area and inferior segments were prepared. Light as well as electron microscopy was performed. Microscopic examination disclosed numerous large drusen measuring up to 200 micro m in height and 280 micro m in diameter and areas of serous RPE detachments in the midperiphery of both eyes. Some of the large drusen had choroidal vascularization. Areas of sub-RPE neovascularization that measured up to 6.5 mm in diameter were present in the midperiphery of both eyes. The choroidal origin for neovascularization was evident in 10 areas. A 1-mm area of hemorrhagic detachment of the RPE contiguous with choroidal neovascularization (CNV) was present in the immediate postequatorial area temporally in the left eye. No drusen, basal deposit, or CNV was present in the macular area. Multifocal midperipheral RPE detachments and CNV can occur in the absence of significant age-related macular disease.

  7. Choroidal neovascular membrane.

    PubMed

    Bhatt, N S; Diamond, J G; Jalali, S; Das, T

    1998-06-01

    Choroidal neovascular membrane in the macular area is one of the leading causes of severe visual loss. Usually a manifestation in elderly population, it is often associated with age-related macular degeneration. The current mainstay of management is early diagnosis, usually by fundus examination, aided by angiography and photocoagulation in selected cases. Various other modalities of treatment including surgery are being considered as alternate options, but with limited success. The purpose of this review is to briefly outline the current concepts and the management strategy from a clinician's viewpoint.

  8. Fluorocoxib A enables targeted detection of cyclooxygenase-2 in laser-induced choroidal neovascularization

    NASA Astrophysics Data System (ADS)

    Uddin, Md. Jashim; Moore, Chauca E.; Crews, Brenda C.; Daniel, Cristina K.; Ghebreselasie, Kebreab; McIntyre, J. Oliver; Marnett, Lawrence J.; Jayagopal, Ashwath

    2016-09-01

    Ocular angiogenesis is a blinding complication of age-related macular degeneration and other retinal vascular diseases. Clinical imaging approaches to detect inflammation prior to the onset of neovascularization in these diseases may enable early detection and timely therapeutic intervention. We demonstrate the feasibility of a previously developed cyclooxygenase-2 (COX-2) targeted molecular imaging probe, fluorocoxib A, for imaging retinal inflammation in a mouse model of laser-induced choroidal neovascularization. This imaging probe exhibited focal accumulation within laser-induced neovascular lesions, with minimal detection in proximal healthy tissue. The selectivity of the probe for COX-2 was validated in vitro and by in vivo retinal imaging with nontargeted 5-carboxy-X-rhodamine dye, and by blockade of the COX-2 active site with nonfluorescent celecoxib prior to injection of fluorocoxib A. Fluorocoxib A can be utilized for imaging COX-2 expression in vivo for further validation as an imaging biomarker in retinal diseases.

  9. Atrial Natriuretic Peptide Reduces Vascular Leakage and Choroidal Neovascularization

    PubMed Central

    Lara-Castillo, Nuria; Zandi, Souska; Nakao, Shintaro; Ito, Yasuhiro; Noda, Kousuke; She, Haicheng; Ahmed, Muna; Frimmel, Sonja; Ablonczy, Zsolt; Hafezi-Moghadam, Ali

    2009-01-01

    Atrial natriuretic peptide (ANP) is a hormone with diuretic, natriuretic, and vasodilatory properties. ANP blocks vascular endothelial growth factor (VEGF) production and signaling in vitro; however, its role in vascular leakage and angiogenesis is unknown. In vitro, retinal barrier permeability (transepithelial electrical resistance (TEER)) was measured in cultured retinal endothelial (HuREC) and retinal epithelial (ARPE-19) cells with VEGF (10 ng/ml), ANP (1 pM to 1 μmol/L), and/or isatin, an ANP receptor antagonist. In vivo, blood-retinal barrier (BRB) leakage was studied using the Evans Blue dye technique in rats treated with intravitreal injections of ANP, VEGF, or vehicle. Choroidal neovascularization was generated by laser injury, and 7 days later, lesion size and leakage was quantitated. ANP significantly reversed VEGF-induced BRB TEER reduction in both HuREC and ARPE-19 cells, modeling the inner and the outer BRB, respectively. Isatin, a specific ANP receptor antagonist, reversed ANP’s effect. ANP reduced the response of ARPE-19 cells to VEGF apically but not basolaterally, suggesting polarized expression of the ANP receptors in these cells. ANP’s TEER response was concentration but not time dependent. In vivo, ANP significantly reduced VEGF-induced BRB leakage and the size of laser-induced choroidal neovascularization lesions. In sum, ANP is an effective inhibitor of VEGF-induced vascular leakage and angiogenesis in vivo. These results may lead to new treatments for ocular diseases where VEGF plays a central role, such as age-related macular degeneration or diabetic retinopathy. PMID:19910509

  10. [Intravitreal bevacizumab for choroidal neovascularization associated with Best's disease].

    PubMed

    Velazquez-Villoria, D; Macià Badia, C; Rigo Quera, J; Velez-Escola, L; Arcos-Algaba, G; Martínez-Castillo, V; García-Arumí, J

    2014-10-01

    A 27-year old woman presented with loss of vision in the right eye (20/200). Ophthalmoscopic examination showed intrarretinal hemorrhage in the macular region with neurosensory detachment in the right eye, and viteliform deposit on the left eye. Fluorescein angiography and the electrooculogram confirmed the diagnosis of choroidal neovascularization associated with Best's disease. Four weeks after a single bevacizumab intravitreal injection, visual acuity was restored (20/25) and remained stable after a 12 month follow-up. Intravitreal bevacizumab appears to be an effective treatment for choroidal neovascularization associated to Best's disease. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  11. Knockdown of the placental growth factor gene inhibits laser induced choroidal neovascularization in a murine model.

    PubMed

    Nourinia, Ramin; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Akrami, Hassan; Rezaei Kanavi, Mozhgan; Samiei, Shahram

    2013-01-01

    To evaluate the effect of placental growth factor (PlGF) gene knockdown in a murine model of laser-induced choroidal neovascularization. Choroidal neovascularization was induced in the left eyes of 11 mice by infrared laser. Small interfering RNA (siRNA, 20 picomoles/10 μl) corresponding to PlGF mRNA was administered intravitreally by Hamilton syringe in all subjects. One month later, fluorescein angiography and histolologic examination were performed. No leakage was apparent in the 11 eyes treated with siRNA cognate to PlGF. The results of histological evaluation were consistent with angiographic findings showing absence of choroidal neovascularization. Knockdown of the PlGF gene can inhibit the growth of laser-induced choroidal neovascularization in mice.

  12. Knockdown of the Placental Growth Factor Gene Inhibits Laser Induced Choroidal Neovascularization in a Murine Model

    PubMed Central

    Nourinia, Ramin; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Akrami, Hassan; Rezaei Kanavi, Mozhgan; Samiei, Shahram

    2013-01-01

    Purpose To evaluate the effect of placental growth factor (PlGF) gene knockdown in a murine model of laser-induced choroidal neovascularization. Methods Choroidal neovascularization was induced in the left eyes of 11 mice by infrared laser. Small interfering RNA (siRNA, 20 picomoles/10 μl) corresponding to PlGF mRNA was administered intravitreally by Hamilton syringe in all subjects. One month later, fluorescein angiography and histolologic examination were performed. Results No leakage was apparent in the 11 eyes treated with siRNA cognate to PlGF. The results of histological evaluation were consistent with angiographic findings showing absence of choroidal neovascularization. Conclusion Knockdown of the PlGF gene can inhibit the growth of laser-induced choroidal neovascularization in mice. PMID:23825706

  13. Successful treatment of toxoplasmosis-associated choroidal neovascular lesions with bevacizumab and antiparasitic therapy.

    PubMed

    Lin, Chun-Ju; Chen, San-Ni; Hwang, Jiunn-Feng; Hu, Pei-Shin

    2011-01-01

    To report the effects of oral trimethoprim/sulfamethoxazole and intravitreal bevacizumab injection in the treatment of ocular toxoplasmosis-associated choroidal neovascular lesions (CNV). This was a noncomparative, nonrandomized, consecutive case series. All eyes with ocular toxoplasmosis-associated CNV received one intravitreal bevacizumab injection under the coverage of oral trimethoprim/sulfamethoxazole. The changes in best-corrected visual acuity were recorded. Serial fundus photography, fluorescein angiography, optical coherence tomography, and indocyanine green angiography were performed to measure the treatment efficacy. Three eyes of two patients with a history of ocular toxoplasmosis had active CNV demonstrated by fluorescein angiography and optical coherence tomography. Each was treated with oral trimethoprim/sulfamethoxazole and one intravitreal bevacizumab injection. Best-corrected visual acuity, fundus photographs, fluorescein angiography, optical coherence tomography, and indocyanine green angiography all showed favorable results. No ocular or systemic complications were noted. In all three eyes, the CNV subsided and vision improved. Oral trimethoprim/sulfamethoxazole is an effective and less expensive antibiotic against Toxoplasma gondii. Intravitreal bevacizumab injection appears to be a well-tolerated treatment for toxoplasmosis-associated CNV and has the potential as an adjuvant therapy to improve final vision. More cases and further studies are required.

  14. Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization.

    PubMed

    Zhang, Han; Sonoda, Koh-Hei; Hijioka, Kuniaki; Qiao, Hong; Oshima, Yuji; Ishibashi, Tatsuro

    2009-04-17

    Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8+ T cells reduced pathological preretinal NV, with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8+ T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.

  15. Management of recurrent inflammatory choroidal neovascular membrane secondary to Vogt-Koyanagi-Harada syndrome, using combined intravitreal injection of bevacizumab and triamcinolone acetate.

    PubMed

    Pai, Sivakami A; Hebri, Sudhira P; Lootah, Afra M

    2012-01-01

    The purpose of this report is to evaluate the efficacy and safety of combined intravitreal injection of bevacizumab and intravitreal triamcinolone acetonide (IVTA) for recurrent inflammatory choroidal neovascular membrane (CNVM). It was a prospective interventional study of a young female, who was a known case of Vogt-Koyanagi-Harada syndrome. She presented with an inflammatory choroidal neovascualar membrane and signs of panuveitis in the right eye. She underwent a complete ophthalmic examination. She was given intravitreal injection of bevacizumab and IVTA at different sites. There was complete regression of CNVM and ocular inflammation within a week. After six months, she had recurrence of CNVM in the same eye, which was treated similarly. There was a complete resolution of CNVM and ocular inflammation after the combination therapy and systemic steroids, until one year of follow-up. No serious systemic or ocular adverse events were noted. Combination therapy appears to be an effective and safe method in the management of recurrent inflammatory CNVM.

  16. Chorioretinal neovascular membranes complicating contusional eye injuries with indirect choroidal ruptures.

    PubMed Central

    Wood, C M; Richardson, J

    1990-01-01

    Chorioretinal neovascular membranes are a recognised but rare cause of late visual loss in eyes suffering contusional injuries. A series of eight cases is presented all with indirect choroidal ruptures involving the perifoveal region. Two main patterns of 'at risk' rupture were noted: a temporally situated rupture passing almost directly through the fovea, and a rupture which curves inferior or superior to the optic disc stopping just short of the fovea. In six of eight cases there was only a partial thickness rupture of the choroid. These neovascular membranes may present at any time after the original injury, either early (within six months of the injury), which could be related to persistence of the normal reparative neovascular response, or late (at least one year after the injury), which are more likely to have resulted from a secondary breakdown of the outer blood-retina barrier. Images PMID:1690025

  17. Antiangiogenic immunotherapy targeting Flk-1, DNA vaccine and adoptive T cell transfer, inhibits ocular neovascularization

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Han; Sonoda, Koh-Hei, E-mail: sonodak@med.kyushu-u.ac.jp; Hijioka, Kuniaki

    2009-04-17

    Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases. The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and so there is no satisfactory therapy for ocular NV. Here, we describe a strategy targeting Flk-1, a self-antigen overexpressed on proliferating endothelial cells in ocular NV, by antiangiogenic immunotherapy-DNA vaccine and adoptive T cell therapy. An oral DNA vaccine encoding Flk-1 carried by attenuated Salmonella typhimurium markedly suppressed development of laser-induced choroidal NV. We further demonstrated that adoptive transfer of vaccine-induced CD8{sup +} T cells reduced pathological preretinal NV,more » with a concomitant facilitation of physiological revascularization after oxygen-induced retinal vessel obliteration. However, physiological retinal vascular development was unaffected in neonatal mice transferred with vaccine-induced CD8{sup +} T cells. These findings suggested that antiangiogenic immunotherapy targeting Flk-1 such as vaccination and adoptive immunotherapy may contribute to future therapies for ocular NV.« less

  18. Animal models of ocular angiogenesis: from development to pathologies.

    PubMed

    Liu, Chi-Hsiu; Wang, Zhongxiao; Sun, Ye; Chen, Jing

    2017-11-01

    Pathological angiogenesis in the eye is an important feature in the pathophysiology of many vision-threatening diseases, including retinopathy of prematurity, diabetic retinopathy, and age-related macular degeneration, as well as corneal diseases with abnormal angiogenesis. Development of reproducible and reliable animal models of ocular angiogenesis has advanced our understanding of both the normal development and the pathobiology of ocular neovascularization. These models have also proven to be valuable experimental tools with which to easily evaluate potential antiangiogenic therapies beyond eye research. This review summarizes the current available animal models of ocular angiogenesis. Models of retinal and choroidal angiogenesis, including oxygen-induced retinopathy, laser-induced choroidal neovascularization, and transgenic mouse models with deficient or spontaneous retinal/choroidal neovascularization, as well as models with induced corneal angiogenesis, are widely used to investigate the molecular and cellular basis of angiogenic mechanisms. Theoretical concepts and experimental protocols of these models are outlined, as well as their advantages and potential limitations, which may help researchers choose the most suitable models for their investigative work.-Liu, C.-H., Wang, Z., Sun, Y., Chen, J. Animal models of ocular angiogenesis: from development to pathologies. © FASEB.

  19. Evaluation of photopoint photosensitizer mv6401, indium chloride methyl pyropheophorbide, as a photodynamic therapy agent in primate choriocapillaris and laser-induced choroidal neovascularization.

    PubMed

    Ciulla, Thomas A; Criswell, Mark H; Danis, Ronald P; Snyder, Wendy J; Small, Ward

    2004-08-01

    To assess the potential of a new photosensitizer, indium chloride methyl pyropheophorbide (PhotoPoint MV6401), for ocular photodynamic therapy (PDT) in normal choriocapillaris vessels and experimentally induced choroidal neovascularization in New-World monkeys (Saimiri sciureus). PhotoPoint MV6401 (Miravant Pharmaceuticals, Inc., Santa Barbara, CA) was activated at 664 nm using a DD3-0665 (Miravant Systems, Inc., Santa Barbara, CA) 0.5 W diode laser. The efficacy of MV6401 was evaluated by indirect ophthalmoscopy, fundus photography, fluorescein angiography, and histology. The drug and light doses were 0.10 micromoles/kg to 0.3 micromoles/kg and 10 J/cm to 40 J/cm, respectively, and post-injection activation times ranged from +10 minutes to +120 minutes. Best closure of normal choriocapillaris was achieved at a dosage level of 0.15 micromoles/kg in primates. Histology demonstrated that increased post-injection activation times (+60 minutes to +90 minutes) and low laser light doses (10 J/cm to 20 J/cm) in the primate model resulted in selective closure of the choriocapillaris and medium sized choroidal vessels with minimal effect to the retina. Histology from neovascular lesions PDT-treated with MV6401 revealed significant diminution of vascularity, correlating with diminution of leakage observed on angiography. PhotoPoint MV6401, indium chloride methyl pyropheophorbide, is a potent photosensitizer that demonstrates both efficacy and selectivity in primate choriocapillaris and laser-induced choroidal neovascularization occlusion. Maximum selectivity was achieved using a post infusion interval of +60 to +90 minutes.

  20. Endothelial TWIST1 Promotes Pathological Ocular Angiogenesis

    PubMed Central

    Li, Jie; Liu, Chi-Hsiu; Sun, Ye; Gong, Yan; Fu, Zhongjie; Evans, Lucy P.; Tian, Katherine T.; Juan, Aimee M.; Hurst, Christian G.; Mammoto, Akiko; Chen, Jing

    2014-01-01

    Purpose. Pathological neovessel formation impacts many blinding vascular eye diseases. Identification of molecular signatures distinguishing pathological neovascularization from normal quiescent vessels is critical for developing new interventions. Twist-related protein 1 (TWIST1) is a transcription factor important in tumor and pulmonary angiogenesis. This study investigated the potential role of TWIST1 in modulating pathological ocular angiogenesis in mice. Methods. Twist1 expression and localization were analyzed in a mouse model of oxygen-induced retinopathy (OIR). Pathological ocular angiogenesis in Tie2-driven conditional Twist1 knockout mice were evaluated in both OIR and laser-induced choroidal neovascularization models. In addition, the effects of TWIST1 on angiogenesis and endothelial cell function were analyzed in sprouting assays of aortic rings and choroidal explants isolated from Twist1 knockout mice, and in human retinal microvascular endothelial cells treated with TWIST1 small interfering RNA (siRNA). Results. TWIST1 is highly enriched in pathological neovessels in OIR retinas. Conditional Tie2-driven depletion of Twist1 significantly suppressed pathological neovessels in OIR without impacting developmental retinal angiogenesis. In a laser-induced choroidal neovascularization model, Twist1 deficiency also resulted in significantly smaller lesions with decreased vascular leakage. In addition, loss of Twist1 significantly decreased vascular sprouting in both aortic ring and choroid explants. Knockdown of TWIST1 in endothelial cells led to dampened expression of vascular endothelial growth factor receptor 2 (VEGFR2) and decreased endothelial cell proliferation. Conclusions. Our study suggests that TWIST1 is a novel regulator of pathologic ocular angiogenesis and may represent a new molecular target for developing potential therapeutic treatments to suppress pathological neovascularization in vascular eye diseases. PMID:25414194

  1. Incremental cost-effectiveness of laser therapy for choroidal neovascularization associated with histoplasmosis.

    PubMed

    Brown, G C; Brown, M M; Sharma, S; Busbee, B; Brown, H

    2000-01-01

    Laser photocoagulation has been shown in a large clinical trial to be efficacious in reducing the degree of vision loss occurring secondary to choroidal neovascularization (CNV) associated with ocular histoplasmosis. Nevertheless, data are lacking concerning the impact of the therapy on quality of life and its value to stakeholders in health care. Recently, information concerning the utility value of visual states has become available. Accordingly, the authors undertook to ascertain the cost-effectiveness of laser photocoagulation for the treatment of extrafoveal CNV occurring in eyes with ocular histoplasmosis. Design--A computer simulation, econometric model is presented to evaluate the incremental cost-effectiveness of laser photocoagulation therapy, as compared with the natural course of the disease, for the treatment of patients with extrafoveal CNV associated with ocular histoplasmosis. The model applies long-term visual data from previous clinical trials, utility analysis (which reflects patient perceptions of quality of life), decision analysis with Markov modeling, and present value analysis with discounting to account for the time value of money. Outcome measure--Cost per quality-adjusted life-year gained from treatment. Laser photocoagulation therapy for extrafoveal CNV associated with ocular histoplasmosis costs $4167 1999 US dollars (at a 3% discount rate) for each quality-adjusted life-year gained from treatment. Sensitivity analysis shows that changing the discount rate substantially alters the cost-effectiveness, with a value of $1339 at a 0% discount rate and $56,250 at a 10% discount rate. Compared with therapeutic modalities for other disease entities, laser therapy for the treatment of extrafoveal CNV associated with ocular histoplasmosis appears to be a cost-effective treatment from the patient preference-based point of view.

  2. Glycobiology of ocular angiogenesis

    PubMed Central

    Markowska, Anna I; Cao, Zhiyi; Panjwani, Noorjahan

    2014-01-01

    Ocular neovascularization can affect almost all the tissues of the eye: the cornea, the iris, the retina, and the choroid. Pathological neovascularization is the underlying cause of vision loss in common ocular conditions such as diabetic retinopathy, retinopathy of prematurity and age-related macular neovascularization. Glycosylation is the most common covalent posttranslational modification of proteins in mammalian cells. A growing body of evidence demonstrates that glycosylation influences the process of angiogenesis and impacts activation, proliferation, and migration of endothelial cells as well as the interaction of angiogenic endothelial cells with other cell types necessary to form blood vessels. Recent studies have provided evidence that members of the galectin class of β-galactoside-binding proteins modulate angiogenesis by novel carbohydrate-based recognition systems involving interactions between glycans of angiogenic cell surface receptors and galectins. This review discusses the significance of glycosylation and the role of galectins in the pathogenesis of ocular neovascularization. PMID:25108228

  3. Choroidal nevus with subretinal pigment epithelial neovascular membrane and a positive P-32 test

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Snip, R.C.; Green, W.R.; Jaegers, K.R.

    A 62-year-old white female was found to have a small, flat pigmented choroidal tumor. After fluorescein angiography and a positive P-32 test, the eye was enucleated for presumed malignant melanoma. Histologically, the tumor proved to be a choroidal nevus with a break in Bruch's membrane and a subretinal-pigment-epithelial neovascular membrane.

  4. Cytochrome P450-generated metabolites derived from ω-3 fatty acids attenuate neovascularization

    PubMed Central

    Yanai, Ryoji; Mulki, Lama; Hasegawa, Eiichi; Takeuchi, Kimio; Sweigard, Harry; Suzuki, Jun; Gaissert, Philipp; Vavvas, Demetrios G.; Sonoda, Koh-Hei; Rothe, Michael; Schunck, Wolf-Hagen; Miller, Joan W.; Connor, Kip M.

    2014-01-01

    Ocular neovascularization, including age-related macular degeneration (AMD), is a primary cause of blindness in individuals of industrialized countries. With a projected increase in the prevalence of these blinding neovascular diseases, there is an urgent need for new pharmacological interventions for their treatment or prevention. Increasing evidence has implicated eicosanoid-like metabolites of long-chain polyunsaturated fatty acids (LCPUFAs) in the regulation of neovascular disease. In particular, metabolites generated by the cytochrome P450 (CYP)–epoxygenase pathway have been shown to be potent modulators of angiogenesis, making this pathway a reasonable previously unidentified target for intervention in neovascular ocular disease. Here we show that dietary supplementation with ω-3 LCPUFAs promotes regression of choroidal neovessels in a well-characterized mouse model of neovascular AMD. Leukocyte recruitment and adhesion molecule expression in choroidal neovascular lesions were down-regulated in mice fed ω-3 LCPUFAs. The serum of these mice showed increased levels of anti-inflammatory eicosanoids derived from eicosapentaenoic acid and docosahexaenoic acid. 17,18-epoxyeicosatetraenoic acid and 19,20-epoxydocosapentaenoic acid, the major CYP-generated metabolites of these primary ω-3 LCPUFAs, were identified as key lipid mediators of disease resolution. We conclude that CYP-derived bioactive lipid metabolites from ω-3 LCPUFAs are potent inhibitors of intraocular neovascular disease and show promising therapeutic potential for resolution of neovascular AMD. PMID:24979774

  5. Characteristics of choroidal neovascularization in the complications of age-related macular degeneration prevention trial.

    PubMed

    Maguire, Maureen G; Alexander, Judith; Fine, Stuart L

    2008-09-01

    To describe the characteristics of incident choroidal neovascularization (CNV) in observed and treated eyes in the Complications of Age-related Macular Degeneration Prevention Trial (CAPT). Cross-sectional descriptive study within a multicenter, randomized clinical trial. Patients who developed CNV during CAPT follow-up. Inclusion criteria for CAPT specified bilateral large drusen (>or=10 drusen at least 125 micro), visual acuity >or=20/40 in each eye, and age >or=50. Exclusion criteria included CNV and geographic atrophy >1 Macular Photocoagulation Study (MPS) disc area or within 500 micro of the foveal center. One eye of each person was selected randomly for low-intensity laser treatment and the contralateral eye was observed. Fluorescein angiography was performed at baseline, annually for >or=5 years, and whenever there were symptoms of CNV. Trained readers at the CAPT Photograph Reading Center assessed color stereo photographs and angiogram negatives to identify CNV. Choroidal neovascularization was classified by type (predominantly classic CNV, minimally classic CNV, occult only CNV, or scar), location, and area. Visual acuity was measured by certified examiners. Symmetry of characteristics between eyes of bilaterally affected patients was examined. Choroidal neovascularization developed in 282 eyes of 225 patients. At the time of detection, 192 (68%) of the lesions were occult only, 153 (54%) were subfoveal, and 157 (56%) were or=20/40 in 123 (69%) of 179 eyes with visual acuity measured at the time of detection. Choroidal neovascularization developed in both eyes in 57 patients (25%) during CAPT follow-up. Lesions in eyes of bilaterally affected patients were no more similar to each other than affected eyes in 2 different patients. When patients are monitored closely, many CNV lesions can be detected outside of the fovea and when they are relatively small. Early detection may lead to improved long-term visual acuity.

  6. A Novel Platelet-Activating Factor Receptor Antagonist Inhibits Choroidal Neovascularization and Subretinal Fibrosis

    PubMed Central

    Zhang, Han; Yang, Yang; Takeda, Atsunobu; Yoshimura, Takeru; Oshima, Yuji; Sonoda, Koh-Hei; Ishibashi, Tatsuro

    2013-01-01

    Choroidal neovascularization (CNV) is a critical pathogenesis in age-related macular degeneration (AMD), the most common cause of blindness in developed countries. To date, the precise molecular and cellular mechanisms underlying CNV have not been elucidated. Platelet-activating factor (PAF) has been previously implicated in angiogenesis; however, the roles of PAF and its receptor (PAF-R) in CNV have not been addressed. The present study reveals several important findings concerning the relationship of the PAF-R signaling with CNV. PAF-R was detected in a mouse model of laser-induced CNV and was upregulated during CNV development. Experimental CNV was suppressed by administering WEB2086, a novel PAF-R antagonist. WEB2086-dependent suppression of CNV occurred via the inhibition of macrophage infiltration and the expression of proangiogenic (vascular endothelial growth factor) and proinflammatory molecules (monocyte chemotactic protein-1 and IL-6) in the retinal pigment epithelium–choroid complex. Additionally, WEB2086-induced PAF-R blockage suppresses experimentally induced subretinal fibrosis, which resembles the fibrotic subretinal scarring observed in neovascular AMD. As optimal treatment modalities for neovascular AMD would target the multiple mechanisms of AMD-associated vision loss, including neovascularization, inflammation and fibrosis, our results suggest PAF-R as an attractive molecular target in the treatment of AMD. PMID:23826375

  7. A Proinflammatory Function of Toll-Like Receptor 2 in the Retinal Pigment Epithelium as a Novel Target for Reducing Choroidal Neovascularization in Age-Related Macular Degeneration.

    PubMed

    Feng, Lili; Ju, Meihua; Lee, Kei Ying V; Mackey, Ashley; Evangelista, Mariasilvia; Iwata, Daiju; Adamson, Peter; Lashkari, Kameran; Foxton, Richard; Shima, David; Ng, Yin Shan

    2017-10-01

    Current treatments for choroidal neovascularization, a major cause of blindness for patients with age-related macular degeneration, treat symptoms but not the underlying causes of the disease. Inflammation has been strongly implicated in the pathogenesis of choroidal neovascularization. We examined the inflammatory role of Toll-like receptor 2 (TLR2) in age-related macular degeneration. TLR2 was robustly expressed by the retinal pigment epithelium in mouse and human eyes, both normal and with macular degeneration/choroidal neovascularization. Nuclear localization of NF-κB, a major downstream target of TLR2 signaling, was detected in the retinal pigment epithelium of human eyes, particularly in eyes with advanced stages of age-related macular degeneration. TLR2 antagonism effectively suppressed initiation and growth of spontaneous choroidal neovascularization in a mouse model, and the combination of anti-TLR2 and antivascular endothelial growth factor receptor 2 yielded an additive therapeutic effect on both area and number of spontaneous choroidal neovascularization lesions. Finally, in primary human fetal retinal pigment epithelium cells, ligand binding to TLR2 induced robust expression of proinflammatory cytokines, and end products of lipid oxidation had a synergistic effect on TLR2 activation. Our data illustrate a functional role for TLR2 in the pathogenesis of choroidal neovascularization, likely by promoting inflammation of the retinal pigment epithelium, and validate TLR2 as a novel therapeutic target for reducing choroidal neovascularization. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  8. Therapeutic efficacy of intravitreal bevacizumab on posterior uveitis complicated by neovascularization

    PubMed Central

    Kurup, Shree; Lew, Julie; Byrnes, Gordon; Yeh, Steven; Nussenblatt, Robert; Levy-Clarke, Grace

    2010-01-01

    Purpose To evaluate the therapeutic effect of intravitreal bevacizumab in patients with uveitis-associated choroidal/retinal neovascularization. Methods Two female patients (40 years, 15 years) with posterior uveitis, (one presumed ocular sarcoidosis, one lupus) were evaluated for neovascularization of the posterior segment. Both patients were given a single dose of 1.25 mg intravitreal bevacizumab. Results Significant anatomical and functional recovery was evident in both patients within a few weeks. Conclusion In selected uveitic patients, bevacizumab may be an option for managing neovascularization. PMID:18513266

  9. Inhibition of Choroidal Neovascularization by Intravenous Injection of Adenoviral Vectors Expressing Secretable Endostatin

    PubMed Central

    Mori, Keisuke; Ando, Akira; Gehlbach, Peter; Nesbitt, David; Takahashi, Kyoichi; Goldsteen, Donna; Penn, Michael; Chen, Cheauyan T.; Mori, Keiko; Melia, Michele; Phipps, Sandrina; Moffat, Diana; Brazzell, Kim; Liau, Gene; Dixon, Katharine H.; Campochiaro, Peter A.

    2001-01-01

    Endostatin is a cleavage product of collagen XVIII that inhibits tumor angiogenesis and growth. Interferon α2a blocks tumor angiogenesis and causes regression of hemangiomas, but has no effect on choroidal neovascularization (CNV). Therefore, inhibitors of tumor angiogenesis do not necessarily inhibit ocular neovascularization. In this study, we used an intravenous injection of adenoviral vectors containing a sig-mEndo transgene consisting of murine immunoglobulin κ-chain leader sequence coupled to sequence coding for murine endostatin to investigate the effect of high serum levels of endostatin on CNV in mice. Mice injected with a construct in which sig-mEndo expression was driven by the Rous sarcoma virus promoter had moderately high serum levels of endostatin and significantly smaller CNV lesions at sites of laser-induced rupture of Bruch’s membrane than mice injected with null vector. Mice injected with a construct in which sig-mEndo was driven by the simian cytomegalovirus promoter had ∼10-fold higher endostatin serum levels and had nearly complete prevention of CNV. There was a strong inverse correlation between endostatin serum level and area of CNV. This study provides proof of principle that gene therapy to increase levels of endostatin can prevent the development of CNV and may provide a new treatment for the leading cause of severe loss of vision in patients with age-related macular degeneration. PMID:11438478

  10. Neuroprotectin D1 Attenuates Laser-induced Choroidal Neovascularization in Mouse

    PubMed Central

    Sheets, Kristopher G.; Zhou, Yongdong; Ertel, Monica K.; Knott, Eric J.; Regan, Cornelius E.; Elison, Jasmine R.; Gordon, William C.; Gjorstrup, Per

    2010-01-01

    Purpose To examine the effects of neuroprotectin D1 (NPD1), a stereospecific derivative of docosahexaenoic acid, on choroidal neovascularization (CNV) in a laser-induced mouse model. Specifically, this was assessed by clinically grading laser-induced lesions, measuring leakage area, and volumetrically quantifying vascular endothelial cell proliferation. Methods C57Bl/6 mice were treated with vehicle control or NPD1, and choroidal neovascularization was induced by laser rupture of Bruch's membrane; treatment was administered throughout the first week of recovery. One and two weeks after CNV induction, fundus fluorescein angiography was performed. Angiograms were clinically graded to assess leakage severity, while leakage area was measured by image analysis of angiograms. Proliferation of vascular endothelial cells was evaluated volumetrically by three-dimensional laser confocal immunofluorescent microscopy of cytoskeletal, nuclear, and endothelial cell markers. Results At seven days after CNV induction, NPD1-treated mice had 60% fewer clinically relevant lesions than controls, dropping to 80% fewer by 14 days. NPD1 mice exhibited 25% smaller leakage area than controls at 7 days and 44% smaller area at 14 days. Volumetric immunofluorescence revealed 46% less vascular endothelial cell volume in 7-day NPD1-treated mice than in 7-day controls, and by 14 days NPD1 treatment was 68% lower than controls. Furthermore, comparison of 7- and 14-day volumes of NPD1-treated mice revealed a 50% reduction at 14 days. Conclusions NPD1 significantly inhibits choroidal neovascularization. There are at least two possible mechanisms that could explain the neuroprotective action of NPD1. Ultimately, nuclear factor-κB could be inhibited with a reduction in cyclooxygenase-2 (COX-2) to reduce vascular endothelial growth factor (VEGF) expression, and/or activation of the resolution phase of the inflammatory response/survival pathways could be upregulated. Moreover, NPD1 continues to be

  11. Suppression of aberrant choroidal neovascularization through activation of the aryl hydrocarbon receptor.

    PubMed

    Choudhary, Mayur; Safe, Stephen; Malek, Goldis

    2018-05-01

    The aryl hydrocarbon receptor (AhR) is a ligand activated transcription factor, initially discovered for its role in regulating xenobiotic metabolism. There is extensive evidence supporting a multi-faceted role for AhR, modulating physiological pathways important in cell health and disease. Recently we demonstrated that the AhR plays a role in the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly. We found that loss of AhR exacerbates choroidal neovascular (CNV) lesion formation in a murine model. Herein we tested the therapeutic impact of AhR activation on CNV lesion formation and factors associated with aberrant neovascularization. We screened a panel of synthetic drugs and endogenous AhR ligands, assessed their ability to activate AhR in choroidal endothelial cells, and inhibit angiogenesis in vitro. Drugs with an anti-angiogenic profile were then administered to a murine model of CNV. Two compounds, leflunomide and flutamide, significantly inhibited CNV formation concurrent with positive modifying effects on angiogenesis, inflammation, extracellular matrix remodeling, and fibrosis. These results validate the role of the AhR pathway in regulating CNV pathogenesis, identify mechanisms of AhR-based therapies in the eye, and argue in favor of developing AhR as a drug target for the treatment of neovascular AMD. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Bevacizumab in choroidal neovascularization secondary to Indian tick typhus: A rare case report.

    PubMed

    Ijeri, Raghavendra; Beladiya, Gautam; Bhomaj, Sharad

    2016-10-01

    Tick typhus causes hemorrhagic lesions over the skin. Retina also shows hemorrhages and exudates. Many cases have been reported in western literature about this condition. To our best of knowledge, this is the first case report of tick typhus in India which was also associated with inflammatory choroidal neovascularization.

  13. MULTIMODAL IMAGING OF CHOROIDAL LESIONS IN DISSEMINATED MYCOBACTERIUM CHIMAERA INFECTION AFTER CARDIOTHORACIC SURGERY.

    PubMed

    Böni, Christian; Al-Sheikh, Mayss; Hasse, Barbara; Eberhard, Roman; Kohler, Philipp; Hasler, Pascal; Erb, Stefan; Hoffmann, Matthias; Barthelmes, Daniel; Zweifel, Sandrine A

    2017-12-04

    To explore morphologic characteristics of choroidal lesions in patients with disseminated Mycobacterium chimaera infection subsequent to open-heart surgery. Nine patients (18 eyes) with systemic M. chimaera infection were reviewed. Activity of choroidal lesions were evaluated using biomicroscopy, fundus autofluorescence, enhanced depth imaging optical coherence tomography, fluorescein angiography/indocyanine green angiography, and optical coherence tomography angiography. Relationships of choroidal findings to systemic disease activity were sought. All 9 male patients, aged between 49 and 66 years, were diagnosed with endocarditis and/or aortic graft infection. Mean follow-up was 17.6 months. Four patients had only inactive lesions (mild disease). In all five patients (10 eyes) with progressive ocular disease, indocyanine green angiography was superior to other tests for revealing new lesions and active lesions correlated with hyporeflective choroidal areas on enhanced depth imaging optical coherence tomography. One eye with a large choroidal granuloma developed choroidal neovascularization. Optical coherence tomography angiography showed areas with reduced perfusion at the inner choroid. All 5 patients with progressive ocular disease had evidence of systemic disease activity within ±6 weeks' duration. Choroidal manifestation of disseminated M. chimaera infection indicates systemic disease activity. Multimodal imaging is suitable to recognize progressive ocular disease. We propose ophthalmologic screening examinations for patients with M. chimaera infection.

  14. Pathogenic role and therapeutic potential of pleiotrophin in mouse models of ocular vascular disease.

    PubMed

    Wang, Weiwen; LeBlanc, Michelle E; Chen, Xiuping; Chen, Ping; Ji, Yanli; Brewer, Megan; Tian, Hong; Spring, Samantha R; Webster, Keith A; Li, Wei

    2017-11-01

    Angiogenic factors play an important role in the pathogenesis of diabetic retinopathy (DR), neovascular age-related macular degeneration (nAMD) and retinopathy of prematurity (ROP). Pleiotrophin, a well-known angiogenic factor, was recently reported to be upregulated in the vitreous fluid of patients with proliferative DR (PDR). However, its pathogenic role and therapeutic potential in ocular vascular diseases have not been defined in vivo. Here using corneal pocket assays, we demonstrated that pleiotrophin induced angiogenesis in vivo. To investigate the pathological role of pleiotrophin we used neutralizing antibody to block its function in multiple in vivo models of ocular vascular diseases. In a mouse model of DR, intravitreal injection of pleiotrophin-neutralizing antibody alleviated diabetic retinal vascular leakage. In a mouse model of oxygen-induced retinopathy (OIR), which is a surrogate model of ROP and PDR, we demonstrated that intravitreal injection of anti-pleiotrophin antibody prevented OIR-induced pathological retinal neovascularization and aberrant vessel tufts. Finally, pleiotrophin-neutralizing antibody ameliorated laser-induced choroidal neovascularization, a mouse model of nAMD, suggesting that pleiotrophin is involved in choroidal vascular disease. These findings suggest that pleiotrophin plays an important role in the pathogenesis of DR with retinal vascular leakage, ROP with retinal neovascularization and nAMD with choroidal neovascularization. The results also support pleiotrophin as a promising target for anti-angiogenic therapy.

  15. EFFECT OF SYSTEMIC BETA-BLOCKERS, ACE INHIBITORS, AND ANGIOTENSIN RECEPTOR BLOCKERS ON DEVELOPMENT OF CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH AGE-RELATED MACULAR DEGENERATION.

    PubMed

    Thomas, Akshay S; Redd, Travis; Hwang, Thomas

    2015-10-01

    Recent studies have suggested that the use of systemic beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers can induce regression of choroidal neovascularization in rodent models. The purpose of this study is to evaluate if these agents have a protective effect against the development of choroidal neovascularization in patients with age-related macular degeneration. In this single-center retrospective case-control study, the charts of 250 patients with neovascular age-related macular degeneration were compared with those of 250 controls with dry age-related macular degeneration. Charts were reviewed for current and past use of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. Frequency tables were generated, and associations were examined using chi-square tests, t-tests, and multivariate logistic regression. There was no statistically significant difference between rates of beta-blocker use (P = 0.57), angiotensin-converting enzyme inhibitors use (P = 0.20), or angiotensin receptor blockers use (P = 0.61) between the 2 groups. Additionally, there was no statistically significant difference between rates of use of combinations of the above drugs between the two groups. Although there is growing evidence that beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers can induce regression of choroidal neovascularization in rodent models, these medications do not seem to confer a protective effect against the development of choroidal neovascularization in patients with age-related macular degeneration.

  16. Nucleoside Reverse Transcriptase Inhibitors Suppress Laser-Induced Choroidal Neovascularization in Mice

    PubMed Central

    Mizutani, Takeshi; Fowler, Benjamin J.; Kim, Younghee; Yasuma, Reo; Krueger, Laura A.; Gelfand, Bradley D.; Ambati, Jayakrishna

    2015-01-01

    Purpose To evaluate the efficacy of nucleoside reverse transcriptase inhibitors (NRTIs) in the laser-induced mouse model of choroidal neovascularization (CNV). Methods We evaluated the NRTIs lamivudine (3TC), zidovudine (AZT), and abacavir (ABC) and the P2X7 antagonist A438079. Choroidal neovascularization was induced by laser injury in C57BL/6J wild-type, Nlrp3−/−, and P2rx7−/− mice, and CNV volume was measured after 7 days by confocal microscopy. Drugs were administered by intravitreous injection immediately after the laser injury. Vascular endothelial growth factor-A in RPE-choroid lysates was measured 3 days after laser injury by ELISA. HEK293 cells expressing human and mouse P2X7 were exposed to the selective P2X7 receptor agonist 2′, 3′-(benzoyl-4-benzoyl)-ATP (Bz-ATP) with or without 3TC, and VEGF-A levels in media were measured by ELISA. Results Intravitreous injection of 3TC, AZT, and ABC significantly suppressed laser-induced CNV in C57BL/6J wild-type and Nlrp3−/− mice (P < 0.05) but not in P2rx7−/− mice. Intravitreous injection of A438079 also suppressed the laser-induced CNV (P < 0.05). The NRTIs 3TC, AZT, and ABC blocked VEGF-A levels in the RPE/choroid after laser injury in wild-type (P < 0.05) but not P2rx7−/− mice. Moreover, there was no additive effect of 3TC on CNV inhibition when coadministered with a neutralizing VEGF-A antibody. Stimulation of human and mouse P2X7-expressing HEK293 cells with Bz-ATP increased VEGF secretion (P < 0.001), which was abrogated by 3TC (P < 0.001). Stimulation of primary human RPE cells with Bz-ATP increased VEGFA and IL6 mRNA levels, which were abrogated by 3TC. Conclusions Multiple clinically relevant NRTIs suppressed laser-induced CNV and downregulated VEGF-A, via P2X7. PMID:26529046

  17. miR-539-5p inhibits experimental choroidal neovascularization by targeting CXCR7.

    PubMed

    Feng, Yifan; Wang, Jing; Yuan, Yuanzhi; Zhang, Xi; Shen, Minqian; Yuan, Fei

    2018-03-01

    Stromal cell-derived factor-1 (SDF-1) has been previously confirmed to participate in the formation of choroidal neovascularization (CNV) via its receptor, CXC chemokine receptor (CXCR) 4; CXCR7 is a recently identified receptor for SDF-1. The molecular mechanisms and therapeutic value of CXCR7 in CNV remain undefined. In this study, experimental CNV was induced by laser photocoagulation in Brown-Norway pigmented rats, and aberrant CXCR7 overexpression was detected in the retinal pigment epithelial/choroid/sclera tissues of laser-injured eyes. Blockade of CXCR7 activation via CXCR7 knockdown or neutralizing Ab administration inhibited SDF-1-induced cell survival and the tubular formation of human retinal microvascular endothelial cells (HRMECs) in vitro and reduced CNV leakage and lesion size in vivo. By using microRNA array screening and bioinformatic analyses, we identified miR-539-5p as a regulator of CXCR7. Transfection of HRMECs and choroid-retinal endothelial (RF/6A) cells with the miR-539-5p mimic inhibited their survival and tube formation, whereas CXCR7 overexpression rescued the suppressive effect of miR-539-5p. The antiangiogenic activities of the miR-539-5p mimic were additionally demonstrated in vivo by intravitreal injection. ERK1/2 and AKT signaling downstream of CXCR7 is involved in the miR-539-5p regulation of endothelial cell behaviors. These findings suggest that the manipulation of miR-539-5p/CXCR7 levels may have important therapeutic implications in CNV-associated diseases.-Feng, Y., Wang, J., Yuan, Y., Zhang, X., Shen, M., Yuan, F. miR-539-5p inhibits experimental choroidal neovascularization by targeting CXCR7.

  18. Automated choroidal neovascularization detection algorithm for optical coherence tomography angiography.

    PubMed

    Liu, Li; Gao, Simon S; Bailey, Steven T; Huang, David; Li, Dengwang; Jia, Yali

    2015-09-01

    Optical coherence tomography angiography has recently been used to visualize choroidal neovascularization (CNV) in participants with age-related macular degeneration. Identification and quantification of CNV area is important clinically for disease assessment. An automated algorithm for CNV area detection is presented in this article. It relies on denoising and a saliency detection model to overcome issues such as projection artifacts and the heterogeneity of CNV. Qualitative and quantitative evaluations were performed on scans of 7 participants. Results from the algorithm agreed well with manual delineation of CNV area.

  19. Placental growth factor and its potential role in diabetic retinopathy and other ocular neovascular diseases.

    PubMed

    Nguyen, Quan Dong; De Falco, Sandro; Behar-Cohen, Francine; Lam, Wai-Ching; Li, Xuri; Reichhart, Nadine; Ricci, Federico; Pluim, Jennifer; Li, William W

    2018-02-01

    The role of vascular endothelial growth factor (VEGF), including in retinal vascular diseases, has been well studied, and pharmacological blockade of VEGF is the gold standard of treatment for neovascular age-related macular degeneration, retinal vein occlusion and diabetic macular oedema. Placental growth factor (PGF, previously known as PlGF), a homologue of VEGF, is a multifunctional peptide associated with angiogenesis-dependent pathologies in the eye and non-ocular conditions. Animal studies using genetic modification and pharmacological treatment have demonstrated a mechanistic role for PGF in pathological angiogenesis. Inhibition decreases neovascularization and microvascular abnormalities across different models, including oxygen-induced retinopathy, laser-induced choroidal neovascularization and in diabetic mice exhibiting retinopathies. High levels of PGF have been found in the vitreous of patients with diabetic retinopathy. Despite these strong animal data, the exact role of PGF in pathological angiogenesis in retinal vascular diseases remains to be defined, and the benefits of PGF-specific inhibition in humans with retinal neovascular diseases and macular oedema remain controversial. Comparative effectiveness research studies in patients with diabetic retinal disease have shown that treatment that inhibits both VEGF and PGF may provide superior outcomes in certain patients compared with treatment that inhibits only VEGF. This review summarizes current knowledge of PGF, including its relationship to VEGF and its role in pathological angiogenesis in retinal diseases, and identifies some key unanswered questions about PGF that can serve as a pathway for future basic, translational and clinical research. © 2016 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation and European Association for Vision & Eye Research.

  20. ADAM9 is involved in pathological retinal neovascularization.

    PubMed

    Guaiquil, Victor; Swendeman, Steven; Yoshida, Tsunehiko; Chavala, Sai; Campochiaro, Peter A; Blobel, Carl P

    2009-05-01

    Pathological ocular neovascularization, caused by diabetic retinopathy, age-related macular degeneration, or retinopathy of prematurity, is a leading cause of blindness, yet much remains to be learned about its underlying causes. Here we used oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) to assess the contribution of the metalloprotease-disintegrin ADAM9 to ocular neovascularization in mice. Pathological neovascularization in both the OIR and CNV models was significantly reduced in Adam9(-/-) mice compared to wild-type controls. In addition, the level of ADAM9 expression was strongly increased in endothelial cells in pathological vascular tufts in the OIR model. Moreover, tumor growth from heterotopically injected B16F0 melanoma cells was reduced in Adam9(-/-) mice compared to controls. In cell-based assays, the overexpression of ADAM9 enhanced the ectodomain shedding of EphB4, Tie-2, Flk-1, CD40, VCAM, and VE-cadherin, so the enhanced expression of ADAM9 could potentially affect pathological neovascularization by increasing the shedding of these and other membrane proteins from endothelial cells. Finally, we provide the first evidence for the upregulation of ADAM9-dependent shedding by reactive oxygen species, which in turn are known to play a critical role in OIR. Collectively, these results suggest that ADAM9 could be an attractive target for the prevention of proliferative retinopathies, CNV, and cancer.

  1. Attenuation of Choroidal Neovascularization by Histone Deacetylase Inhibitor

    PubMed Central

    Chan, Nymph; He, Shikun; Spee, Christine K.; Ishikawa, Keijiro; Hinton, David R.

    2015-01-01

    Choroidal neovascularization (CNV) is a blinding complication of age-related macular degeneration that manifests as the growth of immature choroidal blood vessels through Bruch’s membrane, where they can leak fluid or hemorrhage under the retina. Here, we demonstrate that the histone deacetylase inhibitor (HDACi) trichostatin A (TSA) can down-regulate the pro-angiogenic hypoxia-inducible factor-1α and vascular endothelial growth factor (VEGF), and up-regulate the anti-angiogenic and neuro-protective pigment epithelium derived factor in human retinal pigment epithelial (RPE) cells. Most strikingly, TSA markedly down-regulates the expression of VEGF receptor-2 in human vascular endothelial cells and, thus, can knock down pro-angiogenic cell signaling. Additionally, TSA suppresses CNV-associated wound healing response and RPE epithelial-mesenchymal transdifferentiation. In the laser-induced model of CNV using C57Bl/6 mice, systemic administration of TSA significantly reduces fluorescein leakage and the size of CNV lesions at post—laser days 7 and 14 as well as the immunohistochemical expression of VEGF, VEGFR2, and smooth muscle actin in CNV lesions at post-laser day 7. This report suggests that TSA, and possibly HDACi’s in general, should be further evaluated for their therapeutic potential for the treatment of CNV. PMID:25807249

  2. Ocular pulsation correlates with ocular tension: the choroid as piston for an aqueous pump?

    PubMed

    Phillips, C I; Tsukahara, S; Hosaka, O; Adams, W

    1992-01-01

    In 26 random out-patients, including 13 treated glaucoma patients and ocular hypertensives, the higher the ocular tension, the greater the pulse amplitude, by Alcon pneumotonometry, at a statistically significant level. In a single untreated hypertensive, when 2-hourly pneumotonometry was done for 24 h, the correlation was similar and significant. The higher the diastolic blood pressure, the higher the ocular pulsation, also significantly. Pulsation is suggested to be a pump, the choroid being the piston, contributing (1) to an increase in the outflow of aqueous humour and (2) to a homeostatic mechanism contributing to normalization of the intra-ocular pressure, wherein pulsation increases or decreases, as the intraocular pressure increases or decreases, respectively.

  3. Suppression of Experimental Choroidal Neovascularization by Curcumin in Mice

    PubMed Central

    Xie, Ping; Zhang, WeiWei; Yuan, Songtao; Chen, Zhiqiang; Yang, Qin; Yuan, DongQing; Wang, Feng; Liu, QingHuai

    2012-01-01

    Purpose To investigate the effects of curcumin on the development of experimental choroidal neovascularization (CNV) with underlying cellular and molecular mechanisms. Methods C57BL/6N mice were pretreated with intraperitoneal injections of curcumin daily for 3 days prior to laser-induced CNV, and the drug treatments were continued until the end of the study. The CNV area was analyzed by fluorescein-labeled dextran angiography of retinal pigment epithelium (RPE)-choroid flat mounts on day 7 and 14, and CNV leakage was evaluated by fluorescein angiography (FA) on day 14 after laser photocoagulation. The infiltration of F4/80 positive macrophages and GR-1 positive granulocytes were evaluated by immunohistochemistry on RPE-choroid flat mounts on day 3. Their expression in RPE-choroid complex was quantified by real-time PCR (F4/80) and Western blotting (GR-1) on day 3. RPE-choroid levels of vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, and intercellular adhesion molecule (ICAM)-1 were examined by ELISA on day 3. Double immunostaining of F4/80 and VEGF was performed on cryo-sections of CNV lesions on day 3. The expression of nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)−1α in the RPE-choroid was determined by Western blotting. Results Curcumin-treated mice had significantly less CNV area (P<0.05) and CNV leakage (P<0.001) than vehicle-treated mice. Curcumin treatment led to significant inhibition of F4/80 positive macrophages (P<0.05) and GR-1 positive granulocytes infiltration (P<0.05). VEGF mainly expressed in F4/80 positive macrophages in laser injury sites, which was suppressed by curcumin treatment (P<0.01). Curcumin inhibited the RPE-choroid levels of TNF-α (P<0.05), MCP-1 (P<0.05) and ICAM-1 (P<0.05), and suppressed the activation of NF-κB in nuclear extracts (P<0.05) and the activation of HIF−1α (P<0.05). Conclusion Curcumin treatment led to the suppression of CNV development

  4. Relapse of choroidal neovascularization in Bietti's crystalline retinopathy following anti-vascular endothelial growth factor therapy: A case report.

    PubMed

    Hua, Rui; Chen, Kang; Hu, Yuedong; Wang, Xinling; Chen, Lei

    2015-11-01

    Choroidal neovascularization secondary to retinitis pigmentosa is rarely observed in clinical practice. The present study describes a case of atypical retinitis pigmentosa, crystalline retinal pigmentary degeneration, complicated by choroidal neovascularization (CNV) in a 26-year-old man presenting with blurred vision in the right eye. Heidelberg multimodality imaging was performed to achieve a confirmed diagnosis. Bevacizumab was injected once intravitreally. The 3-month follow-up included visualization of the lesion's regression with spectral domain optical coherence tomography (SD-OCT). However, at 3 months after the injection, the CNV reoccurred. To the best of our knowledge, this is the first time that a case of CNV secondary to retinitis pigmentosa, in which the diagnosis was confirmed via multimodality imaging and the therapeutic efficacy was evaluated by SD-OCT, has been reported in China.

  5. Blockage of PI3K/mTOR Pathways Inhibits Laser-Induced Choroidal Neovascularization and Improves Outcomes Relative to VEGF-A Suppression Alone.

    PubMed

    Ma, Jie; Sun, Yu; López, Francisco J; Adamson, Peter; Kurali, Edit; Lashkari, Kameran

    2016-06-01

    Choroidal neovascularization (CNV) is a major cause of visual loss with age-related macular degeneration (AMD). We evaluated whether blockade of phosphatidyl-inositol-3-kinase (PI3K) and the mammalian target of rapamycin (mTOR), by impairing VEGF-A and other growth factor receptors like platelet-derived growth factor (PDGF), would reduce laser-induced CNV in mice. Choroidal neovascularization lesions were induced in C57BL/6 mice. Two groups of mice received oral GSK2126458 (3 mg/kg) or vehicle for 14 days following laser, whereas three groups were treated with GSK2126458 (6 μg/eye), aflibercept (2 μL/eye), or vehicle intravitreally on days 0 and 7 after laser. Vascular leakage was measured by fluorescein angiography (FA) on day 14. Choroidal neovascularization membranes were evaluated on choroidal flat mounts following FITC-dextran perfusion, as well as ED1 and isolectin B4 (IB4) immunohistochemistry. Oral and intravitreal (IVT) GSK2126458 reduced leakage and area of CNV lesions. Greater probability of leaking lesions (∼60%; P < 0.05) was observed in both vehicle groups. Fluorescein isothiocyanate-dextran-labeled total CNV burden area (total lesion area/eye) was reduced ∼67% (P < 0.05) and 35% (P = 0.0528) after oral and IVT GSK2126458 administration. GSK2126458 treatment reduced lesion size by ∼80% (P < 0.05) and 50% (P < 0.05) for oral and IVT control groups. Aflibercept did not alter lesion size (∼27% reduction). Phosphatidyl-inositol-3-kinase/mTOR is involved in laser-induced CNV angiogenic processes. GSK2126458 effectively reduces CNV size and leakage. Choroidal neovascularization size following IVT GSK2126458 was smaller than after oral administration. Therefore, inhibition of PI3K/mTOR pathways may be more effective due to blockade of action of multiple growth factors.

  6. Low power vs standard power transpupillary thermotherapy in patients with age-related macular degeneration and subfoveal choroidal neovascularization ineligible for photodynamic therapy.

    PubMed

    Hogan, A C; Kilmartin, D J

    2006-06-01

    To assess the effect of standard power vs low power transpupillary thermotherapy (TTT) in patients with active subfoveal choroidal neovascularization secondary to age-related macular degeneration ineligible for photodynamic therapy (PDT) by original treatment of age-related macular degeneration with photodynamic therapy (TAP) study group recommendations. Retrospective review of 79 patients with active predominantly occult subfoveal choroidal neovascularization or predominantly classic subfoveal choroidal neovascularization but Snellen visual acuity <20/200. All patients were treated with TTT administered via a Mainster wide field fundus contact lens with a retinal power/diameter coefficient of 248 mW/mm in the standard power (n=27) and 181 mW/mm in the low power group (n=52). The primary outcome was stabilization (<1 Snellen line change) or improvement (two or more Snellen lines) in visual acuity. Clinical and fluorescein angiographic resolution of overlying exudation was documented. At 24 month follow-up, 17 patients (63%) in the standard power and 36 patients (69%) in the low power group achieved stable or improved vision. Improved vision (mean three lines) was observed in 22% of the standard power and 23% of the low power group. Overlying exudation was reduced clinically with minimal or no leakage on fluorescein angiogram in 85% of standard power and 90% of low power group. Subgroup analysis in the low power group demonstrated a visual benefit in patients with subfoveal lesions, which had any classic component. Low power TTT is as effective as standard power in stabilizing or improving vision and reducing overlying exudation in patients with active subfoveal choroidal neovascularization ineligible for PDT.

  7. Ocular haemodynamic changes after single treatment with photodynamic therapy assessed with non-invasive techniques.

    PubMed

    Maar, Noemi; Pemp, Berthold; Kircher, Karl; Luksch, Alexandra; Weigert, Günther; Polska, Elzbieta; Tittl, Michael; Stur, Michael; Schmetterer, Leopold

    2009-09-01

    To investigate in patients with neovascular age-related macular degeneration (ARMD) the changes in ocular perfusion caused by single treatment with photodynamic therapy (PDT) by different non-invasive methods; to evaluate correlations between relative changes of ocular haemodynamic parameters after PDT among each other and compared to morphological parameters; and to assess this in relation to early changes of visual acuity. 17 consecutive patients with subfoveal choroidal neovascularization (CNV) caused by ARMD scheduled for PDT without previous PDT treatment (four patients with predominantly classic CNV and 13 patients with occult CNV). best-corrected visual acuity (before PDT, 6 and 8 weeks after PDT), fundus photography, fluorescein angiography, haemodynamic measurements with laser Doppler flowmetry (LDF), laser interferometry and ocular blood flow (OBF) tonometry (baseline and 1, 2, 6 and 8 weeks after treatment). choroidal blood flow (CHBF), fundus pulsation amplitude (FPA), pulsatile ocular blood flow (POBF), visual acuity. Changes smaller than 20% were considered clinically irrelevant. Ocular haemodynamic parameters did not change significantly in the follow-up period. Changes of haemodynamic parameters showed no correlation to treatment spot, morphological changes or visual acuity. Changes of visual acuity were comparable to results of earlier studies. Single treatment with PDT did not modify ocular blood flow parameters above 20% as assessed with different non-invasive methods.

  8. Neovascular Glaucoma After Stereotactic Radiotherapy for Juxtapapillary Choroidal Melanoma: Histopathologic and Dosimetric Findings

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fernandes, Bruno F.; Weisbrod, Daniel; Yuecel, Yeni H.

    2011-06-01

    Purpose: Enucleation after stereotactic radiotherapy (SRT) for juxtapapillary choroidal melanoma may be required because of tumor progression (TP) or the development of intractable radiation-induced neovascular glaucoma (NVG). We compare pathologic changes and dosimetric findings in those eyes enucleated secondary to NVG as opposed to TP to better understand potential mechanisms. Methods and Materials: Patients with juxtapapillary choroidal melanoma treated with SRT (70 Gy in 5 fractions, alternate days over a total of 10 days) at the Princess Margaret Hospital, Toronto, Ontario, Canada, who underwent enucleation between 1998 and 2006 were selected. We correlated dosimetric data based on the patient's originalmore » SRT treatment plan with histopathologic findings in the retina, optic nerve head, and anterior chamber. A dedicated ocular pathologist reviewed each case in a blinded fashion. Results: Ten eyes in ten patients were enucleated after SRT. Six were enucleated secondary to NVG and four secondary to because of TP. Aggressive tumor features such as invasion of the sclera and epithelioid cell type were observed predominantly in the TP group. Retinal damage was more predominant in the NVG group, as were findings of radiation-related retinal vascular changes of fibrinoid necrosis and hyalinization. No conclusive radiation-related effects were found in the anterior chamber. The maximum point dose and dose to 0.1 cc were lower for the anterior chamber as compared with the dose to the tumor, retina, and optic nerve head. The mean 0.1-cc doses to the retina were 69.4 Gy and 73.5 Gy and to the anterior chamber were 4.9 Gy and 17.3 Gy for the NVG group and tumor progression group, respectively. Conclusions: Our findings suggest that NVG is due to radiation damage to the posterior chamber of the eye rather than primary radiation damage to the anterior segment.« less

  9. Quantification of choroidal neovascularization vessel length using optical coherence tomography angiography

    NASA Astrophysics Data System (ADS)

    Gao, Simon S.; Liu, Li; Bailey, Steven T.; Flaxel, Christina J.; Huang, David; Li, Dengwang; Jia, Yali

    2016-07-01

    Quantification of choroidal neovascularization (CNV) as visualized by optical coherence tomography angiography (OCTA) may have importance clinically when diagnosing or tracking disease. Here, we present an automated algorithm to quantify the vessel skeleton of CNV as vessel length. Initial segmentation of the CNV on en face angiograms was achieved using saliency-based detection and thresholding. A level set method was then used to refine vessel edges. Finally, a skeleton algorithm was applied to identify vessel centerlines. The algorithm was tested on nine OCTA scans from participants with CNV and comparisons of the algorithm's output to manual delineation showed good agreement.

  10. RECURRENCE OF CHOROIDAL NEOVASCULARIZATION LESION ACTIVITY AFTER AFLIBERCEPT TREATMENT FOR AGE-RELATED MACULAR DEGENERATION.

    PubMed

    Wakazono, Tomotaka; Yamashiro, Kenji; Oishi, Akio; Ooto, Sotaro; Tamura, Hiroshi; Akagi-Kurashige, Yumiko; Hata, Masayuki; Takahashi, Ayako; Tsujikawa, Akitaka; Yoshimura, Nagahisa

    2017-11-01

    To examine the recurrence rate of choroidal neovascularization (CNV) lesion activity in age-related macular degeneration (AMD) and associated factors after 1-year aflibercept treatment. Age-related macular degeneration eyes with 1-year aflibercept fixed-regimen treatment and a follow-up period of at least 18 months from the initial aflibercept injection for treatment-naive exudative AMD were retrospectively evaluated. The recurrence rate was examined. Age, gender, visual acuity, AMD subtype, greatest linear dimension, and retinal and choroidal thicknesses at the 12th month examination were compared between eyes with and without recurrence. Presence of remnant polyps and pigment epithelial detachment (PED) morphology were also compared in polypoidal choroidal vasculopathy (PCV) eyes. Of the 98 eyes studied, 69 displayed a dry macula at the 12th month examination; 43.7% exhibited recurrence during the subsequent 12-month period in Kaplan-Meier analysis. Although no factors associated with recurrence were detected in AMD, remnant polyps and pigment epithelial detachment morphology at the 12th month examination were significantly associated with recurrence in polypoidal choroidal vasculopathy (P = 0.018 and 0.048, respectively). Continuous, proactive treatment would be considered overtreatment for more than half of the AMD eyes that achieved a dry macula. Angiography and optical coherence tomography analyses may be useful for predicting recurrence in polypoidal choroidal vasculopathy eyes.

  11. Treatment of choroidal neovascularization in high myopia.

    PubMed

    Montero, Javier A; Ruiz-Moreno, Jose M

    2010-05-01

    High myopia affects approximately 2% of general population, and is a major cause of legal blindness in many developed countries. Choroidal neovascularization (CNV) is the most common vision-threatening complication of high myopia. Different therapeutic approaches have been attempted such as thermal laser photocoagulation, surgery and photodynamic therapy with verteporfin (PDT). The visual outcome of these therapies has been reported to be better than the natural history of the condition. However, the limited visual acuity improvement after PDT monotherapy and the appearance of subretinal fibrosis and chorioretinal atrophy prompted the association of other therapies. In the past few years a tremendous advance in the knowledge of the mechanisms underling CNV secondary to high myopia and age related macular degeneration has been achieved, leading to new therapeutic targets and novel drugs and combined therapies. These new therapeutic weapons have been designed to achieve a selective shut down of choroidal new vessels. Recent reviews have been published on the natural history and therapies for myopic CNV. Ohno-Matsui reported on the natural history of the condition as well as the outcome of laser photocoagulation, surgical extraction of CNV, foveal translocation and photodynamic therapy on myopic CNV in the short-term. Soubrane et al reviewed the new advances on surgery, laser photocoagulation and PDT, considering some of the potential effects of triamcinolone, pegaptanib and ranibizumab in CNV secondary to age related macular degeneration (AMD). Novack et al reported on the pharmacological therapy of CNV in AMD. The aim of this review is to summarize the recent advances in myopic CNV pathophysiology and the new therapeutic targets and drugs that are changing the clinical management of myopic CNV.

  12. Non-invasive measurement of choroidal volume change and ocular rigidity through automated segmentation of high-speed OCT imaging

    PubMed Central

    Beaton, L.; Mazzaferri, J.; Lalonde, F.; Hidalgo-Aguirre, M.; Descovich, D.; Lesk, M. R.; Costantino, S.

    2015-01-01

    We have developed a novel optical approach to determine pulsatile ocular volume changes using automated segmentation of the choroid, which, together with Dynamic Contour Tonometry (DCT) measurements of intraocular pressure (IOP), allows estimation of the ocular rigidity (OR) coefficient. Spectral Domain Optical Coherence Tomography (OCT) videos were acquired with Enhanced Depth Imaging (EDI) at 7Hz during ~50 seconds at the fundus. A novel segmentation algorithm based on graph search with an edge-probability weighting scheme was developed to measure choroidal thickness (CT) at each frame. Global ocular volume fluctuations were derived from frame-to-frame CT variations using an approximate eye model. Immediately after imaging, IOP and ocular pulse amplitude (OPA) were measured using DCT. OR was calculated from these peak pressure and volume changes. Our automated segmentation algorithm provides the first non-invasive method for determining ocular volume change due to pulsatile choroidal filling, and the estimation of the OR constant. Future applications of this method offer an important avenue to understanding the biomechanical basis of ocular pathophysiology. PMID:26137373

  13. Small laser spot versus standard laser spot photodynamic therapy for idiopathic choroidal neovascularization: a randomized controlled study.

    PubMed

    Li, Xiao-xin; Tao, Yong

    2012-12-01

    Idiopathic choroidal neovascularization (ICNV) affects young patients and thus may have a significant impact on vision and life quality over a patient's lifespan. This study was designed to compare the visual outcome and retinal pigment epithelium (RPE) damage after photodynamic therapy (PDT) with small laser spot and PDT with standard laser spot for idiopathic choroidal neovascularization (ICNV). This was a randomized controlled study. Fifty-two patients with ICNV were enrolled and randomly divided into a study group (small laser spot PDT, n = 27) and a control group (standard laser spot PDT, n = 25). Best corrected visual acuity (BCVA), optic coherence tomography (OCT) and fluorescein angiography (FA) findings were the main measurements. The patients were followed up 1 week, 1, 3, 6, 9 months and 1 year after PDT. BCVA improvement was statistically significantly higher in the study group than the control group at 6-month ((25.53 ± 15.01) letters vs. (14.71 ± 11.66) letters, P = 0.025) and 9-month follow-ups ((27.53 ± 17.78) letters vs. (15.59 ± 12.21) letters, P = 0.039). At 3- and 6-month follow-ups, the quadrants of RPE damage between the two groups varied significantly (P < 0.001 and P = 0.023, respectively). In each follow-up, the number of cases with decreased or unchanged leakage of choroidal neovascularization by FA and reduced subretinal fluid by OCT did not vary significantly between the two groups. Ten cases (37.0%) in the study group and eight cases (32.0%) in the control group suffered from recurrent CNV (P = 0.703). Better visual improvements, less RPE damage, a similar recurrent rate of CNV and change of subretinal fluid were observed in the small laser spot PDT group than in the standard laser spot PDT group for ICNV.

  14. Helicoid peripapillary chorioretinal degeneration complicated by choroidal neovascularization.

    PubMed

    Triantafylla, Magdalini; Panos, Georgios D; Dardabounis, Doukas; Nanos, Panagiotis; Konstantinidis, Aristeidis

    2016-02-15

    Helicoid peripapillary chorioretinal degeneration (HPCD) is a hereditary disease of the fundus that is characterized by atrophic chorioretinal areas that appear early in life and expand gradually from the optic disc towards the macula and the periphery. We describe the case of an elderly man with a known diagnosis of HPCD who developed choroidal neovascular membrane (CNV) in both eyes during the course of the disease. The patient was treated with intravitreal injection of ranibizumab, to which he had excellent response. The CNV subsided with 2 injections in the right eye and 1 in the left. Two years after the initial diagnosis of CNV in the right eye, visual acuity was 5/10 OD and 9/10 OS. Helicoid peripapillary chorioretinal degeneration is rarely complicated by CNV as the fundus lacks the trigger factors that would sustain this process. Although rare, HPCD complicated by CNV can be seen bilaterally, but responds well to few ranibizumab injections.

  15. [Choroidal neovascularization secondary to angioid streaks: A familial case report].

    PubMed

    Benitez-Herreros, J; Camara-Gonzalez, C; Lopez-Guajardo, L; Beckford-Torngren, C; Pareja-Esteban, J

    2014-05-01

    We report a familial case of 2 brothers that suffered choroidal neovascularization (CNV) secondary to angioid streaks. They were both treated with a monthly intravitreal injection of ranibizumab (Lucentis(®)) for 3 months. Visual acuity was stabilized and fluorescein angiography revealed complete resolution of CNV. Neither recurrent CNV lesion nor new hemorrhages were reported during the follow-up period. The use of intravitreal ranibizumab for the treatment of CNV in patients with angioid streaks has shown favorable results. However, further studies with a longer follow-up and larger number of patients are necessary to more precisely determine the results of this therapy. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  16. DETECTION OF NONEXUDATIVE CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION WITH OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

    PubMed

    Palejwala, Neal V; Jia, Yali; Gao, Simon S; Liu, Liang; Flaxel, Christina J; Hwang, Thomas S; Lauer, Andreas K; Wilson, David J; Huang, David; Bailey, Steven T

    2015-11-01

    To evaluate eyes with age-related macular degeneration and high-risk characteristics for choroidal neovascularization (CNV) with optical coherence tomographic (OCT) angiography to determine whether earlier detection of CNV is possible. Eyes with drusen, pigmentary changes, and with CNV in the fellow eye were scanned with a 70-kHz spectral domain OCT system (Optovue RTVue-XR Avanti). The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to distinguish blood flow from static tissue. Two masked graders reviewed scans for CNV, defined as flow in the outer retinal/sub-RPE slab. Choroidal neovascularization flow area repeatability and between-grader reproducibility were calculated. Of 32 eyes, 2 (6%) were found to have Type 1 CNV with OCT angiography. The lesions were not associated with leakage on fluorescein angiography or fluid on OCT. One case was followed for 8 months without treatment, and the CNV flow area enlarged slightly without fluid buildup on OCT or vision loss. Between-grader reproducibility of the CNV flow area was 9.4% (coefficient of variation) and within-visit repeatability was 5.2% (pooled coefficient of variation). Optical coherence tomographic angiography can detect the presence of nonexudative CNV, lesions difficult to identify with fluorescein angiography and OCT. Further study is needed to understand the significance and natural history of these lesions.

  17. T-cell differentiation and CD56+ levels in polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.

    PubMed

    Subhi, Yousif; Nielsen, Marie Krogh; Molbech, Christopher Rue; Oishi, Akio; Singh, Amardeep; Nissen, Mogens Holst; Sørensen, Torben Lykke

    2017-11-20

    Polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (AMD) are prevalent age-related diseases characterized by exudative changes in the macula. Although they share anatomical and clinical similarities, they are also distinctly characterized by their own features, e.g. vascular abnormalities in PCV and drusen-mediated progression in neovascular AMD. PCV remains etiologically uncharacterized, and ongoing discussion is whether PCV and neovascular AMD share the same etiology or constitute two substantially different diseases. In this study, we investigated T-cell differentiation and aging profile in human patients with PCV, patients with neovascular AMD, and age-matched healthy control individuals. Fresh venous blood was prepared for flow cytometry to investigate CD4 + and CD8 + T-cell differentiation (naïve, central memory, effector memory, effector memory CD45ra + ), loss of differentiation markers CD27 and CD28, and expression of aging marker CD56. Patients with PCV were similar to the healthy controls in all aspects. In patients with neovascular AMD we found significantly accelerated T-cell differentiation (more CD28 - CD27 - cells) and aging (more CD56 + cells) in the CD8 + T-cell compartment. These findings suggest that PCV and neovascular AMD are etiologically different in terms of T cell immunity, and that neovascular AMD is associated with T-cell immunosenescence.

  18. Inflammatory Mediators and Angiogenic Factors in Choroidal Neovascularization: Pathogenetic Interactions and Therapeutic Implications

    PubMed Central

    Campa, Claudio; Costagliola, Ciro; Incorvaia, Carlo; Sheridan, Carl; Semeraro, Francesco; De Nadai, Katia; Sebastiani, Adolfo; Parmeggiani, Francesco

    2010-01-01

    Choroidal neovascularization (CNV) is a common and severe complication in heterogeneous diseases affecting the posterior segment of the eye, the most frequent being represented by age-related macular degeneration. Although the term may suggest just a vascular pathological condition, CNV is more properly definable as an aberrant tissue invasion of endothelial and inflammatory cells, in which both angiogenesis and inflammation are involved. Experimental and clinical evidences show that vascular endothelial growth factor is a key signal in promoting angiogenesis. However, many other molecules, distinctive of the inflammatory response, act as neovascular activators in CNV. These include fibroblast growth factor, transforming growth factor, tumor necrosis factor, interleukins, and complement. This paper reviews the role of inflammatory mediators and angiogenic factors in the development of CNV, proposing pathogenetic assumptions of mutual interaction. As an extension of this concept, new therapeutic approaches geared to have an effect on both the vascular and the extravascular components of CNV are discussed. PMID:20871825

  19. PATTERNS OF FUNDUS AUTOFLUORESCENCE DEFECTS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION SUBTYPES.

    PubMed

    Ozkok, Ahmet; Sigford, Douglas K; Tezel, Tongalp H

    2016-11-01

    To test define characteristic fundus autofluorescence patterns of different exudative age-related macular degeneration subtypes. Cross-sectional study. Fifty-two patients with choroidal neovascularization because of three different neovascular age-related macular degeneration subtypes were included in the study. Macular and peripheral fundus autofluorescence patterns of study subjects were compared in a masked fashion. Fundus autofluorescence patterns of all three neovascular age-related macular degeneration subtypes revealed similar patterns. However, peripapillary hypo-autofluorescence was more common among patients with polypoidal choroidal vasculopathy (88.2%) compared with patients with retinal angiomatous proliferation (12.5%) and patients without retinal angiomatous proliferation and polypoidal choroidal vasculopathy (21.1%) (P < 0.0001). Presence of peripapillary fundus autofluorescence defects in neovascular age-related macular degeneration maybe suggestive of polypoidal choroidal vasculopathy as a variant of neovascular age-related macular degeneration.

  20. Molecular Pathogenesis of Retinal and Choroidal Vascular Diseases

    PubMed Central

    Campochiaro, Peter A.

    2015-01-01

    There are two major types of ocular neovascularization that affect the retina, retinal neovascularization (NV) and subretinal or choroidal NV. Retinal NV occurs in a group of diseases referred to as ischemic retinopathies in which damage to retinal vessels results in retinal ischemia. Most prevalent of these are diabetic retinopathy and retinal vein occlusions. Subretinal and choroidal NV occur in diseases of the outer retina and Bruch’s membrane, the most prevalent of which is age-related macular degeneration. Numerous studies in mouse models have helped to elucidate the molecular pathogenesis underlying retinal, subretinal, and choroidal NV. There is considerable overlap because the precipitating event in each is stabilization of hypoxia inducible factor-1 (HIF-1) which leads to upregulation of several hypoxia-regulated gene products, including vascular endothelial growth factor (VEGF), angiopoietin 2, vascular endothelial-protein tyrosine phosphatase (VE-PTP), and several others. Stimulation of VEGF signaling and suppression of Tie2 by angiopoietin 2 and VE-PTP are critical for sprouting of retinal, subretinal, and choroidal NV, with perturbation of Bruch’s membrane also needed for the latter. Additional HIF-1-regulated gene products cause further stimulation of the NV. It is difficult to model macular edema in animals and therefore proof-of-concept clinical trials were done and demonstrated that VEGF plays a central role and that suppression of Tie2 is also important. Neutralization of VEGF is currently the first line therapy for all of the above disease processes, but new treatments directed at some of the other molecular targets, particularly stabilization of Tie2, are likely to provide additional benefit for subretinal/choroidal NV and macular edema. In addition, the chronicity of these diseases as well as the implication of VEGF as a cause of retinal nonperfusion and progression of background diabetic retinopathy make sustained delivery approaches for

  1. Autologous transplantation of the retinal pigment epithelium and choroid in the treatment of neovascular age-related macular degeneration.

    PubMed

    MacLaren, Robert E; Uppal, Gurmit S; Balaggan, Kamaljit S; Tufail, Adnan; Munro, Peter M G; Milliken, Andrew B; Ali, Robin R; Rubin, Gary S; Aylward, G William; da Cruz, Lyndon

    2007-03-01

    To assess excision of choroidal new vessels (CNV) combined with autologous transplantation of the equatorial retinal pigment epithelium (RPE) as a means of restoring vision for patients with acute neovascular age-related macular degeneration (AMD). Prospective interventional cohort study. Twelve patients were recruited into an ethics committee approved trial with informed consent between 2004 and 2005. All had <6 months of acute visual loss owing to subfoveal neovascular AMD and were ineligible for photodynamic therapy. Patients underwent submacular removal of CNV through a single retinotomy. A full-thickness patch graft of RPE, Bruch's membrane, and choroid was harvested from the superior equatorial retina and transplanted into the subfoveal space. The graft was flattened under heavy liquid, before silicone oil exchange. Removal of silicone oil and cataract surgery were performed 3 months later. All patients underwent cataract grading, full refraction, optical coherence tomography, fundus autofluorescence, and fluorescein and indocyanine angiography preoperatively and again 6 months postoperatively. Retinal pigment epithelium samples from 3 patients were tested for ex vivo gene transfer using a recombinant lentiviral vector. Six months after surgery, successful transplantation was determined by the presence of a pigmented subfoveal graft showing RPE autofluorescence and choroidal reperfusion. Visual outcome was assessed by subjective refraction and microperimetry of the retina overlying the graft. Successful viable grafts were seen in 11 patients. Three patients had good visual function on the grafts, with mean logarithm of the minimum angle of resolution (logMAR) improving from 0.88 to 0.79 and maintained beyond 1 year. Operative complications occurred in 8 patients, including retinal detachment in 5 patients and hemorrhage affecting the graft in 4 patients. The mean visual acuity over the whole cohort fell from logMAR 0.82 to 1.16. The excised RPE choroid could

  2. Novel CCR3 Antagonists Are Effective Mono- and Combination Inhibitors of Choroidal Neovascular Growth and Vascular Permeability.

    PubMed

    Nagai, Nori; Ju, Meihua; Izumi-Nagai, Kanako; Robbie, Scott J; Bainbridge, James W; Gale, David C; Pierre, Esaie; Krauss, Achim H P; Adamson, Peter; Shima, David T; Ng, Yin-Shan

    2015-09-01

    Choroidal neovascularization (CNV) is a defining feature of wet age-related macular degeneration. We examined the functional role of CCR3 in the development of CNV in mice and primates. CCR3 was associated with spontaneous CNV lesions in the newly described JR5558 mice, whereas CCR3 ligands localized to CNV-associated macrophages and the retinal pigment epithelium/choroid complex. Intravitreal injection of neutralizing antibodies against vascular endothelial growth factor receptor 2, CCR3, CC chemokine ligand 11/eotaxin-1, and CC chemokine ligand 24/eotaxin-2 all reduced CNV area and lesion number in these mice. Systemic administration of the CCR3 antagonists GW766994X and GW782415X reduced spontaneous CNV in JR5558 mice and laser-induced CNV in mouse and primate models in a dose-dependent fashion. Combination treatment with antivascular endothelial growth factor receptor 2 antibody and GW766994X yielded additive reductions in CNV area and hyperpermeability in mice. Interestingly, topical GW766994X and intravitreal anti-CCR3 antibody yielded strong systemic effects, reducing CNV in the untreated, contralateral eye. Contrarily, ocular administration of GW782415X in primates failed to substantially elevate plasma drug levels or to reduce the development of grade IV CNV lesions. These findings suggest that CCR3 signaling may be an attractive therapeutic target for CNV, utilizing a pathway that is at least partly distinct from that of vascular endothelial growth factor receptor. The findings also demonstrate that systemic exposure to CCR3 antagonists may be crucial for CNV-targeted activity. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Anti-VEGF aptamer (pegaptanib) therapy for ocular vascular diseases.

    PubMed

    Ng, Eugene W M; Adamis, Anthony P

    2006-10-01

    Vascular endothelial growth factor (VEGF) is a central regulator of both physiological and pathological angiogenesis. Pegaptanib, a 28-nucleotide RNA aptamer specific for the VEGF(165) isoform, binds to it in the extracellular space, leaving other isoforms unaffected, and inhibits such key VEGF actions as promotion of endothelial cell proliferation and survival, and vascular permeability. Pegaptanib already has been examined as a treatment for two diseases associated with ocular neovascularization, age-related macular degeneration (AMD) and diabetic macular edema (DME). Preclinical studies have shown that VEGF(165) alone mediates pathological ocular neovascularization and that its inactivation by pegaptanib inhibits the choroidal neovascularization observed in patients with neovascular AMD. In contrast, physiological vascularization, which is supported by the VEGF(121) isoform, is unaffected by this inactivation of VEGF(165). In addition, animal model studies have shown that intravitreous injection of pegaptanib can inhibit the breakdown of the blood-retinal barrier characteristic of diabetes and even can reverse this damage to some degree. These preclinical findings formed the basis for randomized controlled trials examining the efficacy of pegaptanib as a therapy for AMD and DME. The VEGF Inhibition Study in Ocular Neovascularization (VISION) trial comprising two replicate, pivotal phase 3 studies, demonstrated that intravitreous injection of pegaptanib resulted in significant clinical benefit, compared with sham injection, for all prespecified clinical end points, irrespective of patient demographics or angiographic subtype, and led to pegaptanib's approval as a treatment for AMD. A phase 2 trial has provided support for the efficacy of intravitreous pegaptanib in the treatment of DME.

  4. Atypical Presentation of Ocular Toxoplasmosis: A Case Report of Exudative Retinal Detachment and Choroidal Ischemia.

    PubMed

    Al-Zahrani, Yahya A; Al-Dhibi, Hassan A; Al-Abdullah, Abdulelah A

    2016-01-01

    A 24-year-old healthy male presented with a chief complaint of blurred vision in the right eye for 1-week. Fundus examination indicated right exudative retinal detachment and choroidal ischemia. The patient responded well to anti-toxoplasmosis medications and steroids. Exudative retinal detachment and choroidal ischemia are atypical presentations of ocular toxoplasmosis. However, both conditions responded well to anti.parasitic therapy with steroid.

  5. Evolution of Choroidal Neovascular Membrane in Best Disease after Single Intravitreal Bevacizumab. Case Report.

    PubMed

    Celea, Christiana; Pop, Mihai; Avidis-Zamfiroiu, Nicoleta; Celea, Cristian

    2015-03-01

    Best's disease is a hereditary form of macular dystrophy that starts in childhood and progresses until visual symptoms occur. In evolution it can be complicated with choroidal neovascularization, condition very rare in children. We report an important visual improvement in a 8-year-old caucasian girl after successful treatment with one intravitreal bevacizumab injection. There are few cases reported in literature (1-7), and the patient presented here have important particularities: one of the youngest children ever-mentioned with this complication, the third-member of her family with this disease and the first patient who didn't receive a second intravitreal bevacizumab at six weeks after first treatment, even though BCVA was lower than expected. The girl accused decrease of vision in the RE for the past 3-4 months. BCVA at presentation was 1/10. After 6 weeks from the intravitreal treatment, BCVA improved, but not very satisfactory (5/10). Because fundus and OCT aspects were encouraging, we waited another 4 weeks before the second injection. BCVA doubled in this period (8/10). Visual acuity, fundus and OCT aspects stabilized for 18 months of follow-up. We note that choroidal neovascular membrane associated with Best's disease can appear at such young children, this fact being very important in the phase of diagnosis, when the clinician should also take in consideration this possibility. Another important idea underlined here is the long-term efficacy of a single intravitreal anti-VEGF injection and also the no-need for imminent, fast re-treatment when the fundus and OCT aspects are encouraging through the follow-up.

  6. Photodynamic therapy for polypoidal choroidal vasculopathy secondary to choroidal nevus.

    PubMed

    Wong, James G; Lai, Xin Jie; Sarafian, Richard Y; Wong, Hon Seng; Smith, Jeremy B

    2017-01-01

    We report a case of a Caucasian female who developed active polypoidal choroidal vasculopathy (PCV) at the edge of a stable choroidal nevus and was successfully treated with verteporfin photodynamic therapy. No active polyp was detectable on indocyanine green angiography 2 years after treatment, and good vision was maintained. Indocyanine green angiography is a useful investigation to diagnose PCV and may be underutilized. Unlike treatment of choroidal neovascularization secondary to choroidal nevus, management of PCV secondary to nevus may not require intravitreal anti-vascular endothelial growth factor therapy. Photodynamic monotherapy may be an effective treatment of secondary PCV.

  7. Diurnal variations in axial length, choroidal thickness, intraocular pressure, and ocular biometrics.

    PubMed

    Chakraborty, Ranjay; Read, Scott A; Collins, Michael J

    2011-07-11

    To investigate the pattern of diurnal variations in axial length (AL), choroidal thickness, intraocular pressure (IOP), and ocular biometrics over 2 consecutive days. Measurements of ocular biometrics and IOP were collected for 30 young adult subjects (15 myopes, 15 emmetropes) at 10 different times over 2 consecutive days. Five sets of measurements were collected each day at approximately 3-hour intervals, with the first measurement taken at ~9 AM and final measurement at ~9 PM. AL underwent significant diurnal variation (P < 0.0001) that was consistently observed across the 2 measurement days. The longest AL was typically observed at the second measurement session (mean time, 12:26) and the shortest AL at the final session of each day (mean time, 21:06). The mean diurnal change in AL was 0.032 ± 0.018 mm. Choroidal thickness underwent significant diurnal variation (mean change, 0.029 ± 0.016 mm; P < 0.001) and varied approximately in antiphase to the AL changes. Significant diurnal variations were also found in vitreous chamber depth (VCD; mean change, 0.06 ± 0.029 mm; P < 0.0001) and IOP (mean change, 3.54 ± 0.84 mm Hg; P < 0.0001). A positive association was found between the variations of AL and IOP (r(2) = 0.17, P < 0.0001) and AL and VCD (r(2) = 0.31, P < 0.0001) and a negative association between AL and choroidal thickness (r(2) = 0.13, P < 0.0001). There were no significant differences in the magnitude and timing of diurnal variations associated with refractive error. Significant diurnal variations in AL, choroidal thickness, and IOP were consistently observed over 2 consecutive days of testing.

  8. Ketorolac inhibits choroidal neovascularization by suppression of retinal VEGF

    PubMed Central

    Kim, Stephen J.; Toma, Hassanain S.; Barnett, Joshua M.; Penn, John S.

    2011-01-01

    We assessed the effect of topical ketorolac on laser-induced choroidal neovascularization (CNV), measured retinal PGE2 and VEGF levels after laser treatment, and determined the effect of ketorolac on PGE2 and VEGF production. Six laser burns were placed in eyes of rats which then received topical ketorolac 0.4% or artificial tears four times daily until sacrifice. Fluorescein angiography (FA) was performed at 2 and 3 weeks and retinal pigment epithelium-choroid-sclera flat mounts were prepared. The retina and vitreous were isolated at 1, 3, 5, 7, and 14 days after laser treatment and tested for VEGF and PGE2. Additional animals were lasered and treated with topical ketorolac or artificial tears and tested at 3 and 7 days for retinal and vitreous VEGF and PGE2. Ketorolac reduced CNV on FA by 27% at 2 weeks (P < 0.001) and 25% at 3 weeks (P < 0.001). Baseline retina and vitreous PGE2 levels were 29.4 μg/g and 16.5 μg/g respectively, and reached 51.2 μg/g and 26.9 μg/g respectively, 24 h after laser treatment (P < 0.05). Retinal VEGF level was 781 pg/g 24 h after laser treatment and reached 931 pg/g by 7 days (P < 0.01). Ketorolac reduced retinal PGE2 by 35% at 3 days (P < 0.05) and 29% at 7 days (P < 0.001) and retinal VEGF by 31% at 3 days (P = 0.10) and 19% at 7 days (P < 0.001). Topical ketorolac inhibited CNV and suppressed retinal PGE2 and VEGF production. PMID:20659449

  9. Molecular pathogenesis of retinal and choroidal vascular diseases.

    PubMed

    Campochiaro, Peter A

    2015-11-01

    There are two major types of ocular neovascularization that affect the retina, retinal neovascularization (NV) and subretinal or choroidal NV. Retinal NV occurs in a group of diseases referred to as ischemic retinopathies in which damage to retinal vessels results in retinal ischemia. Most prevalent of these are diabetic retinopathy and retinal vein occlusions. Subretinal and choroidal NV occur in diseases of the outer retina and Bruch's membrane, the most prevalent of which is age-related macular degeneration. Numerous studies in mouse models have helped to elucidate the molecular pathogenesis underlying retinal, subretinal, and choroidal NV. There is considerable overlap because the precipitating event in each is stabilization of hypoxia inducible factor-1 (HIF-1) which leads to upregulation of several hypoxia-regulated gene products, including vascular endothelial growth factor (VEGF), angiopoietin 2, vascular endothelial-protein tyrosine phosphatase (VE-PTP), and several others. Stimulation of VEGF signaling and suppression of Tie2 by angiopoietin 2 and VE-PTP are critical for sprouting of retinal, subretinal, and choroidal NV, with perturbation of Bruch's membrane also needed for the latter. Additional HIF-1-regulated gene products cause further stimulation of the NV. It is difficult to model macular edema in animals and therefore proof-of-concept clinical trials were done and demonstrated that VEGF plays a central role and that suppression of Tie2 is also important. Neutralization of VEGF is currently the first line therapy for all of the above disease processes, but new treatments directed at some of the other molecular targets, particularly stabilization of Tie2, are likely to provide additional benefit for subretinal/choroidal NV and macular edema. In addition, the chronicity of these diseases as well as the implication of VEGF as a cause of retinal nonperfusion and progression of background diabetic retinopathy make sustained delivery approaches for VEGF

  10. Selective Blockade of Cytoskeletal Actin Remodeling Reduces Experimental Choroidal Neovascularization

    PubMed Central

    Caballero, Sergio; Yang, Ru; Chaqour, Brahim

    2011-01-01

    Purpose. The efficacy of the peptide Ac-EEED on reducing cell adhesion and proliferation in vitro and choroidal neovascularization (CNV) in vivo was examined. Methods. The peptide chimera containing the Ac-EEED sequence was chemically linked to the N terminus of the XMTM delivery peptide from the Erns viral surface protein. Ac-EEED or scrambled control peptide (SCRAM) was added to cultures of vascular smooth muscle cells, pericytes, endothelial cells, and fibroblasts, and adhesion, growth, and matrix production was assessed. Ac-EEED or SCRAM was injected into the vitreous of mice undergoing laser rupture of Bruch's membrane to induce CNV and lesion volume, neovascularization and lesion fibrosis were assessed. Results. Ac-EEED–induced changes in the morphology of the actin cytoskeleton by inhibiting polymerization of G-actin and disrupting the formation of stress fibers. Pretreatment with Ac-EEED resulted in endothelial cells becoming less responsive to the mitogenic and pro-adhesive effects of VEGF. Ac-EEED treatment in fibroblasts reduced TGF-β–induced fibrosis as assessed by decreased levels of connective tissue growth factor, cysteine-rich 61, collagen I (COL1A2), and collagen III (COL3A1). CNV lesion size and fibrosis were reduced in a concentration-dependent manner by up to 60%. Conclusions. In vitro studies showed that Ac-EEED affects a broad range of mechanical properties associated with cytoskeletal actin to reduce growth factor effects. The utilization of Ac-EEED in vivo may offer a novel therapeutic strategy by both suppressed neovessel growth and curtailing fibrosis typically associated with the involutional stage of CNV. PMID:21178140

  11. Swept Source OCT Angiography of Neovascular Macular Telangiectasia Type 2

    PubMed Central

    Zhang, Qinqin; Wang, Ruikang K.; Chen, Chieh-Li; Legarreta, Andrew D.; Durbin, Mary K.; An, Lin; Sharma, Utkarsh; Stetson, Paul F.; Legarreta, John E.; Roisman, Luiz; Gregori, Giovanni; Rosenfeld, Philip J.

    2015-01-01

    Objective To image subretinal neovascularization in proliferative macular telangiectasia type 2 (MacTel2) using swept source optical coherence tomography based microangiography (OMAG). Study Design Patients with MacTel2 were enrolled in a prospective, observational study known as the MacTel Project and evaluated using a high-speed 1050nm swept-source OCT (SS-OCT) prototype system. The OMAG algorithm generated en face flow images from three retinal layers, as well as the region bounded by the outer retina and Bruch’s membrane, the choriocapillaris, and the remaining choroidal vasculature. The en face OMAG images were compared to images from fluorescein angiography (FA) and indocyanine green angiography (ICGA). Results Three eyes with neovascular MacTel2 were imaged. The neovascularization was best identified from the en face OMAG images that included a layer between the outer retinal boundary and Bruch’s membrane. OMAG images identified these abnormal vessels better than FA and were comparable to the images obtained using ICGA. In all three cases, OMAG identified choroidal vessels communicating with the neovascularization, and these choroidal vessels were evident in the two cases with ICGA imaging. In one case, monthly injections of bevacizumab reduced the microvascular complexity of the neovascularization, as well as the telangiectatic changes within the retinal microvasculature. In another case, less frequent bevacizumab therapy was associated with growth of the subretinal neovascular complex. Conclusions OMAG imaging provided detailed, depth-resolved information about subretinal neovascularization in MacTel2 eyes demonstrating superiority to FA imaging and similarities to ICGA imaging for documenting the retinal microvascular changes, the size and extent of the neovascular complex, the communications between the neovascular complex and the choroidal circulation, and the response to monthly bevacizumab therapy. PMID:26457402

  12. Effects of Human Recombinant PEDF Protein and PEDF-Derived Peptide 34-mer on Choroidal Neovascularization

    PubMed Central

    Amaral, Juan

    2010-01-01

    Purpose. Pigment epithelium-derived factor (PEDF) is a serpin with antiangiogenic properties. Previously, the authors showed that PEDF injected into the subconjunctiva reaches the choroid. Here, they examined the effects of PEDF polypeptide fragments on vessel sprouting and on choroidal neovascularization (CNV) after subconjunctival administration. Methods. Recombinant human PEDF (rhuPEDF) was cleaved at its serpin-exposed loop by limited chymotrypsin proteolysis. Synthetic PEDF peptides 34-mer (Asp44-Asn77) and 44-mer (Val78-Thr121) were used. Ex vivo chick aortic vessel sprouting assays were performed. CNV was induced in rats by laser injury of Bruch's membrane. Daily subconjunctival injections (0.01–10 pmol/d protein) were performed for 5 days starting at day of injury or at the seventh day after injury. New vessel volumes were quantified using optical sections of choroid/RPE flat-mounts labeled with isolectin-Ib4. PEDF distribution was evaluated by immunofluorescence of choroid/RPE/retina cross-sections. Results. Full-length rhuPEDF, cleaved rhuPEDF, or peptide 34-mer exhibited ex vivo antiangiogenic activity, but peptide 44-mer was inefficient. PEDF immunostaining around CNV lesions diminished after laser injury. Subconjunctival administration of rhuPEDF or 34-mer at 0.1 pmol/d decreased CNV lesion volumes by 52% and 47%, respectively, whereas those of 44-mer were similar to vehicle injections. Doses of 0.1 and 1 pmol/d rhuPEDF decreased fully developed CNV complex volumes by 45% and 50%, respectively, compared with vehicle injections. Conclusions. A functional region for the inhibition of vessel sprouting and CNV resides within the 34-mer region of PEDF. Furthermore, subconjunctival administration of optimal range dosages of rhuPEDF or 34-mer can suppress and regress rat CNV lesions, demonstrating that these agents reach the choroid/RPE complex as functionally active molecules. PMID:19850839

  13. [Choroidal neovascularization followed in a patient with "Multiple Evanescent White Dot Syndrome" (MEWDS) -- a case report].

    PubMed

    Löw, U; Palmowski, A M; Weich, C-M; Ruprecht, K W

    2004-12-01

    Since the description of the "multiple evanescent white dot syndrome" (MEWDS) by Jampol et al, choroiditis has been in the focus of interest. But the classical type of MEWDS was an exceptional case in clinical routine. A 48-year-old female presented to our hospital with a sudden unilateral visual acuity decrease and an extension of the blind spot. Ophthalmoscopy and fluorescein angiography revealed typical multiple grey-white chorioretinal patches of the same stage with lesion areas of about 100 - 200 microm compatible with the diagnose of MEWDS. Although visual acuity increased continuously the patient developed a classical choroidal neovascularization within 4 weeks. She was treated with PDT and visual acuity as well as the ophthalmoscopic diagnosis remained stable. In spite of visual improvement in MEWDS, regular control is recommended. In addition we propose to consider the diagnosis of MEWDS if an enlargement of the blind spot and CNV without lesions of the retinal pigment epithelium are diagnosed.

  14. Toll-like receptor 3 polymorphism rs3775291 is not associated with choroidal neovascularization or polypoidal choroidal vasculopathy in Chinese subjects.

    PubMed

    Sng, Chelvin C A; Cackett, Peter D; Yeo, Ian Y; Thalamuthu, Anbupalam; Venkatraman, Anandalakshmi; Venkataraman, Divya; Koh, Adrian H; Tai, E-Shyong; Wong, Tien Y; Aung, Tin; Vithana, Eranga N

    2011-01-01

    Age-related macular degeneration (AMD) is a leading cause of visual impairment. A single-nucleotide polymorphism (SNP; rs3775291) in the Toll-like receptor 3 (TLR3) gene has recently been implicated in the pathogenesis of AMD in Caucasian populations. The aim of this study was to examine this association in Chinese persons with choroidal neovascularization (CNV) secondary to AMD and polypoidal choroidal vasculopathy (PCV). This was an observational cross-sectional study in Singapore. Study subjects were of Chinese ethnicity and included patients with exudative maculopathy and normal control subjects. The diagnoses of CNV and PCV were made based on fundus examination, fluorescein angiography and indocyanine green angiography findings. Genomic DNA was extracted, and genotypes were determined by bidirectional DNA sequencing. We compared the allele and genotype frequencies between subjects with CNV and PCV with controls using the software PLINK. A total of 246 subjects with exudative maculopathy (consisting of 126 with CNV and 120 with PCV) and 274 normal control subjects were recruited. The distribution of rs3775291 SNP genotypes for CNV and PCV was not significantly different from that for normal controls. This study indicates that the TLR3 rs3775291 gene polymorphism is not associated with CNV and PCV in Singaporean Chinese patients. Copyright © 2010 S. Karger AG, Basel.

  15. Mobile Laser Indirect Ophthalmoscope: For the Induction of Choroidal Neovascularization in a Mouse Model.

    PubMed

    Weinberger, Dov; Bor-Shavit, Elite; Barliya, Tilda; Dahbash, Mor; Kinrot, Opher; Gaton, Dan D; Nisgav, Yael; Livnat, Tami

    2017-11-01

    This study aims to evaluate and standardize the reliability of a mobile laser indirect ophthalmoscope in the induction of choroidal neovascularization (CNV) in a mouse model. A diode laser indirect ophthalmoscope was used to induce CNV in pigmented male C57BL/6J mice. Standardization of spot size and laser intensity was determined using different aspheric lenses with increasing laser intensities applied around the optic disc. Development of CNV was evaluated 1, 5, and 14 days post laser application using fluorescein angiography (FA), histology, and choroidal flat mounts stained for the endothelial marker CD31 and FITC-dextran. Correlation between the number of laser hits to the number and size of developed CNV lesions was determined using flat mount choroid staining. The ability of intravitreally injected anti-human and anti-mouse VEGF antibodies to inhibit CNV induced by the mobile laser was evaluated. Laser parameters were standardized on 350 mW for 100 msec, using the 90 diopter lens to accomplish the highest incidence of Bruch's membrane rupture. CNV lesions' formation was validated on days 5 and 14 post laser injury, though FA showed leakage on as early as day 1. The number of laser hits was significantly correlated with the CNV area. CNV growth was successfully inhibited by both anti-human and mouse VEGF antibodies. The mobile laser indirect ophthalmoscope can serve as a feasible and a reliable alternative method for the CNV induction in a mouse model.

  16. Clinical manifestations of ocular toxoplasmosis.

    PubMed

    Delair, Emmanuelle; Latkany, Paul; Noble, A Gwendolyn; Rabiah, Peter; McLeod, Rima; Brézin, Antoine

    2011-04-01

    Clinical manifestations of ocular toxoplasmosis are reviewed. Findings of congenital and acute acquired ocular toxoplasmosis include retinal scars, white-appearing lesions in the active phase often associated with vitritis. Complications can include fibrous bands, secondary serous or rhegmatogenous retinal detachments, optic neuritis and neuropathy, cataracts, increased intraocular pressure during active infection, and choroidal neovascular membranes. Recurrences in untreated congenital toxoplasmosis occur in teenage years. Manifestations at birth are less severe, and recurrences are fewer in those who were treated promptly early in the course of their disease in utero and in the first year of life. Severe retinal involvement is common at diagnosis of symptomatic congenital toxoplasmosis in the United States and Brazil. Acute acquired infections also may be complicated by toxoplasmic retinochoroiditis, with recurrences most common close to the time of acquisition. Suppressive treatment can reduce recurrent disease.

  17. Preferential Hyperacuity Perimeter (PreView PHP) for detecting choroidal neovascularization study.

    PubMed

    Alster, Yair; Bressler, Neil M; Bressler, Susan B; Brimacombe, Judith A; Crompton, R Michael; Duh, Yi-Jing; Gabel, Veit-Peter; Heier, Jeffrey S; Ip, Michael S; Loewenstein, Anat; Packo, Kirk H; Stur, Michael; Toaff, Techiya

    2005-10-01

    To assess the ability of the Preferential Hyperacuity Perimeter (PreView PHP; Carl Zeiss Meditec, Dublin, CA) to detect recent-onset choroidal neovascularization (CNV) resulting from age-related macular degeneration (AMD) and to differentiate it from an intermediate stage of AMD. Prospective, comparative, concurrent, nonrandomized, multicenter study. Eligible participants' study eyes had a corrected visual acuity of 20/160 or better and either untreated CNV from AMD diagnosed within the last 60 days or an intermediate stage of AMD. After obtaining consent, visual acuity with habitual correction, masked PHP testing, stereoscopic color fundus photography, and fluorescein angiography were performed. Photographs and angiograms were evaluated by graders masked to diagnosis and PHP results. The reading center's diagnosis determined if the patient was categorized as having intermediate AMD or neovascular AMD. A successful study outcome was defined a priori as a sensitivity of at least 80% and a specificity of at least 80%. Of 185 patients who gave consent to be enrolled, 11 (6%) had PHP results judged to be unreliable. An additional 52 were not included because they did not meet all eligibility criteria. Of the remaining 122 patients, 57 had an intermediate stage of AMD and 65 had neovascular AMD. The sensitivity to detect newly diagnosed CNV using PHP testing was 82% (95% confidence interval [CI], 70%-90%). The specificity to differentiate newly diagnosed CNV from the intermediate stage of AMD using PHP testing was 88% (95% CI, 76%-95%). Preferential Hyperacuity Perimeter testing can detect recent-onset CNV resulting from AMD and can differentiate it from an intermediate stage of AMD with high sensitivity and specificity. These data suggest that monitoring with PHP should detect most cases of CNV of recent onset with few false-positive results at a stage when treatment usually would be beneficial. Thus, this monitoring should be considered in the management of the

  18. Pegaptanib: choroidal neovascularization in patients with age-related macular degeneration and previous arterial thromboembolic events.

    PubMed

    Battaglia Parodi, Maurizio; Di Bartolo, Emanuele; Brue, Claudia; Cappello, Ezio; Furino, Claudio; Giuffrida, Sebastiano; Imparato, Manuela; Reibaldi, Michele

    2018-01-01

    To evaluate the efficacy and the rate of side effects of the pegylated aptamer pegaptanib in the treatment of patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) and a history of previous arterial thromboembolic events (ATEs). Twenty-three eyes of 23 patients with subfoveal CNV due to AMD and cerebrovascular accidents (n = 12) and myocardial infarction (n = 11) in the previous 6 months received intravitreal pegaptanib 0.3 mg according to a pro re nata regimen and were followed for 12 months. The paired Student t test was used to evaluate mean changes in best-corrected visual acuity (BCVA; primary outcome measure) and central foveal thickness (CFT). The mean patient age was 71.5 ± 4.6 years; there were 14 women and 9 men. The CNV was type 1, 2, and 3 in 18, 3, and 2 eyes, respectively. The mean BCVA improved from 0.67 ± 0.23 logMAR at baseline to 0.52 ± 0.31 logMAR at the end of 12-month follow-up (p = 0.044). Thirty-five percent of patients achieved ≥3 Early Treatment Diabetic Retinopathy Study lines improvement at 12 months. Mean CFT at baseline (381 ± 111 µm) decreased to 304 ± 82 µm at 12 months (p = 0.008). Patients received a mean of 4.3 ± 1.3 (range 3-7) injections. No systemic or ocular side effects occurred; no patient experienced further ATEs. Intravitreal pegaptanib can be considered a viable treatment option for patients with AMD-related CNV who are at high risk of ATEs.

  19. Nonrigid registration of 3D longitudinal optical coherence tomography volumes with choroidal neovascularization

    NASA Astrophysics Data System (ADS)

    Wei, Qiangding; Shi, Fei; Zhu, Weifang; Xiang, Dehui; Chen, Haoyu; Chen, Xinjian

    2017-02-01

    In this paper, we propose a 3D registration method for retinal optical coherence tomography (OCT) volumes. The proposed method consists of five main steps: First, a projection image of the 3D OCT scan is created. Second, the vessel enhancement filter is applied on the projection image to detect vessel shadow. Third, landmark points are extracted based on both vessel positions and layer information. Fourth, the coherent point drift method is used to align retinal OCT volumes. Finally, a nonrigid B-spline-based registration method is applied to find the optimal transform to match the data. We applied this registration method on 15 3D OCT scans of patients with Choroidal Neovascularization (CNV). The Dice coefficients (DSC) between layers are greatly improved after applying the nonrigid registration.

  20. Nanocarriers for treatment of ocular neovascularization in the back of the eye: new vehicles for ophthalmic drug delivery.

    PubMed

    Shen, Hsin-Hui; Chan, Elsa C; Lee, Jia Hui; Bee, Youn-Shen; Lin, Tsung-Wu; Dusting, Gregory J; Liu, Guei-Sheung

    2015-01-01

    Pathologic neovascularization of the retina is a major cause of substantial and irreversible loss of vision. Drugs are difficult to deliver to the lesions in the back of the eye and this is a major obstacle for the therapeutics. Current pharmacological approach involves an intravitreal injection of anti-VEGF agents to prevent aberrant growth of blood vessels, but it has limitations including therapeutic efficacy and side-effects associated with systemic exposure and invasive surgery. Nanotechnology provides novel opportunities to overcome the limitations of conventional delivery system to reach the back of the eye through fabrication of nanostructures capable of encapsulating and delivering small molecules. This review article introduces various forms of nanocarrier that can be adopted by ocular drug delivery systems to improve current therapy. The application of nanotechnology in medicine brings new hope for ocular drug delivery in the back of the eye to manage the major causes of blindness associated with ocular neovascularization.

  1. Inhibition of VEGF secretion and experimental choroidal neovascularization by picropodophyllin (PPP), an inhibitor of the insulin-like growth factor-1 receptor.

    PubMed

    Economou, Mario A; Wu, Jiangmei; Vasilcanu, Daiana; Rosengren, Linda; All-Ericsson, Charlotta; van der Ploeg, Ingeborg; Menu, Eline; Girnita, Leonard; Axelson, Magnus; Larsson, Olle; Seregard, Stefan; Kvanta, Anders

    2008-11-01

    Choroidal neovascularization (CNV) is a debilitating complication of age-related macular degeneration (AMD) and a leading cause of vision loss. Along with other angiogenic factors like vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF-1) and its receptor, IGF-1R, have been implicated in CNV. We have previously shown that the cyclolignan picropodophyllin (PPP) efficiently blocks the insulin-like growth factor-1 receptor (IGF-1R) activity and causes cell death in uveal melanoma cell lines and in an in-vivo model. In this study we investigated the effect of PPP on VEGF expression both in vitro and in vivo and whether this effect has anti-angiogenic consequences in a murine CNV model. C57BL/6J mice with laser-induced CNVs were treated with PPP. Effects on CNV area were assayed by image analysis. VEGF levels in choroids and retinal pigment epithelial cells (APRE-19) were measured by Western blot or ELISA. Transcriptional activation of the VEGF promoter was determined by luciferase reporter gene assay. Mice treated with PPP, administered intraperitoneally or orally, showed 22-32% (p = 0.002) decrease in CNV area. Furthermore, VEGF levels in the choroids were significantly reduced. In cultured APRE-19 cells, IGF-1 was shown to increase VEGF secretion. This increase was completely blocked by PPP. We could confirm that PPP reduced the level of transcriptional activity of VEGF promoter. PPP reduces IGF-1 dependent VEGF expression and CNV in vivo. Accordingly, IGF-1R inhibitors may be useful tools in the therapy of conditions associated with CNV including neovascular AMD.

  2. Inhibition of VEGF secretion and experimental choroidal neovascularization by picropodophyllin (PPP), an inhibitor of the insulin-like growth factor-1 receptor.

    PubMed

    Economou, Mario A; Wu, Jiangmei; Vasilcanu, Daiana; Rosengren, Linda; All-Ericsson, Charlotta; van der Ploeg, Ingeborg; Menu, Eline; Girnita, Leonard; Axelson, Magnus; Larsson, Olle; Seregard, Stefan; Kvanta, Anders

    2008-06-01

    Choroidal neovascularization (CNV) is a debilitating complication of age-related macular degeneration (AMD) and a leading cause of vision loss. Along with other angiogenic factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF)-1 and its receptor, IGF-1R, have been implicated in CNV. A prior study has shown that the cyclolignan picropodophyllin (PPP) efficiently blocks the insulin-like growth factor-1 receptor (IGF-1R) activity and causes cell death in uveal melanoma cell lines and in an in vivo model. In this study we investigated the effect of PPP on VEGF expression, both in vitro and in vivo, and whether this effect has antiangiogenic consequences in a murine CNV model. C57BL/6J mice with laser-induced CNVs were treated with PPP. Effects on CNV area were assayed by image analysis. VEGF levels in the choroid and retinal pigment epithelial cells (ARPE-19) were measured by Western blot or ELISA. Transcriptional activation of the VEGF promoter was determined by luciferase reporter gene assay. Mice treated with PPP, administered intraperitoneally or orally, showed a 22% to 32% (P = 0.002) decrease in CNV area. Furthermore, VEGF levels in the choroid were significantly reduced. In cultured ARPE-19 cells, IGF-1 was shown to increase VEGF secretion. This increase was completely blocked by PPP. PPP reduced the level of transcriptional activity of the VEGF promoter. PPP reduces IGF-1-dependent VEGF expression and CNV in vivo. Accordingly, IGF-1R inhibitors may be useful tools in the treatment of conditions associated with CNV, including neovascular AMD.

  3. IL-18 attenuates experimental choroidal neovascularization as a potential therapy for wet age-related macular degeneration.

    PubMed

    Doyle, Sarah L; Ozaki, Ema; Brennan, Kiva; Humphries, Marian M; Mulfaul, Kelly; Keaney, James; Kenna, Paul F; Maminishkis, Arvydas; Kiang, Anna-Sophia; Saunders, Sean P; Hams, Emily; Lavelle, Ed C; Gardiner, Clair; Fallon, Padraic G; Adamson, Peter; Humphries, Peter; Campbell, Matthew

    2014-04-02

    Age-related macular degeneration (AMD) is the most common form of central retinal blindness globally. Distinct processes of the innate immune system, specifically activation of the NLRP3 inflammasome, have been shown to play a central role in the development of both "dry" and neovascular ("wet") forms of the disease. We show that the inflammatory cytokine interleukin-18 (IL-18) can regulate choroidal neovascularization formation in mice. We observed that exogenous administration of mature recombinant IL-18 has no effect on retinal pigment epithelial (RPE) cell viability, but that overexpression of pro-IL-18 or pro-IL-1β alone can cause RPE cell swelling and subsequent atrophy, a process that can be inhibited by the promotion of autophagy. A direct comparison of local and systemic administration of mature recombinant IL-18 with current anti-VEGF (vascular endothelial growth factor)-based therapeutic strategies shows that IL-18 treatment works effectively alone and more effectively in combination with anti-VEGF therapy and represents a novel therapeutic strategy for the treatment of wet AMD.

  4. Intravitreal Bevacizumab vs.Combination Therapy for CNV Due to Other Than AMD

    ClinicalTrials.gov

    2014-01-13

    Choroidal Neovascularization; Myopia; Punctate Inner Choroidopathy (PIC); Multifocal Choroiditis; Ocular Histoplasmosis Syndrome; Central Serous Chorioretinopathy (CSC); Angioid Streaks; Trauma, or Hereditary Eye Diseases

  5. Intravenous Bevacizumab Causes Regression of Choroidal Neovascularization Secondary to Diseases Other Than Age-related Macular Degeneration

    PubMed Central

    NGUYEN, QUAN DONG; SHAH, SYED MAHMOOD; HAFIZ, GULNAR; DO, DIANA V.; HALLER, JULIA A.; PILI, ROBERTO; ZIMMER-GALLER, INGRID E.; JANJUA, KASHIF; SYMONS, R. C. ANDREW; CAMPOCHIARO, PETER A.

    2016-01-01

    PURPOSE To investigate the safety, tolerability, and bioactivity of intravenous infusions of bevacizumab in patients with choroidal neovascularization (CNV) attributable to causes other than age-related macular degeneration. DESIGN Nonrandomized clinical trial. METHODS Ten patients with CNV received infusions of 5 mg/kg of bevacizumab. The primary efficacy outcome measure was change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study letters read at 4 meters) at 24 weeks and secondary measures were changes from baseline in excess foveal thickness (center subfield thickness), area of fluorescein leakage, and area of CNV. RESULTS Infusions were well tolerated and there were no ocular or systemic adverse events. At baseline, median VA was 25.5 letters read at 4 meters (20/80) and median foveal thickness was 346 μm. At the primary endpoint (24 weeks), median VA was 48.5 letters (20/32), representing four lines of improvement from baseline (P = .005), median foveal thickness was 248 μm representing a 72% reduction in excess foveal thickness (P = .007). Four of nine patients had complete elimination of fluorescein leakage, three had near complete elimination (reductions of 91%, 88%, and 87%), two had modest reductions, and one had no reduction. All patients except one showed a reduction in area of CNV with a median reduction of 43%. CONCLUSIONS Despite the small number of patients studied, the marked improvement in VA accompanied by prominent reductions in foveal thickness, fluorescein leakage, and area of CNV suggest a beneficial effect. It may be worthwhile to consider further evaluation of systemic bevacizumab in young patients with CNV. PMID:18054887

  6. DETECTION OF TYPE 1 CHOROIDAL NEOVASCULAR MEMBRANES USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN TUBERCULAR POSTERIOR UVEITIS.

    PubMed

    Aggarwal, Kanika; Agarwal, Aniruddha; Sharma, Aman; Sharma, Kusum; Gupta, Vishali

    2018-04-23

    To study optical coherence tomography angiography (OCTA) and multimodal imaging features of Type 1 inflammatory choroidal neovascularization (CNV) in tubercular serpiginous-like choroiditis and response to anti-vascular endothelial growth factor therapy. In this study, multimodal imaging was performed using OCTA, enhanced-depth imaging optical coherence tomography, fluorescein angiography, and indocyanine green angiography. Correlation of OCTA with other imaging modalities in the detection of CNV was performed. The changes in CNV configuration after anti-vascular endothelial growth factor therapy were assessed. In this study, nine eyes (8 patients; 5 females; mean age: 32.5 ± 11.57 years) with diagnosis of tubercular serpiginous-like choroiditis were included. All the eyes had presence of low-lying pigment epithelial detachments on enhanced-depth imaging optical coherence tomography. Using OCTA, it was possible to detect Type 1 CNV in all eyes. Type 1 CNV networks comprised fine anastomotic network of vessels, some of which had a hairpin loop configuration. After anti-vascular endothelial growth factor therapy, there was a decrease in branching and anastomosis. The visual acuity significantly improved from 0.49 ± 0.26 (20/60 Snellen equivalent) at baseline to 0.26 ± 0.17 (20/36 Snellen equivalent) (P = 0.03) in all eyes. Type 1 CNV can occur among patients with tubercular serpiginous-like choroiditis, leading to significant visual loss even in the healed stages of the disease. Optical coherence tomography angiography can help in the detection of Type 1 CNV where conventional multimodal imaging, including fluorescein angiography and OCT, fails to make a definitive diagnosis and thereby guide the initiation of anti-vascular endothelial growth factor therapy.

  7. Effects of ranibizumab in patients with subfoveal choroidal neovascularization attributable to age-related macular degeneration.

    PubMed

    Rothenbuehler, Simon P; Waeber, David; Brinkmann, Christian K; Wolf, Sebastian; Wolf-Schnurrbusch, Ute E K

    2009-05-01

    To demonstrate not only prevention of vision loss but also improvement in best-corrected visual acuity (BCVA) after treatment with ranibizumab on a variable-dosing regimen over 24 months in patients with age-related macular degeneration (AMD). Interventional case series. Institutional. One hundred and thirty-eight eyes of 138 patients treated intravitreally with 0.5 mg ranibizumab (Lucentis; Novartis, Basel, Switzerland). Age above 50 years, BCVA 0.2 to 1.2 logarithm of the minimal angle of resolution (logMAR), primary or recurrent subfoveal choroidal neovascularization (CNV) secondary to AMD. After single initial treatment, monthly follow-up examination. Retreatment in case of one of the following: sign of subretinal fluid or intraretinal edema, increase in central retinal thickness (CRT) on optical coherence tomography (OCT), active CNV on fluorescein angiography, increase of metamorphopsia, and loss of BCVA > 5 letters on Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Compared with baseline: proportion of eyes gaining > or = 15 letters, proportion of eyes losing or gaining < 15 letters, change in CRT. After 24 months, 30% of eyes gained > or = 15 letters. After 24 months, 55% of eyes lost or gained < 15 letters. Mean CRT of 386 +/- 145 microm at baseline was significantly reduced to 211 +/- 39 microm after 24 months (P = .036). Mean injection number per patient was 5.6 +/- 2.9 and 4.3 +/- 3.8 from baseline to month 12 and month 12 to 24, respectively. Intravitreal ranibizumab on a variable-dosing regimen was effective in significantly increasing mean BVCA and reducing CRT. This beneficial outcome was achieved with a low-rate of mild ocular adverse effects among our patients.

  8. In vivo retinal and choroidal hypoxia imaging using a novel activatable hypoxia-selective near-infrared fluorescent probe.

    PubMed

    Fukuda, Shinichi; Okuda, Kensuke; Kishino, Genichiro; Hoshi, Sujin; Kawano, Itsuki; Fukuda, Masahiro; Yamashita, Toshiharu; Beheregaray, Simone; Nagano, Masumi; Ohneda, Osamu; Nagasawa, Hideko; Oshika, Tetsuro

    2016-12-01

    Retinal hypoxia plays a crucial role in ocular neovascular diseases, such as diabetic retinopathy, retinopathy of prematurity, and retinal vascular occlusion. Fluorescein angiography is useful for identifying the hypoxia extent by detecting non-perfusion areas or neovascularization, but its ability to detect early stages of hypoxia is limited. Recently, in vivo fluorescent probes for detecting hypoxia have been developed; however, these have not been extensively applied in ophthalmology. We evaluated whether a novel donor-excited photo-induced electron transfer (d-PeT) system based on an activatable hypoxia-selective near-infrared fluorescent (NIRF) probe (GPU-327) responds to both mild and severe hypoxia in various ocular ischemic diseases animal models. The ocular fundus examination offers unique opportunities for direct observation of the retina through the transparent cornea and lens. After injection of GPU-327 in various ocular hypoxic diseases of mouse and rabbit models, NIRF imaging in the ocular fundus can be performed noninvasively and easily by using commercially available fundus cameras. To investigate the safety of GPU-327, electroretinograms were also recorded after GPU-327 and PBS injection. Fluorescence of GPU-327 increased under mild hypoxic conditions in vitro. GPU-327 also yielded excellent signal-to-noise ratio without washing out in vivo experiments. By using near-infrared region, GPU-327 enables imaging of deeper ischemia, such as choroidal circulation. Additionally, from an electroretinogram, GPU-327 did not cause neurotoxicity. GPU-327 identified hypoxic area both in vivo and in vitro.

  9. Homoisoflavonoids as potential antiangiogenic agents for retinal neovascularization.

    PubMed

    Amin, Sk Abdul; Adhikari, Nilanjan; Gayen, Shovanlal; Jha, Tarun

    2017-11-01

    A number of people worldwide have been suffering from ocular neovascularization that may be treated by a variety of drugs but these may possess adverse effects. Therefore, small antiangiogenic molecules with higher potency and lower toxic effects are intended. However, homoisoflavonoids of natural origin show the potential antiangiogenic effect in ocular neovascularization. These homoisoflavonoids are judged quantitatively in terms of statistical validation through multi-chemometric modeling approaches for the betterment and refinement of their structures required for higher antiangiogenic activity targeted to ocular neovascularization. These approaches may be utilized to design better antiangiogenic homoisoflavonoids. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  10. CRISPR-LbCpf1 prevents choroidal neovascularization in a mouse model of age-related macular degeneration.

    PubMed

    Koo, Taeyoung; Park, Sung Wook; Jo, Dong Hyun; Kim, Daesik; Kim, Jin Hyoung; Cho, Hee-Yeon; Kim, Jeungeun; Kim, Jeong Hun; Kim, Jin-Soo

    2018-05-10

    LbCpf1, derived from Lachnospiraceae bacterium ND2006, is a CRISPR RNA-guided endonuclease and holds promise for therapeutic applications. Here we show that LbCpf1 can be used for therapeutic gene editing in a mouse model of age-related macular degeneration (AMD). The intravitreal delivery of LbCpf1, targeted to two angiogenesis-associated genes encoding vascular endothelial growth factor A (Vegfa) and hypoxia inducing factor 1a (Hif1a), using adeno-associated virus, led to efficient gene disruption with no apparent off-target effects in the retina and retinal pigment epithelium (RPE) cells. Importantly, LbCpf1 targeted to Vegfa or Hif1a in RPE cells reduced the area of laser-induced choroidal neovascularization as efficiently as aflibercept, an anti-VEGF drug currently used in the clinic, without inducing cone dysfunction. Unlike aflibercept, LbCpf1 targeted to Vegfa or Hif1a achieved a long-term therapeutic effect on CNV, potentially avoiding repetitive injections. Taken together, these results indicate that LbCpf1-mediated in vivo genome editing to ablate pathologic angiogenesis provides an effective strategy for the treatment of AMD and other neovascularization-associated diseases.

  11. Intravitreal Stanniocalcin-1 Enhances New Blood Vessel Growth in a Rat Model of Laser-Induced Choroidal Neovascularization

    PubMed Central

    Zhao, Min; Xie, Wankun; Tsai, Shu-Huai; Hein, Travis W.; Rocke, Brent A.; Kuo, Lih; Rosa, Robert H.

    2018-01-01

    Purpose The purpose of this study was to investigate the impact of stanniocalcin-1 (STC-1), a photoreceptor-protective glycoprotein, on the development of choroidal neovascularization (CNV) in relation to VEGF and its main receptor (VEGFR2) expression after laser injury. Methods In rats, CNV was induced by laser photocoagulation in both eyes, followed by intravitreal injection of STC-1 in the right eye and vehicle or denatured STC-1 injection in the left eye as control. Two weeks after laser injury, fundus autofluorescence (FAF) imaging and fundus fluorescein angiography (FFA) were performed. Fluorescein leakage from CNV was graded using a defined scale system. The size of CNV was quantified with spectral domain optical coherence tomography (SD-OCT), fluorescein-labeled choroid-sclera flat mounts, and hematoxylin-eosin staining. Protein expressions were evaluated by Western blot. Results Photocoagulation produced a well-circumscribed area of CNV. With STC-1 treatment, CNV lesions assessed by FAF were increased by 50% in both intensity and area. The CNV lesions were also increased with SD-OCT, flat-mount, and histologic analyses. FFA disclosed enhanced fluorescein leakage in CNV lesions in STC-1 treated eyes. The STC-1 protein was detected in the choroidal tissue and its level was increased with CNV lesions in correlation with VEGF and VEGFR2 expressions. Intravitreal administration of STC-1 significantly increased choroidal expression of both VEGF and VEGFR2 proteins. Conclusions Chorodial tissue expresses STC-1, which seemingly acts as a stress response protein by enhancing pathological new blood vessel growth in laser-induced CNV. It is likely that STC-1 promotes CNV development via VEGF signaling. PMID:29490350

  12. Laser targeted photo-occlusion of rat choroidal neovascularization without collateral damage.

    PubMed

    Nishiwaki, Hirokazu; Zeimer, Ran; Goldberg, Morton F; D'Anna, Salvatore A; Vinores, Stanley A; Grebe, Rhonda

    2002-02-01

    Laser targeted photo-occlusion (LTO) is a novel method being developed to treat choroidal neovascular membranes (CNV) in age-related and other macular degenerations. A photosensitive agent, encapsulated in heat-sensitive liposomes, is administered intravenously. A low power laser warms the targeted tissue and releases a bolus of photosensitizer. The photosensitizer is activated after it clears from the normal choriocapillaris but not from the CNV. Forty-five experimental CNV were induced in seven rats. Five weeks after LTO, complete occlusion was observed by laser targeted angiography (LTA) in 76% of treated CNV, and partial occlusion was found in the remaining 24%. The tissues outside the CNV but within the area treated by LTO showed no flow alteration and no dye leakage. All untreated CNV were patent on LTA at 5 weeks. Light microscopy and electron microscopy confirmed the results in treated and control lesions. Moreover, treated areas next to lesions showed normal photoreceptors, retinal pigment epithelium (RPE), Bruch's membrane and choriocapillaris. These results indicate that LTO may improve current photodynamic therapy by alleviating the need for repeated treatments and by avoiding the long-term risks associated with damage to the RPE and occlusion of normal choriocapillaries.

  13. DETECTION OF TREATMENT-NAIVE CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION BY SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

    PubMed

    Ahmed, Daniel; Stattin, Martin; Graf, Alexandra; Forster, Julia; Glittenberg, Carl; Krebs, Ilse; Ansari-Shahrezaei, Siamak

    2017-09-04

    To compare the detection rate of choroidal neovascularization (CNV) in treatment-naive neovascular age-related macular degeneration by swept source optical coherence tomography angiography (SS-OCTA, Topcon's DRI Triton) working at 1,050 nm wavelength versus fluorescence angiography. Cross-sectional analysis of 156 eyes (107 neovascular age-related macular degeneration and 49 dry AMD) in 98 patients, previously diagnosed by multimodal imaging using fluorescein (FA) and indocyanine green angiography (Heidelberg's Spectralis) in a tertiary retina center, evaluated by SS-OCTA 4.5 mm × 4.5 mm and 6 mm × 6 mm macular cubes. Main outcome measures were sensitivity and specificity of SS-OCTA in AMD. Potential factors influencing CNV detection rate were analyzed. Swept source optical coherence tomography angiography detected CNV in 81 of 107 eyes, resulting in a sensitivity of 75.7%. In 49 eyes with dry AMD, no CNV could be identified (specificity 100%). A statistical significance was calculated for nondetection of treatment-naive CNV by SS-OCTA in pigment epithelial detachment over 400 μm (P = 0.0238). Topcon's SS-OCTA was not able to detect all CNV lesions. Large pigment epithelial detachments were associated with signal loss. Fluorescence angiography still remains the gold standard, but the tested SS-OCTA device can be considered as a feasible additional diagnostic tool in AMD.

  14. Risk factors for neovascular glaucoma after carbon ion radiotherapy of choroidal melanoma using dose-volume histogram analysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hirasawa, Naoki; Tsuji, Hiroshi; Ishikawa, Hitoshi

    2007-02-01

    Purpose: To determine the risk factors for neovascular glaucoma (NVG) after carbon ion radiotherapy (C-ion RT) of choroidal melanoma. Methods and Materials: A total of 55 patients with choroidal melanoma were treated between 2001 and 2005 with C-ion RT based on computed tomography treatment planning. All patients had a tumor of large size or one located close to the optic disk. Univariate and multivariate analyses were performed to identify the risk factors of NVG for the following parameters; gender, age, dose-volumes of the iris-ciliary body and the wall of eyeball, and irradiation of the optic disk (ODI). Results: Neovascular glaucomamore » occurred in 23 patients and the 3-year cumulative NVG rate was 42.6 {+-} 6.8% (standard error), but enucleation from NVG was performed in only three eyes. Multivariate analysis revealed that the significant risk factors for NVG were V50{sub IC} (volume irradiated {>=}50 GyE to iris-ciliary body) (p = 0.002) and ODI (p = 0.036). The 3-year NVG rate for patients with V50{sub IC} {>=}0.127 mL and those with V50{sub IC} <0.127 mL were 71.4 {+-} 8.5% and 11.5 {+-} 6.3%, respectively. The corresponding rate for the patients with and without ODI were 62.9 {+-} 10.4% and 28.4 {+-} 8.0%, respectively. Conclusion: Dose-volume histogram analysis with computed tomography indicated that V50{sub IC} and ODI were independent risk factors for NVG. An irradiation system that can reduce the dose to both the anterior segment and the optic disk might be worth adopting to investigate whether or not incidence of NVG can be decreased with it.« less

  15. Focal Choroidal Excavation in Best Vitelliform Macular Dystrophy: Case Report

    PubMed Central

    Esfahani, Mohammad Riazi; Esfahani, Hamid Riazi; Mahmoudi, Alireza; Johari, Mohammad Karim

    2015-01-01

    Focal choroidal excavation (FCE) was first reported as a choroidal posteriorly excavated zone without any scleral change. Choroidal excavation also divided into conforming and nonconforming type. Numerous reports demonstrated association between FCE and other disease such as choroidal neovascularization and central serous choroidoretinopathy. Here, we report a rare case of FCE in a patient with Best disease. The patient was diagnosed by spectoral domain optical coherence tomography (SD-OCT). To the best of our knowledge, our patient is the second report of choroidal excavation in Best vitelliform macular dystrophy. PMID:26155505

  16. Study on choroidal neovascularization with anti-VEGF treatment in the mouse retina using optical coherence tomography angiography (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Park, Jang Ryul; Choi, WooJhon; Kim, Jaeryung; Hong, Hye Kyong; Kim, Yongjoo; Hwang, Yoonha; Park, Sang Jun; Woo, Se Joon; Kim, Pilhan; Park, Kyu Hyung; Koh, Gou Young; Oh, Wang-Yuhl

    2017-02-01

    To understand the pathogenesis of ophthalmic disease, utilizing small animal models such as mouse is necessary because of their ease of maintenance and availability. For identifying pathophysiology and drug development of retinal diseases in mouse model, optical coherence tomography angiography (OCTA) is promising imaging modality visualizing not only microstructure but also microvasculature. In this study, we serially imaged 3D structure and angiography of laser-induced choroidal neovascularization (CNV) in the mouse retina with/without anti-VEGF treatment. Also, the volume changes of CNV and avascular region in choroid layer are measured for identifying effects of anti-VEGF. A lab-built high-speed OCTA prototype using the wavelength-swept laser centered at 1040 nm with 230 kHz A-scan rate acquired 3-D volumetric data consisted of 1024 x 1024 x 3 A-scans. The OCTA scanned 1.7 mm x 1.7 mm area around ONH. For obtaining angiography, amplitude decorrelation from 3 consecutive B-scans at each position was generated. Seven days after the laser photocoagulation at mouse retina for generation of the laser-induced CNV, intravitreal administration of Fc and VEGF-Trap was given in the therapeutic arm. The OCTA were performed at 6, 14, 21 and 35 days after laser photocoagulation. Vasculatures of inner retina, outer retina and choroid layers were separately visualized after RPE flattening and layer segmentation. To investigate therapeutic effects of anti-VEGF treatment, the relative area and volume of CNV in outer retina layer is measured. Also, total volume of avascular zone surrounding the laser injury site in choroid layer is also analyzed.

  17. Dopaminergic agonists that result in ocular growth inhibition also elicit transient increases in choroidal thickness in chicks

    PubMed Central

    Nickla, Debora L.; Totonelly, Kristen; Dhillon, Balprit

    2010-01-01

    The dopaminergic system has been implicated in ocular growth regulation in chicks and monkeys. In both, dopamine D2 agonists inhibit the development of myopia in response to form deprivation, and in chicks, to negative lenses as well. Because there is mounting evidence that the choroidal response to defocus plays a role in ocular growth regulation, we asked whether the effective agonists also elicit transient thickening of the choroid concomitant with the growth inhibition. Negative lenses mounted on velcro rings were worn on one eye starting at age 8-12 days. Intravitreal injections (20 μl; dose=10 nmole) of the agonist (dissolved in saline) or saline, were given through the superior temporal sclera using a 30G needle. Eyes were injected daily at noon, for 4 days, and the lenses immediately replaced. Agonists used were apomorphine (non-specific; n=17), quinpirole (D2; n=10), SKF-38393 (D1; n=9), and saline controls (n=22). For the antagonists, the same protocol was used, but on each day, the lenses were removed for 2 hours. Immediately prior to lens-removal, the antagonist was injected (20 μl; dose=5 nmole). Antagonists used were methylergonovine (non-specific; n=12), spiperone (D2; n=20), SCH-23390 (D1 n=6) and saline controls (n=27). Comparisons to saline (continuous lens wear) controls were from the agonist experiment. Axial dimensions were measured using high frequency A-scan ultrasonography at the start of lens wear, and on day 4 prior to the injections, and then again 3 hours later. Refractive errors were measured using a Hartinger's refractometer at the end of the experiment. Apomorphine and quinpirole inhibited the refractive response to the hyperopic defocus induced by the negative lenses (drug vs saline controls: -1.3 and 1.2 D vs -5.6 D; p<0.005 for both). This effect was axial: both drugs prevented the excessive ocular elongation (change in axial length: 233 and 205 μm vs 417 um; p<0.01 for both). Both drugs were also associated with a transient

  18. Circumscribed choroidal hemangioma: A case report and literature review.

    PubMed

    Berry, Morgan; Lucas, Linda J H

    Choroidal hemangioma is a rare congenital ocular tumor that can present as either circumscribed or diffuse. Circumscribed choroidal hemangioma (CCH) typically manifests as a red-orange mass within the posterior pole and appears similar to other ocular conditions, such as choroidal melanoma and choroidal metastasis. Proper diagnosis is crucial and is aided by the use of ancillary testing. CCH itself is benign but can cause secondary complications such as subretinal fluid accumulation and subsequent retinal detachment. If these conditions should arise, several treatment options are available. Published by Elsevier España, S.L.U.

  19. Liposomes and nanotechnology in drug development: focus on ocular targets

    PubMed Central

    Honda, Miki; Asai, Tomohiro; Oku, Naoto; Araki, Yoshihiko; Tanaka, Minoru; Ebihara, Nobuyuki

    2013-01-01

    Poor drug delivery to lesions in patients’ eyes is a major obstacle to the treatment of ocular diseases. The accessibility of these areas to drugs is highly restricted by the presence of barriers, including the corneal barrier, aqueous barrier, and the inner and outer blood–retinal barriers. In particular, the posterior segment is difficult to reach for drugs because of its structural peculiarities. This review discusses various barriers to drug delivery and provides comprehensive information for designing nanoparticle-mediated drug delivery systems for the treatment of ocular diseases. Nanoparticles can be designed to improve penetration, controlled release, and drug targeting. As highlighted in this review, the therapeutic efficacy of drugs in ocular diseases has been reported to be enhanced by the use of nanoparticles such as liposomes, micro/nanospheres, microemulsions, and dendrimers. Our recent data show that intravitreal injection of targeted liposomes encapsulating an angiogenesis inhibitor caused significantly greater suppression of choroidal neovascularization than did the injection of free drug. Recent progress in ocular drug delivery systems research has provided new insights into drug development, and the use of nanoparticles for drug delivery is thus a promising approach for advanced therapy of ocular diseases. PMID:23439842

  20. Role of NO in the control of choroidal blood flow during a decrease in ocular perfusion pressure.

    PubMed

    Simader, Christian; Lung, Solveig; Weigert, Günther; Kolodjaschna, Julia; Fuchsjäger-Mayrl, Gabriele; Schmetterer, Leopold; Polska, Elzbieta

    2009-01-01

    The study was conducted to investigate whether the L-arginine/nitric oxide system plays a role in choroidal blood flow (ChBF) regulation during a decrease in ocular perfusion pressure (OPP). Experiments were performed on 3 days in a randomized double-masked, placebo-controlled, three-way crossover design. On different study days, subjects received intravenous infusions of N(G)-monomethyl-L-arginine (L-NMMA), phenylephrine, or placebo. Intraocular pressure was raised in stepwise increments using the suction cup Choroidal blood flow (ChBF, laser Doppler flowmetry), mean arterial blood pressure (MAP), and IOP were assessed. Ocular perfusion pressure was calculated as OPP = 23(MAP - IOP). For correlation analysis all OPP/ChBF data pairs from all subjects were pooled independent of time point of measurement. Then, the pooled data were sorted according to OPP, and correlation analyses were performed. L-NMMA and phenylephrine increased resting OPP by +17% +/- 18% and +14% +/- 21%, respectively (P < 0.05). L-NMMA reduced resting ChBF by -21% +/- 17% (P < 0.05). The relative decrease in OPP during suction cup application was comparable with all drugs administered. The decrease in OPP was paralleled by a significant decrease in ChBF (maximum between -39% and -47%), which was less pronounced, however, than the decrease in OPP (maximum between -69% and -74%). Neither placebo nor L-NMMA, nor phenylephrine, influenced the OPP/ChBF relationship. The data confirm previously published observations that the choroid shows some regulatory capacity during reduced OPP. The L-arginine/nitric oxide-system plays a role in the maintenance of basal vascular tone but seems not to be involved in the choroidal vasodilator response when IOP is increased.

  1. Slit2 signaling through Robo1 and Robo2 is required for retinal neovascularization

    PubMed Central

    Rama, Nicolas; Dubrac, Alexandre; Mathivet, Thomas; Chárthaigh, Róisín-Ana Ní; Genet, Gael; Cristofaro, Brunella; Pibouin-Fragner, Laurence; Ma, Le; Eichmann, Anne; Chédotal, Alain

    2016-01-01

    Ocular neovascular diseases are a leading cause of blindness. Vascular endothelial growth factor (VEGF) blockade improves vision, but not all individuals respond to anti-VEGF treatment, making additional means to prevent neovascularization necessary. Slit-family proteins (Slits) are ligands of Roundabout (Robo) receptors that repel developing axons in the nervous system. Robo1 expression is altered in ocular neovascular diseases, and previous in vitro studies have reported both pro- and anti-angiogenic effects of Slits. However, genetic evidence supporting a role for Slits in ocular neovascularization is lacking. Here we generated conditional knockout mice deficient in various Slit and Robo proteins and found that Slit2 potently and selectively promoted angiogenesis via Robo1 and Robo2 in mouse postnatal retina and in a model of ocular neovascular disease. Mechanistically, Slit2 acting through Robo1 and Robo2 promoted the migration of endothelial cells. These receptors are required for both Slit2- and VEGF-induced Rac1 activation and lamellipodia formation. Thus, Slit2 blockade could potentially be used therapeutically to inhibit angiogenesis in individuals with ocular neovascular disease. PMID:25894826

  2. Pediatric genetic macular and choroidal diseases

    PubMed Central

    Bergman, Mica Y.; Nallasamy, Sudha

    2014-01-01

    Genetic diseases of the macula and choroid have various inheritance patterns and varying degrees of impact on vision. Herein, we review the literature including most recent advances in the understanding of the genetics of these diseases. Although many of these disorders have limited treatment options, knowledge of inheritance patterns can aid in early detection and with close monitoring can help the ophthalmologist preserve as much vision as possible (for example with early treatment of choroidal neovascularization). PMID:27625881

  3. Sensitivity and Specificity of OCT Angiography to Detect Choroidal Neovascularization.

    PubMed

    Faridi, Ambar; Jia, Yali; Gao, Simon S; Huang, David; Bhavsar, Kavita V; Wilson, David J; Sill, Andrew; Flaxel, Christina J; Hwang, Thomas S; Lauer, Andreas K; Bailey, Steven T

    2017-01-01

    To determine the sensitivity and specificity of optical coherence tomography angiography (OCTA) in the detection of choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Prospective case series. Prospective series of seventy-two eyes were studied, which included eyes with treatment-naive CNV due to AMD, non-neovascular AMD, and normal controls. All eyes underwent OCTA with a spectral domain (SD) OCT (Optovue, Inc.). The 3D angiogram was segmented into separate en face views including the inner retinal angiogram, outer retinal angiogram, and choriocapillaris angiogram. Detection of abnormal flow in the outer retina served as candidate CNV with OCTA. Masked graders reviewed structural OCT alone, en face OCTA alone, and en face OCTA combined with cross-sectional OCTA for the presence of CNV. The sensitivity and specificity of CNV detection compared to the gold standard of fluorescein angiography (FA) and OCT was determined for structural SD-OCT alone, en face OCTA alone, and with en face OCTA combined with cross-sectional OCTA. Of 32 eyes with CNV, both graders identified 26 true positives with en face OCTA alone, resulting in a sensitivity of 81.3%. Four of the 6 false negatives had large subretinal hemorrhage (SRH) and sensitivity improved to 94% for both graders if eyes with SRH were excluded. The addition of cross-sectional OCTA along with en face OCTA improved the sensitivity to 100% for both graders. Structural OCT alone also had a sensitivity of 100%. The specificity of en face OCTA alone was 92.5% for grader A and 97.5% for grader B. The specificity of structural OCT alone was 97.5% for grader A and 85% for grader B. Cross-sectional OCTA combined with en face OCTA had a specificity of 97.5% for grader A and 100% for grader B. Sensitivity and specificity for CNV detection with en face OCTA combined with cross-sectional OCTA approaches that of the gold standard of FA with OCT, and it is better than en face OCTA alone. Structural OCT alone

  4. Choroidal neovascularization in highly myopic eyes after cataract surgery.

    PubMed

    Hayashi, Kengo; Ohno-Matsui, Kyoko; Futagami, Soh; Ohno, Seiji; Tokoro, Takashi; Mochizuki, Manabu

    2006-01-01

    To determine the incidence and characteristics of choroidal neovascularization (CNV) in patients with high myopia (>or=8 diopters) who underwent cataract surgery in the Department of Ophthalmology, Tokyo Medical and Dental University, or the Ohno Eye Clinic, Tokyo, between September 1991 and March 2000. The medical records of 35 patients (48 eyes) who underwent cataract surgery with phacoemulsification and intraocular lens implantation were studied retrospectively. The development of CNV over a 4-year follow-up period, and its characteristics were determined. All of the eyes had received a comprehensive ophthalmological examination, including best-corrected visual acuity measurements, anterior segment biomicroscopy, and a dilated fundus examination by stereoscopic observation. CNV was found in six eyes (12.5%) of six patients. The mean interval between cataract surgery and the development of CNV was 34+/-17 months (range, 12-48 months). The CNV was subfoveal in all cases. The mean logarithm of the minimum angle of resolution (logMAR) after cataract surgery and before the appearance of CNV was 0.23+/-0.24, and 0.93+/-0.41 after the CNV appeared. This decrease was statistically significant (P=0.0008, paired Student t test). Subfoveal CNV developed more frequently in eyes when the fellow eye showed evidence of CNV preoperatively (40.0%) than in eyes when the fellow eye exhibited no evidence of CNV (9.3%). CNV developed in 12.5% of patients with high myopia after cataract surgery. CNV tended to develop more frequently when the fellow eye had CNV. Copyright (c) Japanese Ophthalmological Society 2006.

  5. Detection of new-onset choroidal neovascularization using optical coherence tomography: the AMD DOC Study.

    PubMed

    Do, Diana V; Gower, Emily W; Cassard, Sandra D; Boyer, David; Bressler, Neil M; Bressler, Susan B; Heier, Jeffrey S; Jefferys, Joan L; Singerman, Lawrence J; Solomon, Sharon D

    2012-04-01

    To determine the sensitivity of time domain optical coherence tomography (OCT) in detecting conversion to neovascular age-related macular degeneration (AMD) in eyes at high risk for choroidal neovascularization (CNV), compared with detection using fluorescein angiography (FA) as the gold standard. Prospective, multicenter, observational study. Individuals aged ≥50 years with nonneovascular AMD at high risk of progressing to CNV in the study eye and evidence of neovascular AMD in the fellow eye. At study entry and every 3 months through 2 years, participants underwent best-corrected visual acuity, supervised Amsler grid testing, preferential hyperacuity perimetry (PHP) testing, stereoscopic digital fundus photographs with FA, and OCT imaging. A central Reading Center graded all images. The sensitivity of OCT in detecting conversion to neovascular AMD by 2 years, using FA as the reference standard. Secondary outcomes included comparison of sensitivity, specificity, positive predictive value, and negative predictive value of OCT, PHP, and supervised Amsler grid relative to FA for detecting incident CNV. A total of 98 participants were enrolled; 87 (89%) of these individuals either completed the 24-month visit or exited the study after developing CNV. Fifteen (17%) study eyes had incident CNV confirmed on FA by the Reading Center. The sensitivity of each modality for detecting CNV was: OCT 0.40 (95% confidence interval [CI], 0.16-0.68), supervised Amsler grid 0.42 (95% CI, 0.15-0.72), and PHP 0.50 (95% CI, 0.23-0.77). Treatment for incident CNV was recommended by the study investigator in 13 study eyes. Sensitivity of the testing modalities for detection of CNV in these 13 eyes was 0.69 (95% CI, 0.39-0.91) for OCT, 0.50 (95% CI, 0.19-0.81) for supervised Amsler grid, and 0.70 (95% CI, 0.35-0.93) for PHP. Specificity of the OCT was higher than that of the Amsler grid and PHP. Time-domain OCT, supervised Amsler grid, and PHP have low to moderate sensitivity for

  6. Photodynamic therapy for treatment subretinal neovascularization

    NASA Astrophysics Data System (ADS)

    Avetisov, Sergey E.; Budzinskaja, Maria V.; Kiseleva, Tatyana N.; Balatskaya, Natalia V.; Gurova, Irina V.; Loschenov, Viktor B.; Shevchik, Sergey A.; Kuzmin, Sergey G.; Vorozhtsov, Georgy N.

    2007-07-01

    This work are devoted our experience with photodynamic therapy (PDT) with <> for patients with choroidal neovascularization (CNV). 18 patients with subfoveal CNV in age-related macular degeneration (AMD), 24 patients with subfoveal CNV in pathological myopia (PM) and 4 patients with subfoveal CNV associated with toxoplasmic retinochoroiditis were observed. CNV was 100% classic in all study patients. Standardized protocol refraction, visual acuity testing, ophthalmologic examinations, biomicroscopy, fluorescein angiography, and ultrasonography were performed before treatment and 1 month, 3 months, 6 months, and 1 year after treatment; were used to evaluate the results of photodynamic therapy with <> (0.02% solution of mixture sulfonated aluminium phtalocyanine 0.05 mg/kg, intravenously). A diode laser (<>, Inc, Moscow) was used operating in the range of 675 nm. Need for retreatment was based on fluorescein angiographic evidence of leakage at 3-month follow-up intervals. At 3, 6, 9 month 26 (56.5%) patients had significant improvement in the mean visual acuity. At the end of the 12-month minimal fluorescein leakage from choroidal neovascularization was seen in 12 (26.1%) patients and the mean visual acuity was slightly worse than 0.2 which was not statistically significant as compared with the baseline visual acuity. Patients with fluorescein leakage from CNV underwent repeated PDT with <>. 3D-mode ultrasound shown the decreasing thickness of chorioretinal complex in CNV area. Photodynamic therapy with <> can safely reduce the risk of severe vision loss in patients with predominantly classic subfoveal choroidal neovascularization secondary to AMD, PM and toxoplasmic retinochoroiditis.

  7. Development of Choroidal Neovascularization in rats with Advanced Intense Cyclic Light-induced Retinal Degeneration

    PubMed Central

    Albert, Daniel M.; Neekhra, Aneesh; Wang, Shoujian; Darjatmoko, Soesiawati R.; Sorenson, Christine M.; Dubielzig, Richard R.; Sheibani, Nader

    2010-01-01

    Objective To study the progressive changes of intense cyclic light-induced retinal degeneration and determine whether it results in choroidal neovascularization (CNV). Methods Albino rats were exposed to 12 h of 3000 lux cyclic light for 1, 3, or 6 months. Prior to euthanization, fundus examination, fundus photographs, fluorescein and indocyanine green angiography, and Optical Coherence Tomography (OCT) evaluations were performed. Light exposed animals were euthanized after 1, 3, or 6 months for histopathological evaluation. Retinas were examined for the presence of 4-hydroxy-2-nonenal (HNE) and nitrotyrosine modified proteins by immunofluorescence staining. Results Chronic intense cyclic light exposure resulted in retinal degeneration with loss of the outer segments of photoreceptors and approximately two-thirds of the outer nuclear layer (ONL) and development of sub-retinal pigment epithelium (RPE) neovascularization after 1 month. Almost the entire ONL was absent with the presence of CNV, which penetrated Bruch’s membrane and extended into the outer retina after 3 months. Absence of the ONL, multiple foci of CNV, RPE fibrous metaplasia, and connective tissue bands containing blood vessels extending into the retina were observed after 6 months. All intense light exposed animals showed an increased presence of HNE and nitrotyrosine staining. OCT and angiographic studies confirmed retinal thinning and leakiness of the newly fromed blood vessels. Conclusions Our results suggest albino rats develop progressive stages of retinal degeneration and CNV after chronic intense cyclic light exposure allowing the detailed study of the pathogenesis and treatment of age-related macular degeneration. PMID:20142545

  8. Plasma-activated medium suppresses choroidal neovascularization in mice: a new therapeutic concept for age-related macular degeneration.

    PubMed

    Ye, Fuxiang; Kaneko, Hiroki; Nagasaka, Yosuke; Ijima, Ryo; Nakamura, Kae; Nagaya, Masatoshi; Takayama, Kei; Kajiyama, Hiroaki; Senga, Takeshi; Tanaka, Hiromasa; Mizuno, Masaaki; Kikkawa, Fumitaka; Hori, Masaru; Terasaki, Hiroko

    2015-01-09

    Choroidal neovascularization (CNV) is the main pathogenesis of age-related macular degeneration (AMD), which leads to severe vision loss in many aged patients in most advanced country. CNV compromises vision via hemorrhage and retinal detachment on account of pathological neovascularization penetrating the retina. Plasma medicine represents the medical application of ionized gas "plasma" that is typically studied in the field of physical science. Here we examined the therapeutic ability of plasma-activated medium (PAM) to suppress CNV. The effect of PAM on vascularization was assessed on the basis of human retinal endothelial cell (HREC) tube formation. In mice, laser photocoagulation was performed to induce CNV (laser-CNV), followed by intravitreal injection of PAM. N-Acetylcysteine was used to examine the role of reactive oxygen species in PAM-induced CNV suppression. Fundus imaging, retinal histology examination, and electroretinography (ERG) were also performed to evaluate PAM-induced retinal toxicity. Interestingly, HREC tube formation and laser-CNV were both reduced by treatment with PAM. N-acetylcysteine only partly neutralized the PAM-induced reduction in laser-CNV. In addition, PAM injection had no effect on regular retinal vessels, nor did it show retinal toxicity in vivo. Our findings indicate the potential of PAM as a novel therapeutic agent for suppressing CNV.

  9. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration: twelve-month MONT BLANC study results.

    PubMed

    Larsen, Michael; Schmidt-Erfurth, Ursula; Lanzetta, Paolo; Wolf, Sebastian; Simader, Christian; Tokaji, Erika; Pilz, Stefan; Weisberger, Annemarie

    2012-05-01

    To compare the efficacy and safety of same-day verteporfin photodynamic therapy (PDT) and intravitreal ranibizumab combination treatment versus ranibizumab monotherapy in neovascular age-related macular degeneration. Prospective, multicenter, double-masked, randomized, active-controlled trial. We included 255 patients with all types of active subfoveal choroidal neovascularization. Patients were randomized 1:1 to as-needed (pro re nata; PRN) combination (standard-fluence verteporfin 6 mg/m(2) PDT and ranibizumab 0.5 mg) or PRN ranibizumab monotherapy (sham infusion [5% dextrose] PDT and ranibizumab 0.5 mg). Patients received 3 consecutive monthly injections followed by PRN retreatments based on protocol-specific retreatment criteria. Mean change in best-corrected visual acuity (BCVA) from baseline to month 12, and the proportion of patients with treatment-free interval ≥3 months at any timepoint after month 2. The mean change in BCVA at month 12 was +2.5 and +4.4 letters in the combination and monotherapy groups, respectively (P = 0.0048; difference: -1.9 letters [95% confidence interval, -5.76 to 1.86], for having achieved noninferiority with a margin of 7 letters). The proportion of patients with a treatment-free interval of ≥3 months at any timepoint after month 2 was high, but did not show a clinically relevant difference between the treatment groups. Secondary efficacy endpoints included the mean number of ranibizumab retreatments after month 2 (1.9 and 2.2 with combination and monotherapy, respectively [P = 0.1373]). The time to first ranibizumab retreatment after month 2 was delayed by 34 days (about 1 monthly visit) with combination (month 6) versus monotherapy (month 5). At month 12, mean ± standard error central retinal thickness decreased by 115.3±9.04 μm in the combination group and 107.7±11.02 μm in the monotherapy group. The mean number of verteporfin/sham PDT treatments was comparable in the 2 groups (combination, 1.7; monotherapy, 1.9). The

  10. Lenticular neovascularization subsequent to traumatic cataract formation.

    PubMed

    Kabat, Alan G

    2011-09-01

    To report a series of cases involving neovascularization within the human crystalline lens-a normally avascular structure-after ocular trauma. This is a retrospective, consecutive observational case series with review of the prevailing literature. Four individuals with a history of ocular trauma and subsequent cataract development were examined between May 2004 and April 2007. All had hypermature cataracts and intraocular inflammation, presumably secondary to phacolysis; two of the four had concurrent hyphema and ocular hypertension in the involved eye. All subjects in this series were found to display a discrete network of blood vessels within the structure of the crystalline lens, just beneath the anterior lens capsule. Neovascularization of the crystalline lens has received little attention in the ophthalmic literature, having been described only rarely in individual case reports. This manuscript details the first known case series involving lenticular neovascularization, and offers insight into its possible developmental mechanism.

  11. In vivo time-serial evaluation of laser-induced choroidal neovascularization in rats simultaneously using photoacoustic microscopy and optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Dai, Cuixia; Li, Lin; Liu, Wenlu; Wang, Fenghua; Zhou, Chuanqing

    2018-02-01

    Determination of the precise location and degree of condition of the Choroidal neovascularization (CNV) lesion is essential for diagnosation Neovascular age-related macular degeneration (AMD) and evaluation the efficacy of treatment. Given the complimentary contrast mechanisms of Photoacoustic microscopy (PAM) and Optical coherence tomography (OCT), the combination of PAM and OCT imaging could potentially provide much sensitive and specific detection of CNV. In this paper, we validated the opportunity to evaluate the information of laser-induced CNV and presented the in vivo time-serial evaluation of the CNV by simultaneously using PAM and OCT techniques. In vivo PAM and OCT examination was performed after laser photocoagulation applied to the rat fundus at days 1, 3, 5, 7, 14. Time-serial results showed that CNV in rats increased to its maximum at day 7 and decreased at day 14. Evolution of CNV information was given in PAM images with a high contrast and details of high axial resolution OCT images were simultaneously given to show the hyperreflective reaction progress.

  12. Inhibition of Placenta Growth Factor Reduces Subretinal Mononuclear Phagocyte Accumulation in Choroidal Neovascularization.

    PubMed

    Crespo-Garcia, Sergio; Corkhill, Caitlin; Roubeix, Christophe; Davids, Anja-Maria; Kociok, Norbert; Strauss, Olaf; Joussen, Antonia M; Reichhart, Nadine

    2017-10-01

    The cellular immune response driven by mononuclear phagocytes (MPs) is crucial for choroidal neovascularization (CNV) progression. Case reports show that a switch from pure anti-vascular endothelial growth factor-A (VEGF-A) intravitreal treatment to aflibercept, a drug with combined anti-VEGF-A and anti-placenta growth factor (PlGF) activity, can be beneficial for patients who do not respond to anti-VEGF-A alone. Since MPs harbor VEGFR1, we hypothesize that the interplay of P1GF/vascular endothelial growth factor receptor 1 (VEGFR1) in immune cells plays a pivotal role for CNV. CNV was induced with laser, and immune cells and neovascularization were analyzed in vivo and ex vivo. Immunohistochemistry was employed for protein detection. Differential expression of angiogenic factors and macrophage polarization markers were assessed by quantitative PCR (qPCR). One day after laser, intravitreal injection of aflibercept or anti-PlGF was performed. In the early inflammatory phase after laser, Plgf but not Vegfa was significantly upregulated. VEGF-A upregulation is limited to the scar, whereas PlGF shows a wider distribution. M1 (proinflammatory) macrophage markers were upregulated in the early phase of CNV. However, M2 (proangiogenic) markers showed more inconsistent dynamics. We demonstrated that both aflibercept and anti-PlGF treatments decrease the overall amount of activated subretinal MPs, and especially of those expressing PlGF. These data correlated with a reduction in leakage associated to CNV. Aflibercept showed a stronger reduction in both parameters. The results hint at an interplay between PlGF/VEGFR1 and MPs that is important in the early phase of CNV. A combined inhibition of VEGF-A and PlGF is superior to a specific anti-PlGF treatment in terms of subretinal MP recruitment.

  13. Neovascular glaucoma after proton beam therapy of choroidal melanoma: incidence and risk factors.

    PubMed

    Riechardt, Aline I; Pilger, Daniel; Cordini, Dino; Seibel, Ira; Gundlach, Enken; Hager, Annette; Joussen, Antonia M

    2017-11-01

    To analyze the risk factors for the development of neovascular glaucoma (NVG) of patients with choroidal melanoma after proton beam therapy (PBT). Clinical case series, retrospective study. We evaluated 629 consecutive patients receiving proton beam therapy for the treatment of a choroidal melanoma at the oncology service at Charité, Berlin and Helmholtz-Zentrum, Berlin between 05/1998 and 11/2008 regarding the development and risk factors of NVG. Patients with tumor resection, salvage proton beam therapy for recurrent disease and known glaucoma of other origin were excluded from the cohort. Of the 629 patients matching the inclusion criteria, 20.8% developed neovascularization of the iris after a mean time of 2.0 years (range 0.45 to 8.4 years) after PBT. Forty-seven percent of the patients with a neovascularization of the iris developed NVG after a mean time of 2.0 years after PBT, ranging from 5 months to 11.6 years. Univariate analysis revealed tumor height [p < 0.001, hazard ratio (HR): 2.71, 95% confidence interval (CI): 1.36-5.35 for tumors >6 mm ≤9 mm and 11.32 (4.03-31.73) for tumors >9 mm], distance of the tumor to the optic disc (p < 0.001, HR: 0.43, 95% CI: 0.24-0.77 for >0 mm ≤3 mm and HR: 0.13, 95% CI: 0.04-0.37 for >3 mm), dose to the ciliary body (p < 0.001, HR: 9.21, 95% CI: 5.08-16.71 (21-40 cobalt gray equivalents (CGE), HR 27.23, 95% CI: 6.33-116.97 (41-60 CGE)), dose to the optic disc (p < 0.001, HR: 3.53, 95% CI: 1.11-11.27 (21-40CGE), HR: 5.37, 95% CI: 2.72-10.63 (41-60CGE)), the irradiated length of the optic nerve (p < 0.001, HR: 4.48, 95% CI: 2.47-8.13) and diabetes mellitus (p < 0.05, HR: 2.53, 95% CI: 1.4-4.5) were found to be risk factors for the development of NVG. Multivariate regression analysis identified the dose to the ciliary body [p < 0.001, HR: 4.39, 95% CI: 2.28-8.44 (21-40 CGE), HR: 11.04, 95% CI: 1.97-61.69 (41-60 CGE)], the irradiated length of the optic nerve (p < 0.001, HR: 3.88, 95% CI: 2

  14. Dopaminergic agonists that result in ocular growth inhibition also elicit transient increases in choroidal thickness in chicks.

    PubMed

    Nickla, Debora L; Totonelly, Kristen; Dhillon, Balprit

    2010-11-01

    The dopaminergic system has been implicated in ocular growth regulation in chicks and monkeys. In both, dopamine D2 agonists inhibit the development of myopia in response to form deprivation, and in chicks, to negative lenses as well. Because there is mounting evidence that the choroidal response to defocus plays a role in ocular growth regulation, we asked whether the effective agonists also elicit transient thickening of the choroid concomitant with the growth inhibition. Negative lenses mounted on velcro rings were worn on one eye starting at age 8-12 days. Intravitreal injections (20 μl; dose = 10 nmole) of the agonist (dissolved in saline) or saline, were given through the superior temporal sclera using a 30G needle. Eyes were injected daily at noon, for 4 days, and the lenses immediately replaced. Agonists used were apomorphine (non-specific; n = 17), quinpirole (D2; n = 10), SKF-38393 (D1; n = 9), and saline controls (n = 22). For the antagonists, the same protocol was used, but on each day, the lenses were removed for 2 h. Immediately prior to lens-removal, the antagonist was injected (20 μl; dose = 5 nmole). Antagonists used were methylergonovine (non-specific; n = 12), spiperone (D2; n = 20), SCH-23390 (D1; n = 6) and saline controls (n = 27). Comparisons to saline (continuous lens wear) controls were from the agonist experiment. Axial dimensions were measured using high frequency A-scan ultrasonography at the start of lens wear, and on day 4 prior to the injections, and then again 3 h later. Refractive errors were measured using a Hartinger's refractometer at the end of the experiment. Apomorphine and quinpirole inhibited the refractive response to the hyperopic defocus induced by the negative lenses (drug vs saline controls: -1.3 and 1.2 D vs -5.6 D; p < 0.005 for both). This effect was axial: both drugs prevented the excessive ocular elongation (change in axial length: 233 and 205 μm vs 417 μm; p < 0.01 for both

  15. [Fundus fluorescein angiography in metastatic choroidal carcinomas and differentiating metastatic choroidal carcinomas from primary choroidal melanomas].

    PubMed

    Li, Lei; Wang, Wen-Ji; Chen, Rong-Jia; Qian, Jiang; Luo, Chuan-Qi; Zhang, Yong-Jin; Shen, Ying; Ye, Xiao-Feng; Gao, Qiao-Yun

    2011-01-01

    To investigate the characteristics of fundus fluorescein angiography (FFA) in metastatic choroidal carcinomas and determine the value of FFA in differentiating metastatic choroidal carcinomas from primary choroidal melanomas. It was a retrospective case series. The retrospective analysis of clinical data and FFA findings was performed in 23 eyes of 22 patients with metastatic choroidal carcinomas and 31 eyes of 31 patients with primary choroidal melanomas as the control. Ocular fundus findings of metastatic choroidal carcinomas were divided into three types: solitary flat (tumor thickness less than 3 mm), solitary elevated (tumor thickness more than 3 mm) or diffuse type. FFA of the three types showed hypofluorescence during the arterial phase and progressive hyperfluorescence during the subsequent phases. The border of the lesions revealed retinal capillary dilation during the arteriovenous phase and persistent pinpoint leakage throughout the angiogram. Retinal capillary dilation and pinpoint leakage were more frequently presented in the solitary flat type. Simultaneous visualization of retinal and tumor circulation (the so called double circulation) was more frequently presented in the solitary elevated type. Pinpoint leakage could be detected in 17 (73.91%) eyes of metastatic choroidal carcinomas and in 5 (16.13%) eyes of primary choroidal melanomas. The difference between the visibility of pinpoint leakage in metastatic choroidal carcinomas and primary choroidal melanomas was statistically significant (P = 0.0000). When pinpoint leakage of FFA was used to differentiate metastatic choroidal carcinomas from primary choroidal melanomas, the sensitivity, specificity, accuracy, positive and negative predictive values were 73.91%, 83.87%, 79.63%, 77.27%, 81.25% respectively. FFA is helpful for the diagnosis of metastatic choroidal carcinomas. Pinpoint leakage on the border of lesions has some value in differentiating metastatic choroidal carcinomas from primary

  16. Combined intravitreal bevacizumab and photodynamic therapy with vertiporfin for management of choroidal neovascularization secondary to age-related macular degeneration

    PubMed Central

    Kabeel, Mamdouh M; El-Batarny, Ashraf M; Tameesh, Mohamed K; Abou El Enein, Moustafa A

    2008-01-01

    Purpose To test the results for patients treated with combined photodynamic therapy (PDT) with vertiporfin (Visudyne, Novartis AG) and intravitreal bevacizumab for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Patients and methods This is a prospective study including 18 eyes with subfoveal or juxtafoveal CNV secondary to AMD. Patients were treated with intravitreal bevacizumab 2.5 mg in the morning then PDT with vertiporfin in the evening of the same day. All patients were followed up for 6 months. The main outcome measures were stabilization (no change) or improvement of best corrected visual acuity (BCVA) with no leakage in fluorescein angiography (FLA) and reduction of central retinal thickness, and retreatment rate. Results At the end of 6 months follow up, all cases had either stabilization or improved BCVA. Fifteen eyes (80%) showed improved BCVA. The overall mean improvement in BCVA (n = 18) was 2.17 lines. Fifteen eyes (80%) required single combined treatment. Only 3 eyes (20%) required retreatment with the same protocol. No systemic or ocular complications were reported. Conclusion Combined intravitreal bevacizumab and PDT as a treatment of CNV secondary to AMD either for predominantly classic or occult subtypes has a positive therapeutic effect with stabilization or improvement of final BCVA and also might reduce the need for retreatment compared with literature retreatment rates of either modality alone. Summary Eighteen patients receiving combined therapy with PDT and intravitreal bevacizumab for CNV secondary to AMD, showed not only significant visual improvement but also reduction in the frequency of retreatment when compared to the results of monotherapy with each modality. PMID:19668400

  17. Comparison of intravitreal aflibercept and ranibizumab injections on subfoveal and peripapillary choroidal thickness in eyes with neovascular age-related macular degeneration.

    PubMed

    Yun, Cheolmin; Oh, Jaeryung; Ahn, Jaemoon; Hwang, Soon-Young; Lee, Boram; Kim, Seong-Woo; Huh, Kuhl

    2016-09-01

    We aimed to compare changes in subfoveal and peripapillary choroidal thickness (CT) after intravitreal aflibercept or ranibizumab injections for neovascular age-related macular degeneration (AMD). Medical records of 54 treatment-naïve, consecutive patients (54 eyes) who were diagnosed with neovascular AMD and received three monthly injections of aflibercept (21 eyes) or ranibizumab (33 eyes) were reviewed. Subfoveal and peripapillary CT were measured with images obtained using spectral domain optical coherence tomography at baseline and at three months. Subfoveal CT decreased from 232.2 ± 94.4 μm at baseline to 207.1 ± 89.3 μm at three months in the aflibercept group (p < 0.001) and from 231.5 ± 102.9 μm to 220.0 ± 98.0 μm in the ranibizumab group (p = 0.006). The reduction was greater in the aflibercept group than in the ranibizumab group (p = 0.024). Peripapillary CT decreased from 157.2 ± 62.2 μm at baseline to 147.4 ± 62.2 μm at three months in the aflibercept group (p < 0.001). However, the change in peripapillary CT from 154.9 ± 46.5 μm at baseline to 152.3 ± 50.0 μm at three months was not significant in the ranibizumab group (p = 0.123). Intravitreally injected aflibercept significantly decreased subfoveal CT more than ranibizumab. Choroidal thinning after aflibercept injection was not limited to the subfoveal area, but extended beyond the macula as well.

  18. Clinical Features of Ocular Ischemic Syndrome and Risk Factors for Neovascular Glaucoma.

    PubMed

    Kim, Yung Hui; Sung, Mi Sun; Park, Sang Woo

    2017-08-01

    We aimed to examine the clinical features and prognosis of ocular ischemic syndrome and to investigate the risk factors for the development of neovascular glaucoma (NVG). The medical records from 25 patients (25 eyes) who were diagnosed with ocular ischemic syndrome were retrospectively analyzed. We recorded the length of time between symptom onset and diagnosis, visual acuity, intraocular pressure, clinical findings of the anterior and posterior segments of the eye, fluorescein angiography, systemic diseases, smoking history, and the extent of any ipsilateral carotid artery stenosis. The risk factors for NVG in patients with ocular ischemic syndrome were investigated. The mean age was 67.9 ± 12.5 years, and 21 men and 4 women were included in this study. At initial examination, the mean logarithm of the minimum angle of resolution (logMAR) was 2.02 ± 1.26, and the mean intraocular pressure was 21.0 ± 10.3 mmHg. Among 25 eyes of the 25 patients, NVG occurred in 17 eyes after a mean period of 12.6 ± 14.0 months. The length of time between symptom onset and diagnosis (p = 0.025) and the extent of ipsilateral carotid artery stenosis (p = 0.032) were identified as significant risk factors for NVG. At the final follow-up, the mean logMAR visual acuity was 3.13 ± 1.24, showing a poor prognosis regardless of whether NVG occurred. Overall, the prognosis for ocular ischemic syndrome is very poor. The risk of NVG increases with the length of time between symptom onset and diagnosis, as well as with the severity of ipsilateral carotid artery stenosis. © 2017 The Korean Ophthalmological Society

  19. Thrombospondin-2 Expression During Retinal Vascular Development and Neovascularization.

    PubMed

    Fei, Ping; Palenski, Tammy L; Wang, Shoujian; Gurel, Zafer; Hankenson, Kurt D; Sorenson, Christine M; Sheibani, Nader

    2015-09-01

    To determine thrombospondin-2 (TSP2) expression and its impact on postnatal retinal vascular development and retinal neovascularization. The TSP2-deficient (TSP2(-/-)) mice and a line of TSP2 reporter mice were used to assess the expression of TSP2 during postnatal retinal vascular development and neovascularization. The postnatal retinal vascularization was evaluated using immunostaining of wholemount retinas prepared at different postnatal days by collagen IV staining and/or TSP2 promoter driven green fluorescent protein (GFP) expression. The organization of astrocytes was evaluated by glial fibrillary acidic protein (GFAP) staining. Retinal vascular densities were determined using trypsin digestion preparation of wholemount retinas at 3- and 6-weeks of age. Retinal neovascularization was assessed during the oxygen-induced ischemic retinopathy (OIR). Choroidal neovascularization (CNV) was assessed using laser-induced CNV. Using the TSP2-GFP reporter mice, we observed significant expression of TSP2 mRNA in retinas of postnatal day 5 (P5) mice, which increased by P7 and remained high up to P42. Similar results were observed in retinal wholemount preparations, and western blotting for GFP with the highest level of GFP was observed at P21. In contrast to high level of mRNA at P42, the GFP fluorescence or protein level was dramatically downregulated. The primary retinal vasculature developed at a faster rate in TSP2(-/-) mice compared with TSP2(+/+) mice up to P5. However, the developing retinal vasculature in TSP2(+/+) mice caught up with that of TSP2(-/-) mice after P7. No significant differences in retinal vascular density were observed at 3- or 6-weeks of age. TSP2(-/-) mice also exhibited a similar sensitivity to the hyperoxia-mediated vessel obliteration and similar level of neovascularization during OIR as TSP2(+/+) mice. Lack of TSP2 expression minimally affected laser-induced CNV compared with TSP2(+/+) mice. Lack of TSP2 expression was associated with

  20. Visual function after strontium-90 plaque irradiation in patients with age-related subfoveal choroidal neovascularization.

    PubMed

    Jaakkola, A; Heikkonen, J; Tarkkanen, A; Immonen, I

    1999-02-01

    To report 2-year visual and angiographic results in eyes treated with strontium plaque irradiation for subfoveal choroidal neovascular membranes (CNVM) in age-related macular degeneration. Twenty eyes with recent subfoveal CNVM were treated with local irradiation. The impact of the treatment on visual function was evaluated by visual acuity, contrast sensitivity and reading speed testing. At 12 months visual acuity had improved or remained the same in 9/ 20 eyes (45%). At 24 months visual acuity was stable in 5/18 eyes (28%). Eyes with signs of CNVM regression (13/18, 72%) lost a mean of 3.3 lines, but eyes with recurrent CNVM lost a mean of 5.1 lines of vision. The mean contrast sensitivity was better in the irradiated eyes than in the fellow eyes with late age-related macular degeneration at 24 months. Six of 17 irradiated eyes (35%) could read at least some words at 24 months. Visual function decreases in patients treated with strontium irradiation, but less in eyes showing regression of the CNVM than in eyes with further growth of the CNVM.

  1. Systemic human CR2-targeted complement alternative pathway inhibitor ameliorates mouse laser-induced choroidal neovascularization.

    PubMed

    Rohrer, Bärbel; Coughlin, Beth; Bandyopadhyay, Mausumi; Holers, V Michael

    2012-08-01

    Genetic associations and the presence of complement components within pathological structures of age-related macular degeneration (AMD) have generated the hypothesis that AMD is caused by chronic local complement activation. Since the majority of activity in the common terminal pathway results from engagement of the amplification loop, the alternative pathway has been proposed as a logical therapeutic target. We recently generated a factor H (fH)-based complement inhibitor (CR2-fH) with the capacity to be "targeted" to sites of complement C3 activation. We asked whether the human therapeutic (TT30) is effective in a mouse model of AMD. Choroidal neovascularization (CNV) was induced by argon laser photocoagulation of Bruch's membrane. Every other day, mice received intravenous injections of TT30 or vehicles, and after 6 days, the presence or absence of CNV and CNV-related changes were evaluated. Area of CNV, photoreceptor cell function, gene expression for complement components and cytokines, vascular endothelial growth factor (VEGF) protein levels, and TT30 bioavailability were determined. CNV development, which has previously been shown to require local complement activation, could be reduced by intravenous TT30 delivery. Specific inhibition of the alternative pathway not only reduced angiogenesis in CNV, but also ameliorated changes in several associated disease-related biomarkers, including diminished retinal function and molecular events known to be involved in AMD such as VEGF production. After intravenous injection, TT30 localized to CNV lesion sites in the retinal pigmented epithelium-choroid. Systemic administration of TT30 was found to reduce CNV pathology. These data may open new avenues for novel systemic AMD treatment strategies.

  2. Edaravone is a free radical scavenger that protects against laser-induced choroidal neovascularization in mice and common marmosets.

    PubMed

    Masuda, Tomomi; Shimazawa, Masamitsu; Takata, Shinsuke; Nakamura, Shinsuke; Tsuruma, Kazuhiro; Hara, Hideaki

    2016-05-01

    Choroidal neovascularization (CNV) is a main characteristic in exudative type of age-related macular degeneration (AMD). Our study aimed to evaluate the effects of edaravone, a free radical scavenger on laser-induced CNV. CNV was induced by laser photocoagulation to the subretinal choroidal area of mice and common marmosets. Edaravone was administered either intraperitoneally twice a day for 2 weeks or intravenously just once after laser photocoagulation. The effects of edaravone on laser-induced CNV were evaluated by fundus fluorescein angiography, CNV area measurements, and the expression of 4-hydroxy-2-nonenal (4-HNE) modified proteins, a marker of oxidative stress. Furthermore, the effects of edaravone on the production of H2O2-induced reactive oxygen species (ROS) and vascular endothelial growth factor (VEGF)-induced cell proliferation were evaluated using human retinal pigment epithelium cells (ARPE-19) and human retinal microvascular endothelial cells, respectively. CNV areas in the edaravone-treated group were significantly smaller in mice and common marmosets. The expression of 4-HNE modified proteins was upregulated 3 h after laser photocoagulation, and intravenously administered edaravone decreased it. In in vitro studies, edaravone inhibited H2O2-induced ROS production and VEGF-induced cell proliferation. These findings suggest that edaravone may protect against laser-induced CNV by inhibiting oxidative stress and endothelial cell proliferation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Detection of Myopic Choroidal Neovascularization Using Optical Coherence Tomography Angiography.

    PubMed

    Miyata, Manabu; Ooto, Sotaro; Hata, Masayuki; Yamashiro, Kenji; Tamura, Hiroshi; Akagi-Kurashige, Yumiko; Nakanishi, Hideo; Ueda-Arakawa, Naoko; Takahashi, Ayako; Kuroda, Yoshimasa; Wakazono, Tomotaka; Yoshikawa, Munemitsu; Yoshimura, Nagahisa

    2016-05-01

    To assess whether optical coherence tomography angiography (OCTA) can be used as an alternative to conventional fundus fluorescein angiography (FFA) for the detection of myopic choroidal neovascularization (CNV). Validity and reliability analysis. Twenty-eight eyes of 26 consecutive Japanese patients with exudative lesions associated with pathologic myopia were included in this institutional study. Myopic CNV was detected in 23 eyes of 22 patients; 5 eyes exhibited simple hemorrhage. The main outcome measure was CNV detection by OCTA and FFA. The CNV area was individually measured by FFA and OCTA. Intraclass correlation coefficients (ICCs) for the CNV area, independently measured by 2 investigators using OCTA and FFA, were determined. OCTA images with sufficient quality for CNV assessment were obtained for 17 eyes with CNV and 4 without. FFA alone detected CNV in all 17 eyes, while OCTA alone detected CNV in 16 (94.1%). The 1 eye for which CNV was not detected by OCTA exhibited a 0.01 mm(2) area on FFA. Both FFA and OCTA did not detect CNV in eyes with simple hemorrhage. The mean CNV areas on FFA and OCTA were 0.59 ± 0.56 mm(2) and 0.51 ± 0.55 mm(2), respectively; the 2 values were significantly correlated (P < .001, r = .86). The ICC (2, 1) values for FFA and OCTA were 0.944 and 0.997, respectively. Our results indicate that OCTA can detect most myopic CNVs if high-quality images are acquired and can preclude the requirement for FFA in these settings. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Activation of the Small GTPase Rap1 Inhibits Choroidal Neovascularization by Regulating Cell Junctions and ROS Generation in Rats.

    PubMed

    Li, Jiajia; Zhang, Rong; Wang, Caixia; Wang, Xin; Xu, Man; Ma, Jingxue; Shang, Qingli

    2018-03-30

    Choroidal neovascularization (CNV) is a common vision-threatening complication associated with many  fundus diseases. The retinal pigment epithelial (RPE) cell junction barrier has critical functions in preventing CNV, and oxidative stress can cause compromise of barrier integrity and induce angiogenesis. Rap1, a small guanosine triphosphatase (GTPase), is involved in regulating endothelial and epithelial cell junctions. In this work, we explored the function and mechanism of Rap1 in CNV in vivo. A laser-induced rat CNV model was developed. Rap1 was activated through intravitreal injection of the Rap1 activator 8CPT-2'-O-Me-cAMP (8CPT). At 14 days after laser treatment, CNV size in RPE/choroid flat mounts was measured by fluorescein isothiocyanate-dextran staining. Expression of vascular endothelial growth factor (VEGF) and cell junction proteins in RPE/choroid tissues were analyzed by western blots and quantitative real-time PCR assays. Reactive oxygen species (ROS) in RPE cells were detectedbydichloro-dihydro-fluorescein diacetate assays. The antioxidant apocynin was intraperitoneally injected into rats. Activating Rap1 by 8CPT significantly reduced CNV size and VEGF expression in the rat CNV model. Rap1 activation enhanced protein and mRNA levels of ZO-1 and occludin, two tight junction proteins in the RPE barrier. In addition, reducing ROS generation by injection of apocynin, a NADPH oxidase inhibitor, inhibited CNV formation. Rap1 activation reduced ROS generation and expression of NADPH oxidase 4. Rap1 activation inhibits CNV through regulating barrier integrity and ROS generation of RPE in vivo, and selectively activating Rap1 may be a way to reduce vision loss from CNV.

  5. Comparison of choroidal and optic nerve head blood flow regulation during changes in ocular perfusion pressure.

    PubMed

    Schmidl, Doreen; Boltz, Agnes; Kaya, Semira; Werkmeister, Rene; Dragostinoff, Nikolaus; Lasta, Michael; Polska, Elzbieta; Garhöfer, Gerhard; Schmetterer, Leopold

    2012-07-01

    We compared the response of choroidal and optic nerve head blood flow (ChBF, ONHBF) in response to an increase in ocular perfusion pressure (OPP) during isometric exercise and during a decrease in OPP during an artificial increase in intraocular pressure (IOP). We included 96 healthy subjects in our study. In 48 subjects OPP was increased by 6 minutes of squatting, and either ONHBF (n = 24) or ChBF (n = 24) was measured continuously. In 48 other healthy subjects either ONHBF (n = 24) or ChBF (n = 24) was measured continuously during a period of artificial increase in IOP using a suction cup. All blood flow measurements were done using laser Doppler flowmetry. During all experiments the response in blood flow was less pronounced than the response in OPP, indicating for flow regulation. During isometric exercise ChBF regulated better than ONHBF (P = 0.023). During artificial IOP increase ONHBF regulated better than ChBF (P = 0.001). Inter-individual variability in blood flow responses was high. During squatting ONHBF decreased considerably below baseline ONHBF when OPP fluctuated in 3 subjects, although OPP still was much higher than at baseline. This phenomenon was not observed in the choroid. Our data indicate that regulation of ChBF and ONHBF during changes in OPP is different and complex. In some subjects performing squatting, considerable ONHBF reductions were observed during OPP fluctuations, although OPP still was high. Whether this predisposes to ocular disease remains unclear.

  6. Doxycycline Inhibits Polarization of Macrophages to the Proangiogenic M2-type and Subsequent Neovascularization*

    PubMed Central

    He, Lizhi; Marneros, Alexander G.

    2014-01-01

    Macrophages occur along a continuum of functional states between M1-type polarized macrophages with antiangiogenic and antitumor activity and M2-type polarized macrophages, which have been implicated to promote angiogenesis and tumor growth. Proangiogenic M2-type macrophages promote various pathologic conditions, including choroidal neovascularization in models of neovascular age-related macular degeneration, or certain cancers, such as glioblastoma multiforme. Thus, a potential novel therapeutic approach to target pathological angiogenesis in these conditions would be to inhibit the polarization of macrophages toward the proangiogenic M2-type. However, no pharmacological inhibitors of M2-type macrophage polarization have been identified yet. Here we performed an unbiased pharmacological and small chemical screen to identify drugs that inhibit proangiogenic M2-type macrophage polarization and block pathologic macrophage-driven neovascularization. We identified the well tolerated and commonly used antibiotic doxycycline as a potent inhibitor of M2-type polarization of macrophages. Doxycycline inhibited, in a dose-dependent manner, M2-type polarization of human and bone marrow-derived mouse macrophages without affecting cell viability. Furthermore, doxycycline inhibited M2-type macrophage polarization and subsequent neovascularization in vivo in a laser injury model of choroidal neovascularization. Thus, doxycycline could be used to enhance current antiangiogenic treatment approaches in various conditions that are promoted by proangiogenic M2-type macrophages, including neovascular age-related macular degeneration and certain cancers. PMID:24505138

  7. The goal of value-based medicine analyses: comparability. The case for neovascular macular degeneration.

    PubMed

    Brown, Gary C; Brown, Melissa M; Brown, Heidi C; Kindermann, Sylvia; Sharma, Sanjay

    2007-01-01

    To evaluate the comparability of articles in the peer-reviewed literature assessing the (1) patient value and (2) cost-utility (cost-effectiveness) associated with interventions for neovascular age-related macular degeneration (ARMD). A search was performed in the National Library of Medicine database of 16 million peer-reviewed articles using the key words cost-utility, cost-effectiveness, value, verteporfin, pegaptanib, laser photocoagulation, ranibizumab, and therapy. All articles that used an outcome of quality-adjusted life-years (QALYs) were studied in regard to (1) percent improvement in quality of life, (2) utility methodology, (3) utility respondents, (4) types of costs included (eg, direct healthcare, direct nonhealthcare, indirect), (5) cost bases (eg, Medicare, National Health Service in the United Kingdom), and (6) study cost perspective (eg, government, societal, third-party insurer). To qualify as a value-based medicine analysis, the patient value had to be measured using the outcome of the QALYs conferred by respective interventions. As with value-based medicine analyses, patient-based time tradeoff utility analysis had to be utilized, patient utility respondents were necessary, and direct medical costs were used. Among 21 cost-utility analyses performed on interventions for neovascular macular degeneration, 15 (71%) met value-based medicine criteria. The 6 others (29%) were not comparable owing to (1) varying utility methodology, (2) varying utility respondents, (3) differing costs utilized, (4) differing cost bases, and (5) varying study perspectives. Among value-based medicine studies, laser photocoagulation confers a 4.4% value gain (improvement in quality of life) for the treatment of classic subfoveal choroidal neovascularization. Intravitreal pegaptanib confers a 5.9% value gain (improvement in quality of life) for classic, minimally classic, and occult subfoveal choroidal neovascularization, and photodynamic therapy with verteporfin confers

  8. THE GOAL OF VALUE-BASED MEDICINE ANALYSES: COMPARABILITY. THE CASE FOR NEOVASCULAR MACULAR DEGENERATION

    PubMed Central

    Brown, Gary C.; Brown, Melissa M.; Brown, Heidi C.; Kindermann, Sylvia; Sharma, Sanjay

    2007-01-01

    Purpose To evaluate the comparability of articles in the peer-reviewed literature assessing the (1) patient value and (2) cost-utility (cost-effectiveness) associated with interventions for neovascular age-related macular degeneration (ARMD). Methods A search was performed in the National Library of Medicine database of 16 million peer-reviewed articles using the key words cost-utility, cost-effectiveness, value, verteporfin, pegaptanib, laser photocoagulation, ranibizumab, and therapy. All articles that used an outcome of quality-adjusted life-years (QALYs) were studied in regard to (1) percent improvement in quality of life, (2) utility methodology, (3) utility respondents, (4) types of costs included (eg, direct healthcare, direct nonhealthcare, indirect), (5) cost bases (eg, Medicare, National Health Service in the United Kingdom), and (6) study cost perspective (eg, government, societal, third-party insurer). To qualify as a value-based medicine analysis, the patient value had to be measured using the outcome of the QALYs conferred by respective interventions. As with value-based medicine analyses, patient-based time tradeoff utility analysis had to be utilized, patient utility respondents were necessary, and direct medical costs were used. Results Among 21 cost-utility analyses performed on interventions for neovascular macular degeneration, 15 (71%) met value-based medicine criteria. The 6 others (29%) were not comparable owing to (1) varying utility methodology, (2) varying utility respondents, (3) differing costs utilized, (4) differing cost bases, and (5) varying study perspectives. Among value-based medicine studies, laser photocoagulation confers a 4.4% value gain (improvement in quality of life) for the treatment of classic subfoveal choroidal neovascularization. Intravitreal pegaptanib confers a 5.9% value gain (improvement in quality of life) for classic, minimally classic, and occult subfoveal choroidal neovascularization, and photodynamic therapy

  9. A case of primary choroidal malignant melanoma in a cat.

    PubMed

    Bourguet, Aurélie; Piccicuto, Virginie; Donzel, Elise; Carlus, Marine; Chahory, Sabine

    2015-07-01

    This report describes the clinical presentation, diagnosis, histological lesions, and prognosis of a primary choroidal malignant melanoma in a 15-year-old cat. The animal was presented for unilateral blindness. On ocular examination, a raised pigmented mass protruding from the posterior pole into the vitreous body was observed by diffuse transillumination and indirect ophthalmoscopy. Ocular ultrasound and computer tomography (CT) scan confirmed localization of the tumor to the posterior segment. The diagnosis of primary choroidal melanoma was confirmed by histopathology after enucleation. To our knowledge, this is the first reported case of a feline malignant melanoma with a primary choroidal localization without iris involvement. © 2014 American College of Veterinary Ophthalmologists.

  10. BILATERAL CHOROIDAL EXCAVATION IN JUVENILE LOCALIZED SCLERODERMA.

    PubMed

    Franklin, Mackenzie L; Day, Shelley

    2018-01-01

    To describe a case of bilateral choroidal excavation in a patient with juvenile localized scleroderma. Case report. An asymptomatic 12-year-old boy with localized scleroderma presented for examination and was found to have bilateral areas of choroidal excavation temporal to the fovea. Previous reports of ocular complications of localized scleroderma have primarily described adnexal and anterior segment changes. This is the second report of choroidal changes in a patient with localized scleroderma, and the first in a pediatric patient.

  11. Vascular endothelial growth factor inhibitor use and treatment approach for choroidal neovascularization secondary to pathologic myopia.

    PubMed

    Pakzad-Vaezi, Kaivon; Mehta, Hemal; Mammo, Zaid; Tufail, Adnan

    2016-07-01

    Myopic choroidal neovascularization (CNV) is the most common cause of CNV in those under 50 years of age. It is a significant cause of visual loss in those with pathologic myopia. The current standard of care involves therapy with intravitreal inhibitors of vascular endothelial growth factor (VEGF). The epidemiology of myopia, high myopia, pathologic myopia, and myopic CNV is reviewed, along with a brief discussion of historical treatments. The pharmacology of the three most commonly used anti-VEGF agents is discussed, with an emphasis on the licensed drugs, ranibizumab and aflibercept. A comprehensive clinical approach to diagnosis and treatment of myopic CNV is presented. The current standard of care for myopic CNV is intravitreal inhibition of VEGF, with ranibizumab and aflibercept licensed for intraocular use. The diagnosis, OCT features of disease activity and retreatment algorithm for myopic CNV is different from wet age-related macular degeneration. In the long-term, myopic CNV may be associated with gradual, irreversible visual loss due to progressive chorioretinal atrophy, for which there is currently no treatment.

  12. Long-term suppression of ocular neovascularization by intraocular injection of biodegradable polymeric particles containing a serpin-derived peptide.

    PubMed

    Shmueli, Ron B; Ohnaka, Masayuki; Miki, Akiko; Pandey, Niranjan B; Lima e Silva, Raquel; Koskimaki, Jacob E; Kim, Jayoung; Popel, Aleksander S; Campochiaro, Peter A; Green, Jordan J

    2013-10-01

    Aberrant angiogenesis can cause or contribute to a number of diseases such as neovascular age-related macular degeneration (NVAMD). While current NVAMD treatments target angiogenesis, these treatments are not effective for all patients and also require frequent intravitreal injections. New agents and delivery systems to treat NVAMD could be beneficial to many patients. We have recently developed a serpin-derived peptide as an anti-angiogenic agent. Here, this peptide is investigated for activity in human retinal endothelial cells in vitro and for reducing angiogenesis in a laser-induced choroidal neovascularization mouse model of NVAMD in vivo. While frequent intravitreal injections can be tolerated clinically, reducing the number of injections can improve patient compliance, safety, and outcomes. To achieve this goal, and to maximize the in vivo activity of injected peptide, we have developed biodegradable polymers and controlled release particle formulations to extend anti-angiogenic therapy. To create these devices, the anionic peptides are first self-assembled into nanoparticles using a biodegradable cationic polymer and then as a second step, these nanoparticles are encapsulated into biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles. In situ, these particles show approximately zero-order, linear release of the anionic peptide over 200 days. These particles are made of safe, hydrolytically degradable polymers and have low endotoxin. Long-term in vivo experiments in the laser-induced neovascularization model for NVAMD show that these peptide-releasing particles decrease angiogenesis for at least fourteen weeks in vivo following a single particle dose and therefore are a promising treatment strategy for NVAMD. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Long-Term Suppression of Ocular Neovascularization by Intraocular Injection of Biodegradable Polymeric Particles Containing a Serpin-Derived Peptide

    PubMed Central

    Shmueli, Ron B.; Ohnaka, Masayuki; Miki, Akiko; Pandey, Niranjan B.; Silva, Raquel Lima e; Koskimaki, Jacob E.; Kim, Jayoung; Popel, Aleksander S.; Campochiaro, Peter A.; Green, Jordan J.

    2013-01-01

    Aberrant angiogenesis can cause or contribute to a number of diseases such as neovascular age-related macular degeneration (NVAMD). While current NVAMD treatments target angiogenesis, these treatments are not effective for all patients and also require frequent intravitreal injections. New agents and delivery systems to treat NVAMD could be beneficial to many patients. We have recently developed a serpin-derived peptide as an anti-angiogenic agent. Here, this peptide is investigated for activity in human retinal endothelial cells in vitro and for reducing angiogenesis in a laser-induced choroidal neovascularization mouse model of NVAMD in vivo. While frequent intravitreal injections can be tolerated clinically, reducing the number of injections can improve patient compliance, safety, and outcomes. To achieve this goal, and to maximize the in vivo activity of injected peptide, we have developed biodegradable polymers and controlled release particle formulations to extend anti-angiogenic therapy. To create these devices, the anionic peptides are first self-assembled into nanoparticles using a biodegradable cationic polymer and then as a second step, these nanoparticles are encapsulated into biodegradable poly(lactic-co-glycolic acid) (PLGA) microparticles. In situ, these particles show approximately zero-order, linear release of the anionic peptide over 200 days. These particles are made of safe, hydrolytically degradable polymers and have low endotoxin. Long-term in vivo experiments in the laser-induced neovascularization model for NVAMD show that these peptide-releasing particles decrease angiogenesis for at least fourteen weeks in vivo following a single particle dose and therefore are a promising treatment strategy for NVAMD. PMID:23849876

  14. Histopathologically proven mucinous cystadenocarcinoma metastatic to the choroid.

    PubMed

    Henderson, Robert H; Cohen, Victoria M; Rath, Pamela P; Luthert, Philip; Hungerford, John L

    2010-01-01

    To report the first case of conventional transcleral choroidal biopsy in the diagnosis of ovarian carcinoma metastatic to the choroid and to summarize the published cases of ovarian carcinoma metastatic to the choroid. Case report and Medline literature review. This is the tenth case reported in the literature and the only case that underwent conventional transcleral choroidal biopsy. Transcleral choroidal biopsy allowed the diagnosis of metastatic mucinous cystadenocarcinoma of the ovary. Choroidal metastases are not associated with central nervous system involvement; however, investigations may reveal distal boney or pulmonary metastases. Ovarian carcinoma rarely metastases to the choroid and unlike breast carcinoma, concurrent central nervous system disease has not been reported. When systemic investigations fail to reveal active intraperitoneal disease or distal metastases, the clinician should consider referral to an ocular oncology center for a choroidal biopsy.

  15. One-year results from clinical practice of epimacular strontium-90 brachytherapy for the treatment of subfoveal choroidal neovascularization secondary to AMD.

    PubMed

    Zur, Dinah; Loewenstein, Anat; Barak, Adiel

    2015-03-01

    To evaluate clinical feasibility, safety, and efficacy of epiretinal strontium-90 brachytherapy in subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) in eyes unresponsive to repeated anti-VEGF injections. A retrospective, single-center study on patients treated with strontium-90 brachytherapy for CNV secondary to neovascular AMD. Patients underwent pars plana vitrectomy with a single 24 Gy dose brachytherapy. They were re-treated with anti-VEGF injections on an as-needed basis if subretinal or intraretinal fluid was detected on optical coherence tomography imaging. Twenty-two patients were treated, and 20 completed 12 months of follow-up. Ten patients maintained stable vision, eight gained vision, and two lost more than three Snellen lines. The mean best corrected visual acuity change from baseline was -8 ± 5.7 letters. A mean of 5.5 ± 4.4 anti-VEGF injections were administered throughout 12 months. Epimacular brachytherapy is feasible in clinical practice. While some patients benefit from the treatment and need significantly fewer as-needed injections, others appear not to react to irradiation treatment after 1 year of follow-up. Larger numbers of patients are needed to evaluate therapeutic efficacy and to determine which patients can benefit from combined radiation and anti-VEGF therapy. Copyright 2015, SLACK Incorporated.

  16. Optical Coherence Tomography Angiography to Distinguish Changes of Choroidal Neovascularization after Anti-VEGF Therapy: Monthly Loading Dose versus Pro Re Nata Regimen.

    PubMed

    Miere, Alexandra; Oubraham, Hassiba; Amoroso, Francesca; Butori, Pauline; Astroz, Polina; Semoun, Oudy; Bruyere, Elsa; Pedinielli, Alexandre; Addou-Regnard, Manar; Jung, Camille; Cohen, Salomon Y; Souied, Eric H

    2018-01-01

    To compare the qualitative and quantitative choroidal neovascularization (CNV) changes after antivascular endothelial growth factor (anti-VEGF) therapy in treatment-naïve and treated eyes with age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA). Consecutive patients with neovascular AMD underwent multimodal imaging, including OCTA (AngioPlex, CIRRUS HD-OCT model 5000; Carl Zeiss Meditec, Inc., Dublin, OH) at baseline and at three monthly follow-up visits. Treatment-naive AMD patients undergoing anti-VEGF loading phase were included in group A, while treated patients were included in group B. Qualitative and quantitative OCTA analyses were performed on outer retina to choriocapillaris (ORCC) slab. CNV size was measured using a free image analysis software (ImageJ, open-source imaging processing software, 2.0.0). Twenty-five eyes of 25 patients were enrolled in our study (mean age 78.32 ± 6.8 years): 13 treatment-naïve eyes in group A and 12 treated eyes in group B. While qualitative analysis revealed no significant differences from baseline to follow-up in the two groups, quantitative analysis showed in group A a significant decrease in lesion area ( P = 0.023); in group B, no significant change in the lesion area was observed during anti-VEGF therapy ( P = 0.93). Treatment-naïve and treated eyes with CNV secondary to neovascular AMD respond differently to anti-VEGF therapy. This should be taken into account when using OCTA for CNV follow-up or planning therapeutic strategies.

  17. Ocular Angiogenesis: Vascular Endothelial Growth Factor and Other Factors.

    PubMed

    Rubio, Roman G; Adamis, Anthony P

    2016-01-01

    Systematic study of the mechanisms underlying pathological ocular neovascularization has yielded a wealth of knowledge about pro- and anti-angiogenic factors that modulate diseases such as neovascular age-related macular degeneration. The evidence implicating vascular endothelial growth factor (VEGF) in particular has led to the development of a number of approved anti-VEGF therapies. Additional proangiogenic targets that have emerged as potential mediators of ocular neovascularization include hypoxia-inducible factor-1, angiopoietin-2, platelet-derived growth factor-B and components of the alternative complement pathway. As for VEGF, knowledge of these factors has led to a product pipeline of many more novel agents that are in various stages of clinical development in the setting of ocular neovascularization. These agents are represented by a range of drug classes and, in addition to novel small- and large-molecule VEGF inhibitors, include gene therapies, small interfering RNA agents and tyrosine kinase inhibitors. In addition, combination therapy is beginning to emerge as a strategy to improve the efficacy of individual therapies. Thus, a variety of agents, whether administered alone or as adjunctive therapy with agents targeting VEGF, offer the promise of expanding the range of treatments for ocular neovascular diseases. © 2016 S. Karger AG, Basel.

  18. Adeno-associated virus type 8 vector–mediated expression of siRNA targeting vascular endothelial growth factor efficiently inhibits neovascularization in a murine choroidal neovascularization model

    PubMed Central

    Igarashi, Tsutomu; Miyake, Noriko; Fujimoto, Chiaki; Yaguchi, Chiemi; Iijima, Osamu; Shimada, Takashi; Takahashi, Hiroshi

    2014-01-01

    Purpose To assess the feasibility of a gene therapeutic approach to treating choroidal neovascularization (CNV), we generated an adeno-associated virus type 8 vector (AAV2/8) encoding an siRNA targeting vascular endothelial growth factor (VEGF), and determined the AAV2/8 vector’s ability to inhibit angiogenesis. Methods We initially transfected 3T3 cells expressing VEGF with the AAV2/8 plasmid vector psiRNA-VEGF using the H1 promoter and found that VEGF expression was significantly diminished in the transfectants. We next injected 1 μl (3 × 1014 vg/ml) of AAV2/8 vector encoding siRNA targeting VEGF (AAV2/8/SmVEGF-2; n = 12) or control vector encoding green fluorescent protein (GFP) (AAV2/8/GFP; n = 14) into the subretinal space in C57BL/6 mice. One week later, CNV was induced by using a diode laser to make four separate choroidal burns around the optic nerve in each eye. After an additional 2 weeks, the eyes were removed for flat mount analysis of the CNV surface area. Results Subretinal delivery of AAV2/8/SmVEGF-2 significantly diminished CNV at the laser lesions, compared to AAV8/GFP (1597.3±2077.2 versus 5039.5±4055.9 µm2; p<0.05). Using an enzyme-linked immunosorbent assay, we found that VEGF levels were reduced by approximately half in the AAV2/8/SmVEGF-2 treated eyes. Conclusions These results suggest that siRNA-VEGF can be expressed across the retina and that long-term suppression of CNV is possible through the use of stable AAV2/8-mediated siRNA-VEGF expression. In vivo gene therapy may thus be a feasible approach to the clinical management of CNV in conditions such as age-related macular degeneration. PMID:24744609

  19. A value-based medicine analysis of ranibizumab for the treatment of subfoveal neovascular macular degeneration.

    PubMed

    Brown, Melissa M; Brown, Gary C; Brown, Heidi C; Peet, Jonathan

    2008-06-01

    To assess the conferred value and average cost-utility (cost-effectiveness) for intravitreal ranibizumab used to treat occult/minimally classic subfoveal choroidal neovascularization associated with age-related macular degeneration (AMD). Value-based medicine cost-utility analysis. MARINA (Minimally Classic/Occult Trial of the Anti-Vascular Endothelial Growth Factor Antibody Ranibizumab in the Treatment of Neovascular AMD) Study patients utilizing published primary data. Reference case, third-party insurer perspective, cost-utility analysis using 2006 United States dollars. Conferred value in the forms of (1) quality-adjusted life-years (QALYs) and (2) percent improvement in health-related quality of life. Cost-utility is expressed in terms of dollars expended per QALY gained. All outcomes are discounted at a 3% annual rate, as recommended by the Panel on Cost-effectiveness in Health and Medicine. Data are presented for the second-eye model, first-eye model, and combined model. Twenty-two intravitreal injections of 0.5 mg of ranibizumab administered over a 2-year period confer 1.039 QALYs, or a 15.8% improvement in quality of life for the 12-year period of the second-eye model reference case of occult/minimally classic age-related subfoveal choroidal neovascularization. The reference case treatment cost is $52652, and the cost-utility for the second-eye model is $50691/QALY. The quality-of-life gain from the first-eye model is 6.4% and the cost-utility is $123887, whereas the most clinically simulating combined model yields a quality-of-life gain of 10.4% and cost-utility of $74169. By conventional standards and the most commonly used second-eye and combined models, intravitreal ranibizumab administered for occult/minimally classic subfoveal choroidal neovascularization is a cost-effective therapy. Ranibizumab treatment confers considerably greater value than other neovascular macular degeneration pharmaceutical therapies that have been studied in randomized

  20. Aging decreases CO2 reactivity in the retinal artery, but not in the ocular choroidal vessels; a cross-sectional study.

    PubMed

    Miyaji, Akane; Ikemura, Tsukasa; Hayashi, Naoyuki

    2018-04-14

    The CO2 reactivity is often used to assess vascular function, but it is still unclear whether this reactivity is affected by aging. To investigate the effects of aging on the CO2 reactivity in ocular and cerebral vessels, both of which are highly sensitive to hypercapnia, we compared the CO2 reactivity in the retinal artery (RA), retinal and choroidal vessels (RCV), optic nerve head (ONH), and middle cerebral artery (MCA) between young and middle-aged subjects. We measured the CO2 reactivity in 14 young and 11 middle-aged males using laser-speckle flowgraphy during a 3-min inhalation of CO2-rich air. The CO2 reactivity in the RA and ONH were lower in the middle-aged group than in the young group, but no significant effect of age was observed in the RCV or MCA. The CO2 reactivity in the RA and ONH were correlated significantly with age, whereas those in the RCV or MCA were not. These findings suggest that there are regional differences in the effect of age on the CO2 reactivity among not only ocular and cerebral vessels, but also the retinal and choroidal vessels, even though these vessels are in neighboring areas.

  1. Risk factors for choroidal neovascularization and geographic atrophy in the complications of age-related macular degeneration prevention trial.

    PubMed

    2008-09-01

    To determine risk factors for choroidal neovascularization (CNV) and of geographic atrophy (GA) in eyes with large drusen. Cohort study within a multicenter, randomized clinical trial of laser treatment for the prevention of vision loss from advanced age-related macular degeneration. One thousand fifty-two participants with 10 or more large drusen (>or=125 microm) and visual acuity of 20/40 or better in each eye. At baseline, participants provided a brief medical history. Trained readers evaluated baseline color photographs for drusen characteristics and pigmentary abnormalities. One eye of each participant was assigned to laser treatment and the contralateral eye was assigned to observation. The Complications of Age-Related Macular Degeneration Prevention Trial (CAPT) Reading Center readers identified CNV and endpoint GA from color photographs and fluorescein angiograms obtained during follow-up visits scheduled for 5 or 6 years. Estimates of relative risks (RRs) and 95% confidence intervals (CIs) were obtained from survival analyses of observed and treated eyes, considered separately and combined. Development of CNV and of endpoint GA. Choroidal neovascularization developed in 141 observed eyes and 141 treated eyes, including 57 patients affected bilaterally. Statistically significant risk factors for CNV in the multivariate model for all eyes were older age (RR, 2.81 [95% CI, 1.33-5.94] for >79 years vs. 50-59 years), cigarette smoking (RR, 1.98 [95% CI, 1.16-3.39] for current vs. never), and focal hyperpigmentation (RR, 1.84 [95% CI, 1.22-2.76] for >or=250 microm vs. none). Among eyes free of GA at baseline, endpoint GA developed in 61 observed eyes and in 58 treated eyes, including 29 patients affected bilaterally. Statistically significant risk factors for GA in the multivariate model for all eyes were older age (RR, 6.39 [95% CI, 1.64-24.9] for >79 years vs. 50-59 years), greater retinal area covered by drusen (RR, 5.10 [95% CI, 2.57-10.1] for >or=25% vs

  2. The Sustained Delivery of Resveratrol or a Defined Grape Powder Inhibits New Blood Vessel Formation in a Mouse Model of Choroidal Neovascularization

    PubMed Central

    Kanavi, Mozhgan Rezaie; Darjatmoko, Soesiawati; Wang, Shoujian; Azari, Amir A.; Farnoodian, Mitra; Kenealey, Jason D.; van Ginkel, Paul R.; Albert, Daniel M.; Sheibani, Nader; Polans, Arthur S.

    2015-01-01

    The objective of this study was to determine whether resveratrol or a defined, reconstituted grape powder can attenuate the formation of new blood vessels in a mouse model of choroidal neovascularization (CNV). To accomplish this objective, C57BL/6J mice were randomized into control or treatment groups which received either resveratrol or grape powder by daily oral gavage, resveratrol or grape powder delivered ad libitum through the drinking water, or resveratrol by slow release via implanted osmotic pumps. A laser was used to rupture Bruch’s membrane to induce CNV which was then detected in sclerochoroidal eyecups stained with antibodies against intercellular adhesion molecule-2. CNV area was measured using fluorescence microscopy and Image J software. Ad libitum delivery of both resveratrol and grape powder was shown to significantly reduce the extent of CNV by 68% and 57%, respectively. Parallel experiments conducted in vitro demonstrated that resveratrol activates p53 and inactivates Akt/protein kinase B in choroidal endothelial cells, contributing to its anti-proliferative and anti-migratory properties. In addition resveratrol was shown to inhibit the formation of endothelial cell networks, augmenting its overall anti-angiogenic effects. The non-toxic nature of resveratrol makes it an especially attractive candidate for the prevention and/or treatment of CNV. PMID:25361423

  3. FIVE-YEAR OUTCOMES OF INTRAVITREAL RANIBIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN PATIENTS WITH PATHOLOGIC MYOPIA.

    PubMed

    Onishi, Yuka; Yokoi, Tae; Kasahara, Kaori; Yoshida, Takeshi; Nagaoka, Natsuko; Shinohara, Kosei; Kaneko, Yuichiro; Suga, Mitsuki; Uramoto, Kengo; Ohno-Tanaka, Akiko; Ohno-Matsui, Kyoko

    2018-05-03

    To determine the 5-year outcome of intravitreal ranibizumab (IVR) for myopic choroidal neovascularization (CNV). We retrospectively analyzed the medical records of 51 eyes of 51 consecutive patients with myopic CNV who had been treated with IVR with a minimum follow-up period of 5 years after the initial IVR injection. The factors that predicted the best-corrected visual acuity (BCVA) at 5 years after IVR were determined by multiple regression analysis. The mean age of the subjects was 63.6 years, and the mean axial length was 29.4 mm. The mean number of IVR was 1.6, and 34 eyes (66.7%) had only a single IVR. At the baseline and at the 1-year, 2-year, 4-year, and 5-year period, the mean BCVAs were 20/49, 20/37, 20/41, 20/45, and 20/42, respectively. Stepwise multiple regression analysis showed that the BCVA at 5-year period was significantly correlated with the baseline BCVA, the number of IVR injections, and the size of the CNV-related macular atrophy. Intravitreal ranibizumab provide a 5-year visual benefit in eyes with myopic CNV compared with the natural course. A lack of enlargement of the CNV-related macular atrophy, a better baseline BCVA, and a minimum number of IVR injections were associated with better visual outcomes.

  4. Local partial depletion of CD11b+ cells and their influence on choroidal neovascularization using the CD11b-HSVTK mouse model.

    PubMed

    Brockmann, Claudia; Kociok, Norbert; Dege, Sabrina; Davids, Anja-Maria; Brockmann, Tobias; Miller, Kelly R; Joussen, Antonia M

    2018-03-14

    To assess the influence of retinal macrophages and microglia on the formation of choroidal neovascularization (CNV). Therefore, we used a transgenic mouse (CD11b-HSVTK) in which the application of ganciclovir (GCV) results in a depletion of CD11b + cells. We first investigated if a local depletion of CD11b + macrophages and microglia in the retina is feasible. In a second step, the influence of CD11b + cell depletion on CNV formation was analysed. One eye of each CD11b-HSVTK mouse was injected with GCV, and the fellow eye received sodium chloride solution (NaCl). Cell counting was performed at day 3 and 7 (one injection) or at day 14 and 21 (two injections). Choroidal neovascularization (CNV) was induced by argon laser and analysed at day 14. The most effective CD11b + cell depletion was achieved 7 days after a single injection and 14 days after two injections of GCV. After two injections of GCV, we found a significant reduction of CD11b + cells in central (52 ± 23.9 cells/mm 2 ) and peripheral retina (53 ± 20.6 cells/mm 2 ); compared to eyes received NaCl (216 ± 49.0 and 210 ± 50.5 cells/mm 2 , p < 0.001, respectively). Regarding CNV areas, no statistical significance was found between the groups. The CD11b-HSVTK mouse is a feasible model for a local depletion of CD11b + cells in the retina. Nevertheless, only a partial depletion of CD11b + cells could be achieved compared to baseline data without any intravitreal injections. Our results did not reveal a significant reduction in CNV areas. In the light of previous knowledge, the potential influence of systemic immune cells on CNV formation might be more relevant than expected. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  5. Choroidal metastases: Origin, features, and therapy

    PubMed Central

    Arepalli, Sruthi; Kaliki, Swathi; Shields, Carol L

    2015-01-01

    The choroid is the most common ocular site for metastatic disease, owing to abundant vascular supply. The primary cancers that most commonly lead to choroidal metastases include breast cancer (40-47%) and lung cancer (21-29%). Bilateral, multifocal metastases are most often secondary to breast cancer, whereas unilateral, unifocal metastasis are more commonly found with lung cancer. The treatment of choroidal metastasis depends on the systemic status of the patient and number, location, and laterality of the choroidal tumors. Treatment options include observation in patients with poor systemic status or those with resolved or asymptomatic disease; systemic chemotherapy, immunotherapy, hormone therapy, or whole eye radiotherapy if the metastases are active, multifocal and bilateral; plaque radiotherapy, transpupillary radiotherapy, or photodynamic therapy for active, solitary metastasis; and enucleation for those with blind painful eye. A database search was performed on PubMed, using the terms “choroidal metastasis,” or “choroidal metastases,” in combination with terms such as “treatment,” “features,” or “diagnosis.” Relevant articles were extracted and reviewed. PMID:25827542

  6. Clinical and Histopathologic Ocular Findings in Disseminated Mycobacterium chimaera Infection after Cardiothoracic Surgery.

    PubMed

    Zweifel, Sandrine A; Mihic-Probst, Daniela; Curcio, Christine A; Barthelmes, Daniel; Thielken, Andrea; Keller, Peter M; Hasse, Barbara; Böni, Christian

    2017-02-01

    To investigate and characterize clinical and histopathologic ocular findings in patients with disseminated infection with Mycobacterium chimaera, a slow-growing nontuberculous mycobacterium (NTM), subsequent to cardiothoracic surgery. Observational case series. Five white patients (10 eyes). Analysis of clinical ocular findings, including visual acuity, slit-lamp biomicroscopy, spectral-domain optical coherence tomography (SD OCT), fundus autofluorescence (FAF), and fluorescein angiography/indocyanine green (ICG) angiography findings, of patients with a disseminated M. chimaera infection. Biomicroscopic and multimodal imaging findings were compared with the histopathology of 1 patient. Clinical and histopathologic ocular findings of M. chimaera. The mean age of the 5 male patients, diagnosed with endocarditis or aortic graft infection, was 57.8 years. Clinical ocular findings included anterior and intermediate uveitis, optic disc swelling, and white-yellowish choroidal lesions. Multifocal choroidal lesions were observed bilaterally in all patients and were hyperfluorescent on fluorescein angiography, hypofluorescent on ICG angiography, and correlated with choroidal lesions on SD OCT. The extent of choroidal lesions varied from few in 2 patients to widespread miliary lesions in 3 patients leading to localized choroidal thickening with elevation of the overlying retinal layers. Spectral-domain optical coherence tomography through regressing lesions revealed altered outer retinal layers and choroidal hypertransmission. The ocular findings were correlated with the course of the systemic disease. Patients with few choroidal lesions had a favorable outcome, whereas all patients with widespread chorioretinitis died of systemic complications of M. chimaera infection despite long-term targeted antimicrobial therapy. Ocular tissue was obtained from 1 patient at autopsy. Necropsy of 2 eyes of 1 patient revealed prominent granulomatous lymphohistiocytic choroiditis with

  7. Prevalence of choroidal nevus and retinal pigment epithelial alterations in vitiligo patients.

    PubMed

    Fleissig, Efrat; Pavlovksy, Mor; Loewenstein, Anat; Zur, Dinah; Newman, Hadas; Keren, Shay; Goldenberg, Dafna; Bar-Ilan, Efrat; Goldstein, Michaella

    2018-05-01

    To investigate ocular manifestations in patients with vitiligo by multimodal imaging, including optical coherence tomography (OCT), color fundus photography, and fundus autofluorescence (FAF). In this prospective, observational clinical study, vitiligo patients underwent ophthalmologic and dermatologic clinical assessment and imaging by spectral-domain OCT, FAF, and color fundus imaging. Ocular echography was performed as indicated. Statistical analysis was performed using paired T test and Pearson correlation. A total of 61 eyes of 31 vitiligo patients were examined. Ocular findings consisted of choroidal nevi (n = 10, 32%), of which four (40%) were bilateral; two patients (6.5%) had a prominent choroidal pattern, two (6.5%) had hypopigmentary retinal pigment epithelium (RPE) lesions, and one (3.2%) had peripapillary atrophy of the RPE. Choroidal nevi were demonstrated only in eyes of patients with generalized vitiligo and were more common with upper body involvement (p = 0.02) and more prevalent in women (p = 0.02). Hypopigmentary lesions were detected in two patients and demonstrated on OCT as RPE atrophy and as photoreceptor/RPE changes. In this case series, vitiligo patients had a higher rate of choroidal nevi than previously reported. The hypopigmentary vitiliginous fundus lesions were depicted on OCT as photoreceptor and RPE atrophy. These findings may suggest the advisability of regular ocular monitoring for vitiligo patients.

  8. Bevacizumab inhibits proliferation of choroidal endothelial cells by regulation of the cell cycle.

    PubMed

    Rusovici, Raluca; Patel, Chirag J; Chalam, Kakarla V

    2013-01-01

    The purpose of this study was to evaluate cell cycle changes in choroidal endothelial cells treated with varying doses of bevacizumab in the presence of a range of concentrations of vascular endothelial growth factor (VEGF). Bevacizumab, a drug widely used in the treatment of neovascular age-related macular degeneration, choroidal neovascularization, and proliferative diabetic retinopathy, neutralizes all isoforms of VEGF. However, the effect of intravitreal administration of bevacizumab on the choroidal endothelial cell cycle has not been established. Monkey choroidal endothelial (RF/6A) cells were treated with VEGF 50 ng/mL and escalating doses of bevacizumab 0.1-2 mg/mL for 72 hours. Cell cycle changes in response to bevacizumab were analyzed by flow cytometry and propidium iodide staining. Cell proliferation was measured using the WST-1 assay. Morphological changes were recorded by bright field cell microscopy. Bevacizumab inhibited proliferation of choroidal endothelial cells by stabilization of the cell cycle in G0/G1 phase. Cell cycle analysis of VEGF-enriched choroidal endothelial cells revealed a predominant increase in the G2/M population (21.84%, P, 0.01) and a decrease in the G0/G1 phase population (55.08%, P, 0.01). Addition of escalating doses of bevacizumab stabilized VEGF-enriched cells in the G0/G1 phase (55.08%, 54.49%, 56.3%, and 64% [P, 0.01]) and arrested proliferation by inhibiting the G2/M phase (21.84%, 21.46%, 20.59%, 20.94%, and 16.1% [P, 0.01]). The increase in G0/G1 subpopulation in VEGF-enriched and bevacizumab-treated cells compared with VEGF-enriched cells alone was dose-dependent. Bevacizumab arrests proliferation of VEGF-enriched choroidal endothelial cells by stabilizing the cell cycle in the G0/G1 phase and inhibiting the G2/M phase in a dose-dependent fashion.

  9. Topical application of a G-Quartet aptamer targeting nucleolin attenuates choroidal neovascularization in a model of age-related macular degeneration.

    PubMed

    Leaderer, Derek; Cashman, Siobhan M; Kumar-Singh, Rajendra

    2015-11-01

    Choroidal neovascularization (CNV) associated with the 'wet' form of age related macular degeneration (AMD) is one of the most common causes of central vision loss among the elderly. The 'wet' form of AMD is currently treated by intravitreal delivery of anti-VEGF agents. However, intravitreal injections are associated with complications and long-term inhibition of VEGF leads to macular atrophy. Thus, there is currently an unmet need for the development of therapies for CNV that target molecules other than VEGF. Here, we describe nucleolin as a novel target for the 'wet' form of AMD. Nucleolin was found on the surface of endothelial cells that migrate from the choroid into the subretinal space in the laser-induced model of 'wet' AMD. AS1411 is a previously described G-quartet oligonucleotide that has been shown to bind nucleolin. We found that AS1411 inhibited the formation of tubes by human umbilical vein endothelial cells (HUVECs) by approximately 27.4% in vitro. AS1411 co-localized with the site of laser induced CNV in vivo. Intravitreally injected AS1411 inhibited laser-induced CNV by 37.6% and attenuated infiltration of macrophages by 40.3%. Finally, topical application of AS1411 led to a 43.4% reduction in CNV. Our observations have potential implications for the development of therapies for CNV and specifically for the 'wet' form of AMD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Changes of choroidal neovascularization in indocyanine green angiography after intravitreal ranibizumab injection.

    PubMed

    Lee, Ji Eun; Kim, Hyun Woong; Lee, Sang Joon; Lee, Joo Eun

    2015-05-01

    To investigate vascular structural changes of choroidal neovascularization (CNV) followed by intravitreal ranibizumab injections using indocyanine green angiography. A total of 31 patients with exudative age-related macular degeneration and CNV whose structures were identifiable in indocyanine green angiography were included. Ranibizumab was injected into the vitreous cavity once a month for 3 months and then as needed for the next 3 months prospectively. Indocyanine green angiography was performed at baseline, 3, and 6 months. Early to midphase images of the indocyanine green angiography in the details of vascular structure of the CNV were discerned the best were used in the image analysis. Vascular structures of CNV were described as arteriovenular and capillary components, and structural changes were assessed. Arteriovenular components were observed in 29 eyes (94%). Regression of the capillary components was observed in most cases. Although regression of arteriovenular component was noted in 14 eyes (48%), complete resolution was not observed. The eyes were categorized into 3 groups according to CNV structural changes: the regressed (Group R, 10 eyes, 31%), the matured (Group M, 7 eyes, 23%), and the growing (Group G, 14 eyes, 45%). In Group R, there was no regrowth of CNV found at 6 months. In Group M, distinct vascular structures were observed at 3 months and persisted without apparent changes at 6 months. In Group G, growth or reperfusion of capillary components from the persisting arteriovenular components was noted at 6 months. Both capillary and arteriovenular components were regressed during monthly ranibizumab injections. However, CNV regrowth was observed in a group of patients during the as-needed treatment phase.

  11. Ranibizumab for choroidal neovascularization secondary to pseudoxanthoma elasticum: 4-year results from the PIXEL study in France.

    PubMed

    Mimoun, Gérard; Ebran, Jean-Marc; Grenet, Typhaine; Donati, Alain; Cohen, Salomon-Yves; Ponthieux, Anne

    2017-08-01

    To evaluate the long-term effectiveness and safety of ranibizumab 0.5 mg in patients with choroidal neovascularization (CNV) secondary to pseudoxanthoma elasticum (PXE) in a real-world setting. A descriptive, observational, multicenter study in a retrospective and prospective cohort was conducted in France that included patients who had received at least one injection of ranibizumab 0.5 mg during the period October 2011 to October 2014, for CNV secondary to PXE. Eligible patients were identified by review of medical records or during routine consultations. The main objectives were to describe patient characteristics, assess changes in best-corrected visual acuity [VA, Early Treatment Diabetic Retinopathy Study (ETDRS) letters] over time, the number and reasons for ranibizumab treatment and overall safety. Of the 72 enrolled patients (98 eyes) from 23 centers, 39 (54.2%) were male and mean [±standard deviation (SD)] age was 59.6 (±8.3) years. The mean VA was 64.6 letters at the first ranibizumab injection, which was maintained at the 1-year follow-up (64.7 letters). Thereafter, the mean VA was stable until the 4-year follow-up. At 4 years, the proportion of eyes with VA gain of ≥15 letters was 3/19 (15.8%) and stable VA (change between -15 and +15 letters) was 10/19 (52.6%). Mean (±SD) annual number of ranibizumab injections was 4.1 (±4.0), lower in the second versus first year. The most common reason for ranibizumab treatment was progression of neovascular activity (42.9%). No deaths or new safety findings were reported. In patients with CNV secondary to PXE, ranibizumab 0.5 mg resulted in stable VA over 4 years with a limited number of injections. Safety findings were consistent with the established safety profile of ranibizumab.

  12. Optical Coherence Tomography Angiography: A Useful Tool for Diagnosis of Treatment-Naïve Quiescent Choroidal Neovascularization.

    PubMed

    Carnevali, Adriano; Cicinelli, Maria Vittoria; Capuano, Vittorio; Corvi, Federico; Mazzaferro, Andrea; Querques, Lea; Scorcia, Vincenzo; Souied, Eric H; Bandello, Francesco; Querques, Giuseppe

    2016-09-01

    To describe the optical coherence tomography angiography (OCT-A) features of treatment-naïve quiescent choroidal neovascularization (CNV) secondary to age-related macular degeneration, and to estimate the detection rate for neovascularization by means of OCT-A. Diagnostic tool validity assessment. Treatment-naïve quiescent CNV were identified from a pool of patients at 2 retina referral centers. Patients underwent a complete ophthalmologic examination including fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and OCT-A. Detection rates of CNV by means of OCT-A were estimated with a second cohort of patients without CNV (negative controls). Twenty-two eyes of 20 consecutive patients with quiescent CNV were included. In 4 out of 22 eyes it was not possible to classify the CNV "shape," "core," "margin," and "location," either because the vascular network was not clearly shown (3 cases) or because it was not visible at all (1 case). CNV shape on OCT-A was rated as circular in 8 eyes and irregular in 10 eyes. CNV core was visible in 2 eyes. CNV margin was considered as well defined in 15 eyes and poorly defined in 3 eyes. CNV margin showed small loops in 9 eyes and large loops in the other 6 eyes. CNV location was foveal-sparing in 12 eyes. Sensitivity and specificity of quiescent CNV detection by OCT-A turned out to be 81.8% and 100%, respectively. OCT-A allows the clinician to noninvasively identify treatment-naïve quiescent CNV and may be considered as a useful tool to guide the frequency of return visits and, possibly, make treatment decisions. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Successful single treatment with ziv-aflibercept for existing corneal neovascularization following ocular chemical insult in the rabbit model.

    PubMed

    Gore, Ariel; Horwitz, Vered; Cohen, Maayan; Gutman, Hila; Cohen, Liat; Gez, Rellie; Kadar, Tamar; Dachir, Shlomit

    2018-06-01

    To evaluate the efficacy of ziv-aflibercept as a treatment for established corneal neovascularization (NV) and to compare its efficacy to that of bevacizumab following ocular chemical insult of sulfur mustard (SM) in the rabbit model. Chemical SM burn was induced in the right eye of NZW rabbits by vapor exposure. Ziv-aflibercept (2 mg) was applied once to neovascularized eyes by subconjunctival injection while subconjunctival bevacizumab (5 mg) was administered twice a week, for 3 weeks. Non-treated exposed eyes served as a control. A clinical follow-up employed by slit-lamp microscope, was performed up to 12 weeks following exposure and digital photographs of the cornea were taken for measurement of blood vessels length using the image analysis software. Eyes were taken for histological evaluation 2, 4 and 8 weeks following treatment for general morphology and for visualization of NV, using H&E and Masson Trichrome stainings, while conjunctival goblet cell density was determined by PAS staining. Corneal NV developed, starting as early as two weeks after exposure. A single subconjunctival treatment of ziv-aflibercept at 4 weeks post exposure, significantly reduced the extent of existing NV already one week following injection, an effect which lasted for at least 8 weeks following treatment, while NV in the non-treated exposed eyes continued to advance. The extensive reduction in corneal NV in the ziv-aflibercept treated group was confirmed by histological evaluation. Bevacizumab multiple treatment showed a benefit in NV reduction, but to a lesser extent compared to the ziv-aflibercept treatment. Finally, ziv-aflibercept increased the density of conjunctival goblet cells as compared to the exposed non-treated group. Subconjunctival ziv-aflibercept single treatment presented a highly efficient long-term therapeutic benefit in reducing existing corneal NV, following ocular sulfur mustard exposure. These findings show the robust anti-angiogenic efficacy of ziv

  14. Antiangiogenic activity of aganirsen in nonhuman primate and rodent models of retinal neovascular disease after topical administration.

    PubMed

    Cloutier, Frank; Lawrence, Matthew; Goody, Robin; Lamoureux, Stéphanie; Al-Mahmood, Salman; Colin, Sylvie; Ferry, Antoine; Conduzorgues, Jean-Pascal; Hadri, Amel; Cursiefen, Claus; Udaondo, Patricia; Viaud, Eric; Thorin, Eric; Chemtob, Sylvain

    2012-03-09

    Aganirsen, an antisense oligonucleotide inhibiting insulin receptor substrate (IRS)-1 expression, has been shown to promote the regression of pathologic corneal neovascularization in patients. In this study, the authors aimed to demonstrate the antiangiogenic activity of aganirsen in animal models of retinal neovascularization. Eyedrops of aganirsen were applied daily in nonhuman primates after laser-induced choroidal neovascularization (CNV; model of wet age-related macular degeneration [AMD]) and in newborn rats after oxygen-induced retinopathy (OIR; model of ischemic retinopathy). Retinal aganirsen concentrations were assessed in rabbits and monkeys after topical delivery (21.5, 43, or 86 μg). Clinical significance was further evaluated by determination of IRS-1 expression in monkey and human retinal biopsy specimens. Topical corneal application of aganirsen attenuated neovascular lesion development dose dependently in African green monkeys. The incidence of high-grade CNV lesions (grade IV) decreased from 20.5% in vehicle-treated animals to 1.7% (P < 0.05) at the 86-μg dose. Topical aganirsen inhibited retinal neovascularization after OIR in rats (P < 0.05); furthermore, a single intravitreal injection of aganirsen reduced OIR as effectively as ranibizumab, and their effects were additive. Significantly, topical applications of aganirsen did not interfere with physiological retinal vessel development in newborn rats. Retinal delivery after topical administration was confirmed, and retinal expression of IRS-1 was demonstrated to be elevated in patients with subretinal neovascularization and AMD. Topical application of aganirsen offers a safe and effective therapy for both choroidal and retinal neovascularization without preventing its normal vascularization. Together, these findings support the clinical testing of aganirsen for human retinal neovascular diseases.

  15. JNK inhibition reduces apoptosis and neovascularization in a murine model of age-related macular degeneration.

    PubMed

    Du, Hongjun; Sun, Xufang; Guma, Monica; Luo, Jing; Ouyang, Hong; Zhang, Xiaohui; Zeng, Jing; Quach, John; Nguyen, Duy H; Shaw, Peter X; Karin, Michael; Zhang, Kang

    2013-02-05

    Age-related macular degeneration (AMD) is the leading cause of registered blindness among the elderly and affects over 30 million people worldwide. It is well established that oxidative stress, inflammation, and apoptosis play critical roles in pathogenesis of AMD. In advanced wet AMD, although, most of the severe vision loss is due to bleeding and exudation of choroidal neovascularization (CNV), and it is well known that vascular endothelial growth factor (VEGF) plays a pivotal role in the growth of the abnormal blood vessels. VEGF suppression therapy improves visual acuity in AMD patients. However, there are unresolved issues, including safety and cost. Here we show that mice lacking c-Jun N-terminal kinase 1 (JNK1) exhibit decreased inflammation, reduced CNV, lower levels of choroidal VEGF, and impaired choroidal macrophage recruitment in a murine model of wet AMD (laser-induced CNV). Interestingly, we also detected a substantial reduction in choroidal apoptosis of JNK1-deficient mice. Intravitreal injection of a pan-caspase inhibitor reduced neovascularization in the laser-induced CNV model, suggesting that apoptosis plays a role in laser-induced pathological angiogenesis. Intravitreal injection of a specific JNK inhibitor decreased choroidal VEGF expression and reduced pathological CNV. These results suggest that JNK1 plays a key role in linking oxidative stress, inflammation, macrophage recruitment apoptosis, and VEGF production in wet AMD and pharmacological JNK inhibition offers a unique and alternative avenue for prevention and treatment of AMD.

  16. Ranibizumab for the treatment of neovascular AMD.

    PubMed

    Kaiser, P K; Do, D V

    2007-03-01

    Age-related macular degeneration (AMD) is the leading cause of adult blindness among individuals aged 50 and older in the Western world, with the neovascular form of AMD responsible for the most severe and rapid visual loss. Although monotherapy with currently available treatments can slow the rate of loss of vision in eyes with neovascular AMD, they do not significantly improve vision. Vascular endothelial growth factor-A (VEGF-A) plays a critical role in the pathogenesis of neovascular AMD, and ranibizumab is a promising new treatment that targets all VEGF-A isoforms and their biologically active degradation products. Clinical trials have reported that ranibizumab treatment resulted in greater proportions of patients achieving a < 15 letter loss of visual acuity and improved vision at 12 and 24 months than control groups. The incidence of serious ocular and systemic adverse events was low in all ranibizumab trials to date. Currently, ranibizumab is the only treatment for neovascular AMD to demonstrate significant improvement in vision for many patients and represents a major advance in treating neovascular AMD.

  17. Role of endothelin-1 in choroidal blood flow regulation during isometric exercise in healthy humans.

    PubMed

    Fuchsjäger-Mayrl, Gabriele; Luksch, Alexandra; Malec, Magdalena; Polska, Elzbieta; Wolzt, Michael; Schmetterer, Leopold

    2003-02-01

    There is evidence that the choroid has some autoregulatory capacity in response to changes in ocular perfusion pressure (OPP). The mediators of this response are hitherto unidentified. The hypothesis for the current study was that endothelin (ET)-1 and/or angiotensin (ANF)-II may be involved in choroidal vasoconstriction during an increase in OPP. To test this hypothesis a randomized, double-masked, placebo-controlled, three way crossover study was performed in 12 healthy male volunteers. Subjects received on different study days intravenous infusions of the specific ET(A) receptor antagonist BQ-123, the angiotensin converting enzyme inhibitor enalapril or placebo. During these infusion periods subjects were asked to squat for 6 minutes. Choroidal blood flow was measured using a confocal laser Doppler flowmeter and ocular perfusion pressure (OPP) was calculated from mean arterial pressure and intraocular pressure. BQ-123 and enalapril had no effect on basal blood pressure, pulse rate, intraocular pressure, or choroidal blood flow. During isometric exercise, a pronounced increase in mean arterial pressure paralleled by an increase in OPP was observed. Although choroidal blood flow slightly increased during squatting, the increase was much less pronounced than the increase in OPP, indicating some regulatory potential of the choroid. Enalapril did not alter the choroidal pressure-flow relationship during isometric exercise, but BQ-123 induced a significant leftward shift of the pressure-flow curve (P < 0.001). The present data indicate that ET-1, but not ANG II, plays a role in choroidal blood flow regulation during isometric exercise in healthy humans. Hence, impaired choroidal autoregulation in patients with ocular vascular diseases may arise from an altered endothelin system. Further studies in such patients are warranted to verify this hypothesis.

  18. Retinopathy of prematurity: inflammation, choroidal degeneration, and novel promising therapeutic strategies.

    PubMed

    Rivera, José Carlos; Holm, Mari; Austeng, Dordi; Morken, Tora Sund; Zhou, Tianwei Ellen; Beaudry-Richard, Alexandra; Sierra, Estefania Marin; Dammann, Olaf; Chemtob, Sylvain

    2017-08-22

    Retinopathy of prematurity (ROP) is an important cause of childhood blindness globally, and the incidence is rising. The disease is characterized by initial arrested retinal vascularization followed by neovascularization and ensuing retinal detachment causing permanent visual loss. Although neovascularization can be effectively treated via retinal laser ablation, it is unknown which children are at risk of entering this vision-threatening phase of the disease. Laser ablation may itself induce visual field deficits, and there is therefore a need to identify targets for novel and less destructive treatments of ROP. Inflammation is considered a key contributor to the pathogenesis of ROP. A large proportion of preterm infants with ROP will have residual visual loss linked to loss of photoreceptor (PR) and the integrity of the retinal pigment epithelium (RPE) in the macular region. Recent studies using animal models of ROP suggest that choroidal degeneration may be associated with a loss of integrity of the outer retina, a phenomenon so far largely undescribed in ROP pathogenesis. In this review, we highlight inflammatory and neuron-derived factors related to ROP progression, as well, potential targets for new treatment strategies. We also introduce choroidal degeneration as a significant cause of residual visual loss following ROP. We propose that ROP should no longer be considered an inner retinal vasculopathy only, but also a disease of choroidal degeneration affecting both retinal pigment epithelium and photoreceptor integrity.

  19. Choroidal Round Hyporeflectivities in Geographic Atrophy.

    PubMed

    Corbelli, Eleonora; Sacconi, Riccardo; De Vitis, Luigi Antonio; Carnevali, Adriano; Rabiolo, Alessandro; Querques, Lea; Bandello, Francesco; Querques, Giuseppe

    2016-01-01

    In geographic atrophy (GA), choroidal vessels typically appear on structural optical coherence tomography (OCT) as hyperreflective round areas with highly reflective borders. We observed that some GA eyes show choroidal round hyporeflectivities with highly reflective borders beneath the atrophy, and futher investigated the charcteristcs by comparing structural OCT, indocyanine green angiography (ICGA) and OCT angiography (OCT-A). Round hyporeflectivities were individuated from a pool of patients with GA secondary to non-neovascular age-related macular degeneration consecutively presenting between October 2015 and March 2016 at the Medical Retina & Imaging Unit of the University Vita-Salute San Raffaele. Patients underwent a complete ophthalmologic examination including ICGA, structural OCT and OCT-A. The correspondence between choroidal round hyporeflectivities beneath GA on structural OCT and ICGA and OCT-A imaging were analyzed. Fifty eyes of 26 consecutive patients (17 females and 9 males; mean age 76.8±6.2 years) with GA were included. Twenty-nine round hyporeflectivities have been found by OCT in choroidal layers in 21 eyes of 21 patients (42.0%; estimated prevalence of 57.7%). All 29 round hyporeflectivities showed constantly a hyperreflective border and a backscattering on structural OCT, and appeared as hypofluorescent in late phase ICGA and as dark foci with non detectable flow in the choroidal segmentation of OCT-A. Interestingly, the GA area was greater in eyes with compared to eyes without round hyporeflectivities (9.30±5.74 and 5.57±4.48mm2, respectively; p = 0.01). Our results suggest that most round hyporeflectivities beneath GA may represent non-perfused or hypo-perfused choroidal vessels with non-detectable flow.

  20. Choroidal and scleral mechanisms of compensation for spectacle lenses in chicks.

    PubMed

    Wildsoet, C; Wallman, J

    1995-05-01

    It is known that when hyperopic or myopic defocus is imposed on chick eyes by spectacle lenses, they rapidly compensate, becoming myopic or hyperopic respectively, by altering the depth of their vitreous chamber. Changes in two components--ocular length and choroidal thickness--underlie this rapid compensation. With monocular lens treatment, hyperopic defocus imposed by negative lenses resulted in substantially increased ocular elongation and a slight thinning of the choroid, both changes resulting in myopia; myopic defocus imposed by positive lenses resulted a dramatic increase in choroidal thickness, which pushed the retina forward toward the image plane, and a slight decrease in ocular elongation, both changes resulting in hyperopia. The refractive error after 5 days of lens wear correlated well with vitreous chamber depth, which reflected the changes in both choroidal thickness and ocular length. The degree of compensation for lenses was not affected by whether the fellow eye was covered or open. Both form-deprivation myopia and lens-induced myopia declined with age in parallel, but wearing a -15 D lens produced more myopia than did form deprivation. The spectacle lenses affected the refractive error not only of the lens-wearing eye, but also, to a much lesser degree, of the untreated fellow eye. At lens removal refractive errors were opposite in sign to the lense worn, and the subsequent changes in choroidal thickness and ocular length were also opposite to those that occurred when the lenses were in place. In this situation as well, effects of the spectacle lenses on the fellow eyes were observed. Eyes with no functional afferent connection to the brain because of either prior optic nerve section or intraocular tetrodotoxin injections showed compensatory changes to imposed defocus, but these were limited to compensation for imposed myopic defocus, at least for the eyes with optic nerve section. In addition, optic nerve section, but not tetrodotoxin treatment

  1. TNF-α mediates choroidal neovascularization by upregulating VEGF expression in RPE through ROS-dependent β-catenin activation.

    PubMed

    Wang, Haibo; Han, Xiaokun; Wittchen, Erika S; Hartnett, M Elizabeth

    2016-01-01

    Inflammation, oxidative stress, and angiogenesis have been proposed to interact in age-related macular degeneration. It has been postulated that external stimuli that cause oxidative stress can increase production of vascular endothelial growth factor (VEGF) in retinal pigment epithelial (RPE) cells. In this study, we tested the hypothesis that the inflammatory cytokine, tumor necrosis factor alpha (TNF-α), contributed to choroidal neovascularization (CNV) by upregulating VEGF in RPE through intracellular reactive oxygen species (ROS)-dependent signaling and sought to understand the mechanisms involved. In a murine laser-induced CNV model, 7 days after laser treatment and intravitreal neutralizing mouse TNF-α antibody or isotype immunoglobulin G (IgG) control, the following measurements were made: 1) TNF-α protein and VEGF protein in RPE/choroids with western blot, 2) CNV volume in RPE/choroidal flatmounts, and 3) semiquantification of oxidized phospholipids stained with E06 antibody within CNV with immunohistochemistry (IHC). In cultured human RPE cells treated with TNF-α or PBS control, 1) ROS generation was measured using the 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence assay, and 2) NOX4 protein and VEGF protein or mRNA were measured with western blot or quantitative real-time PCR in cells pretreated with apocynin or nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) inhibitor, VAS 2870, or transfected with p22phox siRNA, and each was compared to its appropriate control. Western blots of phosphorylated p65 (p-p65), total p65 and β-actin, and quantitative real-time PCR of VEGF mRNA were measured in human RPE cells treated with TNF-α and pretreatment with the nuclear factor kappa B inhibitor, Bay 11-7082 or control. Western blots of β-catenin, VEGF, and p22phox and coimmunoprecipitation of β-catenin and T-cell transcriptional factor were performed in human RPE cells treated with TNF-α following pretreatment with

  2. Role of NO in choroidal blood flow regulation during isometric exercise in healthy humans.

    PubMed

    Luksch, Alexandra; Polska, Elzbieta; Imhof, Andrea; Schering, Joanne; Fuchsjäger-Mayrl, Gabriele; Wolzt, Michael; Schmetterer, Leopold

    2003-02-01

    Nitric oxide (NO) is an important regulator of basal choroidal blood flow. Animal experiments indicate that NO is also involved in choroidal blood flow regulation during changes in ocular perfusion pressure and inhibition of NO synthase (NOS) has been reported to shift choroidal pressure-flow curves to the right. The hypothesis for the study was that inhibition of NOS may influence choroidal blood flow during isometric exercise. To test this hypothesis, a randomized, double-masked, placebo-controlled, three-way crossover study was performed in 12 healthy male volunteers. Subjects received on different study days intravenous infusions of N(G)-monomethyl-L-arginine (L-NMMA), phenylephrine, or placebo. During these infusion periods, subjects were asked to squat for 6 minutes. Choroidal blood flow was assessed with laser Doppler flowmetry, and ocular perfusion pressure (OPP) was calculated from mean arterial pressure and intraocular pressure. L-NMMA and phenylephrine increased resting OPP by 10% and 13%, respectively, but only L-NMMA reduced resting choroidal blood flow (-17%, P < 0.001). The relative increase in OPP during isometric exercise was comparable with all drugs administered. Isometric exercise increased choroidal blood flow during administration of placebo and phenylephrine, but not during administration of L-NMMA (P < 0.001 vs. placebo). These data indicate that NO plays an important role in the regulation of choroidal blood flow during isometric exercise.

  3. [Subretinal neovascular membrane in angioid streaks treated with intravitreal bevacizumab].

    PubMed

    García-López, A; González-Castaño, C

    2014-05-01

    Angioid streaks are breaks in Bruch's membrane that may be associated, among others, with pseudoxanthoma elasticum. Its most common complication is the development of subretinal neovascular membranes (SRNVM) and the decreased vision this entails. A 28 year old woman with angioid streaks and SRNVM in the left eye, who received 3 injections of intravitreal bevacizumab, with rapid improvement in vision and stability during 11 months follow up. The finding of angioid streaks led to the diagnosis of pseudoxanthoma elasticum. Intravitreal bevacizumab should be considered as an effective treatment option for choroidal neovascularization associated with angioid streaks. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  4. Indocyanine green angiographic evidence of choroiditis in scleroderma.

    PubMed

    Abdellatief, Amro; Balasubramaniam, Saranya C; Grube, Thomas J; Gonzalez Santiago, Tania M; Osborn, Thomas G; Pulido, Jose S

    2015-01-01

    The purpose of this case report was to demonstrate evidence of indocyanine green angiography leakage consistent with choroiditis in a patient with scleroderma. In this case report, the patient underwent a variety of tests and examinations, including systemic evaluation, full ocular examination, skin biopsy, indocyanine green, and fluorescein angiography testing. A 52-year-old man had blurred vision centrally in both eyes. Vision was 20/25 and 20/20. Posterior examination showed cotton-wool spots in both eyes. The patient met European League against Rheumatism (EULAR) criteria for scleroderma. Fluorescein angiography confirmed the presence of leakage from the retinal vessels. More importantly, indocyanine green angiography revealed choroidal vessel leakage in both eyes. This provided evidence of choroiditis before vessel obliteration. Previous studies have shown evidence of choriocapillaris obliteration. Choroidal vessel leakage, however, has not been reported in patients with scleroderma. The results of this case demonstrate the usefulness of indocyanine green angiography in detecting the presence of choroiditis in scleroderma.

  5. Effects of a human VEGF antibody (Bevacizumab) on deprivation myopia and choroidal thickness in the chicken.

    PubMed

    Mathis, Ute; Ziemssen, Focke; Schaeffel, Frank

    2014-10-01

    Vascular endothelial growth factor (VEGF) is a dimeric glycoprotein which is responsible for neovascularization and fenestrations of the choriocapillaris. In neovascular maculopathies secondary to age-related degeneration (nAMD) or pathologic myopia (PM-CNV), its inhibition by humanized antibodies is currently the most successful therapy. The choroid has an important role in maintaining retinal health and its thickness declines with age and with myopia. Since choroidal thickness depends on its perfusion rate, one would expect that anti-VEGF agents can also change choroidal thickness. We have tested the hypothesis in the chicken model, using a humanized antibody, Bevacizumab, and also studied the distribution of VEGF-A in the chicken fundal layers by immunohistochemical techniques. Even though it was raised against human VEGF, Bevacizumab had several long lasting effects in the chicken eye (1) after a single unilateral intravitreal injection of 0.5 mg, it partially suppressed the development of deprivation myopia, similarly in both eyes, (2) it completely suppressed choroidal thickening that normally occurs when eyes recover from induced myopia over a time period of about 10 days, (3) it had little effect on the choroidal thickness in eyes that had normal visual experience, (4) VEGF-A was absent in sclera, but highly expressed in the walls of choroidal blood vessels and presumed nerve fiber bundles, as well as in retinal photoreceptors and cells of the inner and outer nuclear layer. One day after the injection of Bevacizumab, the immunoreactivity against VEGF-A had largely disappeared. In conclusion, Bevacizumab is similary effective in human and chicken tissue, has similar time constants (few days), has almost symmetrical effects on myopia in both eyes even after monocular application, and fully suppresses choroidal thickening that normally occurs during recovery from deprivation myopia. The mechanisms by which Bevacizumab acts on the choroidal thickness are

  6. Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization.

    PubMed

    Lee, Jung Eun; Kim, Koung Li; Kim, Danbi; Yeo, Yeongju; Han, Hyounkoo; Kim, Myung Goo; Kim, Sun Hwa; Kim, Hyuncheol; Jeong, Ji Hoon; Suh, Wonhee

    2017-01-01

    Pathological angiogenesis is one of the major symptoms of severe ocular diseases, including corneal neovascularization. The blockade of vascular endothelial growth factor (VEGF) action has been recognized as an efficient strategy for treating corneal neovascularization. In this study, we aimed to investigate whether nanoparticle-based delivery of apatinib, a novel and selective inhibitor of VEGF receptor 2, inhibits VEGF-mediated angiogenesis and suppresses experimental corneal neovascularization. Water-insoluble apatinib was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro angiogenesis assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles potently inhibited VEGF-induced tube formation, scratch wounding migration, and proliferation of human endothelial cells. In a rat model of alkali burn injury-induced corneal neovascularization, a subconjunctival injection of Apa-HSA-PEG nanoparticles induced a significant decrease in neovascularization compared to that observed with an injection of free apatinib solution or phosphate-buffered saline. An in vivo distribution study using HSA-PEG nanoparticles loaded with fluorescent hydrophobic model drugs revealed the presence of a substantial number of nanoparticles in the corneal stroma within 24 h after injection. These in vitro and in vivo results demonstrate that apatinib-loaded nanoparticles may be promising for the prevention and treatment of corneal neovascularization-related ocular disorders.

  7. Apatinib-loaded nanoparticles suppress vascular endothelial growth factor-induced angiogenesis and experimental corneal neovascularization

    PubMed Central

    Lee, Jung Eun; Kim, Koung Li; Kim, Danbi; Yeo, Yeongju; Han, Hyounkoo; Kim, Myung Goo; Kim, Sun Hwa; Kim, Hyuncheol; Jeong, Ji Hoon; Suh, Wonhee

    2017-01-01

    Pathological angiogenesis is one of the major symptoms of severe ocular diseases, including corneal neovascularization. The blockade of vascular endothelial growth factor (VEGF) action has been recognized as an efficient strategy for treating corneal neovascularization. In this study, we aimed to investigate whether nanoparticle-based delivery of apatinib, a novel and selective inhibitor of VEGF receptor 2, inhibits VEGF-mediated angiogenesis and suppresses experimental corneal neovascularization. Water-insoluble apatinib was encapsulated in nanoparticles composed of human serum albumin (HSA)-conjugated polyethylene glycol (PEG). In vitro angiogenesis assays showed that apatinib-loaded HSA-PEG (Apa-HSA-PEG) nanoparticles potently inhibited VEGF-induced tube formation, scratch wounding migration, and proliferation of human endothelial cells. In a rat model of alkali burn injury-induced corneal neovascularization, a subconjunctival injection of Apa-HSA-PEG nanoparticles induced a significant decrease in neovascularization compared to that observed with an injection of free apatinib solution or phosphate-buffered saline. An in vivo distribution study using HSA-PEG nanoparticles loaded with fluorescent hydrophobic model drugs revealed the presence of a substantial number of nanoparticles in the corneal stroma within 24 h after injection. These in vitro and in vivo results demonstrate that apatinib-loaded nanoparticles may be promising for the prevention and treatment of corneal neovascularization-related ocular disorders. PMID:28740387

  8. Surgical removal of subfoveal choroidal neovascularization in pathologic myopia: a 12-year follow-up study.

    PubMed

    Hera, R; Chiquet, C; Romanet, J P

    2013-12-01

    The purpose of this study was to review the 12-year visual outcomes of patients who underwent surgical removal for subfoveal choroidal neovascularization (CNV) attributable to pathologic myopia. This retrospective study included 14 patients, with a mean age of 45.8 years, high myopia (>6 D) and classic subfoveal CNV. They were treated with pars plana vitrectomy and surgical removal of CNV. All patients were followed up every 3 months for 2 years, with visual acuity (VA), fundus examination, and fluorescein angiography and then every year for 5 years. Ten patients underwent a final visit with VA and fundus examination after a minimum 12-year follow-up. The main outcome measurement was VA and the secondary outcome measurement was the lesion size. After 12 years of follow-up, the mean VA did not significantly change over time, with a mean gain of 0.22 logMAR at 1 year, and 0.18, 0.12 and 0.05 at 2, 5 and 12 years, respectively. The anatomical evolution was characterized by a significant enlargement of the lesion size at 5 years. This study showed that final VA after surgical treatment with 12 years of follow-up was poor, due to the significant CNV scar enlargement over time. These results should prompt a prospective randomized study of other medical treatments, particularly anti-vascular endothelial growth factor therapy.

  9. Ocular diseases and nonbattle injuries seen at a tertiary care medical center during the Global War on Terrorism.

    PubMed

    Psolka, Maximilian; Bower, Kraig S; Brooks, Dain B; Donnelly, Steven J; Iglesias, Melissa; Rimm, William R; Ward, Thomas P

    2007-05-01

    We retrospectively reviewed the records of 107 U.S. military personnel referred to the Walter Reed Army Medical Center ophthalmology service with eye diseases and nonbattle injuries diagnosed during Operation Enduring Freedom and Operation Iraqi Freedom. Ocular diseases and nonbattle injuries ranged from minor to vision-threatening, represented a broad variety of conditions, and required the expertise of a number of ophthalmic subspecialists. The most common diagnoses were uveitis (13.1%), retinal detachment (11.2%), infectious keratitis (4.7%), and choroidal neovascularization (4.7%). Eighty-four patients (78.5%) met Army retention standards and were returned to duty. Twenty patients (18.7%) were referred to a medical evaluation board, seven (6.5%) of whom failed to meet retention standards for eye and vision; the retention status of three patients (2.8%) remains to be determined.

  10. The role of PGE2 receptor EP4 in pathologic ocular angiogenesis.

    PubMed

    Yanni, Susan E; Barnett, Joshua M; Clark, Monika L; Penn, John S

    2009-11-01

    PGE(2) binds to PGE(2) receptors (EP(1-4)). The purpose of the present study was to investigate the role of the EP(4) receptor in angiogenic cell behaviors of retinal Müller cells and retinal microvascular endothelial cells (RMECs) and to assess the efficacy of an EP(4) antagonist in rat models of oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (LCNV). Müller cells derived from COX-2-null mice were treated with increasing concentrations of the EP(4) agonist PGE(1)-OH, and wild-type Müller cells were treated with increasing concentrations of the EP(4) antagonist L-161982; VEGF production was assessed. Human RMECs (HRMECs) were treated with increasing concentrations of L-161982, and cell proliferation and tube formation were assessed. Rats subjected to OIR or LCNV were administered L-161982, and the neovascular area was measured. COX-2-null mouse Müller cells treated with increasing concentrations of PGE(1)-OH demonstrated a significant increase in VEGF production (P < or = 0.0165). Wild-type mouse Müller cells treated with increasing concentrations of L-161982 demonstrated a significant decrease in VEGF production (P < or = 0.0291). HRMECs treated with increasing concentrations of L-161982 demonstrated a significant reduction in VEGF-induced cell proliferation (P < or = 0.0033) and tube formation (P < 0.0344). L-161982 treatment significantly reduced pathologic neovascularization in OIR (P < 0.0069) and LCNV (P < or = 0.0329). Preliminary investigation has demonstrated that EP(4) activation or inhibition influences the behaviors of two retinal cell types known to play roles in pathologic ocular angiogenesis. These findings suggest that the EP(4) receptor may be a valuable therapeutic target in neovascular eye disease.

  11. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review

    PubMed Central

    Yang, Shiqi; Zhao, Jingke; Sun, Xiaodong

    2016-01-01

    As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance. PMID:27330279

  12. Theme trends and knowledge structure on choroidal neovascularization: a quantitative and co-word analysis.

    PubMed

    Zhao, Fangkun; Shi, Bei; Liu, Ruixin; Zhou, Wenkai; Shi, Dong; Zhang, Jinsong

    2018-04-03

    The distribution pattern and knowledge structure of choroidal neovascularization (CNV) was surveyed based on literatures in PubMed. Published scientific papers about CNV were retrieved from Jan 1st, 2012 to May 31st, 2017. Extracted MeSH terms were analyzed quantitatively by using Bibliographic Item Co-Occurrence Matrix Builder (BICOMB) and high-frequency MeSH terms were identified. Hierarchical cluster analysis was conducted by SPSS 19.0 according to the MeSH term-source article matrix. High-frequency MeSH terms co-occurrence matrix was constructed to support strategic diagram and social network analysis (SNA). According to the searching strategy, all together 2366 papers were included, and the number of annual papers changed slightly from Jan 1st, 2012 to May 31st, 2017. Among all the extracted MeSH terms, 44 high-frequency MeSH terms were identified and hotspots were clustered into 6 categories. In the strategic diagram, clinical drug therapy, pathology and diagnosis related researches of CNV were well developed. In contrast, the metabolism, etiology, complications, prevention and control of CNV in animal models, and genetics related researches of CNV were relatively immature, which offers potential research space for future study. As for the SNA result, the position status of each component was described by the centrality values. The studies on CNV are relatively divergent and the 6 research categories concluded from this study could reflect the publication trends on CNV to some extent. By providing a quantitative bibliometric research across a 5-year span, it could help to depict an overall command of the latest topics and provide some hints for researchers when launching new projects.

  13. Overexpression of the anti-apoptotic protein BAG3 in human choroidal melanoma: A case report.

    PubMed

    Yunoki, Tatsuya; Tabuchi, Yoshiaki; Kondo, Takashi; Ishii, Yoko; Hayashi, Atsushi

    2017-06-01

    Bcl-2-associated athanogene 3 (BAG3), a co-chaperone of heat shock protein 70 (HSP70), exerts anti-apoptotic effects in various malignant tumors. However, relationships between choroidal melanoma and BAG3 are poorly studied. This study investigated the expression of BAG3 in a case of human choroidal melanoma. Funduscopy, computed tomography, and single-photon emission computed tomography with the intravenous injection of N-isopropyl-p-[ 123 I] iodoamphetamine strongly indicated choroidal melanoma in a 68-year-old woman. Accordingly, we carried out an enucleation and pathological diagnosis. Proteins and total RNA were extracted from normal retinochoroidal and tumor tissues. Proteins were also extracted from ocular nevus tissues of other patients. We examined the expression of BAG3 protein and mRNA using Western blotting and the real-time quantitative polymerase chain reaction, respectively. Immunohistochemical stains were positive for melan-A, HMB-45, and S-100. Histopathology confirmed a choroidal melanoma. The expression of BAG3 protein and mRNA in the choroidal melanoma tissue was upregulated with respect to both normal retinochoroidal tissue and ocular nevus tissues from other patients. Because BAG3 may inhibit apoptosis of choroidal melanoma and facilitate its survival, overexpression of this gene product may be a prognostic marker and therapeutic target.

  14. The cost-effectiveness of photodynamic therapy for fellow eyes with subfoveal choroidal neovascularization secondary to age-related macular degeneration.

    PubMed

    Sharma, S; Brown, G C; Brown, M M; Hollands, H; Shah, G K

    2001-11-01

    Photodynamic therapy (PDT) has recently been demonstrated to be beneficial for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration (AMD). Herein, we determine the cost-effectiveness of PDT for the treatment of subfoveal choroidal neovascularization (CNV) in patients with disciform degeneration in one eye and whose second and better-seeing eye develops visual loss secondary to predominantly classic subfoveal CNV. The analysis was performed from the perspective of a for-profit third-party insurer. Cost-utility Markov models were created to determine the cost-effectiveness of PDT under two different scenarios, by using efficacy data derived from the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy (TAP) Study and patient-based utilities. Decision analyses were performed by incorporating data from the TAP Study, expected longevity data, and patient-based utilities. Cost-effective models were then created by incorporating incremental medical costs. Various sensitivity analyses were carried out to determine the robustness of our models. A Monte Carlo simulation was also used to determine whether there was a significant difference in quality-of-life adjusted years (QALYs) gained between PDT therapy and the placebo. For the hypothetical patient whose second and better-seeing eye becomes affected and who has 20/40 vision at baseline in this affected eye (base case 1), PDT was associated with a 10.7% relative increase in their quality-of-life (treatment conferred an additional undiscounted 0.1342 QALYs over a 2-year period). For the hypothetical patient whose second and better-seeing eye becomes affected and who has 20/200 vision at baseline in this affected eye (base case 2), PDT was associated with a 7.8% relative increase in their quality-of-life (treatment conferred an additional undiscounted 0.0669 QALYs over a 2-year period). Sensitivity analysis showed our models were robust and that PDT was

  15. Nanoparticles in the ocular drug delivery

    PubMed Central

    Zhou, Hong-Yan; Hao, Ji-Long; Wang, Shuang; Zheng, Yu; Zhang, Wen-Song

    2013-01-01

    Ocular drug transport barriers pose a challenge for drug delivery comprising the ocular surface epithelium, the tear film and internal barriers of the blood-aqueous and blood-retina barriers. Ocular drug delivery efficiency depends on the barriers and the clearance from the choroidal, conjunctival vessels and lymphatic. Traditional drug administration reduces the clinical efficacy especially for poor water soluble molecules and for the posterior segment of the eye. Nanoparticles (NPs) have been designed to overcome the barriers, increase the drug penetration at the target site and prolong the drug levels by few internals of drug administrations in lower doses without any toxicity compared to the conventional eye drops. With the aid of high specificity and multifunctionality, DNA NPs can be resulted in higher transfection efficiency for gene therapy. NPs could target at cornea, retina and choroid by surficial applications and intravitreal injection. This review is concerned with recent findings and applications of NPs drug delivery systems for the treatment of different eye diseases. PMID:23826539

  16. Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization.

    PubMed

    Moreno, Miguel; Pow, Poh Yih; Tabitha, Tan Su Teng; Nirmal, Sonali; Larsson, Andreas; Radhakrishnan, Krishna; Nirmal, Jayabalan; Quah, Soo Tng; Geifman Shochat, Susana; Agrawal, Rupesh; Venkatraman, Subbu

    2017-08-01

    This paper describes the synthesis of thiolated chitosan-based hydrogels with varying degrees of crosslinking that has been utilized to modulate release kinetics of two clinically relevant FDA-approved anti-VEGF protein drugs, ranibizumab and aflibercept. These hydrogels have been fabricated into disc shaped structures for potential use as patches on ocular surface. Protein conformational changes and aggregation after loading and release was evaluated by circular dichroism (CD), steady-state tryptophan fluorescence spectroscopy, electrophoresis and size-exclusion chromatography (SEC). Finally, the capacity of both released proteins to bind to VEGF was tested by ELISA and surface plasmon resonance (SPR) technology. The study demonstrates the versatility of thiolated chitosan-based hydrogels for delivering proteins. The effect of various parameters of the hydrogel on protein release kinetics and mechanism of protein release was studied using the Korsmeyer-Peppas release model. Furthermore, we have studied the stability of released proteins in detail while comparing it with non-entrapped proteins under physiological conditions to understand the effect of formulation conditions on protein stability. The disc-shaped thiolated chitosan-based hydrogels provide a potentially useful platform to deliver ranibizumab and aflibercept for the treatments of ocular diseases such as wet AMD, DME and corneal neovascularization.

  17. Stereotactic Fractionated Radiotherapy in the Treatment of Juxtapapillary Choroidal Melanoma: The McGill University Experience

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Al-Wassia, Rolina; Dal Pra, Alan; Shun, Kitty

    2011-11-15

    Purpose: To report our experience with linear accelerator-based stereotactic fractionated radiotherapy in the treatment of juxtapapillary choroidal melanoma. Methods and Materials: We performed a retrospective review of 50 consecutive patients diagnosed with juxtapapillary choroidal melanoma and treated with linear accelerator-based stereotactic fractionated radiotherapy between April 2003 and December 2009. Patients with small to medium sized lesions (Collaborative Ocular Melanoma Study classification) located within 2 mm of the optic disc were included. The prescribed radiation dose was 60 Gy in 10 fractions. The primary endpoints included local control, enucleation-free survival, and complication rates. Results: The median follow-up was 29 months (range,more » 1-77 months). There were 31 males and 29 females, with a median age of 69 years (range, 30-92 years). Eighty-four percent of the patients had medium sized lesions, and 16% of patients had small sized lesions. There were four cases of local progression (8%) and three enucleations (6%). Actuarial local control rates at 2 and 5 years were 93% and 86%, respectively. Actuarial enucleation-free survival rates at 2 and 5 years were 94% and 84%, respectively. Actuarial complication rates at 2 and 5 years were 33% and 88%, respectively, for radiation-induced retinopathy; 9.3% and 46.9%, respectively, for dry eye; 12% and 53%, respectively, for cataract; 30% and 90%, respectively, for visual loss [Snellen acuity (decimal equivalent), <0.1]; 11% and 54%, respectively, for optic neuropathy; and 18% and 38%, respectively, for neovascular glaucoma. Conclusions: Linear accelerator-based stereotactic fractionated radiotherapy using 60 Gy in 10 fractions is safe and has an acceptable toxicity profile. It has been shown to be an effective noninvasive treatment for juxtapapillary choroidal melanomas.« less

  18. Tumoral and Choroidal Vascularization

    PubMed Central

    Jost, Maud; Maillard, Catherine; Lecomte, Julie; Lambert, Vincent; Tjwa, Marc; Blaise, Pierre; Alvarez Gonzalez, Maria-Luz; Bajou, Khalid; Blacher, Silvia; Motte, Patrick; Humblet, Chantal; Defresne, Marie Paule; Thiry, Marc; Frankenne, Francis; Gothot, André; Carmeliet, Peter; Rakic, Jean-Marie; Foidart, Jean-Michel; Noël, Agnès

    2007-01-01

    An adequate balance between serine proteases and their plasminogen activator inhibitor-1 (PAI-1) is critical for pathological angiogenesis. PAI-1 deficiency in mice is associated with impaired choroidal neovascularization (CNV) and tumoral angiogenesis. In the present work, we demonstrate unexpected differences in the contribution of bone marrow (BM)-derived cells in these two processes regulated by PAI-1. PAI-1−/− mice grafted with BM-derived from wild-type mice were able to support laser-induced CNV formation but not skin carcinoma vascularization. Engraftment of irradiated wild-type mice with PAI-1−/− BM prevented CNV formation, demonstrating the crucial role of PAI-1 delivered by BM-derived cells. In contrast, the transient infiltration of tumor transplants by local PAI-1-producing host cells rather than by BM cells was sufficient to rescue tumor growth and angiogenesis in PAI-1-deficient mice. These data identify PAI-1 as a molecular determinant of a local permissive soil for tumor angiogenesis. Altogether, the present study demonstrates that different cellular mechanisms contribute to PAI-1-regulated tumoral and CNV. PAI-1 contributes to BM-dependent choroidal vascularization and to BM-independent tumor growth and angiogenesis. PMID:17717143

  19. Non-cytomegalovirus ocular opportunistic infections in patients with AIDS

    PubMed Central

    Gangaputra, Sapna; Drye, Lea; Vaidya, Vijay; Thorne, Jennifer E.; Jabs, Douglas A; Lyon, Alice T.

    2014-01-01

    Purpose To report the incidence and clinical outcomes of non-cytomegalovirus (non-CMV) ocular opportunistic infections in patients with AIDS in the era of highly active antiretroviral therapy (HAART). Design Multicenter, prospective, observational study of patients with AIDS Methods Medical history, ophthalmologic examination, and laboratory tests were performed at enrollment and every 6 months subsequently. Once an ocular opportunistic infection was diagnosed, patients were seen every 3 months for outcomes. Results At enrollment, 37 non-CMV ocular opportunistic infections were diagnosed: 16 patients, herpetic retinitis; 11 patients, toxoplasmic retinitis; and 10 patients, choroiditis. During the follow-up period, the estimated incidences (and 95% confidence intervals [CI]) of these were: herpetic retinitis, 0.007/100 person-years (PY) (95% CI 0.0004, 0.039); toxoplasmic retinitis, 0.007/100 PY (95% CI 0.004, 0.039); and choroiditis 0.014/100 PY (95% CI 0.0025, 0.050). The mortality rates appeared higher among those patients with newly diagnosed or incident herpetic retinitis and choroiditis (rates=21.7 deaths/100 PY [P=0.02] and 12.8 deaths/100 PY [P=0.04]) respectively, than that for patients with AIDS without an ocular opportunistic infection (4.1 deaths/100 PY); Toxoplasmic retinitis did not appear to be associated with greater mortality (6.4/100 PY, P=0.47). Eyes with newly-diagnosed herpetic retinitis appeared to have a poor visual prognosis with high rates of visual impairment (37.9/100 PY) and blindness (17.5/100 PY), whereas those outcomes in eyes with choroiditis appeared to be lower (2.3/100 PY and 0/100 PY, respectively). Conclusions Although uncommon, non-CMV ocular opportunistic infections may be associated with high rates of visual loss and/or mortality. PMID:23068916

  20. Incidence and clinical characteristics of symptomatic choroidal metastasis from lung cancer.

    PubMed

    Kreusel, Klaus-Martin; Bechrakis, Nikolaos E; Wiegel, Thomas; Krause, Lothar; Foerster, Michael H

    2008-08-01

    To determine the clinical characteristics of symptomatic choroidal metastasis (CM) resulting from metastatic lung cancer. Twenty-two consecutive patients with symptomatic CM resulting from lung cancer were retrospectively reviewed for ocular findings, medical history and systemic disease. All patients underwent a complete screening for further organ metastasis by computed tomography (CT) and bone scintigraphy. Annual frequency of CM was determined and compared with the incidence predicted from ocular screening studies. In eight of 22 (36%; 95% confidence interval [CI] 17-59) patients, lung cancer had been diagnosed before occurrence of CM, with a median interval of 13 months. In 14 patients lung cancer was detected after diagnosis of CM, with a median interval of 1 month. Choroidal metastasis was unilateral, solitary and located close to or at the posterior pole in the majority of patients. Further organ metastasis with a median number of three affected organ systems was present in 19 (86%; 95% CI 65-97) patients. Median survival after diagnosis of symptomatic CM was 13 months, by contrast with 2 months in lung cancer patients with CM identified in an ocular screening study. The mean number of patients in Berlin diagnosed with symptomatic CM was 1.4 per year, which was two orders of magnitude less than predicted from screening studies. Symptomatic choroidal lung cancer metastasis in the majority of patients presents as a solitary tumour before diagnosis of lung cancer in patients with multiple organ systems affected by metastatic disease. Contrary to predictions from ocular screening studies, it is a rare clinical entity.

  1. Twelve hour reproducibility of choroidal blood flow parameters in healthy subjects.

    PubMed

    Polska, E; Polak, K; Luksch, A; Fuchsjager-Mayrl, G; Petternel, V; Findl, O; Schmetterer, L

    2004-04-01

    To investigate the reproducibility and potential diurnal variation of choroidal blood flow parameters in healthy subjects over a period of 12 hours. The choroidal blood flow parameters of 16 healthy non-smoking subjects were measured at five time points during the day (8:00, 11:00, 14:00, 17:00, and 20:00). Outcome parameters were pulsatile ocular blood flow as assessed by pneumotonometry, fundus pulsation amplitude as assessed by laser interferometry, blood velocities in the opthalmic and posterior ciliary arteries as assessed by colour Doppler imaging, and choroidal blood flow, volume, and velocity as assessed by fundus camera based laser Doppler flowmetry. The coefficient of variation and the maximum change from baseline in an individual were calculated for each outcome parameter. None of the techniques used found a diurnal variation in choroidal blood flow. Coefficients of variation were within 2.9% and 13.6% for all outcome parameters. The maximum change from baseline in an individual was much higher, ranging from 11.2% to 58.8%. These data indicate that in healthy subjects the selected techniques provide adequate reproducibility to be used in clinical studies. Variability may, however, be considerably higher in older subjects or subjects with ocular disease. The higher individual differences in flow parameter readings limit the use of the techniques in clinical practice. To overcome problems with measurement validity, a clinical trial should include as many choroidal blood flow outcome parameters as possible to check for consistency.

  2. Evaluation of focal choroidal excavation in the macula using swept-source optical coherence tomography.

    PubMed

    Lim, F P M; Loh, B K; Cheung, C M G; Lim, L S; Chan, C M; Wong, D W K

    2014-09-01

    To evaluate imaging findings of patients with focal choroidal excavation (FCE) in the macula using swept-source optical coherence tomography (SS-OCT) and correlate it clinically. Prospective observational case series. Eleven consecutive patients (12 eyes) with FCE were described. Data on demographics and clinical presentation were collected and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and SS-OCT) were analyzed. The primary diagnosis was epiretinal membrane (two eyes), choroidal neovascularization (one eye), polypoidal choroidal vasculopathy (three eyes), central serous chorioretinopathy (one eye), and dry age-related macular degeneration (two eyes). Eleven out of 12 of the lesions were conforming. One presented with a non-conforming lesion that progressed to a conforming lesion. One eye had multiFCE and two had two overlapping choroidal excavations. Using the SS-OCT, we found the choroid to be thinned out at the area of FCE but sclera remained normal. The choroidal tissue beneath the FCE was abnormal, with high internal reflectivity and poor visualization of choroidal vessels. There was loss of contour of the outer choroidal boundary that appeared to be pulled inward by this abnormal choroidal tissue. A suprachoroidal space was noted beneath this choroidal tissue and the choroidal-scleral interface was smooth. Repeat SS-OCT 6 months after presentation showed the area of excavation to be stable in size. FCE can be associated with epiretinal membrane, central serous chorioretinopathy, and age-related macular degeneration. The choroid was thinned out in the area of FCE.

  3. Removal of choroidal neovascular membrane in a case of macular hole after anti-VEGF therapy for age-related macular degeneration.

    PubMed

    Hirata, Akira; Hayashi, Ken; Murata, Kazuhisa; Nakamura, Kei-Ichiro

    2018-03-01

    The formation of macular hole after receiving anti-vascular endothelial growth factor (anti-VEGF) therapy is rare. We report a case of macular hole that occurred after intravitreal injection of an anti-VEGF agent for age-related macular degeneration (AMD) in a patient, who underwent vitrectomy combined with choroidal neovascularization (CNV) removal. A 64-year-old female with AMD affecting her right eye received an intravitreal injection of an anti-VEGF agent. After treatment, we identified a full thickness macular hole (MH) that was associated with the rapid resolution of the macular edema and contraction of the CNV. After performing vitrectomy combined with CNV removal, the MH closed and her visual acuity improved. Examination of the removed CNV revealed a network of microvessels devoid of pericytes. and Importance: The present findings suggest that rapid resolution of macular edema and contraction of the CNV and/or mild increase in the vitreous traction after anti-VEGF therapy could potentially cause MH. CNV removal via the MH may be an acceptable procedure, if the MH remains open, the CNV is of the classic type, and it spares a central portion of the fovea.

  4. A Pharmacodynamic Analysis of Choroidal Neovascularization in a Porcine Model Using Three Targeted Drugs.

    PubMed

    Tran, Jeffrey; Craven, Caroline; Wabner, Kathy; Schmit, Jenn; Matter, Brock; Kompella, Uday; Grossniklaus, Hans E; Olsen, Timothy W

    2017-07-01

    To compare the efficacy of microneedle-delivered suprachoroidal (SC) pazopanib to intravitreal (Ivit) delivery of pazopanib, bevacizumab, or a fusion protein hI-con1 versus vehicle controls on choroidal neovascularization (CNV) growth in a pig model. Forty-one pigs were injected on the day of CNV induction (hI-con1 on postinduction day 14) with either 2.5 mg Ivit bevacizumab (n = 9), 1 mg Ivit pazopanib (n = 9), 300 Ivit μg hI-con1 (n = 4), or 1 mg SC pazopanib (n = 9), vs. 10 vehicle controls (3 SC + 7 Ivit = 10). Pigs were euthanized at week 2 (11), 3 (8), 4 (11), and 8 (11), and eyes were fixed for histology. The size of the CNV was determined from histology, and CNV height was the primary outcome measure. Immunostaining for cytotoxic T-cells was performed in the hI-con1 study. In 39 of 41 (95%) eyes, type 2 CNV lesions were identified. One CNV lesion was lost during dissection. One animal was euthanized due to surgical complications. For mean CNV size comparisons, Ivit pazopanib had smaller mean height measurements (90 ± 20 μm) versus controls (180 ± 20 μm; P = 0.009), and Ivit pazopanib had smaller maximum CNV height (173 ± 43 μm) compared to SC pazopanib (478 ± 105 μm; P = 0.018). The mean lesion size in hI-con1-treated animals trended smaller than in controls (P = 0.11). Immunostaining did not detect cytotoxic T-cells. Intravitreal pazopanib and to a lesser extent hI-con1 reduced the size of CNV lesions. The pig model has nearly a 100% rate of type 2 CNV induction and is a reliable preclinical model with pharmacodynamics similar to humans.

  5. A Pharmacodynamic Analysis of Choroidal Neovascularization in a Porcine Model Using Three Targeted Drugs

    PubMed Central

    Tran, Jeffrey; Craven, Caroline; Wabner, Kathy; Schmit, Jenn; Matter, Brock; Kompella, Uday; Grossniklaus, Hans E.; Olsen, Timothy W.

    2017-01-01

    Purpose To compare the efficacy of microneedle-delivered suprachoroidal (SC) pazopanib to intravitreal (Ivit) delivery of pazopanib, bevacizumab, or a fusion protein hI-con1 versus vehicle controls on choroidal neovascularization (CNV) growth in a pig model. Methods Forty-one pigs were injected on the day of CNV induction (hI-con1 on postinduction day 14) with either 2.5 mg Ivit bevacizumab (n = 9), 1 mg Ivit pazopanib (n = 9), 300 Ivit μg hI-con1 (n = 4), or 1 mg SC pazopanib (n = 9), vs. 10 vehicle controls (3 SC + 7 Ivit = 10). Pigs were euthanized at week 2 (11), 3 (8), 4 (11), and 8 (11), and eyes were fixed for histology. The size of the CNV was determined from histology, and CNV height was the primary outcome measure. Immunostaining for cytotoxic T-cells was performed in the hI-con1 study. Results In 39 of 41 (95%) eyes, type 2 CNV lesions were identified. One CNV lesion was lost during dissection. One animal was euthanized due to surgical complications. For mean CNV size comparisons, Ivit pazopanib had smaller mean height measurements (90 ± 20 μm) versus controls (180 ± 20 μm; P = 0.009), and Ivit pazopanib had smaller maximum CNV height (173 ± 43 μm) compared to SC pazopanib (478 ± 105 μm; P = 0.018). The mean lesion size in hI-con1–treated animals trended smaller than in controls (P = 0.11). Immunostaining did not detect cytotoxic T-cells. Conclusions Intravitreal pazopanib and to a lesser extent hI-con1 reduced the size of CNV lesions. The pig model has nearly a 100% rate of type 2 CNV induction and is a reliable preclinical model with pharmacodynamics similar to humans. PMID:28738417

  6. Evaluation of focal choroidal excavation in the macula using swept-source optical coherence tomography

    PubMed Central

    Lim, F P M; Loh, B K; Cheung, C M G; Lim, L S; Chan, C M; Wong, D W K

    2014-01-01

    Purpose To evaluate imaging findings of patients with focal choroidal excavation (FCE) in the macula using swept-source optical coherence tomography (SS-OCT) and correlate it clinically. Methods Prospective observational case series. Eleven consecutive patients (12 eyes) with FCE were described. Data on demographics and clinical presentation were collected and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and SS-OCT) were analyzed. Results The primary diagnosis was epiretinal membrane (two eyes), choroidal neovascularization (one eye), polypoidal choroidal vasculopathy (three eyes), central serous chorioretinopathy (one eye), and dry age-related macular degeneration (two eyes). Eleven out of 12 of the lesions were conforming. One presented with a non-conforming lesion that progressed to a conforming lesion. One eye had multiFCE and two had two overlapping choroidal excavations. Using the SS-OCT, we found the choroid to be thinned out at the area of FCE but sclera remained normal. The choroidal tissue beneath the FCE was abnormal, with high internal reflectivity and poor visualization of choroidal vessels. There was loss of contour of the outer choroidal boundary that appeared to be pulled inward by this abnormal choroidal tissue. A suprachoroidal space was noted beneath this choroidal tissue and the choroidal–scleral interface was smooth. Repeat SS-OCT 6 months after presentation showed the area of excavation to be stable in size. Conclusion FCE can be associated with epiretinal membrane, central serous chorioretinopathy, and age-related macular degeneration. The choroid was thinned out in the area of FCE. PMID:24946847

  7. Subfoveal Choroidal Thickness in Eyes with Neovascular Age-Related Macular Degeneration Treated with Anti-Vascular Endothelial Growth Factor Agents.

    PubMed

    Kanadani, Tereza Cristina Moreira; Veloso, Carlos Eduardo; Nehemy, Márcio B

    2018-05-16

    We aimed to assess the subfoveal choroidal thickness (SFChT) and the effect of treatment with anti-vascular endothelial growth factor (anti-VEGF) agents on the SFChT in age-related macular degeneration (AMD) subtypes. We enrolled 128 eyes of 107 patients with neovascular AMD (60 women; 47 men; mean age, 73.6 ± 8.9 years), and prospectively evaluated the best-corrected visual acuity (BCVA) and SFChT at baseline and at 3, 6, and 12 months after treatment with anti-VEGF agents. Patients were assigned to the typical AMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP) subgroups. In total, 85 (66.4%), 31 (24.2%), and 12 (9.4%) eyes were assigned to the typical AMD, PCV, and RAP subgroups, respectively. The baseline mean BCVA was 0.75 ± 0.26, 0.72 ± 0.21, and 0.77 ± 0.24 logMAR in the typical AMD, PCV, and RAP subgroups, respectively (p = 0.774). The mean baseline SFChT was 203.20 ± 35.80, 271.80 ± 24.50, and 182.93 ± 31.31 µm, respectively (p < 0.001). Mean SFChT significantly decreased from baseline to 3, 6, and 12 months after treatment. The RAP subtype presented a significantly higher decrease in SFChT compared to the other subtypes (p = 0.01). The percentage reduction in SFChT was not significantly correlated with the number of injections (r = -0.02; p = 0.823). No association was observed between baseline SFChT and final visual acuity at 12 months (r = 0.0; p = 0.586). SFChT was greatest in eyes with PCV and least in eyes with RAP. The reduction in SFChT after treatment was greater in the RAP cases. The decrease in SFChT after 12 months of anti-VEGF treatment was not associated with the number of injections and there was no correlation between the baseline SFChT and visual acuity in all AMD subtypes. © 2018 S. Karger AG, Basel.

  8. Anti-sphingosine-1-phosphate monoclonal antibodies inhibit angiogenesis and sub-retinal fibrosis in a murine model of laser-induced choroidal neovascularization

    PubMed Central

    Caballero, Sergio; Swaney, James; Moreno, Kelli; Afzal, Aqeela; Kielczewski, Jennifer; Stoller, Glenn; Cavalli, Amy; Garland, William; Hansen, Geneviève; Sabbadini, Roger; Grant, Maria B.

    2013-01-01

    The efficacy of novel monoclonal antibodies that neutralize the pro-angiogenic mediator, sphingosine-1-phosphate (S1P), were tested using in vitro and in vivo angiogenesis models, including choroidal neovascularization (CNV) induced by laser disruption of Bruch’s membrane. S1P receptor levels in human brain choroid plexus endothelial cells (CPEC), human lung microvascular endothelial cells, human retinal vascular endothelial cells, and circulating endothelial progenitor cells were examined by semi-quantitative PCR. The ability of murine or humanized anti-S1P monoclonal antibodies (mAbs) to inhibit S1P-mediated microvessel tube formation by CPEC on Matrigel was evaluated and capillary density in subcutaneous growth factor-loaded Matrigel plugs was determined following anti-S1P treatment. S1P promoted in vitro capillary tube formation in CPEC consistent with the presence of cognate S1P1–5 receptor expression by these cells and the S1P antibody induced a dose-dependent reduction in microvessel tube formation. In a murine model of laser-induced rupture of Bruch’s membrane, S1P was detected in posterior cups of mice receiving laser injury, but not in uninjured controls. Intravitreous injection of anti-S1P mAbs dramatically inhibited CNV formation and sub-retinal collagen deposition in all treatment groups (p < 0.05 compared to controls), thereby identifying S1P as a previously unrecognized mediator of angiogenesis and subretinal fibrosis in this model. These findings suggest that neutralizing S1P with anti-S1P mAbs may be a novel method of treating patients with exudative age-related macular degeneration by reducing angiogenesis and sub-retinal fibrosis, which are responsible for visual acuity loss in this disease. PMID:18723015

  9. Human tears reveal insights into corneal neovascularization.

    PubMed

    Zakaria, Nadia; Van Grasdorff, Sigi; Wouters, Kristien; Rozema, Jos; Koppen, Carina; Lion, Eva; Cools, Nathalie; Berneman, Zwi; Tassignon, Marie-José

    2012-01-01

    Corneal neovascularization results from the encroachment of blood vessels from the surrounding conjunctiva onto the normally avascular cornea. The aim of this study is to identify factors in human tears that are involved in development and/or maintenance of corneal neovascularization in humans. This could allow development of diagnostic tools for monitoring corneal neovascularization and combination monoclonal antibody therapies for its treatment. In an observational case-control study we enrolled a total of 12 patients with corneal neovascularization and 10 healthy volunteers. Basal tears along with reflex tears from the inferior fornix, superior fornix and using a corneal bath were collected along with blood serum samples. From all patients, ocular surface photographs were taken. Concentrations of the pro-angiogenic cytokines interleukin (IL)-6, IL-8, Vascular Endothelial Growth Factor (VEGF), Monocyte Chemoattractant Protein 1 (MCP-1) and Fas Ligand (FasL) were determined in blood and tear samples using a flow cytometric multiplex assay. Our results show that the concentration of pro-angiogenic cytokines in human tears are significantly higher compared to their concentrations in serum, with highest levels found in basal tears. Interestingly, we could detect a significantly higher concentration of IL- 6, IL-8 and VEGF in localized corneal tears of patients with neovascularized corneas when compared to the control group. This is the first study of its kind demonstrating a significant difference of defined factors in tears from patients with neovascularized corneas as compared to healthy controls. These results provide the basis for future research using animal models to further substantiate the role of these cytokines in the establishment and maintenance of corneal neovascularization.

  10. Human Tears Reveal Insights into Corneal Neovascularization

    PubMed Central

    Wouters, Kristien; Rozema, Jos; Koppen, Carina; Lion, Eva; Cools, Nathalie; Berneman, Zwi; Tassignon, Marie-José

    2012-01-01

    Corneal neovascularization results from the encroachment of blood vessels from the surrounding conjunctiva onto the normally avascular cornea. The aim of this study is to identify factors in human tears that are involved in development and/or maintenance of corneal neovascularization in humans. This could allow development of diagnostic tools for monitoring corneal neovascularization and combination monoclonal antibody therapies for its treatment. In an observational case-control study we enrolled a total of 12 patients with corneal neovascularization and 10 healthy volunteers. Basal tears along with reflex tears from the inferior fornix, superior fornix and using a corneal bath were collected along with blood serum samples. From all patients, ocular surface photographs were taken. Concentrations of the pro-angiogenic cytokines interleukin (IL)-6, IL-8, Vascular Endothelial Growth Factor (VEGF), Monocyte Chemoattractant Protein 1 (MCP-1) and Fas Ligand (FasL) were determined in blood and tear samples using a flow cytometric multiplex assay. Our results show that the concentration of pro-angiogenic cytokines in human tears are significantly higher compared to their concentrations in serum, with highest levels found in basal tears. Interestingly, we could detect a significantly higher concentration of IL- 6, IL-8 and VEGF in localized corneal tears of patients with neovascularized corneas when compared to the control group. This is the first study of its kind demonstrating a significant difference of defined factors in tears from patients with neovascularized corneas as compared to healthy controls. These results provide the basis for future research using animal models to further substantiate the role of these cytokines in the establishment and maintenance of corneal neovascularization. PMID:22590547

  11. Ocular involvement in paediatric haemolytic uraemic syndrome.

    PubMed

    Sturm, Veit; Menke, Marcel N; Landau, Klara; Laube, Guido F; Neuhaus, Thomas J

    2010-11-01

    The aim of this study was to estimate the frequency and severity of ocular involvement in paediatric patients with haemolytic uraemic syndrome (HUS). The study was designed as an institutional, retrospective, observational case series. Charts for all 87 paediatric patients with HUS treated at the University Children's Hospital Zurich between 1995 and 2007 were reviewed. Patients with ocular involvement were identified and clinical findings presented. Three of 69 examined patients with HUS showed ocular involvement. Ophthalmic findings in two children were consistent with bilateral Purtscher retinopathy, showing multiple haemorrhages, exudations and superficial retinal whitening. The third child presented with bilateral isolated central intraretinal haemorrhages as a milder form of ocular involvement. In one of the children with Purtscher retinopathy, laser photocoagulation was required for bilateral rubeosis irides and development of disc neovascularization. Longterm outcomes in the two severely affected children showed decreased visual acuity caused by partial atrophy of the optic nerves. In the milder case visual acuity was not impaired at any time. A minority of paediatric patients with HUS developed ocular involvement. Acute ocular findings varied in severity from isolated intraretinal haemorrhages to Purtscher-like retinopathy with retinal ischaemia. Longterm complications included the development of neovascularizations and consecutive optic nerve atrophy. Although ocular involvement in HUS seems to be rare, physicians should be aware of this complication because of its possible vision-endangering consequences. © 2009 The Authors. Journal compilation © 2009 Acta Ophthalmol.

  12. Ranibizumab (Lucentis) in neovascular age-related macular degeneration: evidence from clinical trials.

    PubMed

    Mitchell, P; Korobelnik, J-F; Lanzetta, P; Holz, F G; Prünte, C; Schmidt-Erfurth, U; Tano, Y; Wolf, S

    2010-01-01

    Neovascular age-related macular degeneration (AMD) has a poor prognosis if left untreated, frequently resulting in legal blindness. Ranibizumab is approved for treating neovascular AMD. However, further guidance is needed to assist ophthalmologists in clinical practice to optimise treatment outcomes. An international retina expert panel assessed evidence available from prospective, multicentre studies evaluating different ranibizumab treatment schedules (ANCHOR, MARINA, PIER, SAILOR, SUSTAIN and EXCITE) and a literature search to generate evidence-based and consensus recommendations for treatment indication and assessment, retreatment and monitoring. Ranibizumab is indicated for choroidal neovascular lesions with active disease, the clinical parameters of which are outlined. Treatment initiation with three consecutive monthly injections, followed by continued monthly injections, has provided the best visual-acuity outcomes in pivotal clinical trials. If continued monthly injections are not feasible after initiation, a flexible strategy appears viable, with monthly monitoring of lesion activity recommended. Initiation regimens of fewer than three injections have not been assessed. Continuous careful monitoring with flexible retreatment may help avoid vision loss recurring. Standardised biomarkers need to be determined. Evidence-based guidelines will help to optimise treatment outcomes with ranibizumab in neovascular AMD.

  13. Long-term follow-up of patients with choroidal neovascularization due to angioid streaks.

    PubMed

    Martinez-Serrano, Maria Guadalupe; Rodriguez-Reyes, Abelardo; Guerrero-Naranjo, Jose Luis; Salcedo-Villanueva, Guillermo; Fromow-Guerra, Jans; García-Aguirre, Gerardo; Morales-Canton, Virgilio; Velez-Montoya, Raul

    2017-01-01

    The following case series describes the long-term anatomical and functional outcome of a group of seven patients with choroidal neovascularization (CNV), secondary to angioid streaks (AS), who were treated with antiangiogenic drugs in a pro re nata (PRN) regimen. After the 4-year mark, visual acuity tends to return to pretreatment level. Treatment delays and lack of awareness and self-referral by the patients are believed to be the cause of the PRN regimen failure. To assess the long-term outcomes (>4 years) of patients with CNV due to AS treated with a PRN regimen of antiangiogenic. This was a retrospective, case series, single-center study. We reviewed the electronic medical records from patients with CNV due to AS. From each record, we noted general demographic data and relevant medical history; clinical presentation, changes in best-corrected visual acuity (BCVA) over time, optical coherent tomography parameters, treatment and retreatment details, and systemic associations. Changes in BCVA and central macular thickness were assessed with a Wilcoxon two-sample test, with an alpha value of ≤0.05 for statistical significance. The mean follow-up time was 53.8±26.8 months. BCVA at baseline was: 1.001±0.62 logMAR; at the end of follow-up: 0.996±0.56 logMAR ( P =0.9). Central macular thickness at baseline was: 360.85±173.82 μm; at the end of follow-up: 323.85±100.34 μm ( P =0.6). Mean number of intravitreal angiogenic drugs: 6±4.16 injections (range 4-15). Mean time between injections was 3.8±2.7 months (range 1.9-5.8 months). Despite initial anatomical and functional improvement, patients at the end of the follow-up had no visual improvement after a pro re nata regimen of antiangiogenic drugs. The amount of retreatments, number of recurrences, and time between intravitreal injections were similar to previous reports with shorter follow-up.

  14. Long-term follow-up of patients with choroidal neovascularization due to angioid streaks

    PubMed Central

    Martinez-Serrano, Maria Guadalupe; Rodriguez-Reyes, Abelardo; Guerrero-Naranjo, Jose Luis; Salcedo-Villanueva, Guillermo; Fromow-Guerra, Jans; García-Aguirre, Gerardo; Morales-Canton, Virgilio; Velez-Montoya, Raul

    2017-01-01

    Background The following case series describes the long-term anatomical and functional outcome of a group of seven patients with choroidal neovascularization (CNV), secondary to angioid streaks (AS), who were treated with antiangiogenic drugs in a pro re nata (PRN) regimen. After the 4-year mark, visual acuity tends to return to pretreatment level. Treatment delays and lack of awareness and self-referral by the patients are believed to be the cause of the PRN regimen failure. Purpose To assess the long-term outcomes (>4 years) of patients with CNV due to AS treated with a PRN regimen of antiangiogenic. Methods This was a retrospective, case series, single-center study. We reviewed the electronic medical records from patients with CNV due to AS. From each record, we noted general demographic data and relevant medical history; clinical presentation, changes in best-corrected visual acuity (BCVA) over time, optical coherent tomography parameters, treatment and retreatment details, and systemic associations. Changes in BCVA and central macular thickness were assessed with a Wilcoxon two-sample test, with an alpha value of ≤0.05 for statistical significance. Results The mean follow-up time was 53.8±26.8 months. BCVA at baseline was: 1.001±0.62 logMAR; at the end of follow-up: 0.996±0.56 logMAR (P=0.9). Central macular thickness at baseline was: 360.85±173.82 μm; at the end of follow-up: 323.85±100.34 μm (P=0.6). Mean number of intravitreal angiogenic drugs: 6±4.16 injections (range 4–15). Mean time between injections was 3.8±2.7 months (range 1.9–5.8 months). Conclusion Despite initial anatomical and functional improvement, patients at the end of the follow-up had no visual improvement after a pro re nata regimen of antiangiogenic drugs. The amount of retreatments, number of recurrences, and time between intravitreal injections were similar to previous reports with shorter follow-up. PMID:28031699

  15. Twelve hour reproducibility of choroidal blood flow parameters in healthy subjects

    PubMed Central

    Polska, E; Polak, K; Luksch, A; Fuchsjager-Mayrl, G; Petternel, V; Findl, O; Schmetterer, L

    2004-01-01

    Aims/background: To investigate the reproducibility and potential diurnal variation of choroidal blood flow parameters in healthy subjects over a period of 12 hours. Methods: The choroidal blood flow parameters of 16 healthy non-smoking subjects were measured at five time points during the day (8:00, 11:00, 14:00, 17:00, and 20:00). Outcome parameters were pulsatile ocular blood flow as assessed by pneumotonometry, fundus pulsation amplitude as assessed by laser interferometry, blood velocities in the opthalmic and posterior ciliary arteries as assessed by colour Doppler imaging, and choroidal blood flow, volume, and velocity as assessed by fundus camera based laser Doppler flowmetry. The coefficient of variation and the maximum change from baseline in an individual were calculated for each outcome parameter. Results: None of the techniques used found a diurnal variation in choroidal blood flow. Coefficients of variation were within 2.9% and 13.6% for all outcome parameters. The maximum change from baseline in an individual was much higher, ranging from 11.2% to 58.8%. Conclusions: These data indicate that in healthy subjects the selected techniques provide adequate reproducibility to be used in clinical studies. Variability may, however, be considerably higher in older subjects or subjects with ocular disease. The higher individual differences in flow parameter readings limit the use of the techniques in clinical practice. To overcome problems with measurement validity, a clinical trial should include as many choroidal blood flow outcome parameters as possible to check for consistency. PMID:15031172

  16. MULTIFOCAL CHOROIDITIS IN DISSEMINATED SPOROTRICHOSIS IN PATIENTS WITH HIV/AIDS.

    PubMed

    Biancardi, Ana L; Freitas, Dayvison F S; Valviesse, Vitor R G de A; Andrade, Hugo B; de Oliveira, Manoel M E; do Valle, Antonio C F; Zancope-Oliveira, Rosely M; Galhardo, Maria C G; Curi, Andre L L

    2017-01-01

    In this article, the authors describe multifocal choroiditis related to disseminated sporotrichosis in patients with HIV/AIDS. We conducted a retrospective observational study of three patients infected with HIV who presented with disseminated sporotrichosis characterized by cutaneous lesions, multifocal choroiditis, and other manifestations, including osteomyelitis and involvement of the bone marrow, larynx, pharynx, and nasal and oral mucosa. Five eyes of three patients with HIV/AIDS showed multifocal choroiditis related to disseminated sporotrichosis. The CD4 counts ranged from 25 to 53 mm. All patients were asymptomatic visually. The ocular disease was bilateral in two patients. The lesion size ranged from 1/3 to 2 disc diameters. None of the patients had vitritis. Of the 12 lesions, 9 were localized in the posterior pole (Zone 1) and 3 were localized in the mild periphery (Zone 2). Multifocal choroiditis due to disseminated sporotrichosis can occur in profoundly immunosuppressed patients with HIV/AIDS.

  17. Choroidal retinoic acid synthesis: a possible mediator between refractive error and compensatory eye growth.

    PubMed

    Mertz, J R; Wallman, J

    2000-04-01

    Research over the past two decades has shown that the growth of young eyes is guided by vision. If near- or far-sightedness is artificially imposed by spectacle lenses, eyes of primates and chicks compensate by changing their rate of elongation, thereby growing back to the pre-lens optical condition. Little is known about what chemical signals might mediate between visual effects on the retina and alterations of eye growth. We present five findings that point to choroidal retinoic acid possibly being such a mediator. First, the chick choroid can convert retinol into all-trans-retinoic acid at the rate of 11 +/- 3 pmoles mg protein(-1) hr(-1), compared to 1.3 +/- 0.3 for retina/RPE and no conversion for sclera. Second, those visual conditions that cause increased rates of ocular elongation (diffusers or negative lens wear) produce a sharp decrease in all-trans-retinoic acid synthesis to levels barely detectable with our assay. In contrast, visual conditions which result in decreased rates of ocular elongation (recovery from diffusers or positive lens wear) produce a four- to five-fold increase in the formation of all-trans-retinoic acid. Third, the choroidal retinoic acid is found bound to a 28-32 kD protein. Fourth, a large fraction of the choroidal retinoic acid synthesized in culture is found in a nucleus-enriched fraction of sclera. Finally, application of retinoic acid to cultured sclera at physiological concentrations produced an inhibition of proteoglycan production (as assessed by measuring sulfate incorporation) with a EC50 of 8 x 10(-7) M. These results show that the synthesis of choroidal retinoic acid is modulated by those visual manipulations that influence ocular elongation and that this retinoic acid may reach the sclera in concentrations adequate to modulate scleral proteoglycan formation.

  18. Compensation for spectacle lenses involves changes in proteoglycan synthesis in both the sclera and choroid.

    PubMed

    Nickla, D L; Wildsoet, C; Wallman, J

    1997-04-01

    It has been demonstrated that chick eye growth compensates for defocus imposed by spectacle lenses: the eye elongates in response to hyperopic defocus imposed by negative lenses and slows its elongation in response to myopic defocus imposed by positive lenses. We ask whether the synthesis of scleral extracellular matrix, specifically glycosaminoglycans, changes in parallel with the changes in ocular elongation. In addition, there is a choroidal component to compensation for spectacle lenses; the choroid thickens in response to myopic defocus and thins in response to hyperopic defocus. We ask whether choroidal glycosaminoglycan synthesis changes in parallel with changes in choroidal thickness. Chicks wore either a +15 diopter (D) or -15 D spectacle lens over one eye, or they wore one lens of each power over each eye for 5 days. At the end of this period, we measured refractive errors and ocular dimensions by refractometry and A-scan ultrasonography, respectively. Pieces of the scleras and choroids from these eyes were put into culture and the synthesis of glycosaminoglycans was assessed by measuring the incorporation of radioactive inorganic sulfur. We here report that the compensatory modulation of the length of the eye involves changes in the synthesis of glycosaminoglycans in the sclera, with synthesis increasing in eyes wearing -15 D spectacles lenses and decreasing in eyes wearing +15 D lenses. In addition, changes in the synthesis of glycosaminoglycans in the choroid are correlated with changes in choroidal thickness: eyes wearing +15 D lenses develop thicker choroids and these choroids synthesize more glycosaminoglycans than choroids from eyes wearing -15 D lenses. Changes in scleral glycosaminoglycan synthesis accompany lens-induced changes in the length of the eye. Furthermore, changes in the thickness of the choroid are also associated with changes in the synthesis of glycosaminoglycans. These results are consistent with the regulation of the growth of the

  19. A Quantitative and Standardized Method for the Evaluation of Choroidal Neovascularization Using MICRON III Fluorescein Angiograms in Rats

    PubMed Central

    Wigg, Jonathan P.; Zhang, Hong; Yang, Dong

    2015-01-01

    Introduction In-vivo imaging of choroidal neovascularization (CNV) has been increasingly recognized as a valuable tool in the investigation of age-related macular degeneration (AMD) in both clinical and basic research applications. Arguably the most widely utilised model replicating AMD is laser generated CNV by rupture of Bruch’s membrane in rodents. Heretofore CNV evaluation via in-vivo imaging techniques has been hamstrung by a lack of appropriate rodent fundus camera and a non-standardised analysis method. The aim of this study was to establish a simple, quantifiable method of fluorescein fundus angiogram (FFA) image analysis for CNV lesions. Methods Laser was applied to 32 Brown Norway Rats; FFA images were taken using a rodent specific fundus camera (Micron III, Phoenix Laboratories) over 3 weeks and compared to conventional ex-vivo CNV assessment. FFA images acquired with fluorescein administered by intraperitoneal injection and intravenous injection were compared and shown to greatly influence lesion properties. Utilising commonly used software packages, FFA images were assessed for CNV and chorioretinal burns lesion area by manually outlining the maximum border of each lesion and normalising against the optic nerve head. Net fluorescence above background and derived value of area corrected lesion intensity were calculated. Results CNV lesions of rats treated with anti-VEGF antibody were significantly smaller in normalised lesion area (p<0.001) and fluorescent intensity (p<0.001) than the PBS treated control two weeks post laser. The calculated area corrected lesion intensity was significantly smaller (p<0.001) in anti-VEGF treated animals at 2 and 3 weeks post laser. The results obtained using FFA correlated with, and were confirmed by conventional lesion area measurements from isolectin stained choroidal flatmounts, where lesions of anti-VEGF treated rats were significantly smaller at 2 weeks (p = 0.049) and 3 weeks (p<0.001) post laser. Conclusion The

  20. Non-cytomegalovirus ocular opportunistic infections in patients with acquired immunodeficiency syndrome.

    PubMed

    Gangaputra, Sapna; Drye, Lea; Vaidya, Vijay; Thorne, Jennifer E; Jabs, Douglas A; Lyon, Alice T

    2013-02-01

    To report the incidence and clinical outcomes of non-cytomegalovirus (non-CMV) ocular opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS) in the era of highly active antiretroviral therapy. Multicenter, prospective, observational study of patients with AIDS. Medical history, ophthalmologic examination, and laboratory tests were performed at enrollment and every 6 months subsequently. Once an ocular opportunistic infection was diagnosed, patients were seen every 3 months for outcomes. At enrollment, 37 non-CMV ocular opportunistic infections were diagnosed: 16 patients, herpetic retinitis; 11 patients, toxoplasmic retinitis; and 10 patients, choroiditis. During the follow-up period, the estimated incidences (and 95% confidence intervals [CI]) of these were: herpetic retinitis, 0.007/100 person-years (PY) (95% CI 0.0004, 0.039); toxoplasmic retinitis, 0.007/100 PY (95% CI 0.004, 0.039); and choroiditis, 0.014/ 100 PY (95% CI 0.0025, 0.050). The mortality rates appeared higher among those patients with newly diagnosed or incident herpetic retinitis and choroiditis (rates = 21.7 deaths/100 PY [P = .02] and 12.8 deaths/100 PY [P = .04]), respectively, than those for patients with AIDS without an ocular opportunistic infection (4.1 deaths/100 PY); toxoplasmic retinitis did not appear to be associated with greater mortality (6.4/100 PY, P = .47). Eyes with newly diagnosed herpetic retinitis appeared to have a poor visual prognosis, with high rates of visual impairment (37.9/100 PY) and blindness (17.5/100 PY), whereas those outcomes in eyes with choroiditis appeared to be lower (2.3/100 PY and 0/100 PY, respectively). Although uncommon, non-CMV ocular opportunistic infections may be associated with high rates of visual loss and/or mortality. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Systemic diffuse large B-cell lymphoma masquerading as neovascular glaucoma.

    PubMed

    Bawankar, Pritam; Das, Dipankar; Bhattacharjee, Harsha; Tayab, Shahinur; Deori, Nilutparna; Paulbuddhe, Vivek; Dhar, Shriya; Deka, Apurba

    2018-02-01

    We describe a case of spontaneous hyphema associated with anterior uveitis presents in a 69-year old female as the prominent sign of the intraocular spread of systemic diffuse large B-cell lymphoma (DLBCL). She had a history of diabetes and initially misdiagnosed as neovascular glaucoma. Clinical history of systemic lymphoma, characteristic findings on B-scan ultrasonography and magnetic resonance imaging scan, and identification of atypical lymphoid cells in aqueous sample established the diagnosis of intraocular metastasis of systemic DLBCL. Therefore, this report highlights that life-threatening malignant systemic lymphoma may masquerade as anterior segment ocular inflammation or neovascular glaucoma.

  2. Systemic diffuse large B-cell lymphoma masquerading as neovascular glaucoma

    PubMed Central

    Bawankar, Pritam; Das, Dipankar; Bhattacharjee, Harsha; Tayab, Shahinur; Deori, Nilutparna; Paulbuddhe, Vivek; Dhar, Shriya; Deka, Apurba

    2018-01-01

    We describe a case of spontaneous hyphema associated with anterior uveitis presents in a 69-year old female as the prominent sign of the intraocular spread of systemic diffuse large B-cell lymphoma (DLBCL). She had a history of diabetes and initially misdiagnosed as neovascular glaucoma. Clinical history of systemic lymphoma, characteristic findings on B-scan ultrasonography and magnetic resonance imaging scan, and identification of atypical lymphoid cells in aqueous sample established the diagnosis of intraocular metastasis of systemic DLBCL. Therefore, this report highlights that life-threatening malignant systemic lymphoma may masquerade as anterior segment ocular inflammation or neovascular glaucoma. PMID:29380792

  3. Waardenburg syndrome: iris and choroidal hypopigmentation: findings on anterior and posterior segment imaging.

    PubMed

    Shields, Carol L; Nickerson, Stephanie J; Al-Dahmash, Saad; Shields, Jerry A

    2013-09-01

    Waardenburg syndrome typically manifests with congenital iris pigmentary abnormalities, but careful inspection can reveal additional posterior uveal pigmentary abnormalities. To demonstrate iris and choroidal hypopigmentation in patients with Waardenburg syndrome. Retrospective review of 7 patients referred for evaluation of presumed ocular melanocytosis. To describe the clinical and imaging features of the anterior and posterior uvea. In all patients, the diagnosis of Waardenburg syndrome was established. The nonocular features included white forelock in 4 of 7 (57%), tubular nose in 5 of 6 (83%), and small nasal alae in 5 of 6 (83%) patients. In 2 patients, a hearing deficit was documented on audiology testing. Family history of Waardenburg syndrome was elicited in 5 of 7 (71%) patients. Ocular features (7 patients) included telecanthus in 5 (71%), synophrys in 2 (29%), iris hypopigmentation in 5 (71%), and choroidal hypopigmentation in 5 (71%) patients. No patient had muscle contractures or Hirschsprung disease. Visual acuity was 20/20 to 20/50 in all patients. Iris hypopigmentation in 8 eyes was sector in 6 (75%) and diffuse (complete) in 2 (25%). Choroidal hypopigmentation in 9 eyes (100%) showed a sector pattern in 6 (67%) and a diffuse pattern in 3 (33%). Anterior segment optical coherence tomography revealed the hypopigmented iris to be thinner and with shallower crypts than the normal iris. Posterior segment optical coherence tomography showed a normal retina in all patients, but the subfoveal choroid in the hypopigmented region was slightly thinner (mean, 197 μm) compared with the opposite normal choroid (243 μm). Fundus autofluorescence demonstrated mild hyperautofluorescence (scleral unmasking) in hypopigmented choroid and no lipofuscin abnormality. Waardenburg syndrome manifests hypopigmentation of the iris and choroid with imaging features showing a slight reduction in the thickness of the affected tissue.

  4. A value-based medicine comparison of interventions for subfoveal neovascular macular degeneration.

    PubMed

    Brown, Gary C; Brown, Melissa M; Brown, Heidi C; Kindermann, Sylvia; Sharma, Sanjay

    2007-06-01

    To perform a value-based medicine analysis of clinical trials that evaluate the interventions of laser photocoagulation, intravitreal pegaptanib therapy, and photodynamic therapy (PDT) with verteporfin for the treatment of classic subfoveal choroidal neovascularization. Reference case cost-utility analysis using value-based medicine principles, which use patient-based utility values and standardized, input variable criteria. Data from participants in the Macular Photocoagulation Study, Pegaptanib for Neovascular Age-Related Macular Degeneration Study, and the Treatment of Age-Related Macular Degeneration with Photodynamic Therapy Study. Visual data were converted to a value-based format using time tradeoff utility analysis values from patients with macular degeneration. Costs were obtained from 2005 Medicare data. Outcomes (quality-adjusted life-years [QALYs]) and costs were discounted at a 3% annual rate. Interventional QALYs gained, percent improvement in quality of life, and dollars spent per QALY gained. Laser photocoagulation confers a 4.4% (P = 0.03 versus pegaptanib therapy) improvement in quality of life for the reference case, whereas pegaptanib therapy confers a 5.9% improvement and PDT confers an 8.1% (P = 0.0002 versus pegaptanib therapy) improvement. The cost-utility associated with laser photocoagulation is $8179, that for pegaptanib therapy is $66978, and that for PDT is $31544. All sensitivity analyses remain within the conventional standards of cost-effectiveness. Photodynamic therapy confers greater patient value than intravitreal pegaptanib therapy and laser photocoagulation for the treatment of classic subfoveal choroidal neovascularization. Despite the fact that laser photocoagulation is the most cost-effective intervention, both PDT and pegaptanib therapy deliver greater value, and thus are both preferred over laser photocoagulation. Using an economic measure, photodynamic therapy is the preferred treatment among these 3 interventions.

  5. Choroidal hemodynamic changes during isometric exercise in patients with inactive central serous chorioretinopathy.

    PubMed

    Tittl, Michael; Maar, Noemi; Polska, Elzbieta; Weigert, Günther; Stur, Michael; Schmetterer, Leopold

    2005-12-01

    Imaging studies suggest that the choroidal vasculature may be altered in central serous chorioretinopathy. Little is known, however, about the regulation of ocular blood flow in patients with central serous chorioretinopathy (CSC). The hypothesis for the present study was that choroidal blood flow changes during an increase in ocular perfusion pressure induced by isometric exercise may be altered in CSC. An observer-masked, two-cohort study was performed in 14 nonsmoking patients with chronic-relapsing but inactive CSC and in 14 healthy nonsmoking volunteers. Both groups were matched for age and sex. Subfoveal choroidal blood flow (CBF) was assessed with laser Doppler flowmetry, and ocular perfusion pressure (OPP) was calculated from mean arterial pressure (MAP) and intraocular pressure (IOP). Changes of CBF during isometric exercise over a period of 6 minutes were measured. Whereas the increase of MAP, the pulse rate, and the OPP were comparable between the two study groups, subfoveal CBF increased significantly more in the group of patients with CSC (P < 0.001). IOP remained unchanged in both groups during isometric exercise. At an 85% increase in OPP, subfoveal CBF was approximately twice as high in the patients with CSC compared with the healthy control group. The data indicate an abnormal subfoveal CBF regulation in patients with relapsing CSC compared with age-matched, nonsmoking, healthy volunteers during isometric exercise.

  6. Subthreshold transpupillary thermotherapy reduces experimental choroidal neovascularization in the mouse without collateral damage to the neural retina.

    PubMed

    Ming, Yue; Algvere, Peep V; Odergren, Anne; Berglin, Lennart; van der Ploeg, Ingeborg; Seregard, Stefan; Kvanta, Anders

    2004-06-01

    Transpupillary thermotherapy (TTT) is currently being evaluated for treatment of choroidal neovascularization (CNV) in age-related macular degeneration. To optimize TTT for CNV, the effect was analyzed of invisible (subthreshold) or visible (threshold) doses of TTT on the normal mouse retina and on experimental CNV. TTT was delivered to the normal retina of 42 mice with a diode laser at increasing power settings (50, 60, 70, or 80 mW), to obtain thermal lesions ranging from invisible (subthreshold) to visible (threshold) burns. CNV was induced in 53 mice by krypton laser photocoagulation of the fundus, after which the CNV lesions were treated with TTT (50, 60, or 80 mW). Eyes were enucleated 7 days after TTT and prepared for histology, and the CNV complex was evaluated on hematoxylin-eosin stained serial sections by measuring the maximum height of the CNV lesions. Ultrastructural changes were examined by transmission electron microscopy. Increasing the TTT laser power yielded gradually more visible effects. At 50 mW, which induced subthreshold burns, no damage was seen in the neural retina, retinal pigment epithelium (RPE), or choroid at any time point. By contrast, eyes treated with higher power exhibited progressively more damage to the neural retina, including a complete disruption of the outer nuclear layer. When TTT was applied to the laser-induced CNV lesions, the height of lesions was significantly reduced (P < 0.001) in response to all three power settings at 7 days after treatment. The mean relative thickness of the CNV lesion was 3.29 +/- 0.89 in untreated mice, whereas in TTT-treated mice it was 1.69 +/- 0.35, 1.69 +/- 0.41 and 1.70 +/- 0.17 at power settings of 50, 60, and 80 mW, respectively. The overlying neural retina showed no apparent damage with the 50- or 60-mW settings, whereas outer nuclear layer disruption occurred with a power of 80 mW. Electron microscopy confirmed the presence of vascular occlusion at 1 day and a fibrotic scar at 7 days

  7. γ-Secretase Inhibition of Murine Choroidal Neovascularization Is Associated with Reduction of Superoxide and Proinflammatory Cytokines

    PubMed Central

    Qi, Xiaoping; Cai, Jun; Ruan, Qing; Liu, Li; Boye, Sanford L.; Chen, Zhijuan; Hauswirth, William W.; Ryals, Renee C.; Shaw, Lynn; Caballero, Sergio; Grant, Maria B.

    2012-01-01

    Purpose. This study aimed to determine whether upregulation of γ-secretase could inhibit laser-induced choroidal neovascularization (CNV) and if this was associated with a reduction in both oxidative stress and proinflammatory cytokines. Methods. γ-Secretase, or its catalytic subunit presenilin 1 (PS1), were upregulated by exposure to either pigment epithelial derived factor (PEDF) or an AAV2 vector containing a PS1 gene driven by a vascular endothelial-cadherin promoter. Retinal endothelial cells were infected with AAV2 or exposed to PEDF in the presence or absence of VEGF and in vitro angiogenesis determined. Mouse eyes either received intravitreal injection of PEDF, DAPT (a γ-secretase inhibitor) or PEDF + DAPT at the time of laser injury, or AAV2 infection 3 weeks before receiving laser burns. Lesion volume was determined 14 days post laser injury. Superoxide generation, antioxidant activity and the production of proinflammatory mediators were assessed. Knockdown of γ-secretase was achieved using siRNA. Results. γ-Secretase upregulation and PS1 overexpression suppressed VEGF-induced in vitro angiogenesis and in vivo laser-induced CNV. This was associated with a reduction in the expression of VEGF and angiogenin 1 together with reduced superoxide anion generation and an increase in MnSOD compared with untreated CNV eyes. PS1 overexpression reduced proinflammatory factors and microglial activation in eyes with CNV compared with control. siRNA inhibition of γ-secretase resulted in increased angiogenesis. Conclusions. γ-Secretase, and in particular PS1 alone, are potent regulators of angiogenesis and this is due in part to stabilizing endogenous superoxide generation and reducing proinflammatory cytokine expression during CNV. PMID:22205609

  8. Choroidal microcirculation in patients with rotary cardiac assist device.

    PubMed

    Polska, Elzbieta; Schima, Heinrich; Wieselthaler, Georg; Schmetterer, Leopold

    2007-06-01

    In recent years, fully implanted rotary blood pumps have been used for long-term cardiac assist in patients with end-stage heart failure. With these pumps, the pulsatility of arterial blood flow and arterial pressure pulse is considerably reduced. Effects on end-organ perfusion, particularly microcirculation, have been assessed. The ocular choroid offers a unique opportunity to study the pulsatile component of blood flow by measurement of fundus pulsation amplitude (FPA) as well as the microcirculation by laser Doppler flowmetry. Both techniques were applied in three male patients with rotary pumps (MicroMed DeBakey VAD), in whom pump velocity was adjusted to four levels of flow between individual minimal need and maximal support. In addition, blood flow velocities in the ophthalmic artery (peak, end-diastolic and mean flow velocity--PSV, EDV and MFV, respectively) were measured using color Doppler imaging. Systolic blood pressure increased by 6 to 22 mm Hg with increasing support. At maximal support FPA was reduced by -60% to -52% as compared with minimal pump support. Blood flow in the choroidal microvasculature, however, did not show relevant changes. A reduction in PSV (-31%, range -47% to -21%) and a pronounced rise in EDV (+93%, range +28% to +147%) was observed, whereas MFV was independent of pump flow. Our data indicate that mean choroidal blood flow is maintained when pump support is varied within therapeutic values, whereas the ratio of pulsatile to non-pulsatile choroidal flow changes. This study shows that, in patients with ventricular assist devices, a normal perfusion rate in the ocular microcirculation is maintained over a wide range of support conditions.

  9. Three-year safety and visual acuity results of epimacular 90 strontium/90 yttrium brachytherapy with bevacizumab for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration.

    PubMed

    Avila, Marcos P; Farah, Michael E; Santos, Arturo; Carla, Livia; Fuji, Gildo; Rossi, Juliana; Nau, Jeffrey

    2012-01-01

    To evaluate the long-term safety and visual acuity outcomes associated with epimacular strontium 90 brachytherapy combined with intravitreal bevacizumab for the treatment of subfoveal choroidal neovascularization because of age-related macular degeneration. Thirty-four treatment-naive patients with predominantly classic, minimally classic, and occult subfoveal choroidal neovascularization lesions participated in this prospective, 2-year, nonrandomized multicenter study. Subjects from 1 center (n = 19) were reconsented and followed-up for 3 years. Each subject received a single 24-Gy beta irradiation treatment via an intraocular delivery device and 2 planned injections of bevacizumab at treatment and 1 month later. Additional bevacizumab therapy was permitted based on prespecified retreatment criteria. Adverse events were observed, and best-corrected visual acuity was measured using Early Treatment Diabetic Retinopathy Study vision charts. Subjects were evaluated every 3 months during the first year of follow-up and every 6 months during Years 2 and 3 of follow-up. All 34 subjects were followed-up for 24 months and 19 were followed-up through 36 months. With up to 24 months of follow-up, 12 of 24 phakic patients (50%) exhibited ≥ 2 grades of progression in Lens Opacification Classification System (LOCS) II lens classification; 5 eyes underwent cataract extraction before the Month 36 visit. There was 1 case of nonproliferative retinopathy identified at 36 months of follow-up that did not have an adverse effect on visual acuity, was stable at 43 months of follow-up, and was isolated to the parafoveal region. Mean best-corrected visual acuity demonstrated an average gain of +15.0 and -4.9 letters at 12 months and 24 months, respectively; the drop in mean gain at Month 24 was largely attributable to cataract formation. At 36 months (n = 19), the mean best-corrected visual acuity was +3.9, 90% (17 of 19) of eyes had lost <15 letters from baseline, 53% (10 of 19) had

  10. The cost-utility of photodynamic therapy in eyes with neovascular macular degeneration--a value-based reappraisal with 5-year data.

    PubMed

    Brown, Gary C; Brown, Melissa M; Campanella, Joseph; Beauchamp, George R

    2005-10-01

    To assess the value conferred by photodynamic therapy (PDT) and the cost-utility of PDT for the treatment of classic, subfoveal choroidal neovascularization associated with age-related macular degeneration (ARMD). Average cost-utility analysis utilizing clinical trial data, patient-based time tradeoff utility preferences, and a third party insurer cost perspective. Five-year visual acuity data from the TAP (Treatment of Age-related Macular Degeneration With Photodynamic Therapy) Investigation were modeled into a 12-year, value-based, reference case, cost-utility model utilizing year 2004 Medicare costs and an outcome of dollar/QALY (dollars/quality-adjusted life-year). Discounting of outcomes and costs using net present value analysis with a 3% annual rate was performed as recommended by the Panel for Cost-Effectiveness in Health and Medicine. PDT with verteporfin (Visudyne) dye for classic subfoveal choroidal neovascularization confers an 8.1% quality of life (value) improvement over the 12-year life expectancy of the reference case, while during the last 8 years the value improvement is 9.5%. The average cost-utility of the intervention is dollar 31,103/QALY (quality-adjusted life-year). Extensive one-way sensitivity analysis values range from dollar 20,736/QALY if treatment efficacy is increased by 50% to dollar 62,207 if treatment efficacy is decreased by 50%, indicating robustness of the model. PDT using verteporfin dye to treat classic subfoveal choroidal neovascularization is a very cost-effective treatment by conventional standards. The marked improvement in cost-effectiveness compared with a previous report results from the facts that the treatment benefit increasingly accrues during 5 years of follow-up while the number of yearly treatments diminishes markedly during that time.

  11. Validity of Automated Choroidal Segmentation in SS-OCT and SD-OCT.

    PubMed

    Zhang, Li; Buitendijk, Gabriëlle H S; Lee, Kyungmoo; Sonka, Milan; Springelkamp, Henriët; Hofman, Albert; Vingerling, Johannes R; Mullins, Robert F; Klaver, Caroline C W; Abràmoff, Michael D

    2015-05-01

    To evaluate the validity of a novel fully automated three-dimensional (3D) method capable of segmenting the choroid from two different optical coherence tomography scanners: swept-source OCT (SS-OCT) and spectral-domain OCT (SD-OCT). One hundred eight subjects were imaged using SS-OCT and SD-OCT. A 3D method was used to segment the choroid and quantify the choroidal thickness along each A-scan. The segmented choroidal posterior boundary was evaluated by comparing to manual segmentation. Differences were assessed to test the agreement between segmentation results of the same subject. Choroidal thickness was defined as the Euclidian distance between Bruch's membrane and the choroidal posterior boundary, and reproducibility was analyzed using automatically and manually determined choroidal thicknesses. For SS-OCT, the average choroidal thickness of the entire 6- by 6-mm2 macular region was 219.5 μm (95% confidence interval [CI], 204.9-234.2 μm), and for SD-OCT it was 209.5 μm (95% CI, 197.9-221.0 μm). The agreement between automated and manual segmentations was high: Average relative difference was less than 5 μm, and average absolute difference was less than 15 μm. Reproducibility of choroidal thickness between repeated SS-OCT scans was high (coefficient of variation [CV] of 3.3%, intraclass correlation coefficient [ICC] of 0.98), and differences between SS-OCT and SD-OCT results were small (CV of 11.0%, ICC of 0.73). We have developed a fully automated 3D method for segmenting the choroid and quantifying choroidal thickness along each A-scan. The method yielded high validity. Our method can be used reliably to study local choroidal changes and may improve the diagnosis and management of patients with ocular diseases in which the choroid is affected.

  12. Role of Angiography in Systemic Lupus Erythematosus-Induced Choroiditis.

    PubMed

    Lee, Kenneth Rohan; Peng, Lai Yin; Iqbal, Tajunisah Begum; Subrayan, Visvaraja

    2017-03-31

    To report a case of systemic lupus erythematosus-induced choroidal vasculitis. A 34-year-old woman with a long-standing history of systemic lupus erythematosus had a sudden painless loss of vision in the right eye over 12 hours. Ocular examination revealed a visual acuity of counting fingers of 1 foot on the right eye and 20/20 on the left. There was a relative afferent pupillary defect on the right side with a pink, distinct optic disk margin. Optical coherence tomography of the macula and fundus fluorescein angiogram for the eyes were normal. The MRI brain and orbit with the cerebral MRA did not show signs of optic neuritis or occipital vasculitic changes. However, the indocyanine green angiography revealed patches of ill-defined areas of choroidal hypofluorescence in the early- to mid-phase in the macula region. ICGA becomes the crucial tool in unmasking the presence of choroidal vasculitis.

  13. Corneal Neovascularization with Associated Lipid Keratopathy in a Patient with Obstructive Sleep Apnea-Hypopnea Syndrome Using a Continuous Positive Airway Pressure Machine.

    PubMed

    Oikonomakis, Konstantinos; Petrelli, Myrsini; Andreanos, Konstantinos; Mouchtouris, Andreas; Petrou, Petros; Georgalas, Ilias; Papaconstantinou, Dimitrios; Kymionis, George

    2017-01-01

    To report a case of corneal neovascularization with secondary lipid keratopathy in a patient treated with continuous positive airway pressure (CPAP) for obstructive sleep apnea-hypopnea syndrome (OSAHS). A 49-year-old male had been diagnosed with obstructive sleep apnea syndrome 10 years ago and has been treated with the application of a CPAP machine during night sleep ever since. For the past year, the patient had been complaining for ocular irritation and excessive tearing of the left eye on awakening. Slit-lamp biomicroscopy revealed the presence of neovascularization and lipid exudation in the inferior third of the cornea of the left eye. Ocular patching during night sleep resulted in recession of the reported symptoms and shrinkage of the neovascularization, while the area of lipid exudation ceased to enlarge. To the best of our knowledge, this is the first report of corneal neovascularization in a patient using a CPAP machine for OSAHS.

  14. Outcomes of Anti-Vascular Endothelial Growth Factor Treatment for Choroidal Neovascularization in Fellow Eyes of Previously Treated Patients With Neovascular Age-Related Macular Degeneration.

    PubMed

    Stem, Maxwell S; Moinuddin, Omar; Kline, Noah; Thanos, Aristomenis; Rao, Prethy; Williams, George A; Hassan, Tarek S

    2018-05-10

    Neovascular age-related macular degeneration (nvAMD) is a leading cause of vision loss. The optimal screening protocol to detect choroidal neovascularization (CNV) in fellow eyes of patients undergoing treatment for unilateral CNV has not been determined. To compare the visual outcomes of eyes with established, active nvAMD in index eyes with outcomes of fellow eyes that subsequently developed CNV during the management protocol. In this retrospective single-center case series conducted at a private vitreoretinal practice, data were collected for all patients treated for bilateral nvAMD between October 1, 2015, and October 1, 2016, for whom we could determine the date of index eye and fellow eye conversion to nvAMD (n = 1600). Per institutional protocol, patients were screened for new CNV in the fellow eye at every office visit. Patients were excluded if they had a condition that could result in marked asymmetric vision loss. Development of nvAMD. Visual acuity (VA) at the time of diagnosis of nvAMD and at equivalent time points following conversion to nvAMD for both index eyes and fellow eyes. A total of 264 patients met the inclusion criteria; 197 (74.6%) were women and 253 (95.8%) were white, and the mean (SD) age was 79.1 (8.2) years at time of index eye conversion to nvAMD and 80.6 (8.2) years at time of fellow eye conversion to nvAMD. Fellow eyes presented with better VA (mean VA, 20/50 [0.40 logMAR]) compared with index eyes (mean VA, 20/90 [0.67 logMAR]) at the time of conversion (difference, 14 letters [0.27 logMAR]; 95% CI, 10-17 [0.20-0.34]; P < .001). Index eyes did not achieve the same level of VA as fellow eyes after an equivalent postconversion follow-up of approximately 20 months (mean VA: index eye; 20/70 [0.56 logMAR]; fellow eye, 20/50 [0.40 logMAR]; difference, 8 letters [0.15 logMAR]; 95% CI, 4-11 [0.08-0.22]; P < .001). No difference was detected between the mean number of anti-vascular endothelial growth factor injections received

  15. Measurement of Choroidal Perfusion and Thickness Following Systemic Sildenafil (Viagra®)

    PubMed Central

    Kim, David Y.; Silverman, Ronald H.; Chan, R.V. Paul; Khanifar, Aziz A.; Rondeau, Mark; Lloyd, Harriet; Schlegel, Peter; Coleman, D. Jackson

    2011-01-01

    Objective To demonstrate anatomic and physiologic changes in the human choroid following systemic sildenafil citrate (ViagraR) using enhanced depth imaging spectral domain-optical coherence tomography (EDI-OCT) and swept-scan high frequency digital ultrasound. Methods Seven healthy male subjects (mean age 32.7 years) were evaluated at baseline and two hours after ingesting 50 mg of sildenafil. Swept-scan high frequency digital ultrasound and EDI-OCT were utilized to measure choroidal perfusion and thickness, respectively. Results were read by masked observers. The Wilcoxon signed-rank test and t-test were used to analyze differences in choroidal flow and thickness at baseline and two hours after ingestion of sildenafil. Results Two hours following sildenafil, increased choroidal perfusion was observed in 11 of 12 eyes measured by swept-scan high frequency digital ultrasound. The mean increase was 3.46 (±2.00) times baseline with a range of 0.47 to 7.80 times baseline (p=0.004). Increased choroidal thickness was observed in 12 of 12 eyes measured with EDI-OCT. The average choroidal thickness increased by 11.6% temporal to the fovea, 9.3% nasal to the fovea, and 10.7% underneath the fovea (p<0.001 for all values). Conclusions Choroidal perfusion and thickness both increase in response to systemic sildenafil. These changes could secondarily affect retinal function, explain previously reported clinical symptoms, and potentially be a useful adjunct for treatment of ocular diseases that would benefit from increased choroidal blood flow. PMID:22974308

  16. Preliminary in vitro and in vivo assessment of a new targeted inhibitor for choroidal neovascularization in age-related macular degeneration.

    PubMed

    Li, Wenbo; Dong, Lijie; Ma, Minwang; Hu, Bojie; Lu, Zhenyu; Liu, Xun; Liu, Juping; Li, Xiaorong

    2016-01-01

    Choroidal neovascularization (CNV) in age-related macular degeneration usually causes blindness. We established a novel targeted inhibitor for CNV in age-related macular degeneration. The inhibitor CR2-sFlt 1 comprises a CR2-targeting fragment and an anti-vascular endothelial growth factor (VEGF) domain (sFlt 1). The targeting of CR2-sFlt 1 was studied using the transwell assay in vitro and frozen sections in vivo using green fluorescent labeling. Transwell assay results showed that CR2-sFlt 1 migrated to the interface of complement activation products and was present in the retinal tissue of the CR2-sFlt 1-treated CNV mice. Treatment effects were assessed by investigating the VEGF concentration in retinal pigmented epithelial cell medium and the thickness of the CNV complex in the mice treated with CR2-sFlt 1. CR2-sFlt 1 significantly reduced the VEGF secretion from retinal pigmented epithelial cells in vitro and retarded CNV progress in a mouse model. Expression analysis of VEGF and VEGFRs after CR2-sFlt 1 intervention indicated the existence of feedback mechanisms in exogenous CR2-sFlt 1, endogenous VEGF, and VEGFR interaction. In summary, we demonstrated for the first time that using CR2-sFlt 1 could inhibit CNV with clear targeting and high selectivity.

  17. Partial antagonism of endothelin 1-induced vasoconstriction in the human choroid by topical unoprostone isopropyl.

    PubMed

    Polska, Elzbieta; Doelemeyer, Arno; Luksch, Alexandra; Ehrlich, Paulina; Kaehler, Nils; Percicot, Christine L; Lambrou, George N; Schmetterer, Leopold

    2002-03-01

    There is increasing evidence that reduced ocular blood flow plays a role in the pathogenesis of glaucoma. In patients with normal-tension glaucoma, ocular blood flow abnormalities may be associated with dysfunction of the endothelin 1 (ET-1) regulation system. To test the hypothesis that unoprostone, a topical docosanoid, may affect ET-1--induced vasoconstriction in the human choroid. In a placebo-controlled, randomized, double-masked, 2-way crossover design, ET-1 (2.5 ng/kg per minute for 150 minutes) was administered intravenously to 24 healthy individuals. Thirty minutes after the start of ET-1 infusion, 1 drop of unoprostone or placebo was instilled into the right eye. After another 30 minutes, 2 drops of unoprostone or placebo was topically administered. This procedure was continued and the dose was increased further until 4 drops of unoprostone or placebo was reached. Subfoveal and pulsatile choroidal blood flow were assessed using laser Doppler flowmetry and laser interferometric measurement of fundus pulsation amplitude, respectively. Administration of exogenous ET-1 decreased choroidal blood flow (mean +/- SEM, 17% +/- 2%; P<.001) and fundus pulsation amplitude (mean +/- SEM, 19% +/- 2%; P<.001). This effect was significantly blunted when topical unoprostone was coadministered (mean +/- SEM decrease in choroidal blood flow, 7% +/- 2%; P =.04 vs. placebo; mean +/- SEM decrease in fundus pulsation amplitude, 12% +/- 2%; P<.001 vs. placebo). There is a functional antagonism between ET-1 and topical unoprostone in the choroidal vasculature. Our findings of a functional antagonism between ET-1 and topical unoprostone in the choroidal vasculature may be important in vascular eye diseases associated with increased ET-1.

  18. Interocular symmetry in macular choroidal thickness in children.

    PubMed

    Al-Haddad, Christiane; El Chaar, Lama; Antonios, Rafic; El-Dairi, Mays; Noureddin, Baha'

    2014-01-01

    Objective. To report interocular differences in choroidal thickness in children using spectral domain optical coherence tomography (SD-OCT) and correlate findings with biometric data. Methods. This observational cross-sectional study included 91 (182 eyes) healthy children aged 6 to 17 years with no ocular abnormality except refractive error. After a comprehensive eye exam and axial length measurement, high definition macular scans were performed using SD-OCT. Two observers manually measured the choroidal thickness at the foveal center and at 1500 µm nasally, temporally, inferiorly, and superiorly. Interocular differences were computed; correlations with age, gender, refractive error, and axial length were performed. Results. Mean age was 10.40 ± 3.17 years; mean axial length and refractive error values were similar between fellow eyes. There was excellent correlation between the two observers' measurements. No significant interocular differences were observed at any location. There was only a trend for right eyes to have higher values in all thicknesses, except the superior thickness. Most of the choroidal thickness measurements correlated positively with spherical equivalent but not with axial length, age, or gender. Conclusion. Choroidal thickness measurements in children as performed using SD-OCT revealed a high level of interobserver agreement and consistent interocular symmetry. Values correlated positively with spherical equivalent refraction.

  19. A novel, microscope based, non invasive Laser Doppler flowmeter for choroidal blood flow assessment

    PubMed Central

    Strohmaier, C; Werkmeister, RM; Bogner, B; Runge, C; Schroedl, F; Brandtner, H; Radner, W; Schmetterer, L; Kiel, JW; Grabnerand, G; Reitsamer, HA

    2015-01-01

    Impaired ocular blood flow is involved in the pathogenesis of numerous ocular diseases like glaucoma or AMD. The purpose of the present study was to introduce and validate a novel, microscope based, non invasive laser Doppler flowmeter (NILDF) for measurement of blood flow in the choroid. The custom made NI-LDF was compared with a commercial fiber optic based laser Doppler flowmeter (Perimed PF4000). Linearity and stability of the NI-LDF were assessed in a silastic tubing model (i.d. 0.3 mm) at different flow rates (range 0.4 – 3 ml/h). In a rabbit model continuous choroidal blood flow measurements were performed with both instruments simultaneously. During blood flow measurements ocular perfusion pressure was changed by manipulations of intraocular pressure via intravitreal saline infusions. The NILDF measurement correlated linearly to intraluminal flow rates in the perfused tubing model (r = 0.99, p<0.05) and remained stable during a 1 hour measurement at a constant flow rate. Rabbit choroidal blood flow measured by the PF4000 and the NI-LDF linearly correlated with each other over the entire measurement range (r = 0.99, y = x* 1,01 – 12,35 P.U., p < 0,001). In conclusion, the NI-LDF provides valid, semi quantitative measurements of capillary blood flow in comparison to an established LDF instrument and is suitable for measurements at the posterior pole of the eye. PMID:21443871

  20. Feasibility of Proton Beam Therapy for Ocular Melanoma Using a Novel 3D Treatment Planning Technique

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hartsell, William F., E-mail: whartsell@chicagocancer.org; Kapur, Rashmi; Hartsell, Siobhan O'Connor

    Purpose: We evaluated sparing of normal structures using 3-dimensional (3D) treatment planning for proton therapy of ocular melanomas. Methods and Materials: We evaluated 26 consecutive patients with choroidal melanomas on a prospective registry. Ophthalmologic work-up included fundoscopic photographs, fluorescein angiography, ultrasonographic evaluation of tumor dimensions, and magnetic resonance imaging of orbits. Three tantalum clips were placed as fiducial markers to confirm eye position for treatment. Macula, fovea, optic disc, optic nerve, ciliary body, lacrimal gland, lens, and gross tumor volume were contoured on treatment planning compute tomography scans. 3D treatment planning was performed using noncoplanar field arrangements. Patients were typicallymore » treated with 3 fields, with at least 95% of planning target volume receiving 50 GyRBE in 5 fractions. Results: Tumor stage was T1a in 10 patients, T2a in 10 patients, T2b in 1 patient, T3a in 2 patients, T3b in 1 patient, and T4a in 2 patients. Acute toxicity was mild. All patients completed treatment as planned. Mean optic nerve dose was 10.1 Gy relative biological effectiveness (RBE). Ciliary body doses were higher for nasal (mean: 11.4 GyRBE) than temporal tumors (5.8 GyRBE). Median follow-up was 31 months (range: 18-40 months). Six patients developed changes which required intraocular bevacizumab or corticosteroid therapy, but only 1 patient developed neovascular glaucoma. Five patients have since died: 1 from metastatic disease and 4 from other causes. Two patients have since required enucleation: 1 due to tumor and 1 due to neovascular glaucoma. Conclusions: 3D treatment planning can be used to obtain appropriate coverage of choroidal melanomas. This technique is feasible with relatively low doses to anterior structures, and appears to have acceptable rates of local control with low risk of enucleation. Further evaluation and follow-up is needed to determine optimal dose-volume relationships

  1. Changes in Fundus Autofluorescence after Anti-vascular Endothelial Growth Factor According to the Type of Choroidal Neovascularization in Age-related Macular Degeneration.

    PubMed

    Lee, Ji Young; Chung, Hyewon; Kim, Hyung Chan

    2016-02-01

    To describe the changes of fundus autofluorescence (FAF) in patients with age-related macular degeneration before and after intravitreal injection of anti-vascular endothelial growth factor according to the type of choroidal neovascularization (CNV) and to evaluate the correlation of FAF with spectral domain optical coherence tomography (SD-OCT) parameters and vision. This was a retrospective study. Twenty-one treatment-naïve patients with neovascular age-related macular degeneration were included. Study eyes were divided into two groups according to the type of CNV. Fourteen eyes were type 1 CNV and seven eyes were type 2 CNV. All eyes underwent a complete ophthalmologic examination, including an assessment of best-corrected visual acuity, SD-OCT, fluorescein angiography, and FAF imaging, before and 3 months after intravitreal anti-vascular endothelial growth factor injection. Gray scales of FAF image for CNV areas, delineated as in fluorescein angiography, were analyzed using the ImageJ program, which were adjusted by comparison with normal background areas. Correlation of changes in FAF with changes in SD-OCT parameters, including CNV thickness, photoreceptor inner and outer segment junction disruption length, external limiting membrane disruption length, central macular thickness, subretinal fluid, and intraretinal fluid were analyzed. Eyes with both type 1 and type 2 CNV showed reduced FAF before treatment. The mean gray scales (%) of type 1 and type 2 CNV were 52.20% and 42.55%, respectively. The background values were 106.72 and 96.86. After treatment, the mean gray scales (%) of type 1 CNV and type 2 CNV were changed to 57.61% (p = 0.005) and 57.93% (p = 0.008), respectively. After treatment, CNV thickness, central macular thickness, and inner and outer segment junction disruption length were decreased while FAF increased. FAF was noted to be reduced in eyes with newly diagnosed wet age-related macular degeneration, but increased after anti

  2. Adhesion Failures Determine the Pattern of Choroidal Neovascularization in the Eye: A Computer Simulation Study

    PubMed Central

    Shirinifard, Abbas; Glazier, James Alexander; Swat, Maciej; Gens, J. Scott; Family, Fereydoon; Jiang, Yi; Grossniklaus, Hans E.

    2012-01-01

    Choroidal neovascularization (CNV) of the macular area of the retina is the major cause of severe vision loss in adults. In CNV, after choriocapillaries initially penetrate Bruch's membrane (BrM), invading vessels may regress or expand (CNV initiation). Next, during Early and Late CNV, the expanding vasculature usually spreads in one of three distinct patterns: in a layer between BrM and the retinal pigment epithelium (sub-RPE or Type 1 CNV), in a layer between the RPE and the photoreceptors (sub-retinal or Type 2 CNV) or in both loci simultaneously (combined pattern or Type 3 CNV). While most studies hypothesize that CNV primarily results from growth-factor effects or holes in BrM, our three-dimensional simulations of multi-cell model of the normal and pathological maculae recapitulate the three growth patterns, under the hypothesis that CNV results from combinations of impairment of: 1) RPE-RPE epithelial junctional adhesion, 2) Adhesion of the RPE basement membrane complex to BrM (RPE-BrM adhesion), and 3) Adhesion of the RPE to the photoreceptor outer segments (RPE-POS adhesion). Our key findings are that when an endothelial tip cell penetrates BrM: 1) RPE with normal epithelial junctions, basal attachment to BrM and apical attachment to POS resists CNV. 2) Small holes in BrM do not, by themselves, initiate CNV. 3) RPE with normal epithelial junctions and normal apical RPE-POS adhesion, but weak adhesion to BrM (e.g. due to lipid accumulation in BrM) results in Early sub-RPE CNV. 4) Normal adhesion of RBaM to BrM, but reduced apical RPE-POS or epithelial RPE-RPE adhesion (e.g. due to inflammation) results in Early sub-retinal CNV. 5) Simultaneous reduction in RPE-RPE epithelial binding and RPE-BrM adhesion results in either sub-RPE or sub-retinal CNV which often progresses to combined pattern CNV. These findings suggest that defects in adhesion dominate CNV initiation and progression. PMID:22570603

  3. Multifocal choroiditis - an unusual finding in Crohns disease.

    PubMed

    Vianna, R N G; Ozdal, P C; Deschnes, J

    To report a patient with Crohns disease and acute decreased vision in one eye secondary to multifocal choroiditis and serous retinal detachment. A complete ocular examination, including fluorescein angiography, was performed. Fundus biomicroscopy disclosed multifocal, deep, discretely elevated yellowish lesions at the posterior pole of the affected eye. Fluorescein angiographic study of these lesions revealed early hypofluorescence followed by late yperfluorescence. Subtenonian injection of corticosteroids rapidly induced remission of the choroidal lesions. Chorioretinal involvement in patients with Crohns disease may or may not be related to reactivation of this disorder. Therefore, even patients without gastrointestinal symptoms who present with posterior segment inflammation must be informed of this. The chorioretinal inflammatory lesions do seem to respond promptly to periocular injection of corticosteroids. (Eur J Ophthalmol 2004; 14: 345-9).

  4. Sensitivity and specificity of optical coherence tomography angiography (OCT-A) for detection of choroidal neovascularization in real-life practice and varying retinal expertise level.

    PubMed

    Souedan, Vaël; Souied, Eric H; Caillaux, Violaine; Miere, Alexandra; Ameen, Ala El; Blanco-Garavito, Rocio

    2017-05-25

    To evaluate the diagnostic accuracy of OCT angiography (OCT-A) detecting or predicting choroidal neovascularization (CNV), by ophthalmologists of disparate degrees of skills in retinal diseases, using spectral domain optical coherence tomography (SD-OCT) and fluorescein angiography (FA) as a standard reference. Retrospective observational case series. Patient presenting maculopathy and complete imaging were included. FA, SD-OCT, OCT-A and FA coupled to SD-OCT images were graded independently for presence or absence of CNV by ophthalmologists with varying expertise levels. Overall sensitivity of OCT-A was 85.62% (95% CI 79.04-90.76%) and specificity was 81.51% (95% CI 73.36-88.03). Sensitivity of FA was 74.51% (95% CI 66.84-81.20), and specificity was 82.35% (95% CI 74.30-88.73). Sensitivity of FA + SD-OCT was 92.72% (95% CI 87.34-96.30), and specificity was 90.91% (95% CI 84.31-95.37). OCT-A has good sensitivity and specificity for the detection of CNV in all expertise level groups. OCT-A may soon become a routine tool for CNV diagnosis and follow-up.

  5. Ocular anatomy of the black pacu (Colossoma macropomum): gross, histologic, and diagnostic imaging.

    PubMed

    Gustavsen, Kate A; Paul-Murphy, Joanne R; Weber, Ernest Scott; Zwingenberger, Allison L; Dunker, Freeland H; Dubielzig, Richard R; Reilly, Christopher M; Murphy, Christopher J

    2018-01-30

    To describe the ocular anatomy of the black pacu (Colossoma macropomum), a freshwater teleost fish of the Amazon River basin, including an unusual choroid laden with adipose tissue. Three adult black pacu were anesthetized and examined clinically and with ocular ultrasonography, then euthanized. Three fish were euthanized and their heads imaged immediately postmortem using computed tomography. One fish was euthanized and its exenterated eyes imaged by high-resolution magnetic resonance imaging. The exenterated eyes of all seven fish were fixed in formalin; eyes from three fish were examined grossly and histologically. Additionally, archived histologic sections from two smaller black pacu specimens were examined. Findings were consistent among the ocular imaging modalities used. Intrinsic to the sclera were circumferential ossicles and scleral cartilage. The lens was spherical and protruded through the ovoid pupil with an aphakic space inferiorly when the accommodative mechanism was relaxed under anesthesia. Both a small falciform process and epiretinal vasculature were present in the posterior segment. The retina was cone-rich, and processes of the retinal pigment epithelium enveloped the photoreceptor outer segments. Remarkably, the choroid occupied one-third of the anteroposterior length of the globe; histology confirmed that the bulk of the choroid was composed of adipose tissue. The eye of the pacu overall is typical of teleosts but has the notable and consistent finding of a substantive store of choroidal fat of unknown function. © 2018 American College of Veterinary Ophthalmologists.

  6. [Clinical characteristics of choroidal metastasis].

    PubMed

    Zhang, Hui-rong; Ma, Zhi-zhong; Feng, Yun; Guo, Tong

    2009-04-01

    To study the clinical characteristics of choroidal metastasis (CM) to promote the early diagnosis and differentiate from other choroidal tumors. Retrospective clinical observational cases. All patients with choroidal metastasis underwent ophthalmologic examination including best corrected visual acuity (VA), slit-lamp examination, binocular indirect funduscopy, color photography, fundus fluorescein angiography (FFA), indocyanine-green angiography (ICGA), optical coherence tomography (OCT), A and B scan ultrasound examination, magnetic resonance image (MRI) as well as CT of the thorax, etc. Nine eyes of 5 patients with CM were examined. Unilateral choroidal involvement was present in 1 patient, bilateral in 4 cases. There were 1 case male and 4 case females. The age of these patients ranged from 31 to 56 years, median 45 years. Ocular symptoms included reduced vision in 4 patients and visual distortion in 1 patient. Visual acuity was 20/400- < 20/63 in four eyes; 20/63- < 20/30 in two eyes and >or= 20/30 in three eyes. The primary cancer site was in the lung in 3 patients, in the breast in 1 patient and in the stomach in 1 patient. Fundus characteristics: Typical CM was more often in the plateau-shaped than in the dome-shaped; yellow-white or mottled in color and associated with subretinal fluid and retinal detachment. The tumor was found in the macular area and juxtapapillary area in 6 eyes, in the area between the macula and the equator in 3 eyes. CM was solitary in 5 eyes and showed multiple lesions in 4 eyes. By FA the lesions showed mottled hyperfluorescence in early stage and leakage in late stage. By ICGA the lesion showed blocked fluorescence and hypofluorescence. Choroidal mass showed moderate irregular internal reflectivity in A-scan ultrasound. B-scan showed a plateau-shaped solid mass. MRI examination of the lesion revealed moderate short T1W and T2W signals. The cancer antigen increased to 16.28 and 4.95 microg/L in two cases. CA125 increased to 160.5 k

  7. Quantitative reflection spectroscopy at the human ocular fundus

    NASA Astrophysics Data System (ADS)

    Hammer, Martin; Schweitzer, Dietrich

    2002-01-01

    A new model of the reflection of the human ocular fundus on the basis of the adding-doubling method, an approximate solution of the radiative transport equation, is described. This model enables the calculation of the concentrations of xanthophyll in the retina, of melanin in the retinal pigment epithelium and the choroid, and of haemoglobin in the choroid from fundus reflection spectra. The concentration values found in 12 healthy subjects are in excellent agreement with published data. In individual cases of pathologic fundus alterations, possible benefits to the ophthalmologic diagnostics are demonstrated.

  8. Aflibercept for neovascular age-related macular degeneration

    PubMed Central

    Sarwar, Salman; Clearfield, Elizabeth; Soliman, Mohamed Kamel; Sadiq, Mohammad Ali; Baldwin, Andrew J; Hanout, Mostafa; Agarwal, Aniruddha; Sepah, Yasir J; Do, Diana V; Nguyen, Quan Dong

    2016-01-01

    Background Central vision loss caused by age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Neovascular AMD is characterized by choroidal neovascularization (CNV). Growth of new blood vessels in patients with neovascular AMD is driven by a complex process that involves a signal protein called vascular endothelial growth factor A (VEGF-A). Anti-VEGF drugs that block this protein include ranibizumab, bevacizumab, and aflibercept. Objectives To assess and compare the effectiveness and safety of intravitreal injections of aflibercept versus ranibizumab, bevacizumab, or sham for treatment of patients with neovascular AMD. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (Issue 11, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), PubMed (1948 to November 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched December 4, 2014), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on November 30, 2015. Selection criteria We included randomized controlled trials (RCTs) in which aflibercept monotherapy was compared with ranibizumab, bevacizumab, or sham for participants with neovascular AMD who were treatment-naive. Data collection and analysis We used standard methodological procedures of The Cochrane Collaboration for screening, data abstraction, and study assessment. Two review authors

  9. Retinal injury thresholds for 532, 578, and 630 nm lasers in connection to photodynamic therapy for choroidal neovascularization.

    PubMed

    Chen, Hongxia; Yang, Zaifu; Zou, Xianbiao; Wang, Jiarui; Zhu, Jianguo; Gu, Ying

    2014-01-01

    The purpose of this study was to explore the retinal injury thresholds in rabbits and evaluate the influence of retinal pigmentation on threshold irradiance at laser wavelengths of 532, 578, and 630 nm which might be involved in hypocrellin B (HB) and hematoporphyrin monomethyl ether (HMME) photodynamic therapy (PDT) for choroidal neovascularization (CNV). The eyes of pigmented and non-pigmented rabbits were exposed to 532, 578, and 630 nm lasers coupled to a slit lamp biological microscope. The exposure duration was 100 seconds and the retinal spot size was 2 mm throughout the experiment. The minimum visible lesions were detected by funduscopy at 1 and 24 hours post exposure. Bliss probit analysis was performed to determine the ED50 thresholds, fiducial limits and probit slope. In pigmented rabbits, the 24-hour retinal threshold irradiances at 532, 578, and 630 nm were 1,003, 1,475, and 1,720 mW/cm(2) , respectively. In non-pigmented rabbits, the 24-hour threshold irradiances were 1,657, 1,865, and 15,360 mW/cm(2) , respectively. The ED50 for 24-hour observation differed very little from the ED50 for 1-hour observation. The non-pigmented rabbits required a ninefold increase in threshold irradiance at 630 nm comparing to the pigmented rabbits. This study will contribute to the knowledge base for the limits of laser irradiance in application of HB or HMME PDT for CNV. © 2013 Wiley Periodicals, Inc.

  10. Assessing posterior ocular structures in β-thalassemia minor.

    PubMed

    Arifoglu, Hasan Basri; Kucuk, Bekir; Duru, Necati; Altunel, Orhan; Gulhan, Ahmet; Ozen, Mustafa; Aygun, Bilal; Atas, Mustafa

    2018-02-01

    The aim of this study was to investigate the effect of β-thalassemia minor on choroidal, macular, and peripapillary retinal nerve fiber layer thickness. To form the sample, we recruited 40 patients with β-thalassemia minor and 44 healthy participants. We used spectral-domain optical coherence tomography to take all measurements of ocular thickness, as well as measured intraocular pressure, axial length, and central corneal thickness. We later analyzed correlations of hemoglobin levels with ocular parameters. A statistically significant difference emerged between patients with β-thalassemia minor and the healthy controls in terms of mean values of subfoveal, nasal, and temporal choroidal thickness (p = 0.001, p = 0.016, and p = 0.010, respectively). Except for central macular thickness, differences in paracentral macular thicknesses between the groups were also significant (superior: p < 0.001, inferior: p = 0.007, temporal: p = 0.001, and nasal: p = 0.005). Also, no statistically significant differences were noted for retinal nerve fiber layer thickness between two groups. Mean values of subfoveal, nasal, temporal choroidal, and macular thickness for the four quadrants were significantly lower in patients with β-thalassemia minor than in healthy controls.

  11. Macrophages Inhibit Neovascularization in a Murine Model of Age-Related Macular Degeneration

    PubMed Central

    Apte, Rajendra S; Richter, Jennifer; Herndon, John; Ferguson, Thomas A

    2006-01-01

    Background Age-related macular degeneration (AMD) is the leading cause of blindness in people over 50 y of age in at least three continents. Choroidal neovascularization (CNV) is the process by which abnormal blood vessels develop underneath the retina. CNV develops in 10% of patients with AMD but accounts for up to 90% of the blindness from AMD. Although the precise etiology of CNV in AMD remains unknown, the macrophage component of the inflammatory response, which has been shown to promote tumor growth and support atherosclerotic plaque formation, is thought to stimulate aberrant angiogenesis in blinding eye diseases. The current theory is that macrophage infiltration promotes the development of neovascularization in CNV. Methods and Findings We examined the role of macrophages in a mouse model of CNV. IL-10 −/− mice, which have increased inflammation in response to diverse stimuli, have significantly reduced CNV with increased macrophage infiltrates compared to wild type. Prevention of macrophage entry into the eye promoted neovascularization while direct injection of macrophages significantly inhibited CNV. Inhibition by macrophages was mediated by the TNF family death molecule Fas ligand (CD95-ligand). Conclusions Immune vascular interactions can be highly complex. Normal macrophage function is critical in controlling pathologic neovascularization in the eye. IL-10 regulates macrophage activity in the eye and is an attractive therapeutic target in order to suppress or inhibit CNV in AMD that can otherwise lead to blindness. PMID:16903779

  12. A novel, microscope based, non-invasive laser Doppler flowmeter for choroidal blood flow assessment.

    PubMed

    Strohmaier, C; Werkmeister, R M; Bogner, B; Runge, C; Schroedl, F; Brandtner, H; Radner, W; Schmetterer, L; Kiel, J W; Grabner, G; Reitsamer, H A

    2011-06-01

    Impaired ocular blood flow is involved in the pathogenesis of numerous ocular diseases like glaucoma or AMD. The purpose of the present study was to introduce and validate a novel, microscope based, non-invasive Laser Doppler Flowmeter (NI-LDF) for measurement of blood flow in the choroid. The custom made NI-LDF was compared with a commercial fiber optic based laser Doppler flowmeter (Perimed PF4000). Linearity and stability of the NI-LDF were assessed in a silastic tubing model (i.d. 0.3 mm) at different flow rates (range 0.4-3 ml/h). In a rabbit model continuous choroidal blood flow measurements were performed with both instruments simultaneously. During blood flow measurements ocular perfusion pressure was changed by manipulations of intraocular pressure via intravitreal saline infusions. The NI-LDF measurement correlated linearly to intraluminal flow rates in the perfused tubing model (r = 0.99, p < 0.05) and remained stable during a 1 h measurement at a constant flow rate. Rabbit choroidal blood flow measured by the PF4000 and the NI-LDF linearly correlated with each other over the entire measurement range (r = 0.99, y = x∗1.01-12.35 P.U., p < 0.001). In conclusion, the NI-LDF provides valid, semi quantitative measurements of capillary blood flow in comparison to an established LDF instrument and is suitable for measurements at the posterior pole of the eye. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy.

    PubMed

    Sulaiman, Rania S; Merrigan, Stephanie; Quigley, Judith; Qi, Xiaoping; Lee, Bit; Boulton, Michael E; Kennedy, Breandán; Seo, Seung-Yong; Corson, Timothy W

    2016-05-05

    Ocular neovascularisation underlies blinding eye diseases such as retinopathy of prematurity, proliferative diabetic retinopathy, and wet age-related macular degeneration. These diseases cause irreversible vision loss, and provide a significant health and economic burden. Biologics targeting vascular endothelial growth factor (VEGF) are the major approach for treatment. However, up to 30% of patients are non-responsive to these drugs and they are associated with ocular and systemic side effects. Therefore, there is a need for small molecule ocular angiogenesis inhibitors to complement existing therapies. We examined the safety and therapeutic potential of SH-11037, a synthetic derivative of the antiangiogenic homoisoflavonoid cremastranone, in models of ocular neovascularisation. SH-11037 dose-dependently suppressed angiogenesis in the choroidal sprouting assay ex vivo and inhibited ocular developmental angiogenesis in zebrafish larvae. Additionally, intravitreal SH-11037 (1 μM) significantly reduced choroidal neovascularisation (CNV) lesion volume in the laser-induced CNV mouse model, comparable to an anti-VEGF antibody. Moreover, SH-11037 synergised with anti-VEGF treatments in vitro and in vivo. Up to 100 μM SH-11037 was not associated with signs of ocular toxicity and did not interfere with retinal function or pre-existing retinal vasculature. SH-11037 is thus a safe and effective treatment for murine ocular neovascularisation, worthy of further mechanistic and pharmacokinetic evaluation.

  14. Choroidal metastasis of mixed carcinoma of the parotid gland.

    PubMed

    Pinilla, I; Abecia, E; Oliván, J M; Honrubia, F M

    1997-08-01

    A case of mixed carcinoma of the parotid gland (an epidermoid carcinoma located in a pleomorphic adenoma) metastatic to the choroid is presented. The histopathology of the tumor is discussed. A 65-year-old man was admitted complaining of blurred vision in his right eye for 1 day. He underwent parotidectomy for mixed carcinoma of the parotid gland (an epidermoid carcinoma located in a pleomorphic adenoma that was completely excised) 6 months before. Funduscopic examination showed a nasal retinal detachment, with gray-whitish, minimally elevated nodular choroidal lesions. Fluorescein angiography and contact B-scan ultrasonography confirmed the presence of an underlying mass. The right eye was enucleated and an epidermoid infiltrating carcinoma was identified. Metastatic tumors are the most common intraocular malignancies, and the choroid is by far the most common location for intraocular metastases. There are few cases reported of parotid tumors metastatic to the orbit. To the best of our knowledge, no histological examination of an ocular metastatic mixed carcinoma of the parotid gland has yet been reported.

  15. Ocular ultrasonography focused on the posterior eye segment: what radiologists should know.

    PubMed

    De La Hoz Polo, Marcela; Torramilans Lluís, Anna; Pozuelo Segura, Oscar; Anguera Bosque, Albert; Esmerado Appiani, Catalina; Caminal Mitjana, Josep Maria

    2016-06-01

    Ocular B-mode ultrasonography (US) is an important adjuvant for the clinical assessment of a variety of ocular diseases. When ophthalmoscopy is not possible, mainly due to opacification of the transparent media (e.g., mature cataract or vitreous haemorrhage), US can guide the ophthalmologist in diagnosing disease and choosing treatment. The superficial location and cystic structure of the eye make US ideal for imaging of the eye. Moreover, dynamic study helps distinguish between various conditions that would otherwise be difficult to differentiate in some clinical setting, such as vitreous, retinal, and choroidal detachment. US is also good technique for detecting other pathologic conditions such as lens dislocation, vitreous haemorrhage, asteroid hyalosis, optic disc drusen, and tumors (e.g., choroidal melanoma, metastases, hemangioma). An understanding of the basic anatomy of the eye, the US technique, and common entities that affect the ocular globe will allow radiologists to offer this valuable imaging modality to patients and referring clinicians. This article focuses on the US anatomy and pathologic conditions that affect the posterior ocular segment. • US is specially indicated when ocular fundus cannot be assessed on ophthalmoscopy. • Multipurpose equipment with high-frequency transducers is optimal for imaging the eye. • Ultrasound can reliably depict ocular anatomy and pathology as detachments and tumours. • Dynamic examination is vital for distinguishing certain pathologic conditions as detachments.

  16. Ocular effects of virtual reality headset wear in young adults.

    PubMed

    Turnbull, Philip R K; Phillips, John R

    2017-11-23

    Virtual Reality (VR) headsets create immersion by displaying images on screens placed very close to the eyes, which are viewed through high powered lenses. Here we investigate whether this viewing arrangement alters the binocular status of the eyes, and whether it is likely to provide a stimulus for myopia development. We compared binocular status after 40-minute trials in indoor and outdoor environments, in both real and virtual worlds. We also measured the change in thickness of the ocular choroid, to assess the likely presence of signals for ocular growth and myopia development. We found that changes in binocular posture at distance and near, gaze stability, amplitude of accommodation and stereopsis were not different after exposure to each of the 4 environments. Thus, we found no evidence that the VR optical arrangement had an adverse effect on the binocular status of the eyes in the short term. Choroidal thickness did not change after either real world trial, but there was a significant thickening (≈10 microns) after each VR trial (p < 0.001). The choroidal thickening which we observed suggest that a VR headset may not be a myopiagenic stimulus, despite the very close viewing distances involved.

  17. Choroidal thickness in Chinese patients with non-arteritic anterior ischemic optic neuropathy.

    PubMed

    Jiang, Libin; Chen, Lanlan; Qiu, Xiujuan; Jiang, Ran; Wang, Yaxing; Xu, Liang; Lai, Timothy Y Y

    2016-08-31

    Non-arteritic anterior ischemic optic neuropathy (NA-AION) is one of the most common types of ischemic optic neuropathy. Several recent studies suggested that abnormalities of choroidal thickness might be associated with NA-AION. The main objective of this case-control study was to evaluate whether choroidal thickness is an ocular risk factor for the development of NA-AION by evaluating the peripapillary and subfoveal choroidal thicknesses in affected Chinese patients. Forty-four Chinese patients with unilateral NA-AION were recruited and compared with 60 eyes of 60 normal age and refractive-error matched control subjects. Peripapillary and subfoveal choroidal thicknesses were measured by enhanced depth imaging optical coherence tomography. Choroidal thicknesses of eyes with NA-AION and unaffected fellow eyes were compared with normal controls. Choroidal thicknesses of NA-AION eyes with or without optic disc edema were also compared. The correlation between choroidal thickness and retinal nerve fiber layer (RNFL) thickness, logMAR best-corrected visual acuity (BCVA), and the mean deviation (MD) of Humphrey static perimetry in NA-AION eyes were analyzed. The peripapillary choroidal thicknesses at the nasal, nasal inferior and temporal inferior segments in NA-AION eyes with optic disc edema were significantly thicker compared with that of normal subjects (P < 0.05). There was no significant difference in the choroidal thicknesses between the unaffected fellow eyes of NA-AION patients and normal eyes of healthy controls; or between the NA-AION eyes with resolved optic disc edema and normal eyes (all P > 0.05). No significant correlation between choroidal thickness and RNFL thickness, logMAR BCVA and perimetry MD was found in eyes affected by NA-AION (all P > 0.05). Increase in peripapillary choroid thickness in some segments was found in NA-ION eyes with optic disc edema. However, our findings do not support the hypothesis that choroidal thickness is

  18. Acute systemic histoplasmosis associated with chorioretinitis in an immunocompetent adolescent

    PubMed Central

    Fowler, Brian; Shen, Christopher; Mastellone, Joseph; Chaum, Edward

    2011-01-01

    Summary Histoplasmosis is an endemic, systemic mycosis caused by the dimorphic fungus Histoplasma capsulatum. A minority of patients develop asymptomatic chorioretinitis known as presumed ocular histoplasmosis syndrome (POHS), which is typically associated with chorioretinal scarring and peripapillary atrophy and occasionally with choroidal neovascularization secondary to maculopathy. We report a case of acute severe bilateral chorioretinitis associated with disseminated H. capsulatum in an immunocompetent adolescent boy living in an endemic area. The chorioretinitis did not respond to systemic antifungal therapy, but both his systemic illness and ocular lesions resolved with the addition of systemic steroids. PMID:23362391

  19. Macular Atrophy in the HARBOR Study for Neovascular Age-Related Macular Degeneration.

    PubMed

    Sadda, SriniVas R; Tuomi, Lisa L; Ding, Beiying; Fung, Anne E; Hopkins, J Jill

    2018-06-01

    To evaluate macular atrophy (MA) presence in the 24-month HARBOR study (NCT00891735) for neovascular age-related macular degeneration (AMD). Post hoc analysis of a phase 3 multicenter, prospective, randomized, double-masked, active treatment-controlled clinical trial. Evaluable subjects (N = 1095) with subfoveal choroidal neovascularization (CNV) secondary to neovascular AMD treated with ranibizumab 0.5 mg or 2.0 mg monthly or pro re nata (PRN). Fluorescein angiograms (FAs) and color fundus photographs at baseline and months 3, 12, and 24 were retrospectively graded by masked graders for MA: well-defined areas of depigmentation with increased choroidal vessel visibility, diameter ≥250 μm, corresponding to flat areas of well-demarcated staining on FA, excluding atrophy associated with retinal pigment epithelium tears. Atrophy immediately within, adjacent, and nonadjacent to CNV lesions was included. Macular atrophy incidence, best-corrected visual acuity (BCVA). At baseline, MA was detected in 11.2% (123/1095) of study eyes. At month 24, 29.4% (229/778) of eyes without baseline atrophy had detectable MA. Eyes with and without baseline MA had significant mean BCVA gains from baseline at month 24 (letters [95% confidence interval]: +6.7 [4.1-9.3]; +9.1 [8.0-10.2], respectively). Among eyes with and without MA at month 24, mean month 24 BCVA was 62.0 [60.3-63.7] and 64.7 [63.2-66.3] letters, respectively. Baseline risk factors for month 24 MA presence included intraretinal cysts (hazard ratio [HR], 2.45 [1.76-3.42]) and fellow eye atrophy (HR, 2.02 [1.42-2.87]); subretinal fluid was associated with a lower MA risk (HR, 0.50 [0.33-0.74]). Ranibizumab dose was not associated with MA development. Monthly versus PRN treatment trended toward an association with MA (HR, 1.29 [0.99-1.68]), but was not statistically significant. New MA was detected in 29% of study eyes after 24 months of treatment. Clinically significant BCVA gains were achieved with MA present over 24

  20. Intravitreal dobesilate in the treatment of choroidal neovascularisation associated with age-related macular degeneration: report of two cases

    PubMed Central

    Cuevas, Pedro; Outeiriño, Luis; Azanza, Carlos; Giménez-Gallego, Guillermo

    2012-01-01

    This case report presents the effectiveness of intravitreal administration of dobesilate, a synthetic fibroblast growth factor inhibitor, in two patients showing neovascular age-related macular degeneration of the classic, and of the occult choroidal neovascularisation types, respectively. Our study demonstrates that the treatment induces the regression of both forms of this pathology, as assessed by spectral optical coherence tomography. Improvement of the lesions was accompanied of visual acuity improvement. PMID:22948997

  1. Retcam fluorescein gonioangiography: a new modality for early detection of angle neovascularization in diabetic retinopathy.

    PubMed

    Azad, Rajvardhan; Arora, Tarun; Sihota, Ramanjit; Chandra, Parijat; Mahajan, Deepankur; Sain, Siddarth; Sharma, Yograj

    2013-10-01

    To evaluate the role of Retcam fluorescein gonioangiography in detecting neovascularization of the angle and correlate the same with gonioscopy in diabetic retinopathy. One hundred and fifty eyes of 150 patients (25 each of mild, moderate, severe, very severe nonproliferative diabetic retinopathy (NPDR) proliferative diabetic retinopathy (PDR); and PDR with high-risk characteristics) were recruited. They underwent complete ocular examination including applanation tonometry, gonioscopy, Retcam fluorescein gonioangiography, and fundus fluorescein angiography. Using Retcam fluorescein gonioangiography, of 150 eyes neovascularization of the angle was detected in 37 eyes (24.66%) compared with 22 eyes (14.66%) on gonioscopy (P = 0.04). Small newly formed vessels were evident only with Retcam fluorescein gonioangiography. In 10 of 50 patients (20%) with severe/very severe NPDR, angle neovascularization was appreciable on Retcam fluorescein angiography compared with 5 patients (10%) on gonioscopy. Similarly, 25 of 50 patients (50%) with PDR/PDR with high-risk characteristics had neovascularization of the angle on Retcam gonioangiography compared with 17 (34%) on gonioscopy. Retcam fluorescein gonioangiography is a novel technique for early detection of angle neovascularization in diabetic retinopathy and hence preventing progression to neovascular glaucoma. The objective nature of this test helps in precise decision making compared with gonioscopy for early intervention especially in cases of pre-PDR.

  2. Hypercholesterolemia-induced ocular disorder: Ameliorating role of phytotherapy.

    PubMed

    El-Sayyad, Hassan I H; Elmansi, Ahmed A; Bakr, Eman H M

    2015-01-01

    The ocular region is a complex structure that allows conscious light perception and vision. It is of ecto-mesodermal origin. Cholesterol and polyunsaturated fatty acids are involved in retinal cell function; however, hypercholesterolemia and diabetes impair its function. Retinal damage, neovascularization, and cataracts are the main complications of cholesterol overload. Dietary supplementation of selected plant products can lead to the scavenging of free reactive oxygen species, thereby protecting the ocular regions from the damage of hypercholesterolemia. This review illustrates the dramatic effects of increased cholesterol levels on the ocular regions. The effect of phytotherapy is discussed in relation to the different regions of the eye, including the retina, cornea, and lens. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Choroidal thickness measurement in children using optical coherence tomography.

    PubMed

    Bidaut-Garnier, Mélanie; Schwartz, Claire; Puyraveau, Marc; Montard, Michel; Delbosc, Bernard; Saleh, Maher

    2014-04-01

    To measure choroidal thickness (CT) in children of various ages by using spectral optical coherence tomography with enhanced depth imaging and to investigate the association between subfoveal CT and ocular axial length, age, gender, weight, and height in children. Healthy children were prospectively included between May and August 2012. Optical coherence tomography with the enhanced depth imaging system (Spectralis, Heidelberg, Germany) was used for choroidal imaging at nine defined points of the macula of both eyes. Axial length was measured using IOLMaster (Carl Zeiss Meditec, Dublin, CA). Height, weight, and refraction were recorded. Interobserver agreement in readings was also assessed by the Bland-Altman Method. Three hundred and forty-eight eyes from 174 children aged 3.5 years to 14.9 years were imaged. The mean subfoveal CT in right eyes was 341.96 ± 74.7 µm. Choroidal thickness increased with age (r = 0.24, P = 0.017), height, and weight but not with gender (P > 0.05). It was also inversely correlated to the axial length (r = 0.24, P = 0.001). The nasal choroid appeared thinner than in the temporal area (analysis of variance, P < 0.0001). In children, CT increases with age and is inversely correlated to axial length. There is a significant variation of CT between children of the same age.

  4. Hypericin-enhanced argon laser photocoagulation for subfoveal choroidal neovascular membrane in age-related macular degeneration: a pilot study.

    PubMed

    Sobaci, G; Bayraktar, M Z; Karslioğlu, Y; Durukan, A H; Hürmeriç, V; Aykaş, S

    2006-01-01

    To evaluate the efficacy and safety of hypericin-enhanced argon laser photocoagulation (H-ALP) in the treatment of subfoveal choroidal neovascular membrane (CNM) secondary to age-related macular degeneration (ARMD). After preliminary studies for definition of parameters, argon-green laser was administered 4 hours after single dose of oral 1800 mg hypericin (Saint-John's wort tablets, 0.3%, 300 mg) with a subthreshold light fluence, 24 J/cm2 in 34 eyes (20 with subfoveal classical and 14 with subfoveal occult CNM). Additionally, histopathologic examination was done in two eyes destined for enucleation and exenteration. Maintenance therapy (one tablet, twice a day) was performed for the following 6 months. Anatomic (complete closure of CNM) and functional success (improvement of final visual acuity in three or more Snellen lines) were analyzed with minimum 6-month follow-ups. Histopathologic examinations revealed photothrombosed choriocapillaries together with minimal retinal pigment epithelial disruption in H-ALP exposed areas. One to four (mean 1.88+/-0.91) treatment sessions were applied in 6 to 29 months (mean 12.2+/-5.1 months) follow-up period. Twenty-three (67.6%) eyes had 12 months follow-up. Two eyes in each group had functional success (20% in subfoveal classical and 14.3% in subfoveal occult CNM), which had a minimum 12-month follow-up. Anatomic success was achieved in 16 of 20 (80%) eyes with subfoveal classical and 10 of 14 (71.4%) eyes with subfoveal occult CNM. Severe gastric irritation was noted in 1 (2.9%) and pigment epithelial rupture in 2 (5.9%) patients. H-ALP is a novel and low-cost treatment for subfoveal CNM secondary to ARMD. It seems its efficacy depends on the photodynamic and antiproliferative properties of hypericin. Comparative studies are required to apply this new technique in ophthalmic practice.

  5. Hypericin-enhanced argon laser photocoagulation for subfoveal choroidal neovascular membrane in age-related macular degeneration: a pilot study.

    PubMed

    Sobaci, G; Bayraktar, M Z; Karslioglu, Y; Durukan, A H; Hurmeric, V; Aykas, S

    To evaluate the efficacy and safety of hypericin-enhanced argon laser photocoagulation (H-ALP) in the treatment of subfoveal choroidal neovascular membrane (CNM) secondary to age-related macular degeneration (ARMD). After preliminary studies for definition of parameters, argon-green laser was administered 4 hours after single dose of oral 1800 mg hypericin (Saint-John's wort tablets, 0.3%, 300 mg) with a subthreshold light fluence, 24 J/cm2 in 34 eyes (20 with subfoveal classical and 14 with subfoveal occult CNM). Additionally, histopathologic examination was done in two eyes destined for enucleation and exenteration. Maintenance therapy (one tablet, twice a day) was performed for the following 6 months. Anatomic (complete closure of CNM) and functional success (improvement of final visual acuity in three or more Snellen lines) were analyzed with minimum 6-month follow-ups. Histopathologic examinations revealed photothrombosed choriocapillaries together with minimal retinal pigment epithelial disruption in H-ALP exposed areas. One to four (mean 1.88+/-0.91) treatment sessions were applied in 6 to 29 months (mean 12.2+/-5.1 months) follow-up period. Twenty-three (67.6%) eyes had 12 months follow-up. Two eyes in each group had functional success (20% in subfoveal classical and 14.3% in subfoveal occult CNM), which had a minimum 12-month follow-up. Anatomic success was achieved in 16 of 20 (80%) eyes with subfoveal classical and 10 of 14 (71.4%) eyes with subfoveal occult CNM. Severe gastric irritation was noted in 1 (2.9%) and pigment epithelial rupture in 2 (5.9%) patients. H-ALP is a novel and low-cost treatment for subfoveal CNM secondary to ARMD. It seems its efficacy depends on the photodynamic and antiproliferative properties of hypericin. Comparative studies are required to apply this new technique in ophthalmic practice. (Eur J Ophthalmol 2006; 16: 119-28).

  6. Two-year visual results for older Asian women treated with photodynamic therapy or bevacizumab for myopic choroidal neovascularization.

    PubMed

    Ikuno, Yasushi; Nagai, Yoshimi; Matsuda, Satoshi; Arisawa, Akiko; Sho, Kenichiro; Oshita, Takashi; Takahashi, Kanji; Uchihori, Yasutaka; Gomi, Fumi

    2010-01-01

    To compare the long-term visual and anatomic outcome of treatment with photodynamic therapy (PDT) or intravitreal bevacizumab (IVB; Avastin; Genentech Inc, South San Francisco, California, USA) for choroidal neovascularization attributable to pathologic myopia (mCNV). An open-label, interventional case series. Multi-institutional. Thirty-one eyes of Japanese women who received either PDT or IVB for mCNV. Inclusion criteria were age 50 years or older, greatest linear dimension (GLD) 1200 to 3000 microm, and baseline best-corrected visual acuity (BCVA) 20/200 to 20/40. INTERVENTION PROCEDURES: Patients received either PDT or IVB (1 mg/40 microL) throughout the study, with re-treatment when necessary. BCVA and visual gain/loss at 3, 6, 12, 18, and 24 months after the initial treatment. Age, BCVA, location of CNV, refractive error, and symptom duration at baseline did not differ significantly between groups. BCVA was significantly improved at 3 to 12 months (P < .05); however, the significance was lost at 18 and 24 months in the IVB group. The PDT group showed no significant improvement within the first year, and vision slowly worsened after 12 months, becoming significantly worse at 18 and 24 months compared to baseline (P< .01). BCVA was significantly higher in the IVB group at 6 months (P< .05), and 12 months or further (P < .01). Visual gain was significantly greater in the IVB group at 6, 12, 18, and 24 months (P < .05 for 6, 18, and 24 months and P < .01 for 12 months). These findings indicate that the effects of PDT and IVB have a different time course, and that IVB provides a significantly better BCVA than PDT for mCNV over the long-term. Copyright 2010 Elsevier Inc. All rights reserved.

  7. Optical coherence tomography angiography reproducibility of lesion size measurements in neovascular age-related macular degeneration (AMD).

    PubMed

    Amoroso, Francesca; Miere, Alexandra; Semoun, Oudy; Jung, Camille; Capuano, Vittorio; Souied, Eric H

    2018-06-01

    To evaluate the reproducibility and interuser agreement of measurements of choroidal neovascularisation in optical coherence tomography angiography (OCTA). Prospective non-interventional study. Consecutive patients, presenting with neovascular age-related macular degeneration (AMD), underwent two sequential OCTA examinations (AngioVue, Optovue, Fremont, California, USA), performed by the same trained examiner. Neovascular lesion area was then measured on both examinations in the choriocapillaris automatic segmentation by two masked readers, using the semiautomated measuring software embedded in the instrument. Two measuring features were used: the first corresponding to the total manually contoured lesion area with the flow draw tool (select area) and the second to the total area of solely vessels with high flow within the lesion (vessel area). These measurements were then compared in order to assess both the reproducibility of OCTA examination and the interuser agreement with the embedded software. Forty-eight eyes of 46 patients (77.4 mean age,+/-8.2 SD, range from 62 to 95 years old, eight men, 38 women) were included in our study. Mean choroidal neovascularisation area was of 0.72+/-0.7 mm 2 for the first measurement and 0.75+/-0.76 mm 2 for the second measurement; difference between the first and the second measurement was 0.03 mm 2 . Intrauser agreement was of 0.98 (CI 0.98 to 0.99) for both 'vessel area' and 'select area' features. Interuser agreement was of 0.98 (CI 0.97 to 0.99) for 'select area' and 'vessel area' features. Our data suggest that OCTA provide reproducible imaging for evaluation of the neovascular size in the setting of AMD. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  8. Clinical, legal and ethical implications of the intra-ocular (off-label) use of bevacizumab (avastin)--a South African perspective.

    PubMed

    Jansen, Rita-Marié; Gouws, Chris

    2009-06-01

    Choroidal neovascularisation is a potentially visually devastating element of various forms of eye pathology. Recent research has focused on neurovascular age-related macular degeneration (AMD) as a cause. AMD can be classified as being exudative (wet) or atrophic (dry). Wet AMD is characterised by a pathological process in which new blood vessels develop in the choroids, causing leakage of fluid and haemorrhage under the retina and leading to localised serous detachment and loss of central vision. Vascular endothelial growth factor (VEGF) stimulates growth of neovascular membranes. Treatments have until recently yielded disappointing results. Ophthalmologists are using intra-ocular injections of bevacizumab (Avastin), an anti-VEGF, to treat AMD. Avastin appears to be safe and effective in the short term, but its intra-ocular administration is entirely off-label. Avastin is registered for treating metastatic colorectal and breast cancer. The off-label use of medication is an important part of mainstream, legitimate medical practice worldwide. Lawyers representing plaintiffs injured by drugs increasingly encounter off-label use claims. From a legal/ethical point of view the off-label use of medication represents a delicate balance between the statutory regulation of medication and a physician's prerogative to prescribe medication that in his or her medical opinion will be beneficial to the patient. The main reason for the controversy created by the off-label use of Avastin is that there are anti-VEGF drugs on the market that have formal approval for the treatment of AMD (and other eye conditions). Lucentis, for example, is extremely expensive, with treatment cost approximately 50 times that of Avastin. Many patients suffering from AMD and macular oedema cannot afford the registered product. The off-label use of Avastin has passed the innovative or experimental stages, as ophthalmologists have used it regularly and openly for a long time, with good success. Such use

  9. Characteristics of Neovascularization in Early Stages of Proliferative Diabetic Retinopathy by Optical Coherence Tomography Angiography.

    PubMed

    Pan, Jiandong; Chen, Ding; Yang, Xiaoling; Zou, Ruitao; Zhao, Kuo; Cheng, Dan; Huang, Shenghai; Zhou, Tingye; Yang, Ye; Chen, Feng

    2018-05-25

    To classify retinal neovascularization in untreated early stages of proliferative diabetic retinopathy (PDR) based on optical coherence tomography angiography (OCTA). A cross-sectional study. Thirty-five eyes were included. They underwent color fundus photography, fluorescein angiography (FA), and OCTA examinations. Neovascularizations elsewhere (NVEs), neovascularizations of the optic disc (NVDs), and intraretinal microvascular abnormalities (IRMAs) were scanned by OCTA. The origin and morphology of NVE/NVD/IRMA on OCTA were evaluated. Retinal nonperfusion areas (NPAs) were measured using Image J software. In 35 eyes successfully imaged, 75 NVEs, 35 NVDs and 12 IRMAs were captured. Three proposed subtypes of NVE were indentified based on the origins and morphological features. Type 1 (32 of 75, 42.67%) originated from venous, in a tree-like shape. Type 2 (30 of 75, 40.00%) originated from capillary networks, with an octopus-like appearance. Type 3 (13 of 75, 17.33%) originated from the IRMAs, having a sea fan shape. NVD originated from the retinal artery, the retinal vein, or from the choroid, and arose from the bending vessels near the rim of the optic disc. IRMA originated from and drained into retinal venules, extending in the retina. The initial layer and affiliated NPA were significantly different in the 3 subtypes of NVEs (all P < 0.01). OCTA allowed identification of the origins and morphological patterns of neovascularization in PDR. The new classification of retinal neovascularization may be useful to better understand pathophysiological mechanisms and to guide efficient therapeutic strategies. Copyright © 2018. Published by Elsevier Inc.

  10. SHORT-TERM SAFETY PROFILE OF INTRAVITREAL ZIV-AFLIBERCEPT.

    PubMed

    Chhablani, Jay; Narayanan, Raja; Mathai, Annie; Yogi, Rohit; Stewart, Michael

    2016-06-01

    To evaluate the safety of intravitreal ziv-aflibercept (Zaltrap) in the treatment choroidal neovascularization secondary to age-related macular degeneration. Eligible eyes with choroidal neovascularization secondary to age-related macular degeneration each received a single intravitreal injection of ziv-aflibercept. Comprehensive ophthalmic examinations and detailed systemic evaluations were performed at baseline and Days 1, 7, and 30 after injection, and International Society for Clinical Electrophysiology of Vision standard electroretinography was performed at baseline and Day 30. Primary outcome measures were safety parameters that included signs of clinical and electroretinographic toxicity. Secondary outcome measures included changes in best-corrected visual acuity and central subfield thickness. Twelve eyes of 12 patients were treated. None of the patients complained of blurred vision, ocular pain, or bulbar injection at any of the follow-up visits, nor was intraocular inflammation noted. There were no significant differences in implicit times, "a" and "b" wave amplitudes, or b/a ratios at 1 month when compared with baseline (P = 0.4). None of the patients experienced serious ocular or systemic adverse events. Mean best-corrected visual acuity improved only slightly at 30 days (LogMAR 0.45 ± 0.31 [Snellen equivalent: 20/60]) compared with baseline (LogMAR 0.37 ± 0.24 [Snellen equivalent: 20/50]; P = 0.51). Single intravitreal injections of ziv-aflibercept into eyes with neovascular age-related macular degeneration appear to be safe through 1 month. Ziv-aflibercept could become a safe, low-cost therapy for macular diseases in developing countries and in those where intravitreal aflibercept (Eylea) is not available.

  11. Ocular hemodynamic effects of nitrovasodilators in healthy subjects.

    PubMed

    Schmidl, D; Polska, E; Kiss, B; Sacu, S; Garhofer, G; Schmetterer, L

    2010-01-01

    Nitric oxide (NO) plays a key role in the regulation of ocular blood flow and may be an interesting therapeutic target in ocular ischemic disease. In the present study, we hypothesized that NO-releasing drugs may increase blood flow to the head of the optic nerve and also in the choroid. The study employed a randomized, placebo-controlled, double blind, four-way crossover design. On separate study days, 12 healthy subjects received infusions of nitroglycerin, isosorbide dinitrate, sodium nitroprusside, or placebo. All three study drugs reduced the mean arterial pressure (MAP) and ocular perfusion pressure (OPP) (P < 0.001). None of the administered drugs increased the ocular hemodynamic variables. By contrast, vascular resistance decreased dose dependently during administration of the study drugs (P < 0.001). These results indicate that systemic administration of NO-donor drugs is associated with a decrease in vascular resistance in the ocular vasculature. However, because these drugs also reduce blood pressure, they do not improve perfusion to the posterior eye pole.

  12. Optical Coherence Tomography Angiography of Retinal Microvascular Changes Overlying Choroidal Nodules in Neurofibromatosis Type 1

    PubMed Central

    Cassiman, Catherine; Casteels, Ingele; Stalmans, Peter; Legius, Eric; Jacob, Julie

    2017-01-01

    Purpose To report 3 cases of neurofibromatosis type 1 (NF1) with choroidal nodules associated with retinal microvascular changes imaged with optical coherence tomography angiography (OCTA). Methods Small case series in 3 NF1 patients. OCTA examinations were performed by a trained examiner (J.J.) after pupillary dilation. A standard scan, centered over the macula measuring 6 × 6 mm and 3 × 3 mm was obtained according to the findings on standard color photography. Additional scans were obtained in the zones with microvascular abnormalities. The segmentation provided by the machine software was used. Results Corkscrew retinal vessels were observed in association with “placoid”-type choroidal nodules as shown by near-infrared reflectance imaging. In all cases, multiple lesions were found. They were second- or third-order tortuous vessels originating from the superior or inferior temporal veins. OCTA demonstrated that the tortuous venules were located in the superficial capillary plexus, and no abnormalities were found in the deep capillary plexus. Discussion Corkscrew retinal vessels are part of a spectrum of retinal microvascular alterations seen in association, sometimes overlying choroidal nodules in patients with NF1 and are visualized in the superficial capillary plexus on OCTA. We demonstrated with OCTA that they are not associated with flow loss or ischemia in the superficial and deep capillary plexus. The link between the underlying nodule remains unclear. Since neovascularization was described in choroidal ganglioneuroma, we hypothesize that corresponding secretory substances from Schwann cells, ganglion cells, or melanocytes in choroidal nodules might alter the retinal vasculature. Conclusion We report on 3 cases of NF1 with choroidal nodules in association with retinal microvascular changes imaged with OCTA. OCTA demonstrated preservation of the blood flow in the deep and superficial capillary plexus of the retina. We hypothesize that angiogenic

  13. Suprachoroidal layer and suprachoroidal space delineating the outer margin of the choroid in swept-source optical coherence tomography.

    PubMed

    Michalewska, Zofia; Michalewski, Janusz; Nawrocka, Zofia; Dulczewska-Cichecka, Karolina; Nawrocki, Jerzy

    2015-02-01

    To define the morphology of outer choroidal margins in swept-source optical coherence tomography. This is a prospective observational study of 180 eyes: 20 eyes of healthy volunteers, 20 eyes of myopic patients, and 20 eyes from each of the following groups: macular hole, lamellar macular hole, epiretinal membranes, drusen, dry age-related macular degeneration (AMD), neovascular AMD, and vitreomacular traction. A single 12-mm wide swept-source optical coherence tomography image for each of the examined eyes consisting of 1,024 A-scans has been created. The main outcome measure selected was to estimate the presence of suprachoroidal layer, as well as to estimate the ability to delineate the outer choroidoscleral boundary using the software available (DRI-OCT) and to determine its shape. Suprachoroidal layer was observed in 5% of healthy emmetropic eyes, in 50% of eyes with full-thickness macular holes, and in 60% of eyes with vitreomacular traction syndrome. It was also present in 50% of eyes with dry AMD and in 20% of eyes with neovascular AMD. The outer margin of the choroid in all eyes of the healthy volunteers and in eyes with macular diseases has been delineated correctly. In all healthy and myopic eyes, we recognized the outer choroidoscleral boundary as having a regular shape following the natural oval contour of the globe. In eyes with epiretinal membranes, macular hole, vitreomacular traction, and AMD, the outer choroidoscleral boundary was irregular; the choroid varied in thickness from point to point. Swept-source optical coherence tomography enables exact visualization of the outer choroidoscleral boundary. Suprachoroidal layer consisting of two bands has been recognized, the upper of which is hyperreflective and the lower of which is hyporeflective. It may be supposed that the lower hyporeflective band corresponds to suprachoroidal space, which was not earlier visualized in vivo in eyes without choroidal effusion. Suprachoroidal layer in myopic and

  14. Spectral and time-resolved studies on ocular structures

    NASA Astrophysics Data System (ADS)

    Schweitzer, D.; Jentsch, S.; Schenke, S.; Hammer, M.; Biskup, C.; Gaillard, E.

    2007-07-01

    Measurements of endogeous fluorophores open the possibility for evaluation of metabolic state at the eye. For interpretation of 2-dimensional measurements of time-resolved auto fluorescence in 2 separate spectral ranges at the human eye, comparing measurements were performed on porcine eyes. Determining excitation and emission spectra, attention was drawn of proof of coenzymes NADH and FAD in isolated anatomical structures cornea, aqueous humor, lens, vitreous, neuronal retina, retinal pigment epithelium (RPE), choroid, and sclera. All these structures exhibit auto fluorescence, highest in lens. Excitation at 350 nm results in local fluorescence maxima at 460 nm, corresponding to NADH, in all structures. This short-wave excitation allows metabolic studies only at the anterior eye, because of the limited transmission of the ocular media. During excitation at 446 nm the existence of FAD is expressed by local fluorescence maxima at 530 nm. The composition fluorescence spectra allow no discrimination between single ocular structures. Approximating the dynamic fluorescence by a double exponential function, the shortest lifetimes were detected in RPE and neuronal retina. The histograms of mean lifetime t M cover each other on lens with cornea and also on sclera with choroid. Despite the lifetimes are close between RPE and neuronal retina, the relative contributions Q I are wide different. The gradient of trend lines in cluster diagrams of amplitudes α II vs. α I allows a discrimination of ocular structures.

  15. MicroRNA-188-5p regulates contribution of bone marrow-derived cells to choroidal neovascularization development by targeting MMP-2/13.

    PubMed

    Hou, Huiyuan; Gao, Fan; Liang, Hongliang; Lv, Yang; Li, Manhong; Yao, Libo; Zhang, Jian; Dou, Guorui; Wang, Yusheng

    2018-06-14

    Our previous investigations have shown that bone marrow-derived cells (BMCs), including mesenchymal stem cells (MSCs), contribute to the development of choroidal neovascularization (CNV) as sources of cells and angiogenic factors. Two main steps for circulating BMCs to integrate into CNV lesions are extracellular matrix remodeling and consequential cell migration. MicroRNAs (miRNAs) were found to be involved in CNV development; however, little is known about whether miRNAs regulate the contribution of BMCs to CNV. In the present study, we found that the expression of miR-188-5p was decreased in cultured hypoxic MSCs and BMCs within laser-induced CNV in mice. Matrix metalloproteinase 2 (MMP-2) and MMP-13 were both discovered as targets of miR-188-5p by bioinformatics predictions and dual-luciferase reporter system. Accordingly, increased expression of MMP-2/13 was found in hypoxic MSCs and BMCs in CNV lesions. Furthermore, miR-188-5p mimic transfection caused downregulation of MMP-2/13 in hypoxic MSCs and decreased tube formation of co-cultured vascular endothelial cells. Intravitreal injections of a miR-188-5p agomir attenuated the severity of CNV and inhibited the migration of BMCs into CNV lesions in mice. Our study suggests that miR-188-5p regulates the contribution of BMCs to CNV development by targeting MMP-2/13-mediated extracellular matrix degeneration, and miR-188-5p serves as a therapeutic target to treat CNV-related diseases. Copyright © 2018. Published by Elsevier Ltd.

  16. Evaluation of pigment epithelium-derived factor and complement factor I polymorphisms as a cause of choroidal neovascularization in highly myopic eyes.

    PubMed

    Miyake, Masahiro; Yamashiro, Kenji; Nakanishi, Hideo; Nakata, Isao; Akagi-Kurashige, Yumiko; Kumagai, Kyoko; Oishi, Maho; Tsujikawa, Akitaka; Moriyama, Muka; Ohno-Matsui, Kyoko; Mochizuki, Manabu; Yoshimura, Nagahisa

    2013-06-19

    A case-control study in a relatively large cohort of highly myopic patients was conducted to explore the genetic background of the occurrence of choroidal neovascularization (CNV) secondary to high myopia. We evaluated three single nucleotide polymorphisms (SNPS) from two candidate genes: pigment epithelium-derived factor (PEDF) and complement factor I (CFI). The SNPs were selected based on previous reports. A total of 1082 unrelated highly myopic (i.e., axial length ≥ 26 mm in at least one eye) Japanese individuals with CNV (n = 478) and without CNV (n = 557) who were 50 years of age and older were genotyped by using an SNP assay. Multivariable logistic regression was conducted to adjust for age, sex, and axial length. compared with individuals without CNV, subjects with CNV were significantly older (P 0.01) and more likely to be female (P 0.01), but they did not have a significantly different axial length (P = 0.50). We did not find an association between the three SNPS and the occurrence of CNV. However, a subanalysis using extremely myopic patients (case: control = 284:317) revealed a marginal association of rs12603825 in the PEDF gene (P = 0.045). The contribution of rs1136287 in CFI was not found in any analysis. We demonstrated a marginal association of the PEDF SNP, rs12603825, with myopic CNV in extremely myopic patients. A further study using a larger cohort might elucidate a significant association; rs1136287 in CFI is less likely to be associated in Japanese individuals.

  17. Clinical pattern of ocular toxoplasmosis treated in a referral centre in Serbia

    PubMed Central

    Kovačević-Pavićević, D; Radosavljević, A; Ilić, A; Kovačević, I; Djurković-Djaković, O

    2012-01-01

    Purpose To analyze the clinical pattern of ocular toxoplasmosis (OT) in a referral centre in Serbia. Patients and methods The medical records of consecutive patients admitted for OT to the single referral centre for uveitis in Serbia between 2006 and 2010 were retrospectively analyzed. OT was diagnosed on the basis of typical fundus lesions and positive serology for Toxoplasma. Results In a total of 457 uveitis patients, OT was the third leading cause, with 59 patients (12.9%). Most OT cases (73%) were monocular. An active primary retinal lesion was observed in 36% and recurrent OT in 64% patients. Localization of lesions was central/paracentral (44%), juxtapapillar (27%), peripheral (19%), and multifocal (10%). Other ocular manifestations of inflammation included vitritis (44%), anterior uveitis (19%), and retinal vasculitis (10%). Complications included choroidal neovascularization in two and exudative retinal detachment with cataract, glaucoma, and cystoid macular oedema in one patient each. The detection of Toxoplasma-specific IgM antibodies in a single patient indicates a low rate of OT concomitant with acute infection. After treatment, the mean best-corrected visual acuity (BCVA) increased significantly. However, 14 (24%) patients ended up legally blind in the affected eye, of which 2 (3%) with bilateral blindness, all with a very poor BCVA (0.047±0.055) at presentation. Visual impairment and treatment outcome were both associated with central localization of lesions (P<0.0001 and P=0.006, respectively). Conclusion OT is a significant cause of posterior uveitis in Serbia. Patients should be aware of the recurring nature of OT and react immediately if symptoms occur. PMID:22361847

  18. Subfoveal Choroidal Thickness as a Potential Predictor of Clinical Response to Stereotactic Radiotherapy for Neovascular Age-Related Macular Degeneration.

    PubMed

    Ranjbar, Mahdy; Kurz, Maximilian; Holzhey, Annekatrin; Rades, Dirk; Grisanti, Salvatore

    2018-05-01

    Stereotactic radiotherapy (SRT) is a new adjuvant treatment modality that has been shown to reduce the need for repetitive intravitreal injections (IVIs) in patients with neovascular age-related macular degeneration (nAMD). The authors aimed to determine baseline predictors of clinical response to SRT. This was a retrospective, observational case series of patients with nAMD who underwent SRT and subsequently had at least 12 months of complete follow-up. After SRT and one mandatory IVI, patients were examined every 4 weeks and received further treatment on a pro re nata basis. Examination included enhanced depth imaging spectral-domain optical coherence tomography (SD-OCT) to measure subfoveal choroidal thickness (SFCT) and central macular thickness (CMT). Patients' data were retrieved from medical records and included demographics, disease duration, lesion size, best-corrected visual acuity (BCVA), previous number of IVIs, and type of drug applied. A total of 35 eyes of 35 patients (76.23 years ± 7.05 years) were included, and 21 eyes (60%) responded well to SRT. The annual injection rate decreased from 6.86 before SRT to 3.46 afterward, whereas BCVA improved from 0.49 logMAR at baseline to 0.37 logMAR at final follow-up. From a morphologic point of view, CMT and SFCT decreased by 71 μm and 37 μm, respectively, at 12-month follow-up compared to baseline. Of all investigated parameters, only SFCT proved to be significant, as a higher baseline SFCT was found to be a strong negative predictor for the number of IVIs needed after SRT (regression coefficient: -0.678; P < .001). Baseline SFCT may help predict which patients with nAMD will respond more favorably to SRT. The authors found eyes with a thicker baseline SFCT needed fewer IVIs after SRT. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:320-328.]. Copyright 2018, SLACK Incorporated.

  19. Propranolol and atropine do not alter choroidal blood flow regulation during isometric exercise in healthy humans.

    PubMed

    Polska, Elzbieta; Luksch, Alexandra; Schering, Joanne; Frank, Barbara; Imhof, Andrea; Fuchsjäger-Mayrl, Gabriele; Wolzt, Michael; Schmetterer, Leopold

    2003-01-01

    Recent studies indicate that the human choroid has a considerable capacity to keep blood flow constant despite exercise-induced increases in perfusion pressure. The mechanisms underlying this vasoconstrictor response remain unclear. We hypothesized that pharmacological modulation of the autonomic nervous system may alter the choroidal pressure/flow relationship during squatting. To test this hypothesis, we performed a randomized, double-masked, placebo-controlled, three-way crossover study in 15 healthy male volunteers. Subjects received, on different study days, intravenous infusions of the beta-adrenoceptor antagonist propranolol, the muscarinic receptor antagonist atropine, or placebo. During these infusions, subjects performed squatting for 6 min. Choroidal blood flow was assessed with laser Doppler flowmetry and ocular perfusion pressure (OPP) was calculated from mean arterial pressure and intraocular pressure. As expected, propranolol reduced basal pulse rate, whereas atropine increased pulse rate, indicating that the drugs were administered at systemically effective doses. None of the drugs altered the choroidal pressure/flow relationship during isometric exercise. These data indicate that the regulatory vasoconstrictor capacity of the choroid during exercise is not affected by systemic blockade of beta-adrenoceptors or muscarinic receptors.

  20. Evaluation of posterior ocular changes using enhanced depth imaging-optical coherence tomography in patients with obstructive sleep apnea syndrome.

    PubMed

    Yuvacı, İsa; Pangal, Emine; Bayram, Nurettin; Yüksel, Sevgi Arık; Alabay, Bedirhan; Ağadayı, Alperen; Sırakaya, Ender; Gülhan, Ahmet

    2016-01-01

    Evaluation of the nerve fiber thicknesses of the macula, choroid, and retina using the apnea-hypopnea index in individuals with obstructive sleep apnea syndrome (OSAS) without systemic components. Prospective, controlled study. The central macular, choroidal, and retinal nerve fiber layer (RNFL) thicknesses were evaluated using enhanced depth imaging-spectral domain optical coherence tomography in individuals with OSAS. In people with severe OSAS who had received treatment, posterior ocular structures were examined over 3 months (4th and 12th weeks), and changes were evaluated. Only the right eyes of the participants were evaluated in the study. A total of 72 people were involved in the study, with 18 in the control group and 19 with mild, 16 with moderate, and 19 with severe OSAS. No significant difference was found among the groups in terms of demographic measures. No significant differences were found among the groups in terms of the measures of central macular, central subfoveal choroidal (CSCT), temporal choroidal, nasal choroidal, and RNFL thicknesses. In severe OSAS cases in which treatment was administered, although subjective clinical recovery was observed, statistically significant thinning was detected during the 3-month follow-up period in the CSCT, general RNFL, as well as in the inferior and superior nasal quadrants, and temporal superior quadrant (p=0.005, p=0.009, p=0.039, p=0.003, and p=0.02, respectively). In the group with severe OSAS, thinning in some posterior ocular tissues was observed. Although patients with severe OSAS may experience clinical recovery, we recommend that they would be followed up in terms of ocular ischemic injury.

  1. Retinal and choroidal imaging in vivo using integrated photoacoustic microscopy and optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Tian, Chao; Zhang, Wei; Nguyen, Van Phuc; Huang, Ziyi; Wang, Xueding; Paulus, Yannis M.

    2018-02-01

    Most reported photoacoustic ocular imaging work to date uses small animals, such as mice and rats, the eyes of which are small and less than one-third the size of a human eye, which poses a challenge for clinical translation. Here we achieved chorioretinal imaging of larger animals, i.e. rabbits, using a dual-modality photoacoustic microscopy (PAM) and optical coherence tomography (OCT) system. Preliminary experimental results in living rabbits demonstrate that the PAM can noninvasively visualize depth-resolved retinal and choroidal vessels using a safe laser exposure dose; and the OCT can finely distinguish different retinal layers, the choroid, and the sclera. This reported work might be a major step forward in clinical translation of photoacoustic microscopy.

  2. Interferon-beta signaling in retinal mononuclear phagocytes attenuates pathological neovascularization.

    PubMed

    Lückoff, Anika; Caramoy, Albert; Scholz, Rebecca; Prinz, Marco; Kalinke, Ulrich; Langmann, Thomas

    2016-06-01

    Age-related macular degeneration (AMD) is a leading cause of vision loss among the elderly. AMD pathogenesis involves chronic activation of the innate immune system including complement factors and microglia/macrophage reactivity in the retina. Here, we show that lack of interferon-β signaling in the retina accelerates mononuclear phagocyte reactivity and promotes choroidal neovascularization (CNV) in the laser model of neovascular AMD Complete deletion of interferon-α/β receptor (Ifnar) using Ifnar1(-/-) mice significantly enhanced early microglia and macrophage activation in lesion areas. This triggered subsequent vascular leakage and CNV at later stages. Similar findings were obtained in laser-treated Cx3cr1(Cre) (ER):Ifnar1(fl/fl) animals that allowed the tamoxifen-induced conditional depletion of Ifnar in resident mononuclear phagocytes only. Conversely, systemic IFN-β therapy of laser-treated wild-type animals effectively attenuated microgliosis and macrophage responses in the early stage of disease and significantly reduced CNV size in the late phase. Our results reveal a protective role of Ifnar signaling in retinal immune homeostasis and highlight a potential use for IFN-β therapy in the eye to limit chronic inflammation and pathological angiogenesis in AMD. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

  3. Honokiol inhibits pathological retinal neovascularization in oxygen-induced retinopathy mouse model

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vavilala, Divya Teja; O’Bryhim, Bliss E.; Ponnaluri, V.K. Chaithanya

    2013-09-06

    Highlights: •Aberrant activation of HIF pathway is the underlying cause of ischemic neovascularization. •Honokiol has better therapeutic index as a HIF inhibitor than digoxin and doxorubicin. •Daily IP injection of honokiol in OIR mouse model reduced retinal neovascularization. •Honokiol also prevents vaso-obliteration, the characteristic feature of the OIR model. •Honokiol enhanced physiological revascularization of the retinal vascular plexuses. -- Abstract: Aberrant activation of the hypoxia inducible factor (HIF) pathway is the underlying cause of retinal neovascularization, one of the most common causes of blindness worldwide. The HIF pathway also plays critical roles during tumor angiogenesis and cancer stem cell transformation.more » We have recently shown that honokiol is a potent inhibitor of the HIF pathway in a number of cancer and retinal pigment epithelial cell lines. Here we evaluate the safety and efficacy of honokiol, digoxin, and doxorubicin, three recently identified HIF inhibitors from natural sources. Our studies show that honokiol has a better safety to efficacy profile as a HIF inhibitor than digoxin and doxorubicin. Further, we show for the first time that daily intraperitoneal injection of honokiol starting at postnatal day (P) 12 in an oxygen-induced retinopathy (OIR) mouse model significantly reduced retinal neovascularization at P17. Administration of honokiol also prevents the oxygen-induced central retinal vaso-obliteration, characteristic feature of the OIR model. Additionally, honokiol enhanced physiological revascularization of the retinal vascular plexuses. Since honokiol suppresses multiple pathways activated by HIF, in addition to the VEGF signaling, it may provide advantages over current treatments utilizing specific VEGF antagonists for ocular neovascular diseases and cancers.« less

  4. Brief light exposure at night disrupts the circadian rhythms in eye growth and choroidal thickness in chicks

    PubMed Central

    Nickla, Debora L.; Totonelly, Kristen

    2016-01-01

    Changes in ocular growth that lead to myopia or hyperopia are associated with alterations in the circadian rhythms in eye growth, choroidal thickness and intraocular pressure in animal models of emmetropization. Recent studies have shown that light at night has deleterious effects on human health, acting via “circadian disruptions” of various diurnal rhythms, including changes in phase or amplitude. The purpose of this study was to determine the effects of brief, 2-hour episodes of light in the middle of the night on the rhythms in axial length and choroidal thickness, and whether these alter eye growth and refractive error in the chick model of myopia. Starting at 2 weeks of age, birds received 2 hours of light between 12:00 am and 2:00 am for 7 days (n=12; total hours of light: 14 hrs). Age-matched controls had a continuous dark night (n=14; 14L/10D). Ocular dimensions were measured using high-frequency A-scan ultrasonography on the first day of the experiment, and again on day 7, at 6-hour intervals, starting at noon (12pm, 6pm, 12am, 6am, 12pm). Measurements during the night were done under a photographic safe-light. These data were used to determine rhythm parameters of phase and amplitude. 2 groups of birds, both experimental (light at night) and control, were measured with ultrasound at various intervals over the course of 4 weeks to determine growth rates. Refractive errors were measured in 6 experimental and 6 control birds at the end of 2 weeks. Eyes of birds in a normal L/D cycle showed sinusoidal 24-hour period diurnal rhythms in axial length and choroid thickness. Light in the middle of the night caused changes in both the rhythms in axial length and choroidal thickness, such that neither could be fit to a sine function having a period of 24 hours. Light caused an acute, transient stimulation in ocular growth rate in the subsequent 6-hour period (12 am to 6 am), that may be responsible for the increased growth rate seen 4 weeks later, and the more

  5. EFFECT OF INTRAVITREAL RANIBIZUMAB ON GANGLION CELL COMPLEX AND PERIPAPILLARY RETINAL NERVE FIBER LAYER IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION USING SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY.

    PubMed

    Zucchiatti, Ilaria; Cicinelli, Maria V; Parodi, Maurizio Battaglia; Pierro, Luisa; Gagliardi, Marco; Accardo, Agostino; Bandello, Francesco

    2017-07-01

    To analyze the changes in ganglion cell complex and peripapillary retinal nerve fiber layer thickness, in central macular thickness and choroidal thickness on spectral domain optical coherence tomography in patients with neovascular age-related macular degeneration treated with intravitreal ranibizumab injections. All consecutive patients with untreated neovascular age-related macular degeneration received loading phase of three monthly intravitreal ranibizumab, followed by retreatments on a pro re nata protocol for 12 months. changes in ganglion cell complex and retinal nerve fiber layer at the end of follow-up. Secondary outcome: changes in best-corrected visual acuity, central macular thickness, and choroidal thickness at the end of follow-up. Choroidal thickness was measured at 500 μm, 1000 μm, and 1,500 μm intervals nasally, temporally, superiorly, and inferiorly to the fovea, respectively, on horizontal and vertical line scans centered on the fovea. Twenty-four eyes were included. Ganglion cell complex and peripapillary retinal nerve fiber layer thickness did not show statistically significant changes through 12 months (55.6 ± 18.5 and 81.9 ± 9.9 μm at baseline, 52.7 ± 19.3 and 84.6 ± 15.5 μm at month 12, P > 0.05). Central macular thickness showed progressive decrease from baseline to month 12, with maximum reduction at month 3 (P < 0.001). Statistically significant reduction in choroidal thickness was registered in the nasal 500, 1000, and 1,500 μm from the fovea, corresponding to the papillomacular region (from 169.6 ± 45.3 to 153.9 ± 46.9, P < 0.001). Intravitreal ranibizumab injections did not affect retinal nerve fiber layer and ganglion cell complex thickness in 1-year follow-up. Choroidal thickness in papillomacular area and central macular thickness was significantly reduced at the end of treatment. Further studies, with larger sample, longer follow-up, and greater number of injections, are warranted.

  6. Effect of dorzolamide and timolol on ocular blood flow in patients with primary open angle glaucoma and ocular hypertension

    PubMed Central

    Fuchsjäger-Mayrl, G; Wally, B; Rainer, G; Buehl, W; Aggermann, T; Kolodjaschna, J; Weigert, G; Polska, E; Eichler, H-G; Vass, C; Schmetterer, L

    2005-01-01

    Background: There is evidence that perfusion abnormalities of the optic nerve head are involved in the pathogenesis of glaucoma. There is therefore considerable interest in the effects of topical antiglaucoma drugs on ocular blood flow. A study was undertaken to compare the ocular haemodynamic effects of dorzolamide and timolol in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT). Methods: One hundred and forty patients with POAG or OHT were included in a controlled, randomised, double blind study in two parallel groups; 70 were randomised to receive timolol and 70 to receive dorzolamide for a period of 6 months. Subjects whose intraocular pressure (IOP) did not respond to either of the two drugs were switched to the alternative treatment after 2 weeks. Scanning laser Doppler flowmetry was used to measure blood flow in the temporal neuroretinal rim and the cup of the optic nerve head. Pulsatile choroidal blood flow was assessed using laser interferometric measurement of fundus pulsation amplitude. Results: Five patients did not respond to timolol and were changed to the dorzolamide group, and 18 patients changed from dorzolamide treatment to timolol. The effects of both drugs on IOP and ocular perfusion pressure were comparable. Dorzolamide, but not timolol, increased blood flow in the temporal neuroretinal rim (8.5 (1.6)%, p<0.001 versus timolol) and the cup of the optic nerve head (13.5 (2.5)%, p<0.001 versus timolol), and fundus pulsation amplitude (8.9 (1.3)%, p<0.001 versus timolol). Conclusions: This study indicates augmented blood flow in the optic nerve head and choroid after 6 months of treatment with dorzolamide, but not with timolol. It remains to be established whether this effect can help to reduce visual field loss in patients with glaucoma. PMID:16170119

  7. IMPROVING THE AGE-RELATED MACULAR DEGENERATION CONSTRUCT: A New Classification System.

    PubMed

    Spaide, Richard F

    2018-05-01

    Previous models of disease in age-related macular degeneration (AMD) were incomplete in that they did not encompass subretinal drusenoid deposits (pseudodrusen), subtypes of neovascularization, and polypoidal choroidal vasculopathy. In addition, Type 3 neovascularization starts in the retina and may not necessarily involve the choroid. As such, the term choroidal neovascularization is not appropriate for these eyes. The new aspects in the AMD construct are to include specific lipoprotein extracellular accumulations, namely drusen and subretinal drusenoid deposits, as early AMD. The deposition of specific types of deposit seems to be highly correlated with choroidal thickness and topographical location in the macula. Late AMD includes macular neovascularization or atrophy. The particular type of extracellular deposit is predictive of the future course of the patient. For example, eyes with subretinal drusenoid deposits have a propensity to develop outer retinal atrophy, complete outer retinal and retinal pigment epithelial atrophy, or Type 3 neovascularization as specific forms of late AMD. Given Type 3 neovascularization may never involve the choroid, the term macular neovascularization is suggested for the entire spectrum of neovascular disease in AMD. In contrast to older classification systems, the proposed system encompasses the relevant presentations of disease and more precisely predicts the future course of the patient. In doing so, the concept was developed that there may be genetic risk alleles, which are not necessarily the same alleles that influence disease expression.

  8. Space Flight-Associated Neuro-ocular Syndrome.

    PubMed

    Lee, Andrew G; Mader, Thomas H; Gibson, C Robert; Tarver, William

    2017-09-01

    New and unique physiologic and pathologic systemic and neuro-ocular responses have been documented in astronauts during and after long-duration space flight. Although the precise cause remains unknown, space flight-associated neuro-ocular syndrome (SANS) has been adopted as an appropriate descriptive term. The Space Medicine Operations Division of the US National Aeronautics and Space Administration (NASA) has documented the variable occurrence of SANS in astronauts returning from long-duration space flight on the International Space Station. These clinical findings have included unilateral and bilateral optic disc edema, globe flattening, choroidal and retinal folds, hyperopic refractive error shifts, and nerve fiber layer infarcts. The clinical findings of SANS have been correlated with structural changes on intraorbital and intracranial magnetic resonance imaging and in-flight and terrestrial ultrasonographic studies and ocular optical coherence tomography. Further study of SANS is ongoing for consideration of future manned missions to space, including a return trip to the moon or Mars.

  9. ADAM9 Is Involved in Pathological Retinal Neovascularization▿

    PubMed Central

    Guaiquil, Victor; Swendeman, Steven; Yoshida, Tsunehiko; Chavala, Sai; Campochiaro, Peter A.; Blobel, Carl P.

    2009-01-01

    Pathological ocular neovascularization, caused by diabetic retinopathy, age-related macular degeneration, or retinopathy of prematurity, is a leading cause of blindness, yet much remains to be learned about its underlying causes. Here we used oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) to assess the contribution of the metalloprotease-disintegrin ADAM9 to ocular neovascularization in mice. Pathological neovascularization in both the OIR and CNV models was significantly reduced in Adam9−/− mice compared to wild-type controls. In addition, the level of ADAM9 expression was strongly increased in endothelial cells in pathological vascular tufts in the OIR model. Moreover, tumor growth from heterotopically injected B16F0 melanoma cells was reduced in Adam9−/− mice compared to controls. In cell-based assays, the overexpression of ADAM9 enhanced the ectodomain shedding of EphB4, Tie-2, Flk-1, CD40, VCAM, and VE-cadherin, so the enhanced expression of ADAM9 could potentially affect pathological neovascularization by increasing the shedding of these and other membrane proteins from endothelial cells. Finally, we provide the first evidence for the upregulation of ADAM9-dependent shedding by reactive oxygen species, which in turn are known to play a critical role in OIR. Collectively, these results suggest that ADAM9 could be an attractive target for the prevention of proliferative retinopathies, CNV, and cancer. PMID:19273593

  10. [Macular choroidal blood flow in concurrent age-related macular degeneration and primary open-angle glaucoma].

    PubMed

    Panova, I E; Ermak, E M; Shaimova, T A; Shaimova, V A

    2016-01-01

    Ocular circulation disorders are an important factor in the development of primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD). To date, however, there have been no studies on choroidal blood flow peculiarities in case of concurrent AMD and POAG. to determine distinctive features of choroidal blood flow characteristic of concurrent AMD and POAG and to assess their role in disease pathogenesis. Macular choroidal blood flow, including blood supply, was assessed in 54 patients (102 eyes) by means of Doppler ultrasound. Three groups were formed: group 1 - 38 eyes with both AMD and POAG; group 2 - 41 eyes with AMD and no signs of optic nerve pathology; and group 3 - 23 eyes with POAG and no signs of AMD. Groups 1 and 2 were subdivided into two subgroups each: А - atrophic AMD and B - macular drusen. The mean patient age was 78.7±8.4 years. The following parameters of choroidal blood flow were of interest: peak systolic velocity (Vps), end diastolic velocity (Ved), time-averaged maximum velocity (Vtamax), and resistance index (RI). Groups 1, 3, and 2A had an evident choroidal hypoperfusion in the macular area (decreased Vtamax) with uncompensated perfusion deficit, despite autoregulation efforts (decreased Vps, Ved, decreased or normal RI). Group 2B demonstrated a significantly higher rate of choroidal hyperperfusion (increased Vps, Ved, Vtamax, and RI). Concurrent AMD and POAG are notable for choroidal hypoperfusion in the macular area that leads to inadequate trophism of the neurosensory retina and can aggravate the course of AMD contributing to progression of its atrophic form.

  11. Surveillance of Ocular Parameters and Visual Function in Bed Rest Subjects

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita L.

    2011-01-01

    Recent visual changes in astronauts have raised concern about ocular health during long duration spaceflight. Seven cases have been documented in astronauts who spent 6 months aboard the International Space Station. These astronauts were male ranging in age from 45 to 55 years old. All astronauts exhibited pre- to post flight refractive changes. Decreased intraocular pressure (IOP) post flight was observed in 3 cases. Fundoscopic exams revealed post flight findings of choroidal folds in 4 cases, optic disc edema in 5 cases and the presence of cotton wool spots in 3 cases. Optical coherence tomography (OCT) confirmed findings of choroidal folds and disc edema, and also documented retinal nerve fiber layer thickening (5 cases). Findings from MRI examinations showed posterior globe flattening (5 cases), optic nerve sheath distention (6 cases) and torturous optic nerves (2 cases). Of the 7 cases, intracranial pressure was measured on 4 astronauts. These 4 showed elevated ICP post-flight that remained elevated for as long as 19 months in one case. While the etiology remains unknown, hypotheses speculate that venous insufficiency or hypertension in the brain caused by cephalad fluid shifts during spaceflight are possible mechanisms for ocular changes seen in astronauts. Head-down tilt bed rest is a spaceflight analog that induces cephalad fluid shifts. This study is designed to provide ocular monitoring of bed rest subjects and determine whether clinically relevant changes are found. Ocular Changes

  12. Long-term Results of Carbon Ion Radiation Therapy for Locally Advanced or Unfavorably Located Choroidal Melanoma: Usefulness of CT-based 2-Port Orthogonal Therapy for Reducing the Incidence of Neovascular Glaucoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Toyama, Shingo; Department of Heavy Particle Therapy and Radiation Oncology, Faculty of Medicine, Saga University, Saga; Tsuji, Hiroshi, E-mail: h_tsuji@nirs.go.jp

    2013-06-01

    Purpose: To determine the long-term results of carbon ion radiation therapy (C-ion RT) in patients with choroidal melanoma, and to assess the usefulness of CT-based 2-port irradiation in reducing the risk of neovascular glaucoma (NVG). Methods and Materials: Between January 2001 and February 2012, a total of 116 patients with locally advanced or unfavorably located choroidal melanoma received CT-based C-ion RT. Of these patients, 114 were followed up for more than 6 months and their data analyzed. The numbers of T3 and T2 patients (International Union Against Cancer [UICC], 5th edition) were 106 and 8, respectively. The total dose ofmore » C-ion RT varied from 60 to 85 GyE, with each dose given in 5 fractions. Since October 2005, 2-port therapy (51 patients) has been used in an attempt to reduce the risk of NVG. A dose-volume histogram analysis was also performed in 106 patients. Results: The median follow-up was 4.6 years (range, 0.5-10.6 years). The 5-year overall survival, cause-specific survival, local control, distant metastasis-free survival, and eye retention rates were 80.4% (95% confidence interval 89.0%-71.8%), 82.2% (90.6%-73.8%), 92.8% (98.5%-87.1%), 72.1% (81.9%-62.3%), and 92.8% (98.1%-87.5%), respectively. The overall 5-year NVG incidence rate was 35.9% (25.9%-45.9%) and that of 1-port group and 2-port group were 41.6% (29.3%-54.0%) and 13.9% (3.2%-24.6%) with statistically significant difference (P<.001). The dose-volume histogram analysis showed that the average irradiated volume of the iris-ciliary body was significantly lower in the non-NVG group than in the NVG group at all dose levels, and significantly lower in the 2-port group than in the 1-port group at high dose levels. Conclusions: The long-term results of C-ion RT for choroidal melanoma are satisfactory. CT-based 2-port C-ion RT can be used to reduce the high-dose irradiated volume of the iris-ciliary body and the resulting risk of NVG.« less

  13. Radiogenic Side Effects After Hypofractionated Stereotactic Photon Radiotherapy of Choroidal Melanoma in 212 Patients Treated Between 1997 and 2007

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dunavoelgyi, Roman; Dieckmann, Karin; Gleiss, Andreas

    2012-05-01

    Purpose: To evaluate side effects of hypofractionated stereotactic photon radiotherapy for patients with choroidal melanoma. Patients and Methods: Two hundred and twelve patients with choroidal melanoma unsuitable for ruthenium-106 brachytherapy or local resection were treated stereotactically at the Medical University of Vienna between 1997 and 2007 with a Linac with 6-MV photon beams in five fractions with 10, 12, or 14 Gy per fraction. Examinations for radiogenic side effects were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and then once a year thereafter until 10 years after radiotherapy.more » Adverse side effects were assessed using slit-lamp examination, funduscopy, gonioscopy, tonometry, and, if necessary, fundus photography and fluorescein angiography. Evaluations of incidence of side effects are based on an actuarial analysis. Results: One hundred and eighty-nine (89.2%) and 168 (79.2%) of the tumors were within 3 mm of the macula and the optic disc, respectively. The five most common radiotherapy side effects were retinopathy and optic neuropathy (114 cases and 107 cases, respectively), cataract development (87 cases), neovascular glaucoma (46 cases), and corneal epithelium defects (41 cases). In total, 33.6%, 38.5%, 51.2%, 75.5%, and 77.6% of the patients were free of any radiation retinopathy, optic neuropathy, cataract, neovascular glaucoma, or corneal epithelium defects 5 years after radiotherapy, respectively. Conclusion: In centrally located choroidal melanoma hypofractionated stereotactic photon radiotherapy shows a low to moderate rate of adverse long-term side effects comparable with those after proton beam radiotherapy. Future fractionation schemes should seek to further reduce adverse side effects rate while maintaining excellent local tumor control.« less

  14. Choroidal OCT

    NASA Astrophysics Data System (ADS)

    Esmaeelpour, Marieh; Drexler, Wolfgang

    Novel imaging devices, imaging strategies and automated image analysis with optical coherence tomography have improved our understanding of the choroid in health and pathology. Non-invasive in-vivo high resolution choroidal imaging has had its highest impact in the investigation of macular diseases such as diabetes macular edema and age-related macular degeneration. Choroidal thickness may provide a clinically feasible measure of disease stage and treatment success. It will even support disease diagnosis and phenotyping as is demonstrated in this chapter. Utilizing color coded thickness mapping of the choroid and its Sattler's and Haller's layer may further strengthen the sensitivity of the investigation findings.

  15. Ocular Lesions in Red-Tailed Hawks ( Buteo jamaicensis) With Naturally Acquired West Nile Disease.

    PubMed

    Wünschmann, A; Armién, A G; Khatri, M; Martinez, L C; Willette, M; Glaser, A; Alvarez, J; Redig, P

    2017-03-01

    Ocular lesions are common in red-tailed hawks with West Nile (WN) disease. These lesions consist of pectenitis, choroidal or retinal inflammation, or retinal necrosis, but detailed investigation of the ocular lesions is lacking. Postmortem examination of the eyes of 16 red-tailed hawks with naturally acquired WN disease and 3 red-tailed hawks without WN disease was performed using histopathology, immunohistochemistry for West Nile virus (WNV) antigen, glial fibrillary acid protein, cleaved caspase-3, and the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling method. Retinal lesions were classified as type I or type II lesions. Type I lesions were characterized by lymphoplasmacytic infiltrates in the subjacent choroid with degeneration limited to the outer retina (type Ia lesion) or with degeneration and necrosis of the outer retina or outer and inner retina (type Ib lesion) while retinal collapse, atrophy, and scarring were hallmarks of type II lesions. Type II retinal lesions were associated with a more pronounced choroiditis. Although not statistically significant, WNV antigen tended to be present in larger quantity in type Ib lesions. Type I lesions are considered acute while type II lesions are chronic. The development of retinal lesions was associated with the presence of an inflammatory infiltrate in the choroid. A breakdown of the blood-retina barrier is suspected to be the main route of infection of the retina. Within the retina, virus appeared to spread via both neuronal and Müller cell processes.

  16. Technetium-99 conjugated with methylene diphosphonate (99Tc-MDP) inhibits experimental choroidal neovascularization in vivo and VEGF-induced cell migration and tube formation in vitro.

    PubMed

    Lai, Kunbei; Xu, Li; Jin, Chenjin; Wu, Kaili; Tian, Zhen; Huang, Chuangxin; Zhong, Xiaojing; Ye, Haiyun

    2011-07-29

    To investigate the effects of (99)Tc-MDP, a decay product of (99m)Tc-MDP, on the development of choroidal neovascularization (CNV), together with its underlying mechanisms. C57BL/6J mice were used to induce CNV by laser photocoagulation. (99)Tc-MDP at the doses of 0.5 × 10(-1), 1 × 10(-1), and 2 × 10(-1) μg/kg or the same volume of PBS was intraperitoneally injected daily after photocoagulation until the end of the experiment. Seven days after laser injury, mice were perfused with fluorescein-labeled dextran, and areas of CNV were measured. Numbers of infiltrating macrophages, protein levels of VEGF, and inflammation-related molecules including intercellular adhesion molecule (ICAM)-1, tumor necrosis factor (TNF)-α, and matrix metalloproteinases (MMPs) in the RPE-choroid complex were detected 3 days after laser photocoagulation. Effects of (99)Tc-MDP on VEGF-induced endothelial cell migration and tube formation were also studied. Toxicity of (99)Tc-MDP was evaluated in vivo and in vitro. Areas of CNV were significantly suppressed by (99)Tc-MDP treatment without toxicity to the retina compared with PBS treatment in a dose-dependent manner: (99)Tc-MDP treatment of 0.5 × 10(-1) μg/kg (5698.60 ± 1037.70 μm(2)), 1 × 10(-1) μg/kg (3678.34 ± 1328.18 μm(2)), and 2 × 10(-1) μg/kg (2365.78 ± 923.80 μm(2)) suppressed the development of CNV by 36.12%, 58.76%, and 73.48%, respectively, compared with that in the PBS treatment group (8920.36 ± 1097.29 μm(2); P < 0.001). (99)Tc-MDP treatment led to significant inhibition of macrophages infiltrating to CNV together with downregulated protein expressions of VEGF, ICAM-1, TNF-α, and MMP-2. (99)Tc-MDP also showed an inhibitive effect on cell proliferation and VEGF-induced migration and capillary-like tube formation of endothelial cells. Anti-inflammatory treatment with (99)Tc-MDP has therapeutic potential for CNV-related diseases.

  17. RADIANCE: a randomized controlled study of ranibizumab in patients with choroidal neovascularization secondary to pathologic myopia.

    PubMed

    Wolf, Sebastian; Balciuniene, Vilma Jurate; Laganovska, Guna; Menchini, Ugo; Ohno-Matsui, Kyoko; Sharma, Tarun; Wong, Tien Y; Silva, Rufino; Pilz, Stefan; Gekkieva, Margarita

    2014-03-01

    To compare the efficacy and safety of ranibizumab 0.5 mg, guided by visual acuity (VA) stabilization or disease activity criteria, versus verteporfin photodynamic therapy (vPDT) in patients with visual impairment due to myopic choroidal neovascularization (CNV). Phase III, 12-month, randomized, double-masked, multicenter, active-controlled study. Patients (N = 277) with visual impairment due to myopic CNV. Patients were randomized to receive ranibizumab on day 1, month 1, and thereafter as needed guided by VA stabilization criteria (group I, n = 106); ranibizumab on day 1 and thereafter as needed guided by disease activity criteria (group II, n=116); or vPDT on day 1 and disease activity treated with ranibizumab or vPDT at investigators' discretion from month 3 (group III, n = 55). Mean average best-corrected visual acuity (BCVA) change from baseline to month 1 through months 3 (primary) and 6, mean BCVA change and safety over 12 months. Ranibizumab treatment in groups I and II was superior to vPDT based on mean average BCVA change from baseline to month 1 through month 3 (group I: +10.5, group II: +10.6 vs. group III: +2.2 Early Treatment Diabetic Retinopathy Study [ETDRS] letters; both P<0.0001). Ranibizumab treatment guided by disease activity was noninferior to VA stabilization-guided retreatment based on mean average BCVA change from baseline to month 1 through month 6 (group II: +11.7 vs. group I: +11.9 ETDRS letters; P<0.00001). Mean BCVA change from baseline to month 12 was +13.8 (group I), +14.4 (group II), and +9.3 ETDRS letters (group III). At month 12, 63.8% to 65.7% of patients showed resolution of myopic CNV leakage. Patients received a median of 4.0 (group I) and 2.0 (groups II and III) ranibizumab injections over 12 months. No deaths or cases of endophthalmitis and myocardial infarction occurred. Ranibizumab treatment, irrespective of retreatment criteria, provided superior BCVA gains versus vPDT up to month 3. Ranibizumab treatment guided by

  18. Clinical and histological characteristics of canine ocular gliovascular syndrome.

    PubMed

    Treadwell, Amy; Naranjo, Carolina; Blocker, Tiffany; Zarfoss, Mitzi; Dubielzig, Richard R

    2015-09-01

    To characterize the clinical, diagnostic, and histopathologic findings in dogs with canine ocular gliovascular syndrome (COGS). The archives at the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) were used to identify eyes with COGS. Histopathological inclusion criteria included: a neovascular membrane extending from the optic nerve head or retina, clusters of spindle cells lacking vascularization within the vitreous, and histological signs of glaucoma. Special and immunohistochemical (IHC) staining techniques were performed. Clinical data, treatments, and outcomes were obtained from case records and information provided by submitting veterinarians. Thirty-seven eyes of 36 dogs were identified with COGS. The average age at diagnosis was 8.8 years (±2.2). The relative risk for a Labrador retriever affected by COGS was significantly greater (9.3 times) (P < 0.0001) when compared to all other dog breeds within the COPLOW database. Most dogs presented with hyphema and secondary glaucoma; average intraocular pressure was 39 mmHg (±19). Average time to enucleation or evisceration was 27 days. Vitreal cells stained positive with IHC for glial fibrillary acidic protein in 14 of 17 globes, and vascular endothelial growth factor was expressed in the vitreal cells in five of five globes. We have defined a syndrome associated with vitreal glial cell aggregates and neovascular proliferation from the optic nerve or retina, which leads to neovascular glaucoma. The inflammation and secondary glaucoma resulting from this syndrome appear poorly responsive to conventional medical therapies. The exact etiology of COGS remains undetermined, but a systemic etiology is unlikely. © 2014 American College of Veterinary Ophthalmologists.

  19. Molecular screening of the CYP4V2 gene in Bietti crystalline dystrophy that is associated with choroidal neovascularization

    PubMed Central

    Mamatha, Gandra; Umashankar, Vetrivel; Kasinathan, Nachiappan; Krishnan, Tandava; Sathyabaarathi, Ravichandran; Karthiyayini, Thirumalai; Amali, John; Rao, Chetan

    2011-01-01

    Purpose Bietti crystalline dystrophy (BCD) is an autosomal recessive disease characterized by intraretinal deposits of multiple small crystals, with or without associated crystal deposits in the cornea. The disease is caused by mutation in the cytochrome p450, family 4, subfamily v, polypeptide 2 (CYP4V2) gene. Choroidal neovascularization (CNV) is a rare event in BCD. We report two cases of BCD associated with CNV. CYP4V2 and exon 5 of tissue inhibitor of metalloproteinase 3 (TIMP3) were screened in both cases. A patient with BCD, but without CNV, was also screened to identify pathogenic variations. Methods Three BCD families of Asian Indian origin were recruited after a comprehensive ophthalmic examination. Genomic DNA was isolated from blood leukocytes, and coding exons and flanking introns of CYP4V2 and exon 5 of TIMP3 were amplified via polymerase chain reaction (PCR) and were sequenced. Family segregation, control screening, and bioinformatics tools were used to assess the pathogenicity of the novel variations. Results Of the three BCD patients, two had parafoveal CNV. The patient with BCD, but without CNV had novel single base-pair duplication (c.1062_1063dupA). This mutation results in a structurally defective and unstable protein with impaired protein function. Four novel benign variations (three in exons and one in an intron) were observed in the cohort. Screening of exon 5 of TIMP3 did not reveal any variation in these families. Conclusions A novel mutation was found in a patient with BCD but without CNV, while patients with BCD and CNV did not show any pathogenic variation. The modifier role of TIMP3 in the pathogenesis of CNV in BCD was partly ruled out, as no variation was observed in exon 5 of the gene. A larger BCD cohort with CNV needs to be studied and screened to understand the genetics of CNV in BCD. PMID:21850171

  20. LOCATING AND CHARACTERIZING ANGIOID STREAKS WITH EN FACE OPTICAL COHERENCE TOMOGRAPHY.

    PubMed

    Hanhart, Joel; Greifner, Hillel; Rozenman, Yaakov

    2017-01-01

    To characterize angioid streaks (AS) with en face optical coherence tomography (OCT). Case report of a patient with myopia presenting with choroidal neovascularization secondary to AS. Swept-source en face OCT ability to image the streaks was compared with spectral-domain and swept-source B-scans as well as color and red-free pictures. A 48-year-old man with myopia presented with sudden central visual loss. Choroidal neovascularization secondary to AS was diagnosed and intraocular anti-vascular endothelial growth factor given with clinical and OCT features improvement. Angioid streaks were visualized as less dark than the overlying retinal and the underlying choroidal vasculature. En face OCT located the changes at the level of Bruch membrane. An AS was found to be interrupted by the choroidal neovascularization, what was not captured by other modalities. En face OCT allows to assess the extent of changes in Bruch membrane and their spatial relationship to choroidal neovascularization.

  1. Detailed Functional and Structural Phenotype of Bietti Crystalline Dystrophy Associated with Mutations in CYP4V2 Complicated by Choroidal Neovascularization

    PubMed Central

    Fuerst, Nicole M.; Serrano, Leona; Han, Grace; Morgan, Jessica I. W.; Maguire, Albert M.; Leroy, Bart P.; Kim, Benjamin J.; Aleman, Tomas S.

    2016-01-01

    Purpose To describe in detail the phenotype of a patient with Bietti crystalline dystrophy (BCD) complicated by choroidal neovascularization (CNV) and the response to intravitreal Bevacizumab (Avastin ®; Genentech/Roche). Methods A 34-year-old woman with BCD and mutations in CYP4V2 (c.802-8_806del13/p.H331P:c992A>C) underwent a complete ophthalmic examination, full-field flash electroretinography (ERG), kinetic and two-color dark-adapted perimetry, and dark-adaptometry. Imaging was performed with spectral domain optical coherence tomography (SD-OCT), near infrared (NIR) and short wavelength (SW) fundus autofluorescence (FAF), and fluorescein angiography (FA). Results Best-corrected visual acuity (BCVA) was 20/20 and 20/60 for the right and left eye, respectively. There were corneal paralimbal crystal-like deposits. Kinetic fields were normal in peripheral extent. Retinal crystals were most obvious on NIR-reflectance and corresponded with hyperreflectivities within the RPE on SD-OCT. There was parafoveal/perifoveal hypofluorescence on SW-FAF and NIR-FAF. Rod > cone sensitivity loss surrounded fixation and extended to ~10° of eccentricity corresponding to regions of photoreceptor outer segment-retinal pigmented epithelium (RPE) interdigitation abnormalities. The outer nuclear layer was normal in thickness. Recovery of sensitivity following a ~76% rhodopsin bleach was normal. ERGs were normal. A subretinal hemorrhage in the left eye co-localized with elevation of the RPE on SD-OCT and leakage on FA, suggestive of CNV. Three monthly intravitreal injections of Bevacizumab led to restoration of BCVA to baseline (20/25). Conclusion Crystals in BCD were predominantly located within the RPE. Photoreceptor outer segment and apical RPE abnormalities underlie the relatively extensive retinal dysfunction observed in relatively early-stage BCD. Intravitreal Bevacizumab was effective in treating CNV in this setting. PMID:27028354

  2. Detailed functional and structural phenotype of Bietti crystalline dystrophy associated with mutations in CYP4V2 complicated by choroidal neovascularization.

    PubMed

    Fuerst, Nicole M; Serrano, Leona; Han, Grace; Morgan, Jessica I W; Maguire, Albert M; Leroy, Bart P; Kim, Benjamin J; Aleman, Tomas S

    2016-12-01

    To describe in detail the phenotype of a patient with Bietti crystalline dystrophy (BCD) complicated by choroidal neovascularization (CNV) and the response to intravitreal Bevacizumab (Avastin ® ; Genentech/Roche). A 34-year-old woman with BCD and mutations in CYP4V2 (c.802-8_806del13/p.H331P:c992A>C) underwent a complete ophthalmic examination, full-field flash electroretinography (ERG), kinetic and two-color dark-adapted perimetry, and dark-adaptometry. Imaging was performed with spectral domain optical coherence tomography (SD-OCT), near infrared (NIR) and short wavelength (SW) fundus autofluorescence (FAF), and fluorescein angiography (FA). Best-corrected visual acuity (BCVA) was 20/20 and 20/60 for the right and left eye, respectively. There were corneal paralimbal crystal-like deposits. Kinetic fields were normal in the peripheral extent. Retinal crystals were most obvious on NIR-reflectance and corresponded with hyperreflectivities within the RPE on SD-OCT. There was parafoveal/perifoveal hypofluorescence on SW-FAF and NIR-FAF. Rod > cone sensitivity loss surrounded fixation and extended to ~10° of eccentricity corresponding to regions of photoreceptor outer segment-retinal pigmented epithelium (RPE) interdigitation abnormalities. The outer nuclear layer was normal in thickness. Recovery of sensitivity following a ~76% rhodopsin bleach was normal. ERGs were normal. A subretinal hemorrhage in the left eye co-localized with elevation of the RPE on SD-OCT and leakage on FA, suggestive of CNV. Three monthly intravitreal injections of Bevacizumab led to restoration of BCVA to baseline (20/25). crystals in BCD were predominantly located within the RPE. Photoreceptor outer segment and apical RPE abnormalities underlie the relatively extensive retinal dysfunction observed in relatively early-stage BCD. Intravitreal Bevacizumab was effective in treating CNV in this setting.

  3. Ocular inflammatory disease and ocular tuberculosis in a cohort of patients co-infected with HIV and multidrug-resistant tuberculosis in Mumbai, India: a cross-sectional study

    PubMed Central

    2013-01-01

    Background The prevalence and the patterns of ocular inflammatory disease and ocular tuberculosis (TB) are largely undocumented among Multidrug Resistant TB (MDR-TB) patients co-infected with Human Immunodeficiency Virus (HIV) and on antituberculosis and antiretroviral therapy (ART). Methods Lilavati Hospital and Research Center and Médecins Sans Frontières (MSF) organized a cross-sectional ophthalmological evaluation of HIV/MDR-TB co-infected patients followed in an MSF-run HIV-clinic in Mumbai, India, which included measuring visual acuity, and slit lamp and dilated fundus examinations. Results Between February and April 2012, 47 HIV/MDR-TB co-infected patients (including three patients with extensively drug-resistant TB) were evaluated. Sixty-four per cent were male, mean age was 39 years (standard deviation: 8.7) and their median (IQR) CD4 count at the time of evaluation was 264 cells/μL (158–361). Thirteen patients (27%) had detectable levels of HIV viremia (>20 copies/ml). Overall, examination of the anterior segments was normal in 45/47 patients (96%). A dilated fundus examination revealed active ocular inflammatory disease in seven eyes of seven patients (15.5%, 95% Confidence Intervals (CI); 5.1-25.8%). ‘These included five eyes of five patients (10%) with choroidal tubercles, one eye of one patient (2%) with presumed tubercular chorioretinitis and one eye of one patient (2%) with evidence of presumed active CMV retinitis. Presumed ocular tuberculosis was thus seen in a total of six patients (12.7%, 95% CI; 3.2-22.2%). Two patients who had completed anti-TB treatment had active ocular inflammatory disease, in the form of choroidal tubercles (two eyes of two patients). Inactive scars were seen in three eyes of three patients (6%). Patients with extrapulmonary TB and patients <39 years old were at significantly higher risk of having ocular TB [Risk Ratio: 13.65 (95% CI: 2.4-78.5) and 6.38 (95% CI: 1.05-38.8) respectively]. Conclusions Ocular

  4. Depth-resolved imaging of capillary networks in retina and choroid using ultrahigh sensitive optical microangiography

    PubMed Central

    Wang, Ruikang K.; An, Lin; Francis, Peter; Wilson, David J.

    2010-01-01

    We demonstrate the depth-resolved and detailed ocular perfusion maps within retina and choroid can be obtained from an ultrahigh sensitive optical microangiography (OMAG). As opposed to the conventional OMAG, we apply the OMAG algorithm along the slow scanning axis to achieve the ultrahigh sensitive imaging to the slow flows within capillaries. We use an 840nm system operating at an imaging rate of 400 frames/sec that requires 3 sec to complete one 3D scan of ~3x3 mm2 area on retina. We show the superior imaging performance of OMAG to provide functional images of capillary level microcirculation at different land-marked depths within retina and choroid that correlate well with the standard retinal pathology. PMID:20436605

  5. Dark adaptation in relation to choroidal thickness in healthy young subjects: a cross-sectional, observational study.

    PubMed

    Munch, Inger Christine; Altuntas, Cigdem; Li, Xiao Qiang; Jackson, Gregory R; Klefter, Oliver Niels; Larsen, Michael

    2016-07-11

    Dark adaptation is an energy-requiring process in the outer retina nourished by the profusely perfused choroid. We hypothesized that variations in choroidal thickness might affect the rate of dark adaptation. Cross-sectional, observational study of 42 healthy university students (mean age 25 ± 2.0 years, 29 % men) who were examined using an abbreviated automated dark adaptometry protocol with a 2° diameter stimulus centered 5° above the point of fixation. The early, linear part of the rod-mediated dark adaptation curve was analyzed to extract the time required to reach a sensitivity of 5.0 × 10(-3) cd/m2 (time to rod intercept) and the slope (rod adaptation rate). The choroid was imaged using enhanced-depth imaging spectral-domain optical coherence tomography (EDI-OCT). The time to the rod intercept was 7.3 ± 0.94 (range 5.1 - 10.2) min. Choroidal thickness 2.5° above the fovea was 348 ± 104 (range 153-534) μm. There was no significant correlation between any of the two measures of rod-mediated dark adaptation and choroidal thickness (time to rod intercept versus choroidal thickness 0.072 (CI95 -0.23 to 0.38) min/100 μm, P = 0.64, adjusted for age and sex). There was no association between the time-to-rod-intercept or the dark adaptation rate and axial length, refraction, gender or age. Choroidal thickness, refraction and ocular axial length had no detectable effect on rod-mediated dark adaptation in healthy young subjects. Our results do not support that variations in dark adaptation can be attributed to variations in choroidal thickness.

  6. The effect of rebreathing and hyperventilation on retinal and choroidal vessels measured by spectral domain optical coherence tomography.

    PubMed

    Ozcimen, Muammer; Sakarya, Yasar; Goktas, Sertan; Sakarya, Rabia; Alpfidan, Ismail; Yener, Halil I; Demir, Lutfi S

    2015-01-01

    The purpose of this study was to examine the vasoreactivity in retina and choroid of the healthy eyes in response to experimentally altered partial arterial pressure of carbon dioxide (PaCO(2)) using a non-invasive technique, spectral domain optical coherence tomography (SD-OCT). The study included non-smoking participants between 18 and 35 years of age, having visual acuity of 20/20 and with no systemic and ocular diseases. At baseline, the participants breathed room air (normocapnia). Hypocapnia was created with the help of hyperventilation; for this, the participants were instructed to draw deep and quick breaths, resulting one breathing cycle per 2 s. To create hypercapnia subjects rebreathed from a 5 l bag at least 3 min. Choroidal thickness and retinal artery diameter were measured at baseline, and hyperventilation and rebreathing conditions by SD-OCT. Twenty eyes of 20 healthy subjects were included in this study. Their mean age was 24.90 ± 5.32 years. Hyperventilation caused a significant reduction in choroidal thickness, compared with baseline, at all points; whereas rebreathing caused no significant change at all points. The mean diameters of the arteries were 151.80 ± 7.88 μm, with a significant decline to 148.90 ± 7.25 μm at hyperventilation condition and a significant increase to 153.50 ± 7.88 μm at rebreathing condition (p = 0.018, p = 0.043, respectively). This study demonstrated that, SD-OCT was a useful tool in measuring the ocular vascular response under hypercapnia and hypocapnia conditions. These findings may be helpful for further understanding the physiological nature of ocular blood flow and this preliminary study provides a basis for future studies.

  7. Forecasting the prognosis of choroidal melanoma with an artificial neural network.

    PubMed

    Kaiserman, Igor; Rosner, Mordechai; Pe'er, Jacob

    2005-09-01

    To develop an artificial neural network (ANN) that will forecast the 5-year mortality from choroidal melanoma. Retrospective, comparative, observational cohort study. One hundred fifty-three eyes of 153 consecutive patients with choroidal melanoma (age, 58.4+/-14.6 years) who were treated with ruthenium 106 brachytherapy between 1988 and 1998 at the Department of Ophthalmology, Hadassah University Hospital, Jerusalem, Israel. Patients were observed clinically and ultrasonographically (A- and B-mode standardized ultrasonography). Metastatic screening included liver function tests and liver imaging. Backpropagation ANNs composed of 3 or 4 layers of neurons with various types of transfer functions and training protocols were assessed for their ability to predict the 5-year mortality. The ANNs were trained on 77 randomly selected patients and tested on a different set of 76 patients. Artificial neural networks were compared based on their sensitivity, specificity, forecasting accuracy, area under the receiver operating curves, and likelihood ratios (LRs). The best ANN was compared with the results of logistic regression and the performance of an ocular oncologist. The ability of the ANNs to forecast the 5-year mortality from choroidal melanoma. Thirty-one patients died during the follow-up period of metastatic choroidal melanoma. The best ANN (one hidden layer of 16 neurons) had 84% forecasting accuracy and an LR of 31.5. The number of hidden neurons significantly influenced the ANNs' performance (P<0.001). The performance of the ANNs was not significantly influenced by the training protocol, the number of hidden layers, or the type of transfer function. In comparison, logistic regression reached 86% forecasting accuracy, with a very low LR (0.8), whereas the human expert forecasting ability was <70% (LR, 1.85). Artificial neural networks can be used for forecasting the prognosis of choroidal melanoma and may support decision-making in treating this malignancy.

  8. Platform for Rapid Delivery of Biologics and Drugs to Ocular Cells and Tissues Following Combat Associated Trauma

    DTIC Science & Technology

    2016-09-01

    by DOD to further develop and test protein delivery for the retina. Ongoing Research Support W81XWH-16-1-0650 09/30/16-09/29/19 U.S...Medical Research Institute to test small molecules for inhibition of MAC in laser induced choroidal neovascularization PI Robert Liddington; No...streptavidin594 conjugation and dosing studies. Bonferroni’s multiple comparison tests were used for Post hoc analysis. One-way analysis of variance

  9. Neovascular Glaucoma: A Retrospective Review from a Tertiary Eye Care Center in Mexico.

    PubMed

    Lazcano-Gomez, Gabriel; R Soohoo, Jeffrey; Lynch, Anne; N Bonell, Levi; Martinez, Karina; Turati, Mauricio; Gonzalez-Salinas, Roberto; Jimenez-Roman, Jesus; Y Kahook, Malik

    2017-01-01

    To describe the demographic characteristics, ocular comorbidities, and clinical outcomes of patients with neovascular glaucoma (NVG) and to determine the number of patients who returned for a follow-up eye examination. We examined the clinical data of patients with NVG, who attended a glaucoma clinic between July 2010 and November 2014. We collected information on the demographic characteristics of the patients to include the level of education, ocular comorbidities, NVG stage, visual acuity, glaucoma medications, intraocular pressure (IOP), and the number of patients who had a follow-up ocular examination at month 1, 3, 6, and 12. Data from 350 patients (473 eyes) with NVG were collected. We found 91% of the cohort had proliferative diabetic retinopathy (PDR). We found blindness in both or one eye in 14% and 31% of the cohort respectively. Low vision was found in both or one eye in 14% and 32% of the eyes respectively. By 6 months follow-up, only 32% of the patients were seen at our clinic and by 12 months follow-up, this number decreased to 15%. Around 60% of the patients were on no IOP lowering drugs at the first visit. We found 53% of the cohort had an incomplete elementary school education. The results suggest that advanced NVG is a significant ocular problem for patients referred to our clinic with just over half of the patients presenting as blind. We also found that several socioeconomic factors that had an important role in the development of PDR and NVG, specifically, educational status. We described the characteristics of a large cohort of patients with very advanced NVG, reflecting the fact that the strict control of the underlying disease must be the main goal of the Mexican national health system. Lazcano-Gomez G, Soohoo JR, Lynch A, Bonell LN, Martinez K, Turati M, González-Salinas R, Jimenez-Roman J, Kahook MY. Neovascular Glaucoma: A Retrospective Review from a Tertiary Eye Care Center in Mexico. J Curr Glaucoma Pract 2017;11(2):48-51.

  10. High-resolution 3D MR microangiography of the rat ocular circulation.

    PubMed

    Shih, Yen-Yu I; Muir, Eric R; Li, Guang; De La Garza, Bryan H; Duong, Timothy Q

    2012-07-01

    To develop high-spatial-resolution magnetic resonance (MR) microangiography techniques to image the rat ocular circulation. Animal experiments were performed with institutional Animal Care Committee approval. MR microangiography (resolution, 84×84×84 μm or 42×42×84 μm) of the rat eye (eight rats) was performed by using a custom-made small circular surface coil with an 11.7-T MR unit before and after monocrystalline iron oxide nanoparticle (MION) injection. MR microangiography measurements were made during air, oxygen, and carbogen inhalation. From three-dimensional MR microangiography, the retina was virtually flattened to enable en face views of various retinal depths, including the retinal and choroidal vascular layers. Signal intensity changes within the retinal or choroidal arteries and veins associated with gas challenges were analyzed. Statistical analysis was performed by using paired t tests, with P<.05 considered to indicate a significant difference. Bonferroni correction was used to adjust for multiple comparisons. The central retinal artery, long posterior ciliary arteries, and choroidal vasculature could be distinguished on MR microangiograms of the eye. With MR microangiography, retinal arteries and veins could be distinguished on the basis of blood oxygen level-dependent contrast. Carbogen inhalation-enhanced MR microangiography signal intensity in both the retina (P=.001) and choroid (P=.027) compared with oxygen inhalation. Carbogen inhalation showed significantly higher signal intensity changes in the retinal arteries (P=.001, compared with oxygen inhalation), but not in the veins (P=.549). With MION administration, MR microangiography depicted retinal arterial vasoconstriction when the animals were breathing oxygen (P=.02, compared with animals breathing air). MR microangiography of the eye allows depth-resolved imaging of small angiographic details of the ocular circulation. This approach may prove useful in studying microvascular

  11. Lenalidomide, an anti-tumor drug, regulates retinal endothelial cell function: Implication for treating ocular neovascular disorder

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dong, Ling-Feng; Yao, Jin; Wang, Xiao-Qun

    Ocular angiogenesis is an important pathologic character of several ocular diseases, such as retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration (AMD). Inhibition of ocular angiogenesis has great therapeutic value for treating these dieses. Here we show that lenalidomide, an anti-tumor drug, has great anti-angiogenic potential in ocular diseases. Lenalidomide inhibits retinal endothelial cell viability in normal and pathological condition, and inhibits VEGF-induced endothelial cell migration and tube formation in vitro. Moreover, lenalidomide inhibits ocular angiogenesis in vivo through the reduction of angiogenesis- and inflammation-related protein expression. Collectively, lenalidomide is a promising drug for treating ocular angiogenesis through its anti-proliferative andmore » anti-inflammatory property. - Highlights: • Lenalidomide inhibits retinal endothelial cell viability in vitro. • Lenalidomide inhibits retinal endothelial cell migration and tube formation. • Lenalidomide inhibits pathological ocular angiogenesis in vivo. • Lenalidomide inhibits angiogenesis- and inflammation-related protein expression.« less

  12. A novel space ocular syndrome is driving technology advances on and off the planet

    NASA Astrophysics Data System (ADS)

    Donoviel, Dorit B.; Zimmer, Cheryl N.; Clayton, Richard

    2017-05-01

    Astronauts are experiencing ophthalmological changes including optic disc edema, globe flattening, choroidal folds, and significant hyperopic shifts. In a handful of cases in which it was measured, intracranial pressure as measured by lumbar punctures was elevated post-flight. The severity of symptoms is highly variable and the underlying etiology is unknown, but a spaceflight associated cephalad-fluid shift is thought to play a role. NASA requires portable, non-invasive, clinically-validated approaches to assessing the ocular and the cerebral physiological, anatomical, and functional changes. Multispectral Imaging (MSI) that enables instruments installed on satellites in space to observe Earth was applied in an ophthalmic medical device that is clinically being used on Earth and now being evaluated for use on humans in space. The Annidis RHA™ (Ottawa, Canada) uses narrow band light emitting diodes (LEDs) to create discrete slices of anatomical structures of the posterior pole of the eye. The LEDs cover a frequency range from 520 to 940 nm, which allow for specific visualization of the different features of the posterior segment of the eye including retina, choroid and optic nerve head. Interestingly, infrared illumination at 940 nm reflects from the posterior sclera, retro-illuminating the choroidal vasculature without the need for invasive contrast agents. Abnormalities in retinal, choroidal or cerebral venous drainage and/or arterial flow may contribute to the microgravity ocular syndrome (MOS) in astronauts; hence this space technology may prove to be invaluable for diagnosing not only the health of our planet but also of the humans living on it and above it.

  13. Toward earlier detection of choroidal neovascularization secondary to age-related macular degeneration: multicenter evaluation of a preferential hyperacuity perimeter designed as a home device.

    PubMed

    Loewenstein, Anat; Ferencz, Joseph R; Lang, Yaron; Yeshurun, Itamar; Pollack, Ayala; Siegal, Ruth; Lifshitz, Tova; Karp, Joseph; Roth, Daniel; Bronner, Guri; Brown, Justin; Mansour, Sam; Friedman, Scott; Michels, Mark; Johnston, Richards; Rapp, Moshe; Havilio, Moshe; Rafaeli, Omer; Manor, Yair

    2010-01-01

    The primary purpose of this study was to evaluate the ability of a home device preferential hyperacuity perimeter to discriminate between patients with choroidal neovascularization (CNV) and intermediate age-related macular degeneration (AMD), and the secondary purpose was to investigate the dependence of sensitivity on lesion characteristics. All participants were tested with the home device in an unsupervised mode. The first part of this work was retrospective using tests performed by patients with intermediate AMD and newly diagnosed CNV. In the second part, the classifier was prospectively challenged with tests performed by patients with intermediate AMD and newly diagnosed CNV. The dependence of sensitivity on lesion characteristics was estimated with tests performed by patients with CNV of both parts. In 66 eyes with CNV and 65 eyes with intermediate AMD, both sensitivity and specificity were 0.85. In the retrospective part (34 CNV and 43 intermediate AMD), sensitivity and specificity were 0.85 +/- 0.12 (95% confidence interval) and 0.84 +/- 0.11 (95% confidence interval), respectively. In the prospective part (32 CNV and 22 intermediate AMD), sensitivity and specificity were 0.84 +/- 0.13 (95% confidence interval) and 0.86 +/- 0.14 (95% confidence interval), respectively. Chi-square analysis showed no dependence of sensitivity on type (P = 0.44), location (P = 0.243), or size (P = 0.73) of the CNV lesions. A home device preferential hyperacuity perimeter has good sensitivity and specificity in discriminating between patients with newly diagnosed CNV and intermediate AMD. Sensitivity is not dependent on lesion characteristics.

  14. Adenosine receptor distribution in Rhesus monkey ocular tissue.

    PubMed

    Beach, Krista M; Hung, Li-Fang; Arumugam, Baskar; Smith, Earl L; Ostrin, Lisa A

    2018-05-21

    2a expression was higher in brain and retina, ADORA2b expression was higher in retina, and ADORA3 was higher in the choroid. In conclusion, immunohistochemistry and RT-qPCR indicated differential patterns of expression of the four adenosine receptors in the ocular tissues of the normal non-human primate. The presence of ADORs in scleral fibroblasts and the choroid may support mechanisms by which ADOR antagonists prevent myopia. The potential effects of ADOR inhibition on both anterior and posterior ocular structures warrant investigation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Space flight-associated neuro-ocular syndrome (SANS).

    PubMed

    Lee, Andrew G; Mader, Thomas H; Gibson, C Robert; Brunstetter, Tyson J; Tarver, William J

    2018-03-12

    Interesting novel and somewhat perplexing physiologic and pathologic neuro-ocular findings have been documented in astronauts during and after long duration space flight (LDSF). These findings collectively have been termed the "space flight-associated neuro-ocular syndrome" (SANS). The National Aeronautics and Space Administration (NASA) in the United States has meticulously and prospectively documented the clinical, ultrasound, optical coherence tomography imaging, and radiographic findings of SANS including unilateral and bilateral optic disc edema, globe flattening, choroidal and retinal folds, hyperopic refractive error shifts, and nerve fiber layer infarcts (i.e., cotton wool spots). NASA and collaborating researchers continue to study SANS in preparation for future manned missions to space, including continued trips to the ISS, a return to the moon, or perhaps new voyages to the asteroid belt, or the planet, Mars.

  16. Verteporfin photodynamic therapy combined with intravitreal bevacizumab for neovascular age-related macular degeneration.

    PubMed

    Kaiser, Peter K; Boyer, David S; Garcia, Raul; Hao, Yong; Hughes, Mark S; Jabbour, N M; Kaiser, Peter K; Mieler, William; Slakter, Jason S; Samuel, Michael; Tolentino, Michael J; Roth, Daniel; Sheidow, Thomas; Strong, H Andrew

    2009-04-01

    To assess outcomes for patients with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) treated with verteporfin photodynamic therapy (PDT) and bevacizumab. Retrospective, case series database study (registry). We included 1196 patients with CNV due to AMD who received > or =1 combination treatment of 1.25 mg intravitreal bevacizumab within 14 days of verteporfin PDT. Retrospective analysis of baseline data with ongoing follow-up. Physicians from 45 clinical centers entered patient data at baseline and follow-up examinations, including subsequent treatments, into a secure, Web-accessed database. Snellen visual acuity (VA) was converted to logarithm of the minimum angle of resolution (logMAR) for statistical analyses. Change from baseline in VA and retreatment rates of any therapy after the initial combination treatment. Of 1196 patients, 1073 patients had > or =6 months of follow-up. For these 1073 patients, mean baseline VA was 0.967 logMAR (approximate Snellen 20/185) and 56.3% of patients (604/1073) were treatment naïve. After their baseline combination treatment, patients received a mean of 0.6 additional verteporfin PDT retreatments and 2.0 bevacizumab retreatments over a mean follow-up period of 15.0 months. By 12 months, 82% of patients (578/701) had stable or improved vision (loss of <3 lines or a gain in VA), 36% (255/701) improved by > or =3 lines, and 17% (121/701) improved by > or =6 lines. By 12 months, patients gained approximately 1.2 lines (6 letters) of VA from baseline. Patients who were treatment naïve gained significantly more VA by month 12 (+8.4 letters) compared with those who had been previously treated (+2.4 letters; P<0.01). Most serious adverse events (26/30) were judged by investigators as not related to any study treatment, although 3 ocular events were judged related to bevacizumab alone, and 1 ocular event was judged related to both bevacizumab and PDT. Combination therapy with PDT and bevacizumab led

  17. Effect of ranibizumab on high-speed indocyanine green angiography and minimum intensity projection optical coherence tomography findings in neovascular age-related macular degeneration.

    PubMed

    Nicholson, Benjamin P; Nigam, Divya; Toy, Brian; Stetson, Paul F; Agrón, Elvira; Jacobs-El, Naima; Cunningham, Denise; Cukras, Catherine; Wong, Wai; Wiley, Henry; Chew, Emily; Ferris, Frederick; Meyerle, Catherine B

    2015-01-01

    The purpose of this 1-year prospective study was to investigate how induction/pro re nata ranibizumab intravitreal treatment of eyes with neovascular age-related macular degeneration affects the anatomy of choroidal neovascularization (CNV) and the overlying outer retinal tissue. High-speed indocyanine green (HS-ICG) angiography measurements provided quantification of the CNV size in 60 patients followed for 1 year. Minimum intensity projection optical coherence tomography (MinIP OCT), a novel algorithm assessing minimum optical intensity between the internal limiting membrane and retinal pigment epithelium, measured the area of outer retinal disruption overlying the CNV. Fluorescein angiography was also assessed to evaluate late retinal leakage. After 1 year, the mean area of CNV measured with indocyanine green angiography decreased by 5.8%. The mean area of MinIP OCT of outer retinal disruption overlying the CNV decreased by 4.2%. Mean area of fluorescein angiography leakage decreased by 6.3%. Both the area of outer retinal disruption measured with MinIP OCT and the area of leakage on fluorescein angiography typically exceeded the area of CNV on indocyanine green angiography at baseline and 1 year. Choroidal neovascularization treated with induction/pro re nata intravitreal ranibizumab for 1 year essentially remained static. Minimum intensity projection optical coherence tomography suggests that the area of outer retinal disruption overlying the CNV may be greater than the CNV itself and often correlates with the leakage area on fluorescein angiography. Additionally, there was minimal change in the area of outer retinal disruption on MinIP OCT even when fluid resolved. Measurements of the extent of CNV lesions based on indocyanine green angiography and MinIP OCT may provide useful outcome variables to help assess the CNV complex longitudinally and warrant further validation.

  18. Progression of choroid plexus papilloma.

    PubMed

    Dhillon, Rana S; Wang, Yi Yuen; McKelvie, Penny A; O'Brien, Brendan

    2013-12-01

    Choroid plexus papillomas are rare neoplasms that arise from choroid plexus epithelium. The World Health Organization classification describes three histological grades. Grade I is choroid plexus papilloma, grade II is atypical choroid plexus papilloma and grade III is choroid plexus carcinoma. Progression between grades is rare but documented. We present two adult cases, a 53-year-old female and a 70-year-old male, who demonstrated clear interval histological progression from grade I choroid plexus papilloma to higher grades. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Optic Disc Drusen in Children

    PubMed Central

    Chang, Melinda Y.; Pineles, Stacy L.

    2016-01-01

    Optic disc drusen occur in 0.4% of children and consist of acellular intracellular and extracellular deposits that often become calcified over time. They are typically buried early in life and generally become superficial, and therefore visible, later in childhood, at the average age of 12 years. Their main clinical significance lies in the ability of optic disc drusen, particularly when buried, to simulate true optic disc edema. Misdiagnosing drusen as true disc edema may lead to an invasive and unnecessary workup for elevated intracranial pressure. Ancillary testing, including ultrasonography, fluorescein angiography, fundus autofluorescence, and optical coherence tomography, may aid in the correct diagnosis of optic disc drusen. Complications of optic disc drusen in children include visual field defects, hemorrhages, choroidal neovascular membrane, non-arteritic anterior ischemic optic neuropathy, and retinal vascular occlusions. Treatment options for these complications include ocular hypotensive agents for visual field defects and intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents for choroidal neovascular membranes. In most cases, however, children with optic disc drusen can be managed by observation with serial examinations and visual field testing, once true optic disc edema has been excluded. PMID:27033945

  20. Effects of inhibition of nitric oxide synthase on basal anterior segment ocular blood flows and on potential autoregulatory mechanisms.

    PubMed

    Koss, M C

    2001-08-01

    Experiments were undertaken to determine the role played by nitric oxide (NO) in basal ocular blood flow in the anterior aspect of the eye. Subsequent studies focused on existence of autoregulatory mechanisms and on the potential involvement of NO. Cats were anesthetized with pentobarbital (36 mg/kg, i.p.). A femoral artery and vein were cannulated for measuring blood pressure and for drug administration, respectively. Anterior segment blood flow was measured in a continuous fashion from the long posterior ciliary artery (LPCA) using ultrasonic flowmetry and from the anterior choroid using laser-Doppler flowmetry. A needle was placed into the anterior chamber, and autoregulatory mechanisms were studied by decreasing ocular perfusion pressure via stepwise elevations of IOP. Non-selective inhibition of NO synthase with L-NAME (20 mg/kg, i.v.) significantly decreased basal blood flow from both sites. L-NAME (5 mg/kg, i.v.) was without effect as was D-NAME (25 mg/kg, i.v.). Increasing IOP produced a linear decrease on LPCA blood flow indicating absence of autoregulation. In contrast, stepwise elevation of IOP produced a delayed, non-linear response in the anterior choroid suggestive of a strong autoregulatory response. Neither response to elevated ocular perfusion pressure was further altered by inhibition of NO synthase with L-NAME (20 mg/kg, i.v.). The results confirm previous reports that nitric oxide plays a pivotal role in maintenance of basal ocular blood flow. Autoregulation was not seen in the LPCA. In contrast, there was a clear autoregulatory response in the anterior choroid, although neither response was altered by inhibition of NO synthase.

  1. Ocular Response of Choroidal Melanoma With Monosomy 3 Versus Disomy 3 After Iodine-125 Brachytherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Marathe, Omkar S.; Wu, Jeffrey; Lee, Steve P.

    2011-11-15

    Purpose: To report the ocular response of choroidal melanoma with monosomy 3 vs. disomy 3 after {sup 125}I brachytherapy. Methods and Materials: We evaluated patients with ciliochoroidal melanoma managed with fine needle aspiration biopsy immediately before plaque application for {sup 125}I brachytherapy between January 1, 2005 and December 31, 2008. Patients with (1) cytopathologic diagnosis of melanoma, (2) melanoma chromosome 3 status identified by fluorescence in situ hybridization, and (3) 6 or more months of follow-up after brachytherapy were sorted by monosomy 3 vs. disomy 3 and compared by Kruskal-Wallis test. Results: Among 40 ciliochoroidal melanomas (40 patients), 15 hadmore » monosomy 3 and 25 had disomy 3. Monosomy 3 melanomas had a median greatest basal diameter of 12.00 mm and a median tumor thickness of 6.69 mm before brachytherapy; at a median of 1.75 years after brachytherapy, median thickness was 3.10 mm. Median percentage decrease in tumor thickness was 48.3%. Disomy 3 melanomas had a median greatest basal diameter of 10.00 mm and median tumor thickness of 3.19 mm before brachytherapy; at a median of 2.00 years after brachytherapy, median tumor thickness was 2.37 mm. The median percentage decrease in tumor thickness was 22.7%. Monosomy 3 melanomas were statistically greater in size than disomy 3 melanomas (p < 0.001) and showed a greater decrease in tumor thickness after brachytherapy (p = 0.006). Conclusion: In this study, ciliochoroidal melanomas with monosomy 3 were significantly greater in size than disomy 3 melanoma and showed a significantly greater decrease in thickness at a median of 1.75 years after brachytherapy. The greater decrease in monosomy 3 melanoma thickness after brachytherapy is consistent with other malignancies in which more aggressive pathology has been shown to be associated with a greater initial response to radiotherapy.« less

  2. [Ocular graft-versus-host disease: An often misdiagnosed etiology of dry eye syndrome].

    PubMed

    Moyal, L; Adam, R; Akesbi, J; Rodallec, F T; Nordmann, J-P

    2017-02-01

    To report a case of severe ocular graft-versus-host disease (GVHD) after cataract surgery. Observational case report. We describe the case of a 59-year-old man with postoperative corneal ulcer on his only functional eye. His past history reported allogenic bone marrow transplant. His visual acuity (VA) was limited to hand motions. Slit lamp examination revealed diffuse conjunctival hyperemia, severe blepharitis, Meibomian dysfunction, total corneal opacification with epithelial and stromal keratitis and neovascular invasion. Because of the severe dry eye symptoms and history of allogenic hematological stem cell transplantation, ocular GVHD was diagnosed. Functional and anatomical improvement occurred rapidly with topical cyclosporine 2%, with improved VA after treatment. With any severe dry eye syndrome in the context of allogenic bone marrow transplant, ocular GVHD must be considered. For planned ocular surgery, we recommend adding cyclosporine 0.1% treatment before and after surgery to prevent severe ocular GVHD. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Macular retinal and choroidal thickness in unilateral amblyopia using swept-source optical coherence tomography.

    PubMed

    Araki, Syunsuke; Miki, Atsushi; Goto, Katsutoshi; Yamashita, Tsutomu; Takizawa, Go; Haruishi, Kazuko; Ieki, Yoshiaki; Kiryu, Junichi; Yaoeda, Kiyoshi

    2017-09-15

    To investigate macular retinal and choroidal thickness in amblyopic eyes compared to that in fellow and normal eyes using swept-source optical coherence tomography (SS-OCT). This study examined 31 patients with hyperopic anisometropic amblyopia (6.9 ± 3.8 years, mean ± standard deviation), 15 patients with strabismic amblyopia without anisometropia (7.9 ± 4.2 years), and 24 age-matched controls (7.8 ± 3.3 years). Retinal and choroidal thickness was measured by 3D scans using SS-OCT. A 6-mm area around the fovea was automatically analyzed using the Early Treatment Diabetic Retinopathy Study map. The thickness from SS-OCT was corrected for magnification error using individual axial length, spherical refraction, cylinder refraction, and corneal radius. Retinal thickness was divided into the macular retinal nerve fiber layer (mRNFL), ganglion cell layer + inner plexiform layer (GCL+IPL), ganglion cell complex (GCC), and the inner limiting membrane to the retinal pigment epithelium (ILM-RPE) thickness. Retinal and choroidal thickness was compared among amblyopic, fellow, and normal eyes. In both amblyopia groups, there was no significant difference in the mRNFL, GCL+IPL, and GCC thicknesses among the amblyopic, fellow, and control eyes. In the anisometropic amblyopia group, choroidal thickness (subfovea, center 1 mm, nasal and inferior of the inner ring, nasal of the outer ring, and center 6 mm) of amblyopic eyes were significantly greater than that of fellow and normal eyes. In contrast, none of the choroidal thicknesses were significantly different among the investigated eyes in the strabismic amblyopia group. We found no significant difference in inner retinal thickness in patients with unilateral amblyopia. Although there were significant differences in choroidal thickness with hyperopic anisometropic amblyopia, there was no significant difference for the strabismic amblyopia. The discrepancy in choroidal thickness between the two types of amblyopia may be due

  4. Cellular and molecular mechanisms of age-related macular degeneration: from impaired autophagy to neovascularization.

    PubMed

    Klettner, Alexa; Kauppinen, Anu; Blasiak, Janusz; Roider, Johan; Salminen, Antero; Kaarniranta, Kai

    2013-07-01

    Age-related macular degeneration (AMD) is a complex, degenerative and progressive disease involving multiple genetic and environmental factors. It can result in severe visual loss e.g. AMD is the leading cause of blindness in the elderly in the western countries. Although age, genetics, diet, smoking, and many cardiovascular factors are known to be linked with this disease there is increasing evidence that long-term oxidative stress, impaired autophagy clearance and inflammasome mediated inflammation are involved in the pathogenesis. Under certain conditions these may trigger detrimental processes e.g. release of vascular endothelial growth factor (VEGF), causing choroidal neovascularization e.g. in wet AMD. This review ties together these crucial pathological threads in AMD. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

    PubMed

    Solomon, Sharon D; Lindsley, Kristina; Vedula, Satyanarayana S; Krzystolik, Magdalena G; Hawkins, Barbara S

    2014-08-29

    Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to neovascular AMD accounts for most AMD-related severe vision loss. Anti-vascular endothelial growth factor (anti-VEGF) agents, injected intravitreally, aim to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, improve vision. To investigate: (1) the ocular and systemic effects of, and quality of life associated with, intravitreally injected anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) for the treatment of neovascular AMD compared with no anti-VEGF treatment; and (2) the relative effects of one anti-VEGF agent compared with another when administered in comparable dosages and regimens. We searched Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2014), EMBASE (January 1980 to March 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 27 March 2014. We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or a control treatment (e.g., sham treatment or photodynamic therapy). All trials followed participants for at least one year. Two review authors independently screened records, extracted data, and

  6. Automated choroidal segmentation method in human eye with 1050nm optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Liu, Cindy; Wang, Ruikang K.

    2014-02-01

    Choroidal thickness (ChT), defined as the distance between the retinal pigment epithelium (RPE) and the choroid-sclera interface (CSI), is highly correlated with various ocular disorders like high myopia, diabetic retinopathy, and central serous chorioretinopathy. Long wavelength Optical Coherence Tomography (OCT) has the ability to penetrate deep to the CSI, making the measurement of the ChT possible. The ability to accurately segment the CSI and RPE is important in extracting clinical information. However, automated CSI segmentation is challenging due to the weak boundary in the lower choroid and inconsistent texture with varied blood vessels. We propose a K-means clustering based automated algorithm, which is effective in segmenting the CSI and RPE. The performance of the method was evaluated using 531 frames from 4 normal subjects. The RPE and CSI segmentation time was about 0.3 seconds per frame, and the average time was around 0.5 seconds per frame with correction among frames, which is faster than reported algorithms. The results from the proposed method are consistent with the manual segmentation results. Further investigation includes the optimization of the algorithm to cover more OCT images captured from patients and the increase of the processing speed and robustness of the segmentation method.

  7. Varix of the vortex vein ampulla simulating choroidal melanoma: report of four cases.

    PubMed

    Gündüz, K; Shields, C L; Shields, J A

    1998-01-01

    Varix of the vortex vein ampulla is a condition that can cause diagnostic confusion with choroidal melanoma. A case series review was performed from the Ocular Oncology Service, Wills Eye Hospital. In all four cases, the patients were referred with the diagnosis of a small choroidal melanoma. The lesions were located in the nasal quadrant of the fundus near the equator. One patient had two lesions in the same quadrant. In all cases, the fundus lesion became more prominent when the eye gazed in the direction of the lesion and diminished in primary gaze. The mass measured up to 6.0 mm in base diameter and 2.5 mm in thickness in proper gaze. B-scan ultrasonography showed acoustic solidity and gaze-evoked dynamic enlargement of the lesion. Indocyanine green angiography demonstrated early pooling of dye and gaze-evoked fluctuation of the hyperfluorescence in the lesion. Color Doppler imaging, performed in one patient, showed a vascular lesion of venous origin that filled when the eye was placed in the direction of the lesion. Varix of the vortex vein is a condition that should be considered in the differential diagnosis of equatorial small choroidal melanoma. The dynamic nature of the lesion is characteristic and diagnostic.

  8. The retina/RPE proteome in chick myopia and hyperopia models: Commonalities with inherited and age-related ocular pathologies

    PubMed Central

    Riddell, Nina; Faou, Pierre; Murphy, Melanie; Giummarra, Loretta; Downs, Rachael A.; Rajapaksha, Harinda

    2017-01-01

    Purpose Microarray and RNA sequencing studies in the chick model of early optically induced refractive error have implicated thousands of genes, many of which have also been linked to ocular pathologies in humans, including age-related macular degeneration (AMD), choroidal neovascularization, glaucoma, and cataract. These findings highlight the potential relevance of the chick model to understanding both refractive error development and the progression to secondary pathological complications. The present study aimed to determine whether proteomic responses to early optical defocus in the chick share similarities with these transcriptome-level changes, particularly in terms of dysregulation of pathology-related molecular processes. Methods Chicks were assigned to a lens condition (monocular +10 D [diopters] to induce hyperopia, −10 D to induce myopia, or no lens) on post-hatch day 5. Biometric measures were collected following a further 6 h and 48 h of rearing. The retina/RPE was then removed and prepared for liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) on an LTQ-Orbitrap Elite. Raw data were processed using MaxQuant, and differentially abundant proteins were identified using moderated t tests (fold change ≥1.5, Benjamini-Hochberg adjusted p<0.05). These differentially abundant proteins were compared with the genes and proteins implicated in previous exploratory transcriptome and proteomic studies of refractive error, as well as the genes and proteins linked to the ocular pathologies listed above for which myopia or hyperopia are risk factors. Finally, gene set enrichment analysis (GSEA) was used to assess whether gene sets from the Human Phenotype Ontology database were enriched in the lens groups relative to the no lens groups, and at the top or bottom of the protein data ranked by Spearman’s correlation with refraction at 6 and 48 h. Results Refractive errors of −2.63 D ± 0.31 D (mean ± standard error, SE) and 3

  9. Effects of Retinal Morphology on Contrast Sensitivity and Reading Ability in Neovascular Age-Related Macular Degeneration

    PubMed Central

    Keane, Pearse A.; Patel, Praveen J.; Ouyang, Yanling; Chen, Fred K.; Ikeji, Felicia; Walsh, Alexander C.; Tufail, Adnan

    2010-01-01

    Purpose. To investigate the effect of changes in retinal morphology on contrast sensitivity and reading ability in patients with neovascular age-related macular degeneration (AMD) in the Avastin (bevacizumab; Genentech, South San Francisco, CA) for choroidal neovascularization (ABC) Trial. Methods. Contrast sensitivity obtained with Pelli-Robson charts, reading ability assessed with Minnesota Reading charts, and Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA) obtained by protocol refraction, were recorded. Raw Stratus optical coherence tomography (OCT; Carl Zeiss Meditec, Inc., Dublin, CA) images were analyzed with the publicly available software OCTOR, which allows precise delineation of any retinal compartment of interest. Thickness and volume were calculated for neurosensory retina, subretinal fluid (SRF), subretinal tissue, and pigment epithelium detachment, and the resulting measurements were correlated with each visual function parameter. Results. One hundred twenty-two patients with newly diagnosed neovascular AMD and enrolled in the ABC Trial, were evaluated. Increased subretinal tissue volume correlated with decreased contrast sensitivity (Pearson's correlation coefficient, r = −0.4944, P = 0.001). A modest correlation was detected between SRF volume and contrast sensitivity (r = −0.2562, P = 0.004). Increased retinal thickness at the foveal center also correlated with decreased visual function (ETDRS VA: r = −0.4530, P < 0.001). Conclusions. The strongest correlation detected between the functional parameters assessed and any of the OCT-derived morphologic parameters was that between decreased contrast sensitivity and increased subretinal tissue. In the future, assessment of contrast sensitivity and reading ability, in combination with quantitative subanalysis of retinal compartments, may lead to the identification of parameters relevant to functional improvement and ultimate prognosis in patients with newly diagnosed

  10. Massive spontaneous choroidal hemorrhage in a patient with chronic renal failure and coronary artery disease treated with Plavix.

    PubMed

    De Marco, Rocco; Aurilia, Pasquale; Mele, Alessandro

    2009-01-01

    To report a case of massive spontaneous choroidal hemorrhage in a patient with chronic renal failure and coronary artery disease treated with clopidogrel bisulfate (Plavix). Case report. A 75-year-old man presented with pain and loss of vision in the left eye for 1 week. His medical history was remarkable for systemic hypertension, chronic renal failure, and artery coronary disease. For 6 months, he had been taking 75 mg/day of Plavix after coronary angioplasty. Ocular examination revealed the patient to be in angle closure. Ultrasonography and computed tomography scan revealed a massive choroidal hemorrhage pushing the iris-lens diaphragm forward. Pain and intraocular pressure were treated successfully with evacuative sclerotomies, but the final exitus after 6 months was bulbar phthisis. Massive spontaneous choroidal hemorrhage is an extremely rare event that usually has been described in older patients (65-87 years old) receiving anticoagulants or thrombolytic agents. Systemic hypertension, generalized atherosclerosis, and age-related macular degeneration are additional risk factors. In the present case, massive choroidal hemorrhage was associated with use of clopidogrel bisulfate (Plavix) in a patient with chronic renal failure. Our report indicates that Plavix should be administered with caution in patients with chronic renal failure owing to the risk of serious choroidal bleeding. Chronic renal failure should be also included in the list of risk factors for massive spontaneous choroidal hemorrhage. Evacuative sclerotomies may have value in the relief of pain and elevated intraocular pressure but has not been shown to be beneficial in visual and anatomic outcomes.

  11. Effects of adenosine on intraocular pressure, optic nerve head blood flow, and choroidal blood flow in healthy humans.

    PubMed

    Polska, Elzbieta; Ehrlich, Paulina; Luksch, Alexandra; Fuchsjäger-Mayrl, Gabriele; Schmetterer, Leopold

    2003-07-01

    There is evidence from a variety of animal studies that the adenosine system plays a role in the control of intraocular pressure (IOP) and ocular blood flow. However, human data on the effect of adenosine on IOP and choroidal and optic nerve blood flow are not available. The effect of stepwise increases in doses of adenosine (10, 20, and 40 micro g/kg per minute, 30 minutes per infusion step) on optic nerve head blood flow, choroidal blood flow, and IOP was determined in a placebo-controlled double-masked clinical trial in 12 healthy male volunteers. Blood flow in the optic nerve head and choroid was measured with laser Doppler flowmetry. In addition, fundus pulsation amplitude in the macula (FPAM) and the optic nerve head (FPAO) were assessed with laser interferometry. Adenosine induced a small but significant decrease in IOP (at 40 microg/kg per minute: 12% +/- 13%), which was significant versus placebo (P = 0.046). In addition, adenosine induced a significant increase in choroidal blood flow (P < 0.001) and optic nerve head blood flow (P = 0.037), and FPAM (P = 0.0014) and tended to increase FPAO (P = 0.057). At the highest administered dose, the effect on choroidal hemodynamic parameters between 14% and 17%, whereas the effect on optic nerve hemodynamic parameters was between 3% and 11%. These data are consistent with adenosine inducing choroidal and optic nerve head vasodilatation and reducing IOP in healthy humans. Considering the neuroprotective properties of adenosine described in previous animal experiments the adenosine system is an attractive target system for therapeutic approaches in glaucoma.

  12. Neovascular Glaucoma: A Retrospective Review from a Tertiary Eye Care Center in Mexico

    PubMed Central

    R Soohoo, Jeffrey; Lynch, Anne; N Bonell, Levi; Martinez, Karina; Turati, Mauricio; Gonzalez-Salinas, Roberto; Jimenez-Roman, Jesus; Y Kahook, Malik

    2017-01-01

    ABSTRACT Aim To describe the demographic characteristics, ocular comorbidities, and clinical outcomes of patients with neovascular glaucoma (NVG) and to determine the number of patients who returned for a follow-up eye examination. Materials and methods We examined the clinical data of patients with NVG, who attended a glaucoma clinic between July 2010 and November 2014. We collected information on the demographic characteristics of the patients to include the level of education, ocular comorbidities, NVG stage, visual acuity, glaucoma medications, intraocular pressure (IOP), and the number of patients who had a follow-up ocular examination at month 1, 3, 6, and 12. Results Data from 350 patients (473 eyes) with NVG were collected. We found 91% of the cohort had proliferative diabetic retinopathy (PDR). We found blindness in both or one eye in 14% and 31% of the cohort respectively. Low vision was found in both or one eye in 14% and 32% of the eyes respectively. By 6 months follow-up, only 32% of the patients were seen at our clinic and by 12 months follow-up, this number decreased to 15%. Around 60% of the patients were on no IOP lowering drugs at the first visit. We found 53% of the cohort had an incomplete elementary school education. Conclusion The results suggest that advanced NVG is a significant ocular problem for patients referred to our clinic with just over half of the patients presenting as blind. We also found that several socioeconomic factors that had an important role in the development of PDR and NVG, specifically, educational status. Clinical significance We described the characteristics of a large cohort of patients with very advanced NVG, reflecting the fact that the strict control of the underlying disease must be the main goal of the Mexican national health system. How to cite this article Lazcano-Gomez G, Soohoo JR, Lynch A, Bonell LN, Martinez K, Turati M, González-Salinas R, Jimenez-Roman J, Kahook MY. Neovascular Glaucoma: A Retrospective

  13. Incidence of choroidal neovascularization in the fellow eye in the comparison of age-related macular degeneration treatments trials.

    PubMed

    Maguire, Maureen G; Daniel, Ebenezer; Shah, Ankoor R; Grunwald, Juan E; Hagstrom, Stephanie A; Avery, Robert L; Huang, Jiayan; Martin, Revell W; Roth, Daniel B; Castellarin, Alessandro A; Bakri, Sophie J; Fine, Stuart L; Martin, Daniel F

    2013-10-01

    To assess the influence of drug; dosing regimen; and traditional, nontraditional, and genetic risk factors on the incidence of choroidal neovascularization (CNV) in the fellow eye of patients treated for CNV with ranibizumab or bevacizumab. Cohort study of patients enrolled in a multicenter, randomized clinical trial. Patients with no CNV in the fellow eye at the time of enrollment in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Eligibility criteria for the clinical trial required that study eyes have evidence on fluorescein angiography and optical coherence tomography of CNV secondary to age-related macular degeneration (AMD) and visual acuity between 20/25 and 20/320. Treatment for the study eye was assigned randomly to either ranibizumab or bevacizumab and to 3 different regimens for dosing over a 2-year period. The genotypes for 4 single nucleotide polymorphisms (SNPs) associated with risk of AMD were determined. Only patients without CNV in the fellow eye at baseline were considered at risk. The CATT ophthalmologists examined patients every 4 weeks through 2 years and recorded treatment for CNV in the fellow eye. Development of CNV in the fellow eye. Among 1185 CATT participants, 727 (61%) had no CNV in the fellow eye at enrollment. At 2 years, CNV had developed in 75 (20.6%) of 365 patients treated with ranibizumab and in 60 (16.6%) of 362 patients treated with bevacizumab (absolute difference, 4.0%; 95% confidence interval [CI], -1.7% to 9.6%; P = 0.17). The risk ratio for pro re nata dosing relative to monthly dosing was 1.1 (95% CI, 0.8-1.6). Greater elevation of the retinal pigment epithelium and fluid in the foveal center of the study eye were associated with increased incidence of CNV in the fellow eye. Incidence was not associated with genotype on rs1061170 (CFH), rs10490924 (ARMS2), rs11200638 (HTRA1), and rs2230199 (C3; P>0.35). Through 2 years, there was no statistically significant difference between ranibizumab and

  14. Increased levels of circulating CD34+ cells in neovascular age-related macular degeneration: relation with clinical and OCT features.

    PubMed

    Kara, Caner; Özdal, Pınar Ç; Beyazyıldız, Emrullah; Özcan, Nurgül E; Teke, Mehmet Y; Vural, Gülden; Öztürk, Faruk

    2018-01-01

    To investigate the levels of circulating CD34+ stem cells in patients with neovascular type age-related macular degeneration (AMD) and its relation with clinical and optical coherence tomography (OCT) findings. The study consisted of 55 patients: 28 patients (18 male and 10 female) with neovascular type AMD as a study group and 27 patients (12 male and 15 female) scheduled for cataract surgery as a control group. The level of CD34+ stem cells was measured by flow cytometry. Demographic and clinical data were recorded. The mean ages of patients in the study and control groups were 71 ± 8 and 68 ± 6 years, respectively. There was no statistically significant difference in terms of age, sex, or systemic disease association between study and control groups. However, smoking status was significantly higher in the study group (67.9% vs 37.0%; p = 0.02). Stem cell levels were significantly higher in the study group (1.5 ± 0.9 vs 0.5 ± 0.3; p<0.001), but there was no relation between stem cell levels and clinical and OCT findings. Increased circulating CD34+ stem cell levels were observed in patients with choroidal neovascular membrane associated with AMD, but no significant relation was found between cell levels and clinical and OCT findings.

  15. A simplified technique for in situ excision of cornea and evisceration of retinal tissue from human ocular globe.

    PubMed

    Parekh, Mohit; Ferrari, Stefano; Di Iorio, Enzo; Barbaro, Vanessa; Camposampiero, Davide; Karali, Marianthi; Ponzin, Diego; Salvalaio, Gianni

    2012-06-12

    Enucleation is the process of retrieving the ocular globe from a cadaveric donor leaving the rest of the globe undisturbed. Excision refers to the retrieval of ocular tissues, especially cornea, by cutting it separate from the ocular globe. Evisceration is the process of removing the internal organs referred here as retina. The ocular globe consists of the cornea, the sclera, the vitreous body, the lens, the iris, the retina, the choroid, muscles etc (Suppl. Figure 1). When a patient is suffering from corneal damage, the cornea needs to be removed and a healthy one must be transplanted by keratoplastic surgeries. Genetic disorders or defects in retinal function can compromise vision. Human ocular globes can be used for various surgical procedures such as eye banking, transplantation of human cornea or sclera and research on ocular tissues. However, there is little information available on human corneal and retinal excision, probably due to the limited accessibility to human tissues. Most of the studies describing similar procedures are performed on animal models. Research scientists rely on the availability of properly dissected and well-conserved ocular tissues in order to extend the knowledge on human eye development, homeostasis and function. As we receive high amount of ocular globes out of which approximately 40% (Table 1) of them are used for research purposes, we are able to perform huge amount of experiments on these tissues, defining techniques to excise and preserve them regularly. The cornea is an avascular tissue which enables the transmission of light onto the retina and for this purpose should always maintain a good degree of transparency. Within the cornea, the limbus region, which is a reservoir of the stem cells, helps the reconstruction of epithelial cells and restricts the overgrowth of the conjunctiva maintaining corneal transparency and clarity. The size and thickness of the cornea are critical for clear vision, as changes in either of them

  16. En-face optical coherence tomography in the diagnosis and management of age-related macular degeneration and polypoidal choroidal vasculopathy.

    PubMed

    Lau, Tiffany; Wong, Ian Y; Iu, Lawrence; Chhablani, Jay; Yong, Tao; Hideki, Koizumi; Lee, Jacky; Wong, Raymond

    2015-05-01

    Optical coherence tomography (OCT) is a noninvasive imaging modality providing high-resolution images of the central retina that has completely transformed the field of ophthalmology. While traditional OCT has produced longitudinal cross-sectional images, advancements in data processing have led to the development of en-face OCT, which produces transverse images of retinal and choroidal layers at any specified depth. This offers additional benefit on top of longitudinal cross-sections because it provides an extensive overview of pathological structures in a single image. The aim of this review was to discuss the utility of en-face OCT in the diagnosis and management of age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). En-face imaging of the inner segment/outer segment junction of retinal photoreceptors has been shown to be a useful indicator of visual acuity and a predictor of the extent of progression of geographic atrophy. En-face OCT has also enabled high-resolution analysis and quantification of pathological structures such as reticular pseudodrusen (RPD) and choroidal neovascularization, which have the potential to become useful markers for disease monitoring. En-face Doppler OCT enables subtle changes in the choroidal vasculature to be detected in eyes with RPD and AMD, which has significantly advanced our understanding of their pathogenesis. En-face Doppler OCT has also been shown to be useful for detecting the polypoid lesions and branching vascular networks diagnostic of PCV. It may therefore serve as a noninvasive alternative to fluorescein and indocyanine green angiography for the diagnosis of PCV and other forms of the exudative macular disease.

  17. Choroidal vasculature characteristics based choroid segmentation for enhanced depth imaging optical coherence tomography images

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Qiang; Niu, Sijie; Yuan, Songtao

    Purpose: In clinical research, it is important to measure choroidal thickness when eyes are affected by various diseases. The main purpose is to automatically segment choroid for enhanced depth imaging optical coherence tomography (EDI-OCT) images with five B-scans averaging. Methods: The authors present an automated choroid segmentation method based on choroidal vasculature characteristics for EDI-OCT images with five B-scans averaging. By considering the large vascular of the Haller’s layer neighbor with the choroid-sclera junction (CSJ), the authors measured the intensity ascending distance and a maximum intensity image in the axial direction from a smoothed and normalized EDI-OCT image. Then, basedmore » on generated choroidal vessel image, the authors constructed the CSJ cost and constrain the CSJ search neighborhood. Finally, graph search with smooth constraints was utilized to obtain the CSJ boundary. Results: Experimental results with 49 images from 10 eyes in 8 normal persons and 270 images from 57 eyes in 44 patients with several stages of diabetic retinopathy and age-related macular degeneration demonstrate that the proposed method can accurately segment the choroid of EDI-OCT images with five B-scans averaging. The mean choroid thickness difference and overlap ratio between the authors’ proposed method and manual segmentation drawn by experts were −11.43 μm and 86.29%, respectively. Conclusions: Good performance was achieved for normal and pathologic eyes, which proves that the authors’ method is effective for the automated choroid segmentation of the EDI-OCT images with five B-scans averaging.« less

  18. Density of ocular components of the bovine eye.

    PubMed

    Su, Xiao; Vesco, Christina; Fleming, Jacquelyn; Choh, Vivian

    2009-10-01

    Density is essential for acoustic characterization of tissues and provides a basic input for ultrasound backscatter and absorption models. Despite the existence of extensive compilations of acoustic properties, neither unified data on ocular density nor comparisons of the densities between all ocular components can be found. This study was undertaken to determine the mass density of all the ocular components of the bovine eye. Liquid components were measured through mass/volume ratio, whereas solid tissues were measured with two different densitometry techniques based on Archimedes Principle. The first method determines the density by measuring dry and wet weight of the tissues. The second method consists of immersing the tissues in sucrose solutions of varying densities and observing their buoyancy. Although the mean densities for all tissues were found to be within 0.02 g/cm by both methods, only the sucrose solution method offered a consistent relative order for all measured ocular components, as well as a considerably smaller standard deviation (a maximum standard deviation of 0.004 g/cm for cornea). The lens was found to be the densest component, followed by the sclera, cornea, choroid, retina, aqueous, and vitreous humors. The consistent results of the sucrose solution tests suggest that the ocular mass density is a physical property that is more dependent on the compositional and structural characteristics of the tissue and than on population variability.

  19. Ocular toxoplasmosis II: clinical features, pathology and management

    PubMed Central

    Butler, Nicholas J; Furtado, João M; Winthrop, Kevin L; Smith, Justine R

    2014-01-01

    The term, ocular toxoplasmosis, refers to eye disease related to infection with the parasite, Toxoplasma gondii. Recurrent posterior uveitis is the typical form of this disease, characterized by unilateral, necrotizing retinitis with secondary choroiditis, occurring adjacent to a pigmented retinochoroidal scar and associated with retinal vasculitis and vitritis. Multiple atypical presentations are also described, and severe inflammation is observed in immunocompromised patients. Histopathological correlations demonstrate focal coagulative retinal necrosis, and early in the course of the disease, this inflammation is based in the inner retina. For typical ocular toxoplasmosis, a diagnosis is easily made on clinical examination. In atypical cases, ocular fluid testing to detect parasite DNA by polymerase chain reaction or to determine intraocular production of specific antibody may be extremely helpful for establishing aetiology. Given the high seroprevalence of toxoplasmosis in most communities, serological testing for T. gondii antibodies is generally not useful. Despite a lack of published evidence for effectiveness of current therapies, most ophthalmologists elect to treat patients with ocular toxoplasmosis that reduces or threatens to impact vision. Classic therapy consists of oral pyrimethamine and sulfadiazine, plus systemic corticosteroid. Substantial toxicity of this drug combination has spurred interest in alternative antimicrobials, as well as local forms of drug delivery. At this time, however, no therapeutic approach is curative of ocular toxoplasmosis. PMID:22712598

  20. [Ocular complication in children with Stevens-Johnson syndrome].

    PubMed

    Gotz-Wieckowska, Anna; Bernardczyk-Meller, Jadwiga; Rakowicz, Piotr

    2003-01-01

    Presentation of serious cases of Stevens-Johnson syndrome (SJS) with acute and chronic ocular manifestations and methods of their treatment. 3 children aged between 6 to 12 years. Follow-up time was from 5, months up to 6 years. CONSERVATIVE TREATMENT WAS: Symblepharon massage, topical antibiotics, steroids, artificial tears. In chronic stage mitomycin C as eye drops was use in one case. Surgical treatment--intubation of lacrimal ducts and removal of eye lashes were performed in 2 cases. In 2 cases, in which ophthalmological therapy was introduced very early, the results of treatment were very good. In one case with corneal neovascularization and posterior lid margin keratinization, the results of treatment were not satisfactory. 1. The children with SJS should be treated by ophthalmologists as soon as possible. 2. Some pathological changes of conjunctiva, cornea and lacrimal ducts disappeared after few weeks of intensive topical therapy often. 3. The results of treatment of cicatrical changes of lids, conjunctiva and neovascularization of the cornea were not satisfactory.

  1. Bilateral polypoidal choroidal vasculopathy coexisting with exudative and atrophic age-related macular degeneration.

    PubMed

    Aronés-Santivañez, J R; Dyrda, A; Alarcón Valero, I

    2016-12-01

    To present the case of simultaneous presentation of polypoidal choroidal vasculopathy (PCV) and aged-related macular degeneration (AMD). An 83-year-old woman presented with decreased vision in the left eye (LE). In the examination there was an orange peripapillary lesion surrounded by lipid exudates and another subfoveal greyish lesion in the LE. Disciform scarring was observed in the right eye. Fluorescein angiography showed a classic neovascular membrane in in the LE fovea. Indocyanine angiography (ICGA) showed a polyp-like peri-papillary aneurysmal dilation in both eyes. The patient was treated with photodynamic therapy and anti-VEFG injections with stabilisation of the lesions. PCV and AMD can co-exist in unusual cases. When PCV is suspected, ICGA is mandatory for diagnosis. Copyright © 2016. Publicado por Elsevier España, S.L.U.

  2. Intravitreal injection of (99)Tc-MDP inhibits the development of laser-induced choroidal neovascularization in rhesus monkeys.

    PubMed

    Lai, Kunbei; Jin, Chenjin; Tu, Shu; Xiong, Yunfan; Huang, Rui; Ge, Jian

    2014-07-01

    The aim of this study was to investigate the safety and efficacy of intravitreal injection of (99)Tc-MDP, a decay product of (99m)Tc-MDP, on the development of laser-induced choroidal neovascularization (CNV) in rhesus monkeys. Experimental CNV was induced by argon laser with a small high-energy laser spot. Monkeys were given 50 μL of (99)Tc-MDP at a concentration of 0.005 μg/mL (n = 6) or 0.01 μg/mL (n = 6) by intravitreal injection once a week immediately after laser injury for a period of 56 days. Control animals were treated with the same volume of PBS (n = 6) in the same way. Eyes were monitored by ophthalmic examination, color fundus photography, fluorescence fundus angiography (FFA), optical coherence tomography (OCT) and histology. Incidences of grade 4 CNV lesions as well as the leakage areas of grade 4 CNVs on the late-phase of fluorescein angiograms were measured in a standardized, randomized and masked fashion fortnightly. The maximum widths and heights of grade 4 CNVs were also calculated by histology at the end of the experiment. Toxicity of (99)Tc-MDP on the retina was evaluated by electroretinogram (ERG) and histologic analysis. (99)Tc-MDP reduced the incidences of grade 4 CNVs by 33.33 % and 39.40 % in the 0.005 μg/mL and 0.01 μg/mL groups, respectively, compared with the PBS group on day 28 (P < 0.05; n = 6). The leakage areas of grade 4 CNVs were smaller in the 0.005 μg/mL (0.7136 ± 0.0283 mm(2), p <0.01; n = 6) and 0.01 μg/mL (0.4351 ± 0.0349 mm(2), p < 0.01; n = 6) groups than those in the PBS control group (0.9373 ± 0.0455 mm(2); n = 6) in a dose-dependent manner on day 28. OCT and histology also showed that the sizes of CNVs were smaller in the (99)Tc-MDP treated groups than those in the PBS group. Although intravitreal injection of (99)Tc-MDP led to mild inflammatory reaction in the anterior chamber, histology and ERG findings demonstrated that (99)Tc-MDP did not cause any change in

  3. Clinical evaluation of pazopanib eye drops versus ranibizumab intravitreal injections in subjects with neovascular age-related macular degeneration.

    PubMed

    Csaky, Karl G; Dugel, Pravin U; Pierce, Amy J; Fries, Michael A; Kelly, Deborah S; Danis, Ronald P; Wurzelmann, John I; Xu, Chun-Fang; Hossain, Mohammad; Trivedi, Trupti

    2015-03-01

    To evaluate pazopanib eye drops in subjects with active subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Multicountry, randomized, parallel-group, double-masked, active and placebo-controlled, dose-ranging study of eye drops. A total of 510 subjects (93% white; 58% female; mean age, 75.3 years) whose AMD was previously managed by anti-vascular endothelial growth factor intravitreal injections. Treatments administered for 52 weeks included placebo eye drops instilled 4 times daily (n=73); pazopanib 5 mg/ml instilled 3 (n=72) or 4 times daily (n=74); pazopanib 10 mg/ml instilled 2 (n=73), 3 (n=73), or 4 times daily (n=72); or ranibizumab injection administered once every 4 weeks (n=73). In addition, for all eye drop treatment groups, open-label ranibizumab was administered as needed. The main outcome measures were best-corrected visual acuity (BCVA) and injection frequency assessed at week 52. Safety was assessed every 4 weeks and pazopanib plasma concentrations were determined at weeks 4 and 24. At week 52, pazopanib, with allowance for as-needed ranibizumab injections, was noninferior to monthly ranibizumab as well as to as-needed ranibizumab administered with placebo eye drops in maintaining BCVA (estimated BCVA gains of 0.3-1.8 vs. 1.4 vs. 0.2 letters, respectively). Pazopanib treatment did not reduce as-needed ranibizumab injections by ≥50% (prespecified efficacy criterion). At week 52, there were no clinically meaningful changes from baseline in retinal thickness or morphology, CNV size, or lesion characteristics on optical coherence tomography or fluorescein angiography. Complement factor H genotype had no effect on the responses to pazopanib and/or ranibizumab (BCVA, injection rate, or optical coherence tomography/fluorescein angiography changes). Steady-state concentrations of pazopanib in plasma seemed to be reached by week 4. The most common ocular adverse events related to pazopanib and ranibizumab were

  4. Effect of trapping vascular endothelial growth factor-A in a murine model of dry eye with inflammatory neovascularization.

    PubMed

    Kwon, Jin Woo; Choi, Jin A; Shin, Eun Young; La, Tae Yoon; Jee, Dong Hyun; Chung, Yeon Woong; Cho, Yang Kyung

    2016-01-01

    To evaluate whether trapping vascular endothelial growth factor A (VEGF-A) would suppress angiogenesis and inflammation in dry eye corneas in a murine corneal suture model. We established two groups of animals, one with non-dry eyes and the other with induced dry eyes. In both groups, a corneal suture model was used to induce inflammation and neovascularization. Each of two groups was again divided into three subgroups according to the treatment; subgroup I (aflibercept), subgroup II (dexamethasone) and subgroup III (phosphate buffered saline, PBS). Corneas were harvested and immunohistochemical staining was performed to compare the extents of neovascularization and CD11b+ cell infiltration. Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and VEGF-A in the corneas. Trapping VEGF-A with aflibercept resulted in significantly decreased angiogenesis and inflammation compared with the dexamethasone and PBS treatments in the dry eye corneas (all P <0.05), but with no such effects in non-dry eyes. The anti-inflammatory and anti-angiogenic effects of VEGF-A trapping were stronger than those of dexamethasone in both dry eye and non-dry eye corneas (all P <0.05). The levels of RNA expression of VEGF-A, TNF-alpha, and IL-6 in the aflibercept subgroup were significantly decreased compared with those in the PBS subgroup in the dry eye group. Compared with non-dry eye corneas, dry eye corneas have greater amounts of inflammation and neovascularization and also have a more robust response to anti-inflammatory and anti-angiogenic agents after ocular surface surgery. Trapping VEGF-A is effective in decreasing both angiogenesis and inflammation in dry eye corneas after ocular surface surgery.

  5. Choroidal Thinning Associated With Hydroxychloroquine Retinopathy.

    PubMed

    Ahn, Seong Joon; Ryu, So Jung; Joung, Joo Young; Lee, Byung Ro

    2017-11-01

    To investigate choroidal thickness in patients using hydroxychloroquine (HCQ) and compare choroidal thickness between eyes with and without HCQ retinopathy. Retrospective case series. Setting: Institutional. We included 124 patients with systemic lupus erythematosus or rheumatoid arthritis who were treated with HCQ. The patients were divided into an HCQ retinopathy group and a control group, according to the presence or absence of HCQ retinopathy. Total choroidal thickness and choriocapillaris-equivalent thickness were measured manually by 2 independent investigators using swept-source optical coherence tomography (SS-OCT; DRI-OCT, Topcon Inc, Tokyo, Japan). These measurements were made at the fovea and at nasal and temporal locations 0.5, 1.5, and 3 mm from the fovea. Medium-to-large vessel layer thickness was calculated accordingly. The thicknesses were compared between the HCQ retinopathy and control groups. We performed correlation analyses between choroidal thicknesses and details regarding HCQ use. Total choroidal thickness and choriocapillaris-equivalent thickness. Choroidal thicknesses were significantly decreased (P < .05) in the HCQ retinopathy group compared to the control group, except at the temporal choroid 1.5 mm from the fovea. Choriocapillaris-equivalent thicknesses were significantly different in all choroidal locations between the groups. In contrast, the medium-to-large vessel layer thickness was only significantly different at a few locations. The cumulative dose/body weight was significantly correlated with subfoveal choroidal and choriocapillaris-equivalent thicknesses (both P = .001). The association between presence of HCQ retinopathy and choroidal thicknesses was also statistically significant after adjusting for age, diagnosis for HCQ use, refractive errors, and duration of HCQ use (P = .001 and P = .003 for subfoveal choroidal and choriocapillaris-equivalent thickness, respectively). These results all suggest that HCQ retinopathy is

  6. Transforming Growth Factor-Beta Inhibition Reduces Progression of Early Choroidal Neovascularization Lesions in Rats: P17 and P144 Peptides

    PubMed Central

    Zarranz-Ventura, Javier; Fernández-Robredo, Patricia; Recalde, Sergio; Salinas-Alamán, Angel; Borrás-Cuesta, Francisco; Dotor, Javier; García-Layana, Alfredo

    2013-01-01

    The purpose of this study was to assess the effects of transforming growth factor beta (TGF-β) inhibitor peptides (P17 & P144) on early laser-induced choroidal neovascularization (LI-CNV) lesions in rats, two weeks after laser CNV induction. Seventy-one Long Evans rats underwent diode laser application in an established LI-CNV model. Baseline fluorescein angiography (FA) was performed 14 days following laser procedure, and treatments were administered 16 days post-laser application via different administration routes. Intravenous groups included control (IV-Control), P17 (IV-17), and P144 (IV-144) groups, whereas intravitreal groups included P17 (IVT-17), P144 (IVT-144), and a mixture of both peptides (IVT-17+144) (with fellow eyes receiving vehicle alone). CNV evolution was assessed using FA performed weekly for four weeks after treatment. Following sacrifice, VEGF, TGF-β, COX-2, IGF-1, PAI-1, IL-6, MMP-2, MMP-9, and TNF-α gene expression was assessed using RT-PCR. VEGF and p-SMAD2 protein levels were also assessed by western-blot, while MMP-2 activity was assessed with gelatin zymography. Regarding the FA analysis, the mean CNV area was lower from the 3rd week in IVT-17 and IVT-144 groups, and also from the 2nd week in IVT-17+144. Biochemical analysis revealed that gene expression was lower for VEGF and COX-2 genes in IV-17 and IV-144 groups, VEGF gene in IVT-17+144 group and MMP-2 gene in IVT-17 and IVT-144 groups. VEGF protein expression was also decreased in IV-17, IV-144, IVT-17 and IVT-144, whereas pSMAD-2 levels were lower in IV-17, IV-144 and IVT-17+144 groups. Zymogram analysis revealed decreased MMP-2 activity in IV-17, IV-144, IVT-17 and IVT-144 groups. These data suggest that the use of TGF-β inhibitor peptides (P17 & P144) decrease the development of early CNV lesions by targeting different mediators than those typically affected using current anti-angiogenic therapies. Its potential role in the treatment of early CNV appears promising as a single

  7. Molecular diagnosis and ocular imaging of West Nile virus retinitis and neuroretinitis.

    PubMed

    Sivakumar, Rathinam R; Prajna, Lalitha; Arya, Lalan Kumar; Muraly, Praveen; Shukla, Jyoti; Saxena, Divyasha; Parida, Manmohan

    2013-09-01

    To describe the ocular features of West Nile virus (WNV) infection proven by serology and molecular diagnostic techniques. Prospective case series. Fifty-two patients who presented to the uveitis clinic with ocular inflammatory signs and history of fever preceding ocular symptoms between January 2010 and January 2012 were enrolled for laboratory diagnosis. Serum samples were collected from 30 healthy controls from the same geographic area. Patients were tested for all endemic infectious diseases that can cause ocular inflammation by serology or molecular diagnostics. When patients had positive antibodies for WNV, serum/plasma samples were tested by real-time reverse transcription (RT) polymerase chain reaction (PCR) and RT loop-mediated isothermal gene amplification assays. The PCR product was subjected to nucleotide sequencing. Fundus fluorescence angiography (FFA), optical coherence tomography (OCT), and indocyanine green angiography were performed. Visual prognosis was analyzed. Clinical signs (retinitis, neuroretinitis, and choroiditis) and ocular complications (decrease in vision). A total of 37 of 52 patients (71%) showed positive results for at least 2 laboratory tests for WNV. Fundus examination revealed discrete, superficial, white retinitis; arteritis; phlebitis; and retinal hemorrhages with or without macular star. The FFA revealed areas of retinal inflammation with indistinct borders, vascular and optic disc leakage, vessel wall staining, or capillary nonperfusion. Indocyanine green angiography confirmed choroidal inflammation in 1 of the patients who was diabetic. The OCT scan of the macula revealed inner retinal layer edema in active inflammation and retinal atrophy in late stage. At the final visit, 43% of patients had visual acuity better than 6/12. In addition to previously reported clinical signs, retinitis, neuroretinitis, and retinal vasculitis were seen in this population. Atrophy of the inner retinal layer was seen on OCT after resolution of

  8. Polymerase chain reaction for Mycobacterium tuberculosis DNA detection from ocular fluids in patients with various types of choroiditis in a referral eye center in India

    PubMed Central

    Biswas, Jyotirmay; Kazi, Mohmmad Salman; Agarwal, Vishvesh Ashokkumar; Alam, Md. Shahid; Therese, K Lily

    2016-01-01

    Aims: The aim of this study was to detect Mycobacterium tuberculosis (MTB) DNA with polymerase chain reaction (PCR) in aqueous or vitreous samples of patients suffering from choroiditis presumed to be infectious origin. Settings and Design: Hospital-based, retrospective case–control study. Subjects and Methods: In all, forty eyes of forty patients with choroiditis divided into two groups – Group A (serpiginous-like choroiditis, ampiginous choroiditis, multifocal choroiditis) and Group B (choroidal abscess, miliary tuberculosis (TB), choroidal tubercle) were analyzed retrospectively. In 27 controls (patients without uveitis undergoing phacoemulsification), anterior chamber aspirate was done and sample subjected to real-time PCR. Patients underwent nested PCR for MTB using IS6110 and MPB64 primers from aqueous (n = 39) or vitreous (n = 1). All patients underwent detailed ophthalmological examination by slit-lamp biomicroscopy, fundus examination by indirect ophthalmoscopy, and fundus photograph and fundus fluorescein angiography if required. Statistical Analysis: Positive results of PCR for MTB within the group and between two groups were statistically analyzed using Chi-square test. Results: There were 25 males and 15 females. Mean age at presentation was 34.66 years (range, 14–62). PCR positivity rates were 41.3% (n = 12/29) and 81.82% (n = 9/11) in Groups A and B, respectively. No controls had PCR-positive result. Comparison of PCR positivity rates showed statistically significant difference between Groups A and B (P = 0.028). Systemic TB was detected in 57.14% (n = 12/21) of all PCR-positive cases (Group A - 33.3%, n = 4/12; Group B - 88.9%, n = 8/9). Systemic antitubercular treatment (ATT) for 9 months and oral steroids were successful in resolution of choroiditis in all PCR-positive patients (n = 21) without disease recurrence. Conclusions: Eyes with choroiditis of suspected/presumed tubercular origin should be subjected to PCR for diagnosis of TB and

  9. let-7 Contributes to Diabetic Retinopathy but Represses Pathological Ocular Angiogenesis

    PubMed Central

    Zhou, Qinbo; Frost, Robert J. A.; Anderson, Chastain; Zhao, Fangkun; Ma, Jing; Yu, Bo

    2017-01-01

    ABSTRACT The in vivo function of microRNAs (miRs) in diabetic retinopathy (DR) and age-related macular degeneration (AMD) remains unclear. We report here that let-7 family members are expressed in retinal and choroidal endothelial cells (ECs). In ECs, overexpression of let-7 by adenovirus represses EC proliferation, migration, and networking in vitro, whereas inhibition of the let-7 family with a locked nucleic acid (LNA)–anti-miR has the opposite effect. Mechanistically, silencing of the let-7 target HMGA2 gene mimics the phenotype of let-7 overexpression in ECs. let-7 transgenic (let-7-Tg) mice show features of nonproliferative DR, including tortuous retinal vessels and defective pericyte coverage. However, these mice develop significantly less choroidal neovascularization (CNV) compared to wild-type controls after laser injury. Consistently, silencing of let-7 in the eye increased laser-induced CNV in wild-type mice. Together, our data establish a causative role of let-7 in nonproliferative diabetic retinopathy and a repressive function of let-7 in pathological angiogenesis, suggesting distinct implications of let-7 in the pathogenesis of DR and AMD. PMID:28584193

  10. Ocular toxoplasmosis II: clinical features, pathology and management.

    PubMed

    Butler, Nicholas J; Furtado, João M; Winthrop, Kevin L; Smith, Justine R

    2013-01-01

    The term, ocular toxoplasmosis, refers to eye disease related to infection with the parasite, Toxoplasma gondii. Recurrent posterior uveitis is the typical form of this disease, characterized by unilateral, necrotizing retinitis with secondary choroiditis, occurring adjacent to a pigmented retinochoroidal scar and associated with retinal vasculitis and vitritis. Multiple atypical presentations are also described, and severe inflammation is observed in immunocompromised patients. Histopathological correlations demonstrate focal coagulative retinal necrosis, and early in the course of the disease, this inflammation is based in the inner retina. For typical ocular toxoplasmosis, a diagnosis is easily made on clinical examination. In atypical cases, ocular fluid testing to detect parasite DNA by polymerase chain reaction or to determine intraocular production of specific antibody may be extremely helpful for establishing aetiology. Given the high seroprevalence of toxoplasmosis in most communities, serological testing for T. gondii antibodies is generally not useful. Despite a lack of published evidence for effectiveness of current therapies, most ophthalmologists elect to treat patients with ocular toxoplasmosis that reduces or threatens to impact vision. Classic therapy consists of oral pyrimethamine and sulfadiazine, plus systemic corticosteroid. Substantial toxicity of this drug combination has spurred interest in alternative antimicrobials, as well as local forms of drug delivery. At this time, however, no therapeutic approach is curative of ocular toxoplasmosis. © 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

  11. An atypical case of neurosarcoidosis presenting with neovascular glaucoma.

    PubMed

    Vereecken, Melissa; Hollanders, Karolien; De Bruyn, Deborah; Ninclaus, Virginie; De Zaeytijd, Julie; De Schryver, Ilse

    2018-04-18

    Sarcoidosis, a multisystem, granulomatous disorder, sometimes manifests with a neuro-ophthalmic subtype. The latter can pose a diagnostic challenge, especially when ocular symptoms appear before systemic involvement, as the clinical picture then can be non-specific and systemic laboratory and standard imaging investigations can be negative. A 71-year-old woman presented with a 4-month history of sudden-onset visual loss in the left eye. Slit lamp examination revealed anterior chamber cells, iris, and angle neovascularization. Fundoscopy showed a pale edematous optic nerve head surrounded with intraretinal hemorrhages and yellow retinal infiltrates. The vasculature was very narrow to absent. Indeed, fluorescein angiography filling was limited to the (juxta-)papillary region. An extensive systemic work-up revealed a monoclonal gammopathy and absence of any inflammatory markers. On MRI, a mass infiltration of the intraorbital and the intracranial optic nerve was visible. Additional PET-CT scan revealed hilar lymph nodes. A transbronchial biopsy demonstrating a non-caseating granulomatous lesion led to the diagnosis of sarcoidosis and thus neurosarcoidosis. Treatment with high-dose prednisone and azathioprine was started to avoid progression and subsequent visual loss in the other eye. A patient with neurosarcoidosis presenting with compressive ischemic optic disc edema and neovascular glaucoma is described, increasing the diversity of clinical presentations and confirming the diagnostic challenge of neurosarcoidosis.

  12. OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY SHOWS INNER CHOROIDAL ISCHEMIA IN ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY.

    PubMed

    Dolz-Marco, Rosa; Sarraf, David; Giovinazzo, Vincent; Freund, K Bailey

    2017-01-01

    To describe multimodal imaging findings of an evolving case of acute posterior multifocal placoid pigment epitheliopathy occurring in a young healthy male. Case report of a patient with acute posterior multifocal placoid pigment epitheliopathy including comprehensive systemic and ocular examinations. Ultra-widefield autofluorescence, fluorescein angiography, indocyanine green angiography, and serial optical coherence tomography angiography were performed. A 34-year-old male presented with acute vision loss in his left eye for 2 weeks. His best-corrected visual acuity was 20/20 in his right eye and 20/200 in his left eye. Dilated funduscopic examination revealed multiple creamy white deep retinal lesions showing macular involvement of the left eye with a diffuse area of pigmentary changes. The presence of multiple areas of hypoperfusion of the inner choroid were demonstrated with fluorescein and indocyanine green angiography. Serial optical coherence tomography angiography showed multiple evolving areas of decreased flow at the level of the inner choroid. Although the pathogenesis of acute posterior multifocal placoid pigment epitheliopathy remains unknown, there is growing evidence of a primary choroidal involvement with secondary damage to the overlying retinal pigment epithelium and the outer retinal layers. Optical coherence tomography angiography may provide valuable information for the diagnosis and follow-up of this condition avoiding invasive angiographic procedures.

  13. Carbon-ion radiotherapy for locally advanced or unfavorably located choroidal melanoma: A Phase I/II dose-escalation study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tsuji, Hiroshi; Ishikawa, Hitoshi; Yanagi, Takeshi

    2007-03-01

    Purpose: To evaluate the applicability of carbon ion beams for the treatment of choroidal melanoma with regard to normal tissue morbidity and local tumor control. Methods and Materials: Between January 2001 and February 2006, 59 patients with locally advanced or unfavorably located choroidal melanoma were enrolled in a Phase I/II clinical trial of carbon-ion radiotherapy at the National Institute of Radiologic Sciences. The primary endpoint of this study was normal tissue morbidity, and secondary endpoints were local tumor control and patient survival. Of the 59 subjects enrolled, 57 were followed >6 months and analyzed. Results: Twenty-three patients (40%) developed neovascularmore » glaucoma, and three underwent enucleation for eye pain due to elevated intraocular pressure. Incidence of neovascular glaucoma was dependent on tumor size and site. Five patients had died at analysis, three of distant metastasis and two of concurrent disease. All but one patient, who developed marginal recurrence, were controlled locally. Six patients developed distant metastasis, five in the liver and one in the lung. Three-year overall survival, disease-free survival, and local control rates were 88.2%, 84.8%, and 97.4%, respectively. No apparent dose-response relationship was observed in either tumor control or normal tissue morbidity at the dose range applied. Conclusion: Carbon-ion radiotherapy can be applied to choroidal melanoma with an acceptable morbidity and sufficient antitumor effect, even with tumors of unfavorable size or site.« less

  14. Effect of trapping vascular endothelial growth factor-A in a murine model of dry eye with inflammatory neovascularization

    PubMed Central

    Kwon, Jin Woo; Choi, Jin A; Shin, Eun Young; La, Tae Yoon; Jee, Dong Hyun; Chung, Yeon Woong; Cho, Yang Kyung

    2016-01-01

    AIM To evaluate whether trapping vascular endothelial growth factor A (VEGF-A) would suppress angiogenesis and inflammation in dry eye corneas in a murine corneal suture model. METHODS We established two groups of animals, one with non-dry eyes and the other with induced dry eyes. In both groups, a corneal suture model was used to induce inflammation and neovascularization. Each of two groups was again divided into three subgroups according to the treatment; subgroup I (aflibercept), subgroup II (dexamethasone) and subgroup III (phosphate buffered saline, PBS). Corneas were harvested and immunohistochemical staining was performed to compare the extents of neovascularization and CD11b+ cell infiltration. Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and VEGF-A in the corneas. RESULTS Trapping VEGF-A with aflibercept resulted in significantly decreased angiogenesis and inflammation compared with the dexamethasone and PBS treatments in the dry eye corneas (all P<0.05), but with no such effects in non-dry eyes. The anti-inflammatory and anti-angiogenic effects of VEGF-A trapping were stronger than those of dexamethasone in both dry eye and non-dry eye corneas (all P<0.05). The levels of RNA expression of VEGF-A, TNF-alpha, and IL-6 in the aflibercept subgroup were significantly decreased compared with those in the PBS subgroup in the dry eye group. CONCLUSION Compared with non-dry eye corneas, dry eye corneas have greater amounts of inflammation and neovascularization and also have a more robust response to anti-inflammatory and anti-angiogenic agents after ocular surface surgery. Trapping VEGF-A is effective in decreasing both angiogenesis and inflammation in dry eye corneas after ocular surface surgery. PMID:27990354

  15. Suppression of Retinal Neovascularization in vivo by Inhibition of Vascular Endothelial Growth Factor (VEGF) Using Soluble VEGF-Receptor Chimeric Proteins

    NASA Astrophysics Data System (ADS)

    Aiello, Lloyd Paul; Pierce, Eric A.; Foley, Eliot D.; Takagi, Hitoshi; Chen, Helen; Riddle, Lavon; Ferrara, Napoleone; King, George L.; Smith, Lois E. H.

    1995-11-01

    The majority of severe visual loss in the United States results from complications associated with retinal neovascularization in patients with ischemic ocular diseases such as diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. Intraocular expression of the angiogenic protein vascular endothelial growth factor (VEGF) is closely correlated with neovascularization in these human disorders and with ischemia-induced retinal neovascularization in mice. In this study, we evaluated whether in vivo inhibition of VEGF action could suppress retinal neovascularization in a murine model of ischemic retinopathy. VEGF-neutralizing chimeric proteins were constructed by joining the extracellular domain of either human (Flt) or mouse (Flk) high-affinity VEGF receptors with IgG. Control chimeric proteins that did not bind VEGF were also used. VEGF-receptor chimeric proteins eliminated in vitro retinal endothelial cell growth stimulation by either VEGF (P < 0.006) or hypoxic conditioned medium (P < 0.005) without affecting growth under nonstimulated conditions. Control proteins had no effect. To assess in vivo response, animals with bilateral retinal ischemia received intravitreal injections of VEGF antagonist in one eye and control protein in the contralateral eye. Retinal neovascularization was quantitated histologically by a masked protocol. Retinal neovascularization in the eye injected with human Flt or murine Flk chimeric protein was reduced in 100% (25/25; P < 0.0001) and 95% (21/22; P < 0.0001) of animals, respectively, compared to the control treated eye. This response was evident after only a single intravitreal injection and was dose dependent with suppression of neovascularization noted after total delivery of 200 ng of protein (P < 0.002). Reduction of histologically evident neovascular nuclei per 6-um section averaged 47% ± 4% (P < 0.001) and 37% ± 2% (P < 0.001) for Flt and Flk chimeric proteins with maximal inhibitory effects of 77% and 66

  16. Dark and white lesions observed in central serous chorioretinopathy on optical coherence tomography angiography.

    PubMed

    De Bats, Flore; Cornut, Pierre-Loïc; Wolff, Benjamin; Kodjikian, Laurent; Mauget-Faÿsse, Martine

    2018-03-01

    To describe abnormal dark (hyposignal) and white (hypersignal) lesions observed on optical coherence tomography angiography in central serous chorioretinopathy. Prospective, multicenter, and descriptive study including patients with active or quiescent central serous chorioretinopathy. All patients had undergone a complete ophthalmic examination. Abnormal dark lesions were detected as "dark spots" and "dark areas" on optical coherence tomography angiography. A "dark spot" could correspond to six different abnormalities: pigment epithelium detachment, subretinal deposit, "Lucency" within surrounding subretinal fibrin, choroidal cavitation, choroidal excavation, and choroidal fluid. A "dark area" could be related to a serous retinal detachment or choriocapillary compression. Abnormal white lesions were also detected: A "white spot" could correspond with the leaking point on fluorescein angiography or with hyper-reflective dots; A "white filamentous pattern" at the Brüch's membrane level corresponded to abnormal choroidal neovascular vessels. A semiology is described using optical coherence tomography angiography in central serous chorioretinopathy as abnormal dark and white lesions. Multimodal imaging is mandatory in addition to optical coherence tomography angiography to diagnose non-neovascular retinal and choroidal central serous chorioretinopathy lesions. However, optical coherence tomography angiography alone is helpful in detecting choroidal neovascular membrane in central serous chorioretinopathy.

  17. Transport across the choroid plexus epithelium.

    PubMed

    Praetorius, Jeppe; Damkier, Helle Hasager

    2017-06-01

    The choroid plexus epithelium is a secretory epithelium par excellence. However, this is perhaps not the most prominent reason for the massive interest in this modest-sized tissue residing inside the brain ventricles. Most likely, the dominant reason for extensive studies of the choroid plexus is the identification of this epithelium as the source of the majority of intraventricular cerebrospinal fluid. This finding has direct relevance for studies of diseases and conditions with deranged central fluid volume or ionic balance. While the concept is supported by the vast majority of the literature, the implication of the choroid plexus in secretion of the cerebrospinal fluid was recently challenged once again. Three newer and promising areas of current choroid plexus-related investigations are as follows: 1 ) the choroid plexus epithelium as the source of mediators necessary for central nervous system development, 2 ) the choroid plexus as a route for microorganisms and immune cells into the central nervous system, and 3 ) the choroid plexus as a potential route for drug delivery into the central nervous system, bypassing the blood-brain barrier. Thus, the purpose of this review is to highlight current active areas of research in the choroid plexus physiology and a few matters of continuous controversy. Copyright © 2017 the American Physiological Society.

  18. Modern Diagnostic Techniques for the Assessment of Ocular Blood Flow in Myopia: Current State of Knowledge.

    PubMed

    Grudzińska, Ewa; Modrzejewska, Monika

    2018-01-01

    Myopia is the most common refractive error and the subject of interest of various studies assessing ocular blood flow. Increasing refractive error and axial elongation of the eye result in the stretching and thinning of the scleral, choroid, and retinal tissues and the decrease in retinal vessel diameter, disturbing ocular blood flow. Local and systemic factors known to change ocular blood flow include glaucoma, medications and fluctuations in intraocular pressure, and metabolic parameters. Techniques and tools assessing ocular blood flow include, among others, laser Doppler flowmetry (LDF), retinal function imager (RFI), laser speckle contrast imaging (LSCI), magnetic resonance imaging (MRI), optical coherence tomography angiography (OCTA), pulsatile ocular blood flowmeter (POBF), fundus pulsation amplitude (FPA), colour Doppler imaging (CDI), and Doppler optical coherence tomography (DOCT). Many researchers consistently reported lower blood flow parameters in myopic eyes regardless of the used diagnostic method. It is unclear whether this is a primary change that causes secondary thinning of ocular tissues or quite the opposite; that is, the mechanical stretching of the eye wall reduces its thickness and causes a secondary lower demand of tissues for oxygen. This paper presents a review of studies assessing ocular blood flow in myopes.

  19. Intravitreal triamcinolone with transpupillary therapy for subfoveal choroidal neovascularization in age related macular degeneration. A randomized controlled pilot study [ISRCTN74123635

    PubMed Central

    Agurto-Rivera, Ricardo; Diaz-Rubio, Jose; Torres-Bernal, Luis; Macky, Tamer A; Colina-Luquez, Juner; Papa-Oliva, Gabriela; Jager, Rama D; Martinez-Jardon, Susana; Fromow-Guerra, Jans; Quiroz-Mercado, Hugo

    2005-01-01

    Background To assess the effect of intravitreal triamcinolone acetonide (iTA) as an adjunctive treatment to transpupillary therapy (TTT) for new subfoveal choroidal neovascular membranes (CNV) in age-related macular degeneration (AMD). Methods This prospective randomized controlled pilot study comprised 26 patients scheduled to receive TTT, due to either absent indications for photodynamic therapy or financial issues. Patients were assigned into; Group A (n = 14) received TTT alone and Group B (n = 12) received iTA (4 mg) followed by TTT within one week. Follow ups were at 2 weeks, and 1, 3 and 6 months for; best-corrected visual acuity (BCVA) by ETDRS chart at 4 meters, intraocular pressures (IOP), fluorescein angiography (FAG), and central foveal thickness by optical coherence tomography (OCT). Results All 26 patients completed 6 months of follow ups. The average age for both groups was 74 years. Occult CNV formed 64% and 41%; classis/predominately classic 21% and 16.6%; and minimally classic 15% and 42.4% of group A and B respectively. At baseline; the mean BCVA was 0.045 for group A and 0.04 for group B; mean CNV size was 6.15 disc diameter (DD) and 2.44 DD; mean OCT foveal thickness was 513 um and 411 um for group A and B respectively with no statistical differences (P = 0.8, 0.07, and 0.19). At six months the proportion of patients gained ≥ 1 lines was 14% and 25% (P = 0.136) and stabilization was 86% and 66% (P = 0.336); the mean size of the CNV was 5.63 DD and 2.67 DD (P = 0.162); rate of CNV closure was 64% and 83% (P = 0.275); and the mean OCT central foveal thickness was 516.36 um and 453.67 um (P = 0.341), for group A and B respectively. Conclusion The use of iTA as an adjunctive to TTT for new subfoveal CNV in AMD showed a tendency towards better functional results. However due to the small sample size of the study a statistically significant results could not be reached. PMID:16309554

  20. Difference between age-related macular degeneration and polypoidal choroidal vasculopathy in the hereditary contribution of the A69S variant of the age-related maculopathy susceptibility 2 gene (ARMS2).

    PubMed

    Yanagisawa, Suiho; Kondo, Naoshi; Miki, Akiko; Matsumiya, Wataru; Kusuhara, Sentaro; Tsukahara, Yasutomo; Honda, Shigeru; Negi, Akira

    2011-01-01

    To investigate whether the A69S variant of the age-related maculopathy susceptibility 2 gene (ARMS2) has a different hereditary contribution in neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). We initially conducted a comparative genetic analysis of neovascular AMD and PCV, genotyping the ARMS2 A69S variant in 181 subjects with neovascular AMD, 198 subjects with PCV, and 203 controls in a Japanese population. Genotyping was conducted using TaqMan technology. Results were then integrated into a meta-analysis of previous studies representing an assessment of the association between the ARMS2 A69S variant and neovascular AMD and/or PCV, comprising a total of 3,828 subjects of Asian descent. The Q-statistic test was used to assess between-study heterogeneity. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a fixed effects model. The genetic effect of the A69S variant was stronger in neovascular AMD (allelic summary OR=3.09 [95% CI, 2.71-3.51], fixed effects p<0.001) than in PCV (allelic summary OR=2.13 [95% CI, 1.91-2.38], fixed effects p<0.001). The pooled risk allele frequency was significantly higher in neovascular AMD (64.7%) than in PCV (55.6%). The population attributable risks for the variant allele were estimated to be 43.9% (95% CI, 39.0%-48.4%) and 29.7% (95% CI, 25.4%-34.0%) for neovascular AMD and PCV, respectively. No significant between-study heterogeneity was observed in any statistical analysis in this meta-analysis. Our meta-analysis provides substantial evidence that the ARMS2 A69S variant confers a significantly higher risk of neovascular AMD than PCV. Furthermore, there is compelling evidence that the risk attributable to the A69S variant differs between geographic atrophy and neovascular AMD. Together with defining the molecular basis of susceptibility, understanding the relationships between this genomic region and disease subtypes will yield important insights

  1. Plaque radiotherapy for choroidal melanoma encircling the optic disc (circumpapillary choroidal melanoma).

    PubMed

    Sagoo, Mandeep S; Shields, Carol L; Mashayekhi, Arman; Freire, Jorge; Emrich, Jacqueline; Reiff, Jay; Komarnicky, Lydia; Shields, Jerry A

    2007-09-01

    To report results of plaque radiotherapy for choroidal melanoma that completely encircles the optic disc (circumpapillary melanoma). Retrospective medical record review over a 31-year period of 37 consecutive patients. The main outcome measures were treatment complications, long-term visual acuity, enucleation, tumor recurrence, metastasis, and death. The median patient age at treatment was 69 years (range, 20-86 years). The presenting complaint was visual loss in 19 eyes (51%), photopsia in 5 (14%), and visual field loss in 3 (8%). All tumors touched and encircled the optic disc for 360 degrees . The quadrantic location of the main tumor epicenter was superior in 8 eyes (22%), nasal in 10 (27%), inferior in 9 (24%), and temporal in 10 (27%). The median tumor basal diameter was 11 mm (range, 4.8-20 mm) and median tumor thickness was 3.6 mm (range, 1.8-14.8 mm). The optic disc was obscured to some extent by overhanging tumor in 19 cases (52%). The most commonly used isotope for plaque radiotherapy was iodine 125 (n = 34 cases; 92%), and a notched plaque design was used in 34 cases (92%). Planned adjunctive treatment included transpupillary thermotherapy in 17 cases (49%) and argon laser photocoagulation in 6 of 35 cases (17%) with follow-up. Of the 28 eyes with more than 5 months' follow-up (mean, 52 months; median, 46 months; range, 5-234 months), treatment complications included nonproliferative and proliferative retinopathy in 11 (39%) and 7 eyes (25%); maculopathy in 7 (25%); papillopathy in 9 eyes (32%); neovascular glaucoma in 5 (18%); and vitreous hemorrhage in 13 (46%). Pars plana vitrectomy was required in only 2 of 13 eyes (15%) with persistent vitreous hemorrhage. Long-term visual acuity of 20/200 or worse was observed in 13 eyes (62%), and 12 eyes (57%) lost more than 5 Snellen visual acuity lines, excluding 7 cases (25%) in which enucleation was necessary. Recurrence was noted in 4 cases (14%), of which 3 were treated with enucleation and 1 with

  2. Choroidal thickness in traumatic optic neuropathy.

    PubMed

    Lee, Ju-Yeun; Eo, Doo-Ri; Park, Kyung-Ah; Oh, Sei Yeul

    2017-12-01

    To examine the choroidal thickness in patients with indirect traumatic optic neuropathy (TON) Methods: Patients with unilateral traumatic optic neuropathy over a period of 4 years were included in this study. Horizontal and vertical enhanced-depth imaging (EDI) from spectral-domain optical coherence tomography (SD-OCT) scans of the fovea were obtained in patients with unilateral TON within 2 weeks of injury. The main outcome measure was the choroidal thickness at nine locations. The choroidal thickness was compared between affected and unaffected eyes in the TON group, and the mean difference in the choroidal thickness in both eyes was compared between TON and control groups. A total of 16 patients and 20 control subjects were included. The choroidal thickness at horizontal, vertical and average subfoveal, inner temporal, and outer inferior locations was significantly thicker (13-23%) in affected eyes than in unaffected fellow eyes (p = 0.042, 0.046, 0.024, 0.013, 0.018, and 0.027, respectively). The mean difference value between choroidal thickness measurements in both eyes was significantly larger in the TON group than in the control group at the horizontal, vertical and average subfoveal, inner temporal, inner nasal, inner superior, inner inferior, and outer superior locations (p = 0.001, 0.011, <0.001, 0.001, 0.033, 0.014, 0.011, and 0.014, respectively). The choroidal thickness at subfoveal locations showed no statistical difference between TON and control eyes (p > 0.05). Eyes affected by TON showed a regionally thicker choroid than unaffected fellow eye. This thick choroid might be due to impaired blood circulation and vascular remodeling of the optic nerve head and choroid. These results help to better understand the pathophysiology of TON.

  3. Intracameral air injection during Ahmed glaucoma valve implantation in neovascular glaucoma for the prevention of tube obstruction with blood clot: Case Report.

    PubMed

    Hwang, Sung Ha; Yoo, Chungkwon; Kim, Yong Yeon; Lee, Dae Young; Nam, Dong Heun; Lee, Jong Yeon

    2017-12-01

    Glaucoma drainage implant surgery is a treatment option for the management of neovascular glaucoma. However, tube obstruction by blood clot after Ahmed glaucoma valve (AGV) implantation is an unpredictable clinically challenging situation. We report 4 cases using intracameral air injection for the prevention of the tube obstruction of AGV by blood clot. The first case was a 57-year-old female suffering from ocular pain because of a tube obstruction with blood clot after AGV implantation in neovascular glaucoma. Surgical blood clot removal was performed. However, intractable bleeding was noted during the removal of the blood clot, and so intracameral air injection was performed to prevent a recurrent tube obstruction. After the procedure, although blood clots formed around the tube, the tube opening where air could touch remained patent. In 3 cases of neovascular glaucoma with preoperative severe intraocular hemorrhages, intracameral air injection and AGV implantation were performed simultaneously. In all 3 cases, tube openings were patent. It appears that air impeded the blood clots formation in front of the tube opening. Intracameral air injection could be a feasible option to prevent tube obstruction of AGV implant with a blood clot in neovascular glaucoma with high risk of tube obstruction. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  4. Clinical features of ocular toxoplasmosis in Korean patients.

    PubMed

    Park, Young-Hoon; Han, Jae-Hyung; Nam, Ho-Woo

    2011-06-01

    We report here the records of 10 consecutive Korean patients (10 eyes) with ocular toxoplasmosis which showed the typical clinical manifestations with seropositivity for Toxoplasma gondii specific IgG antibodies by micro-ELISA between 2006 and 2010. Nine patients were males and 1 was female; their age was 50.5 ± 13.8 years. The most common accompanying signs were vitritis (100%), anterior uveitis (70%), and scattered white deposit (80%). Pre-existing retinochoroidal scar was found in 1 (10%) patient. All patients received antiparasitic chemotherapy and systemic corticosteroid treatment, which resolved the presenting attack and recovered the visual acuity better than initial one in 9 patients and worse in 1. Optic atrophy, cataract, and retinal neovascularization were observed during the follow-up period and recurrence was detected in 3 eyes (30%) 6 to 20 months after the initial attack. In Korea, although rarely detected and reported, ocular toxoplasmosis needs more attention in clinical field of retinal diseases.

  5. Visual and anatomic outcomes of golf ball-related ocular injuries.

    PubMed

    Park, S J; Park, K H; Heo, J W; Woo, S J

    2014-03-01

    To investigate the characteristics and prognoses of golf ball-related ocular injuries (GROIs) using standardized terminology, classification, and scoring systems. Twenty-two GROI patients were assessed using the Birmingham Eye Trauma Terminology, Ocular Trauma Classification Group (OTCG) classification, and Ocular Trauma Score. Globe preservation and final visual acuity (FVA) were assessed according to the injury severity categorical designation. Fourteen patients were injured on golf courses and eight on driving ranges. Nine patients (40.9%) had open-globe injuries (five ruptures (22.7%), four penetrating injuries (18.2%)). All rupture cases required enucleation, whereas penetrating injury cases did not (the FVA ranged from 20/100 to no light perception). In open-globe injuries, wearing glasses protected against rupture (P=0.008). Thirteen patients sustained closed-globe injuries that were accompanied by lens subluxation (38.5%), choroidal rupture (30.8%), macular commotio retinae (38.5%), and traumatic optic neuropathy (7.7%). Twelve (54.5%) patients had orbital wall fractures. The mean number of related surgeries required was 1.5±1.7 across all patients. Eyes with GROIs had devastating FVA and globe preservation status, especially those with open-globe injuries. Observing golf rules and improving driving-range facilities are essential for preventing GROIs. Protective eyewear may reduce ocular damage from GROIs, especially globe rupture.

  6. Role of miR-132 in Angiogenesis after Ocular Infection with Herpes Simplex Virus

    PubMed Central

    Mulik, Sachin; Xu, John; Reddy, Pradeep B.J.; Rajasagi, Naveen K.; Gimenez, Fernanda; Sharma, Shalini; Lu, Patrick Y.; Rouse, Barry T.

    2013-01-01

    MicroRNAs (miRNAs) are small regulatory molecules that control diverse biological processes that include angiogenesis. Herpes simplex virus (HSV) causes a chronic immuno-inflammatory response in the eye that may result in corneal neovascularization during blinding immunopathological lesion stromal keratitis (SK). miR-132 is a highly conserved miRNA that is induced in endothelial cells in response to growth factors, such as vascular endothelial growth factor (VEGF). In this study, we show that miR-132 expression was up-regulated (10- to 20-fold) after ocular infection with HSV, an event that involved the production of both VEGF-A and IL-17. Consequently, blockade of VEGF-A activity using soluble VEGF receptor 1 resulted in significantly lower levels of corneal miR-132 after HSV infection. In addition, low levels of corneal miR-132 were detected in IL-17 receptor knockout mice after HSV infection. In vivo silencing of miR-132 by the provision of anti-miR-132 (antagomir-132) nanoparticles to HSV-infected mice led to reduced corneal neovascularization and diminished SK lesions. The anti-angiogenic effect of antagomir-132 was reflected by a reduction in angiogenic Ras activity in corneal CD31-enriched cells (presumably blood vessel endothelial cells) during SK. To our knowledge, this is one of the first reports of miRNA involvement in an infectious ocular disease. Manipulating miRNA expression holds promise as a therapeutic approach to control an ocular lesion that is an important cause of human blindness. PMID:22659469

  7. Development and origins of zebrafish ocular vasculature.

    PubMed

    Kaufman, Rivka; Weiss, Omri; Sebbagh, Meyrav; Ravid, Revital; Gibbs-Bar, Liron; Yaniv, Karina; Inbal, Adi

    2015-03-27

    The developing eye receives blood supply from two vascular systems, the intraocular hyaloid system and the superficial choroidal vessels. In zebrafish, a highly stereotypic and simple set of vessels develops on the surface of the eye prior to development of choroidal vessels. The origins and formation of this so-called superficial system have not been described. We have analyzed the development of superficial vessels by time-lapse imaging and identified their origins by photoconversion experiments in kdrl:Kaede transgenic embryos. We show that the entire superficial system is derived from a venous origin, and surprisingly, we find that the hyaloid system has, in addition to its previously described arterial origin, a venous origin for specific vessels. Despite arising solely from a vein, one of the vessels in the superficial system, the nasal radial vessel (NRV), appears to acquire an arterial identity while growing over the nasal aspect of the eye and this happens in a blood flow-independent manner. Our results provide a thorough analysis of the early development and origins of zebrafish ocular vessels and establish the superficial vasculature as a model for studying vascular patterning in the context of the developing eye.

  8. MULTIMODAL IMAGING OF ANGIOID STREAKS ASSOCIATED WITH TURNER SYNDROME.

    PubMed

    Chiu, Bing Q; Tsui, Edmund; Hussnain, Syed Amal; Barbazetto, Irene A; Smith, R Theodore

    2018-02-13

    To report multimodal imaging in a novel case of angioid streaks in a patient with Turner syndrome with 10-year follow-up. Case report of a patient with Turner syndrome and angioid streaks followed at Bellevue Hospital Eye Clinic from 2007 to 2017. Fundus photography, fluorescein angiography, and optical coherence tomography angiography were obtained. Angioid streaks with choroidal neovascularization were noted in this patient with Turner syndrome without other systemic conditions previously correlated with angioid streaks. We report a case of angioid streaks with choroidal neovascularization in a patient with Turner syndrome. We demonstrate that angioid streaks, previously associated with pseudoxanthoma elasticum, Ehlers-Danlos syndrome, Paget disease of bone, and hemoglobinopathies, may also be associated with Turner syndrome, and may continue to develop choroidal neovascularization, suggesting the need for careful ophthalmic examination in these patients.

  9. Topical Delivery of Anti-VEGF Drugs to the Ocular Posterior Segment Using Cell-Penetrating Peptides.

    PubMed

    de Cogan, Felicity; Hill, Lisa J; Lynch, Aisling; Morgan-Warren, Peter J; Lechner, Judith; Berwick, Matthew R; Peacock, Anna F A; Chen, Mei; Scott, Robert A H; Xu, Heping; Logan, Ann

    2017-05-01

    To evaluate the efficacy of anti-VEGF agents for treating choroidal neovascularization (CNV) when delivered topically using novel cell-penetrating peptides (CPPs) compared with delivery by intravitreal (ivit) injection. CPP toxicity was investigated in cell cultures. Ivit concentrations of ranibizumab and bevacizumab after topical administration were measured using ELISA. The biological efficacy of topical anti-VEGF + CPP complexes was compared with ivit anti-VEGF injections using an established model of CNV. CPPs were nontoxic in vitro. In vivo, after topical eye drop delivery, CPPs were present in the rat anterior chamber within 6 minutes. A single application of CPP + bevacizumab eye drop delivered clinically relevant concentrations of bevacizumab to the posterior chamber of the rat eye in vivo. Similarly, clinically relevant levels of CPP + ranibizumab and CPP + bevacizumab were detected in the porcine vitreous and retina ex vivo. In an established model of CNV, mice treated with either a single ivit injection of anti-VEGF, twice daily CPP + anti-VEGF eye drops or daily dexamethasone gavage for 10 days all had significantly reduced areas of CNV when compared with lasered eyes without treatment. CPPs are nontoxic to ocular cells and can be used to deliver therapeutically relevant doses of ranibizumab and bevacizumab by eye drop to the posterior segment of mouse, rat, and pig eyes. The CPP + anti-VEGF drug complexes were cleared from the retina within 24 hours, suggesting a daily eye drop dosing regimen. Daily, topically delivered anti-VEGF with CPP was as efficacious as a single ivit injection of anti-VEGF in reducing areas of CNV in vivo.

  10. Efficacy of treat-and-extend regimen with aflibercept for pachychoroid neovasculopathy and Type 1 neovascular age-related macular degeneration.

    PubMed

    Matsumoto, Hidetaka; Hiroe, Takashi; Morimoto, Masahiro; Mimura, Kensuke; Ito, Arisa; Akiyama, Hideo

    2018-03-01

    To evaluate the efficacy of intravitreal aflibercept therapy using a treat-and-extend regimen on treatment-naïve pachychoroid neovasculopathy (PNV) and Type 1 neovascular age-related macular degeneration (AMD). We retrospectively studied 42 eyes with PNV and 60 eyes with Type 1 neovascular AMD. We assessed best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), and total number of injections over 2 years. The BCVA and CMT improvements during the 2-year treatment period did not differ significantly between PNV and AMD; however, CCT decreased significantly in PNV than in AMD (P<0.05). Management of PNV required significantly fewer injections than AMD during the 2-year period (P<0.05). There were no significant differences in BCVA, CMT and CCT changes between PNV with and without polypoidal lesions (28 vs. 14 eyes) during the 2 year period. Significantly fewer injections were needed for PNV with polypoidal lesions than for PNV without (P<0.01). There were no significant differences in BCVA, CMT and CCT changes, or in the number of injections during the 2-year treatment period, between AMD with and without polypoidal lesions (30 vs. 30 eyes). Treat-and-extend regimen of intravitreal aflibercept injection may be equally effective in terms of improvement of BCVA and exudative changes both in eyes with PNV and those with Type 1 neovascular AMD requiring fewer injections for the former. Among eyes with PNV, those with polypoidal lesions needed fewer injections than those without polypoidal lesions.

  11. Macular Choroidal Thickness May Be the Earliest Determiner to Detect the Onset of Diabetic Retinopathy in Patients with Prediabetes: A Prospective and Comparative Study.

    PubMed

    Yazgan, Serpil; Arpaci, Dilek; Celik, Haci Ugur; Dogan, Mustafa; Isık, Irem

    2017-07-01

    To evaluate the macular and peripapillary choroidal thickness and retinal volume in prediabetes. This prospective comparative study included 53 patients with prediabetes and 53 age- and sex-matched healthy subjects. Only right eyes were selected. Choroidal thicknesses (CT) and retinal volume were measured by optical coherence tomography. Macular CT was measured at the seven points including macular center, 1, 2, and 3 mm distances along the temporal and nasal scans. Peripapillary CT was measured at the eight points of the optic disk area. Systemic and laboratory findings of the subjects were also recorded. There were no significant differences in blood pressures, ocular findings including intraocular pressure, visual acuity, and refractive powers, and macular volumes between the two groups (p > 0.005). Macular and peripapillary CT at all measuring points, body mass index (BMI), fasting blood glucose (FBG), hemoglobinA1C, and lipid profile were significantly higher in prediabetic patients (p < 0.05). There was a significant positive correlation between all points of macular choroidal thicknesses with BMI, FBG, and hemoglobin A1C (p < 0.05). Prediabetic factors including impaired FBG, increased hemoglobinA1C, and BMI are independent risk factors for increase in choroidal thickness. Increased macular choroidal thickness may be the earliest determiner to detect the onset of diabetic retinopathy in prediabetes.

  12. Fourier domain optical coherence tomographic and auto-fluorescence findings in indeterminate choroidal melanocytic lesions.

    PubMed

    Singh, Arun D; Belfort, Rubens N; Sayanagi, Kaori; Kaiser, Peter K

    2010-04-01

    To compare detection rates of drusen and subretinal fluid by Fourier domain optical coherence tomography (FD OCT) and orange pigment by fundus autofluorescence (FAF) with ophthalmoscopy in indeterminate choroidal melanocytic lesions. In a consecutive case series of 38 patients with indeterminate choroidal melanocytic lesion that would have been categorised as a small tumour according to the size-based nomenclature used in the Collaborative Ocular Melanoma Study, each eye was submitted to ophthalmoscopic examination, FD OCT and FAF. The presence of drusen, subretinal fluid and orange pigment was recorded for each lesion by a single observer at the time of initial ophthalmoscopic evaluation and on fundus photographs. FD OCT and autofluorescence images were reviewed in all cases in a masked fashion. The ophthalmoscopic examination revealed drusen in 42%, subretinal fluid in 53% and orange pigment in 50% of patients. FD-OCT detected drusen in 45% and subretinal fluid in 58% of cases, and FAF detected orange pigment in 58% of cases. Based on the McNemar test, none of the differences were statistically significant at the 0.05 level. FD OCT and FAF complement clinical examination by verifying and documenting retinal and RPE changes associated with indeterminate choroidal melanocytic lesions. The detection rates by FD OCT and FAF of important qualitative prognostic factors appear to be equivalent to ophthalmoscopy by a trained observer. Once validated in a larger number of patients, FD OCT and FAF findings can be incorporated into diagnostic algorithms.

  13. [Rapid imaging in orbito-ocular pathology. Contribution of gadolinium].

    PubMed

    Pigeau, I; Legeais, J M; D'Hermies, F; Fayet, B; Leport, M; Abenhaim, A; Guinet, C; Levy, C; Renard, G; Vadrot, D

    1990-01-01

    To evaluate Gradient-Echo Imaging (GEI) in orbito-ocular pathology, 15 volunteers and 34 patients (40 lesions) were examined with GEA T1 and GEA T2 (0.5 T). Results were compared with SE T1 in all cases, with SE T2 in 20 cases and with other imaging modalities (CT). 30 patients were examined before and after injection of gadolinium. Final diagnosis was obtained by surgery or biopsy in 24 cases or by combined results of imaging and clinical findings in 16 cases. Compared with SE, GEA demonstrated a better visualisation of optic nerve, orbital muscles, choroidal-retinal layer, lens capsule and episclera and a better detection of small lesions. It is very helpful for characterisation of lesions containing hemorrhages or paramagnetic components (melanine, gadolinium) or of vascular nature (angioma). Gadolinium was useful for detection of small lesions or characterisation of a few lesions. Thus GEA seems to be an efficient method for the evaluation of orbito-ocular pathology.

  14. Characteristics of patients with neovascular age-related macular degeneration who are non-responders to intravitreal aflibercept.

    PubMed

    Hara, Chikako; Wakabayashi, Taku; Toyama, Hiroshi; Fukushima, Yoko; Sayanagi, Kaori; Sato, Shigeru; Sakaguchi, Hirokazu; Nishida, Kohji

    2018-06-15

    To investigate the frequency and patient characteristics that influence anatomic response of intravitreal aflibercept in treatment-naïve neovascular age-related macular degeneration (AMD). Retrospective, interventional, consecutive case series. Three hundred and sixty-five eyes of 365 patients with AMD who underwent 3 monthly intravitreal aflibercept treatments with follow-up for at least 12 months were investigated. Treatment response was evaluated as follows. Responders were defined as those with complete resolution of exudation, including intraretinal oedema, subretinal fluid and pigment epithelial detachment, or more than a 100 µm decrease of central retinal thickness at 3 months compared with baseline. Non-responders were defined as patients exhibiting an increase in exudation or a decreased central retinal thickness of less than 100 µm. Nineteen (5.2%) of 365 eyes were identified as non-responders. The remaining were responders to intravitreal aflibercept. The non-responders group was significantly associated with choroidal vascular hyperpermeability on indocyanine green angiography and lower frequency of subretinal hyper-reflective materials on optical coherence tomography. The central choroidal thickness at baseline and after 3 monthly injections tended to be thicker in the non-responder group than the responder group, although the differences did not meet statistical significance (p=0.066 and p=0.051, respectively). Additional treatments with either intravitreal ranibizumab or PDT in combination with aflibercept were effective in 15 (79%) of 19 non-responders. Intravitreal aflibercept is effective for treating eye pathology in most naïve AMD cases. However, non-responsiveness may occur in small subgroup of patients with choroidal vascular hyperpermeability. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly

  15. Bright light induces choroidal thickening in chickens.

    PubMed

    Lan, Weizhong; Feldkaemper, Marita; Schaeffel, Frank

    2013-11-01

    Bright light is a potent inhibitor of myopia development in animal models. Because development of refractive errors has been linked to changes in choroidal thickness, we have studied in chickens whether bright light may exert its effects on myopia also through changes in choroidal thickness. Three-day-old chickens were exposed to "bright light" (15,000 lux; n = 14) from 10 AM to 4 PM but kept under "normal light" (500 lux) during the remaining time of the light phase for 5 days (total duration of light phase 8 AM to 6 PM). A control group (n = 14) was kept under normal light during the entire light phase. Choroidal thickness was measured in alert, hand-held animals with optical coherence tomography at 10 AM, 4 PM, and 8 PM every day. Complete data sets were available for 12 chicks in bright light group and nine in normal light group. The striking inter-individual variability in choroidal thickness (coefficient of variance: 23%) made it necessary to normalize changes to the individual baseline thickness of the choroid. During the 6 hours of exposure to bright light, choroidal thickness decreased by -5.2 ± 4.0% (mean ± SEM). By contrast, in the group kept under normal light, choroidal thickness increased by +15.4 ± 4.7% (difference between both groups p = 0.003). After an additional 4 hours, choroidal thickness increased also in the "bright light group" by +17.8 ± 3.5%, while there was little further change (+0.6 ± 4.0%) in the "normal light group" (difference p = 0.004). Finally, the choroid was thicker in the "bright light group" (+7.6 ± 26.0%) than in the "normal light group" (day 5: -18.6 ± 26.9%; difference p = 0.036). Bright light stimulates choroidal thickening in chickens, although the response is smaller than with experimentally imposed myopic defocus, and it occurs with some time delay. It nevertheless suggests that choroidal thickening is also involved in myopia inhibition by bright light.

  16. [In vivo measurement of ocular circulation with the laser speckle method--development of apparatus and application in ophthalmological research].

    PubMed

    Araie, M

    1999-12-01

    We have developed an apparatus utilizing laser speckle phenomenon which can measure the peripheral circulation in the iris, choroid, retina and optic nerve head (ONH) and blood velocity through retinal vessels in the living eye non-invasively and quantitatively. A blue-component argon laser (wavelength 488 nm) was used for measurement of peripheral circulation in the retina and a diode laser (wavelength 808 nm) for measurements of peripheral circulation in the iris, posterior choroid and ONH, and measurement of centerline blood velocity through retinal vessels. A fundus camera (TRC-WT 3, Topcon) was equipped with a laser source and an image sensor where the speckle pattern from the fundus appears, and the data were analyzed with a personal computer to give a normalized blur (NB) value or a square blur rate (SBR) value, both quantitative indices of blood velocity. The NB value, whose computation requires much less time, was adopted to evaluate peripheral circulation because of non-linear correlation between the NB and actual blood velocity in the range above 20 mm/sec. The SBR value, whose computation requires a longer time, was adopted for measurement of blood velocity through retinal vessels. Measurement field in the living eye was 1.06 x 1.06 mm at its maximum and reproducibility index of the in vivo measurement in the rabbit iris, choroid, retina, and ONH was approximately 10%. When blood flow was changed by intraocular pressure (IOP) change in rabbit eyes, NB values obtained from the iris, choroid, and retina showed a significant correlation with the blood flow simultaneously determined with the colored microsphere technique in the same eye, and the NB obtained from the ONH also correlated with the blood flow determined with the H2 gas clearance method. Stepwise reduction in the ocular perfusion pressure (OPP) by stepwise increment of IOP resulted in proportional reduction in the iris- and choroid-NB. On the other hand, the retina- or ONH-NB remained almost

  17. CHOROIDAL MELANOMA IN A PATIENT WITH WAARDENBURG SYNDROME.

    PubMed

    Itty, Sujit; Richter, Elizabeth R; McCannel, Tara A

    2015-01-01

    To report a case of choroidal malignant melanoma in a patient with Waardenburg syndrome and bilateral choroidal pigmentary abnormalities. Clinical examination and multimodal imaging of the case. A 45-year-old woman presented with asymptomatic flat choroidal pigmentation abnormalities in both eyes. A choroidal lesion was identified in the inferotemporal periphery of the left eye arising from an area of hyperpigmentation; ultrasonography findings were consistent with a choroidal melanoma. The patient endorsed a personal and family history of premature graying of hair and was identified to have dystopia canthorum consistent with the diagnosis of Waardenburg syndrome. The authors present the first reported case of concurrent Waardenburg syndrome and choroidal malignant melanoma. This cooccurrence may suggest that the relative hyperpigmented regions in affected fundi may be abnormal and should be monitored closely for the development of choroidal melanoma.

  18. Material Properties of Human Ocular Tissue at 7-µm Resolution.

    PubMed

    Rohrbach, Daniel; Ito, Kazuyo; Lloyd, Harriet O; Silverman, Ronald H; Yoshida, Kenji; Yamaguchi, Tadashi; Mamou, Jonathan

    2017-09-01

    Quantitative assessment of the material properties of ocular tissues can provide valuable information for investigating several ophthalmic diseases. Quantitative acoustic microscopy (QAM) offers a means of obtaining such information, but few QAM investigations have been conducted on human ocular tissue. We imaged the optic nerve (ON) and iridocorneal angle in 12-µm deparaffinized sections of the human eye using a custom-built acoustic microscope with a 250-MHz transducer (7-µm lateral resolution). The two-dimensional QAM maps of ultrasound attenuation (α), speed of sound ( c), acoustic impedance ( Z), bulk modulus ( K), and mass density (ρ) were generated. Scanned samples were then stained and imaged by light microscopy for comparison with QAM maps. The spatial resolution and contrast of scanning acoustic microscopy (SAM) maps were sufficient to resolve anatomic layers of the retina (Re); anatomic features in SAM maps corresponded to those seen by light microscopy. Significant variations of the acoustic parameters were found. For example, the sclera was 220 MPa stiffer than Re, choroid, and ON tissue. To the authors' knowledge, this is the first systematic study to assess c, Z, K, ρ, and α of human ocular tissue at the high ultrasound frequencies used in this study.

  19. Posture changes and subfoveal choroidal blood flow.

    PubMed

    Longo, Antonio; Geiser, Martial H; Riva, Charles E

    2004-02-01

    To evaluate the effect of posture change on subfoveal choroidal blood flow (ChBF) in normal volunteers. The pulsatile, nonpulsatile, and mean ChBF were measured with laser Doppler flowmetry in 11 healthy volunteers with a mean age of 32 +/- 13 (SD) years. The posture of the subjects was changed from standing (90 degrees ), to supine (-8 degrees ), and back to standing, with a mechanically driven table. During the whole experimental procedure, ChBF and heart rate (HR) were continuously recorded. After 30 seconds in standing position, the subjects were tilted to supine during approximately 30 seconds. They remained in this position for approximately 2 minutes, after which they were tilted back to the standing position (recovery), where they remained for another approximately 2 minutes. Systemic brachial artery blood pressure (BP) was measured in the baseline, supine, and recovery positions. This procedure was repeated to measure the intraocular pressure (IOP) at the different postures. Mean BP did not change significantly throughout the experimental procedure. As the body was tilted from standing to supine, HR decreased by 16% (P < 0.0004), IOP increased by 29% (P < 0.001), and mean ChBF increased by 11% (P < 0.01). The increase in ChBF was primarily due to an increase in the nonpulsatile component of the blood velocity. Based on previously reported experimental data that indicate that the ocular perfusion pressure increases less than predicted by purely hydrostatic considerations when the body is tilted from the standing to the supine position, the observed increase in ChBF suggests a passive response of the choroidal circulation to the posture change.

  20. Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq.

    PubMed

    Whitmore, S Scott; Wagner, Alex H; DeLuca, Adam P; Drack, Arlene V; Stone, Edwin M; Tucker, Budd A; Zeng, Shemin; Braun, Terry A; Mullins, Robert F; Scheetz, Todd E

    2014-12-01

    Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with

  1. Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq

    PubMed Central

    Whitmore, S. Scott; Wagner, Alex H.; DeLuca, Adam P.; Drack, Arlene V.; Stone, Edwin M.; Tucker, Budd A.; Zeng, Shemin; Braun, Terry A.; Mullins, Robert F.; Scheetz, Todd E.

    2014-01-01

    Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell-types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with

  2. Effects of Dorzolamide on Retinal and Choroidal Blood Flow in the DBA/2J Mouse Model of Glaucoma

    PubMed Central

    Chandra, Saurav; Muir, Eric R.; Deo, Kaiwalya; Kiel, Jeffrey W.; Duong, Timothy Q.

    2016-01-01

    Purpose To test the hypothesis that acute topical dorzolamide (DZ) decreases intraocular pressure (IOP) and increases retinal and choroidal blood flow in the DBA/2J mouse model of glaucoma. Methods Retinal and choroidal blood flow were measured in 4- and 9-month-old DBA/2J mice, and 4-month C57BL/6 (control) mice under isoflurane anesthesia using magnetic resonance imaging. Ocular blood flow was measured at baseline, and 1 and 2 hours after topical dorzolamide. Intraocular pressure was measured using a rebound tonometer in a subset of animals at the same time points. Results Baseline IOP in the 4-month-old DBA/2J mice and C57BL/6 mice was not significantly different (P > 0.05), and IOP in both groups was less than in the 9-month-old DBA/2J mice (P < 0.05 for both). Compared to baseline, dorzolamide reduced IOP at 1 and 2 hours after dorzolamide in the 4- (P < 0.05) and 9-month-old (P < 0.01) DBA/2J mice, but not in the C57BL/6J mice (P > 0.05). Baseline retinal blood flow was lower in the 4-month and 9-month-old DBA/2J mice compared with the 4-month-old C57BL/6J mice (P < 0.05). Baseline choroidal blood flow in the 9-month-old DBA/2J mice was less than in the C57BL/6J mice (P < 0.05). Compared with baseline, both retinal and choroidal blood flow increased at 1-hour post-dorzolamide and remained elevated 2 hours later in the 9-month-old DBA/2J mice (P < 0.05). Conclusions Dorzolamide lowers IOP and raises retinal and choroidal blood flow in older DBA/2J mice, consistent with the study hypothesis. PMID:26934140

  3. Role of miR-132 in angiogenesis after ocular infection with herpes simplex virus.

    PubMed

    Mulik, Sachin; Xu, John; Reddy, Pradeep B J; Rajasagi, Naveen K; Gimenez, Fernanda; Sharma, Shalini; Lu, Patrick Y; Rouse, Barry T

    2012-08-01

    MicroRNAs (miRNAs) are small regulatory molecules that control diverse biological processes that include angiogenesis. Herpes simplex virus (HSV) causes a chronic immuno-inflammatory response in the eye that may result in corneal neovascularization during blinding immunopathological lesion stromal keratitis (SK). miR-132 is a highly conserved miRNA that is induced in endothelial cells in response to growth factors, such as vascular endothelial growth factor (VEGF). In this study, we show that miR-132 expression was up-regulated (10- to 20-fold) after ocular infection with HSV, an event that involved the production of both VEGF-A and IL-17. Consequently, blockade of VEGF-A activity using soluble VEGF receptor 1 resulted in significantly lower levels of corneal miR-132 after HSV infection. In addition, low levels of corneal miR-132 were detected in IL-17 receptor knockout mice after HSV infection. In vivo silencing of miR-132 by the provision of anti-miR-132 (antagomir-132) nanoparticles to HSV-infected mice led to reduced corneal neovascularization and diminished SK lesions. The anti-angiogenic effect of antagomir-132 was reflected by a reduction in angiogenic Ras activity in corneal CD31-enriched cells (presumably blood vessel endothelial cells) during SK. To our knowledge, this is one of the first reports of miRNA involvement in an infectious ocular disease. Manipulating miRNA expression holds promise as a therapeutic approach to control an ocular lesion that is an important cause of human blindness. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  4. Anterior but not posterior choroid changed before and during Valsalva manoeuvre in healthy Chinese: a UBM and SS-OCT study

    PubMed Central

    Li, Fei; Gao, Kai; Li, Xingyi; Chen, Shida; Huang, Wenbin; Zhang, Xiulan

    2017-01-01

    Purpose To determine if the anterior choroid is involved in ocular change during the Valsalva manoeuvre (VM). Materials and methods Fifty-three healthy volunteers aged 18–65 years with normal visual field test results and no history of intraocular pressure (IOP) exceeding 21 mm Hg were recruited. Anterior and posterior choroidal changes before and during VM were recorded by ultrasound microscope and swept-source optical coherence tomography, respectively. Parameters of the anterior segment included ciliary body thickness (CBT0), thickness of the choroid at a distance of 4 mm from the root of the iris (CT4), anterior placement of the ciliary body (APCB) and trabecular–ciliary angle (TCA). Thickness of different layers of retina and posterior choroid were also measured and compared before and during VM. IOP, blood pressure (BP), heart rate (HR), axial length, spherical equivalent refractive error and pupil diameter (PD) were also recorded and analysed. Results VM caused elevated IOP, systolic BP, diastolic BP and increased HR. There was a significant increase in anterior parameters including CBT0, CT4 and APCB (p<0.001), but not in TCA or PD (p>0.05). The mean change of CBT0, CT4 and APCB were: from 1.00±0.09 mm to 1.11±0.10 mm (p<0.001), from 0.29±0.04 mm to 0.36±0.05 mm (p<0.001), from 0.76±0.11 mm to 0.88±0.13 mm (p<0.001), respectively. However, there is no significant change in posterior choroid (from 215.74±60.23 µm to 214.82±61.32 µm, p=0.17). Conclusion We found that VM did not affect the posterior choroid, but it did cause thickening of the anterior choroid and the ciliary body, both of which led to a larger anterior placement of the ciliary body and a narrowed anterior chamber. The anterior (but not the posterior) choroid could be related to IOP elevation and a narrowed anterior chamber in primary angle closure diseases. PMID:28432110

  5. Visual and anatomic outcomes of golf ball-related ocular injuries

    PubMed Central

    Park, S J; Park, K H; Heo, J W; Woo, S J

    2014-01-01

    Aims To investigate the characteristics and prognoses of golf ball-related ocular injuries (GROIs) using standardized terminology, classification, and scoring systems. Methods Twenty-two GROI patients were assessed using the Birmingham Eye Trauma Terminology, Ocular Trauma Classification Group (OTCG) classification, and Ocular Trauma Score. Globe preservation and final visual acuity (FVA) were assessed according to the injury severity categorical designation. Results Fourteen patients were injured on golf courses and eight on driving ranges. Nine patients (40.9%) had open-globe injuries (five ruptures (22.7%), four penetrating injuries (18.2%)). All rupture cases required enucleation, whereas penetrating injury cases did not (the FVA ranged from 20/100 to no light perception). In open-globe injuries, wearing glasses protected against rupture (P=0.008). Thirteen patients sustained closed-globe injuries that were accompanied by lens subluxation (38.5%), choroidal rupture (30.8%), macular commotio retinae (38.5%), and traumatic optic neuropathy (7.7%). Twelve (54.5%) patients had orbital wall fractures. The mean number of related surgeries required was 1.5±1.7 across all patients. Conclusion Eyes with GROIs had devastating FVA and globe preservation status, especially those with open-globe injuries. Observing golf rules and improving driving-range facilities are essential for preventing GROIs. Protective eyewear may reduce ocular damage from GROIs, especially globe rupture. PMID:24384962

  6. Choroidal metastasis from primary bone leiomyosarcoma.

    PubMed

    Cristina, Nieto Gómez; Francisco, Escudero Domínguez; Vanesa, Rivero Gutiérrez; Fernando, Cruz González; Luis, Cacharro Moras; Emiliano, Hernández Galilea

    2015-10-01

    Choroidal metastases, the most common form of intraocular malignancies, are principally caused by primary tumors from breast, lung, and gastrointestinal tract. These lesions are mostly symptomatic and rarely detected incidentally in the extension study of a previously diagnosed tumor. Leiomyosarcoma is a neoplasm of mesenchymal cells with smooth muscle differentiation and represents the most prevalent soft-tissue sarcoma. Leiomyosarcoma is a notably rare tumor in ophthalmic region. We report a case of primary bone leiomyosarcoma metastatic to the choroid that was treated with chemotherapy and surgery. Although three cases of choroidal metastasis from leiomyosarcomas have been already reported, to our knowledge this is the first case of choroidal metastasis from primary bone leiomyosarcoma.

  7. Ocular findings in coal miners diagnosed with pneumoconiosis.

    PubMed

    Ayar, Orhan; Orcun Akdemir, Mehmet; Erboy, Fatma; Yazgan, Serpil; Hayri Ugurbas, Suat

    2017-06-01

    Our study aimed at evaluating ocular findings and structural changes in coal mine workers who were chronically exposed to coal mine dust and diagnosed with pneumoconiosis. Ocular findings of 161 eyes of 81 patients diagnosed with pneumoconiosis who had previously worked or are currently working in coal mines were analyzed. Forty-six coal mine workers and sex matched healthy people (n = 20) participated in the study. Workers who had early changes of pneumoconiosis were included in Group 1 (n = 17), workers diagnosed with pneumoconiosis were included in Group 2 (n = 29), and healthy subjects were included in Group 3 (n = 20). Outcome measures were the difference in peripapillary retinal nerve fiber layer (RNFL) thickness, choroidal thickness (CT), central macular thickness (CMT) and tear function tests between the groups. RNFL thickness values in Group 1 and 2 were lower than in Group 3, the control group, in all quadrants except the temporal quadrant. However, there was no statistically significant difference in peripapillary RNFL thickness values in any quadrants among the three groups (p > 0.05). Central subfoveal choroidal thickness and CMT measurements were thinner in Group 1 and 2 than in the control group. However, this difference among groups was not statistically significant (p > 0.05). Mean schirmer's test result was 8.8 ± 1.6 mm in group 1, 7.1 ± 1.8 mm in Group 2 and 11.5 ± 3.6 mm in the control group. Mean tear break up time (BUT) test result was 7.1 ± 1.3 seconds (sec) in Group 1, 6.5 ± 1.8 sec in Group 2 and 10.4 ± 2.9 s in the control group. The Schirmer's test and BUT test results were both statistically significantly lower in coal mine workers (Group 1 and 2) compared to the control group. Group 1 and Group 2 did not show statistically significant difference in terms of Schirmer's test and BUT test results. The association between pneumoconiosis and coal mine dust contiguity is

  8. The Choroidal Eye Oximeter - An instrument for measuring oxygen saturation of choroidal blood in vivo

    NASA Technical Reports Server (NTRS)

    Laing, R. A.; Danisch, L. A.; Young, L. R.

    1975-01-01

    The Choroidal Eye Oximeter is an electro-optical instrument that noninvasively measures the oxygen saturation of choroidal blood in the back of the human eye by a spectrophotometric method. Since choroidal blood is characteristic of blood which is supplied to the brain, the Choroidal Eye Oximeter can be used to monitor the amount of oxygen which is supplied to the brain under varying external conditions. The instrument consists of two basic systems: the optical system and the electronic system. The optical system produces a suitable bi-chromatic beam of light, reflects this beam from the fundus of the subject's eye, and onto a low-noise photodetector. The electronic system amplifies the weak composite signal from the photodetector, computes the average oxygen saturation from the area of the fundus that was sampled, and displays the value of the computed oxygen saturation on a panel meter.

  9. Choroidal Involvement in Acute Posterior Multifocal Placoid Pigment Epitheliopathy.

    PubMed

    Mrejen, Sarah; Sarraf, David; Chexal, Saradha; Wald, Kenneth; Freund, K Bailey

    2016-01-01

    To evaluate choroidal involvement in acute posterior multifocal placoid pigment epitheliopathy (APMPPE). Retrospective study in five eyes of three patients evaluated through multimodal imaging, including enhanced-depth imaging optical coherence tomography (OCT), ultra-wide field color photography, fundus autofluorescence, and fluorescein angiography (FA). Choroidal thickness and structure were evaluated on OCT. During the acute phase, choroidal OCT showed choroidal thickening and a lucency at the level of the inner choroid. Subclinical lesions detected in the retinal periphery using wide-field retinal imaging were isoautofluorescent and corresponded to choriocapillaris filling-defects on FA. At final follow-up, all patients showed resolution of choroidal thickening and the inner choroidal lucency, as well as the disappearance of subclinical lesions. These results suggest a transient ischemic choroiditis in APMPPE that may lead to secondary permanent retinal pigment epithelium damage in the posterior pole but not in the retinal periphery. Copyright 2016, SLACK Incorporated.

  10. RES-loaded pegylated CS NPs: for efficient ocular delivery.

    PubMed

    Pandian, Saravanakumar; Jeevanesan, Vinoth; Ponnusamy, Chandrasekar; Natesan, Subramanian

    2017-02-01

    The objective of this study is to develop resveratrol (RES) loaded polyethylene glycols (PEGs) modified chitosan (CS) nanoparticles (NPs) by ionic gelation method for the treatment of glaucoma. While increasing the concentration of PEG, the particle size and polydispersity index of the formulations increased. Entrapment efficiency and RES loading (RL) of NPs decreased while increasing PEG concentration. The in vitro release of NPs showed an initial burst release of RES (45%) followed by controlled release. Osmolality of formulations revealed that the prepared NPs were iso-osmolar with the tear. Ocular tolerance of the NPs was evaluated using hen's egg test on the chorioallantoic membrane and it showed that the NPs were non-irritant. RES-loaded PEG-modified CS NPs shows an improved corneal permeation compared with RES dispersion. Fluorescein isothiocyanate loaded CS NPs accumulated on the surface of the cornea but the PEG-modified CS NPs crossed the cornea and reached retinal choroid. RES-loaded PEG-modified CS NPs reduced the intra-ocular pressure (IOP) by 4.3 ± 0.5 mmHg up to 8 h in normotensive rabbits. These results indicate that the developed NPs have efficient delivery of RES to the ocular tissues and reduce the IOP for the treatment of glaucoma.

  11. Randomized trial of a home monitoring system for early detection of choroidal neovascularization home monitoring of the Eye (HOME) study.

    PubMed

    Chew, Emily Y; Clemons, Traci E; Bressler, Susan B; Elman, Michael J; Danis, Ronald P; Domalpally, Amitha; Heier, Jeffrey S; Kim, Judy E; Garfinkel, Richard

    2014-02-01

    To determine whether home monitoring with the ForeseeHome device (Notal Vision Ltd, Tel Aviv, Israel), using macular visual field testing with hyperacuity techniques and telemonitoring, results in earlier detection of age-related macular degeneration-associated choroidal neovascularization (CNV), reflected in better visual acuity, when compared with standard care. The main predictor of treatment outcome from anti-vascular endothelial growth factor (VEGF) agents is the visual acuity at the time of CNV treatment. Unmasked, controlled, randomized clinical trial. One thousand nine hundred and seventy participants 53 to 90 years of age at high risk of CNV developing were screened. Of these, 1520 participants with a mean age of 72.5 years were enrolled in the Home Monitoring of the Eye study at 44 Age-Related Eye Disease Study 2 clinical centers. In the standard care and device arms arm, investigator-specific instructions were provided for self-monitoring vision at home followed by report of new symptoms to the clinic. In the device arm, the device was provided with recommendations for daily testing. The device monitoring center received test results and reported changes to the clinical centers, which contacted participants for examination. The main outcome measure was the difference in best-corrected visual acuity scores between baseline and detection of CNV. The event was determined by investigators based on clinical examination, color fundus photography, fluorescein angiography, and optical coherence tomography findings. Masked graders at a central reading center evaluated the images using standardized protocols. Seven hundred sixty-three participants were randomized to device monitoring and 757 participants were randomized to standard care and were followed up for a mean of 1.4 years between July 2010 and April 2013. At the prespecified interim analysis, 82 participants progressed to CNV, 51 in the device arm and 31 in the standard care arm. The primary analysis

  12. Ocular trauma resulting from paintball injury.

    PubMed

    Pahk, Patricia J; Adelman, Ron A

    2009-04-01

    Paintball-related ocular injuries result in severe damage and loss of vision. Despite efforts to increase public awareness and improve safety features, the incidence of eye injuries has increased over time. We examined the characteristics and ocular effects of paintball injury at our tertiary referral center. Retrospective review of charts of patients with paintball injury between 1998-2005. Fourteen patients were evaluated for paintball injury; 13 (93%) were male and one (7%) was female. Average age was 17 years (range from 9 to 30). Thirteen patients (95%) did not wear eye protection; one is unknown. Injuries occurred while playing paintball in three patients (21%); ten (71%) were injured in either accidental (four patients) or intentional (six patients) shootings not associated with play. Minimum follow-up was 6 weeks, except for one patient who was lost to follow-up. Seven patients (50%) had final visual acuity (VA) better than 20/200, six patients (43%) were 20/200 or worse, and information on one patient was not available. VA, except in one case, improved with treatment. Decreased VA in this case was due to proliferative vitreoretinopathy (PVR). Hyphema was noted in ten patients (71%), vitreous hemorrhage in eight (57%), retinal hemorrhage in six (43%), retinal tear or detachment in six (43%), commotio retinae in six (43%), iris injury in five (36%), keratopathy in four (29%), lens injury in two (14%), subluxation of lens in two (14%), secondary glaucoma in two (14%), open globe/intraocular foreign body (IOFB) in one (7%), choroidal rupture in one (7%), and proliferative vitreoretinopathy (PVR) in one (7%). Ten patients (71%) required intervention (surgery, laser retinopexy or cryotherapy). Paintball trauma results in significant ocular injury and loss of vision. Most injuries occur in unsupervised settings without proper eye protection. Ten patients (71%) were injured in accidental or intentional shootings. Lack of supervision and use of paintball materials

  13. Presumed choroidal metastasis of Merkel cell carcinoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Small, K.W.; Rosenwasser, G.O.; Alexander, E. III

    1990-05-01

    Merkel cell carcinoma is a rare skin tumor of neural crest origin and is part of the amine precursor uptake and decarboxylase system. It typically occurs on the face of elderly people. Distant metastasis is almost uniformly fatal. Choroidal metastasis, to our knowledge, has not been described. We report a patient with Merkel cell carcinoma who had a synchronous solid choroidal tumor and a biopsy-proven brain metastasis. Our 56-year-old patient presented with a rapidly growing, violaceous preauricular skin tumor. Computed tomography of the head disclosed incidental brain and choroidal tumors. Light and electron microscopy of biopsy specimens of both themore » skin and the brain lesions showed Merkel cell carcinoma. Ophthalmoscopy, fluorescein angiography, and A and B echography revealed a solid choroidal mass. The brain and skin tumors responded well to irradiation. A radioactive episcleral plaque was applied subsequently to the choroidal tumor. All tumors regressed, and the patient was doing well 28 months later. To our knowledge this is the first case of presumed choroidal metastasis of Merkel cell carcinoma.« less

  14. Expressed sequence tag analysis of human RPE/choroid for the NEIBank Project: over 6000 non-redundant transcripts, novel genes and splice variants.

    PubMed

    Wistow, Graeme; Bernstein, Steven L; Wyatt, M Keith; Fariss, Robert N; Behal, Amita; Touchman, Jeffrey W; Bouffard, Gerald; Smith, Don; Peterson, Katherine

    2002-06-15

    The retinal pigment epithelium (RPE) and choroid comprise a functional unit of the eye that is essential to normal retinal health and function. Here we describe expressed sequence tag (EST) analysis of human RPE/choroid as part of a project for ocular bioinformatics. A cDNA library (cs) was made from human RPE/choroid and sequenced. Data were analyzed and assembled using the program GRIST (GRouping and Identification of Sequence Tags). Complete sequencing, Northern and Western blots, RH mapping, peptide antibody synthesis and immunofluorescence (IF) have been used to examine expression patterns and genome location for selected transcripts and proteins. Ten thousand individual sequence reads yield over 6300 unique gene clusters of which almost half have no matches with named genes. One of the most abundant transcripts is from a gene (named "alpha") that maps to the BBS1 region of chromosome 11. A number of tissue preferred transcripts are common to both RPE/choroid and iris. These include oculoglycan/opticin, for which an alternative splice form is detected in RPE/choroid, and "oculospanin" (Ocsp), a novel tetraspanin that maps to chromosome 17q. Antiserum to Ocsp detects expression in RPE, iris, ciliary body, and retinal ganglion cells by IF. A newly identified gene for a zinc-finger protein (TIRC) maps to 19q13.4. Variant transcripts of several genes were also detected. Most notably, the predominant form of Bestrophin represented in cs contains a longer open reading frame as a result of splice junction skipping. The unamplified cs library gives a view of the transcriptional repertoire of the adult RPE/choroid. A large number of potentially novel genes and splice forms and candidates for genetic diseases are revealed. Clones from this collection are being included in a large, nonredundant set for cDNA microarray construction.

  15. Choroidal Nevi in USAF Aviators

    DTIC Science & Technology

    1990-12-01

    in macula , although none were situated directly under the fovea. Only 5 (4.4%) nevi were located forward of the equator. The distribution of choroidal...melanomas (1). The fact that none of the choroidal nevi followed in this study underwent growth or malignant degeneration , which would have prompted a

  16. Transconjunctival drainage of serous and hemorrhagic choroidal detachment.

    PubMed

    Rezende, Flávio A; Kickinger, Mônica C; Li, Gisèle; Prado, Renata F; Regis, Luiz Gustavo T

    2012-02-01

    To describe a novel surgical technique for drainage of bullous serous and hemorrhagic choroidal detachments. A prospective, consecutive case series of 6 eyes with serous and/or hemorrhagic choroidal detachments secondary to intraocular surgery was documented to evaluate the feasibility of using the 25-gauge and 20-gauge transconjunctival trocar/cannula systems to drain choroidal detachments. Two eyes had expulsive hemorrhagic choroidal detachments and 4 eyes had serous choroidal detachments after glaucoma surgeries. A 25-gauge infusion line was placed in the anterior chamber. A 20-gauge (in eyes with hemorrhagic choroidal detachments) or a 25-gauge (in eyes with serous detachments) trocar/cannula system was inserted into the suprachoroidal space 7.0 mm from limbus. After drainage, the cannulas were removed and no sutures were placed. Pars plana vitrectomy was performed only in eyes with concomitant pathology that demanded the additional procedure. The primary outcome measure was presence of choroidal detachment at 1 week, 2 weeks, and 1 month postoperatively. Secondary outcome measures were visual acuity at 6 months and intraocular pressure at 1 week and 1, 3, and 6 months postoperatively. Drainage of hemorrhagic choroidal detachments resulted in resolution of the detachments by 1 month postoperatively. In eyes with serous detachments, resolution was achieved by 1 week postdrainage. In both groups, intraocular pressure increased to at least 10 mmHg by postoperative Week 1. The visual acuity improved in all eyes. No complications related to the transconjunctival technique were noted. Transconjunctival drainage of serous and hemorrhagic choroidal detachments seems to be a feasible and simple surgical option with minimal scleral and conjunctival damage. Pars plana vitrectomy may not be necessary when draining choroidal detachments in this manner.

  17. Distribution and characterisation of rat choroidal mast cells.

    PubMed Central

    Steptoe, R J; McMenamin, P G; McMenamin, C

    1994-01-01

    Despite the implication that choroidal mast cells are involved in the onset of experimental autoimmune uveoretinitis (EAU), a widely used animal model of uveoretinitis, little is known of these cells. In the present study the distribution, total number, regional density, and phenotype of choroidal mast cells were examined in Lewis, Wistar Furth, PVG/c, and brown Norway rats. Choroidal mast cells were predominantly associated with arteries and arterioles of more than 30 microns diameter which lie in the outer (sclerad) choroid. The density of mast cells was greatest in the posterior choroid with density diminishing anteriorly. The choroid of male Lewis rats contained significantly greater number of mast cells than that of females (p < 0.01). Histochemical (Alcian blue/safranin) and immunohistochemical (anti-rat mast cell protease I and II monoclonal antibodies) studies revealed choroidal mast cells were of the connective tissue type. However, granule proteinase content appeared less than that of well characterised connective tissue mast cell populations such as those in mesentery and skin. Lewis rats exhibited the highest density of choroidal mast cells (23.6 (SD 1.2)/mm2), Wistar Furth approximately half that of Lewis (13.5 (0.7)/mm2) while PVG/c and brown Norway rats had very low densities (3.06(0.3); 1.95(0.2/mm2 respectively). These studies provide valuable choroidal mast cell data for rats which may have implications for our understanding of experimental models of intraocular inflammation and clinical uveitis. Images PMID:8148338

  18. Subretinal fluid in eyes with active ocular toxoplasmosis observed using spectral domain optical coherence tomography.

    PubMed

    Ouyang, Yanling; Li, Fuqiang; Shao, Qing; Heussen, Florian M; Keane, Pearse A; Stübiger, Nicole; Sadda, Srinivas R; Pleyer, Uwe

    2015-01-01

    To describe the clinical finding of subretinal fluid (SRF) in the posterior pole by spectral domain optical coherence tomography (SD-OCT) in eyes with active ocular toxoplasmosis (OT). Retrospective case series. Thirty-nine eyes from 38 patients with active OT [corrected].. Eyes with active OT which underwent SD-OCT were reviewed. SRFs in the posterior pole were further analyzed. Presence of SRF; its accompanying features, e.g. retinal necrosis, cystoid macular edema (CME), choroidal neovascularization (CNV); and longitudinal changes of SRF, including maximum height and total volume before and after treatment. SRF presented in 45.5% (or 15/33) of eyes with typical active OT and in 51.3% (or 20/39) of eyes with active OT. The mean maximum height and total volume of SRF were 161.0 (range: 23-478) µm and 0.47 (range: 0.005-4.12) mm3, respectively. For 12 eyes with SRF related to active retinal necrosis, SRF was observed with complete absorption after conventional anti-toxoplasmosis treatment. The mean duration for observation of SRF clearance was 33.8 (range: 7-84) days. The mean rate of SRF clearance was 0.0128 (range: 0.0002-0.0665) mm3/day. SRF (i.e., serous retinal detachment) is a common feature in patients with active OT when SD-OCT is performed. The majority of SRF was associated with retinal necrosis and reacted well to conventional therapy, regardless of total fluid volume. However, SRF accompanying with CME or CNV responded less favorably or remained refractory to conventional or combined intravitreal treatment, even when the SRF was small in size.

  19. A Comparison of the Effects of Benzalkonium Chloride on Ocular Surfaces between C57BL/6 and BALB/c Mice

    PubMed Central

    Yang, Qian; Zhang, Yafang; Liu, Xiuping; Wang, Nan; Song, Zhenyu; Wu, Kaili

    2017-01-01

    Models of benzalkonium chloride (BAC)-induced ocular disruption have been created and are widely used in various animals. This study aimed to compare the effects of BAC on the ocular surfaces of C57BL/6 and BALB/c mice. C57BL/6 and BALB/c mice were treated separately with BAC eye-drops at different concentrations. Eyes were evaluated by scoring epithelial disruption, corneal opacity and neovascularization in vivo, and by histological assays with hematoxylin/eosin (H/E) and periodic acid-Schiff stainings and by determining the expression of inflammatory factors in vitro on Days 7 and 14. The in vivo corneal epithelial disruption, corneal edema/opacity and neovascularization, which were in accordance with the results of the H/E staining and peaked at Day 7, were observed in a dose-dependent manner in the BAC-treated mice, with more severe signs in the C57BL/6 mice than the BALB/c mice. The loss of conjunctival goblet cells in the conjunctivas and the increasing expression of monocyte chemoattractant protein 1 (MCP-1), growth-regulated protein alpha (GROa) and macrophage inflammatory protein-1 alpha (MIP-1a) in the corneas were found in a dose-dependent manner in both strains of mice. Topical application of BAC can dramatically disrupt the ocular surfaces of C57BL/6 and BALB/c mice, and the disruptions were much more severe in the C57BL/6 mice that received high doses of BAC. PMID:28245636

  20. Use of CD25 as an immunohistochemical marker for acquired ocular toxoplasmosis.

    PubMed

    Miyamoto, Cristina; Mattos Neto, Rubens Belfort; Cesare, Sebastian Di; Belfort Junior, Rubens; Burnier, Miguel N

    2010-01-01

    Toxoplasmosis is the most common cause of posterior infectious uveitis worldwide. It is often impossible to determine its congenital or acquired nature. Interleukin-2 (IL-2) in peripheral blood has been described as a possible marker for acquired toxoplasmosis. The purpose of this study is to evaluate the histopathological characteristics of ocular toxoplasmosis cases using CD25 as a marker for the expression of interleukin-2. Ten formalin-fixed, paraffin-embedded enucleated globes from ten immunocompetent patients with clinical diagnosis of toxoplasmosis were evaluated. Four patients had the acquired form of ocular toxoplasmosis (positive IgM) while six were IgM negative and IgG positive for toxoplasmosis. Histopathological slides were reviewed for the extension of the retinal necrosis, number of toxo cysts, the granulomatous inflammatory reaction, the presence of T and B cells within the choroid and the IL-2 expression. Immunohistochemistry using monoclonal antibodies was performed to observe the expression of CD4, CD8, CD20, CD25, and CD68. The histopathological evaluation disclosed no differences between acquired and the other ocular toxoplasmosis cases regarding the characteristics studied. However, CD25 showed a higher expression of IL-2 on the 4 acquired cases of ocular toxoplasmosis compared to the remainders. To the best of our knowledge, this is the first report showing that the use of CD25 as a marker for interleukin-2 could differentiate acquired ocular toxoplasmosis.

  1. Canine choroidal melanoma with metastases.

    PubMed

    Hyman, Jennifer A; Koch, Seth A; Wilcock, Brian P

    2002-06-01

    A 3-year-old-female, spayed Golden Retriever was examined for a unilateral retinal detachment with exophthalmos. Ultrasonographically, a mass was detected with intra- and extraocular extension. The orbit was exenterated and the dog recovered uneventfully. Histopathologic diagnosis was a primary choroidal melanoma with orbital extension, however, the behavioral and cytologic features were benign. Routine examinations postsurgically were nonremarkable. Twenty-one months after surgery the dog was euthanized for respiratory collapse with radiographic signs of metastasis. Necropsy revealed black lesions in the lung and liver. Histopathologic diagnosis was metastatic melanoma with morphology and behavior identical to the primary choroidal melanoma. This is the first definitive case of a canine choroidal melanoma with metastasis.

  2. Choroidal Infiltration by Retinoblastoma: Predictive Clinical Features and Outcome.

    PubMed

    Kaliki, Swathi; Tahiliani, Prerana; Iram, Sadiya; Ali, Mohammed Hasnat; Mishra, Dilip K; Reddy, Vijay Anand P

    2016-11-01

    To identify the clinical features predictive of choroidal infiltration by retinoblastoma on histopathology and to report the outcome in these patients. Retrospective study. Of the 403 patients who underwent primary enucleation for retinoblastoma, 113 patients had choroidal tumor infiltration and 290 patients had no choroidal tumor infiltration. There was a higher incidence of metastasis and related death in the choroidal tumor infiltration group compared to the no choroidal tumor infiltration group (4% vs 1%; P = .02). On multivariate analysis, the clinical features predictive of histopathologic massive choroidal infiltration included prolonged duration of symptoms for more than 6 months (hazard ratio [HR] = 3.04; P = .001) and secondary glaucoma (HR = 2.24; P = .005). In this study, the patients with retinoblastoma with prolonged duration of symptoms (> 6 months) had a three-fold greater risk and those with secondary glaucoma at presentation had a two-fold greater risk of massive choroidal tumor infiltration. [J Pediatr Ophthalmol Strabismus. 2016;53(6):349-356.]. Copyright 2016, SLACK Incorporated.

  3. Effect of ultrasound radiation force on the choroid.

    PubMed

    Silverman, Ronald H; Urs, Raksha; Lloyd, Harriet O

    2013-01-10

    While visualization of the retina and choroid has made great progress, functional imaging techniques have been lacking. Our aim was to utilize acoustic radiation force impulse (ARFI) response to probe functional properties of these tissues. A single element 18-MHz ultrasound transducer was focused upon the retina of the rabbit eye. The procedure was performed with the eye proptosed and with the eye seated normally in the orbit. The transducer was excited to emit ARFI over a 10-ms period with a 25% duty cycle. Phase resolved pulse/echo data were acquired before, during, and following ARFI. In the proptosed eye, ARFI exposure produced tissue displacements ranging from 0 to 10 μm, and an immediate increase in choroidal echo amplitude to over 6 dB, decaying to baseline after about 1 second. In the normally seated eye, ultrasound phase shifts consistent with flow were observed in the choroid, but enhanced backscatter following ARFI rarely occurred. ARFI-induced displacements of about 10 μm were observed at the choroidal margins. Larger displacements occurred within the choroid and in orbital tissues. We hypothesize that elevated intraocular pressure occurring during proptosis induced choroidal ischemia and that acoustic radiation force produced a transient local decompression and reperfusion. With the eye normally seated, choroidal flow was observed and little alteration in backscatter resulted from exposure. Clinical application of this technique may provide new insights into diseases characterized by altered choroidal hemodynamics, including maculopathies, diabetic retinopathy, and glaucoma.

  4. Regulation of choroidal blood flow during combined changes in intraocular pressure and arterial blood pressure.

    PubMed

    Polska, Elzbieta; Simader, Christian; Weigert, Günter; Doelemeyer, Arno; Kolodjaschna, Julia; Scharmann, Ole; Schmetterer, Leopold

    2007-08-01

    To test the hypothesis that human choroidal blood flow (ChBF) may depend, not only on ocular perfusion pressure (OPP), but also on absolute mean arterial pressure (MAP) and intraocular pressure (IOP). There were two study days in an open design. On the first day, OPP was varied by elevating IOP during a squatting-induced increase in MAP (28 subjects). On the second day, only the IOP was increased (17 subjects). IOP was raised in stepwise increments by using the suction cup Subfoveal ChBF (laser Doppler flowmetry), MAP, and IOP were assessed, and OPP was calculated as (2/3)(MAP - IOP). For correlation analysis, data from all subjects were pooled according to IOP and MAP, and correlation analyses were performed. When data from study day 1 were grouped according to IOP, no correlation was observed between ChBF and MAP; but ChBFs were lower, the higher the IOP (P < 0.001). When data were grouped according to MAP, a significant correlation was found between ChBF and IOP (P < 0.001), but correlations were independent of MAP. When data of study day 2 were pooled according to IOP, a correlation between ChBF and OPP was seen only at IOP > 40 mm Hg (P < 0.05). The data confirm previously published observations that the choroid shows some autoregulatory capacity during changes in OPP. In addition, the data indicate that the choroid regulates its blood flow better during exercise-induced changes in MAP than during an experimental increase in IOP.

  5. Ultrahigh field magnetic resonance and colour Doppler real-time fusion imaging of the orbit--a hybrid tool for assessment of choroidal melanoma.

    PubMed

    Walter, Uwe; Niendorf, Thoralf; Graessl, Andreas; Rieger, Jan; Krüger, Paul-Christian; Langner, Sönke; Guthoff, Rudolf F; Stachs, Oliver

    2014-05-01

    A combination of magnetic resonance images with real-time high-resolution ultrasound known as fusion imaging may improve ophthalmologic examination. This study was undertaken to evaluate the feasibility of orbital high-field magnetic resonance and real-time colour Doppler ultrasound image fusion and navigation. This case study, performed between April and June 2013, included one healthy man (age, 47 years) and two patients (one woman, 57 years; one man, 67 years) with choroidal melanomas. All cases underwent 7.0-T magnetic resonance imaging using a custom-made ocular imaging surface coil. The Digital Imaging and Communications in Medicine volume data set was then loaded into the ultrasound system for manual registration of the live ultrasound image and fusion imaging examination. Data registration, matching and then volume navigation were feasible in all cases. Fusion imaging provided real-time imaging capabilities and high tissue contrast of choroidal tumour and optic nerve. It also allowed adding a real-time colour Doppler signal on magnetic resonance images for assessment of vasculature of tumour and retrobulbar structures. The combination of orbital high-field magnetic resonance and colour Doppler ultrasound image fusion and navigation is feasible. Multimodal fusion imaging promises to foster assessment and monitoring of choroidal melanoma and optic nerve disorders. • Orbital magnetic resonance and colour Doppler ultrasound real-time fusion imaging is feasible • Fusion imaging combines the spatial and temporal resolution advantages of each modality • Magnetic resonance and ultrasound fusion imaging improves assessment of choroidal melanoma vascularisation.

  6. Cell-penetrating peptide for enhanced delivery of nucleic acids and drugs to ocular tissues including retina and cornea.

    PubMed

    Johnson, Leslie N; Cashman, Siobhan M; Kumar-Singh, Rajendra

    2008-01-01

    As in other organ systems, gene and drug delivery to ocular tissues such as the retina and cornea is hampered by inefficient penetration of therapeutic molecules across the plasma membrane. We describe the use of a novel peptide for ocular delivery (POD) with protein transduction properties, for delivery of small and large molecules across the plasma membrane. POD enters cells within 5 minutes in a temperature dependent manner. POD can compact and deliver plasmid DNA, achieving transgene expression in >50% of human embryonic retinoblasts. Delivery of small interfering RNA (siRNA) duplexes to cells using POD, allowed for silencing of transgene expression by >50%. POD could also be used to deliver quantum dots in vitro and in vivo. Upon ocular delivery, POD rapidly entered neural retina and localized to retinal pigment epithelium (RPE), photoreceptor, and ganglion cells. Additionally, POD was able to enter corneal epithelium, sclera, choroid, and the dura of the optic nerve via topical application. POD also functions as a bacteriostatic, a useful property for a carrier of molecules to post mitotic neural ocular tissues.

  7. Clinical progression of ocular injury following arsenical vesicant lewisite exposure.

    PubMed

    Tewari-Singh, Neera; Croutch, Claire R; Tuttle, Richard; Goswami, Dinesh G; Kant, Rama; Peters, Eric; Culley, Tara; Ammar, David A; Enzenauer, Robert W; Petrash, J Mark; Casillas, Robert P; Agarwal, Rajesh

    2016-12-01

    Ocular injury by lewisite (LEW), a potential chemical warfare and terrorist agent, results in edema of eyelids, inflammation, massive corneal necrosis and blindness. To enable screening of effective therapeutics to treat ocular injury from LEW, useful clinically-relevant endpoints are essential. Hence, we designed an efficient exposure system capable of exposing up to six New-Zealand white rabbits at one time, and assessed LEW vapor-induced progression of clinical ocular lesions mainly in the cornea. The right eye of each rabbit was exposed to LEW (0.2 mg/L) vapor for 2.5, 5.0, 7.5 and 10.0 min and clinical progression of injury was observed for 28 days post-exposure (dose-response study), or exposed to same LEW dose for 2.5 and 7.5 min and clinical progression of injury was observed for up to 56 days post-exposure (time-response study); left eye served as an unexposed control. Increasing LEW exposure caused corneal opacity within 6 h post-exposure, which increased up to 3 days, slightly reduced thereafter till 3 weeks, and again increased thereafter. LEW-induced corneal ulceration peaked at 1 day post-exposure and its increase thereafter was observed in phases. LEW exposure induced neovascularization starting at 7 days which peaked at 22-35 days post-exposure, and remained persistent thereafter. In addition, LEW exposure caused corneal thickness, iris redness, and redness and swelling of the conjunctiva. Together, these findings provide clinical sequelae of ocular injury following LEW exposure and for the first time establish clinically-relevant quantitative endpoints, to enable the further identification of histopathological and molecular events involved in LEW-induced ocular injury.

  8. Why choroid vessels appear dark in clinical OCT images

    NASA Astrophysics Data System (ADS)

    Kirby, Mitchell A.; Li, Chenxi; Choi, Woo June; Gregori, Giovanni; Rosenfeld, Philip; Wang, Ruikang

    2018-02-01

    With the onset of clinically available spectral domain (SD-OCT) and swept source (SS-OCT) systems, clinicians are now easily able to recognize sub retinal microstructure and vascularization in the choroidal and scleral regions. As the bloodrich choroid supplies nutrients to the upper retinal layers, the ability to monitor choroid function accurately is of vital importance for clinical assessment of retinal health. However, the physical appearance of the choroid blood vessels (darker under a healthy Retinal Pigmented Epithelium (RPE) compared to regions displaying an RPE atrophic lesion) has led to confusion within the OCT ophthalmic community. The differences in appearance between each region in the OCT image may be interpreted as different vascular patterns when the vascular networks are in fact very similar. To explain this circumstance, we simulate light scattering phenomena in the RPE and Choroid complexes using the finite difference time domain (FDTD) method. The simulation results are then used to describe and validate imaging features in a controlled multi-layered tissue phantom designed to replicate human RPE, choroid, and whole blood microstructure. Essentially, the results indicate that the strength of the OCT signal from choroidal vasculature is dependent on the health and function of the RPE, and may not necessarily directly reflect the health and function of the choroidal vasculature.

  9. Polarisation-sensitive OCT is useful for evaluating retinal pigment epithelial lesions in patients with neovascular AMD.

    PubMed

    Schütze, Christopher; Teleky, Katharina; Baumann, Bernhard; Pircher, Michael; Götzinger, Erich; Hitzenberger, Christoph K; Schmidt-Erfurth, Ursula

    2016-03-01

    To examine the reproducibility of lesion dimensions of the retinal pigment epithelium (RPE) in neovascular age-related macular degeneration (AMD) with polarisation-sensitive optical coherence tomography (PS-OCT), specifically imaging the RPE. Twenty-six patients (28 eyes) with neovascular AMD were included in this study, and examined by a PS-OCT prototype. Each patient was scanned five times at a 1-day visit. The PS-OCT B-scan located closest to the macular centre presenting with RPE atrophy was identified, and the longitudinal diameter of the lesion was quantified manually using AutoCAD 2008. This procedure was followed for the identical B-scan position in all five scans per eye and patient. Reproducibility of qualitative changes in PS-OCT was evaluated. Interobserver variability was assessed. Results were compared with intensity-based spectral-domain OCT (SD-OCT) imaging. Mean variability of all atrophy lesion dimensions was 0.10 mm (SD±=0.06 mm). Coefficient of variation (SD±/mean) was 0.06 on average (SD±=0.03). Interobserver variability assessment showed a mean difference of 0.02 mm across all patients regarding RPE lesion size evaluation (paired t test: p=0.38). Spearman correlation coefficient was r=0.98, p<0.001. Results revealed a good overall reproducibility of ∼90%. PS-OCT specifically detected the RPE in all eyes compared with conventional intensity-based SD-OCT that was not capable to clearly identify RPE atrophy in 25 eyes (89.3%, p<0.01). PS-OCT offers good reproducibility of RPE atrophy assessment in neovascular AMD, and may be suitable for precise RPE evaluation in clinical practice. PS-OCT unambiguously identifies RPE changes in choroidal neovascularisation compared with intensity-based SD-OCT that does not identify the RPE status reliably. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  10. Practice Patterns Analysis of Ocular Proton Therapy Centers: The International OPTIC Survey.

    PubMed

    Hrbacek, Jan; Mishra, Kavita K; Kacperek, Andrzej; Dendale, Remi; Nauraye, Catherine; Auger, Michel; Herault, Joel; Daftari, Inder K; Trofimov, Alexei V; Shih, Helen A; Chen, Yen-Lin E; Denker, Andrea; Heufelder, Jens; Horwacik, Tomasz; Swakoń, Jan; Hoehr, Cornelia; Duzenli, Cheryl; Pica, Alessia; Goudjil, Farid; Mazal, Alejandro; Thariat, Juliette; Weber, Damien C

    2016-05-01

    To assess the planning, treatment, and follow-up strategies worldwide in dedicated proton therapy ocular programs. Ten centers from 7 countries completed a questionnaire survey with 109 queries on the eye treatment planning system (TPS), hardware/software equipment, image acquisition/registration, patient positioning, eye surveillance, beam delivery, quality assurance (QA), clinical management, and workflow. Worldwide, 28,891 eye patients were treated with protons at the 10 centers as of the end of 2014. Most centers treated a vast number of ocular patients (1729 to 6369). Three centers treated fewer than 200 ocular patients. Most commonly, the centers treated uveal melanoma (UM) and other primary ocular malignancies, benign ocular tumors, conjunctival lesions, choroidal metastases, and retinoblastomas. The UM dose fractionation was generally within a standard range, whereas dosing for other ocular conditions was not standardized. The majority (80%) of centers used in common a specific ocular TPS. Variability existed in imaging registration, with magnetic resonance imaging (MRI) rarely being used in routine planning (20%). Increased patient to full-time equivalent ratios were observed by higher accruing centers (P=.0161). Generally, ophthalmologists followed up the post-radiation therapy patients, though in 40% of centers radiation oncologists also followed up the patients. Seven centers had a prospective outcomes database. All centers used a cyclotron to accelerate protons with dedicated horizontal beam lines only. QA checks (range, modulation) varied substantially across centers. The first worldwide multi-institutional ophthalmic proton therapy survey of the clinical and technical approach shows areas of substantial overlap and areas of progress needed to achieve sustainable and systematic management. Future international efforts include research and development for imaging and planning software upgrades, increased use of MRI, development of clinical protocols

  11. Practice Patterns Analysis of Ocular Proton Therapy Centers: The International OPTIC Survey

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hrbacek, Jan, E-mail: Jan.hrbacek@psi.ch; Mishra, Kavita K.; Kacperek, Andrzej

    Purpose: To assess the planning, treatment, and follow-up strategies worldwide in dedicated proton therapy ocular programs. Methods and Materials: Ten centers from 7 countries completed a questionnaire survey with 109 queries on the eye treatment planning system (TPS), hardware/software equipment, image acquisition/registration, patient positioning, eye surveillance, beam delivery, quality assurance (QA), clinical management, and workflow. Results: Worldwide, 28,891 eye patients were treated with protons at the 10 centers as of the end of 2014. Most centers treated a vast number of ocular patients (1729 to 6369). Three centers treated fewer than 200 ocular patients. Most commonly, the centers treated uvealmore » melanoma (UM) and other primary ocular malignancies, benign ocular tumors, conjunctival lesions, choroidal metastases, and retinoblastomas. The UM dose fractionation was generally within a standard range, whereas dosing for other ocular conditions was not standardized. The majority (80%) of centers used in common a specific ocular TPS. Variability existed in imaging registration, with magnetic resonance imaging (MRI) rarely being used in routine planning (20%). Increased patient to full-time equivalent ratios were observed by higher accruing centers (P=.0161). Generally, ophthalmologists followed up the post–radiation therapy patients, though in 40% of centers radiation oncologists also followed up the patients. Seven centers had a prospective outcomes database. All centers used a cyclotron to accelerate protons with dedicated horizontal beam lines only. QA checks (range, modulation) varied substantially across centers. Conclusions: The first worldwide multi-institutional ophthalmic proton therapy survey of the clinical and technical approach shows areas of substantial overlap and areas of progress needed to achieve sustainable and systematic management. Future international efforts include research and development for imaging and planning software

  12. Autofluorescence of choroidal nevus in 64 cases.

    PubMed

    Shields, Carol L; Pirondini, Cesare; Bianciotto, Carlos; Materin, Miguel A; Harmon, Sarah A; Shields, Jerry A

    2008-10-01

    To describe the autofluorescence features of choroidal nevi. Noncomparative case series. Sixty-four consecutive patients. Correlation of fundus photography with autofluorescence photography. Autofluorescence features of choroidal nevus and overlying retinal pigment epithelium (RPE). The mean patient age was 62 years. The choroidal nevus was a mean of 5 mm from the optic disk and foveola. The mean tumor basal dimension was 5.0 mm and mean tumor thickness was 1.0 mm. The choroidal nevus showed hypoautofluorescence in 56%, isoautofluorescence in 19%, and hyperautofluorescence in 25%. The autofluorescence features appeared unaffected by tumor thickness, but increasing tumor base and disrupted overlying RPE appeared to produce slightly brighter autofluorescence. Nevi located in the macular region showed darker hypoautofluorescence than those outside the macular region. Overlying RPE hyperplasia, atrophy, and fibrous metaplasia were generally hypoautofluorescent. Drusen, subretinal fluid, and orange pigment were generally hyperautofluorescent. The brightest hyperautofluorescence was found with orange pigment. Choroidal nevus shows little intrinsic autofluorescence. Overlying RPE alterations show dramatic autofluorescence ranging from dark hypoautofluorescence of RPE atrophy to bright hyperautofluorescence of orange pigment.

  13. Changes in ocular flora in eyes exposed to ophthalmic antibiotics.

    PubMed

    Dave, Sarita B; Toma, Hassanain S; Kim, Stephen J

    2013-05-01

    To determine changes in ocular flora in individuals repeatedly exposed to topical macrolide or fluoroquinolone antibiotics. Prospective, controlled, longitudinal study with 1-year follow-up. Forty-eight eyes of 24 patients undergoing serial unilateral intravitreal injection for choroidal neovascularization. Patients received 4 consecutive monthly unilateral intravitreal injections and were then treated as needed. Each patient was randomized to 1 of 4 antibiotics (azithromycin 1%, gatifloxacin 0.3%, moxifloxacin 0.5%, ofloxacin 0.3%) and used only their assigned antibiotic for 4 days after each injection. Conjunctival cultures of the treated eye and untreated fellow eye (control) were taken at baseline and before each injection. All bacterial isolates were tested for antibiotic susceptibility to 16 different antibiotics using the Kirby-Bauer disc diffusion technique. Changes in bacteria composition of the conjunctiva over time. In azithromycin-treated eyes, Staphylococcus epidermidis and Staphylococcus aureus accounted for 54.5% and 18.2% of cultured isolates, respectively, at baseline and 90.9% (P<0.01) and 4.5% (P<0.01), respectively, after azithromycin exposure. In fluoroquinolone-treated eyes, 45.7% and 6.5% of cultured isolates at baseline were S epidermidis and S aureus, respectively, but these percentages increased to 63.4% (P<0.03) and 13% (P = 0.24), respectively, after fluoroquinolone exposure. In contrast, the percentage of gram-negative species decreased from 8.7% at baseline to 1.6% (P<0.05) in fluoroquinolone-treated eyes. The percentage of S epidermidis isolated from azithromycin-treated eyes was significantly greater when compared with fellow control eyes (P<0.01) or fluoroquinolone-treated eyes (P<0.01). The percentage of S epidermidis isolated from the conjunctival surface significantly increases after repeated exposure to azithromycin and to a lesser degree fluoroquinolone antibiotics at the expense of other commensal flora. The author(s) have no

  14. Rare ocular manifestations in an 11-year-old girl with incomplete Kawasaki disease: A case report.

    PubMed

    Gao, Yunxia; Zhang, Yifan; Lu, Fang; Wang, Xiaoyue; Zhang, Ming

    2018-06-01

    Kawasaki disease is a necrotizing vasculitis featuring fever, erythema, conjunctivitis, and lymphadenopathy. Ocular manifestations in Kawasaki disease are commonly limited to anterior segment, posterior segment lesions are rarely reported. We report a unique case of ocular manifestations in an 11-year-old girl with incomplete Kawasaki disease. An 11-year-old Asian girl presented with severe enophthalmos, retinitis, retinal detachment, and choroidal detachment secondary to an unexplained fever for 10 days. To the best of our knowledge, this is the first documented case of incomplete Kawasaki disease with severe posterior segment lesions. The local use of dexamethasone in the eye was effective in our patient. Surgical intervention might not be necessary even though the initial symptoms could be devastating. The eye should be monitoring the eye routinely in patients with Kawasaki disease.

  15. A pilot study on the combination treatment of reduced-fluence photodynamic therapy, intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for neovascular age-related macular degeneration.

    PubMed

    Sivaprasad, S; Patra, S; DaCosta, J; Adewoyin, T; Shona, O; Pearce, E; Chong, N V

    2011-01-01

    To assess the safety and efficacy of the combined treatment of reduced-fluence verteporfin photodynamic therapy (PDT), intravitreal ranibizumab, intravitreal dexamethasone and oral minocycline for choroidal neovascularisa- tion (CNV) secondary to age-related macular degeneration (AMD). Nineteen patients with subfoveal CNV secondary to AMD were recruited into the trial. All study eyes (n = 19) received a single cycle of reduced-fluence (25 mJ/cm(2)) PDT with verteporfin followed by an intravitreal injection of ranibizumab 0.3 mg/0.05 ml and dexamethasone 200 μg at baseline. Oral minocycline 100 mg daily was started the following day and continued for 3 months. Patients were followed up monthly for 12 months. Repeat intravitreal ranibizumab was given if best-corrected visual acuity (BCVA) deteriorated by >5 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart or central retinal thickness (CRT) on ocular coherence tomography increased >100 μm. Eighteen patients completed the 12-month study. Stable vision (loss of ≤15 ETDRS letters) was maintained in 89% eyes (16/18). The mean change in BCVA was -5.0 ± 10.5 ETDRS letters. The mean number of ranibizumab injections was 3.4 (range 2-6). The mean reduction in the CRT was 66.3 μm (±75). This open-label clinical trial has demonstrated the safety in terms of adverse effects and maintenance of stable vision of combination treatment with verteporfin, ranibizumab, dexamethasone and minocycline in exudative AMD. However, the outcomes with reduced-fluence PDT combination therapy does not differ significantly with outcomes of clinical trials on combination treatment with standard dose PDT and intravitreal ranibizumab in neovascular AMD. Copyright © 2011 S. Karger AG, Basel.

  16. Neovascular glaucoma in a patient with X-linked juvenile retinoschisis.

    PubMed

    Zuo, Chengguo; Chen, Changzheng; Xing, Yiqiao; Du, Lei

    2005-09-01

    To report the rubeosis iridis and neovascular glaucoma findings in one patient of X-linked juvenile retinoschisis(XLRS). Color fundus photography, fluorescein angiography (FFA), OCT and B-scan were performed in a patient with X-linked juvenile retinoschisis complicated with neovascular glaucoma. Color fundus photography, fluorescein angiography (FFA), OCT and B-scan unveiled a rare condition of XLRS complicated with neovascular glaucoma. XLRS may complicate with neovascular glaucoma. It is necessary to test OCT, FFA, ERG and carefully examine the fundus of the follow eye when it comes to uncertain neovascular glaucoma of youth and child. And only in this way, can we exclude XLRS.

  17. A pilot study to image the vascular network of small melanocytic choroidal tumors with speckle noise-free 1050-nm swept source optical coherence tomography (OCT choroidal angiography).

    PubMed

    Maloca, Peter; Gyger, Cyrill; Hasler, Pascal W

    2016-06-01

    To visualize and measure the vascular network of melanocytic choroidal tumors with speckle noise-free swept source optical coherence tomography (SS-OCT choroidal angiography). Melanocytic choroidal tumors from 24 eyes were imaged with 1050-nm optical coherence tomography (Topcon DRI OCT-1 Atlantis). A semi-automated algorithm was developed to remove speckle noise and to extract and measure the volume of the choroidal vessels from the obtained OCT data. In all cases, analysis of the choroidal vessels could be performed with SS-OCT without the need for pupillary dilation. The proposed method allows speckle noise-free, structure-guided visualization and measurement of the larger choroidal vessels in three dimensions. The obtained data suggest that speckle noise-free OCT may be more effective at identifying choroidal structures than traditional OCT methods. The measured volume of the extracted choroidal vessels of Haller's layer and Sattler's layer in the examined tumorous eyes was on average 0.982463955 mm(3) /982463956 μm(3) (range of 0.209764406 mm(3) /209764405.9 μm(3)to 1.78105544 mm(3) /1781055440 μm(3)). Full thickness obstruction of the choroidal vasculature by the tumor was found in 18 cases (72 %). In seven cases (18 %), choroidal vessel architecture did not show pronounced morphological abnormalities (18 %). Speckle noise-free OCT may serve as a new illustrative imaging technology and enhance visualization of the choroidal vessels without the need for dye injection. OCT can be used to identify and evaluate the choroidal vessels of melanocytic choroidal tumors, and may represent a potentially useful tool for imaging and monitoring of choroidal nevi and melanoma.

  18. Delivery of therapeutics for deep-seated ocular conditions - status quo.

    PubMed

    Nguyen, Hubert; Eng, Shawn; Ngo, Thanh; Dass, Crispin R

    2018-04-19

    There is a need for research into designing effective pharmaceutical systems for delivering therapeutic drugs to the posterior of the eye for glaucoma-related pathology, macular degeneration, diabetic retinopathy, macular oedema, retinitis and choroiditis. Conventionally, eye drops have been extensively utilised for topical drug delivery to the anterior segment of the eye, but are less effective for delivery of therapeutics to the back of the eye due to significant barriers hampering drug penetration into the target intraocular tissue. This review explores some of the current and novel delivery systems employed to deliver therapeutics to the back of the eye such as those using liposomes, ocular implants, in situ gels, and nanoparticles, and how they can overcome some of these limitations. Issues such as blinking, precorneal fluid drainage, tear dilution and turnover, conjunctiva and nasal drug absorption, the corneal epithelium, vitreous drug clearance, and the blood-ocular barriers are reviewed and discussed. Further studies are needed to address their shortcomings such as drug compatibility and stability, economic viability and patient compliance. © 2018 Royal Pharmaceutical Society.

  19. Choroidal thickness evaluation in paediatric patients with adenotonsillar hypertrophy.

    PubMed

    Yenigun, A; Elbay, A; Hafiz, A M; Ozturan, O

    2017-09-01

    To investigate choroidal thickness using enhanced-depth imaging optical coherence tomography in paediatric patients with adenotonsillar hypertrophy, with comparison to healthy children, three months after adenotonsillectomy. The patients were assigned to three groups: an adenotonsillar hypertrophy group, an adenotonsillectomy group and a healthy control group. In all groups, subfoveal, temporal and nasal choroidal thickness measurements were taken. In the subfoveal, temporal and nasal regions, choroidal tissue was found to be significantly thinner in adenotonsillar hypertrophy children than healthy children (p = 0.012, p = 0.027 and p = 0.020). The subfoveal and temporal choroidal thickness measurements of adenotonsillar hypertrophy group cases were significantly decreased compared to those in the adenotonsillectomy group (p = 0.038 and p = 0.048). There was a significant association between decreased choroidal thickness and adenotonsillar hypertrophy. Adenotonsillar hypertrophy may play an important role in decreased choroidal thickness.

  20. Psammoma bodies - friends or foes of the aging choroid plexus.

    PubMed

    Jovanović, Ivan; Ugrenović, Sladjana; Vasović, Ljiljana; Petrović, Dragan; Cekić, Sonja

    2010-06-01

    Psammoma bodies are structures classified in the group of dystrophic calcifications, which occur in some kind of tumors and in choroid plexus during the aging process. Despite early discovery of their presence in choroid plexus stroma, mechanisms responsible for their formation remained unclear. Their presence in some kind of tumors was even more extensively studied, but significant breakthrough in the field of their etiology was not attained, too. However, till today correlation between their presence in tumors and aging is not established. Also, there are not any data about structural differences between ones found in tumors and ones found in choroid plexus. This might points to the assumption that besides the aging, some other causes might be involved in their formation in choroid plexus. Furthermore, it is contradictory that forms, like psammoma bodies, present in such malignant formations as tumors, represent quite benign phenomenon in choroid plexus. Literature data and the results of our previous researches revealed that there might be connections between, these, on the first sight quite different processes. Firstly, psammoma bodies are present in stroma of tumors with predominantly papillomatous morphology, which is present in choroid plexus, too. Initial forms of psammoma bodies might be formed in fibrovascular core of choroid plexus villi, similarly like in tumors papillae of papillary thyroid cancer. Their further growth leads to the progressive destruction of both tumors papillae and choroidal villi. Choroid plexus stroma is characterized by the fenestrated blood vessels presence, which are similar to newly formed vessels in tumors. This makes it vulnerable to the noxious agents from circulation. It can contain lymphocytes, macrophages, dendritic cells and myofibroblasts in cases with psammoma bodies, similarly to tumors stroma which is in activated, proinflammatory state. So, all these facts can suggest that similar processes can lead to psammoma

  1. Choroidal neovascularisation as an unusual ophthalmic manifestation of cat-scratch disease in an 8-year-old girl.

    PubMed

    Latanza, L; Viscogliosi, F; Solimeo, A; Calabrò, F; De Angelis, V; De Rosa, P

    2015-10-01

    To report the first case of choroidal neovascularisation (CNV) that appeared during the primary Bartonella henselae infection in an 8-year-old girl. An 8-year-old girl was referred to our clinic complaining of a central scotoma in the right eye. Fundus examination revealed a bilateral disc oedema and in the right eye neuroretinitis with macular star and CNV, which was confirmed by fluorescein angiography. The optical coherence tomography revealed the presence of macular serous retinal detachment. Laboratory analysis showed rising IgM and IgG titres for B. henselae. Cat-scratch disease was diagnosed, and an 8-week treatment with azithromycin was initiated. In addition, an intravitreal injection of ranibizumab was performed in the right eye to treat the CNV. A month later, we decided to administer a systemic antibiotic again for an additional 5 months, due to the persistence of papillitis. Cat-scratch disease should be considered among the different causes of inflammatory CNV secondary to infectious uveitis. Our case was the first described in the literature in which a CNV appeared during the primary infection and not as a later complication. The combination of systemic antibiotic treatment with intravitreal anti-VEGF therapy was a successful choice because it allowed us to obtain the complete resolution of neuroretinitis, associated with the scarring of the choroidal neovascular membrane, with a final visual acuity of 20/20 in both eyes.

  2. Visualizing microvascular flow variation in OCTA using variable interscan time analysis (VISTA) (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Moult, Eric M.; Ploner, Stefan A.; Choi, WooJhon; Lee, ByungKun; Husvogt, Lennart A.; Lu, Chen D.; Novais, Eduardo; Cole, Emily D.; Potsaid, Benjamin M.; Duker, Jay S.; Hornegger, Joachim; Meier, Andreas K.; Waheed, Nadia K.; Fujimoto, James G.

    2017-02-01

    OCT angiography (OCTA) has recently garnered immense interest in clinical ophthalmology, permitting ocular vasculature to be viewed in exquisite detail, in vivo, and without the injection of exogenous dyes. However, commercial OCTA systems provide little information about actual erythrocyte speeds; instead, OCTA is typically used to visualize the presence and/or absence of vasculature. This is an important limitation because in many ocular diseases, including diabetic retinopathy (DR) and age-related macular degeneration (AMD), alterations in blood flow, but not necessarily only the presence or absence of vasculature, are thought to be important in understanding pathogenesis. To address this limitation, we have developed an algorithm, variable interscan time analysis (VISTA), which is capable of resolving different erythrocyte speeds. VISTA works by acquiring >2 repeated B-scans, and then computing multiple OCTA signals corresponding to different effective interscan times. The OCTA signals corresponding to different effective interscan times contain independent information about erythrocyte speed. In this study we provide a theoretical overview of VISTA, and investigate the utility of VISTA in studying blood flow alterations in ocular disease. OCTA-VISTA images of eyes with choroidal neovascularization, geographic atrophy, and diabetic retinopathy are presented.

  3. Ocular pathology in melanomatous Sinclair miniature swine.

    PubMed Central

    Feeney-Burns, L.; Burns, R. P.; Gao, C. L.

    1988-01-01

    Eyes of cutaneous melanoma-bearing miniature Sinclair swine were examined by light and electron microscopy during growth and maturation of animals. The histology of ocular depigmentation, which occurs during melanoma arrest and skin depigmentation, was studied in eyes of animals that had successful and unsuccessful tumor regression. In 12 animals one eye was removed at an early stage and the second eye at a later stage of disease or maturation. The histologic and clinical course of the ocular changes was correlated with changes in the cutaneous tumors. Animals showing rapid cutaneous tumor regression developed acute uveitis that was characterized by an influx of mononuclear cells into the stroma of the ciliary body; later this spread to the iris and choroid. In late stages the cornea sometimes developed a band of calcium precipitates beneath the basal epithelial cells (band keratopathy). Uveal melanocytes developed watery cytoplasm typical of cells with ruptured plasma membranes. Released melanin granules were taken up initially into the lysosomal compartment of mononuclear cells having the various morphologic features of lymphocytes and monocytes; later, melanin also appeared in fibrocyte lysosomes. The relationship of these processes to various cell-mediated immunity phenomena is being studied. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:3354645

  4. Cerebrovascular accidents in patients treated for choroidal neovascularization with ranibizumab in randomized controlled trials.

    PubMed

    Bressler, Neil M; Boyer, David S; Williams, David F; Butler, Steven; Francom, Steven F; Brown, Benton; Di Nucci, Flavia; Cramm, Timothy; Tuomi, Lisa L; Ianchulev, Tsontcho; Rubio, Roman G

    2012-10-01

    To analyze cerebrovascular accidents (CVAs) pooled from large, randomized, controlled clinical trials of ranibizumab treatment for neovascular age-related macular degeneration. Events in five trials (FOCUS, MARINA, ANCHOR, PIER, and SAILOR) were analyzed using a standard safety monitoring process. Exact methods, stratified by study, were used to test for treatment differences based on odds ratios. A stepwise logistic regression model was fit to classify subjects' risk for CVA based on medical history. Treatment differences in CVA rates at 1 year or 2 years were evaluated within risk groups using stratified exact methods. Pooled 2-year CVA rates were <3%; odds ratios (95% confidence intervals) for CVA risk were 1.2 (0.4-4.4) for ranibizumab 0.3-mg versus control, 2.2 (0.8-7.1) for 0.5 mg versus control, and 1.5 (0.8-3.0) for 0.5-mg versus 0.3-mg ranibizumab. No substantial increased risk of CVA for 0.5 mg versus 0.3 mg was identified in pooled analyses or any of the individual trials. In pooled analyses, the difference between 0.5-mg ranibizumab and control was larger (7.7 [1.2-177]) among high-risk CVA patients. This analysis provided some evidence, although not definitive, of a potential increased risk of CVA with ranibizumab versus control or with 0.5-mg versus 0.3-mg ranibizumab. Continued monitoring for CVA within clinical trials seems warrented.

  5. Novel micelle carriers for cyclosporin A topical ocular delivery: in vivo cornea penetration, ocular distribution and efficacy studies.

    PubMed

    Di Tommaso, Claudia; Bourges, Jean-Louis; Valamanesh, Fatemeh; Trubitsyn, Gregory; Torriglia, Alicia; Jeanny, Jean-Claude; Behar-Cohen, Francine; Gurny, Robert; Möller, Michael

    2012-06-01

    Cornea transplantation is one of the most performed graft procedures worldwide with an impressive success rate of 90%. However, for "high-risk" patients with particular ocular diseases in addition to the required surgery, the success rate is drastically reduced to 50%. In these cases, cyclosporin A (CsA) is frequently used to prevent the cornea rejection by a systemic treatment with possible systemic side effects for the patients. To overcome these problems, it is a challenge to prepare well-tolerated topical CsA formulations. Normally high amounts of oils or surfactants are needed for the solubilization of the very hydrophobic CsA. Furthermore, it is in general difficult to obtain ocular therapeutic drug levels with topical instillations due to the corneal barriers that efficiently protect the intraocular structures from foreign substances thus also from drugs. The aim of this study was to investigate in vivo the effects of a novel CsA topical aqueous formulation. This formulation was based on nanosized polymeric micelles as drug carriers. An established rat model for the prevention of cornea graft rejection after a keratoplasty procedure was used. After instillation of the novel formulation with fluorescent labeled micelles, confocal analysis of flat-mounted corneas clearly showed that the nanosized carriers were able to penetrate into all corneal layers. The efficacy of a 0.5% CsA micelle formulation was tested and compared to a physiological saline solution and to a systemic administration of CsA. In our studies, the topical CsA treatment was carried out for 14 days, and the three parameters (a) cornea transparency, (b) edema, and (c) neovascularization were evaluated by clinical observation and scoring. Compared to the control group, the treated group showed a significant higher cornea transparency and significant lower edema after 7 and 13 days of the surgery. At the end point of the study, the neovascularization was reduced by 50% in the CsA-micelle treated

  6. Effects of water drinking test on ocular blood flow waveform parameters: A laser speckle flowgraphy study.

    PubMed

    Bhatti, Mehwish Saba; Tang, Tong Boon; Laude, Augustinus

    2017-01-01

    The water-drinking test (WDT) is a provocative test used in glaucoma research to assess the effects of elevated intraocular pressure (IOP). Defective autoregulation due to changes in perfusion pressure may play a role in the pathophysiology of several ocular diseases. This study aims to examine the effects of WDT on ocular blood flow (in the form of pulse waveform parameters obtained using laser speckle flowgraphy) to gain insight into the physiology of ocular blood flow and its autoregulation in healthy individuals. Changes in pulse waveform parameters of mean blur rate (MBR) in the entire optic nerve head (ONH), the vasculature of the ONH, the tissue area of the ONH, and the avascular tissue area located outside of the ONH were monitored over time. Significant increases in the falling rate of MBR over the entire ONH and its tissue area and decreases in blowout time (BOT) of the tissue area were observed only at 10 minutes after water intake. Significant increases in the skew of the waveform and the falling rate were observed in the vasculature of the ONH at 40 and 50 minutes after water intake, respectively. In the avascular region of the choroid, the average MBR increased significantly up to 30 minutes after water intake. Furthermore, the rising rate in this region increased significantly at 20 and 40 minutes, and the falling rate and acceleration-time index were both significantly increased at 40 minutes after water intake. Our results indicate the presence of effective autoregulation of blood flow at the ONH after WDT. However, in the choroidal region, outside of the ONH, effective autoregulation was not observed until 30 minutes after water intake in healthy study participants. These pulse waveform parameters could potentially be used in the diagnosis and/or monitoring of patients with glaucoma.

  7. Effects of water drinking test on ocular blood flow waveform parameters: A laser speckle flowgraphy study

    PubMed Central

    Bhatti, Mehwish Saba; Laude, Augustinus

    2017-01-01

    The water-drinking test (WDT) is a provocative test used in glaucoma research to assess the effects of elevated intraocular pressure (IOP). Defective autoregulation due to changes in perfusion pressure may play a role in the pathophysiology of several ocular diseases. This study aims to examine the effects of WDT on ocular blood flow (in the form of pulse waveform parameters obtained using laser speckle flowgraphy) to gain insight into the physiology of ocular blood flow and its autoregulation in healthy individuals. Changes in pulse waveform parameters of mean blur rate (MBR) in the entire optic nerve head (ONH), the vasculature of the ONH, the tissue area of the ONH, and the avascular tissue area located outside of the ONH were monitored over time. Significant increases in the falling rate of MBR over the entire ONH and its tissue area and decreases in blowout time (BOT) of the tissue area were observed only at 10 minutes after water intake. Significant increases in the skew of the waveform and the falling rate were observed in the vasculature of the ONH at 40 and 50 minutes after water intake, respectively. In the avascular region of the choroid, the average MBR increased significantly up to 30 minutes after water intake. Furthermore, the rising rate in this region increased significantly at 20 and 40 minutes, and the falling rate and acceleration-time index were both significantly increased at 40 minutes after water intake. Our results indicate the presence of effective autoregulation of blood flow at the ONH after WDT. However, in the choroidal region, outside of the ONH, effective autoregulation was not observed until 30 minutes after water intake in healthy study participants. These pulse waveform parameters could potentially be used in the diagnosis and/or monitoring of patients with glaucoma. PMID:28742142

  8. Cathepsin L is required for endothelial progenitor cell-induced neovascularization

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Urbich, Carmen; Heeschen, Christopher; Aicher, Alexandra

    Infusion of endothelial progenitor cells (EPCs), but not of mature endothelial cells (ECs), promotes neovascularization after ischemia. We performed a gene expression profiling of EPCs and ECs to identify genes, which might be important for the neovascularization capacity of EPCs. Intriguingly, the protease cathepsin L (CathL) was highly expressed in EPCs as opposed to ECs and is essential for matrix degradation and invasion by EPCs in vitro. CathL deficient mice showed impaired functional recovery after hind limb ischemia supporting the concept for an important role of CathL in postnatal neovascularization. Infused CathL deficient progenitor cells failed to home to sitesmore » of ischemia and to augment neovascularization. In contrast, over expression of CathL in mature ECs significantly enhanced their invasive activity and induced their neovascularization capacity in vivo. Taken together, CathL plays a crucial role for the integration of circulating EPCs into the ischemic tissue and is required for neovascularization mediated by EPCs.« less

  9. Bim expression in endothelial cells and pericytes is essential for regression of the fetal ocular vasculature.

    PubMed

    Wang, Shoujian; Zaitoun, Ismail S; Johnson, Ryan P; Jamali, Nasim; Gurel, Zafer; Wintheiser, Catherine M; Strasser, Andreas; Lindner, Volkhard; Sheibani, Nader; Sorenson, Christine M

    2017-01-01

    Apoptosis plays a central role in developmental and pathological angiogenesis and vessel regression. Bim is a pro-apoptotic Bcl-2 family member that plays a prominent role in both developmental and pathological ocular vessel regression, and neovascularization. Endothelial cells (EC) and pericytes (PC) each play unique roles during vascular development, maintenance and regression. We recently showed that germline deletion of Bim results in persistent hyaloid vasculature, increased retinal vascular density and prevents retinal vessel regression in response to hyperoxia. To determine whether retinal vascular regression is attributable to Bim expression in EC or PC we generated mice carrying a conditional Bim allele (BimFlox/Flox) and VE-cadherin-cre (BimEC mice) or Pdgfrb-cre (BimPC mice). BimEC and BimPC mice demonstrated attenuated hyaloid vessel regression and postnatal retinal vascular remodeling. We also observed decreased retinal vascular apoptosis and proliferation. Unlike global Bim -/- mice, mice conditionally lacking Bim in EC or PC underwent hyperoxia-mediated vessel obliteration and subsequent retinal neovascularization during oxygen-induced ischemic retinopathy similar to control littermates. Thus, understanding the cell autonomous role Bim plays in the retinal vascular homeostasis will give us new insight into how to modulate pathological retinal neovascularization and vessel regression to preserve vision.

  10. Factors associated with early detection of choroidal neovascularization in age-related macular degeneration in the clinic setting.

    PubMed

    Lichtinger, Alejandro; Caraza, Mauricio; Galbinur, Tural; Chowers, Itay

    2012-06-01

    Delayed diagnosis of choroidal neovas cularization (CNV) in age-related macular degeneration (AMD) adversely affects visual outcome. To identify factors associated with early detection of CNV in the clinic setting. Demographic and clinical data and lesion characteristics were retrospectively collected from 76 consecutive AMD patients who had a history of CNV in one eye and presented with CNV in the second eye. These data were evaluated for association with visual acuity (VA) at the time of presentation. Better VA was associated with a history of CNV in the fellow eye (P < 0.0001), adherence to follow-up every 4 months (P = 0.015), younger age (P = 0.03), smaller lesion (P < 0.0001), and non-subfoveal location (P = 0.048). VA of the fellow eye did not correlate with VA at presentation with CNV. These data suggest that patients' experience of CNV, regardless of VA, facilitates early diagnosis in the fellow eye. Adherence to follow-up in the routine clinic setting also facilitates early detection of CNV.

  11. Clinical profile, treatment, and visual outcome of ampiginous choroiditis.

    PubMed

    Jyotirmay, Biswas; Jafferji, Shafiq S; Sudharshan, Sridharan; Kalpana, Badami

    2010-01-01

    To report the clinical profile and management of patients diagnosed to have ampiginous choroiditis in a tertiary care referral centre in India. Retrospective cohort study. Twenty-six eyes of 16 patients were included in the study, which was diagnosed as choroiditis, serpiginous choroiditis, and acute posterior multifocal placoid pigment epitheliopathy (APMPPE) or ampiginous choroiditis. Those who were initially diagnosed as having other forms of choroiditis were later classified as having ampiginous choroiditis clinically. Systemic steroids and immunosuppressives were the mainstay of therapy. There was a male preponderance (7:3). Age at presentation ranged from 22 years to 57 years with a (median 34 years); 81% had bilateral involvement and 35% had recurrences. Vision improved or maintained in 24 eyes, whereas it deteriorated in 2 eyes due to subretinal fibrosis and macula involvement, respectively. Resolution of lesions and improvement or stability of vision can occur with administration of timely steroids and immunosuppressive therapy. Regular follow-up is necessary to monitor the disease progression, recurrences, and involvement of the other eye. Ampiginous choroiditis is a separate disease entity due to its distinct clinical features. It is a disease with multiple relapses, which can be effectively controlled with a combination of immunosuppressive therapy, and a good visual acuity can be maintained on long-term follow-up.

  12. Feasibility of laser-targeted photoocclusion of the choriocapillary layer in rats.

    PubMed

    Asrani, S; Zou, S; D'Anna, S; Lutty, G; Vinores, S A; Goldberg, M F; Zeimer, R

    1997-12-01

    A new method, laser-targeted photoocclusion, was developed to occlude choroidal neovascularization while minimizing damage to the overlying retina. The ability to occlude normal choriocapillary layer in rats was evaluated as a first test of the feasibility of treating choroidal neovascularization with this method. A photosensitive agent, aluminum phthalocyanine tetrasulfonate, encapsulated in heat-sensitive liposomes, was administered intravenously along with carboxyfluorescein liposomes. A low-power argon laser (retinal power density of 5.7 W/cm2) locally released a photosensitizer bolus, monitored by the simultaneous release of carboxyfluorescein. A diode laser (operating at 675 nm with a retinal power density of 0.27 W/cm2) activated the photosensitizer with its release. Vessels in the choriocapillary layer were occluded at day 3 after laser treatment and remained unchanged during the 30-day follow-up. Larger choroidal vessels and retinal capillaries remained perfused. Control experiments excluded possible effects of heat or activation of free photosensitizer. Pilot histologic studies showed no damage to the retinal pigment epithelium. Laser-targeted photoocclusion caused selective occlusion of normal choriocapillaries while sparing overlying retinal pigment epithelium and retinal vessels. The method has potential as a treatment of choroidal neovascularization that may minimize iatrogenic loss of vision.

  13. Combined 60° Wide-Field Choroidal Thickness Maps and High-Definition En Face Vasculature Visualization Using Swept-Source Megahertz OCT at 1050 nm.

    PubMed

    Mohler, Kathrin J; Draxinger, Wolfgang; Klein, Thomas; Kolb, Jan Philip; Wieser, Wolfgang; Haritoglou, Christos; Kampik, Anselm; Fujimoto, James G; Neubauer, Aljoscha S; Huber, Robert; Wolf, Armin

    2015-10-01

    To demonstrate ultrahigh-speed swept-source optical coherence tomography (SS-OCT) at 1.68 million A-scans/s for choroidal imaging in normal and diseased eyes over a ∼60° field of view. To investigate and correlate wide-field three-dimensional (3D) choroidal thickness (ChT) and vascular patterns using ChT maps and coregistered high-definition en face images extracted from a single densely sampled Megahertz-OCT (MHz-OCT) dataset. High-definition, ∼60° wide-field 3D datasets consisting of 2088 × 1024 A-scans were acquired using a 1.68 MHz prototype SS-OCT system at 1050 nm based on a Fourier-domain mode-locked laser. Nine subjects (nine eyes) with various chorioretinal diseases or without ocular pathology are presented. Coregistered ChT maps, choroidal summation maps, and depth-resolved en face images referenced to either the retinal pigment epithelium or the choroidal-scleral interface were generated using manual segmentation. Wide-field ChT maps showed a large inter- and intraindividual variance in peripheral and central ChT. In only four of the nine eyes, the location with the largest ChT was coincident with the fovea. The anatomy of the large lumen vessels of the outer choroid seems to play a major role in determining the global ChT pattern. Focal ChT changes with large thickness gradients were observed in some eyes. Different ChT and vascular patterns could be visualized over ∼60° in patients for the first time using OCT. Due to focal ChT changes, a high density of thickness measurements may be favorable. High-definition depth-resolved en face images are complementary to cross sections and thickness maps and enhance the interpretation of different ChT patterns.

  14. Prospective evaluation of subretinal vessel location in polypoidal choroidal vasculopathy (PCV) and response of hemorrhagic and exudative PCV to high-dose antiangiogenic therapy (an American Ophthalmological Society thesis).

    PubMed

    Kokame, Gregg T

    2014-07-01

    The purpose of this study was to determine the following: (1) Is polypoidal choroidal vasculopathy (PCV) a subretinal neovascular process, rather than a choroidal vascular anomaly? and (2) Is a higher dose of ranibizumab (2.0 mg/0.05 mL) more effective in treating PCV than the current dose (0.5 mg/0.05 mL) approved for treatment of age-related macular degeneration? Retrospective evaluation of PCV in 104 eyes of 86 patients was accomplished with use of indocyanine green angiography plus optical coherence tomography to localize the branching vascular network and the polyps. Nineteen eyes of 19 patients with active leaking and exudation underwent a prospective open-label trial of monthly high-dose intravitreal ranibizumab (2.0 mg/0.05 mL). The primary outcome was prevention of major vision loss (≤15 ETDRS letters). Secondary outcomes included adverse events, improved vision, and changes in subretinal hemorrhage, subretinal fluid, macular edema, and polypoidal complexes at 6 months. The PCV vessels were localized beneath the retinal pigment epithelium (RPE) and above Bruch's membrane in 103 (99%) of 104 eyes. In the high-dose ranibizumab trial at 6 months, none of the patients lost ≥15 letters in visual acuity, and 5 (26%) of 19 gained ≥15 letters. Decreases were noted in subretinal fluid in 14 (82%) of 17 eyes, subretinal hemorrhage in 12 (100%) of 12, RPE detachment in 14 (88%) of 16, macular edema in 11 (92%) of 12, and polyps in 15 (79%) of 19 eyes. PCV vessels are a subtype of subretinal neovascularization located above Bruch's membrane and below RPE. High-dose ranibizumab (2.0 mg/0.05 mL) decreased exudation and hemorrhage and resulted in significant polyp regression, although branching vascular networks persisted.

  15. Pathophysiology of Tumor Neovascularization

    PubMed Central

    Furuya, Mitsuko; Nishiyama, Mariko; Kasuya, Yoshitoshi; Kimura, Sadao; Ishikura, Hiroshi

    2005-01-01

    Neovascularization is essential to the process of development and differentiation of tissues in the vertebrate embryo, and is also involved in a wide variety of physiological and pathological conditions in adults, including wound repair, metabolic diseases, inflammation, cardiovascular disorders, and tumor progression. Thanks to cumulative studies on vasculature, new therapeutic approaches have been opened for us to some life-threatening diseases by controlling angiogenesis in the affected organs. In cancer therapy, for example, modulation of factors responsible for tumor angiogenesis may be beneficial in inhibiting of tumor progression. Several antiangiogenic approaches are currently under preclinical trial. However, the mechanisms of neovascularization in tumors are complicated and each tumor shows unique features in its vasculature, depending on tissue specificity, angiogenic micromilieu, grades and stages, host immunity, and so on. For better understanding and effective therapeutic approaches, it is important to clarify both the general mechanism of angiogenic events and the disease-specific mechanism of neovascularization. This review discusses the general features of angiogenesis under physiological and pathological conditions, mainly in tumor progression. In addition, recent topics such as contribution of the endothelial progenitor cells, tumor vasculogenic mimicry, markers for tumor-derived endothelial cells and pericytes, and angiogenic/angiostatic chemokines are summarized. PMID:17315600

  16. Measurements in the peripheral retina using LDF and laser interferometry are mainly influenced by the choroidal circulation.

    PubMed

    Polska, Elzbieta; Luksch, Alexandra; Ehrlich, Paulina; Sieder, Anna; Schmetterer, Leopold

    2002-04-01

    Two laser based methods for the assessment of ocular hemodynamics in humans have been investigated: laser Doppler flowmetry (LDF) and laser interferometric measurement of fundus pulsation amplitude (FPA). When the laser with either of the two methods is focused onto the fovea it is obvious that only choroidal blood flow contributes to the signals. When the laser is, however, directed to other parts of the retina the situation is more complex. Whereas the retina shows a pronounced vasoconstrictor response to systemic hyperoxia the effect in the choroid is small. We therefore investigated the effect of 100% O2 breathing on results as obtained with the above mentioned techniques at different fundus locations. Twelve healthy subjects were included. Four 15-minutes 100% O2 breathing periods were scheduled for each subject. During two of these breathing periods LDF was performed at the fovea (ChBFf) and at a fundus location approximately 7.5 degrees nasally to the fovea (ChBFp), respectively. During the other two periods FPA was assessed at the same fundus locations (FPAf, FPAp). ChBFf tended to decrease during 100% oxygen breathing (6 +/- 4%), but this effect was not significant. The decrease in ChBFp (10 +/- 4%), was comparable. FPAf (10 +/- 2%; P < 0.001) and FPAp (13 +/- 2%; P < 0.001) decreased significantly during systemic hyperoxia, but again there was no difference in the response obtained at the two fundus locations. When LDF and FPA are applied at the peripheral retina the obtained signal is mainly influenced by the choroidal circulation.

  17. Comparison of Ocular Outcomes in Two 14-Day Bed Rest Studies

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita L.; Zanello, S. B.; Yarbough, P. O.; Tabbi, G.; Vizzeri, G.

    2012-01-01

    Reports of astronauts' visual changes have raised concern about ocular health during long-duration spaceflight. Some of these findings include globe flattening with hyperopic shifts, choroidal folds, optic disc edema, retinal nerve fiber layer (RNFL) thickening, and cotton wool spots. While the etiology remains unknown, it is hypothesized that, in predisposed individuals, hypertension in the brain may follow cephalad fluid shifts during spaceflight. This possible mechanism of ocular changes may also apply to analogous cases of idiopathic intracranial hypertension (IIH) or pseudotumor cerebri on Earth patients. Head-down t ilt (HDT) bed rest is a spaceflight analog that induces cephalad fluid shifts. Previous studies of the HDT position demonstrated body fluid shifts associated with changes in intraocular pressure (IOP) but the conditions of bed rest varied among experiments, making it difficult to compare data and draw conclusions. For these reasons, vision evaluation of bed rest subjects was implemented for NASA bed rest studies since 2010, in an attempt to monitor vision health in subjects subjected to bed rest. Vision monitoring is thus currently performed in all NASA-conducted bed rest campaigns

  18. Evaluation of the siRNA PF-04523655 versus ranibizumab for the treatment of neovascular age-related macular degeneration (MONET Study).

    PubMed

    Nguyen, Quan Dong; Schachar, Ronald A; Nduaka, Chudy I; Sperling, Marvin; Klamerus, Karen J; Chi-Burris, Katherine; Yan, Eric; Paggiarino, Dario A; Rosenblatt, Irit; Aitchison, Roger; Erlich, Shai S

    2012-09-01

    To evaluate the efficacy of different dosing paradigms of PF-04523655 (PF) versus ranibizumab (comparator) in subjects with neovascular age-related macular degeneration (AMD). Multicenter, open-label, prospective, randomized, comparator-controlled exploratory study. A total of 151 patients with subfoveal choroidal neovascularization (CNV) secondary to neovascular AMD who were naive to AMD therapy. In this phase 2 study, patients were randomized to 1 of 5 treatment groups with equal ratio. All groups received ranibizumab 0.5 mg at baseline and (a) PF 1 mg every 4 weeks (Q4W) from week 4 to week 12; (b) PF 3 mg Q4W from week 4 to week 12; (c) PF 3 mg every 2 weeks (Q2W) from week 4 to week 12; (d) PF 1 mg + ranibizumab (combination) Q4W from baseline to week 12; and (e) ranibizumab Q4W to week 12. All study treatments were given as intravitreal injections. The primary end point was the mean change in best-corrected visual acuity (BCVA) from baseline at week 16; secondary end points included the percentage of patients gaining ≥ 10 and ≥ 15 letters in BCVA and mean change in retinal central subfield thickness, lesion thickness, and CNV area. At week 16, the PF 1 mg + ranibizumab combination group achieved numerically greater improvement in mean BCVA from baseline (9.5 letters) than the ranibizumab group (6.8 letters). The difference was not statistically significant. The BCVA improvement in the PF monotherapy groups was less than in the ranibizumab group. Similar trends were observed in the percentage of patients who gained ≥ 10 and ≥ 15 letters. From baseline to week 16 (last observed carried forward), the combination and ranibizumab groups had similar mean reductions in central subfield retinal thickness and total CNV area, which were greater than in all PF monotherapy groups. There were no clinically meaningful differences in reduction of lesion thickness among treatment groups. In this early, underpowered study evaluating treatments for neovascular AMD, the

  19. The acute effect of pseudoephedrine on choroidal thickness.

    PubMed

    Ovet, G; Alpfidan, I; Sakarya, Y; Sakarya, R; Ozcimen, M; Göktaş, S; Erdoğan, E

    2016-01-01

    To investigate the acute effects of pseudoephedrine (PE) on choroidal thickness in healthy young patients. Fifty patients with nasal and sinus congestion who were prescribed 60 mg oral PE at the otolaryngology department were recruited for this study. The enhanced depth imaging (EDI) optic coherence tomography (OCT) (Spectralis OCT; Heidelberg Engineering, Heidelberg, Germany) choroidal thickness measurements were performed at baseline and 1, 3 and 6 hours at 7 points. The right eyes of 50 healthy subjects (22 women and 28 men) were included in this study. The mean choroidal thickness at fovea was 293.12 μm, 279.80 μm, 295.80 μm, and 294.52 μm at baseline, 1, 3 and 6 hours respectively. A significant reduction in choroidal thickness versus baseline was observed at all points at 1 hour. The choroidal thickness decreased 1 hour after oral administration of PE and returned to baseline thickness at 3 hours. We suppose that this transient decrease might be associated with vasoconstriction due to activation of sympathetic alpha adrenoceptors.

  20. Ocular Outcomes Comparison Between 14- and 70-day Head-down Tilt Bed Rest

    NASA Technical Reports Server (NTRS)

    Cromwell, R.L.; Taibbi, G.; Zanello, S.B.; Yarbough, P.O.; Ploutz-Snyder, R.J.; Vizzen, G.

    2015-01-01

    INTRODUCTION: Ophthalmological changes, including optic disc edema with optic nerve sheath distension, posterior globe flattening with hyperopic shift, choroidal folds and cotton wool spots have been detected in some astronauts involved in long-duration spaceflights. (sup 1) It is hypothesized that elevated intracranial pressure resulting from microgravity-induced cephalad fluid shifts may be responsible for most of these findings. Head-down tilt bed rest (HTDBR) is a ground-based microgravity analog which also produces cephalad fluid shifts. It is conceivable that prolonged HDTBR exposure may induce ocular changes similar to those experienced in microgravity. Therefore, the purpose of the present study was to compare structural and functional ocular outcomes between 14- and 70-day HDTBR in healthy human subjects. It is hypothesized that 70-d HDTBR induced ocular changes of greater magnitude as compared to 14-d HDTBR. METHODS: Two HDTBR studies were conducted at the NASA Flight Analogs Research Unit, located at The University of Texas Medical Branch at Galveston, TX. Identical NASA standard screening procedures and BR conditions (e.g., strict sleep-wake cycle, standardized diet, continuous video monitoring) were implemented in both studies. Participants spent 14 and/or 70 consecutive days in a 6deg HDT position and did not engage in exercise. Subjects received weekly ocular examinations before, during, and after HDTBR. Ocular testing included: distance and near best-corrected visual acuity (BCVA), cycloplegic refraction, intraocular pressure (IOP) measurement, color vision, red dot test, modified Amsler grid test, confrontational visual field, color fundus photography and Spectral-domain OCT scans of the macula and the optic disc. Pre/post HDTBR differences between the two studies will be evaluated for BCVA, spherical equivalent, IOP, retinal nerve fiber layer (RNFL) thickness and macular OCT parameters. RESULTS: 16 (12 males and 4 females) and 6 (5 males and 1

  1. Vascular tumors of the choroid and retina

    PubMed Central

    Shanmugam, P Mahesh; Ramanjulu, Rajesh

    2015-01-01

    Vascular tumors of the retina and choroid can be seen occasionally. In the following article, the key clinical and diagnostic features of the major retinal and choroidal vascular tumors, their systemic associations, and the literature pertaining to the most currently available treatment strategies are reviewed. PMID:25827544

  2. Effect of nifedipine on choroidal blood flow regulation during isometric exercise.

    PubMed

    Schmidl, Doreen; Prinz, Ana; Kolodjaschna, Julia; Polska, Elzbieta; Luksch, Alexandra; Fuchsjager-Mayrl, Gabriele; Garhofer, Gerhard; Schmetterer, Leopold

    2012-01-25

    To determine whether nifedipine, an L-type calcium channel blocker, alters choroidal blood flow (ChBF) regulation during isometric exercise in healthy subjects. The study was carried out in a randomized, placebo-controlled, double-masked, two-way crossover design. Fifteen healthy male subjects were randomly assigned to receive either placebo or nifedipine on two different study days. Subfoveal ChBF was measured with laser Doppler flowmetry while the study participants performed isometric exercise (squatting). This was performed before drug administration and during infusion of nifedipine and placebo, respectively. Mean arterial pressure (MAP) and intraocular pressure (IOP) were measured noninvasively, and ocular perfusion pressure (OPP) was calculated as ⅔ MAP-IOP. MAP and OPP increased significantly during all squatting periods (P < 0.01). The increase in ChBF was less pronounced than the increase in OPP during isometric exercise. Nifedipine did not alter the OPP increase in response to isometric exercise, but it significantly augmented the exercise-induced increase in ChBF (P < 0.001 vs. placebo). Although ChBF increased by a maximum of 14.2% ± 9.2% during the squatting period when placebo was administered, the maximum increase during administration of nifedipine was 23.2% ± 7.2%. In conclusion, the data of the present study suggest that nifedipine augments the ChBF response to an experimental increase in OPP. In addition, it confirms that the choroidal vasculature has a significant regulatory capacity over wide ranges of OPPs during isometric exercise. (ClinicalTrials.gov number, NCT00280462.).

  3. Ocular oxygen consumption during vitreoperfusion in the cat.

    PubMed

    Blair, N P

    2000-01-01

    Little is known about the total ocular oxygen consumption rate (QO2) in human diseases. Reductions in QO2 may indicate the amount of tissue loss produced by conditions such as retinal ischemia. We sought a method to estimate QO2 that eventually could be used in patients during vitrectomy surgery. We performed vitreoperfusion (perfusion of the vitreous cavity after vitrectomy) in 22 cat eyes with no ocular blood flow. The solution contained nutrients and a high partial pressure of oxygen (PO2). In 8 eyes we placed an oxygen electrode on the sclera, choroid, or outer retina to evaluate oxygen delivery from the vitreoperfusion solution (group 1). In 8 eyes the retinas were undisturbed (group 2), and in 6 eyes we excised the retinas (group 3). In groups 2 and 3 we estimated QO2 from the temporal decline of PO2 in the vitreoperfusion solution according to a pharmacokinetic model. Group 1 demonstrated oxygenation of the entire retina. The means and standard deviations of QO2 were 3.2 +/- 0.8 and 0.4 +/- 0.7 microL/min in groups 2 and 3, respectively, the difference being the retinal contribution, 88%. In group 2, metabolism accounted for an average of 82% of the oxygen loss from the vitreoperfusion solution, whereas flow and diffusion accounted for 13% and 5%, respectively. Ocular oxygen consumption can be estimated by means of vitreoperfusion. Further developments may allow measurements in patients during vitreous surgery to clarify the pathophysiology of their diseases and assess the amount of retinal tissue that has been lost.

  4. Retinal sensitivity and choroidal thickness in high myopia.

    PubMed

    Zaben, Ahmad; Zapata, Miguel Á; Garcia-Arumi, Jose

    2015-03-01

    To estimate the association between choroidal thickness in the macular area and retinal sensitivity in eyes with high myopia. This investigation was a transversal study of patients with high myopia, all of whom had their retinal sensitivity measured with macular integrity assessment microperimetry. The choroidal thicknesses in the macular area were then measured by optical coherence tomography, and statistical correlations between their functionality and the anatomical structuralism, as assessed by both types of measurements, were analyzed. Ninety-six eyes from 77 patients with high myopia were studied. The patients had a mean age ± standard deviation of 38.9 ± 13.2 years, with spherical equivalent values ranging from -6.00 diopter to -20.00 diopter (8.74 ± 2.73 diopter). The mean central choroidal thickness was 159.00 ± 50.57. The mean choroidal thickness was directly correlated with sensitivity (r = 0.306; P = 0.004) and visual acuity but indirectly correlated with the spherical equivalent values and patient age. The mean sensitivity was not significantly correlated with the macular foveal thickness (r = -0.174; P = 0.101) or with the overall macular thickness (r = 0.103; P = 0.334); furthermore, the mean sensitivity was significantly correlated with visual acuity (r = 0.431; P < 0.001) and the spherical equivalent values (r = -0.306; P = 0.003). Retinal sensitivity in highly myopic eyes is directly correlated with choroidal thickness and does not seem to be associated with retinal thickness. Thus, in patients with high myopia, accurate measurements of choroidal thickness may provide more accurate information about this pathologic condition because choroidal thickness correlates to a greater degree with the functional parameters, patient age, and spherical equivalent values.

  5. Improved Ocular Delivery of Nepafenac by Cyclodextrin Complexation.

    PubMed

    Shelley, Haley; Grant, Makenzie; Smith, Forrest T; Abarca, Eva M; Jayachandra Babu, R

    2018-06-13

    Nepafenac is a nonsteroidal anti-inflammatory drug (NSAID), currently only available as 0.1% ophthalmic suspension (Nevanac®). This study utilized hydroxypropyl-β-cyclodextrin (HPBCD) to increase the water solubility and trans-corneal permeation of nepafenac. The nepafenac-HPBCD complexation in the liquid and solid states were confirmed by phase solubility, differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance spectroscopy (NMR) analyses. Nepafenac 0.1% ophthalmic solution was formulated using HPBCD (same pH and osmolality as that of Nevanac®) and pig eye trans-corneal permeation was studied versus Nevanac®. Furthermore, nepafenac content in cornea, sclera, iris, lens, aqueous humor, choroid, ciliary body, retina, and vitreous humor was studied in a continuous isolated pig eye perfusion model in comparison to the suspension and Nevanac®. Permeation studies using porcine corneas revealed that the solution formulation had a permeation rate 18 times higher than Nevanac®. Furthermore, the solution had 11 times higher corneal retention than Nevanac®. Drug distribution studies using porcine eyes revealed that the solution formulation enables detectable levels in various ocular tissues while the drug was undetectable by Nevanac®. The ocular solution formulation had a significantly higher drug concentration in the cornea compared to the suspension or Nevanac®.

  6. Neovascularization prevalence in the supraspinatus of patients with rotator cuff tendinopathy.

    PubMed

    Kardouni, Joseph R; Seitz, Amee L; Walsworth, Matthew K; Michener, Lori A

    2013-11-01

    A high prevalence of neovascularity in lower extremity tendinopathies has been reported. Neovascularity in those with rotator cuff tendinopathy exclusively has not been examined. The objective was to determine the prevalence of neovascularization in patients with rotator cuff tendinopathy compared with asymptomatic controls. Single-blind cross-sectional study. Research laboratory. Participants (n = 40; age = 44.9 years, 23-62 years; 20 females) with rotator cuff tendinopathy (n = 20) but without full-thickness rotator cuff tears, and asymptomatic controls that were age, gender, and hand dominance matched (n = 20) to the patients. The participants laying in supine had their shoulder positioned in internal rotation and extension. Ultrasound images were collected of the supraspinatus tendon and subacromial bursae in the transverse and longitudinal planes using a linear transducer in color Doppler mode. Images were assessed for neovascularization by 2 trained raters who were blinded to group (rotator cuff tendinopathy or asymptomatic group). No statistically significant difference in neovascularization was identified between participants with and without rotator cuff tendinopathy (χ = 0.13, df = 1, P = 0.72). Neovascularization was identified in 6 of 20 patients with rotator cuff tendinopathy (30%) and 5 of 20 asymptomatic control participants (25%). The authors found no differences in neovascularization rate in patients with rotator cuff tendinopathy (30%) and asymptomatic controls (25%). The study indicates that neovascularization is not related to presence of symptomatic tendinopathy in those with rotator cuff tendinopathy. Neovascularization may not be a relevant sonographic finding to aid the clinical assessment of those with rotator cuff tendinopathy.

  7. Choroidal melanoma in a dog.

    PubMed

    Miwa, Yasutsugu; Matsunaga, Satoru; Kato, Kumiko; Ogawa, Hiroyuki; Nakayama, Hiroyuki; Tsujimoto, Saori; Sasaki, Nobuo

    2005-08-01

    A 7-year-old intact female golden Retriever was referred for evaluation of an intraorbital mass of the left eye. Based on ophthalmoscopy, ultrasonography and magnetic resonance imaging (MRI), the tentative diagnosis was made as an intraocular neoplasia, especially choroidal melanoma. The orbital exenteration of the affected eye was performed. The mass was histologically diagnosed as malignant choroidal melanoma. No signs of recurrence and metastasis were detected by thoracic radiographs, blood examinations and MR images, and the dog was clinically healthy for 23 months after operation.

  8. Subretinal neovascularization from the retina in radiation retinopathy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Boozalis, G.T.; Schachat, A.P.; Green, W.R.

    In a 66-year-old woman with radiation retinopathy, subretinal neovascularization was present, originating from telangiectatic retinal vessels in the macular area. The patient showed no clinical or histologic evidence of age-related macular degeneration or other conditions that may have contributed to the subretinal neovascularization.

  9. A simple method for in vivo labelling of infiltrating leukocytes in the mouse retina using indocyanine green dye.

    PubMed

    Sim, Dawn A; Chu, Colin J; Selvam, Senthil; Powner, Michael B; Liyanage, Sidath; Copland, David A; Keane, Pearse A; Tufail, Adnan; Egan, Catherine A; Bainbridge, James W B; Lee, Richard W; Dick, Andrew D; Fruttiger, Marcus

    2015-11-01

    We have developed a method to label and image myeloid cells infiltrating the mouse retina and choroid in vivo, using a single depot injection of indocyanine green dye (ICG). This was demonstrated using the following ocular models of inflammation and angiogenesis: endotoxin-induced uveitis, experimental autoimmune uveoretinitis and laser-induced choroidal neovascularization model. A near-infrared scanning ophthalmoscope was used for in vivo imaging of the eye, and flow cytometry was used on blood and spleen to assess the number and phenotype of labelled cells. ICG was administered 72 h before the induction of inflammation to ensure clearance from the systemic circulation. We found that in vivo intravenous administration failed to label any leukocytes, whereas depot injection, either intraperitoneal or subcutaneous, was successful in labelling leukocytes infiltrating into the retina. Progression of inflammation in the retina could be traced over a period of 14 days following a single depot injection of ICG. Additionally, bright-field microscopy, spectrophotometry and flow cytometric analysis suggest that the predominant population of cells stained by ICG are circulating myeloid cells. The translation of this approach into clinical practice would enable visualization of immune cells in situ. This will not only provide a greater understanding of pathogenesis, monitoring and assessment of therapy in many human ocular diseases but might also open the ability to image immunity live for neurodegenerative disorders, cardiovascular disease and systemic immune-mediated disorders. © 2015. Published by The Company of Biologists Ltd.

  10. Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging

    PubMed Central

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-01-01

    Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD. PMID:23933169

  11. Neovascular glaucoma after helium ion irradiation for uveal melanoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, M.K.; Char, D.H.; Castro, J.L.

    1986-02-01

    Neovascular glaucoma developed in 22 of 169 uveal melanoma patients treated with helium ion irradiation. Most patients had large melanomas; no eyes containing small melanomas developed anterior segment neovascularization. The mean onset of glaucoma was 14.1 months (range, 7-31 months). The incidence of anterior segment neovascularization increased with radiation dosage; there was an approximately three-fold increase at 80 GyE versus 60 GyE of helium ion radiation (23% vs. 8.5%) (P less than 0.05). Neovascular glaucoma occurred more commonly in larger tumors; the incidence was not affected by tumor location, presence of subretinal fluid, nor rate of tumor regression. Fifty-three percentmore » of patients had some response with intraocular pressures of 21 mmHg or less to a combination of antiglaucoma treatments.« less

  12. Ocular blood flow parameters after pars plana vitrectomy in patients with diabetic retinopathy.

    PubMed

    Krepler, Katharina; Polska, Elzbieta; Wedrich, Andreas; Schmetterer, Leopold

    2003-04-01

    Whereas the anatomic result of vitrectomy in patients with vitreoretinal complications due to diabetes is usually satisfying, the functional outcome is sometimes poor. The authors investigated whether this may be related in part to effects of vitrectomy on ocular perfusion. Ocular hemodynamics were measured before vitrectomy and 1 and 4 weeks postoperatively in 13 consecutive diabetic patients. Pulsatile choroidal blood flow was assessed with laser interferometric measurement of fundus pulsation amplitude. In addition, mean blood flow velocity and resistive index in the ophthalmic artery, the central retinal artery, and the posterior ciliary arteries were measured with color Doppler imaging. Fundus pulsation amplitude was significantly reduced after surgery as compared to baseline (baseline: 3.7 +/- 1.0 microm; 4 weeks: 3.1 +/- 0.8; P < 0.001). Postoperatively, mean blood flow velocity in the central retinal artery (P = 0.009) and the posterior ciliary arteries (P = 0.0006) was significantly reduced, whereas resistive index was increased in the central retinal artery (P = 0.028) but not in the posterior ciliary arteries. The current data suggest that vitrectomy induces significant reductions in ocular blood flow in patients with diabetic retinopathy. Whether this may affect the visual outcome after vitrectomy or whether this reflects improved retinal oxygenation after vitrectomy remains to be established.

  13. Comparative study between a spectral domain and a high-speed single-beam swept source OCTA system for identifying choroidal neovascularization in AMD

    NASA Astrophysics Data System (ADS)

    Told, R.; Ginner, L.; Hecht, A.; Sacu, S.; Leitgeb, R.; Pollreisz, A.; Schmidt-Erfurth, U.

    2016-12-01

    This comparative study between a SD- and SS-OCTA system for visualizing neovascular patterns in AMD, also assessed the influence of cataract on OCTA imaging. 25 eyes with active CNV (AMD) were documented by FA, ICGA and SD-OCT. Two OCTA devices were used: A custom built SS-OCTA (1050 nm, 400,000 A-scans/s, 5 × 5 mm, no image segmentation); AngioVue (OptoVue, CA, USA) SD-OCTA (840 nm, 70.000 A-scans/s, 3 × 3 mm, SSADA technology). Two retina experts graded CNV types and vascular patterns. Cataract influence on OCTA image quality was reported for the superficial retinal plexus (6 eyes). The SS-OCTA prototype showed more CNV lesions compared to the SD-OCTA system (p = 0.01). Overall sensitivity of SD- and SS-OCTA systems to detect CNV lesions was.32 and.68, respectively. The SS-OCTA system was able to detect discrete lesion characteristics better than the SD-OCTA. No significant difference was found in the ability to identify CNV in treatment-naïve eyes. There was no significant influence of cataract. The SS-OCTA prototype detected CNV-associated vascular patterns more reliably than the SD-OCTA system. This is attributed to the SS-OCTA system’s longer center wavelength and higher A-scan rate yielding higher definition and contrast of small neovascular structures. The SS-OCTA system used showed no advantage regarding cataract influence.

  14. Sarcoid granuloma of the choroid.

    PubMed

    Marcus, D F; Bovino, J A; Burton, T C

    1982-12-01

    Two patients were found to have macular choroidal granulomas associated with systemic sarcoidosis. This unusual fundus picture was documented by serial fundus photography and fluorescein angiography. Both patients had a similar clinical picture of decreased vision, chorioretinal granulomas, and overlying neurosensory detachments. Staining of the inflammatory mass with fluorescein and leakage of dye into the neurosensory space was typical. Lymph node biopsies were performed to substantiate the diagnosis. Both patients responded promptly to systemic corticosteroid therapy with dramatic improvement in visual acuity and resolution of the choroidal lesions.

  15. The ocular lesions of naturally occurring lymphocystis in fish.

    PubMed

    Dukes, T W; Lawler, A R

    1975-10-01

    Six cases of ocular lymphocystis, a virus disease, are described. Lymphocystis is generally known as a benigh, unique, giant cell disease of fishes causing nodules on the skin and fins. It has been studied extensively because of the virus-host cell relationship that results in extreme size and lack of quick cellular destruction or stimulation to neoplasia. Lymphocystis cells were found behind or in one or both eyes and were also found on the cornea or adjacent skin surfaces. A retrobulbar mass produced extreme exophthalmos. Uveal (choroid and iris) masses were present in most cases. Optic nerve involvement was also seen. It is probable that the virus reached the eye by the blood with the resulting masses forming in situ rather than by direct extension from skin lesions.

  16. Bilateral choroidal osteomas associated with fatal systemic illness.

    PubMed

    Kline, L B; Skalka, H W; Davidson, J D; Wilmes, F J

    1982-02-01

    An 11-year-old black boy complained of intermittent occipital headaches with nausea and projectile vomiting. Previous skin and lung biopsy specimens were interpreted as histiocytosis X. Cranial computed tomographic scanning disclosed a mass lesion in the region of the choroid plexus of the left lateral ventricle. This was surgically removed but proved nondiagnostic despite extensive histologic examination. An ophthalmologic evaluation showed discrete, elevated, yellow-white choroidal tumors in both maculas. The ophthalmoscopic appearance, as well as ultrasonography and computed tomography, led to the diagnosis of choroidal osteomas.

  17. Choroidal metastasis from early rectal cancer: Case report and literature review

    PubMed Central

    Tei, Mitsuyoshi; Wakasugi, Masaki; Akamatsu, Hiroki

    2014-01-01

    INTRODUCTION Choroidal metastasis from colorectal cancer is rare, and there have been no reported cases of such metastasis from early colorectal cancer. We report a case of choroidal metastasis from early rectal cancer. PRESENTATION OF CASE A 61 year-old-man experienced myodesopsia in the left eye 2 years and 6 months after primary rectal surgery for early cancer, and was diagnosed with left choroidal metastasis and multiple lung metastases. Radiotherapy was initiated for the left eye and systemic chemotherapy is initiated for the multiple lung metastases. The patient is living 2 years and 3 months after the diagnosis of choroidal metastasis without signs of recurrence in the left eye, and continues to receive systemic chemotherapy for multiple lung metastases. DISCUSSION Current literatures have few recommendations regarding the appropriate treatment of choroidal metastasis from colorectal cancer, but an aggressive multi-disciplinary approach may be effective in local regression. CONCLUSION This is the first report of choroidal metastasis from early rectal cancer. We consider it important to enforce systemic chemotherapy in addition to radiotherapy for choroidal metastasis from colorectal cancer. PMID:25460493

  18. Ocular abnormalities in congenital Zika syndrome: are the ophthalmoscopic findings "the top of the iceberg"?

    PubMed

    de Oliveira Dias, João Rafael; Ventura, Camila V; de Paula Freitas, Bruno; Prazeres, Juliana; Ventura, Liana O; Bravo-Filho, Vasco; Aleman, Tomas; Ko, Albert Icksang; Zin, Andréa; Belfort, Rubens; Maia, Mauricio

    2018-04-23

    Zika virus (ZIKV) is an arbovirus mainly transmitted to humans by mosquitoes from Aedes genus. Other ways of transmission include the perinatal and sexual routes, blood transfusion, and laboratory exposure. Although the first human cases were registered in 1952 in African countries, outbreaks were only reported since 2007, when entire Pacific islands were affected. In March 2015, the first cases of ZIKV acute infection were notified in Brazil and, to date, 48 countries and territories in the Americas have confirmed local mosquito-borne transmission of ZIKV. Until 2015, ZIKV infection was thought to only cause asymptomatic or mild exanthematous febrile infections. However, after explosive ZIKV outbreaks in Polynesia and Latin American countries, it was confirmed that ZIKV could also lead to Guillain-Barré syndrome and congenital birth abnormalities. These abnormalities, which can include neurologic, ophthalmologic, audiologic, and skeletal findings, are now considered congenital Zika syndrome (CZS). Brain abnormalities in CZS include cerebral calcifications, malformations of cortical development, ventriculomegaly, lissencephaly, hypoplasia of the cerebellum and brainstem. The ocular findings, which are present in up to 70% of infants with CZS, include iris coloboma, lens subluxation, cataract, congenital glaucoma, and especially posterior segment findings. Loss of retinal pigment epithelium, the presence of a thin choroid, a perivascular choroidal inflammatory infiltrate, and atrophic changes within the optic nerve were seen in histologic analyses of eyes from deceased fetuses. To date, there is no ZIKV licensed vaccines or antiviral therapies are available for treatment. Preventive measures include individual protection from mosquito bites, control of mosquito populations and the use of barriers measures such as condoms during sexual intercourse or sexual abstinence for couples either at risk or after confirmed infection. A literature review based on studies that

  19. Comparison of clinical features and 3-month treatment response among three different choroidal thickness groups in polypoidal choroidal vasculopathy.

    PubMed

    Kong, Mingui; Kim, Sung Min; Ham, Don-Il

    2017-01-01

    Eyes with polypoidal choroidal vasculopathy (PCV) were recently reported to have various choroidal thickness, and choroidal thickness might be associated with visual outcome in the treatment of many retinal disorders. The range of subfoveal choroidal thickness (SFCT), clinical features, and 3-month treatment response among three groups having different range of SFCT were investigated in PCV eyes. In 78 treatment-naïve eyes with PCV, SFCT was measured using optical coherence tomography. Eyes were classified into thin, medium, and thick groups, using mean and one standard deviation of SFCT. Clinical features and imaging findings were compared among the three groups. Some eyes were treated with three consecutive monthly injection of anti-vascular endothelial growth factor (VEGF) as an initial treatment. They were also classified into three thickness groups, and the short-term post-treatment improvement in visual acuity and central retinal thickness were compared among groups. The mean SFCT was 271.9 ± 135.6 μm. Twelve, 53, and 13 eyes were classified into thin (<136.3 μm), medium (136.3-407.5 μm), and thick (>407.5 μm) groups, respectively. The thin group showed older age, lower visual acuity, and a higher prevalence of fundus tessellation than the other two groups (P <0.05). In multiple linear regression analyses, baseline BCVA was correlated with baseline SFCT. Forty-six eyes completed three consecutive anti-VEGF treatments. The thin group showed no visual improvement after treatment (P = 0.141), unlike the other two groups showing visual improvement (P<0.05). Eyes with PCV have a broad range of SFCT, and PCV eyes with a thin choroid manifest worse visual function than eyes with a medium or thick choroid.

  20. Perilimbal bevacizumab injection for interface neovascularization after deep anterior lamellar keratoplasty.

    PubMed

    Foroutan, Alireza; Fariba, Beigzadeh; Pejman, Bakhtiari; Mahmoud, Joshaghani; Khalil, Ghasemi Falavarjani; Arash, Ehteshami Afshar; Foroutan, Pooria

    2010-11-01

    To evaluate the effect of perilimbal bevacizumab injection on neovascularization at the interface of donor and recipient tissues after deep anterior lamellar keratoplasty (DALK). This interventional case series included 4 patients with interface neovascularization after DALK (3 patients with advanced keratoconus and 1 patient with scarring because of herpetic keratitis). Bevacizumab (2.5 mg/0.1 mL) was injected subconjunctivally near the limbus adjacent to the abnormal blood vessels. Depending on regression of new vessels, injections were repeated. If neovascularization occurred in more than 1 quadrant, injections were administered at 2 sites (2.5 mg for each injection). Total corneal neovascularization, longest neovascular length, and degree of neovascular circumference were evaluated by digital slit lamp corneal photography before injection and 1 week, 1, 3, and 6 months afterward. The mean follow-up period was 14 ± 7.52 months from the first bevacizumab injection. Corneal neovascularization, on average,was 33.70% ± 7.8% (SD) of the total corneal surface before the injections, which decreased to 4.83% ± 3.3% (P = 0.005, t test) at the last follow-up examination. Mean degree of neovascularized circumference decreased from 165 degrees before injection to 77.5 degrees (P = 0.023) at the last follow-up examination. Mean longest neovascularized length decreased from 6.714 mm before injection to 1.497 mm (P = 0.021) at the last follow-up examination. At the end of the study, all patients had clear grafts with no sign of graft failure. Mean best-corrected visual acuity before injection was 20/100, which improved to 20/30 at the last examination. This small case series suggests that perilimbal bevacizumab injection is safe and effective for partial regression of new blood vessels at the interface of donor and recipient tissues after DALK and may effectively prevent graft rejection.

  1. A novel in vivo model of puncture-induced iris neovascularization.

    PubMed

    Beaujean, Ophélie; Locri, Filippo; Aronsson, Monica; Kvanta, Anders; André, Helder

    2017-01-01

    To assess iris neovascularization by uveal puncture of the mouse eye and determine the role of angiogenic factors during iris neovascularization. Uveal punctures were performed on BalbC mouse eyes to induce iris angiogenesis. VEGF-blockage was used as an anti-angiogenic treatment, while normoxia- and hypoxia-conditioned media from retinal pigment epithelium (RPE) cells was used as an angiogenic-inducer in this model. Iris vasculature was determined in vivo by noninvasive methods. Iris blood vessels were stained for platelet endothelial cell adhesion molecule-1 and vascular sprouts were counted as markers of angiogenesis. Expression of angiogenic and inflammatory factors in the puncture-induced model were determined by qPCR and western blot. Punctures led to increased neovascularization and sprouting of the iris. qPCR and protein analysis showed an increase of angiogenic factors, particularly in the plasminogen-activating receptor and inflammatory systems. VEGF-blockage partly reduced iris neovascularization, and treatment with hypoxia-conditioned RPE medium led to a statistically significant increase in iris neovascularization. This study presents the first evidence of a puncture-induced iris angiogenesis model in the mouse. In a broader context, this novel in vivo model of neovascularization has the potential for noninvasive evaluation of angiogenesis modulating substances.

  2. A novel in vivo model of puncture-induced iris neovascularization

    PubMed Central

    Aronsson, Monica; Kvanta, Anders

    2017-01-01

    Purpose To assess iris neovascularization by uveal puncture of the mouse eye and determine the role of angiogenic factors during iris neovascularization. Methods Uveal punctures were performed on BalbC mouse eyes to induce iris angiogenesis. VEGF-blockage was used as an anti-angiogenic treatment, while normoxia- and hypoxia-conditioned media from retinal pigment epithelium (RPE) cells was used as an angiogenic-inducer in this model. Iris vasculature was determined in vivo by noninvasive methods. Iris blood vessels were stained for platelet endothelial cell adhesion molecule-1 and vascular sprouts were counted as markers of angiogenesis. Expression of angiogenic and inflammatory factors in the puncture-induced model were determined by qPCR and western blot. Results Punctures led to increased neovascularization and sprouting of the iris. qPCR and protein analysis showed an increase of angiogenic factors, particularly in the plasminogen-activating receptor and inflammatory systems. VEGF-blockage partly reduced iris neovascularization, and treatment with hypoxia-conditioned RPE medium led to a statistically significant increase in iris neovascularization. Conclusions This study presents the first evidence of a puncture-induced iris angiogenesis model in the mouse. In a broader context, this novel in vivo model of neovascularization has the potential for noninvasive evaluation of angiogenesis modulating substances. PMID:28658313

  3. ASSOCIATION OF DRUSEN VOLUME WITH CHOROIDAL PARAMETERS IN NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION.

    PubMed

    Balasubramanian, Siva; Lei, Jianqin; Nittala, Muneeswar G; Velaga, Swetha B; Haines, Jonathan; Pericak-Vance, Margaret A; Stambolian, Dwight; Sadda, SriniVas R

    2017-10-01

    The choroid is thought to be relevant to the pathogenesis of nonneovascular age-related macular degeneration, but its role has not yet been fully defined. In this study, we evaluate the relationship between the extent of macular drusen and specific choroidal parameters, including thickness and intensity. Spectral domain optical coherence tomography images were collected from two distinct, independent cohorts with nonneovascular age-related macular degeneration: Amish (53 eyes of 34 subjects) and non-Amish (40 eyes from 26 subjects). All spectral domain optical coherence tomography scans were obtained using the Cirrus HD-OCT with a 512 × 128 macular cube (6 × 6 mm) protocol. The Cirrus advanced retinal pigment epithelium analysis tool was used to automatically compute drusen volume within 3 mm (DV3) and 5 mm (DV5) circles centered on the fovea. The inner and outer borders of the choroid were manually segmented, and the mean choroidal thickness and choroidal intensity (i.e., brightness) were calculated. The choroidal intensity was normalized against the vitreous and nerve fiber layer reflectivity. The correlation between DV and these choroidal parameters was assessed using Pearson and linear regression analysis. A significant positive correlation was observed between normalized choroidal intensity and DV5 in the Amish (r = 0.42, P = 0.002) and non-Amish (r = 0.33, P = 0.03) cohorts. Also, DV3 showed a significant positive correlation with normalized choroidal intensity in both the groups (Amish: r = 0.30, P = 0.02; non-Amish: r = 0.32, P = 0.04). Choroidal thickness was negatively correlated with normalized choroidal intensity in both Amish (r = -0.71, P = 0.001) and non-Amish (r = -0.43, P = 0.01) groups. Normalized choroidal intensity was the most significant constant predictor of DV in both the Amish and non-Amish groups. Choroidal intensity, but not choroidal thickness, seems to be associated with drusen volume in Amish and non-Amish populations. These

  4. Methylation profiling of choroid plexus tumors reveals 3 clinically distinct subgroups.

    PubMed

    Thomas, Christian; Sill, Martin; Ruland, Vincent; Witten, Anika; Hartung, Stefan; Kordes, Uwe; Jeibmann, Astrid; Beschorner, Rudi; Keyvani, Kathy; Bergmann, Markus; Mittelbronn, Michel; Pietsch, Torsten; Felsberg, Jörg; Monoranu, Camelia M; Varlet, Pascale; Hauser, Peter; Olar, Adriana; Grundy, Richard G; Wolff, Johannes E; Korshunov, Andrey; Jones, David T; Bewerunge-Hudler, Melanie; Hovestadt, Volker; von Deimling, Andreas; Pfister, Stefan M; Paulus, Werner; Capper, David; Hasselblatt, Martin

    2016-06-01

    Choroid plexus tumors are intraventricular neoplasms derived from the choroid plexus epithelium. A better knowledge of molecular factors involved in choroid plexus tumor biology may aid in identifying patients at risk for recurrence. Methylation profiles were examined in 29 choroid plexus papillomas (CPPs, WHO grade I), 32 atypical choroid plexus papillomas (aCPPs, WHO grade II), and 31 choroid plexus carcinomas (CPCs, WHO grade III) by Illumina Infinium HumanMethylation450 Bead Chip Array. Unsupervised hierarchical clustering identified 3 subgroups: methylation cluster 1 (pediatric CPP and aCPP of mainly supratentorial location), methylation cluster 2 (adult CPP and aCPP of mainly infratentorial location), and methylation cluster 3 (pediatric CPP, aCPP, and CPC of supratentorial location). In methylation cluster 3, progression-free survival (PFS) accounted for a mean of 72 months (CI, 55-89 mo), whereas only 1 of 42 tumors of methylation clusters 1 and 2 progressed (P< .001). On stratification of outcome data according to WHO grade, all CPCs clustered within cluster 3 and were associated with shorter overall survival (mean, 105 mo [CI, 81-128 mo]) and PFS (mean, 55 mo [CI, 36-73 mo]). The aCPP of methylation cluster 3 also progressed frequently (mean, 69 mo [CI, 44-93 mo]), whereas no tumor progression was observed in aCPP of methylation clusters 1 and 2 (P< .05). Only 1 of 29 CPPs recurred. Methylation profiling of choroid plexus tumors reveals 3 distinct subgroups (ie, pediatric low-risk choroid plexus tumors [cluster 1], adult low-risk choroid plexus tumors [cluster 2], and pediatric high-risk choroid plexus tumors [cluster 3]) and may provide useful prognostic information in addition to histopathology. Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  5. Opposite Effects of Glucagon and Insulin on Compensation for Spectacle Lenses in Chicks

    PubMed Central

    Zhu, Xiaoying; Wallman, Josh

    2009-01-01

    Purpose Chick eyes compensate for defocus imposed by positive or negative spectacle lenses. Glucagon may signal the sign of defocus. Do insulin (or IGF-1) and glucagon act oppositely in controlling eye growth, as they do in metabolic pathways and in control of retinal neurogenesis? Methods Chicks, wearing either lenses or diffusers or neither over both eyes, were injected with glucagon, a glucagon antagonist, insulin, or IGF-1 in one eye (saline in other eye). Alternatively, chicks without lenses received insulin plus glucagon in one eye, and either glucagon or insulin in the fellow eye. Ocular dimensions, refractive errors and glycosaminoglycan synthesis were measured over 2-4 days. Results Glucagon attenuated the myopic response to negative lenses or diffusers by slowing ocular elongation and thickening the choroid; in contrast, with positive lenses, it increased ocular elongation to normal levels and reduced choroidal thickening, as did a glucagon antagonist. Insulin prevented the hyperopic response to positive lenses by speeding ocular elongation and thinning the choroid. In eyes without lenses, both insulin and IGF-1 speeded, and glucagon slowed, ocular elongation, but either glucagon or insulin increased the rate of thickening of the crystalline lens. When injected together, insulin blocked choroidal thickening by glucagon, at a dose that did not, by itself, thin the choroid. Conclusions Glucagon and insulin (or IGF-1) cause generally opposite modulations of eye-growth, with glucagon mostly increasing choroidal thickness and insulin mostly increasing ocular elongation. These effects are mutually inhibitory and depend on the visual input. PMID:18791176

  6. Choroid plexus adenoma in a child: expanding the clinical and pathological spectrum.

    PubMed

    Prendergast, Nicole; Goldstein, Jeffrey D; Beier, Alexandra D

    2018-04-01

    Primary choroid plexus tumors encompass a variety of tumors, with choroid plexus papilloma and carcinoma being the most common. Also in the differential diagnosis is the rare benign choroid plexus adenoma. As these tumors are infrequently described, the histological profile continues to evolve. The authors present a case with unusual characteristics that will broaden the pathological spectrum for choroid plexus adenomas.

  7. Choroidal metastasis from early rectal cancer: Case report and literature review.

    PubMed

    Tei, Mitsuyoshi; Wakasugi, Masaki; Akamatsu, Hiroki

    2014-01-01

    Choroidal metastasis from colorectal cancer is rare, and there have been no reported cases of such metastasis from early colorectal cancer. We report a case of choroidal metastasis from early rectal cancer. A 61 year-old-man experienced myodesopsia in the left eye 2 years and 6 months after primary rectal surgery for early cancer, and was diagnosed with left choroidal metastasis and multiple lung metastases. Radiotherapy was initiated for the left eye and systemic chemotherapy is initiated for the multiple lung metastases. The patient is living 2 years and 3 months after the diagnosis of choroidal metastasis without signs of recurrence in the left eye, and continues to receive systemic chemotherapy for multiple lung metastases. Current literatures have few recommendations regarding the appropriate treatment of choroidal metastasis from colorectal cancer, but an aggressive multi-disciplinary approach may be effective in local regression. This is the first report of choroidal metastasis from early rectal cancer. We consider it important to enforce systemic chemotherapy in addition to radiotherapy for choroidal metastasis from colorectal cancer. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Syringomyelia with intramedullary ectopic choroid plexus: Case report.

    PubMed

    Duan, Hongzhou; Zhang, Jiayong; Xu, Feifan; Zhang, Zongqiang; Zhao, Xiaowen

    2018-06-01

    Intramedullary ectopic choroid plexus is rarely reported, here, we reported a rare case of symptomatic syringomyelia resulted of intramedullary ectopic choroid plexus. The patient was a 30-year-old female who presented with a 2-month history of progressive pain of upper back and bilateral ankle joint and progressive loss of upper-extremity function. MRI examination showed an intramedullary cystic lesion at T2-T4 without enhancement. Operative exploration was indicated. A reddish vascular villus-like lesion was found being located in the left dorsal part of the cyst, which was enblock removed and was confirmed as an ectopic choroid plexus tissue by pathological examination. The patient recovered uneventful and the symptom resolved during follow-up. Although ectopic choroid plexus is extremely rare, it should be taken into acount in the differential diagnosis of pathogenesis in syringomyelia or intramedullary cyst, aggressive surgical exploration should be considered when necessary. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Altered gravity downregulates aquaporin-1 protein expression in choroid plexus.

    PubMed

    Masseguin, C; Corcoran, M; Carcenac, C; Daunton, N G; Güell, A; Verkman, A S; Gabrion, J

    2000-03-01

    Aquaporin-1 (AQP1) is a water channel expressed abundantly at the apical pole of choroidal epithelial cells. The protein expression was quantified by immunocytochemistry and confocal microscopy in adult rats adapted to altered gravity. AQP1 expression was decreased by 64% at the apical pole of choroidal cells in rats dissected 5.5-8 h after a 14-day spaceflight. AQP1 was significantly overexpressed in rats readapted for 2 days to Earth's gravity after an 11-day flight (48% overshoot, when compared with the value measured in control rats). In a ground-based model that simulates some effects of weightlessness and alters choroidal structures and functions, apical AQP1 expression was reduced by 44% in choroid plexus from rats suspended head down for 14 days and by 69% in rats suspended for 28 days. Apical AQP1 was rapidly enhanced in choroid plexus of rats dissected 6 h after a 14-day suspension (57% overshoot, in comparison with control rats) and restored to the control level when rats were dissected 2 days after the end of a 14-day suspension. Decreases in the apical expression of choroidal AQP1 were also noted in rats adapted to hypergravity in the NASA 24-ft centrifuge: AQP1 expression was reduced by 47% and 85% in rats adapted for 14 days to 2 G and 3 G, respectively. AQP1 is downregulated in the apical membrane of choroidal cells in response to altered gravity and is rapidly restored after readaptation to normal gravity. This suggests that water transport, which is partly involved in the choroidal production of cerebrospinal fluid, might be decreased during spaceflight and after chronic hypergravity.

  10. Establishment of a tumor neovascularization animal model with biomaterials in rabbit corneal pouch.

    PubMed

    Chu, Yu-Ping; Li, Hong-Chuan; Ma, Ling; Xia, Yang

    2018-06-01

    The present animal model of tumor neovascularization most often used by researchers is zebrafish. For studies on human breast cancer cell neovascularization, a new animal model was established to enable a more convenient study of tumor neovascularization. A sodium alginate-gelatin blend gel system was used to design the new animal model. The model was established using rabbit corneal pouch implantation. Then, the animal model was validated by human breast cancer cell lines MCF-7-Kindlin-2 and MCF-7-CMV. The experiment intuitively observed the relationship between tumor and neovascularization, and demonstrated the advantages of this animal model in the study of tumor neovascularization. The use of sodium alginate-gelatin blends to establish tumor neovascularization in a rabbit corneal pouch is a novel and ideal method for the study of neovascularization. It may be a better animal model for expanding the research in this area. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Triple therapy for age-related macular degeneration.

    PubMed

    Augustin, Albert

    2009-06-01

    Choroidal neovascularization is a hallmark sign of wet age-related macular degeneration (AMD) but it is not an isolated feature. Several processes are likely to contribute to the fibrotic scarring and vision loss that accompanies progressive disease. In a case series, a triple therapy approach to wet AMD was based on the goals of halting choroidal neovascularization, controlling the inflammatory response, and modifying proliferative factors. To address each of these goals, respectively, patients received photodynamic therapy, bevacizumab, and the steroid dexamethasone. The encouraging rate of response, including significant improvements in visual acuity, is consistent with the combined activities of these agents and provides the basis for more definitive studies.

  12. [Choroid plexus tumors].

    PubMed

    Pianetti, G; Fonseca, L F

    1998-06-01

    This analysis comprises 15 children under 16 years of age, with choroid plexus tumors, seen in the Service of Paediatric Neurosurgery, Hospital das Clínicas and Hospital São Francisco de Assis in Belo Horizonte, Brazil, between 1981 and 1996. The patients were aged between 4 months and 16 years (average of 3 years and a half); 10 were less than 2 years, 9 were female; 14 children had clinical evidence of intracranial hypertension. All the children underwent CT scan and the choroid plexus tumors were clearly demonstrated in 14 of then. In 8 children the tumors were located in one lateral ventricle, 5 in the fourth ventricle and 2 had the tumors in more than one ventricle, 11 children required ventriculo-peritoneal shunt; 14 cases were operated on, 13 with total excision; 2 children died, respectively 7 days and one year after the surgery. Pathological examination revealed papillomas in 12 cases and carcinoma in two cases.

  13. Immunotherapy for choroidal neovascularization in a laser-induced mouse model simulating exudative (wet) macular degeneration

    NASA Astrophysics Data System (ADS)

    Bora, Puran S.; Hu, Zhiwei; Tezel, Tongalp H.; Sohn, Jeong-Hyeon; Kang, Shin Goo; Cruz, Jose M. C.; Bora, Nalini S.; Garen, Alan; Kaplan, Henry J.

    2003-03-01

    Age-related macular degeneration (AMD) is the leading cause of blindness after age 55 in the industrialized world. Severe loss of central vision frequently occurs with the exudative (wet) form of AMD, as a result of the formation of a pathological choroidal neovasculature (CNV) that damages the macular region of the retina. We tested the effect of an immunotherapy procedure, which had been shown to destroy the pathological neovasculature in solid tumors, on the formation of laser-induced CNV in a mouse model simulating exudative AMD in humans. The procedure involves administering an Icon molecule that binds with high affinity and specificity to tissue factor (TF), resulting in the activation of a potent cytolytic immune response against cells expressing TF. The Icon binds selectively to TF on the vascular endothelium of a CNV in the mouse and pig models and also on the CNV of patients with exudative AMD. Here we show that the Icon dramatically reduces the frequency of CNV formation in the mouse model. After laser treatment to induce CNV formation, the mice were injected either with an adenoviral vector encoding the Icon, resulting in synthesis of the Icon by vector-infected mouse cells, or with the Icon protein. The route of injection was i.v. or intraocular. The efficacy of the Icon in preventing formation of laser-induced CNV depends on binding selectively to the CNV. Because the Icon binds selectively to the CNV in exudative AMD as well as to laser-induced CNV, the Icon might also be efficacious for treating patients with exudative AMD.

  14. Submacular hemorrhage in neovascular age-related macular degeneration: A synthesis of the literature.

    PubMed

    Stanescu-Segall, Dinu; Balta, Florian; Jackson, Timothy L

    2016-01-01

    Large submacular hemorrhage, an uncommon manifestation of neovascular age-related macular degeneration, may also occur with idiopathic polypoidal choroidal vasculopathy. Submacular hemorrhage damages photoreceptors owing to iron toxicity, fibrin meshwork contraction, and reduced nutrient flux, with subsequent macular scarring. Clinical and experimental studies support prompt treatment, as tissue damage can occur within 24 hours. Without treatment the natural history is poor, with a mean final visual acuity (VA) of 20/1600. Reported treatments include retinal pigment epithelial patch, macular translocation, pneumatic displacement, intravitreal or subretinal tissue plasminogen activator, intravitreal anti-vascular endothelial growth factor (VEGF) drugs, and combinations thereof. In the absence of comparative studies, we combined eligible studies to assess the VA change before and after each treatment option. The greatest improvement occurred after combined pars plana vitrectomy, subretinal tissue plasminogen activator, intravitreal gas, and anti-vascular endothelial growth factor treatment, with VA improving from 20/1000 to 20/400. The best final VA occurred using combined intravitreal tissue plasminogen activator, gas, and anti-vascular endothelial growth factor therapy, with VA improving from 20/200 to 20/100. Both treatments had an acceptable safety profile, but most studies were small, and larger randomized controlled trials are needed to determine both safety and efficacy. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  15. Choroid plexus papilloma in a beluga whale (Delphinapterus leucas).

    PubMed

    Thomas, Christian; Mergl, June; Gehring, Erica; Paulus, Werner; Martineau, Daniel; Hasselblatt, Martin

    2016-07-01

    We report herein a choroid plexus papilloma in a beluga whale (Delphinapterus leucas). This case was positive for choroid plexus tumor marker Kir7.1 on immunohistochemistry. These results and the high conservation of Kir7.1 across species at the amino acid sequence level strongly suggest that antibodies directed against Kir7.1 not only can be employed for the diagnosis of choroid plexus tumors in cetaceans, but are also likely to be diagnostically useful in other animal species. © 2016 The Author(s).

  16. MACULAR CHOROIDAL VOLUME CHANGES AFTER INTRAVITREAL BEVACIZUMAB FOR EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

    PubMed

    Palkovits, Stefan; Seidel, Gerald; Pertl, Laura; Malle, Eva M; Hausberger, Silke; Makk, Johanna; Singer, Christoph; Osterholt, Julia; Herzog, Sereina A; Haas, Anton; Weger, Martin

    2017-12-01

    To evaluate the effect of intravitreal bevacizumab on the macular choroidal volume and the subfoveal choroidal thickness in treatment naïve eyes with exudative age-related macular degeneration. The macular choroidal volume and the subfoveal choroidal thickness were measured using enhanced depth imaging optical coherence tomography. After a screening examination, each patient received 3 monthly intravitreal injections of 1.25 mg bevacizumab. One month after the third injection was a final assessment. Forty-seven patients with a mean age of 80 ± 6.4 years were included. The macular choroidal volume decreased significantly from median 4.1 mm (interquartile range 3.4-5.9) to median 3.9 mm (interquartile range 3.1-5.6) between the baseline and final examination (difference -0.46 mm, 95% confidence interval: -0.57 to 0.35, P < 0.001). Similarly, subfoveal choroidal thickness had decreased from 157.0 μm (interquartile range 116.0-244.5) at baseline to 139.0 μm (interquartile range 102.5-212.0) at the final examination (P < 0.001). Both parameters macular choroidal volume at baseline and subfoveal choroidal thickness at baseline were not associated with the response to treatment. The macular choroidal volume and the subfoveal choroidal thickness decreased significantly after 3 monthly bevacizumab injections for exudative age-related macular degeneration.

  17. Severe Ocular Inflammation Following Ranibizumab or Aflibercept Injections for Age-Related Macular Degeneration: A Retrospective Claims Database Analysis

    PubMed Central

    Souied, Eric H.; Dugel, Pravin U.; Ferreira, Alberto; Hashmonay, Ron; Lu, Jingsong; Kelly, Simon P.

    2016-01-01

    ABSTRACT Purpose: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents including ranibizumab and aflibercept are used to treat patients with ocular disorders such as neovascular age-related macular degeneration (nAMD); however, the injections are associated with rare instances of severe ocular inflammation. This study compared severe ocular inflammation rates in patients treated with ranibizumab versus aflibercept. Methods: United States physician-level claims data covering an 18-month period for each therapy were analyzed. The primary analysis compared severe ocular inflammation event rates per 1000 injections. Sensitivity and subgroup analyses evaluated the impact of factors including intraocular surgery, intravitreal antibiotic administration, and previous intravitreal injections. Results: The analysis included 432,794 injection claims (ranibizumab n = 253,647, aflibercept n = 179,147); significantly, more unique severe ocular inflammation events occurred in patients receiving aflibercept than ranibizumab (1.06/1000 injections, 95% confidence interval [CI], 0.91–1.21, vs. 0.64/1000 injections, 95% CI 0.54–0.74; p < 0.0001). Comparable results were observed for analyses of patients who had undergone glaucoma or cataract surgeries, had antibiotic-associated endophthalmitis, had non-antibiotic-associated endophthalmitis, and were non-treatment-naive. In contrast, no significant differences in severe ocular inflammation claims were recorded in treatment-naive patients who had no record of anti-VEGF treatment in the 6 months preceding the index claim. No significant change occurred in the rate of severe ocular inflammation claims over time following ranibizumab treatment. Conclusions: Severe ocular inflammation was more frequent following intravitreal injection with aflibercept than with ranibizumab during routine clinical use in patients with nAMD. This highlights the importance of real-world, post-approval, observational monitoring

  18. The ocular lesions of naturally occurring lymphocystis in fish.

    PubMed Central

    Dukes, T W; Lawler, A R

    1975-01-01

    Six cases of ocular lymphocystis, a virus disease, are described. Lymphocystis is generally known as a benigh, unique, giant cell disease of fishes causing nodules on the skin and fins. It has been studied extensively because of the virus-host cell relationship that results in extreme size and lack of quick cellular destruction or stimulation to neoplasia. Lymphocystis cells were found behind or in one or both eyes and were also found on the cornea or adjacent skin surfaces. A retrobulbar mass produced extreme exophthalmos. Uveal (choroid and iris) masses were present in most cases. Optic nerve involvement was also seen. It is probable that the virus reached the eye by the blood with the resulting masses forming in situ rather than by direct extension from skin lesions. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:1175076

  19. Association between choroidal pigmentation and posterior uveal melanoma in a white population

    PubMed Central

    Harbour, J W; Brantley, M A; Hollingsworth, H; Gordon, M

    2004-01-01

    Background/aims: It is well known that light skin pigmentation is a risk factor for cutaneous melanoma. The aim of this study was to investigate the analogous association between choroidal pigmentation and posterior uveal melanoma. Methods: Cross sectional study of 65 consecutive patients diagnosed with posterior uveal melanoma (melanoma group) and 218 consecutive patients referred for general retinal evaluation (control group). All patients were white. A clinical grading system for estimating choroidal pigmentation was developed and histologically validated in seven patients. Results: Melanoma patients with light iris colour were significantly more likely to have darker choroidal pigmentation than controls (p = 0.005). Darker choroidal pigmentation was associated histologically with increased density of choroidal melanocytes (p = 0.005). Conclusions: Increased choroidal pigmentation, as a result of an increase in the density of pigmented choroidal melanocytes, is not protective but may actually be a risk factor for the development of posterior uveal melanoma in white patients. This finding may have implications for understanding the pathogenesis of uveal melanoma. PMID:14693770

  20. En Face Optical Coherence Tomography for Visualization of the Choroid.

    PubMed

    Savastano, Maria Cristina; Rispoli, Marco; Savastano, Alfonso; Lumbroso, Bruno

    2015-05-01

    To assess posterior pole choroid patterns in healthy eyes using en face optical coherence tomography (OCT). This observational study included 154 healthy eyes of 77 patients who underwent en face OCT. The mean age of the patients was 31.2 years (standard deviation: 13 years); 40 patients were women, and 37 patients were men. En face imaging of the choroidal vasculature was assessed using an OCT Optovue RTVue (Optovue, Fremont, CA). To generate an appropriate choroid image, the best detectable vessels in Haller's layer below the retinal pigment epithelium surface parallel plane were selected. Images of diverse choroidal vessel patterns at the posterior pole were observed and recorded with en face OCT. Five different patterns of Haller's layer with different occurrences were assessed. Pattern 1 (temporal herringbone) represented 49.2%, pattern 2 (branched from below) and pattern 3 (laterally diagonal) represented 14.2%, pattern 4 (doubled arcuate) was observed in 11.9%, and pattern 5 (reticular feature) was observed in 10.5% of the reference plane. In vivo assessment of human choroid microvasculature in healthy eyes using en face OCT demonstrated five different patterns. The choroid vasculature pattern may play a role in the origin and development of neuroretinal pathologies, with potential importance in chorioretinal diseases and circulatory abnormalities. Copyright 2015, SLACK Incorporated.

  1. Comparison of pro re nata versus Bimonthly Injection of Intravitreal Aflibercept for Typical Neovascular Age-Related Macular Degeneration.

    PubMed

    Mori, Ryusaburo; Tanaka, Koji; Haruyama, Miho; Kawamura, Akiyuki; Furuya, Koichi; Yuzawa, Mitsuko

    2017-01-01

    The aim of this study was to clarify the 1-year outcomes of pro re nata (PRN) and bimonthly intravitreal injections of aflibercept (IVA) for typical neovascular age-related macular degeneration (tAMD) after the initial 3 monthly IVA. We conducted a prospective, interventional study. Fifty-eight treatment-naïve patients with tAMD were randomly assigned to the PRN (30 patients) or the bimonthly (28 patients) treatment group. Both groups initially received 3 monthly IVA. Visual acuity, central macular retinal thickness (CRT), and central choroidal thickness (CCT) were evaluated at 12 months. Subanalysis was performed to identify factors associated with the best-corrected visual acuity (BCVA). BCVA was significantly improved only in the bimonthly group at 12 months. CRT and CCT were significantly decreased in both groups. Subanalysis showed that the only factor associated with BCVA improvement at 12 months was the existence of pigment epithelial detachment at baseline. BCVA showed significant improvement only in the bimonthly group but not in the PRN group at 12 months. © 2017 S. Karger AG, Basel.

  2. Numerical Modeling of Ocular Dysfunction in Space

    NASA Technical Reports Server (NTRS)

    Nelson, Emily S.; Mulugeta, Lealem; Vera, J.; Myers, J. G.; Raykin, J.; Feola, A. J.; Gleason, R.; Samuels, B.; Ethier, C. R.

    2014-01-01

    Upon introduction to microgravity, the near-loss of hydrostatic pressure causes a marked cephalic (headward) shift of fluid in an astronaut's body. The fluid shift, along with other factors of spaceflight, induces a cascade of interdependent physiological responses which occur at varying time scales. Long-duration missions carry an increased risk for the development of the Visual Impairment and Intracranial Pressure (VIIP) syndrome, a spectrum of ophthalmic changes including posterior globe flattening, choroidal folds, distension of the optic nerve sheath, kinking of the optic nerve and potentially permanent degradation of visual function. In the cases of VIIP found to date, the initial onset of symptoms occurred after several weeks to several months of spaceflight, by which time the gross bodily fluid distribution is well established. We are developing a suite of numerical models to simulate the effects of fluid shift on the cardiovascular, central nervous and ocular systems. These models calculate the modified mean volumes, flow rates and pressures that are characteristic of the altered quasi-homeostatic state in microgravity, including intracranial and intraocular pressures. The results of the lumped models provide initial and boundary data to a 3D finite element biomechanics simulation of the globe, optic nerve head and retrobulbar subarachnoid space. The integrated set of models will be used to investigate the evolution of the biomechanical stress state in the ocular tissues due to long-term exposure to microgravity.

  3. Ranibizumab for the Prevention of Radiation Complications in Patients Treated With Proton Beam Irradiation for Choroidal Melanoma (An American Ophthalmological Society Thesis)

    PubMed Central

    Kim, Ivana K.; Lane, Anne Marie; Jain, Purva; Awh, Caroline; Gragoudas, Evangelos S.

    2016-01-01

    Purpose: To investigate the safety and potential efficacy of ranibizumab for prevention of radiation complications in patients treated with proton irradiation for choroidal melanoma Methods: Forty patients with tumors located within 2 disc diameters of the optic nerve and/or macula were enrolled in this open-label study. Participants received ranibizumab 0.5 mg or 1.0 mg at tumor localization and every 2 months thereafter for the study duration of 24 months. The incidence of adverse events, visual acuity, and other measures of ocular morbidity related to radiation complications were assessed. Historical controls with similar follow-up meeting the eligibility criteria for tumor size, location, and baseline visual acuity were assembled for comparison. Results: Fifteen patients with large tumors and 25 patients with small/medium tumors were enrolled. Thirty-two patients completed the month 24 visit. No serious ocular or systemic adverse events related to ranibizumab were observed. At 24 months, the proportion of patients with visual acuity ≥ 20/200 was 30/31 (97%) in the study group versus 92/205 (45%) in historical controls (P < .001). The proportion of patients with visual acuity ≥20/40 was 24/31 (77%) in the study group versus 46/205 (22%) in controls at 24 months (P<.001). Clinical evidence of radiation maculopathy at month 24 was seen in 8/24 (33%) patients with small/medium tumors versus 42/62 (68%) of controls (P = .004). Three patients with large tumors developed metastases. Conclusions: In this small pilot study, prophylactic ranibizumab appears generally safe in patients treated with proton irradiation for choroidal melanoma. High rates of visual acuity retention were observed through 2 years. PMID:27630373

  4. Choroid plexus papillomas: advances in molecular biology and understanding of tumorigenesis.

    PubMed

    Safaee, Michael; Oh, Michael C; Bloch, Orin; Sun, Matthew Z; Kaur, Gurvinder; Auguste, Kurtis I; Tihan, Tarik; Parsa, Andrew T

    2013-03-01

    Choroid plexus papillomas are rare, benign tumors originating from the choroid plexus. Although generally found within the ventricular system, they can arise ectopically in the brain parenchyma or disseminate throughout the neuraxis. We sought to review recent advances in our understanding of the molecular biology and oncogenic pathways associated with this disease. A comprehensive PubMed literature review was conducted to identify manuscripts discussing the clinical, molecular, and genetic features of choroid plexus papillomas. Articles concerning diagnosis, treatment, and long-term patient outcomes were also reviewed. The introduction of atypical choroid plexus papilloma as a distinct entity has increased the need for accurate histopathologic diagnosis. Advances in immunohistochemical staining have improved our ability to differentiate choroid plexus papillomas from other intracranial tumors or metastatic lesions using combinations of key markers and mitotic indices. Recent findings have implicated Notch3 signaling, the transcription factor TWIST1, platelet-derived growth factor receptor, and the tumor necrosis factor-related apoptosis-inducing ligand pathway in choroid plexus papilloma tumorigenesis. A combination of commonly occurring chromosomal duplications and deletions has also been identified. Surgical resection remains the standard of care, although chemotherapy and radiotherapy may be considered for recurrent or metastatic lesions. While generally considered benign, these tumors possess a complex biology that sheds insight into other choroid plexus tumors, particularly malignant choroid plexus carcinomas. Improving our understanding of the molecular biology, genetics, and oncogenic pathways associated with this tumor will allow for the development of targeted therapies and improved outcomes for patients with this disease.

  5. Neovascular growth in an experimental alkali corneal burn model.

    PubMed

    Figueroa-Ortiz, L C; Martín Rodríguez, O; García-Ben, A; García-Campos, J

    2014-08-01

    To analyse the length and area of corneal surface occupied by vessels, and their location in an experimental model of alkali burn-induced corneal neovascularization. An injury to the central cornea of the right eye in 91 Sprague-Dawley rats was induced using a silver nitrate pencil. The rats were divided in 7 groups that were sacrificed 2, 4, 6, 8, 10, 12 and 14 days post-injury, and then perfused with a mixture of Chinese ink in PBS -phosphate buffer saline-. Corneas were flat-mounted processed and divided in 4 quadrants. Corneal neovascular growth parameters (length and area) and the location of these vessels were performed blind. The results were statistically analysed. Neovascular growth was observed from day 2, reaching its maximum peak in length and area on the 12th day post-injury. A slight reduction in corneal neovascularization was observed after this day. The vessels were initially located in the middle third of the stroma and tended to be observed in the anterior third during the course of the experiment. Neovascularisation was observed on day 2 post-injury in all sectors of corneal surface. Neovascular growth was uniform during the experiment. Neovessels were located in the middle and anterior third of the cornea. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  6. Choroidal Haller's and Sattler's Layers Thickness in Normal Indian Eyes.

    PubMed

    Roy, Rupak; Saurabh, Kumar; Vyas, Chinmayi; Deshmukh, Kaustubh; Sharma, Preeti; Chandrasekharan, Dhileesh P; Bansal, Aditya

    2018-01-01

    This study aims to study normative choroidal thickness (CT) and Haller's and Sattler's layers thickness in normal Indian eyes. The choroidal imaging of 73 eyes of 43 healthy Indian individuals was done using enhanced depth imaging feature of spectralis optical coherence tomography. Rraster scan protocol centered at fovea was used for imaging separately by two observers. CT was defined as the length of the perpendicular line drown from the outer border of hypereflective RPE-Bruch's complex to inner margin of choroidoscleral junction. Choroidal vessel layer thickness was measured after defining a largest choroidal vessel lumen within 750 μ on either side of the subfoveal CT vector. A perpendicular line was drawn to the innermost border of this lumen, and the distance between the perpendicular line and innermost border of choroidoscleral junction gave large choroidal vessel layer thickness (LCVLT, Haller's layer). Medium choroidal vessel layer thickness (MCVLT, Sattler's layer) was measured as the distance between same perpendicular line and outer border of hypereflective RPE-Bruch's complex. The mean age of individuals was 28.23 ± 15.29 years (range 14-59 years). Overall, the mean subfoveal CT was 331.6 ± 63.9 μ. Mean LCVLT was 227.08 ± 51.24 μ and the mean MCVLT was 95.65 ± 23.62 μ. CT was maximum subfoveally with gradual reduction in the thickness as the distance from the fovea increased. This is the first study describing the choroidal sublayer thickness, i.e., Haller's and Sattler's layer thickness along with CT in healthy Indian population.

  7. Choroidal Haller's and Sattler's Layers Thickness in Normal Indian Eyes

    PubMed Central

    Roy, Rupak; Saurabh, Kumar; Vyas, Chinmayi; Deshmukh, Kaustubh; Sharma, Preeti; Chandrasekharan, Dhileesh P.; Bansal, Aditya

    2018-01-01

    AIM: This study aims to study normative choroidal thickness (CT) and Haller's and Sattler's layers thickness in normal Indian eyes. MATERIALS AND METHODS: The choroidal imaging of 73 eyes of 43 healthy Indian individuals was done using enhanced depth imaging feature of spectralis optical coherence tomography. Rraster scan protocol centered at fovea was used for imaging separately by two observers. CT was defined as the length of the perpendicular line drown from the outer border of hypereflective RPE-Bruch's complex to inner margin of choroidoscleral junction. Choroidal vessel layer thickness was measured after defining a largest choroidal vessel lumen within 750 μ on either side of the subfoveal CT vector. A perpendicular line was drawn to the innermost border of this lumen, and the distance between the perpendicular line and innermost border of choroidoscleral junction gave large choroidal vessel layer thickness (LCVLT, Haller's layer). Medium choroidal vessel layer thickness (MCVLT, Sattler's layer) was measured as the distance between same perpendicular line and outer border of hypereflective RPE-Bruch's complex. RESULTS: The mean age of individuals was 28.23 ± 15.29 years (range 14–59 years). Overall, the mean subfoveal CT was 331.6 ± 63.9 μ. Mean LCVLT was 227.08 ± 51.24 μ and the mean MCVLT was 95.65 ± 23.62 μ. CT was maximum subfoveally with gradual reduction in the thickness as the distance from the fovea increased. CONCLUSION: This is the first study describing the choroidal sublayer thickness, i.e., Haller's and Sattler's layer thickness along with CT in healthy Indian population. PMID:29899646

  8. Adaptive Optics of Small Choroidal Melanoma.

    PubMed

    Rodrigues, Murilo W; Say, Emil A; Shields, Carol L; Jorge, Rodrigo

    2017-04-01

    The authors report the use of an adaptive optics (AO) system in an asymptomatic patient with small choroidal melanoma. A noninvasive, novel assessment that detected potential photoreceptor abnormalities in the retina overlying the choroidal lesion and adjacent retina is presented. These findings may help current clinical evaluation to monitor structural damage to the outer retina and possibly justify earlier intervention in borderline cases. Future research is warranted to recognize full potential of this imaging modality. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:354-357.]. Copyright 2017, SLACK Incorporated.

  9. Implants for draining neovascular glaucoma.

    PubMed Central

    Molteno, A C; Van Rooyen, M M; Bartholomew, R S

    1977-01-01

    The implant design, surgical technique, and pharmacological methods of controlling bleb fibrosis, used to treat neovascular glaucoma, are described, together with the results of 14 operations performed on 12 eyes. Images PMID:843508

  10. Gelsolin Restores Aβ-Induced Alterations in Choroid Plexus Epithelium

    PubMed Central

    Vargas, Teo; Antequera, Desiree; Ugalde, Cristina; Spuch, Carlos; Carro, Eva

    2010-01-01

    Histologically, Alzheimer's disease (AD) is characterized by senile plaques and cerebrovascular amyloid deposits. In previous studies we demonstrated that in AD patients, amyloid-β (Aβ) peptide also accumulates in choroid plexus, and that this process is associated with mitochondrial dysfunction and epithelial cell death. However, the molecular mechanisms underlying Aβ accumulation at the choroid plexus epithelium remain unclear. Aβ clearance, from the brain to the blood, involves Aβ carrier proteins that bind to megalin, including gelsolin, a protein produced specifically by the choroid plexus epithelial cells. In this study, we show that treatment with gelsolin reduces Aβ-induced cytoskeletal disruption of blood-cerebrospinal fluid (CSF) barrier at the choroid plexus. Additionally, our results demonstrate that gelsolin plays an important role in decreasing Aβ-induced cytotoxicity by inhibiting nitric oxide production and apoptotic mitochondrial changes. Taken together, these findings make gelsolin an appealing tool for the prophylactic treatment of AD. PMID:20369065

  11. Combined 60° Wide-Field Choroidal Thickness Maps and High-Definition En Face Vasculature Visualization Using Swept-Source Megahertz OCT at 1050 nm

    PubMed Central

    Mohler, Kathrin J.; Draxinger, Wolfgang; Klein, Thomas; Kolb, Jan Philip; Wieser, Wolfgang; Haritoglou, Christos; Kampik, Anselm; Fujimoto, James G.; Neubauer, Aljoscha S.; Huber, Robert; Wolf, Armin

    2015-01-01

    Purpose To demonstrate ultrahigh-speed swept-source optical coherence tomography (SS-OCT) at 1.68 million A-scans/s for choroidal imaging in normal and diseased eyes over a ∼60° field of view. To investigate and correlate wide-field three-dimensional (3D) choroidal thickness (ChT) and vascular patterns using ChT maps and coregistered high-definition en face images extracted from a single densely sampled Megahertz-OCT (MHz-OCT) dataset. Methods High-definition, ∼60° wide-field 3D datasets consisting of 2088 × 1024 A-scans were acquired using a 1.68 MHz prototype SS-OCT system at 1050 nm based on a Fourier-domain mode-locked laser. Nine subjects (nine eyes) with various chorioretinal diseases or without ocular pathology are presented. Coregistered ChT maps, choroidal summation maps, and depth-resolved en face images referenced to either the retinal pigment epithelium or the choroidal–scleral interface were generated using manual segmentation. Results Wide-field ChT maps showed a large inter- and intraindividual variance in peripheral and central ChT. In only four of the nine eyes, the location with the largest ChT was coincident with the fovea. The anatomy of the large lumen vessels of the outer choroid seems to play a major role in determining the global ChT pattern. Focal ChT changes with large thickness gradients were observed in some eyes. Conclusions Different ChT and vascular patterns could be visualized over ∼60° in patients for the first time using OCT. Due to focal ChT changes, a high density of thickness measurements may be favorable. High-definition depth-resolved en face images are complementary to cross sections and thickness maps and enhance the interpretation of different ChT patterns. PMID:26431482

  12. A preliminary evaluation of dexamethasone palmitate emulsion: a novel intravitreal sustained delivery of corticosteroid for treatment of macular edema.

    PubMed

    Daull, Philippe; Paterson, Christopher A; Kuppermann, Baruch D; Garrigue, Jean-Sébastien

    2013-03-01

    Dexamethasone palmitate (DXP) is a lipophilic prodrug of dexamethasone (DXM), a potent corticosteroid used to treat a variety of ophthalmic diseases. The aim of the study was to characterize the sustained release capacity (in rabbit), efficacy (in rat and rabbit), and safety (in rabbit, cat, and minipig) of intravitreal (IVT) DXP emulsions in preclinical models. Oil-in-water emulsions of DXP were administered by IVT injections in rats, rabbits, cats, or minipigs. Efficacy was assessed in rabbits by the inhibition of VEGF-induced vascular leakage and in rats by inhibition of laser-induced choroidal neovascularization. Concentrations of DXP and DXM in aqueous humor, vitreous, retina, choroid, and blood were determined to characterize the ocular and systemic pharmacokinetic (PK) profile. Complete ophthalmic examinations (indirect ophthalmoscopy, slit-lamp biomacroscopy, electroretinography, tonometry) were performed to assess the ocular safety of IVT DXP doses up to 2,600 μg in minipig, followed by histopathologic examinations. A validated feline model of DXM-induced elevated intraocular pressure (IOP) was used to assess the ocular hypertensive impact (i.e., the safety) of an IVT injection of DXP emulsion. Rat and rabbit efficacy data demonstrated that IVT injections of DXP emulsions were effective. Rabbit PK data demonstrated that following a single 1,280 μg IVT injection resulted in sustained DXM levels in the retina and choroid (1,179.6 and 577.7 ng/g with a half-life of 189 and 103 days, respectively) sufficient to inhibit VEGF-induced vascular hyper-permeability for up to 9 months. No adverse ocular findings were observed in the rabbit at the 1,280 μg DXP dose. Plasma levels of DXP and DXM were close to the lower limit of quantification (0.5 ng/mL). In minipigs, no systemic effects were observed at a dose up to 2,600 μg DXP. In steroid responsive cats, IVT DXP emulsions increased IOP to a lesser extent than triamcinolone acetonide with a more rapid return to

  13. Fundus autofluorescence in serpiginouslike choroiditis.

    PubMed

    Gupta, Amod; Bansal, Reema; Gupta, Vishali; Sharma, Aman

    2012-04-01

    To report the fundus autofluorescence characteristics in serpiginouslike choroiditis. Twenty-nine patients with presumed tubercular serpiginouslike choroiditis between November 2008 and January 2010 underwent fundus autofluorescence imaging during the acute stage and at regular intervals till the lesions healed. All patients received antitubercular therapy with oral corticosteroids. The autofluorescence images were compared with color fundus photography and fundus fluorescein angiography. The main outcome measure was fundus autofluorescence characteristics of lesions during the course of the disease. The pattern of fundus autofluorescence changed as the lesions evolved from the acute to the healed stage. In acute stage, the lesions showed an ill-defined halo of increased autofluorescence (hyperautofluorescence), giving it a diffuse, amorphous appearance (Stage I, acute). As the lesions began to heal, a thin rim of decreased autofluorescence (hypoautofluorescence) surrounded the lesion, defining its edges. The lesions showed predominantly hyperautofluorescence with stippled pattern (Stage II, subacute). With further healing, the hypoautofluorescence progressed and the lesion appeared predominantly hypoautofluorescent with stippled pattern (Stage III, nearly resolved). On complete healing, the lesions became uniformly hypoautofluorescent (Stage IV, completely resolved). Fundus autofluorescence highlighted the areas of disease activity and was a quick imaging tool for monitoring the course of lesions in serpiginouslike choroiditis.

  14. Photo-mediated ultrasound therapy (PUT): a novel method of selectively treating neovascularization (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Zhang, Haonan; Hu, Zi Zhong; Li, Jia; Mordovanakis, Aghapi G.; Yang, Xinmai; Paulus, Yannis M.; Wang, Xueding

    2017-02-01

    Retinal and choroidal neovascularization play a pivotal role in the leading causes of blindness including macular degeneration and diabetic retinopathy (DR). Current therapy by focal laser photocoagulation can damage the normal surrounding cells, such as the photoreceptor inner and outer segments which are adjacent to the retinal pigment epithelium (RPE), due to the use of high laser energy and millisecond pulse duration. Therapies with pharmaceutical agents involve systemic administration of drugs, which can cause adverse effects and patients may become drug-resistant. We have developed a noninvasive photo-mediated ultrasound therapy (PUT) technique as a localized antivascular method, and applied it to remove micro blood vessels in the retina. PUT takes advantage of the high native optical contrast among biological tissues, and has the unique capability to self-target microvessels without causing unwanted damages to the surrounding tissues. This technique promotes cavitation activity in blood vessels by synergistically applying nanosecond laser pulses and ultrasound bursts. Through the interaction between cavitation and blood vessel wall, blood clots in microvessels and vasoconstriction can be induced. As a result, microvessels can be occluded. In comparison with other techniques that involves cavitation, both laser and ultrasound energy needed in PUT is significantly lower, and hence improves the safety in therapy.

  15. TYPE 3 NEOVASCULARIZATION IMAGED WITH CROSS-SECTIONAL AND EN FACE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

    PubMed

    Tan, Anna C S; Dansingani, Kunal K; Yannuzzi, Lawrence A; Sarraf, David; Freund, K Bailey

    2017-02-01

    To study the cross-sectional and en face optical coherence tomography angiography (OCTA) findings in Type 3 neovascularization (NV). Optical coherence tomography angiography imaging of 27 eyes of 23 patients with Type 3 NV was analyzed with 9 eyes having consecutive follow-up OCTA studies. Type 3 NV appeared as a linear high-flow structure on cross-sectional OCTA corresponding to a high-flow tuft of vessels seen on en face OCTA. Cross-sectional OCTA seemed to enable the distinction between vascular and nonvascular intraretinal hyperreflective foci. Two patterns of flow were observed; Pattern 1 (11%): a flow signal confined to the neurosensory retina and Pattern 2 (74%): a flow signal extending through the retinal pigment epithelium. No definitive retinal-choroidal anastomosis was observed; however, projection artifacts confounded the interpretation of deeper structures. An increase in the intensity of the high-flow tuft was seen during the progression or recurrence of Type 3 NV. Intravitreal anti-vascular endothelial growth factor therapy caused a reduction in the intensity of the high-flow tuft which was not sustained. Compared with conventional imaging, OCTA may improve detection and delineation of vascular changes occurring in Type 3 NV. Cross-sectional and en face OCTA may prove useful in studying the pathogenesis and guiding the management of these lesions.

  16. Phenotype-based Discovery of 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol as a Novel Regulator of Ocular Angiogenesis*

    PubMed Central

    Reynolds, Alison L.; Alvarez, Yolanda; Sasore, Temitope; Waghorne, Nora; Butler, Clare T.; Kilty, Claire; Smith, Andrew J.; McVicar, Carmel; Wong, Vickie H. Y.; Galvin, Orla; Merrigan, Stephanie; Osman, Janina; Grebnev, Gleb; Sjölander, Anita; Stitt, Alan W.; Kennedy, Breandán N.

    2016-01-01

    Retinal angiogenesis is tightly regulated to meet oxygenation and nutritional requirements. In diseases such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, uncontrolled angiogenesis can lead to blindness. Our goal is to better understand the molecular processes controlling retinal angiogenesis and discover novel drugs that inhibit retinal neovascularization. Phenotype-based chemical screens were performed using the ChemBridge DiversetTM library and inhibition of hyaloid vessel angiogenesis in Tg(fli1:EGFP) zebrafish. 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol, (quininib) robustly inhibits developmental angiogenesis at 4–10 μm in zebrafish and significantly inhibits angiogenic tubule formation in HMEC-1 cells, angiogenic sprouting in aortic ring explants, and retinal revascularization in oxygen-induced retinopathy mice. Quininib is well tolerated in zebrafish, human cell lines, and murine eyes. Profiling screens of 153 angiogenic and inflammatory targets revealed that quininib does not directly target VEGF receptors but antagonizes cysteinyl leukotriene receptors 1 and 2 (CysLT1–2) at micromolar IC50 values. In summary, quininib is a novel anti-angiogenic small-molecule CysLT receptor antagonist. Quininib inhibits angiogenesis in a range of cell and tissue systems, revealing novel physiological roles for CysLT signaling. Quininib has potential as a novel therapeutic agent to treat ocular neovascular pathologies and may complement current anti-VEGF biological agents. PMID:26846851

  17. Three-dimensional choroidal segmentation in spectral OCT volumes using optic disc prior information

    NASA Astrophysics Data System (ADS)

    Hu, Zhihong; Girkin, Christopher A.; Hariri, Amirhossein; Sadda, SriniVas R.

    2016-03-01

    Recently, much attention has been focused on determining the role of the peripapillary choroid - the layer between the outer retinal pigment epithelium (RPE)/Bruchs membrane (BM) and choroid-sclera (C-S) junction, whether primary or secondary in the pathogenesis of glaucoma. However, the automated choroidal segmentation in spectral-domain optical coherence tomography (SD-OCT) images of optic nerve head (ONH) has not been reported probably due to the fact that the presence of the BM opening (BMO, corresponding to the optic disc) can deflect the choroidal segmentation from its correct position. The purpose of this study is to develop a 3D graph-based approach to identify the 3D choroidal layer in ONH-centered SD-OCT images using the BMO prior information. More specifically, an initial 3D choroidal segmentation was first performed using the 3D graph search algorithm. Note that varying surface interaction constraints based on the choroidal morphological model were applied. To assist the choroidal segmentation, two other surfaces of internal limiting membrane and innerouter segment junction were also segmented. Based on the segmented layer between the RPE/BM and C-S junction, a 2D projection map was created. The BMO in the projection map was detected by a 2D graph search. The pre-defined BMO information was then incorporated into the surface interaction constraints of the 3D graph search to obtain more accurate choroidal segmentation. Twenty SD-OCT images from 20 healthy subjects were used. The mean differences of the choroidal borders between the algorithm and manual segmentation were at a sub-voxel level, indicating a high level segmentation accuracy.

  18. Automated choroid segmentation of three-dimensional SD-OCT images by incorporating EDI-OCT images.

    PubMed

    Chen, Qiang; Niu, Sijie; Fang, Wangyi; Shuai, Yuanlu; Fan, Wen; Yuan, Songtao; Liu, Qinghuai

    2018-05-01

    The measurement of choroidal volume is more related with eye diseases than choroidal thickness, because the choroidal volume can reflect the diseases comprehensively. The purpose is to automatically segment choroid for three-dimensional (3D) spectral domain optical coherence tomography (SD-OCT) images. We present a novel choroid segmentation strategy for SD-OCT images by incorporating the enhanced depth imaging OCT (EDI-OCT) images. The down boundary of the choroid, namely choroid-sclera junction (CSJ), is almost invisible in SD-OCT images, while visible in EDI-OCT images. During the SD-OCT imaging, the EDI-OCT images can be generated for the same eye. Thus, we present an EDI-OCT-driven choroid segmentation method for SD-OCT images, where the choroid segmentation results of the EDI-OCT images are used to estimate the average choroidal thickness and to improve the construction of the CSJ feature space of the SD-OCT images. We also present a whole registration method between EDI-OCT and SD-OCT images based on retinal thickness and Bruch's Membrane (BM) position. The CSJ surface is obtained with a 3D graph search in the CSJ feature space. Experimental results with 768 images (6 cubes, 128 B-scan images for each cube) from 2 healthy persons, 2 age-related macular degeneration (AMD) and 2 diabetic retinopathy (DR) patients, and 210 B-scan images from other 8 healthy persons and 21 patients demonstrate that our method can achieve high segmentation accuracy. The mean choroid volume difference and overlap ratio for 6 cubes between our proposed method and outlines drawn by experts were -1.96µm3 and 88.56%, respectively. Our method is effective for the 3D choroid segmentation of SD-OCT images because the segmentation accuracy and stability are compared with the manual segmentation. Copyright © 2017. Published by Elsevier B.V.

  19. In vivo analysis of the time and spatial activation pattern of microglia in the retina following laser-induced choroidal neovascularization.

    PubMed

    Crespo-Garcia, Sergio; Reichhart, Nadine; Hernandez-Matas, Carlos; Zabulis, Xenophon; Kociok, Norbert; Brockmann, Claudia; Joussen, Antonia M; Strauss, Olaf

    2015-10-01

    Microglia play a major role in retinal neovascularization and degeneration and are thus potential targets for therapeutic intervention. In vivo assessment of microglia behavior in disease models can provide important information to understand patho-mechanisms and develop therapeutic strategies. Although scanning laser ophthalmoscope (SLO) permits the monitoring of microglia in transgenic mice with microglia-specific GFP expression, there are fundamental limitations in reliable identification and quantification of activated cells. Therefore, we aimed to improve the SLO-based analysis of microglia using enhanced image processing with subsequent testing in laser-induced neovascularization (CNV). CNV was induced by argon laser in MacGreen mice. Microglia was visualized in vivo by SLO in the fundus auto-fluorescence (FAF) mode and verified ex vivo using retinal preparations. Three image processing algorithms based on different analysis of sequences of images were tested. The amount of recorded frames was limiting the effectiveness of the different algorithms. Best results from short recordings were obtained with a pixel averaging algorithm, further used to quantify spatial and temporal distribution of activated microglia in CNV. Morphologically, different microglia populations were detected in the inner and outer retinal layers. In CNV, the peak of microglia activation occurred in the inner layer at day 4 after laser, lacking an acute reaction. Besides, the spatial distribution of the activation changed by the time over the inner retina. No significant time and spatial changes were observed in the outer layer. An increase in laser power did not increase number of activated microglia. The SLO, in conjunction with enhanced image processing, is suitable for in vivo quantification of microglia activation. This surprisingly revealed that laser damage at the outer retina led to more reactive microglia in the inner retina, shedding light upon a new perspective to approach

  20. Treatment of neovascular age-related macular degeneration with a variable ranibizumab dosing regimen and one-time reduced-fluence photodynamic therapy: the TORPEDO trial at 2 years.

    PubMed

    Spielberg, Leigh; Leys, Anita

    2010-07-01

    The combination of verteporfin photodynamic therapy (PDT) and anti-angiogenics has been shown to be safe and efficacious in the treatment of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). The purpose of this study is to demonstrate long-term prevention of vision loss and improvement in best-corrected visual acuity (BCVA) after treatment with one-time reduced-fluence-rate PDT followed by administration of ranibizumab on a variable dosing regimen over 24 months in patients with neovascular AMD. Secondary outcome measures included the change in central macular thickness (CMT), reinjection frequency, and safety. This prospective, nonrandomized, open-label, single-center study enrolled 27 consecutive patients (27 eyes) presenting at the Leuven University Eye Hospital with previously untreated, active neovascular AMD between September 2006 and January 2007. All patients were treated with one-time, reduced-fluence-rate verteporfin PDT, followed by intravitreal ranibizumab 0.5 mg on the same day. A second and third ranibizumab injection were given at weeks 4 and 8, respectively, after which patients were followed up monthly for 24 months. Additional treatment with ranibizumab was administered to eyes with active neovascularization as indicated clinically and on imaging studies. Retreatment was based on the following criteria: (1) presence of subretinal fluid (SRF), intraretinal edema or sub-retinal pigment epithelial fluid, as seen on OCT; (2) increase of CMT by >100 mm on OCT; (3) signs of active CNV leakage on fluorescein angiography; (4) new sub- or intraretinal hemorrhage; and (5) BCVA decreased of > or =5 letters on the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart. If any single criterion for reinjection was fulfilled, retreatment with ranibizumab was administered. Twenty-five patients completed the 2-year study. Occult CNV was present in 64% and retinal angiomatous proliferative (RAP) lesions were present in 24

  1. Ocular changes in TgF344-AD rat model of Alzheimer's disease.

    PubMed

    Tsai, Yuchun; Lu, Bin; Ljubimov, Alexander V; Girman, Sergey; Ross-Cisneros, Fred N; Sadun, Alfredo A; Svendsen, Clive N; Cohen, Robert M; Wang, Shaomei

    2014-01-29

    Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by progressive decline in learning, memory, and executive functions. In addition to cognitive and behavioral deficits, vision disturbances have been reported in early stage of AD, well before the diagnosis is clearly established. To further investigate ocular abnormalities, a novel AD transgenic rat model was analyzed. Transgenic (Tg) rats (TgF344-AD) heterozygous for human mutant APPswe/PS1ΔE9 and age-matched wild type (WT) rats, as well as 20 human postmortem retinal samples from both AD and healthy donors were used. Visual function in the rodent was analyzed using the optokinetic response and luminance threshold recording from the superior colliculus. Immunohistochemistry on retinal and brain sections was used to detect various markers including amyloid-β (Aβ) plaques. As expected, Aβ plaques were detected in the hippocampus, cortex, and retina of Tg rats. Plaque-like structures were also found in two AD human whole-mount retinas. The choroidal thickness was significantly reduced in both Tg rat and in AD human eyes when compared with age-matched controls. Tg rat eyes also showed hypertrophic retinal pigment epithelial cells, inflammatory cells, and upregulation of complement factor C3. Although visual acuity was lower in Tg than in WT rats, there was no significant difference in the retinal ganglion cell number and retinal vasculature. In this study, we observed pathological changes in the choroid and in RPE cells in the TgF344-AD rat model; choroidal thinning was observed further in human AD retina. Along with Ab deposition, the inflammatory response was manifested by microglial recruitment and complement activation. Further studies are needed to elucidate the significance and mechanisms of these pathological changes [corrected].

  2. Choroidal metastasis in disseminated lung cancer: frequency and risk factors.

    PubMed

    Kreusel, Klaus-Martin; Wiegel, Thomas; Stange, Marit; Bornfeld, Norbert; Hinkelbein, Wolfgang; Foerster, Michael H

    2002-09-01

    To determine frequency, risk factors, and benefit of a prospective screening for intraocular metastasis in patients with metastatic lung cancer. Consecutive observational case series. An ophthalmologic screening was performed on 84 consecutive patients suffering from metastatic lung cancer. Medical history and disease stage were evaluated in regard to the risk for intraocular metastasis. In six patients (7.1%) choroidal metastasis (CM) was detected. Choroidal metastasis was present only when at least two other organ system were affected by metastasis (P =.03). The choroid was the sixth common site of organ metastasis. Mean remaining life span in patients with CM was 1.9 (0.2-5.9) months. Choroidal metastasis is common in advanced metastatic lung cancer. However, due to the short survival of affected individuals, a systematic screening of at-risk patients for CM seems to be of limited benefit.

  3. Intrastromal Delivery of Bevacizumab Using Microneedles to Treat Corneal Neovascularization

    PubMed Central

    Kim, Yoo C.; Grossniklaus, Hans E.; Edelhauser, Henry F.; Prausnitz, Mark R.

    2014-01-01

    Purpose. This study tested the hypothesis that highly targeted intrastromal delivery of bevacizumab using coated microneedles allows dramatic dose sparing compared with subconjunctival and topical delivery for treatment of corneal neovascularization. Methods. Stainless steel microneedles 400 μm in length were coated with bevacizumab. A silk suture was placed in the cornea approximately 1 mm from the limbus to induce corneal neovascularization in the eyes of New Zealand white rabbits that were divided into different groups: untreated, microneedle delivery, topical eye drop, and subconjunctival injection of bevacizumab. All drug treatments were initiated 4 days after suture placement and area of neovascularization was measured daily by digital photography for 18 days. Results. Eyes treated once with 4.4 μg bevacizumab using microneedles reduced neovascularization compared with untreated eyes by 44% (day 18). Eyes treated once with 2500 μg bevacizumab using subconjunctival injection gave similar results to microneedle-treated eyes. Eyes treated once with 4.4 μg subconjunctival bevacizumab showed no significant effect compared with untreated eyes. Eyes treated with 52,500 μg bevacizumab by eye drops three times per day for 14 days reduced the neovascularization area compared with untreated eyes by 6% (day 18), which was significantly less effective than the single microneedle treatment. Visual exam and histological analysis showed no observable effect of microneedle treatment on corneal transparency or microanatomical structure. Conclusions. This study shows that microneedles can target drug delivery to corneal stroma in a minimally invasive way and demonstrates effective suppression of corneal neovascularization after suture-induced injury using a much lower dose compared with conventional methods. PMID:25212779

  4. Choroidal and skin metastases from colorectal cancer.

    PubMed

    Ha, Joo Young; Oh, Edward Hynseung; Jung, Moon Ki; Park, Song Ee; Kim, Ji Tak; Hwang, In Gyu

    2016-11-21

    Choroidal and skin metastasis of colon cancer is rare. In women, the frequency of cutaneous metastasis from colon cancer as the primary lesion in is 9% and skin metastasis occurs in 0.81% of all colorectal cancers. We report a patient with colonic adenocarcinoma who presented with visual disorder in her right eye and scalp pain as her initial symptoms. Contrast-enhance orbital magnetic resonance imaging with fat suppression revealed an infrabulbar mass, and skin biopsy of the posterior parietal scalp confirmed adenocarcinoma. These symptoms were diagnosed as being caused by choroidal and skin metastases of colonic adenocarcinoma. We started palliative chemotherapy with oral capecitabine (1000 mg/m 2 , twice a day, on days 1-14) every 3 wk, which was effective at shrinking the brain masses and improving the visual disorder. This is the first report that capecitabine is effective at reducing a choroidal and cutaneous metastatic lesion from right-sided colorectal cancer.

  5. Clearance of amyloid-β peptide across the choroid plexus in Alzheimer's disease.

    PubMed

    Alvira-Botero, Ximena; Carro, Eva M

    2010-12-01

    Aging and several neurodegenerative diseases bring about changes in the anatomy and physiology of the choroid plexus. The identification of specific membrane receptors that bind and internalize extracellular ligands has revolutionized the traditional roles of this tissue. Amyloid beta peptide (Aβ), the major constituent of the amyloid core of senile plaques in patients with Alzheimer's disease (AD) is known to contribute to disease neuropathology and progression. Recent emphasis on comorbidity of AD and a deficient clearance of Aβ across the blood-brain barrier and blood-cerebrospinal fluid barrier have highlighted the importance of brain Aβ clearance in AD. The megalin receptor has also been implicated in the pathogenesis of AD. Faulty Aβ clearance from the brain across the choroid plexus epithelium by megalin appears to mediate focal Aβ accumulation in AD. Patients with AD have reduced levels of megalin at the choroid plexus, which in turn seem to increase brain levels of Aβ through a decreased efflux of brain Aβ. Therapies that increase megalin expression at the choroid plexus could potentially control accumulation of brain Aβ. This review covers in depth the anatomy and function of the choroid plexus, focusing on the brain barrier at the choroid plexus, as it actively participates in Aβ clearance. In addition, we describe the role of the choroid plexus in brain functions, aging and AD, as well as the role of megalin in the process of Aβ clearance. Finally, we present current data on the use of choroid plexus cells to repair the damaged brain.

  6. Choroidal Thickness Changes in the Acute Attack Period in Patients with Familial Mediterranean Fever.

    PubMed

    Gundogan, Fatih C; Akay, Fahrettin; Uzun, Salih; Ozge, Gokhan; Toyran, Sami; Genç, Halil

    2016-01-01

    The aim of this study was to evaluate choroidal thickness changes during acute attacks of familial Mediterranean fever (FMF). Fifty patients with FMF and 50 healthy controls were included. Choroidal thickness of each participant was measured at the foveola and horizontal nasal and temporal quadrants at 500-µm intervals to 1,500 µm from the foveola using spectral-domain optical coherence tomography. White blood cell count, erythrocyte sedimentation rate (ESR) and serum levels of fibrinogen and C-reactive protein (CRP) were evaluated. The clinical findings (peritonitis, arthritis and pleuritis) were noted. Choroidal thickness was significantly thicker at all measurement points in FMF patients compared to healthy controls during an acute attack (p < 0.05). There were positive correlations between the choroidal thickness and ESR, fibrinogen and, particularly, CRP levels. Clinical findings did not change the choroidal thickness significantly (p > 0.05). Increased choroidal thickness in the acute phase of FMF is possibly related to the inflammatory edematous changes in the choroid. © 2015 S. Karger AG, Basel.

  7. Ocular biodistribution of bevasiranib following a single intravitreal injection to rabbit eyes

    PubMed Central

    Dejneka, Nadine S.; Wan, Shanhong; Bond, Ottrina S.; Kornbrust, Douglas J.

    2008-01-01

    Purpose The primary objective of these investigations was to determine the ocular biodistribution of bevasiranib, a small interfering RNA (siRNA) targeting vascular endothelial growth factor A (VEGF-A), following a single intravitreal injection to rabbit eyes. Methods A tissue distribution and pharmacokinetic study was conducted with 3H-bevasiranib prepared in balanced-salt solution (BSS). Single doses of either 0.5 mg/eye or 2.0 mg/eye of 3H-bevasiranib were given by intravitreal injection to Dutch-Belted rabbits (both eyes were treated). Subgroups of rabbits were serially-sacrificed at various times up to 7 days following dosing for collection of tissue samples. The right eye of each rabbit was collected whole, and the left eye was dissected to isolate five ocular tissues. All samples were analyzed by liquid scintillation counting to determine the concentrations of bevasiranib equivalents. An ocular disposition study was also performed with non-radiolabeled bevasiranib, which was administered to Dutch-Belted rabbit eyes via intravitreal injection at a dose of 2.0 mg/eye. Twenty-four hours post-dose, the eyes were enucleated and dissected into eight individual ocular structures that were analyzed for intact bevasiranib using a locked nuleic acid (LNA) noncompetitive hybridization-ligation enzyme-linked immunosorbent assay. Results Following intravitreal injection of 0.5 mg or 2.0 mg radiolabeled bevasiranib to Dutch-Belted rabbits, bevasiranib was detected in the vitreous, iris, retina, retinal pigment epithelium (RPE), and sclera (+choroid). As expected, the highest concentrations were found in the vitreous, and vitreous levels steadily decreased over time, while concentrations of radioactivity in the other ocular tissues increased to maximum values between 24 h and 72 h after dosing. Of these tissues, the highest concentration of radioactivity was detected in the retina. The LNA assay further confirmed the presence of intact bevasiranib in these tissues 24 h

  8. Value-based medicine and interventions for macular degeneration.

    PubMed

    Brown, Melissa M; Brown, Gary C; Brown, Heidi

    2007-05-01

    The aim of this article is to review the patient value conferred by interventions for neovascular macular degeneration. Value-based medicine is the practice of medicine based upon the patient value (improvement in quality of life and length of life) conferred by an intervention. For ophthalmologic interventions, in which length-of-life is generally unaffected, the value gain is equivalent to the improvement in quality of life. Photodynamic therapy delivers a value gain (improvement in quality of life) of 8.1% for the average person with classic subfoveal choroidal neovascularization, while laser photocoagulation for the same entity confers a 4.4% improvement in quality of life. Preliminary data suggest the value gain for the treatment of occult/minimally classic choroidal neovascularization with ranibizumab is greater than 15%. The average value gain for statins for the treatment of hyperlipidemia is 3.9%, while that for the use of biphosphonates for the treatment of osteoporosis is 1.1% and that for drugs to treat benign prostatic hyperplasia is 1-2%. Interventions, especially ranibizumab therapy, for neovascular macular degeneration appear to deliver an extraordinary degree of value compared with many other interventions across healthcare.

  9. Hypofractionated stereotactic photon radiotherapy of posteriorly located choroidal melanoma with five fractions at ten Gy--clinical results after six years of experience.

    PubMed

    Dunavoelgyi, Roman; Zehetmayer, Martin; Gleiss, Andreas; Geitzenauer, Wolfgang; Kircher, Karl; Georg, Dietmar; Schmidt-Erfurth, Ursula; Poetter, Richard; Dieckmann, Karin

    2013-08-01

    To evaluate long-term safety and efficacy of hypofractionated stereotactic photon radiotherapy with 5 five fractions at 10 Gy each in patients with centrally located choroidal melanoma. Ninety-one patients with centrally located choroidal melanoma were treated stereotactically at a linear accelerator with 6 MV photon beams with 5 fractions at 10 Gy each. Examinations were performed at baseline and every 3 months in the first 2 years, then every 6 months until 5 years and yearly thereafter. Median follow-up was 37.8 months (IQR 19.2-49.9). They included visual acuity assessment, routine ophthalmological examinations with fundoscopy, echography for measurement of tumor dimensions, medical examinations and, if necessary, fluorescein angiography. Initial tumor base diameters, height and volume were 11.20mm (IQR 9.10-13.70), 9.80 mm (IQR 7.80-11.70), 4.53 mm (IQR 3.33-6.43) and 253.8mm(3) (IQR 127.5-477.0). Local tumor control and eye retention rates were 97.7% and 86.4% after 5 years, respectively. Eight patients developed metastatic disease and 3 of them died due to metastatic disease during the follow-up period. Median visual acuity decreased from 0.67 initially to 0.05 at the last individual follow-up (p<0.001). The most common toxicities (any grade) were radiation retinopathy (n=39), optic neuropathy (n=32), radiogenic cataract (n=21), neovascular glaucoma (n=15) and dry eye syndrome (n=10). The 5 year probabilities to remain free of these side effects (any grade) were 26.0%, 45.4%, 55.4%, 72.6% and 80.5%, respectively. The most important prognostic factors for toxicities were the largest tumor base diameter, tumor height and tumor distance to the optic disk. Hypofractionated stereotactic photon radiotherapy with a total dose of 50 Gy delivered in 5 fractions is a highly effective treatment option in patients with centrally located choroidal melanoma and has a moderate toxicity profile. Copyright © 2013. Published by Elsevier Ireland Ltd.

  10. Real-world use of ranibizumab for neovascular age-related macular degeneration in Taiwan.

    PubMed

    Chang, Yi-Sheng; Lee, Wan-Ju; Lim, Chen-Chee; Wang, Shih-Hao; Hsu, Sheng-Min; Chen, Yi-Chian; Cheng, Chia-Yi; Teng, Yu-Ti; Huang, Yi-Hsun; Lai, Chun-Chieh; Tseng, Sung-Huei

    2018-05-10

    This study investigated the "real-world" use of ranibizumab for neovascular age-related macular degeneration (nAMD) in Taiwan and assessed the visual outcome. We reviewed the medical records at National Cheng Kung University Hospital, Taiwan, during 2012-2014 for 264 consecutive eyes of 229 patients with nAMD, who applied for ranibizumab covered by national health insurance. A total of 194 eyes (73.5%) in 179 patients (65.5% men; mean ± standard deviation age 69.4 ± 10.7 years) were pre-approved for treatment. Applications for treatment increased year by year, but approval rates decreased during this time. The major causes of rejection for funding were diseases mimicking nAMD, including macular pucker/epiretinal membrane, macular scarring, dry-type AMD, and possible polypoidal choroidal vasculopathy. After completion of three injections in 147 eyes, visual acuity significantly improved, gaining ≥1 line in 51.8% of eyes and stabilising in 38.3% of 141 eyes in which visual acuity was measured. The 114 eyes approved with only one application had a better visual outcome than the 27 eyes approved after the second or third applications. In conclusion, ranibizumab is effective for nAMD; however, approval after the second or third application for national health insurance cover is a less favourable predictor of visual outcome.

  11. Corticosteroids for ocular toxoplasmosis

    PubMed Central

    Jasper, Smitha; Vedula, Satyanarayana S; John, Sheeja S; Horo, Saban; Sepah, Yasir J; Nguyen, Quan Dong

    2014-01-01

    Background Ocular infestation with Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea and consequently lead to complications such as glaucoma, cataract, and posterior synechiae. Objectives The objective of this systematic review was to assess the effects of adjunctive use of corticosteroids for ocular toxoplasmosis. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to October 2012), EMBASE (January 1980 to October 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We searched the reference lists of included studies for any additional studies not identified by the electronic searches. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 October 2012. Selection criteria We planned to include randomized and quasi-randomized controlled trials. Eligible trials would have enrolled participants of any age who were immunocompetent and were diagnosed with active ocular toxoplasmosis. Included trials would have compared anti-parasitic therapy plus corticosteroids versus anti-parasitic therapy alone, or different doses or times of initiation of corticosteroids. Data collection and analysis Two authors independently screened titles and abstracts retrieved from the electronic searches. We retrieved full-text articles of studies categorized as ‘unsure’ or ‘include’ after review of the abstracts. Two authors independently reviewed each full-text article. Discrepancies were

  12. Ocular inflammatory effects of intravitreally-injected tumor necrosis factor.

    PubMed Central

    Rosenbaum, J. T.; Howes, E. L.; Rubin, R. M.; Samples, J. R.

    1988-01-01

    Many of the pathophysiologic effects of bacterial endotoxin have recently been attributed to a monokine, tumor necrosis factor (TNF). The rabbit eye is extremely sensitive to locally injected endotoxin. The authors have investigated the possible contribution of TNF to ocular inflammation in a rabbit model. The intravitreal injection of 10(5) to 5 X 10(5) units of recombinant human TNF produced a sustained disruption of the blood-aqueous barrier as manifested by elevated aqueous humor protein levels. In addition, 83% of rabbits receiving this dose of TNF developed hyperemia of limbal vessels and early neovascularization of the cornea. Many developed posterior synechiae (fibrous adhesions between the iris and the lens). TNF induced only a slight cellular response in the anterior chamber. Histologic studies confirmed the presence of new vessels and demonstrated a marked mononuclear infiltrate within and beneath the epithelium of the iris and ciliary body. Lower doses of TNF produced inconsistent results. Heating TNF completely destroyed its inflammatory effects. The time course of the ocular response to TNF and the quantity of recombinant protein needed to produce consistent effects were vastly different from effects observed with interleukin-1. For example, 24 hours after an intravitreal injection, 2.2 X 10(4) ng of TNF (5 X 10(5) units) produced significantly less protein extravasation and polymorphonuclear leukocyte infiltration than 4 ng of recombinant interleukin-1. Similarly, 24 hours after intravitreal injection, 1 ng of Escherichia coli endotoxin tended to be a more potent inflammatory stimulus than this quantity of TNF. These observations indicate that the ocular pathophysiologic effects of TNF can be readily distinguished from changes induced by either endotoxin or another endotoxin induced monokine, interleukin-1. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:3263050

  13. Macular Choroidal Small-Vessel Layer, Sattler's Layer and Haller's Layer Thicknesses: The Beijing Eye Study.

    PubMed

    Zhao, Jing; Wang, Ya Xing; Zhang, Qi; Wei, Wen Bin; Xu, Liang; Jonas, Jost B

    2018-03-13

    To study macular choroidal layer thickness, 3187 study participants from the population-based Beijing Eye Study underwent spectral-domain optical coherence tomography with enhanced depth imaging for thickness measurements of the macular small-vessel layer, including the choriocapillaris, medium-sized choroidal vessel layer (Sattler's layer) and large choroidal vessel layer (Haller's layer). In multivariate analysis, greater thickness of all three choroidal layers was associated (all P < 0.05) with higher prevalence of age-related macular degeneration (AMD) (except for geographic atrophy), while it was not significantly (all P > 0.05) associated with the prevalence of open-angle glaucoma or diabetic retinopathy. There was a tendency (0.07 > P > 0.02) toward thinner choroidal layers in chronic angle-closure glaucoma. The ratio of small-vessel layer thickness to total choroidal thickness increased (P < 0.001; multivariate analysis) with older age and longer axial length, while the ratios of Sattler's layer and Haller's layer thickness to total choroidal thickness decreased. A higher ratio of small-vessel layer thickness to total choroidal thickness was significantly associated with a lower prevalence of AMD (early type, intermediate type, late geographic type). Axial elongation-associated and aging-associated choroidal thinning affected Haller's and Sattler's layers more markedly than the small-vessel layer. Non-exudative and exudative AMD, except for geographic atrophy, was associated with slightly increased choroidal thickness.

  14. Acute choroidal ischemia associated with toxoplasmic retinochoroiditis.

    PubMed

    Khairallah, Moncef; Yahia, Salim Ben; Zaouali, Sonia; Jenzeri, Salah; Attia, Sonia; Messaoud, Riadh

    2007-09-01

    To describe eight patients with active toxoplasmic retinochoroiditis (RC) who had features suggestive of acute choroidal ischemia. A retrospective review of the clinical records of 23 consecutive patients with acute toxoplasmic RC was performed. All patients underwent detailed ophthalmic examination at presentation and throughout follow-up, including dilated biomicroscopic fundus examination, fundus photography, fluorescein angiography, and indocyanine green (ICG) angiography. Of 23 patients, 8 (34.8%) had a large area of retinal whitening surrounding a small focus of RC. Fluorescein as well as ICG angiography showed a well demarcated geographic area of early choroidal hypofluorescence that extended beyond the clinical borders of the white retinal lesion, particularly by ICG angiography. Associated findings for these 8 patients included old retinochoroidal scars (7 [87.5%]), serous retinal detachment (3 [37.5%]), retinal hemorrhages (1 [12.5%]), and multiple satellite dark dots by ICG angiography (6 [75%]). Seven of eight patients were treated using a combination of antitoxoplasmic drugs and corticosteroids. All findings seen at the acute stage resolved in 2 weeks to 6 weeks. A small atrophic retinochoroidal scar replaced the active toxoplasmic lesion and was surrounded with mild or moderate retinal pigment epithelium changes that were associated with decreased final visual acuity in 2 patients (25%). Patients with toxoplasmic RC may develop features suggestive of choroidal ischemia that can result in a transient or permanent decrease in vision. Choroidal ischemia can only be suspected clinically, and fluorescein angiography and ICG angiography are required to establish the definitive diagnosis.

  15. Variability of disease activity in patients treated with ranibizumab for neovascular age-related macular degeneration.

    PubMed

    Enders, P; Scholz, P; Muether, P S; Fauser, S

    2016-08-01

    PurposeTo analyze choroidal neovasularization (CNV) activity and recurrence patterns in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab, and the correlation with individual intraocular vascular endothelial growth factor (VEGF) suppression time (VST).MethodsPost-hoc analysis of data from a prospective, non-randomized clinical study. Patients with nAMD treated with ranibizumab on a pro re nata regimen. Disease activity was analyzed monthly by spectral-domain optical coherence tomography and correlated with VSTs.ResultsOverall, 73 eyes of 73 patients were included in the study with a mean follow-up of 717 days (range: 412-1239 days). Overall, the mean CNV-activity-free interval was 76.5 days (range: 0-829 days). The individual range of the length of dry intervals was high. A total of 42% of patients had a range of more than 90 days. Overall, 16% of patients showed persistent activity. And 12% stayed dry after the initial ranibizumab treatment. No significant correlation was found between the CNV-recurrence pattern and VST (P=0.12).ConclusionsCNV activity in nAMD is irregular, which is reflected in the range of the duration of dry intervals and late recurrences. The biomarker VST solely seems not to be sufficient to explain recurrence pattern of CNV in all AMD patients.

  16. Does the treatment of amblyopia normalise subfoveal choroidal thickness in amblyopic children?

    PubMed

    Öner, Veysi; Bulut, Asker

    2017-03-01

    Recent studies have found a choroidal thickening in amblyopic eyes and suggested that there might be a relationship between the choroid and amblyopia. The present study aimed to evaluate the effect of a six-month treatment of amblyopia on choroidal thickness in anisometropic hyperopic amblyopic children. Thirty-two anisometropic hyperopic children with unilateral amblyopia were included in this prospective study. Subfoveal choroidal thickness was measured as the distance between the retinal pigment epithelium and the chorioscleral edge, by using spectral domain enhanced depth imaging optical coherence tomography. The treatment of amblyopia was performed based on the full correction of the refractive error with eyeglasses, a refractive adaptation phase and occlusion by patching the fellow eye. The mean visual acuity of the amblyopic eyes significantly increased from 0.35 ± 0.3 to 0.16 ± 0.2 logMAR after the treatment (p < 0.001). The mean initial choroidal thickness was significantly higher in the amblyopic eyes than in the fellow eyes (p = 0.019). There were no significant differences between the pre- and post-treatment mean choroidal thickness in the amblyopic eyes (p = 0.428) and in the fellow eyes (p = 0.343). The mean choroidal thickness was still higher in the amblyopic eyes than in the fellow eyes after the treatment (p = 0.006). Although a six-month treatment of amblyopia increased the visual acuity of the anisometropic hyperopic amblyopic eyes, it could not significantly change choroidal thickness. Our results were in accordance with the conventional explanation, which suggests visual cortex and lateral geniculate nucleus abnormalities in the pathophysiology of amblyopia. © 2016 Optometry Australia.

  17. Effect of topical epigallocatechin gallate on corneal neovascularization in rabbits.

    PubMed

    Koh, Chang Hyun; Lee, Hyun Soo; Chung, Sung Kun

    2014-05-01

    The aim of this study was to evaluate the efficacy of topical application of epigallocatechin gallate (EGCG) for the treatment of corneal neovascularization in a rabbit model. Corneal neovascularization was induced in 12 rabbits by placing a black silk suture in the corneal stroma (24 eyes) for a week. After suturing, 1 randomly chosen eye of the 12 rabbits was treated with topical EGCG at 2 different concentrations: 0.01% (group 1) and 0.1% (group 2), whereas the contralateral eyes were treated with sterilized balanced salt solution as the control. All eye drops were applied for 2 weeks after suturing. The suture materials were removed from all eyes on day 7. The surface area of corneal neovascularization was measured and analyzed in all eyes on days 7 and 14. On day 14, all eyes were extracted to measure the concentrations of vascular endothelial growth factor (VEGF) messenger RNA and cyclooxygenase-2 (COX-2) protein. The surface area of induced corneal neovascularization was significantly smaller only in group 2 compared with that of the control group on days 7 and 14 (P < 0.001). The change in surface area of corneal neovascularization after removal of the suture material was not significantly different between all 3 groups. VEGF messenger RNA levels were significantly lower in group 2 than in the control group (P < 0.001). The concentration of COX-2 was significantly lower in group 2 than in the control group (P = 0.043), but no significant difference was observed between group 1 and the control group. Topical administration of EGCG effectively inhibits corneal neovascularization in rabbits. This inhibitory effect is probably related to the suppression of VEGF and COX-2 meditated angiogenesis.

  18. SOLITARY IDIOPATHIC CHOROIDITIS IN THE SETTING OF EXTENSIVE ANIMAL EXPOSURE.

    PubMed

    Kumar, Vivek; Khoo, Chloe T L; Shields, Carol L

    2016-01-01

    To describe solitary idiopathic choroiditis in the setting of extensive animal exposure. A 56-year-old asymptomatic female equestrian with an extensive history of exposure to horses and dogs and a trapper of wild animals and rodents was discovered to have an amelanotic choroidal mass in the macular region and referred for suspicious atypical nevus. Funduscopy revealed a deep yellow mass with overlying retinal pigment epithelial thinning and without visible subretinal fluid or lipofuscin. Mild hyperautofluorescence represented unmasking of scleral autofluorescence. Ultrasonography showed a 1.8-mm-thick echodense lesion. Enhanced depth imaging-optical coherence tomography disclosed a dense, elevated scleral mass with "volcanic" configuration, demonstrating choroidal compression and trace overlying subretinal fluid. These features were consistent with solitary idiopathic choroiditis/scleritis. Systemic evaluation for standard cat-related bartonellosis, tuberculosis, sarcoidosis, and syphilis were negative. Horse-, dog-, and rodent-related bartonellosis testing was not available. Observation was advised, and the findings remained stable at 6 months. Solitary idiopathic choroiditis is best imaged on enhanced depth imaging-optical coherence tomography as a scleral lesion with "volcanic" configuration and often secondary to previous Bartonella infection. Serologic positivity for cat-related Bartonella decays over time, and testing for horse-, dog-, or rodent-related Bartonella is not commonly used.

  19. Baseline predictors for one-year visual outcomes with ranibizumab or bevacizumab for neovascular age-related macular degeneration.

    PubMed

    Ying, Gui-shuang; Huang, Jiayan; Maguire, Maureen G; Jaffe, Glenn J; Grunwald, Juan E; Toth, Cynthia; Daniel, Ebenezer; Klein, Michael; Pieramici, Dante; Wells, John; Martin, Daniel F

    2013-01-01

    To determine the baseline predictors of visual acuity (VA) outcomes 1 year after treatment with ranibizumab or bevacizumab for neovascular age-related macular degeneration (AMD). Cohort study within the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). A total of 1105 participants with neovascular AMD, baseline VA 20/25 to 20/320, and VA measured at 1 year. Participants were randomly assigned to ranibizumab or bevacizumab on a monthly or as-needed schedule. Masked readers evaluated fundus morphology and features on optical coherence tomography (OCT). Visual acuity was measured using electronic VA testing. Independent predictors were identified using regression techniques. The VA score, VA score change from baseline, and ≥3-line gain at 1 year. At 1 year, the mean VA score was 68 letters, mean improvement from baseline was 7 letters, and 28% of participants gained ≥3 lines. Older age, larger area of choroidal neovascularization (CNV), and elevation of retinal pigment epithelium (RPE) were associated with worse VA (all P<0.005), less gain in VA (all P<0.02), and a lower proportion gaining ≥3 lines (all P<0.04). Better baseline VA was associated with better VA at 1 year, less gain in VA, and a lower proportion gaining ≥3 lines (all P<0.0001). Predominantly or minimally classic lesions were associated with worse VA than occult lesions (66 vs. 69 letters; P=0.0003). Retinal angiomatous proliferans (RAP) lesions were associated with more gain in VA (10 vs. 7 letters; P=0.03) and a higher proportion gaining ≥3 lines (odds ratio, 1.9; 95% confidence interval, 1.2-3.1). Geographic atrophy (GA) was associated with worse VA (64 vs. 68 letters; P=0.02). Eyes with total foveal thickness in the second quartile (325-425 μm) had the best VA (P=0.01) and were most likely to gain ≥3 lines (P=0.004). Predictors did not vary by treatment group. For all treatment groups, older age, better baseline VA, larger CNV area, predominantly or minimally

  20. Neurogenic effects of β-amyloid in the choroid plexus epithelial cells in Alzheimer's disease.

    PubMed

    Bolos, Marta; Spuch, Carlos; Ordoñez-Gutierrez, Lara; Wandosell, Francisco; Ferrer, Isidro; Carro, Eva

    2013-08-01

    β-amyloid (Aβ) can promote neurogenesis, both in vitro and in vivo, by inducing neural progenitor cells to differentiate into neurons. The choroid plexus in Alzheimer's disease (AD) is burdened with amyloid deposits and hosts neuronal progenitor cells. However, neurogenesis in this brain tissue is not firmly established. To investigate this issue further, we examined the effect of Aβ on the neuronal differentiation of choroid plexus epithelial cells in several experimental models of AD. Here we show that Aβ regulates neurogenesis in vitro in cultured choroid plexus epithelial cells as well as in vivo in the choroid plexus of APP/Ps1 mice. Treatment with oligomeric Aβ increased proliferation and differentiation of neuronal progenitor cells in cultured choroid plexus epithelial cells, but decreased survival of newly born neurons. These Aβ-induced neurogenic effects were also observed in choroid plexus of APP/PS1 mice, and detected also in autopsy tissue from AD patients. Analysis of signaling pathways revealed that pre-treating the choroid plexus epithelial cells with specific inhibitors of TyrK or MAPK diminished Aβ-induced neuronal proliferation. Taken together, our results support a role of Aβ in proliferation and differentiation in the choroid plexus epithelial cells in Alzheimer's disease.