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Sample records for myopic choroidal neovascular

  1. Current and emerging treatment options for myopic choroidal neovascularization

    PubMed Central

    El Matri, Leila; Chebil, Ahmed; Kort, Fedra

    2015-01-01

    Choroidal neovascularization (CNV) is the main cause of visual impairment in highly myopic patients younger than 50 years of age. There are different treatments for myopic CNV (mCNV), with 5- to 10-year outcomes currently. Chorioretinal atrophy is still the most important determinant factor for visual outcome. The purpose of this study is to provide an overview of the current treatments for mCNV, including laser, surgical management, verteporfin photodynamic therapy, and mainly anti-vascular endothelial growth factor therapy. Emerging treatment options are also discussed. PMID:25987831

  2. Multimodal imaging and diagnosis of myopic choroidal neovascularization in Caucasians

    PubMed Central

    Milani, Paolo; Massacesi, Amedeo; Moschini, Stefania; Setaccioli, Marco; Bulone, Ennio; Tremolada, Gemma; Ciaccia, Stefano; Mantovani, Elena; Morale, Daniela; Bergamini, Fulvio

    2016-01-01

    Purpose To investigate myopic choroidal neovascularization (mCNV) by fluorescein angiography (FA), spectral-domain optical coherence tomography (SD-OCT), near-infrared (NIR) reflectance, and autofluorescence (AF). Methods This retrospective study included 65 eyes of 62 Caucasian patients with a mean age of 66.72 years (95% confidence interval [CI] 63–70 years) and a mean refraction of −9.72 diopters (95% CI −8.74 to −10.70 diopters). Results Most of the mCNV cases were foveal-juxtafoveal (60/65, 92.3%), with thickening of the corresponding retina (62/65, 95.3%) and leakage on FA (44/65, 67.6%). No retinal fluid was detectable in 32 (49.2%) eyes and there was no hemorrhage in 25 (38.4%) eyes. Papillary chorioretinal atrophy was evident in 58 (89.2%), a shadowing effect in 48 (73.8%), and an epiretinal membrane in 38 (58.4%) eyes. If an area of macular chorioretinal atrophy was present, mCNV frequently developed adjacent to it and was hyperfluorescent rather than with leakage (P⩽0.001). In eyes with edema or hemorrhage, hyper-reflective foci were more frequent (P⩽0.005). NIR and AF features were indeterminable in 19 (29.2%) and 27 (41.5%) eyes, respectively. The predominant feature was black or grayish on NIR (34/65, 52.3%) and patchy (hypo- and hyperfluorescence was observed) on AF (25/65, 38.4%). FA and SD-OCT correctly detected mCNV in 49 (75.3%) and 48 (73.8%) eyes, respectively, whereas NIR and AF exhibited limited diagnostic sensitivity. Doubtful diagnosis was associated with hyperfluorescent mCNV (P⩽0.001), absence of retinal fluid and epiretinal membrane (P⩽0.05), and presence of macular chorioretinal atrophy (P⩽0.01). Conclusion Tomographic, angiographic, AF, and NIR features of mCNV are described in this study. Combination of SD-OCT and FA is recommendable for diagnosis. PMID:27672306

  3. Multimodal imaging and diagnosis of myopic choroidal neovascularization in Caucasians

    PubMed Central

    Milani, Paolo; Massacesi, Amedeo; Moschini, Stefania; Setaccioli, Marco; Bulone, Ennio; Tremolada, Gemma; Ciaccia, Stefano; Mantovani, Elena; Morale, Daniela; Bergamini, Fulvio

    2016-01-01

    Purpose To investigate myopic choroidal neovascularization (mCNV) by fluorescein angiography (FA), spectral-domain optical coherence tomography (SD-OCT), near-infrared (NIR) reflectance, and autofluorescence (AF). Methods This retrospective study included 65 eyes of 62 Caucasian patients with a mean age of 66.72 years (95% confidence interval [CI] 63–70 years) and a mean refraction of −9.72 diopters (95% CI −8.74 to −10.70 diopters). Results Most of the mCNV cases were foveal-juxtafoveal (60/65, 92.3%), with thickening of the corresponding retina (62/65, 95.3%) and leakage on FA (44/65, 67.6%). No retinal fluid was detectable in 32 (49.2%) eyes and there was no hemorrhage in 25 (38.4%) eyes. Papillary chorioretinal atrophy was evident in 58 (89.2%), a shadowing effect in 48 (73.8%), and an epiretinal membrane in 38 (58.4%) eyes. If an area of macular chorioretinal atrophy was present, mCNV frequently developed adjacent to it and was hyperfluorescent rather than with leakage (P⩽0.001). In eyes with edema or hemorrhage, hyper-reflective foci were more frequent (P⩽0.005). NIR and AF features were indeterminable in 19 (29.2%) and 27 (41.5%) eyes, respectively. The predominant feature was black or grayish on NIR (34/65, 52.3%) and patchy (hypo- and hyperfluorescence was observed) on AF (25/65, 38.4%). FA and SD-OCT correctly detected mCNV in 49 (75.3%) and 48 (73.8%) eyes, respectively, whereas NIR and AF exhibited limited diagnostic sensitivity. Doubtful diagnosis was associated with hyperfluorescent mCNV (P⩽0.001), absence of retinal fluid and epiretinal membrane (P⩽0.05), and presence of macular chorioretinal atrophy (P⩽0.01). Conclusion Tomographic, angiographic, AF, and NIR features of mCNV are described in this study. Combination of SD-OCT and FA is recommendable for diagnosis.

  4. Evaluation of 10 AMD Associated Polymorphisms as a Cause of Choroidal Neovascularization in Highly Myopic Eyes.

    PubMed

    Velazquez-Villoria, Alvaro; Recalde, Sergio; Anter, Jaouad; Bezunartea, Jaione; Hernandez-Sanchez, Maria; García-García, Laura; Alonso, Elena; Ruiz-Moreno, Jose María; Araiz-Iribarren, Javier; Fernandez-Robredo, Patricia; García-Layana, Alfredo

    2016-01-01

    Choroidal neovascularization (CNV) commonly occurs in age related macular degeneration and pathological myopia patients. In this study we conducted a case-control prospective study including 431 participants. The aim of this study was to determine the potential association between 10 single nucleotide polymorphisms (SNPs) located in 4 different genetic regions (CFI, COL8A1, LIPC, and APOE), and choroidal neovascularization in age-related macular degeneration and the development of choroidal neovascularization in highly myopic eyes of a Caucasian population. Univariate and multivariate logistic regression analysis adjusted for age, sex and hypertension was performed for each allele, genotype and haplotype frequency analysis. We found that in the univariate analysis that both single-nucleotide polymorphisms in COL8A1 gene (rs13095226 and rs669676) together with age, sex and hypertension were significantly associated with myopic CNV development in Spanish patients (p<0.05). After correcting for multiple testing none of the polymorphisms studied remained significantly associated with myopic CNV (p>0.05); however, analysis of the axial length between genotypes of rs13095226 revealed an important influence of COL8A1 in the development of CNV in high myopia. Furthermore we conducted a meta-analysis of COL8A1, CFI and LIPC genes SNPs (rs669676, rs10033900 and rs10468017) and found that only rs669676 of these SNPs were associated with high myopia neovascularization. PMID:27643879

  5. Evaluation of 10 AMD Associated Polymorphisms as a Cause of Choroidal Neovascularization in Highly Myopic Eyes

    PubMed Central

    Anter, Jaouad; Bezunartea, Jaione; Hernandez-Sanchez, Maria; García-García, Laura; Alonso, Elena; Ruiz-Moreno, Jose María; Araiz-Iribarren, Javier; Fernandez-Robredo, Patricia; García-Layana, Alfredo

    2016-01-01

    Choroidal neovascularization (CNV) commonly occurs in age related macular degeneration and pathological myopia patients. In this study we conducted a case-control prospective study including 431 participants. The aim of this study was to determine the potential association between 10 single nucleotide polymorphisms (SNPs) located in 4 different genetic regions (CFI, COL8A1, LIPC, and APOE), and choroidal neovascularization in age-related macular degeneration and the development of choroidal neovascularization in highly myopic eyes of a Caucasian population. Univariate and multivariate logistic regression analysis adjusted for age, sex and hypertension was performed for each allele, genotype and haplotype frequency analysis. We found that in the univariate analysis that both single-nucleotide polymorphisms in COL8A1 gene (rs13095226 and rs669676) together with age, sex and hypertension were significantly associated with myopic CNV development in Spanish patients (p<0.05). After correcting for multiple testing none of the polymorphisms studied remained significantly associated with myopic CNV (p>0.05); however, analysis of the axial length between genotypes of rs13095226 revealed an important influence of COL8A1 in the development of CNV in high myopia. Furthermore we conducted a meta-analysis of COL8A1, CFI and LIPC genes SNPs (rs669676, rs10033900 and rs10468017) and found that only rs669676 of these SNPs were associated with high myopia neovascularization. PMID:27643879

  6. 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. PMID:20196722

  7. 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.

  8. Choroidal neovascular membrane in radiation retinopathy.

    PubMed

    Berker, Nilufer; Aslan, Ozlem; Batman, Cosar; Elgin, Ufuk; Ozkan, Seyhan Sonar

    2006-08-01

    Radiation retinopathy can occur years after the initial radiotherapy of the cancers of head and neck. It generally has a fulminant course, and can cause a variety of severe retinal abnormalities. Choroidal neovascularization has been rarely reported in radiation retinopathy. In this case report, a 21-year-old boy is presented who developed fulminant radiation retinopathy and choroidal neovascular membrane 4 years after receiving radiotherapy for his nasopharyngeal carcinoma.

  9. Choroidal neovascular membrane in a treated choroidal hemangioma.

    PubMed

    Nagesha, Chokkahalli K; Walinjkar, Jaydeep Avinash; Khetan, Vikas

    2016-08-01

    Association of choroidal neovascular (CNV) membrane with circumscribed choroidal hemangioma is rare, and the CNV development after photodynamic therapy (PDT) is also rare. Etiopathogenesis of these associations is poorly understood. We noted the development of CNV over choroidal hemangioma after PDT therapy in a young female patient in our hospital. Temporal association of CNV development after PDT treatment points toward the possible side effects of PDT. Repeat injections of antivascular endothelial growth factor (ranibizumab) regressed the CNV resulting in a favorable visual outcome. PMID:27688287

  10. Pachychoroid neovasculopathy in extramacular choroidal neovascularization

    PubMed Central

    Gupta, Mrinali Patel; Rusu, Irene; Seidman, Carly; Orlin, Anton; D’Amico, Donald J; Kiss, Szilard

    2016-01-01

    Purpose To review a series of extramacular choroidal neovascular membranes (CNVMs) in the context of their choroidal features, as determined by optical coherence tomography (OCT). Methods Patients with extramacular CNVMs were identified from a tertiary care center through a review of records. The charts and cases were reviewed using multimodal imaging including fundus photography, OCT, fluorescein angiography (FA), and indocyanine angio-graphy (ICG). Results Of six patients with extramacular CNVMs evaluated in this series, four patients (66.7%) exhibited pachychoroidopathy on OCT imaging under or adjacent to the extramacular CNVM. All four of these patients also exhibited pachychoroidopathy in the macular OCT distant from the CNVM. Conclusion Pachychoroidopathy is implicated in some cases of extramacular CNVMs. This represents the first report, to our knowledge, of pachychoroidopathy in extramacular CNVM. PMID:27471372

  11. Doxycycline-mediated Inhibition of Choroidal Neovascularization

    PubMed Central

    Samtani, S.; Amaral, J.; Campos, M.; Fariss, R. N.; Becerra, S. P.

    2010-01-01

    Purpose Doxycycline, a broad spectrum antibiotic, has certain anti-angiogenic properties and can inhibit matrix metalloproteinases (MMPs/gelatinases). We investigated the effects of doxycycline on choroidal neovascularization (CNV), and regulation of MMP-2/-9 and pigment epithelium-derived factor (PEDF). Methods Doxycycline was orally administered to rats at 500, 50, 5, and 0.5 mg/kg/day, using non-treated animals as controls. Experimental CNV was induced with laser 7 days after doxycycline treatment started. At seven days post-induction, animals were euthanized, and eyes collected. RPE/choroid flat-mounts were labeled with isolectin IB4 to determine CNV lesion volumes using confocal microscopy and Volocity® software. MMP-2, MMP-9 and PEDF protein levels were determined by ELISA. MMP catalytic activity was determined in solution using fluorogenic gelatin and peptide substrates, by gelatin zymography in SDS-PAGE and by in situ DQ-gelatin zymography in RPE/choroid sections. Results CNV complex lesion volumes decreased with doxycycline in a dose-response relationship. A dosage of 500 mg/kg/day caused a 70% inhibition of CNV complex volume compared to control animals. Doxycycline elevated PEDF levels in plasma, and did not affect the plasma pro- and active MMP-2 and MMP-9 levels. However, the in vitro enzymatic activities of purified MMP-2 and MMP-9 declined significantly with doxycycline. MMP-2, MMP-9 and gelatinolytic activities in situ increased early in CNV lesion development. Doxycycline treatments and exogenous additions inhibited gelatinolytic activities in CNV lesions. Conclusions Doxycycline effectively hampered the progression of experimental CNV. The results suggest that orally administrated doxycycline can reach the choroid to attenuate proteolytic enzymes that remodel Bruch's membrane and promote the anti-angiogenic PEDF to inhibit neovascularization. PMID:19516001

  12. Retinal pigment epithelium tear formation following intravitreal ranibizumab injection in choroidal neovascularization secondary to choroidal osteoma.

    PubMed

    Erol, Muhammet K; Coban, Deniz Turgut; Ceran, Basak Bostanci; Bulut, Mehmet

    2014-09-01

    Choroidal osteoma is an extremely rare osseous tumor of the choroid where choroidal neovascularization (CNV) is the major cause of visual loss. We report the case of a 28-year-old female with CNV secondary to choroidal osteoma, who developed RPE tear after intravitreal ranibizumab treatment.

  13. Intravitreal Bevacizumab for Management of Choroidal Osteoma without Choroidal Neovascularization

    PubMed Central

    Najafabadi, Farhad Fazel; Hendimarjan, Seyyed Moien; Zarrin, Yasaman; Najafabadi, Mohammadreza Fazel

    2015-01-01

    To report a patient with juxtapapillary choroidal osteoma (CO) with serous retinal detachment (SRD) not associated with choroidal neovascularization (CNV) who was successfully treated with a single intravitreal injection of bevacizumab. A 20-year-old woman presented with decreased vision in her right eye. Ultrasonography, fundus autofluorescence, fluorescein angiography (FA) and optical coherence tomography (OCT) were performed. She was diagnosed with juxtapapillary CO with SRD in the absence of CNV. The treatment involved a single intravitreal injection of bevacizumab. Visual acuity (VA) was 20/100 pre-injection which was dramatically improved to 20/20 one week after the injection without any additional treatment. Fundus examination and OCT one week after the injection revealed complete absorption of the subretinal fluid (SRF) in the macula. Eighteen months after the injection, vision remained stable and she did not show re-accumulation of SRF in her right eye. Intravitreal injection of bevacizumab may be effective in managing CO associated with SRF without CNV. PMID:27051495

  14. Is Asthma Related to Choroidal Neovascularization?

    PubMed Central

    Hou, Jing; Gong, Peihua; Zheng, Yi; Zhao, Mingwei; Zhou, Peng; Li, Xiaoxin

    2012-01-01

    Background Age-related degeneration(AMD) and asthma are both diseases that are related to the activation of the complement system. The association between AMD and asthma has been debated in previous studies. The authors investigated the relationship between AMD and asthma systemically. Principal Findings The epidemiological study showed that asthma was related to choroidal neovascularization(CNV) subtype(OR = 1.721, P = 0.023). However, the meta-analysis showed there was no association between AMD and asthma. In an animal model, we found more fluoresce in leakage of CNV lesions by FA analysis and more angiogenesis by histological analysis in rats with asthma. Western blot demonstrated an elevated level of C3α-chain, C3α’-chain and VEGF. After compstatin was intravitreally injected, CNV leakage decreased according to FA analysis, with the level of C3 and VEGF protein decreasing at the same time. Significance This study first investigated the relationship between AMD and asthma systematically, and it was found that asthma could be a risk factor for the development of AMD. The study may provide a better understanding of the disease, which may advance the potential for screening asthma patients in clinical practice. PMID:22567103

  15. Bilateral choroidal osteoma with choroidal neovascular membrane treated with bevacizumab in a child.

    PubMed

    Agarwal, Manisha; Kantha, Meha; Mayor, Rahul; Venkatesh, Ramesh; Shroff, Cyrus M

    2014-01-01

    Choroidal osteoma is a rare benign tumor. We report a male child diagnosed with bilateral choroidal osteoma, high myopia and secondary choroidal neovascularization (CNV) membrane in one eye. Co-existence of posterior staphyloma made the clinical diagnosis of choroidal osteoma difficult due to the osteoma filling the depression of the posterior staphyloma. Typical findings on fundus fluorescein angiography, optical coherence tomography, B-scan and indocyanine green angiography confirmed the diagnosis. A review of literature was performed. CNV secondary to choroidal osteoma was treated with intravitreal bevacizumab and it responded well. Regular follow-up is essential for recurrence of CNV and decalcification of the osteoma.

  16. Phosphatidylserine (PS) Is Exposed in Choroidal Neovascular Endothelium: PS-Targeting Antibodies Inhibit Choroidal Angiogenesis In Vivo and Ex Vivo

    PubMed Central

    Li, Tao; Aredo, Bogale; Zhang, Kaiyan; Zhong, Xin; Pulido, Jose S.; Wang, Shusheng; He, Yu-Guang; Huang, Xianming; Brekken, Rolf A.; Ufret-Vincenty, Rafael L.

    2015-01-01

    Purpose Choroidal neovascularization (CNV) accounts for 90% of cases of severe vision loss in patients with advanced age-related macular degeneration. Identifying new therapeutic targets for CNV may lead to novel combination therapies to improve outcomes and reduce treatment burden. Our goal was to test whether phosphatidylserine (PS) becomes exposed in the outer membrane of choroidal neovascular endothelium, and whether this could provide a new therapeutic target for CNV. Methods Choroidal neovascularization was induced in C57BL/6J mice using laser photocoagulation. Choroidal neovascularization lesions costained for exposed PS and for intercellular adhesion molecule 2 (or isolectin B4) were imaged in flat mounts and in cross sections. The laser CNV model and a choroidal sprouting assay were used to test the effect of PS-targeting antibodies on choroidal angiogenesis. Choroidal neovascularization lesion size was determined by intercellular adhesion molecule 2 (ICAM-2) staining of flat mounts. Results We found that PS was exposed in CNV lesions and colocalized with vascular endothelial staining. Treatment with PS-targeting antibodies led to a 40% to 80% reduction in CNV lesion area when compared to treatment with a control antibody. The effect was the same as that seen using an equal dose of an anti-VEGF antibody. Results were confirmed using the choroid sprouting assay, an ex vivo model of choroidal angiogenesis. Conclusions We demonstrated that PS is exposed in choroidal neovascular endothelium. Furthermore, targeting this exposed PS with antibodies may be of therapeutic value in CNV. PMID:26529048

  17. Optical Coherence Tomography Angiography for Detecting Choroidal Neovascularization Secondary to Choroidal Osteoma.

    PubMed

    Szelog, Jason T; Bonini Filho, Marco A; Lally, David R; de Carlo, Talisa E; Duker, Jay S

    2016-01-01

    Choroidal osteoma is an ossifying tumor that is found predominantly in the peripapillary and macular areas. It typically affects otherwise healthy females. Vision loss may occur secondary to the development of choroidal neovascularization (CNV). Fluorescein angiography (FA) remains the gold standard for diagnosing CNV; however, the use of optical coherence tomography angiography (OCTA) as an adjunct to FA is growing. In this report, a 16-year-old female with a large, unilateral peripapillary choroidal osteoma presented with blurred vision. Exam revealed scattered intraretinal hemorrhage, but FA was unable to detect CNV overlying the tumor. OCTA detected abnormal flow in the outer retina corresponding to a type 2 CNV. Following intravitreal anti-vascular endothelial growth factor therapy, the CNV regressed, the hemorrhage resolved, and there was less fluid. OCTA may be helpful in detecting CNV noninvasively in eyes in which FA is equivocal, such as those with choroidal osteoma.

  18. Photodynamic therapy combined with intravitreal bevacizumab in a patient with choroidal neovascularization secondary to choroidal osteoma.

    PubMed

    Jang, Jung Hyun; Kim, Keong Hwan; Lee, Soo Jung; Park, Jung Min

    2012-12-01

    Choroidal osteoma is a benign ossified tumor that is found predominantly in healthy young women during their second and third decades of life. The lesions are white-to-cream or orange in color, are located in the peripapillary and macular areas, and are unilateral in most patients. The symptoms of choroidal osteoma include decreased visual acuity and metamorphopsia or scotoma corresponding to the location of the osteoma, but some patients have no symptoms. Prognosis of vision varies according to tumor location, retinal pigment epithelial and sensory retinal degeneration, subretinal fluid and hemorrhage, and development of a subretinal neovascular membrane.

  19. OCT Angiography Identification of Choroidal Neovascularization Secondary to Acute Zonal Occult Outer Retinopathy.

    PubMed

    Levison, Ashleigh L; Baynes, Kimberly; Lowder, Careen Y; Srivastava, Sunil K

    2016-01-01

    A 74-year-old female with acute zonal occult outer retinopathy presented with a new lesion suspicious for choroidal neovascularization (CNV) in her right eye. Optical coherence tomography angiography (OCTA) confirmed the presence of CNV. OCTA is a new imaging technique that may help guide diagnosis and management of choroidal neovascular membranes in uveitic diseases.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26417524

  1. Recombinant Human VEGF165b Inhibits Experimental Choroidal Neovascularization

    PubMed Central

    Hua, Jing; Spee, Christine; Kase, Satoru; Rennel, Emma S.; Magnussen, Anette L.; Qiu, Yan; Varey, Alex; Dhayade, Sandeep; Churchill, Amanda J.; Harper, Steven J.; Hinton, David R.

    2010-01-01

    Purpose. Vascular endothelial growth factor (VEGF-A) is the principal stimulator of angiogenesis in wet age-related macular degeneration (AMD). However, VEGF-A is generated by alternate splicing into two families, the proangiogenic VEGF-Axxx family and the antiangiogenic VEGF-Axxxb family. It is the proangiogenic family that is responsible for the blood vessel growth seen in AMD. Methods. To determine the role of antiangiogenic isoforms of VEGF-A as inhibitors of choroidal neovascularization, the authors used a model of laser-induced choroidal neovascularization in the mouse eye and investigated VEGF-A165b effects on endothelial cells and VEGFRs in vitro. Results. VEGF-A165b inhibited VEGF-A165–mediated endothelial cell migration with a dose effect similar to that of ranibizumab and bevacizumab and 200-fold more potent than that of pegaptanib. VEGF-A165b bound both VEGFR1 and VEGFR2 with affinity similar to that of VEGF-A165. After laser injury, mice were injected either intraocularly or subcutaneously with recombinant human VEGF-A165b. Intraocular injection of rhVEGF-A165b gave a pronounced dose-dependent inhibition of fluorescein leakage, with an IC50 of 16 pg/eye, neovascularization (IC50, 0.8 pg/eye), and lesion as assessed by histologic staining (IC50, 8 pg/eye). Subcutaneous administration of 100 μg twice a week also inhibited fluorescein leakage and neovascularization and reduced lesion size. Conclusions. These results show that VEGF-A165b is a potent antiangiogenic agent in a mouse model of age-related macular degeneration and suggest that increasing the ratio of antiangiogenic-to-proangiogenic isoforms may be therapeutically effective in this condition. PMID:20237252

  2. Dye-enhanced diode laser photocoagulation of choroidal neovascularizations

    NASA Astrophysics Data System (ADS)

    Klingbeil, Ulrich; Puliafito, Carmen A.; McCarthy, Dan; Reichel, Elias; Olk, Joseph; Lesiecki, Michael L.

    1994-06-01

    Dye-enhanced diode laser photocoagulation, using the dye indocyanine green (ICG), has shown some potential in the treatment of choroidal neovascularizations (CNV). A diode laser system was developed and optimized to emit at the absorption maximum of ICG. In a clinical study at two retinal centers, more than 70 patients, the majority of which had age-related macular degeneration, were treated. Eighteen cases with ill-defined subfoveal CNV were followed an average of 11 months after laser treatment. The results show success in resolving the CNV with an average long-term preservation of visual function equal to or superior to data provided by the Macular Photocoagulation Study for confluent burns of low intensity applied to the CNV. Details of the technique and discussion of the controversies inherent in such a treatment strategy will be presented.

  3. An Angiogenic Role for Adrenomedullin in Choroidal Neovascularization

    PubMed Central

    Sakimoto, Susumu; Kidoya, Hiroyasu; Kamei, Motohiro; Naito, Hisamichi; Yamakawa, Daishi; Sakaguchi, Hirokazu; Wakabayashi, Taku; Nishida, Kohji; Takakura, Nobuyuki

    2013-01-01

    Purpose Adrenomedullin (ADM) has been shown to take part in physiological and pathological angiogenesis. The purpose of this study was to investigate whether ADM signaling is involved in choroidal neovascularization (CNV) using a mouse model. Methods and Results CNV was induced by laser photocoagulation in 8-week-old C57BL/6 mice. ADM mRNA expression significantly increased following treatment, peaking 4 days thereafter. The expression of ADM receptor (ADM-R) components (CRLR, RAMP2 and RAMP 3) was higher in CD31+CD45− endothelial cells (ECs) than CD31−CD45− non-ECs. Inflammatory stimulation upregulated the expression of ADM not only in cell lines but also in cells in primary cultures of the choroid/retinal pigment epithelium complex. Supernatants from TNFα-treated macrophage cell lines potentiated the proliferation of ECs and this was partially suppressed by an ADM antagonist, ADM (22–52). Intravitreous injection of ADM (22–52) or ADM neutralizing monoclonal antibody (mAb) after laser treatment significantly reduced the size of CNV compared with vehicle-treated controls (p<0.01). Conclusions ADM signaling is involved in laser-induced CNV formation, because both an ADM antagonist and ADM mAb significantly inhibited it. Suppression of ADM signaling might be a valuable alternative treatment for CNV associated with age-related macular degeneration. PMID:23520487

  4. Macrophage polarization in experimental and clinical choroidal neovascularization

    PubMed Central

    Yang, Yu; Liu, Fang; Tang, Miao; Yuan, Miner; Hu, Andina; Zhan, Zongyi; Li, Zijing; Li, Jiaqing; Ding, Xiaoyan; Lu, Lin

    2016-01-01

    Macrophages play an important role in the development of age-related macular degeneration (AMD). In this study, the spatial and temporal changes and the polarization of macrophages in murine laser-induced choroidal neovascularization (CNV) were investigated, and the polarized M1 and M2 biomarkers in the aqueous humors of neovascular AMD (nAMD) patients were studied. Macrophages, the main infiltrating inflammatory cells in CNV lesions, were evidenced by a significant increase in F4/80 mRNA expression and by the infiltration of F4/80+ cells in the lesions and the vicinity of laser-induced CNV. The mRNA expressions of M1-related markers were dramatically upregulated in the early stage, while the M2-related markers were slightly upregulated in the middle stage and sustained until the late stage. The results of immunostaining showed a similar early-but-transient M1 pattern and a delayed-but-sustained M2 pattern in laser-induced CNV. In addition, a higher M2/M1 ratio was found in both the murine models (Arg-1/iNOS and CCL22/CXCL10) and the aqueous humors of nAMD patients (CCL22/CXCL10) than in the controls. Our results suggested that the dynamic patterns of M1 and M2 were different in both the experimental and clinical CNV. The M2 macrophages were predominant and may play a more important role in the development of CNV. PMID:27489096

  5. Optical Coherence Tomography Angiography in Retinal Vascular Diseases and Choroidal Neovascularization

    PubMed Central

    Mastropasqua, Rodolfo; Di Antonio, Luca; Di Staso, Silvio; Agnifili, Luca; Di Gregorio, Angela; Ciancaglini, Marco; Mastropasqua, Leonardo

    2015-01-01

    Purpose. To assess the ability of optical coherence tomography-angiography (OCT-A) to show and analyze retinal vascular patterns and the choroidal neovascularization (CNV) in retinal vascular diseases. Methods. Seven eyes of seven consecutive patients with retinal vascular diseases were examined. Two healthy subjects served as controls. All eyes were scanned with the SD-OCT XR Avanti (Optovue Inc, Fremont CA, USA). Split spectrum amplitude decorrelation angiography algorithm was used to identify the blood flow within the tissue. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) with Spectralis HRA + OCT (Heidelberg Engineering GmbH) were performed. Results. In healthy subjects OCT-A visualized major macular vessels and detailed capillary networks around the foveal avascular zone. Patients were affected with myopic CNV (2 eyes), age-related macular degeneration related (2), branch retinal vein occlusion (BRVO) (2), and branch retinal artery occlusion (BRAO) (1). OCT-A images provided distinct vascular patterns, distinguishing perfused and nonperfused areas in BRVO and BRAO and recognizing the presence, location, and size of CNV. Conclusions. OCT-A provides detailed images of retinal vascular plexuses and quantitative data of pathologic structures. Further studies are warranted to define the role of OCT-A in the assessment of retinovascular diseases, with respect to conventional FA and ICG-A. PMID:26491548

  6. IKK2 Inhibition Attenuates Laser-Induced Choroidal Neovascularization

    PubMed Central

    Lu, Huayi; Lu, Qingxian; Gaddipati, Subhash; Kasetti, Ramesh Babu; Wang, Wei; Pasparakis, Manolis; Kaplan, Henry J.; Li, Qiutang

    2014-01-01

    Choroidal neovascularization (CNV) is aberrant angiogenesis associated with exudative age-related macular degeneration (AMD), a leading cause of blindness in the elderly. Inflammation has been suggested as a risk factor for AMD. The IKK2/NF-κB pathway plays a key role in the inflammatory response through regulation of the transcription of cytokines, chemokines, growth factors and angiogenic factors. We investigated the functional role of IKK2 in development of the laser-induced CNV using either Ikk2 conditional knockout mice or an IKK2 inhibitor. The retinal neuronal tissue and RPE deletion of IKK2 was generated by breeding Ikk2−/flox mice with Nestin-Cre mice. Deletion of Ikk2 in the retina caused no obvious defect in retinal development or function, but resulted in a significant reduction in laser-induced CNV. In addition, intravitreal or retrobulbar injection of an IKK2 specific chemical inhibitor, TPCA-1, also showed similar inhibition of CNV. Furthermore, in vitro inhibition of IKK2 in ARPE-19 cells significantly reduced heat shock-induced expression of NFKBIA, IL1B, CCL2, VEGFA, PDGFA, HIF1A, and MMP-2, suggesting that IKK2 may regulate multiple molecular pathways involved in laser-induced CNV. The in vivo laser-induced expression of VEGFA, and HIF1A in RPE and choroidal tissue was also blocked by TPCA-1 treatment. Thus, IKK2/NF-κB signaling appears responsible for production of pro-inflammatory and pro-angiogenic factors in laser-induced CNV, suggesting that this intracellular pathway may serve as an important therapeutic target for aberrant angiogenesis in exudative AMD. PMID:24489934

  7. Inhibition of choroidal neovascularization by homoisoflavanone, a new angiogenesis inhibitor

    PubMed Central

    Kim, Jeong Hun; Kim, Jin Hyoung; Jun, Hyoung-Oh; Kwon, Ho Jeong; Park, Kyu Hyung; Kim, Kyu-Won

    2008-01-01

    Purpose Age-related macular degeneration (AMD) is the leading cause of blindness in elderly. The detailed mechanism of choroidal neovascularization (CNV) leads to severe vision loss in patients with AMD. This study was undertaken to evaluate the inhibitory effect of homoisoflavanone on CNV. Methods Antiangiogenic activity of homoisoflavanone was evaluated by in vitro tube formation assay of human umbilical vein endothelial cells (HUVECs) and cell migration assay of HUVECs., Homoisoflavanone or PBS was injected intravitreously into a mouse model of laser-photocoagulation-induced CNV. Fluorescein angiography and vessel counting in cross sections were employed to examine CNV lesions. The toxicity of homoisoflavanone was evaluated through 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) assay in HUVECs as well as histological examination and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining in the retina. Results Homoisoflavanone effectively inhibited in vitro tube formation and cell migration of HUVECs. Interestingly, homoisoflavanone significantly reduced CNV and its leakage in a mouse model of laser-photocoagulation-induced CNV. In addition, homoisoflavanone showed no effect on cell viability of HUVECs and no retinal toxicity in a concentration range of 1-10 μM. Conclusions Our data suggest that homoisoflavanone is a potent inhibitor of CNV and may be applied in the treatment of other vasoproliferative retinopathies and tumor. PMID:18385791

  8. Choroidal thickness profiles in myopic eyes of young adults in the Correction of Myopia Evaluation Trial cohort

    PubMed Central

    Harb, Elise; Hyman, Leslie; Gwiazda, Jane; Marsh-Tootle, Wendy; Zhang, Qinghua; Hou, Wei; Norton, Thomas T; Weise, Katherine; Dirkes, Keri; Zangwill, Linda M

    2015-01-01

    Purpose To examine the relationship of choroidal thickness with axial length (AL) and myopia in young adult eyes in the ethnically diverse Correction of Myopia Evaluation Trial (COMET) cohort. Design Cross-sectional, multi-center, study Methods In addition to measures of myopia by cycloplegic autorefraction and AL by A-scan ultrasonography, participants underwent optical coherence tomography imaging of the choroid (RTVue) in both eyes at their last visit (14 years after baseline). Using digital calipers, two independent readers measured choroidal thickness in the right eye (left eye if poor quality; n=37) at seven locations: fovea and 750, 1500, 2250μm nasal (N) and temporal (T) to the fovea. Results Choroidal thickness measurements were available from 294/346 (85%) of imaged participants (mean age: 24.3±1.4 years; 44.9% male) with mean myopia of -5.3±2.0D and mean AL of 25.5±1.0mm. Overall, choroidal thickness varied by location (p<0.0001) and was thickest at the fovea (273.8±70.9 μm) and thinnest nasally (N2250,191.5±69.3 μm). Multivariable analyses showed significantly thinner choroids in eyes with more myopia and longer AL at all locations except T2250 (p≤0.001) and presence of peri-papillary crescent at all locations except T1500 and T2250 (p≤0.0001). Choroidal thickness varied by ethnicity at N2250 (p<0.0001), with Asians having the thinnest and African Americans the thickest choroids. Conclusion Choroids are thinner in longer, more myopic young adult eyes. The thinning was most prominent nasally and in eyes with a crescent. In the furthest nasal location, ethnicity was associated with choroidal thickness. The findings suggest that choroidal thickness should be evaluated, especially in the nasal regions where myopic degenerations are most commonly seen clinically. PMID:25896460

  9. Modifying Choroidal Neovascularization Development with a Nutritional Supplement in Mice

    PubMed Central

    Ivanescu, Alina Adriana; Fernández-Robredo, Patricia; Heras-Mulero, Henar; Sádaba-Echarri, Luis Manuel; García-García, Laura; Fernández-García, Vanessa; Moreno-Orduna, Maite; Redondo-Exposito, Aitor; Recalde, Sergio; García-Layana, Alfredo

    2015-01-01

    We examined the effect of nutritional supplements (modified Age Related Eye Disease Study (AREDS)-II formulation containing vitamins, minerals, lutein, resveratrol, and omega-3 fatty acids) on choroidal neovascularization (CNV). Supplements were administered alone and combined with intravitreal anti-VEGF in an early-CNV (diode laser-induced) murine model. Sixty mice were evenly divided into group V (oral vehicle, intravitreal saline), group S (oral supplement, intravitreal saline), group V + aVEGF (oral vehicle, intravitreal anti-VEGF), and group S + aVEGF (oral supplement, intravitreal anti-VEGF). Vehicle and nutritional supplements were administered daily for 38 days beginning 10 days before laser. Intravitreal injections were administered 48 h after laser. Fluorescein angiography (FA) and flat-mount CD31 staining evaluated leakage and CNV lesion area. Expression of VEGF, MMP-2 and MMP-9 activity, and NLRP3 were evaluated with RT-PCR, zymography, and western-blot. Leakage, CNV size, VEGF gene and protein expression were lower in groups V + aVEGF, S + aVEGF, and S than in V (all p < 0.05). Additionally, MMP-9 gene expression differed between groups S + aVEGF and V (p < 0.05) and MMP-9 activity was lower in S + aVEGF than in V and S (both p < 0.01). Levels of MMP-2 and NLRP3 were not significantly different between groups. Nutritional supplements either alone or combined with anti-VEGF may mitigate CNV development and inhibit retinal disease involving VEGF overexpression and CNV. PMID:26153682

  10. Modifying Choroidal Neovascularization Development with a Nutritional Supplement in Mice.

    PubMed

    Ivanescu, Alina Adriana; Fernández-Robredo, Patricia; Heras-Mulero, Henar; Sádaba-Echarri, Luis Manuel; García-García, Laura; Fernández-García, Vanessa; Moreno-Orduna, Maite; Redondo-Exposito, Aitor; Recalde, Sergio; García-Layana, Alfredo

    2015-07-01

    We examined the effect of nutritional supplements (modified Age Related Eye Disease Study (AREDS)-II formulation containing vitamins, minerals, lutein, resveratrol, and omega-3 fatty acids) on choroidal neovascularization (CNV). Supplements were administered alone and combined with intravitreal anti-VEGF in an early-CNV (diode laser-induced) murine model. Sixty mice were evenly divided into group V (oral vehicle, intravitreal saline), group S (oral supplement, intravitreal saline), group V + aVEGF (oral vehicle, intravitreal anti-VEGF), and group S + aVEGF (oral supplement, intravitreal anti-VEGF). Vehicle and nutritional supplements were administered daily for 38 days beginning 10 days before laser. Intravitreal injections were administered 48 h after laser. Fluorescein angiography (FA) and flat-mount CD31 staining evaluated leakage and CNV lesion area. Expression of VEGF, MMP-2 and MMP-9 activity, and NLRP3 were evaluated with RT-PCR, zymography, and western-blot. Leakage, CNV size, VEGF gene and protein expression were lower in groups V + aVEGF, S + aVEGF, and S than in V (all p < 0.05). Additionally, MMP-9 gene expression differed between groups S + aVEGF and V (p < 0.05) and MMP-9 activity was lower in S + aVEGF than in V and S (both p < 0.01). Levels of MMP-2 and NLRP3 were not significantly different between groups. Nutritional supplements either alone or combined with anti-VEGF may mitigate CNV development and inhibit retinal disease involving VEGF overexpression and CNV. PMID:26153682

  11. Modifying Choroidal Neovascularization Development with a Nutritional Supplement in Mice.

    PubMed

    Ivanescu, Alina Adriana; Fernández-Robredo, Patricia; Heras-Mulero, Henar; Sádaba-Echarri, Luis Manuel; García-García, Laura; Fernández-García, Vanessa; Moreno-Orduna, Maite; Redondo-Exposito, Aitor; Recalde, Sergio; García-Layana, Alfredo

    2015-07-06

    We examined the effect of nutritional supplements (modified Age Related Eye Disease Study (AREDS)-II formulation containing vitamins, minerals, lutein, resveratrol, and omega-3 fatty acids) on choroidal neovascularization (CNV). Supplements were administered alone and combined with intravitreal anti-VEGF in an early-CNV (diode laser-induced) murine model. Sixty mice were evenly divided into group V (oral vehicle, intravitreal saline), group S (oral supplement, intravitreal saline), group V + aVEGF (oral vehicle, intravitreal anti-VEGF), and group S + aVEGF (oral supplement, intravitreal anti-VEGF). Vehicle and nutritional supplements were administered daily for 38 days beginning 10 days before laser. Intravitreal injections were administered 48 h after laser. Fluorescein angiography (FA) and flat-mount CD31 staining evaluated leakage and CNV lesion area. Expression of VEGF, MMP-2 and MMP-9 activity, and NLRP3 were evaluated with RT-PCR, zymography, and western-blot. Leakage, CNV size, VEGF gene and protein expression were lower in groups V + aVEGF, S + aVEGF, and S than in V (all p < 0.05). Additionally, MMP-9 gene expression differed between groups S + aVEGF and V (p < 0.05) and MMP-9 activity was lower in S + aVEGF than in V and S (both p < 0.01). Levels of MMP-2 and NLRP3 were not significantly different between groups. Nutritional supplements either alone or combined with anti-VEGF may mitigate CNV development and inhibit retinal disease involving VEGF overexpression and CNV.

  12. Bone Marrow Transplantation Transfers Age-Related Susceptibility to Neovascular Remodeling in Murine Laser-Induced Choroidal Neovascularization

    PubMed Central

    Espinosa-Heidmann, Diego G.; Malek, Goldis; Mettu, Priyatham S.; Caicedo, Alejandro; Saloupis, Peter; Gach, Sarah; Dunnon, Askia K.; Hu, Peng; Spiga, Maria-Grazia; Cousins, Scott W.

    2013-01-01

    Purpose. Neovascular remodeling (NVR), the progression of small capillaries into large-caliber arterioles with perivascular fibrosis, represents a major therapeutic challenge in neovascular age-related macular degeneration (AMD). Neovascular remodeling occurs after laser-induced choroidal neovascularization (CNV) in aged but not young mice. Additionally, bone marrow–derived cells, including macrophages, endothelial precursor cells, and mesenchymal precursor cells, contribute to CNV severity. In this study, we investigated the impact of aged bone marrow transplantation (BMT) on the degree of fibrosis, size, and vascular morphology of CNV lesions in a mouse model of laser-induced CNV. Methods. Young (2 months) and old (16 months) mice were transplanted with green fluorescent protein (GFP)-labeled bone marrow isolated from either young or old donors. Laser CNV was induced 1 month following transplant, and eyes were analyzed via choroidal flat mounts and immunohistochemistry 1 month postlaser. The identity of cells infiltrating CNV lesions was determined using specific markers for the labeled transplanted cells (GFP+), macrophages (F4/80+), perivascular mesenchymal-derived cells (smooth muscle actin, SMA+), and endothelial cells (CD31+). Results. Bone marrow transplantation from aged mice transferred susceptibility to NVR into young recipients. Inversely, transplantation of young marrow into old mice prevented NVR, preserving small size and minimal fibrosis. Mice with NVR demonstrated a greater relative contribution of marrow-derived SMA+ perivascular mesenchymal cells as compared to other cells. Conclusions. Our findings indicate that the status of bone marrow is an important determining factor of neovascular severity. Furthermore, we find that perivascular mesenchymal cells, rather than endothelial cells, derived from aged bone marrow may contribute to increased CNV severity in this murine model of experimental neovascularization. PMID:24135751

  13. VEGF-Production by CCR2-Dependent Macrophages Contributes to Laser-Induced Choroidal Neovascularization

    PubMed Central

    Krause, Torsten A.; Alex, Anne F.; Engel, Daniel R.; Kurts, Christian; Eter, Nicole

    2014-01-01

    Age-related macular degeneration (AMD) is the most prevalent cause of blindness in the elderly, and its exsudative subtype critically depends on local production of vascular endothelial growth factor A (VEGF). Mononuclear phagocytes, such as macrophages and microglia cells, can produce VEGF. Their precursors, for example monocytes, can be recruited to sites of inflammation by the chemokine receptor CCR2, and this has been proposed to be important in AMD. To investigate the role of macrophages and CCR2 in AMD, we studied intracellular VEGF content in a laser-induced murine model of choroidal neovascularisation. To this end, we established a technique to quantify the VEGF content in cell subsets from the laser-treated retina and choroid separately. 3 days after laser, macrophage numbers and their VEGF content were substantially elevated in the choroid. Macrophage accumulation was CCR2-dependent, indicating recruitment from the circulation. In the retina, microglia cells were the main VEGF+ phagocyte type. A greater proportion of microglia cells contained VEGF after laser, and this was CCR2-independent. On day 6, VEGF-expressing macrophage numbers had already declined, whereas numbers of VEGF+ microglia cells remained increased. Other sources of VEGF detectable by flow cytometry included in dendritic cells and endothelial cells in both retina and choroid, and Müller cells/astrocytes in the retina. However, their VEGF content was not increased after laser. When we analyzed flatmounts of laser-treated eyes, CCR2-deficient mice showed reduced neovascular areas after 2 weeks, but this difference was not evident 3 weeks after laser. In summary, CCR2-dependent influx of macrophages causes a transient VEGF increase in the choroid. However, macrophages augmented choroidal neovascularization only initially, presumably because VEGF production by CCR2-independent eye cells prevailed at later time points. These findings identify macrophages as a relevant source of VEGF in laser

  14. Intravitreal removal of large, fibrotic choroidal neovascular membrane complexes in submacular surgery.

    PubMed

    Haivala, Darin R; Nanda, Sumit K

    2002-01-01

    Submacular surgery is a current alternative technique for the treatment of subfoveal choroidal neovascular membranes (CNVM). One of the difficulties often encountered with this technique is the actual removal of the neovascular membrane complex from the eye. It is often too large and fibrotic to be removed directly through a sclerotomy site without risking significant sclerotomy site complications. The vitreous cutter can be used, but despite high aspiration settings, the large, fibrotic neovascular membrane complex may still not be able to be completely removed safely and expeditiously. We describe an alternative technique using the phacofragmentation handpiece to remove large fibrotic neovascular membranes from the vitreous cavity thereby reducing sclerotomy site complications and surgical time. PMID:12358301

  15. Hedgehog Signaling Components Are Expressed in Choroidal Neovascularization in Laser-induced Retinal Lesion.

    PubMed

    Nochioka, Katsunori; Okuda, Hiroaki; Tatsumi, Kouko; Morita, Shoko; Ogata, Nahoko; Wanaka, Akio

    2016-04-28

    Choroidal neovascularization is one of the major pathological changes in age-related macular degeneration, which causes devastating blindness in the elderly population. The molecular mechanism of choroidal neovascularization has been under extensive investigation, but is still an open question. We focused on sonic hedgehog signaling, which is implicated in angiogenesis in various organs. Laser-induced injuries to the mouse retina were made to cause choroidal neovascularization. We examined gene expression of sonic hedgehog, its receptors (patched1, smoothened, cell adhesion molecule down-regulated by oncogenes (Cdon) and biregional Cdon-binding protein (Boc)) and downstream transcription factors (Gli1-3) using real-time RT-PCR. At seven days after injury, mRNAs for Patched1 and Gli1 were upregulated in response to injury, but displayed no upregulation in control retinas. Immunohistochemistry revealed that Patched1 and Gli1 proteins were localized to CD31-positive endothelial cells that cluster between the wounded retina and the pigment epithelium layer. Treatment with the hedgehog signaling inhibitor cyclopamine did not significantly decrease the size of the neovascularization areas, but the hedgehog agonist purmorphamine made the areas significantly larger than those in untreated retina. These results suggest that the hedgehog-signaling cascade may be a therapeutic target for age-related macular degeneration. PMID:27239075

  16. Hedgehog Signaling Components Are Expressed in Choroidal Neovascularization in Laser-induced Retinal Lesion

    PubMed Central

    Nochioka, Katsunori; Okuda, Hiroaki; Tatsumi, Kouko; Morita, Shoko; Ogata, Nahoko; Wanaka, Akio

    2016-01-01

    Choroidal neovascularization is one of the major pathological changes in age-related macular degeneration, which causes devastating blindness in the elderly population. The molecular mechanism of choroidal neovascularization has been under extensive investigation, but is still an open question. We focused on sonic hedgehog signaling, which is implicated in angiogenesis in various organs. Laser-induced injuries to the mouse retina were made to cause choroidal neovascularization. We examined gene expression of sonic hedgehog, its receptors (patched1, smoothened, cell adhesion molecule down-regulated by oncogenes (Cdon) and biregional Cdon-binding protein (Boc)) and downstream transcription factors (Gli1-3) using real-time RT-PCR. At seven days after injury, mRNAs for Patched1 and Gli1 were upregulated in response to injury, but displayed no upregulation in control retinas. Immunohistochemistry revealed that Patched1 and Gli1 proteins were localized to CD31-positive endothelial cells that cluster between the wounded retina and the pigment epithelium layer. Treatment with the hedgehog signaling inhibitor cyclopamine did not significantly decrease the size of the neovascularization areas, but the hedgehog agonist purmorphamine made the areas significantly larger than those in untreated retina. These results suggest that the hedgehog-signaling cascade may be a therapeutic target for age-related macular degeneration. PMID:27239075

  17. The Application of OCTA in Assessment of Anti-VEGF Therapy for Idiopathic Choroidal Neovascularization

    PubMed Central

    Sun, Zihan; Dai, Hong

    2016-01-01

    Purpose. To assess the morphology of idiopathic choroidal neovascularization (ICNV) by optical coherence tomography angiography (OCTA) and determine the therapeutic effects of intravitreal antivascular endothelial growth factor (anti-VEGF). Method. Patients with naive ICNV were assessed by spectral domain optical coherence tomography (SD-OCT) and OCTA in this observational study. The timing of observation was before treatment, 1 day after treatment with intravitreal anti-VEGF injection, and 1 month after the treatment. The central retina thickness (CRT) on SD-OCT, selected CNV area, and flow area on OCTA were measured. Results. A total of 17 eyes from 17 patients with ICNV were included in this study. OCTA showed visible irregular choroidal neovascularization with “tree-in-bud” form on outer retinal layer. After treatment, as well as in the 1-day follow-up, CNV decreased in size from the periphery, and the vessel density was reduced. As shown on OCTA, the selected CNV area and flow area were significantly reduced compared to pretreatment. The rate of CNV vessel area changes was higher on OCTA than the changes in CRT on SD-OCT at 1-day and 1-month follow-up. Conclusion. Intravitreal injection of anti-VEGF is effective for idiopathic choroidal neovascularization, and the treatment outcomes are observable after 1 day. OCTA provides a useful approach for monitoring and evaluating the treatment of intravitreal anti-VEGF for CNV. PMID:27471600

  18. The Application of OCTA in Assessment of Anti-VEGF Therapy for Idiopathic Choroidal Neovascularization.

    PubMed

    Chen, Qin; Yu, Xiaobing; Sun, Zihan; Dai, Hong

    2016-01-01

    Purpose. To assess the morphology of idiopathic choroidal neovascularization (ICNV) by optical coherence tomography angiography (OCTA) and determine the therapeutic effects of intravitreal antivascular endothelial growth factor (anti-VEGF). Method. Patients with naive ICNV were assessed by spectral domain optical coherence tomography (SD-OCT) and OCTA in this observational study. The timing of observation was before treatment, 1 day after treatment with intravitreal anti-VEGF injection, and 1 month after the treatment. The central retina thickness (CRT) on SD-OCT, selected CNV area, and flow area on OCTA were measured. Results. A total of 17 eyes from 17 patients with ICNV were included in this study. OCTA showed visible irregular choroidal neovascularization with "tree-in-bud" form on outer retinal layer. After treatment, as well as in the 1-day follow-up, CNV decreased in size from the periphery, and the vessel density was reduced. As shown on OCTA, the selected CNV area and flow area were significantly reduced compared to pretreatment. The rate of CNV vessel area changes was higher on OCTA than the changes in CRT on SD-OCT at 1-day and 1-month follow-up. Conclusion. Intravitreal injection of anti-VEGF is effective for idiopathic choroidal neovascularization, and the treatment outcomes are observable after 1 day. OCTA provides a useful approach for monitoring and evaluating the treatment of intravitreal anti-VEGF for CNV. PMID:27471600

  19. VEGF Mediates ApoE4-Induced Neovascularization and Synaptic Pathology in the Choroid and Retina.

    PubMed

    Antes, Ran; Salomon-Zimri, Shiran; Beck, Susanne C; Garcia Garrido, Marina; Livnat, Tami; Maharshak, Idit; Kadar, Tamar; Seeliger, Mathias; Weinberger, Dov; Michaelson, Daniel M

    2015-01-01

    Apolipoprotein E4 (apoE4), the most prevalent genetic risk factor for Alzheimer's disease (AD), is associated with neuronal and vascular impairments. Recent findings suggest that retina of apoE4 mice have synaptic and functional impairments. We presently investigated the effects of apoE4 on retinal and choroidal vasculature and the possible role of VEGF in these effects. There were no histological differences between the retinal and choroidal vasculatures of naïve apoE3 and apoE4 mice. In contrast, laserdriven choroidal injury induced higher levels of choroidal neovascularization (CNV) in apoE4 than in apoE3 mice. These effects were associated with an inflammatory response and with activation of the Muller cells and asrocytic markers gluthatione synthetase and GFAP, all of which were more pronounced in the apoE4 mice. CNV also induced a transient increase in the levels of the synaptic markers synaptophysin and PSD95 which were however similar in the apoE4 and apoE3 naive mice. Retinal and choroidal VEGF and apoE levels were lower in naïve apoE4 than in corresponding apoE3 mice. In contrast, VEGF and apoE levels rose more pronouncedly following laser injury in the apoE4 than in apoE3 mice. Taken together, these findings suggest that the apoE4-induced retinal impairments, under basal conditions, may be related to reduced VEGF levels in the eyes of these mice. The hyper-neovascularization in the apoE4 mice might be driven by increased inflammation and the associated surge in VEGF following injury. Retinal and choroidal VEGF and apoE levels were lower in naïve apoE4 than in corresponding apoE3 mice. In contrast, VEGF and apoE levels rose more pronouncedly following laser injury in the apoE4 than in apoE3 mice. Taken together, these findings suggest that the apoE4-induced retinal impairments, under basal conditions, may be related to reduced VEGF levels in the eyes of these mice. The hyper-neovascularization in the apoE4 mice might be driven by increased inflammation

  20. OCT angiography in the management of choroidal neovascular membrane secondary to Sorsby fundus dystrophy.

    PubMed

    Mohla, Aditi; Khan, Kamron; Kasilian, Melissa; Michaelides, Michel

    2016-01-01

    We describe the management of a woman aged 52 years with molecularly confirmed Sorsby fundus dystrophy, who presented with acute visual deterioration in her right eye. Fundus examination identified a right macular lesion suggestive of a choroidal neovascular membrane (CNVM). Optical coherence tomography angiography (OCTA) confirmed the presence of a CNVM. She was treated with 2 monthly intravitreal injections of bevacizumab, associated with OCTA evidence of regression of the CNVM and improvement in her visual acuity. OCTA is a novel, non-invasive method of imaging the retinal vasculature. Images are acquired rapidly, with no associated side effects, offering advantages over the current gold standard technique-fundus fluorescein angiography. PMID:27587748

  1. OCT angiography in the management of choroidal neovascular membrane secondary to Sorsby fundus dystrophy

    PubMed Central

    Mohla, Aditi; Khan, Kamron; Kasilian, Melissa; Michaelides, Michel

    2016-01-01

    We describe the management of a woman aged 52 years with molecularly confirmed Sorsby fundus dystrophy, who presented with acute visual deterioration in her right eye. Fundus examination identified a right macular lesion suggestive of a choroidal neovascular membrane (CNVM). Optical coherence tomography angiography (OCTA) confirmed the presence of a CNVM. She was treated with 2 monthly intravitreal injections of bevacizumab, associated with OCTA evidence of regression of the CNVM and improvement in her visual acuity. OCTA is a novel, non-invasive method of imaging the retinal vasculature. Images are acquired rapidly, with no associated side effects, offering advantages over the current gold standard technique—fundus fluorescein angiography. PMID:27587748

  2. 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.

  3. Anti-VEGF PolysiRNA Polyplex for the Treatment of Choroidal Neovascularization.

    PubMed

    Lee, Jihwang; Ryoo, Na-Kyung; Han, Hyounkoo; Hong, Hye Kyoung; Park, Ji Yeon; Park, Sang Jun; Kim, Yong-Kyu; Sim, Changbeom; Kim, Kwangmeyung; Woo, Se Joon; Park, Kyu Hyung; Kim, Hyuncheol

    2016-06-01

    Choroidal neovascularization (CNV) is a major cause of severe vision loss in patients with age-related macular degeneration (AMD). Present ocular siRNA delivery technology is limited due to poor delivery through the retina to the choroid, where CNV originates. Our goal was to develop an optimized nanosized polyRNAi-based therapeutic delivery system to the subretinal space. We developed it by siRNA multimerization (polysiRNA) followed by coating with branched polyethylenimine and hyaluronic acid, and then evaluated its efficacy in vitro and in vivo. The polysiRNA polyplex showed a narrow size distribution (260.7 ± 43.27 nm) and negative charge (-4.98 ± 0.47 mV) owing to the hyaluronic acid outer layer. In vitro uptake of the polysiRNA polyplex by human ARPE cells was discovered, and the direct inhibition of VEGF mRNA translation was confirmed in B16F10 cells. The intravitreally administered polysiRNA polyplex overcame both the vitreous and retina barriers in vivo and reached the subretinal space efficiently. Intravitreal injection of the polysiRNA polyplex was not toxic to the retina in histopathology. Furthermore, intravitreal injections of the polysiRNA polyplex at both 1 and 7 days after laser photocoagulation inhibited laser-induced choroidal neovascularization, compared to that of the control (p < 0.05). These results suggest that anti-VEGF polysiRNA polyplexes show great potential in delivering multimeric RNAi-based therapeutics to treat retinal or choroidal disorders. PMID:27173745

  4. Aryl hydrocarbon receptor knock-out exacerbates choroidal neovascularization via multiple pathogenic pathways.

    PubMed

    Choudhary, Mayur; Kazmin, Dmitri; Hu, Peng; Thomas, Russell S; McDonnell, Donald P; Malek, Goldis

    2015-01-01

    The aryl hydrocarbon receptor (AhR) is a heterodimeric transcriptional regulator with pleiotropic functions in xenobiotic metabolism and detoxification, vascular development and cancer. Herein, we report a previously undescribed role for the AhR signalling pathway in the pathogenesis of the wet, neovascular subtype of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly in the Western world. Comparative analysis of gene expression profiles of aged AhR(-/-) and wild-type (wt) mice, using high-throughput RNA sequencing, revealed differential modulation of genes belonging to several AMD-related pathogenic pathways, including inflammation, angiogenesis and extracellular matrix regulation. To investigate AhR regulation of these pathways in wet AMD, we experimentally induced choroidal neovascular lesions in AhR(-/-) mice and found that they measured significantly larger in area and volume compared to age-matched wt mice. Furthermore, these lesions displayed a higher number of ionized calcium-binding adaptor molecule 1-positive (Iba1(+) ) microglial cells and a greater amount of collagen type IV deposition, events also seen in human wet AMD pathology specimens. Consistent with our in vivo observations, AhR knock-down was sufficient to increase choroidal endothelial cell migration and tube formation in vitro. Moreover, AhR knock-down caused an increase in collagen type IV production and secretion in both retinal pigment epithelial (RPE) and choroidal endothelial cell cultures, increased expression of angiogenic and inflammatory molecules, including vascular endothelial growth factor A (VEGFA) and chemokine (C-C motif) ligand 2 (CCL2) in RPE cells, and increased expression of secreted phosphoprotein 1 (SPP1) and transforming growth factor-β1 (TGFβ1) in choroidal endothelial cells. Collectively, our findings identify AhR as a regulator of multiple pathogenic pathways in experimentally induced choroidal neovascularization, findings that

  5. Aryl hydrocarbon receptor knock-out exacerbates choroidal neovascularization via multiple pathogenic pathways

    PubMed Central

    Choudhary, Mayur; Kazmin, Dmitri; Hu, Peng; Thomas, Russell S; McDonnell, Donald P; Malek, Goldis

    2015-01-01

    The aryl hydrocarbon receptor (AhR) is a heterodimeric transcriptional regulator with pleiotropic functions in xenobiotic metabolism and detoxification, vascular development and cancer. Herein, we report a previously undescribed role for the AhR signalling pathway in the pathogenesis of the wet, neovascular subtype of age-related macular degeneration (AMD), the leading cause of vision loss in the elderly in the Western world. Comparative analysis of gene expression profiles of aged AhR−/− and wild-type (wt) mice, using high-throughput RNA sequencing, revealed differential modulation of genes belonging to several AMD-related pathogenic pathways, including inflammation, angiogenesis and extracellular matrix regulation. To investigate AhR regulation of these pathways in wet AMD, we experimentally induced choroidal neovascular lesions in AhR−/− mice and found that they measured significantly larger in area and volume compared to age-matched wt mice. Furthermore, these lesions displayed a higher number of ionized calcium-binding adaptor molecule 1-positive (Iba1+) microglial cells and a greater amount of collagen type IV deposition, events also seen in human wet AMD pathology specimens. Consistent with our in vivo observations, AhR knock-down was sufficient to increase choroidal endothelial cell migration and tube formation in vitro. Moreover, AhR knock-down caused an increase in collagen type IV production and secretion in both retinal pigment epithelial (RPE) and choroidal endothelial cell cultures, increased expression of angiogenic and inflammatory molecules, including vascular endothelial growth factor A (VEGFA) and chemokine (C–C motif) ligand 2 (CCL2) in RPE cells, and increased expression of secreted phosphoprotein 1 (SPP1) and transforming growth factor-β1 (TGFβ1) in choroidal endothelial cells. Collectively, our findings identify AhR as a regulator of multiple pathogenic pathways in experimentally induced choroidal neovascularization, findings that

  6. Quantitative optical coherence tomography angiography of choroidal neovascularization in age-related macular degeneration

    PubMed Central

    Jia, Yali; Bailey, Steven T.; Wilson, David J.; Tan, Ou; Klein, Michael L.; Flaxel, Christina J.; Potsaid, Benjamin; Liu, Jonathan J.; Lu, Chen D.; Kraus, Martin F.; Fujimoto, James G.; Huang, David

    2014-01-01

    Purpose To detect and quantify choroidal neovascularization (CNV) in age-related macular degeneration (AMD) patients using optical coherence tomography (OCT) angiography. Design Observational, cross-sectional study. Participants Five normal subjects and five neovascular AMD patients were included. Methods Five eyes with neovascular AMD and five normal age-matched controls were scanned by a high-speed (100,000 A-scans/sec) 1050 nm wavelength swept-source OCT. The macular angiography scan covered a 3×3 mm area and comprised 200×200×8 A-scans acquired in 3.5 sec. Flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Motion artifacts were removed by three dimensional (3D) orthogonal registration and merging of 4 scans. The 3D angiography was segmented into 3 layers: inner retina (to show retinal vasculature), outer retina (to identify CNV), and choroid. En face maximum projection was used to obtain 2D angiograms from the 3 layers. CNV area and flow index were computed from the en face OCT angiogram of the outer retinal layer. Flow (decorrelation) and structural data were combined in composite color angiograms for both en face and cross-sectional views. Main Outcome Measurements CNV angiogram, CNV area, and CNV flow index. Results En face OCT angiograms of CNVs showed sizes and locations that were confirmed by fluorescein angiography. OCT angiography provided more distinct vascular network patterns that were less obscured by subretinal hemorrhage. The en face angiograms also showed areas of reduced choroidal flow adjacent to the CNV in all cases and significantly reduced retinal flow in one case. Cross-sectional angiograms were used to visualize CNV location relative to the retinal pigment epithelium and Bruch’s layer and classify type I and type II CNV. A feeder vessel could be identified in one case. Higher flow indexes were associated with larger CNV and type II CNV. Conclusions OCT angiography provides depth

  7. Role of Intravitreal Antivascular Endothelial Growth Factor Injections for Choroidal Neovascularization due to Choroidal Osteoma.

    PubMed

    Mansour, Ahmad M; Arevalo, J Fernando; Al Kahtani, Eman; Zegarra, Hernando; Abboud, Emad; Anand, Rajiv; Ahmadieh, Hamid; Sisk, Robert A; Mirza, Salman; Tuncer, Samuray; Navea Tejerina, Amparo; Mataix, Jorge; Ascaso, Francisco J; Pulido, Jose S; Guthoff, Rainer; Goebel, Winfried; Roh, Young Jung; Banker, Alay S; Gentile, Ronald C; Martinez, Isabel Alonso; Morris, Rodney; Panday, Neeraj; Min, Park Jung; Mercé, Emilie; Lai, Timothy Y Y; Massoud, Vicky; Ghazi, Nicola G

    2014-01-01

    We treated 26 eyes of 25 young patients having a mean age of 30 years with intravitreal vascular endothelial growth factor (VEGF) inhibitor for choroidal new vessel (CNV) formation overlying choroidal osteoma over a mean follow-up of 26 months. Mean number of injections was 2.4 at 6 months, 3.2 at 12 months, and 5.5 at 24 months. CNV was subfoveal in 14 eyes, juxtafoveal in 5, extrafoveal in 5, and peripapillary in 2. By paired comparison, mean decrease from baseline was 119.7 microns at 6 months (n = 15; P = 0.001), 105.3 microns at 1 year (n = 10; P = 0.03), and 157.6 microns at 2 years (n = 7; P = 0.08). BCVA improved by 3.3 lines at 6 months after therapy (n = 26; P < 0.001), 2.8 lines (n = 20; P = 0.01) at 1 year, and 3.1 lines (n = 13; P = 0.049) at 2 years. We conclude that intravitreal anti-VEGF injections improve vision in majority of eyes with CNV from choroidal osteoma.

  8. Significance of retinal laser lesion location and subretinal hemorrhage in bridging choroidal neovascular complexes

    NASA Astrophysics Data System (ADS)

    Schuschereba, Steven T.; Clarkson, Donna R.; Valo, Lynn M.; Brown, Jeremiah, Jr.; Stuck, Bruce E.

    2003-06-01

    Purpose: To determine funduscopic criteria that will help predict when bridging choroidal neovascular (CNV) complexes will develop after laser retinal trauma and to define early preventive treatment targets. Methods: Ten rhesus monkeys were used and retinal lesions were produced by Nd:YAG exposures (20ns, 1-2mJ, 1064nm, min. spot size) simulating human accidental laser trauma to the central fundus. Funduscopy and fluorescein/ICG angiography were conducted at day 1, 4, and 14, and at 2 and 4 months, and animals terminated for histologic evaluation. Predisposition for bridging fibrovascular complexes was evaluated for single lesions, two small lesions showing coalescing hemorrhages, and multiple lesions involved with large field subretinal and vitreous hemorrhages. Results: Elevated CNVs were present in all single lesions with confined subretinal hemorrhages. All lesion sets that showed initial and small coalescing subretinal hemorrhages formed bridging CNV scars. No bridging CNVs occurred in lesion sets involving a vitreous hemorrhage adjacent to a confined, but small subretinal hemorrhage. In large field subretinal hemorrhages involving multiple laser lesions, complex CNV formation occurred. Extensive secondary photoreceptor losses occurred in confined hemorrhage and CNV zones. Conclusion: Trauma presenting with evidence of coalescing and confined subretinal hemorrhages between two adjacent lesions has a high chance of forming choroidal neovascular bridge complexes between the involved lesions. CNV formation may be related to the long residence time, break down products, and clearance processes of extravasated blood. Removal of trapped blood and curtailing angiogenesis and cellular proliferation may be helpful treatment strategies.

  9. Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization.

    PubMed

    Cousins, Scott W; Espinosa-Heidmann, Diego G; Miller, Daniel M; Pereira-Simon, Simone; Hernandez, Eleut P; Chien, Hsin; Meier-Jewett, Courtney; Dix, Richard D

    2012-01-01

    The neovascular (wet) form of age-related macular degeneration (AMD) leads to vision loss due to choroidal neovascularization (CNV). Since macrophages are important in CNV development, and cytomegalovirus (CMV)-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV), laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF), an outcome that requires active virus replication. PMID:22570607

  10. Macrophage Activation Associated with Chronic Murine Cytomegalovirus Infection Results in More Severe Experimental Choroidal Neovascularization

    PubMed Central

    Cousins, Scott W.; Espinosa-Heidmann, Diego G.; Miller, Daniel M.; Pereira-Simon, Simone; Hernandez, Eleut P.; Chien, Hsin; Meier-Jewett, Courtney; Dix, Richard D.

    2012-01-01

    The neovascular (wet) form of age-related macular degeneration (AMD) leads to vision loss due to choroidal neovascularization (CNV). Since macrophages are important in CNV development, and cytomegalovirus (CMV)-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV), laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF), an outcome that requires active virus replication. PMID:22570607

  11. Influence of Choroidal Neovascularization and Biodegradable Polymeric Particle Size on Transscleral Sustained Delivery of Triamcinolone Acetonide

    PubMed Central

    Kadam, Rajendra S.; Tyagi, Puneet; Edelhauser, Henry F.; Kompella, Uday B.

    2012-01-01

    Purpose One objective of this study was to determine whether polymeric nanoparticles and/or microparticles sustain transscleral choroidal and retinal delivery of triamcinolone acetonide (TA) for two months in therapeutically effective concentrations after single periocular administration. Another objective of this study was to assess the influence of choroidal neovascularization on transscleral delivery of TA. Methods Polymeric nano- and micro-particles of TA were prepared by o/w emulsion- solvent evaporation method using poly-L-lactide (PLA). Particles were characterized for drug loading, size, surface morphology, and the in vitro drug release profile. Choroidal neovascularization (CNV) was induced in brown Norway (BN) rats using a 532 nm diode argon laser and the CNV induction was assessed using fluorescein angiography. In vivo delivery was assessed in control and CNV induced rats at 2 months after periocular injection of TA loaded nano- or micro-particle suspension, or plain TA suspension in PBS (pH7.4). Ocular tissue levels of TA were estimated using LC-MS/MS following liquid-liquid extraction of drug from tissue samples. Nile red loaded microparticles entrapped in periocular tissue at the end of the study were visualized using scanning electron microscopy and confocal microscopy. Inhibitory effect of TA on VEGF secretion was evaluated in ARPE-19 cells. Results Triamcinolone acetonide-PLA nano- (551 nm) and micro-particles (2090 nm), with 14.7 and 29.5 % drug loading, respectively, sustained in vitro TA release for about 45 and 120 days. After subconjunctival injection, microparticles were able to sustain the delivery in all intraocular tissues for 2 months; whereas no drug levels were detected for TA loaded nanoparticles and plain suspension of TA. Intraocular delivery of TA from microparticles was higher in CNV induced rats when compared to control rats. Significant amount of microparticles remained in periocular tissue at 2 months after injection, and

  12. 3D choroid neovascularization growth prediction based on reaction-diffusion model

    NASA Astrophysics Data System (ADS)

    Zhu, Shuxia; Chen, Xinjian; Shi, Fei; Xiang, Dehui; Zhu, Weifang; Chen, Haoyu

    2016-03-01

    Choroid neovascularization (CNV) is a kind of pathology from the choroid and CNV-related disease is one important cause of vision loss. It is desirable to predict the CNV growth rate so that appropriate treatment can be planned. In this paper, we seek to find a method to predict the growth of CNV based on 3D longitudinal Optical Coherence Tomography (OCT) images. A reaction-diffusion model is proposed for prediction. The method consists of four phases: pre-processing, meshing, CNV growth modeling and prediction. We not only apply the reaction-diffusion model to the disease region, but also take the surrounding tissues into consideration including outer retinal layer, inner retinal layer and choroid layer. The diffusion in these tissues is considered as isotropic. The finite-element-method (FEM) is used to solve the partial differential equations (PDE) in the diffusion model. The curve of CNV growth with treatment are fitted and then we can predict the CNV status in a future time point. The preliminary results demonstrated that our proposed method is accurate and the validity and feasibility of our model is obvious.

  13. Idiopathic Choroidal Neovascularization: Intraocular Inflammatory Cytokines and the Effect of Intravitreal Ranibizumab Treatment

    PubMed Central

    Yin, Houfa; Fang, Xiaoyun; Ma, Jian; Chen, Min; Yang, Yabo; Guo, Shenchao; Chen, Zhiqing; Su, Zhaoan; Feng, Lei; Ye, Panpan; Wu, Fang; Yin, Jinfu

    2016-01-01

    Idiopathic choroidal neovascularization (ICNV) is a disorder that primarily affecting patients younger than 50 years and can cause severe loss of vision. Choroidal abnormalities, especially choroidal inflammation, have been thought to be involved in the pathophysiology of ICNV. However, the exact pathogenesis of ICNV remains unclear. The aim of our study was investigate the levels of 27 inflammatory cytokines in the aqueous humor of eyes with ICNV, and to determine the effect of intravitreal injection of ranibizumab (IVR) on cytokine levels. Significantly higher levels of IL-2, IL-10, IL-15, IL-17, basic FGF, and GM-CSF were observed in patients with ICNV compared with controls. However, only IL-17 levels were significantly higher in patients with ICNV compared with controls after adjusting for axial length. Furthermore, there were significant correlations between the levels of IL-10, IL-17, GM-CSF, and VEGF and the lesion area. Significant changes in visual acuity and central retinal thickness were observed after IVR. Besides VEGF, IVR also significantly reduced the levels of IL-2, IL-10, basic FGF, and IL-12, however, the IL-6 levels were significantly increased. Our results suggest that there may be an involvement of IL-17-related inflammatory processes in the etiology of ICNV. PMID:27558944

  14. Intravitreal TSG-6 suppresses laser-induced choroidal neovascularization by inhibiting CCR2+ monocyte recruitment

    PubMed Central

    Jin Kim, Sang; Ju Lee, Hyun; Yun, Ji-Hyun; Hwa Ko, Jung; Choi, Da Ye; Youn Oh, Joo

    2015-01-01

    Choroidal neovascularization (CNV) is the hallmark of wet age-related macular degeneration (AMD), one of the leading causes of blindness in the elderly. Although the pathogenesis of CNV is not clear, a number of studies show that ocular-infiltrating macrophages and inflammation play a critical role in the development of CNV. TNFα-stimulated gene/protein (TSG)-6 is a multifunctional endogenous protein that has anti-inflammatory activities partly by regulating macrophage activation. Therefore, we here investigated the therapeutic potential of TSG-6 in a rat model of CNV induced by laser photocoagulation. Time course analysis showed that the expression of VEGF and pro-inflammatory cytokines in the choroid was up-regulated early after laser injury, and gradually decreased to baseline over 14 days. An intravitreal injection of TSG-6 suppressed the expression of VEGF and pro-inflammatory cytokines including CCL2, and reduced the size of CNV. Also, the number of Iba+ and CCR2+ cells including infiltrating macrophages was markedly lower in the CNV lesion of TSG-6-treated eyes. Further analysis identified CCR2+ CD11b+ CD11c+ cells and CCR2+ CD11b-CD11c+ cells as the cell populations that were increased by laser injury and reduced by TSG-6 treatment. Together, the results demonstrate that TSG-6 inhibits inflammation and CCR2+ monocyte recruitment into the choroid, and suppresses the development of CNV. PMID:26149224

  15. Acute stroke after intravitreal bevacizumab to treat choroidal neovascularization due to angioid streaks in pseudoxanthoma elasticum : a severe systemic adverse event after an off-label procedure.

    PubMed

    Besozzi, Gianluca; Ferrara, Andrea; Epifani, Enrico; Intini, Daniela; Apruzzese, Margherita; Provenzano, Antonio; Vetrugno, Michele

    2013-04-01

    To report the occurrence of acute stroke after intravitreal bevacizumab administration to treat choroidal neovascularization due to angioid streaks in a patient affected by pseudoxanthoma elasticum. A 54-year-old man with pseudoxanthoma elasticum had vision loss because of choroidal neovascularization due to angioid streaks. He underwent two intravitreal bevacizumab injections. Three days after the second procedure the patient was afflicted by acute stroke. Intravitreal injection of bevacizumab to treat choroidal neovascularization due to angioid streaks in pseudoxanthoma elasticum could lead to severe systemic adverse events. PMID:23065017

  16. 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

  17. Rap1 GTPase Activation and Barrier Enhancement in RPE Inhibits Choroidal Neovascularization In Vivo

    PubMed Central

    McCloskey, Manabu; Wang, Haibo; Quilliam, Lawrence A.; Chrzanowska-Wodnicka, Magdalena; Hartnett, M. Elizabeth

    2013-01-01

    Loss of barrier integrity precedes the development of pathologies such as metastasis, inflammatory disorders, and blood-retinal barrier breakdown present in neovascular age-related macular degeneration. Rap1 GTPase is involved in regulating both endothelial and epithelial cell junctions; the specific role of Rap1A vs. Rap1B isoforms is less clear. Compromise of retinal pigment epithelium barrier function is a contributing factor to the development of AMD. We utilized shRNA of Rap1 isoforms in cultured human retinal pigment epithelial cells, along with knockout mouse models to test the role of Rap1 on promoting RPE barrier properties, with emphasis on the dynamic junctional regulation that is triggered when the adhesion between cells is challenged. In vitro, Rap1A shRNA reduced steady-state barrier integrity, whereas Rap1B shRNA affected dynamic junctional responses. In a laser-induced choroidal neovascularization (CNV) model of macular degeneration, Rap1b−/− mice exhibited larger CNV volumes compared to wild-type or Rap1a−/−. In vivo, intravitreal injection of a cAMP analog (8CPT-2′-O-Me-cAMP) that is a known Rap1 activator significantly reduced laser-induced CNV volume, which correlated with the inhibition of CEC transmigration across 8CPT-2′O-Me-cAMP-treated RPE monolayers in vitro. Rap1 activation by 8CPT-2′-O-Me-cAMP treatment increased recruitment of junctional proteins and F-actin to cell-cell contacts, increasing both the linearity of junctions in vitro and in cells surrounding laser-induced lesions in vivo. We conclude that in vitro, Rap1A may be important for steady state barrier integrity, while Rap1B is involved more in dynamic junctional responses such as resistance to junctional disassembly induced by EGTA and reassembly of cell junctions following disruption. Furthermore, activation of Rap1 in vivo inhibited development of choroidal neovascular lesions in a laser-injury model. Our data suggest that targeting Rap1 isoforms in vivo with 8

  18. Retinal Inhibition of CCR3 Induces Retinal Cell Death in a Murine Model of Choroidal Neovascularization

    PubMed Central

    Wang, Haibo; Han, Xiaokun; Gambhir, Deeksha; Becker, Silke; Kunz, Eric; Liu, Angelina Jingtong; Hartnett, M. Elizabeth

    2016-01-01

    Inhibition of chemokine C-C motif receptor 3 (CCR3) signaling has been considered as treatment for neovascular age-related macular degeneration (AMD). However, CCR3 is expressed in neural retina from aged human donor eyes. Therefore, broad CCR3 inhibition may be harmful to the retina. We assessed the effects of CCR3 inhibition on retina and choroidal endothelial cells (CECs) that develop into choroidal neovascularization (CNV). In adult murine eyes, CCR3 colocalized with glutamine-synthetase labeled Műller cells. In a murine laser-induced CNV model, CCR3 immunolocalized not only to lectin-stained cells in CNV lesions but also to the retina. Compared to non-lasered controls, CCR3 mRNA was significantly increased in laser-treated retina. An intravitreal injection of a CCR3 inhibitor (CCR3i) significantly reduced CNV compared to DMSO or PBS controls. Both CCR3i and a neutralizing antibody to CCR3 increased TUNEL+ retinal cells overlying CNV, compared to controls. There was no difference in cleaved caspase-3 in laser-induced CNV lesions or in overlying retina between CCR3i- or control-treated eyes. Following CCR3i, apoptotic inducible factor (AIF) was significantly increased and anti-apoptotic factor BCL2 decreased in the retina; there were no differences in retinal vascular endothelial growth factor (VEGF). In cultured human Műller cells exposed to eotaxin (CCL11) and VEGF, CCR3i significantly increased TUNEL+ cells and AIF but decreased BCL2 and brain derived neurotrophic factor, without affecting caspase-3 activity or VEGF. CCR3i significantly decreased AIF in RPE/choroids and immunostaining of phosphorylated VEGF receptor 2 (p-VEGFR2) in CNV with a trend toward reduced VEGF. In cultured CECs treated with CCL11 and/or VEGF, CCR3i decreased p-VEGFR2 and increased BCL2 without increasing TUNEL+ cells and AIF. These findings suggest that inhibition of retinal CCR3 causes retinal cell death and that targeted inhibition of CCR3 in CECs may be a safer if CCR3 inhibition

  19. Thy-1 Regulates VEGF-Mediated Choroidal Endothelial Cell Activation and Migration: Implications in Neovascular Age-Related Macular Degeneration

    PubMed Central

    Wang, Haibo; Han, Xiaokun; Kunz, Eric; Hartnett, M. Elizabeth

    2016-01-01

    Purpose This study addresses the hypothesis that age-related stresses upregulate Thy-1 in choroidal endothelial cells (CECs) and contribute to CEC activation and migration, processes important in choroidal neovascularization (CNV). Methods Measurements were made of Thy-1 protein (Western blot) in CECs and Thy-1 mRNA (real time quantitative PCR) in CECs treated with VEGF, CCL11, or PBS or in RPE/choroids from young or old donors or lasered or nonlasered mice. Immunolabeled Thy-1 in ocular sections was compared from young versus old human donor eyes or those with or without neovascular AMD or from lasered versus nonlasered mice. Choroidal endothelial cells transfected with Thy-1 or control siRNA or pretreated with Thy-1 blocking peptide or control were stimulated with VEGF or 7-ketocholesterol (7-KC). Choroidal endothelial cell migration, proliferation, cytoskeletal stress fibers, Rac1 activation, and phosphorylated VEGF receptor 2 (VEGFR2), integrin β3, and Src were measured. Statistics were performed using ANOVA. Results Thy-1 was expressed in retinal ganglion cells and in vascular endothelial-cadherin–labeled choroid and localized to human or mouse laser-induced CNV lesions. Thy-1 protein and mRNA were significantly increased in CECs treated with VEGF or CCL11 and in RPE/choroids from aged versus young donor eyes or from lasered mice versus nonlasered controls. Knockdown or inhibition of Thy-1 in CECs significantly reduced VEGF-induced CEC migration and proliferation, stress fiber formation and VEGFR2, Src, integrin β3 and Rac1 activation, and 7-KC–induced Rac1 and Src activation. Conclusions Thy-1 in CECs regulates VEGF-induced CEC activation and migration and links extracellular 7-KC to intracellular signaling. Future studies elucidating Thy-1 mechanisms in neovascular AMD are warranted. PMID:27768790

  20. Minimizing projection artifacts for accurate presentation of choroidal neovascularization in OCT micro-angiography

    PubMed Central

    Zhang, Anqi; Zhang, Qinqin; Wang, Ruikang K.

    2015-01-01

    Current optical coherence tomography (OCT) based micro-angiography is prone to a projection (or tailing) effect due to the high scattering property of blood within overlying patent vessels, creating artifacts that interfere with the interpretation of retinal angiographic results. In this work, the projection effect in OCT micro-angiography is examined and its causality is explained by strong light scattering and photon propagation within blood. A simple practical approach is then introduced to minimize these artifacts presented in the outer retinal avascular space, especially useful for examining clinical cases with choroidal neovascularization (CNV). Demonstrated through in-vivo human posterior eye imaging of healthy and CNV subjects, the proposed method is shown effective to eliminate the projection artifacts in outer retinal space of OCT micro-angiography, resulting in better visualization of the pathological neovascularization when compared with the current common approaches. In addition, it is also shown that the proposed method is applicable to minimize the projection artifacts appearing in deep retinal layers. PMID:26504660

  1. Minimizing projection artifacts for accurate presentation of choroidal neovascularization in OCT micro-angiography.

    PubMed

    Zhang, Anqi; Zhang, Qinqin; Wang, Ruikang K

    2015-10-01

    Current optical coherence tomography (OCT) based micro-angiography is prone to a projection (or tailing) effect due to the high scattering property of blood within overlying patent vessels, creating artifacts that interfere with the interpretation of retinal angiographic results. In this work, the projection effect in OCT micro-angiography is examined and its causality is explained by strong light scattering and photon propagation within blood. A simple practical approach is then introduced to minimize these artifacts presented in the outer retinal avascular space, especially useful for examining clinical cases with choroidal neovascularization (CNV). Demonstrated through in-vivo human posterior eye imaging of healthy and CNV subjects, the proposed method is shown effective to eliminate the projection artifacts in outer retinal space of OCT micro-angiography, resulting in better visualization of the pathological neovascularization when compared with the current common approaches. In addition, it is also shown that the proposed method is applicable to minimize the projection artifacts appearing in deep retinal layers. PMID:26504660

  2. Inhibition of choroidal neovascularization by lentivirus-mediated PEDF gene transfer in rats

    PubMed Central

    Yu, Ya-Jie; Mo, Bin; Liu, Lu; Yue, Yan-Kun; Yue, Chang-Li; Liu, Wu

    2016-01-01

    AIM To evaluate the effects of lentivirus-mediated pigment epithelium-derived factor (PEDF) gene transfer performed in treatment of rats with established choroidal neovascularization (CNV), and investigates the mechanism by which PEDF inhibits CNV in rats. METHODS Brown Norway (BN) rats (n=204) were induced by exposure to a laser, and then randomly assigned to 3 groups: no treatment; treatments with intravitreal injection of lentivirus-PEDF-green fluorescent protein (GFP) or lentivirus-control GFP (free fluorescent protein). Following induction and treatment, the CNV tissue was assessed for form, size and vessel leakage by fluorescein fundus angiography (FFA), optical coherence tomography (OCT), histopathology, and examination of choroidal flat mounts. VEGF, Flk-1, and PEDF expression were evaluated by real-time polymerase chain reaction (PCR) and Western blot. RESULTS A stable laser-induced rat model of CNV was successfully established, and used to demonstrate lentivirus-mediated PEDG gene transfer by intravitreal injection. Expression of green fluorescence labelled PEDF was observed in the retina up to 28d after injection. An intravitreal injection of lentivirus-PEDF-GFP at 7d led to a significant reduction in the size, thickness and area of CNV showed by FFA, OCT and choroidal flat mounts. PEDF was up-regulated while VEGF and Flk-1 were down-regulated in the lentivirus-PEDF-GFP group. The differences in VEGF and Flk-1 expression in the control and lentivirus-PEDF groups at 7, 14, 21 and 28d after laser induction were all statistically significant. CONCLUSION Lentivirus-mediated PEDF gene transfer is effective for use in treatment of laser-induced CNV, and PEDF exerts its therapeutic effects by inhibiting expression of VEGF and Flk-1. PMID:27588264

  3. Enhanced depth imaging optical coherence tomography of choroidal osteoma with secondary neovascular membranes: report of two cases.

    PubMed

    Mello, Patrícia Correa de; Berensztejn, Patricia; Brasil, Oswaldo Ferreira Moura

    2016-01-01

    We report enhanced depth imaging optical coherence tomography (EDI-OCT) features based on clinical and imaging data from two newly diagnosed cases of choroidal osteoma presenting with recent visual loss secondary to choroidal neovascular membranes. The features described in the two cases, compression of the choriocapillaris and disorganization of the medium and large vessel layers, are consistent with those of previous reports. We noticed a sponge-like pattern previously reported, but it was subtle. Both lesions had multiple intralesional layers and a typical intrinsic transparency with visibility of the sclerochoroidal junction. PMID:27463635

  4. Enhanced depth imaging optical coherence tomography of choroidal osteoma with secondary neovascular membranes: report of two cases.

    PubMed

    Mello, Patrícia Correa de; Berensztejn, Patricia; Brasil, Oswaldo Ferreira Moura

    2016-01-01

    We report enhanced depth imaging optical coherence tomography (EDI-OCT) features based on clinical and imaging data from two newly diagnosed cases of choroidal osteoma presenting with recent visual loss secondary to choroidal neovascular membranes. The features described in the two cases, compression of the choriocapillaris and disorganization of the medium and large vessel layers, are consistent with those of previous reports. We noticed a sponge-like pattern previously reported, but it was subtle. Both lesions had multiple intralesional layers and a typical intrinsic transparency with visibility of the sclerochoroidal junction.

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

    PubMed Central

    HUA, RUI; CHEN, KANG; HU, YUEDONG; WANG, XINLING; CHEN, LEI

    2015-01-01

    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. PMID:26640540

  6. Metabolic Syndrome Triggered by High-Fructose Diet Favors Choroidal Neovascularization and Impairs Retinal Light Sensitivity in the Rat

    PubMed Central

    Thierry, Magalie; Pasquis, Bruno; Acar, Niyazi; Grégoire, Stéphane; Febvret, Valérie; Buteau, Bénédicte; Gambert-Nicot, Ségolène; Bron, Alain M.; Creuzot-Garcher, Catherine P.; Bretillon, Lionel

    2014-01-01

    Diabetic retinopathy and age-related macular degeneration are the leading causes of blindness in Western populations. Although it is a matter of controversy, large-scale population-based studies have reported increased prevalence of age-related macular degeneration in patients with diabetes or diabetic retinopathy. We hypothesized that metabolic syndrome, one of the major risk factors for type 2 diabetes, would represent a favorable environment for the development of choroidal neovascularization, the main complication of age-related macular degeneration. The fructose-fed rat was used as a model for metabolic syndrome in which choroidal neovascularization was induced by laser photocoagulation. Male Brown Norway rats were fed for 1, 3, and 6 months with a standard equilibrated chow diet or a 60%-rich fructose diet (n = 24 per time point). The animals expectedly developed significant body adiposity (+17%), liver steatosis at 3 and 6 months, hyperleptinemia at 1 and 3 months (two-fold increase) and hyperinsulinemia at 3 and 6 months (up to two-fold increase), but remained normoglycemic and normolipemic. The fructose-fed animals exhibited partial loss of rod sensitivity to light stimulus and reduced amplitude of oscillatory potentials at 6 months. Fructose-fed rats developed significantly more choroidal neovascularization at 14 and 21 days post-laser photocoagulation after 1 and 3 months of diet compared to animals fed the control diet. These results were consistent with infiltration/activation of phagocytic cells and up-regulation of pro-angiogenic gene expression such as Vegf and Leptin in the retina. Our data therefore suggested that metabolic syndrome would exacerbate the development of choroidal neovascularization in our experimental model. PMID:25380250

  7. Metabolic syndrome triggered by high-fructose diet favors choroidal neovascularization and impairs retinal light sensitivity in the rat.

    PubMed

    Thierry, Magalie; Pasquis, Bruno; Acar, Niyazi; Grégoire, Stéphane; Febvret, Valérie; Buteau, Bénédicte; Gambert-Nicot, Ségolène; Bron, Alain M; Creuzot-Garcher, Catherine P; Bretillon, Lionel

    2014-01-01

    Diabetic retinopathy and age-related macular degeneration are the leading causes of blindness in Western populations. Although it is a matter of controversy, large-scale population-based studies have reported increased prevalence of age-related macular degeneration in patients with diabetes or diabetic retinopathy. We hypothesized that metabolic syndrome, one of the major risk factors for type 2 diabetes, would represent a favorable environment for the development of choroidal neovascularization, the main complication of age-related macular degeneration. The fructose-fed rat was used as a model for metabolic syndrome in which choroidal neovascularization was induced by laser photocoagulation. Male Brown Norway rats were fed for 1, 3, and 6 months with a standard equilibrated chow diet or a 60%-rich fructose diet (n = 24 per time point). The animals expectedly developed significant body adiposity (+17%), liver steatosis at 3 and 6 months, hyperleptinemia at 1 and 3 months (two-fold increase) and hyperinsulinemia at 3 and 6 months (up to two-fold increase), but remained normoglycemic and normolipemic. The fructose-fed animals exhibited partial loss of rod sensitivity to light stimulus and reduced amplitude of oscillatory potentials at 6 months. Fructose-fed rats developed significantly more choroidal neovascularization at 14 and 21 days post-laser photocoagulation after 1 and 3 months of diet compared to animals fed the control diet. These results were consistent with infiltration/activation of phagocytic cells and up-regulation of pro-angiogenic gene expression such as Vegf and Leptin in the retina. Our data therefore suggested that metabolic syndrome would exacerbate the development of choroidal neovascularization in our experimental model.

  8. Loculated fluid. A previously undescribed fluorescein angiographic finding in choroidal neovascularization associated with macular degeneration. Macular Photocoagulation Study Reading Center.

    PubMed

    Bressler, N M; Bressler, S B; Alexander, J; Javornik, N; Fine, S L; Murphy, R P

    1991-02-01

    The Foveal Photocoagulation Study, a component of the Macular Photocoagulation Study, is designed to evaluate whether laser treatment can reduce the risk of severe visual loss in eyes with well-defined choroidal neovascular membranes associated with macular degeneration that extend through the foveal center. On one third of the 554 baseline angiograms of study patients enrolled in and whose eyes were graded in the study as of January 31, 1990, the Reading Center staff has noted an unusual pattern of hyperfluorescence in the late-transit frames that has not been described previously. This pattern, which we call "loculated fluid," consists of a well-demarcated area of hyperfluorescence that appears to represent pooling of fluorescein in a compartmentalized space anterior to the choroidal neovascular leakage. Although the loculated fluid may conform to a pattern of typical cystoid macular edema, it can also pool within an area deep to the sensory retina in a shape that does not bear any resemblance to cystoid macular edema. This pattern is important to recognize because it (1) should not be confused with the angiographic pattern or extent of choroidal neovascularization and (2) should be differentiated from a serous detachment or tear of the retinal pigment epithelium.

  9. The Chinese medicine formula HB01 reduces choroidal neovascularization by regulating the expression of vascular endothelial growth factor

    PubMed Central

    2012-01-01

    Background Choroidal neovascularization (CNV) remains the leading cause of newly acquired blindness in the developed world. Currently anti-vascular endothelial growth factor (VEGF) therapies are broadly used to treat neovascular ocular disorders. Here we demonstrate the effect of a traditional Chinese medicine formula, HB01, on CNV. Methods A rat model of laser-induced CNV was used to investigate the effect of HB01 in vivo. The CNV lesions in the eye were evaluated using fundus fluorescein angiography and visualized/quantified using confocal microscopy. Expression of VEGF in the choroidal and retinal tissues was measured using quantitative real-time PCR and immunohistochemistry. Results We demonstrated that a traditional Chinese Medicine formula, named HB01, significantly reduced neovascularization in a rat CNV model. The effect of HB01 on CNV was comparable to the intravitreal injection of bevacizumab (Avastin). Our results also suggested that HB01 may reduce CNV partially through inhibiting the expression of VEGF. Conclusions These data support HB01 as an alternative therapy for ocular neovascular disorders. PMID:22676316

  10. Surgery for Subfoveal Choroidal Neovascularization in Age-Related Macular Degeneration: Ophthalmic Findings

    PubMed Central

    2005-01-01

    Purpose To present visual acuity (VA) and related findings from patients enrolled in one of the Submacular Surgery Trials (SST) evaluating surgical removal versus observation of subfoveal choroidal neovascularization secondary to age-related macular degeneration (SST Group N Trial). Design Randomized clinical trial. Participants Eligible patients had age-related macular degeneration with subfoveal choroidal neovascularization, some with a classic pattern on fluorescein angiography, and best-corrected VA (BCVA) of 20/100 to 20/800 in one eye (study eye) that had received no treatment in the macula. Any contiguous blood had to account for <50% of the total area occupied by the subfoveal lesion (maximum size, 9.0 disc areas [22.9 mm2]). Methods Randomization was stratified by VA and by clinical center. All patients were scheduled for study examinations at 3, 6, 12, and 24 months after enrollment for assessment of study outcomes. Main Outcome Measure A successful outcome was defined a priori to be either improvement of BCVA or VA no more than 1 line (7 letters) worse than baseline at the 24-month examination. Results Of 454 patients enrolled, 228 study eyes were assigned to observation and 226 to surgery. The percentages of eyes that had successful outcomes were similar in the 2 arms: 44% assigned to observation and 41% assigned to surgery. Median VA losses from baseline to the 24-month examination were 2.1 lines (10.5 letters) in the observation arm and 2.0 lines (10 letters) in the surgery arm. Median VA declined from 20/100 at baseline to 20/400 at 24 months in both arms. No subgroup of patients was identified in which submacular surgery led to better VA outcomes. In the surgery arm, 55 (39%) of 142 initially phakic eyes had cataract surgery by the 24-month examination, compared with 6 (5%) of 133 eyes in the observation arm. Rhegmatogenous retinal detachment occurred in 12 surgery eyes (5%) and 1 observation eye. Conclusions Submacular surgery, as performed in this

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

    SciTech Connect

    Fernandes, Bruno F.; Weisbrod, Daniel; Yuecel, Yeni H.; Follwell, Matthew; Krema, Hatem; Heydarian, Mostafa; Xu Wei; Payne, David; McGowan, Hugh; Simpson, Ernest R.; Laperriere, Normand; Sahgal, Arjun

    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 original 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.

  12. Optimization of an Image-Guided Laser-Induced Choroidal Neovascularization Model in Mice.

    PubMed

    Gong, Yan; Li, Jie; Sun, Ye; Fu, Zhongjie; Liu, Chi-Hsiu; Evans, Lucy; Tian, Katherine; Saba, Nicholas; Fredrick, Thomas; Morss, Peyton; Chen, Jing; Smith, Lois E H

    2015-01-01

    The mouse model of laser-induced choroidal neovascularization (CNV) has been used in studies of the exudative form of age-related macular degeneration using both the conventional slit lamp and a new image-guided laser system. A standardized protocol is needed for consistent results using this model, which has been lacking. We optimized details of laser-induced CNV using the image-guided laser photocoagulation system. Four lesions with similar size were consistently applied per eye at approximately double the disc diameter away from the optic nerve, using different laser power levels, and mice of various ages and genders. After 7 days, the mice were sacrificed and retinal pigment epithelium/choroid/sclera was flat-mounted, stained with Isolectin B4, and imaged. Quantification of the area of the laser-induced lesions was performed using an established and constant threshold. Exclusion criteria are described that were necessary for reliable data analysis of the laser-induced CNV lesions. The CNV lesion area was proportional to the laser power levels. Mice at 12-16 weeks of age developed more severe CNV than those at 6-8 weeks of age, and the gender difference was only significant in mice at 12-16 weeks of age, but not in those at 6-8 weeks of age. Dietary intake of omega-3 long-chain polyunsaturated fatty acid reduced laser-induced CNV in mice. Taken together, laser-induced CNV lesions can be easily and consistently applied using the image-guided laser platform. Mice at 6-8 weeks of age are ideal for the laser-induced CNV model.

  13. Optimization of an Image-Guided Laser-Induced Choroidal Neovascularization Model in Mice

    PubMed Central

    Sun, Ye; Fu, Zhongjie; Liu, Chi-Hsiu; Evans, Lucy; Tian, Katherine; Saba, Nicholas; Fredrick, Thomas; Morss, Peyton; Chen, Jing; Smith, Lois E. H.

    2015-01-01

    The mouse model of laser-induced choroidal neovascularization (CNV) has been used in studies of the exudative form of age-related macular degeneration using both the conventional slit lamp and a new image-guided laser system. A standardized protocol is needed for consistent results using this model, which has been lacking. We optimized details of laser-induced CNV using the image-guided laser photocoagulation system. Four lesions with similar size were consistently applied per eye at approximately double the disc diameter away from the optic nerve, using different laser power levels, and mice of various ages and genders. After 7 days, the mice were sacrificed and retinal pigment epithelium/choroid/sclera was flat-mounted, stained with Isolectin B4, and imaged. Quantification of the area of the laser-induced lesions was performed using an established and constant threshold. Exclusion criteria are described that were necessary for reliable data analysis of the laser-induced CNV lesions. The CNV lesion area was proportional to the laser power levels. Mice at 12-16 weeks of age developed more severe CNV than those at 6-8 weeks of age, and the gender difference was only significant in mice at 12-16 weeks of age, but not in those at 6-8 weeks of age. Dietary intake of omega-3 long-chain polyunsaturated fatty acid reduced laser-induced CNV in mice. Taken together, laser-induced CNV lesions can be easily and consistently applied using the image-guided laser platform. Mice at 6-8 weeks of age are ideal for the laser-induced CNV model. PMID:26161975

  14. Surgical Removal vs Observation for Subfoveal Choroidal Neovascularization, Either Associated With the Ocular Histoplasmosis Syndrome or Idiopathic

    PubMed Central

    2005-01-01

    Objective To present visual acuity findings and related outcomes from eyes of patients enrolled in a randomized trial conducted by the Submacular Surgery Trials (SST) Research Group (SST Group H Trial) to compare surgical removal vs observation of subfoveal choroidal neovascular lesions that were either idiopathic or associated with ocular histoplasmosis. Methods Eligible patients 18 years or older had subfoveal choroidal neovascularization (new or recurrent) that included a classic component on fluorescein angiography and best-corrected visual acuity of 20/50 to 20/800 in 1 eye (“study eye”). Patients were examined 3, 6, 12, and 24 months after enrollment to assess study outcomes and adverse events. Best-corrected visual acuity was measured by a masked examiner at the 24-month examination. A successful outcome was defined a priori as 24-month visual acuity better or no more than 1 line (7 letters) worse than at baseline. Results Among 225 patients enrolled (median visual acuity 20/100), 113 study eyes were assigned to observation and 112 to surgery. Forty-six percent of the eyes in the observation arm and 55% in the surgery arm had a successful outcome (success ratio, 1.18; 95% confidence interval, 0.89–1.56). Median visual acuity at the 24-month examination was 20/250 among eyes in the observation arm and 20/160 for eyes in the surgery arm. The prespecified subgroup of eyes with visual acuity worse than 20/100 at baseline (n=92) had more successes with surgery; 31 (76%) of 41 eyes in the surgery arm vs 20 (50%) of 40 eyes in the observation arm examined at 24 months (success ratio, 1.53; 95% confidence interval, 1.08–2.16). Five (4%) of 111 eyes in the surgery arm subsequently had a rhegmatogenous retinal detachment. Twenty-seven (24%) of 112 initially phakic eyes in the surgery arm (none in the observation arm) had cataract surgery during follow-up, all among patients older than 50 years. Recurrent choroidal neovascularization developed by the 24-month

  15. Melissa officinalis Extract Inhibits Laser-Induced Choroidal Neovascularization in a Rat Model

    PubMed Central

    Lee, Eun Kyoung; Kim, Young Joo; Kim, Jin Young; Song, Hyun Beom; Yu, Hyeong Gon

    2014-01-01

    Purpose This study investigated the effect of Melissa officinalis extract on laser-induced choroidal neovascularization (CNV) in a rat model. The mechanism by which M. officinalis extract acted was also investigated. Methods Experimental CNV was induced by laser photocoagulation in Brown Norway rats. An active fraction of the Melissa leaf extract was orally administered (50 or 100 mg/kg/day) beginning 3 days before laser photocoagulation and ending 14 days after laser photocoagulation. Optical coherence tomography and fluorescein angiography were performed in vivo to evaluate the thickness and leakage of CNV. Choroidal flat mount and histological analysis were conducted to observe the CNV in vitro. Vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, and MMP-9 expression were measured in retinal and choroidal-scleral lysates 7 days after laser injury. Moreover, the effect of M. officinalis extract on tertiary-butylhydroperoxide (t-BH)-induced VEGF secretion and mRNA levels of VEGF, MMP-2, and MMP-9 were evaluated in human retinal epithelial cells (ARPE-19) as well as in human umbilical vein endothelial cells (HUVECs). Results The CNV thickness in M. officinalis-treated rats was significantly lower than in vehicle-treated rats by histological analysis. The CNV thickness was 33.93±7.64 µm in the high-dose group (P<0.001), 44.09±12.01 µm in the low-dose group (P = 0.016), and 51.00±12.37 µm in the control group. The proportion of CNV lesions with clinically significant fluorescein leakage was 9.2% in rats treated with high-dose M. officinalis, which was significantly lower than in control rats (53.4%, P<0.001). The levels of VEGF, MMP-2, and MMP-9 were significantly lower in the high-dose group than in the control group. Meanwhile, M. officinalis extract suppressed t-BH-induced transcription of VEGF and MMP-9 in ARPE-19 cells and HUVECs. Conclusions Systemic administration of M. officinalis extract suppressed laser-induced CNV

  16. Measurements of retinal temperature increase during photodynamic therapy for choroidal neovascularization

    NASA Astrophysics Data System (ADS)

    Chen, Hongxia; Yang, Zaifu; Gu, Ying; Li, Xiaoxia; Zhao, Youquan; Zhang, Luyong; Qiu, Haixia

    2010-11-01

    To study the risk of retinal thermal injury from 532 nm laser during photodynamic therapy (PDT) for choroidal neovascularization (CNV) by measuring the retinal temperature increase of rabbit eyes. A microthermocouple technique was developed to measure retinal temperature increase during PDT in pigmented and non-pigmented rabbit eyes. The 532 nm laser exposures were performed with 100-s duration, 2-mm spot size, and retinal irradiance ranging from 400 to 1600 mW/cm2. A K-type microthermocouple was inserted through the sclerotomy and advanced until the tip reached the retina at the posterior pole. The thermocouple was connected a computer that recorded and analyzed retinal temperature data. The results showed that the retinal temperature increase during laser exposure was proportional to retinal irradiance with a particular spot diameter, exposure duration, wavelength, and fundus pigmentation. And the measured retinal temperature increases in pigmented rabbits were a little higher than those in albino rabbits under the same radiant condition. Retinal threshold irradiance required for visible lesions at laser wavelength of 532 nm with 2.0-mm spot size and 100-s duration was 1657 mW/cm2 in albino and 1003 mW/cm2 in pigmented rabbits, respectively, corresponding to retinal temperature increase of about 8 °C and 6 °C. The measured temperatures in albino and pigmented rabbit eyes were both lower than the model predictions, especially in pigmented rabbits. Therefore, further parameter modifying should be performed to obtain accuracy prediction of retinal temperature.

  17. Aflibercept: a review of its use in the treatment of choroidal neovascularization due to age-related macular degeneration

    PubMed Central

    Balaratnasingam, Chandrakumar; Dhrami-Gavazi, Elona; McCann, Jesse T; Ghadiali, Quraish; Freund, K Bailey

    2015-01-01

    Choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) is an important cause of visual morbidity globally. Modern treatment strategies for neovascular AMD achieve regression of CNV by suppressing the activity of key growth factors that mediate angiogenesis. Vascular endothelial growth factor (VEGF) has been the major target of neovascular AMD therapy for almost two decades, and there have been several intravitreally-administered agents that have enabled anatomical restitution and improvement in visual function with continual dosing. Aflibercept (EYLEA®), initially named VEGF Trap-eye, is the most recent anti-VEGF agent to be granted US Food and Drug Administration approval for the treatment of neovascular AMD. Biologic advantages of aflibercept include its greater binding affinity for VEGF, a longer intravitreal half-life relative to other anti-VEGF agents, and the capacity to antagonize growth factors other than VEGF. This paper provides an up-to-date summary of the molecular mechanisms mediating CNV. The structural, pharmacodynamic, and pharmacokinetic advantages of aflibercept are also reviewed to rationalize the utility of this agent for treating CNV. Results of landmark clinical investigations, including VIEW 1 and 2 trials, and other important studies are then summarized and used to illustrate the efficacy of aflibercept for managing treatment-naïve CNV, recalcitrant CNV, and CNV due to polypoidal choroidal vasculopathy. Safety profile, patient tolerability, and quality of life measures related to aflibercept are also provided. The evidence provided in this paper suggests aflibercept to be a promising agent that can be used to reduce the treatment burden of neovascular AMD. PMID:26719668

  18. Aflibercept: a review of its use in the treatment of choroidal neovascularization due to age-related macular degeneration.

    PubMed

    Balaratnasingam, Chandrakumar; Dhrami-Gavazi, Elona; McCann, Jesse T; Ghadiali, Quraish; Freund, K Bailey

    2015-01-01

    Choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) is an important cause of visual morbidity globally. Modern treatment strategies for neovascular AMD achieve regression of CNV by suppressing the activity of key growth factors that mediate angiogenesis. Vascular endothelial growth factor (VEGF) has been the major target of neovascular AMD therapy for almost two decades, and there have been several intravitreally-administered agents that have enabled anatomical restitution and improvement in visual function with continual dosing. Aflibercept (EYLEA(®)), initially named VEGF Trap-eye, is the most recent anti-VEGF agent to be granted US Food and Drug Administration approval for the treatment of neovascular AMD. Biologic advantages of aflibercept include its greater binding affinity for VEGF, a longer intravitreal half-life relative to other anti-VEGF agents, and the capacity to antagonize growth factors other than VEGF. This paper provides an up-to-date summary of the molecular mechanisms mediating CNV. The structural, pharmacodynamic, and pharmacokinetic advantages of aflibercept are also reviewed to rationalize the utility of this agent for treating CNV. Results of landmark clinical investigations, including VIEW 1 and 2 trials, and other important studies are then summarized and used to illustrate the efficacy of aflibercept for managing treatment-naïve CNV, recalcitrant CNV, and CNV due to polypoidal choroidal vasculopathy. Safety profile, patient tolerability, and quality of life measures related to aflibercept are also provided. The evidence provided in this paper suggests aflibercept to be a promising agent that can be used to reduce the treatment burden of neovascular AMD. PMID:26719668

  19. The complement regulatory protein CD59: insights into attenuation of choroidal neovascularization.

    PubMed

    Schnabolk, Gloriane; Tomlinson, Stephen; Rohrer, Bärbel

    2014-01-01

    Complement activation is associated with age-related macular degeneration (AMD), with the retinal pigment epithelium (RPE) being one of the main target tissues. In AMD, disease severity is correlated with the formation of the membrane attack complex (MAC), the terminal step in the complement cascade, as well as diminished RPE expression of CD59, a membrane-bound regulatory protein of MAC formation. This has prompted the search for therapeutic strategies based on MAC inhibition, and soluble forms of CD59 (sCD59) have been investigated in mouse laser-induced choroidal neovascularization, a model for "wet" AMD. Unlike membrane-bound CD59, sCD59 provides relatively poor cell protection from complement, and different strategies to increase sCD59 activity at the cell membrane level have been investigated. These include increasing the circulatory half-life of sCD59 by the addition of an Fc moiety; increasing the half-life of sCD59 in target tissues by modifying CD59 with a (non-specific) membrane-targeting domain; and by locally overexpressing sCD59 via adenoviral vectors. Finally, a different strategy currently under investigation employs complement receptor (CR)2-mediated targeting of CD59 exclusively to membranes under complement attack. CR2 recognizes long-lasting membrane-bound breakdown activation fragments of complement C3. CR2-CD59 may have greater therapeutic potential than other complement inhibitory approaches, since it can be administered either systemically or locally, it will bind specifically to membranes containing activated complement activation fragments, and dosing can be regulated. Hence, this strategy might offer opportunities for site-specific inhibition of complement in diseases with restricted sites of inflammation such as AMD.

  20. Clinicopathological correlation of an excised choroidal neovascular membrane in pseudotumour cerebri

    PubMed Central

    Castellarin, A.; Sugino, I.; Nasir, M.; Zarbin, M.

    1997-01-01

    AIMS/BACKGROUND—To correlate the histopathology of an excised choroidal neovascular membrane (CNV) with the clinical and angiographic findings in a 32-year-old woman with pseudotumour cerebri and a peripapillary CNV with subfoveal extension.
METHODS—The patient's visual acuity was assessed by individuals experienced in low vision refraction and who were not members of the surgical team. The CNV was excised via a conventional three port vitrectomy with subretinal dissection. The excised tissue was studied with light and electron microscopy. Preoperative and serial postoperative fluorescein angiograms (FAs) and fundus photographs were obtained to study the dissection bed.
RESULTS—One week after surgery, the FA showed mottled subfoveal choriocapillaris perfusion. Three weeks after surgery, this area showed retinal pigment epithelium (RPE) atrophy clinically, and the FA showed choriocapillaris non-perfusion. Six months after surgery, the area of RPE atrophy and the corresponding area of choriocapillaris non-perfusion had expanded. Histologically, the excised CNV disclosed hyperplastic RPE, fibrovascular tissue, and no choriocapillaris. Fragments of RPE basement were present along the external edge of the specimen. The patient's visual acuity did not improve significantly after surgery.
CONCLUSIONS—Choriocapillaris non-perfusion can develop even in young patients following CNV excision. In this particular case, it is believed that choriocapillaris atrophy was caused by incomplete ingrowth of RPE into the dissection bed following RPE removal with CNV excision. As far as is known, this is the first report describing the results of surgery for CNV secondary to papilloedema associated with pseudotumour cerebri.

 PMID:9505826

  1. Methallothionein-3 contributes to vascular endothelial growth factor induction in a mouse model of choroidal neovascularization.

    PubMed

    Choi, Jeong A; Hwang, Jong-uk; Yoon, Young Hee; Koh, Jae-Young

    2013-10-01

    In the present study, we investigated possible roles of the zinc (Zn)-binding protein metallothionein-3 (MT3) and cellular Zn in a mouse model of laser-induced choroidal neovascularization (CNV) using wild-type (WT) and MT3-knockout (KO) mice. Quantitative RT-PCR was used for the detection of MT3 mRNA. CNV was induced in mice between 8 and 12 weeks of age by disrupting the Bruch's membrane using an argon laser. Fundus photography and fluorescein angiography (FA) were performed 2 weeks following laser photocoagulation. The possible connection between MT3 and vascular endothelial growth factor (VEGF) expression was explored by quantifying VEGF levels in WT and MT3-KO mouse retinas by enzyme-linked immunosorbent assay. The role of Zn in VEGF expression was tested in WT and MT3-KO cells treated with pyrithione, with or without additional Zn, using immunoblotting and fluorescence photomicrography. Following laser-treatment, MT3-KO mice exhibited substantially smaller areas of CNV compared to WT mice. In addition, retinal angiograms revealed less severe fluorescein leakage in MT3-KO mice than in WT mice. On day 14 following the induction of CNV, VEGF expression was markedly increased in WT mice, but remained unchanged in MT3-KO mice. Consistent with the possible involvement of Zn released from MT3, raising intracellular Zn levels increased VEGF levels and activated its receptor, Flk-1, in both WT and MT3-KO retinal cells. Present results demonstrated that neural retinal cells express high levels of MT3, which might play a role in the process of CNV development. Moreover, Zn released from MT3 may contribute to VEGF induction. PMID:23962989

  2. The complement regulatory protein CD59: insights into attenuation of choroidal neovascularization.

    PubMed

    Schnabolk, Gloriane; Tomlinson, Stephen; Rohrer, Bärbel

    2014-01-01

    Complement activation is associated with age-related macular degeneration (AMD), with the retinal pigment epithelium (RPE) being one of the main target tissues. In AMD, disease severity is correlated with the formation of the membrane attack complex (MAC), the terminal step in the complement cascade, as well as diminished RPE expression of CD59, a membrane-bound regulatory protein of MAC formation. This has prompted the search for therapeutic strategies based on MAC inhibition, and soluble forms of CD59 (sCD59) have been investigated in mouse laser-induced choroidal neovascularization, a model for "wet" AMD. Unlike membrane-bound CD59, sCD59 provides relatively poor cell protection from complement, and different strategies to increase sCD59 activity at the cell membrane level have been investigated. These include increasing the circulatory half-life of sCD59 by the addition of an Fc moiety; increasing the half-life of sCD59 in target tissues by modifying CD59 with a (non-specific) membrane-targeting domain; and by locally overexpressing sCD59 via adenoviral vectors. Finally, a different strategy currently under investigation employs complement receptor (CR)2-mediated targeting of CD59 exclusively to membranes under complement attack. CR2 recognizes long-lasting membrane-bound breakdown activation fragments of complement C3. CR2-CD59 may have greater therapeutic potential than other complement inhibitory approaches, since it can be administered either systemically or locally, it will bind specifically to membranes containing activated complement activation fragments, and dosing can be regulated. Hence, this strategy might offer opportunities for site-specific inhibition of complement in diseases with restricted sites of inflammation such as AMD. PMID:24664728

  3. Intravitreal Topotecan Inhibits Laser-induced Choroidal Neovascularization in a Rat Model

    PubMed Central

    Gholipour, Mohammad Ali; Kanavi, Mozhgan Rezaei; Ahmadieh, Hamid; Aldavood, Seyed Javid; Nourinia, Ramin; Hosseini, Seyed Bagher; Daftarian, Narsis; Nashtaei, Ebrahim Mohammad; Tousi, Adib; Safi, Sare

    2015-01-01

    Purpose: A two-phase preclinical study was designed to determine the safe dose of intravitreal topotecan and its inhibitory effect on experimental choroidal neovascularization (CNV) in a rat model. Methods: In phase I, 42 rats were categorized into 6 groups, 5 of which received intravitreal topotecan injections of 0.125 μg, 0.25 μg, 0.5 μg, 0.75 μg, and 1.0 μg/5 μl, respectively; the control group received an injection of normal saline. Ophthalmic examination and electroretinography (ERG) were performed on days 7 and 28, and enucleated globes were processed for histopathology and immunostaining for glial fibrillary acidic protein. In phase II, CNV was induced via laser burns in 20 rats and the animals were divided into 2 groups. One group received topotecan and the other received normal saline intravitreally. Four weeks later, mean scores of fluorescein leakage on fluorescein angiography as well as mean CNV areas on histology sections were compared. Results: In phase I, clinical, ERG and histopathologic results were unremarkable in terms of retinal toxicity in all groups. Based on the results of phase I, a dose of 1 μg/5 μl topotecan was chosen for phase II. Leakage scores obtained from late-phase fluorescein angiography were significantly lower in topotecan-treated than control eyes (P < 0.01) four weeks after induction of CNV. Compared to control eyes, topotecan-treated eyes showed a significantly lower incidence of fibrovascular proliferation (8.7% vs. 96.2%) and significantly smaller areas of CNV (P < 0.01). Conclusion: Intravitreal injection of topotecan at a dose of 1 μg/5 μl is safe and may be a promising treatment for CNV. PMID:26730316

  4. Diagnosis and Follow-Up of Nonexudative Choroidal Neovascularization With Multiple Optical Coherence Tomography Angiography Devices: A Case Report.

    PubMed

    Lane, Mark; Ferrara, Daniela; Louzada, Ricardo Noguera; Fujimoto, James G; Seddon, Johanna M

    2016-08-01

    Nonexudative choroidal neovascularization (CNV) is a new phenomenon that has only recently been described in the literature with the advent of optical coherence tomography angiography (OCTA) imaging. The authors present a 1-year longitudinal follow-up of a nonexudative CNV lesion secondary to age-related macular degeneration. This report describes the appearance of the lesion on two commercially available spectral-domain OCTA devices and one prototype swept-source OCTA device. Management of these cases is still debatable. Watchful waiting with regular follow-up using serial OCTA to monitor disease progression has been valuable in this case. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:778-781.]. PMID:27548457

  5. In vivo bioluminescence imaging of hyperglycemia exacerbating stem cells on choroidal neovascularization in mice

    PubMed Central

    Gao, Xiang; Wang, Yu; Hou, Hui-Yuan; Lyu, Yang; Wang, Hai-Yan; Yao, Li-Bo; Zhang, Jian; Cao, Feng; Wang, Yu-Sheng

    2016-01-01

    AIM To investigate the influence of hyperglycemia on the severity of choroidal neovascularization (CNV), especially the involvement of bone marrow-derived cells (BMCs) and underlying mechanisms. METHODS BMCs from firefly luciferase (Fluc)/green fluorescent protein (GFP) double transgenic mice were transplanted into C57BL/6J wide-type mice. The recipient mice were injected intraperitoneally with streptozotocin (STZ) daily for 5 consecutive days to induce diabetes mellitus (DM), followed by CNV laser photocoagulation. The BMCs recruitment in CNV exposed to hyperglycemia was firstly examined in Fluc/GFP chimeric mice by in vivo optical bioluminescence imaging (BLI) and in vitro Fluc assays. The CNV severity was evaluated by H&E staining and choroidal flatmount. The expression of vascular endothelial growth factor (VEGF) and stromal cell derived factor-1 (SDF-1) was detected by Western Blot. RESULTS BLI showed that the BMCs exerted dynamic effects in CNV model in Fluc/GFP chimeric mice exposed to hyperglycemia. The signal intensity of transplanted Fluc+GFP+ BMCs in the DM chimeric mice was significantly higher than that in the control chimeric mice with CNV induction at days 5, 7, 14 and 21 (121861.67±9948.81 vs 144998.33±13787.13 photons/second/cm2/sr for control and DM mice, P5d<0.05; 178791.67±30350.8 vs 240166.67±22605.3, P7d<0.05; 124176.67±16253.52 vs 196376.67±18556.79, P14d<0.05; 97951.60±10343.09 vs 119510.00±14383.76, P21d<0.05), which was consistent with in vitro Fluc assay at day 7 [relative light units of Fluc (RLU1)], 215.00±52.05 vs 707.33±88.65, P<0.05; RLU1/ relative light units of renilla luciferase (RLU2), 0.90±0.17 vs 1.83±0.17, P<0.05]. The CNVs in the DM mice were wider than those in the control group at days 5, 7, 14 and 21 (147.83±17.36 vs 220.33±20.17 µm, P5d<0.05; 212.17±24.63 vs 326.83±19.49, P7d<0.05; 163.17±18.24 vs 265.17±20.55, P14d<0.05; 132.00±10.88 vs 205.33±12.98, P21d<0.05). The average area of CNV in the DM

  6. Retinal pigment epithelial cell expression of active Rap 1a by scAAV2 inhibits choroidal neovascularization

    PubMed Central

    Wang, Haibo; Han, Xiaokun; Bretz, Colin A; Becker, Silke; Gambhir, Deeksha; Smith, George W; Samulski, R Jude; Wittchen, Erika S; Quilliam, Lawrence A; Chrzanowska-Wodnicka, Magdalena; Hartnett, M Elizabeth

    2016-01-01

    To test the hypothesis that increased Rap1a activity specifically in retinal pigment epithelial cells resists choroidal neovascularization (CNV), self-complementary adeno-associated virus 2 (scAAV2) with RPE65-promoter-driven GFP vectors were generated and introduced subretinally into Rap1b-deficient mice. Six-week-old mice that received subretinal control (scAAV2-Con) or constitutively active Rap1a (scAAV2-CARap1a) showed strong GFP at the 5 × 108 viral particle/µl dose 5 weeks later without altering retinal morphology or function. Compared to scAAV2-Con- or phosphate-buffered saline (PBS)-injected, eyes injected with scAAV2-CARap1a had increased Rap1 in retinal pigment epithelial (RPE)/choroidal lysates and a significant reduction in CNV volume 7 days after laser, comparable to eyes that received intravitreal anti-VEGF versus IgG control. scAAV2-CARap1a-, but not anti-VEGF-, injected eyes had increased pan-cadherin in RPE/choroids. In cultured RPE cells, increased active Rap1a inhibited TNFα-induced disassociation of junctional pan-cadherin/β-catenin complexes, increased transepithelial electrical resistance through an interaction of β-catenin with phosphorylated scaffold protein, IQGAP1, and inhibited choroidal endothelial cell (CEC) transmigration of an RPE monolayer. This evidence shows that increased Rap1a activity specifically in RPE cells is sufficient to reduce CEC transmigration and CNV and involves IQGAP1-mediated protection of RPE junctional complexes. PMID:27606349

  7. Retinal pigment epithelial cell expression of active Rap 1a by scAAV2 inhibits choroidal neovascularization.

    PubMed

    Wang, Haibo; Han, Xiaokun; Bretz, Colin A; Becker, Silke; Gambhir, Deeksha; Smith, George W; Samulski, R Jude; Wittchen, Erika S; Quilliam, Lawrence A; Chrzanowska-Wodnicka, Magdalena; Hartnett, M Elizabeth

    2016-01-01

    To test the hypothesis that increased Rap1a activity specifically in retinal pigment epithelial cells resists choroidal neovascularization (CNV), self-complementary adeno-associated virus 2 (scAAV2) with RPE65-promoter-driven GFP vectors were generated and introduced subretinally into Rap1b-deficient mice. Six-week-old mice that received subretinal control (scAAV2-Con) or constitutively active Rap1a (scAAV2-CARap1a) showed strong GFP at the 5 × 10(8) viral particle/µl dose 5 weeks later without altering retinal morphology or function. Compared to scAAV2-Con- or phosphate-buffered saline (PBS)-injected, eyes injected with scAAV2-CARap1a had increased Rap1 in retinal pigment epithelial (RPE)/choroidal lysates and a significant reduction in CNV volume 7 days after laser, comparable to eyes that received intravitreal anti-VEGF versus IgG control. scAAV2-CARap1a-, but not anti-VEGF-, injected eyes had increased pan-cadherin in RPE/choroids. In cultured RPE cells, increased active Rap1a inhibited TNFα-induced disassociation of junctional pan-cadherin/β-catenin complexes, increased transepithelial electrical resistance through an interaction of β-catenin with phosphorylated scaffold protein, IQGAP1, and inhibited choroidal endothelial cell (CEC) transmigration of an RPE monolayer. This evidence shows that increased Rap1a activity specifically in RPE cells is sufficient to reduce CEC transmigration and CNV and involves IQGAP1-mediated protection of RPE junctional complexes.

  8. Retinal pigment epithelial cell expression of active Rap 1a by scAAV2 inhibits choroidal neovascularization

    PubMed Central

    Wang, Haibo; Han, Xiaokun; Bretz, Colin A; Becker, Silke; Gambhir, Deeksha; Smith, George W; Samulski, R Jude; Wittchen, Erika S; Quilliam, Lawrence A; Chrzanowska-Wodnicka, Magdalena; Hartnett, M Elizabeth

    2016-01-01

    To test the hypothesis that increased Rap1a activity specifically in retinal pigment epithelial cells resists choroidal neovascularization (CNV), self-complementary adeno-associated virus 2 (scAAV2) with RPE65-promoter-driven GFP vectors were generated and introduced subretinally into Rap1b-deficient mice. Six-week-old mice that received subretinal control (scAAV2-Con) or constitutively active Rap1a (scAAV2-CARap1a) showed strong GFP at the 5 × 108 viral particle/µl dose 5 weeks later without altering retinal morphology or function. Compared to scAAV2-Con- or phosphate-buffered saline (PBS)-injected, eyes injected with scAAV2-CARap1a had increased Rap1 in retinal pigment epithelial (RPE)/choroidal lysates and a significant reduction in CNV volume 7 days after laser, comparable to eyes that received intravitreal anti-VEGF versus IgG control. scAAV2-CARap1a-, but not anti-VEGF-, injected eyes had increased pan-cadherin in RPE/choroids. In cultured RPE cells, increased active Rap1a inhibited TNFα-induced disassociation of junctional pan-cadherin/β-catenin complexes, increased transepithelial electrical resistance through an interaction of β-catenin with phosphorylated scaffold protein, IQGAP1, and inhibited choroidal endothelial cell (CEC) transmigration of an RPE monolayer. This evidence shows that increased Rap1a activity specifically in RPE cells is sufficient to reduce CEC transmigration and CNV and involves IQGAP1-mediated protection of RPE junctional complexes.

  9. Retinal pigment epithelial cell expression of active Rap 1a by scAAV2 inhibits choroidal neovascularization.

    PubMed

    Wang, Haibo; Han, Xiaokun; Bretz, Colin A; Becker, Silke; Gambhir, Deeksha; Smith, George W; Samulski, R Jude; Wittchen, Erika S; Quilliam, Lawrence A; Chrzanowska-Wodnicka, Magdalena; Hartnett, M Elizabeth

    2016-01-01

    To test the hypothesis that increased Rap1a activity specifically in retinal pigment epithelial cells resists choroidal neovascularization (CNV), self-complementary adeno-associated virus 2 (scAAV2) with RPE65-promoter-driven GFP vectors were generated and introduced subretinally into Rap1b-deficient mice. Six-week-old mice that received subretinal control (scAAV2-Con) or constitutively active Rap1a (scAAV2-CARap1a) showed strong GFP at the 5 × 10(8) viral particle/µl dose 5 weeks later without altering retinal morphology or function. Compared to scAAV2-Con- or phosphate-buffered saline (PBS)-injected, eyes injected with scAAV2-CARap1a had increased Rap1 in retinal pigment epithelial (RPE)/choroidal lysates and a significant reduction in CNV volume 7 days after laser, comparable to eyes that received intravitreal anti-VEGF versus IgG control. scAAV2-CARap1a-, but not anti-VEGF-, injected eyes had increased pan-cadherin in RPE/choroids. In cultured RPE cells, increased active Rap1a inhibited TNFα-induced disassociation of junctional pan-cadherin/β-catenin complexes, increased transepithelial electrical resistance through an interaction of β-catenin with phosphorylated scaffold protein, IQGAP1, and inhibited choroidal endothelial cell (CEC) transmigration of an RPE monolayer. This evidence shows that increased Rap1a activity specifically in RPE cells is sufficient to reduce CEC transmigration and CNV and involves IQGAP1-mediated protection of RPE junctional complexes. PMID:27606349

  10. IKK2 Inhibition Using TPCA-1-Loaded PLGA Microparticles Attenuates Laser-Induced Choroidal Neovascularization and Macrophage Recruitment

    PubMed Central

    Gaddipati, Subhash; Lu, Qingxian; Kasetti, Ramesh Babu; Miller, M. Clarke; Lu, Qingjun; Trent, John O.; Kaplan, Henry J.; Li, Qiutang

    2015-01-01

    The inhibition of NF-κB by genetic deletion or pharmacological inhibition of IKK2 significantly reduces laser-induced choroid neovascularization (CNV). To achieve a sustained and controlled intraocular release of a selective and potent IKK2 inhibitor, 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) (MW: 279.29), we developed a biodegradable poly-lactide-co-glycolide (PLGA) polymer-delivery system to further investigate the anti-neovascularization effects of IKK2 inhibition and in vivo biosafety using laser-induced CNV mouse model. The solvent-evaporation method produced spherical TPCA-1-loaded PLGA microparticles characterized with a mean diameter of 2.4 ¼m and loading efficiency of 80%. Retrobulbar administration of the TPCA-1-loaded PLGA microparticles maintained a sustained drug level in the retina during the study period. No detectable TPCA-1 level was observed in the untreated contralateral eye. The anti-CNV effect of retrobulbarly administrated TPCA-1-loaded PLGA microparticles was assessed by retinal fluorescein leakage and isolectin staining methods, showing significantly reduced CNV development on day 7 after laser injury. Macrophage infiltration into the laser lesion was attenuated as assayed by choroid/RPE flat-mount staining with anti-F4/80 antibody. Consistently, laser induced expressions of Vegfa and Ccl2 were inhibited by the TPCA-1-loaded PLGA treatment. This TPCA-1 delivery system did not cause any noticeable cellular or functional toxicity to the treated eyes as evaluated by histology and optokinetic reflex (OKR) tests; and no systemic toxicity was observed. We conclude that retrobulbar injection of the small-molecule IKK2 inhibitor TPCA-1, delivered by biodegradable PLGA microparticles, can achieve a sustained and controllable drug release into choroid/retina and attenuate laser-induced CNV development without causing apparent systemic toxicity. Our results suggest a potential clinical application of TPCA-1 delivered

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

    SciTech Connect

    Hirasawa, Naoki . E-mail: naoki_h@nirs.go.jp; Tsuji, Hiroshi; Ishikawa, Hitoshi; Koyama-Ito, Hiroko; Kamada, Tadashi; Mizoe, Jun-Etsu; Ito, Yoshiyuki; Naganawa, Shinji; Ohnishi, Yoshitaka; Tsujii, Hirohiko

    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 glaucoma 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.

  12. 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

    2015-01-01

    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.

  13. Correlation of In Vivo and In Vitro Methods in Measuring Choroidal Vascularization Volumes Using a Subretinal Injection Induced Choroidal Neovascularization Model

    PubMed Central

    Nie, Chuang; Zhang, Mao-Nian; Zhao, Hong-Wei; Olsen, Thomas D; Jackman, Kyle; Hu, Lian-Na; Ma, Wen-Ping; Chen, Xiao-Fei; Wang, Juan; Zhang, Ying; Gao, Tie-Shan; Uehara, Hiro; Ambati, Balamurali K; Luo, Ling

    2015-01-01

    Background: In vivo quantification of choroidal neovascularization (CNV) based on noninvasive optical coherence tomography (OCT) examination and in vitro choroidal flatmount immunohistochemistry stained of CNV currently were used to evaluate the process and severity of age-related macular degeneration (AMD) both in human and animal studies. This study aimed to investigate the correlation between these two methods in murine CNV models induced by subretinal injection. Methods: CNV was developed in 20 C57BL6/j mice by subretinal injection of adeno-associated viral delivery of a short hairpin RNA targeting sFLT-1 (AAV.shRNA.sFLT-1), as reported previously. After 4 weeks, CNV was imaged by OCT and fluorescence angiography. The scaling factors for each dimension, x, y, and z (μm/pixel) were recorded, and the corneal curvature standard was adjusted from human (7.7) to mice (1.4). The volume of each OCT image stack was calculated and then normalized by multiplying the number of voxels by the scaling factors for each dimension in Seg3D software (University of Utah Scientific Computing and Imaging Institute, available at http://www.sci.utah.edu/cibc-software/seg3d.html). Eighteen mice were prepared for choroidal flatmounts and stained by CD31. The CNV volumes were calculated using scanning laser confocal microscopy after immunohistochemistry staining. Two mice were stained by Hematoxylin and Eosin for observing the CNV morphology. Results: The CNV volume calculated using OCT was, on average, 2.6 times larger than the volume calculated using the laser confocal microscopy. The correlation statistical analysis showed OCT measuring of CNV correlated significantly with the in vitro method (R2 =0.448, P = 0.001, n = 18). The correlation coefficient for CNV quantification using OCT and confocal microscopy was 0.693 (n = 18, P = 0.001). Conclusions: There is a fair linear correlation on CNV volumes between in vivo and in vitro methods in CNV models induced by subretinal injection

  14. Krypton laser photocoagulation induces retinal vascular remodeling rather than choroidal neovascularization.

    PubMed

    Behar-Cohen, F; Benezra, D; Soubrane, G; Jonet, L; Jeanny, J C

    2006-08-01

    The purpose of this study is to analyze the retina and choroid response following krypton laser photocoagulation. Ninety-two C57BL6/Sev129 and 32 C57BL/6J, 5-6-week-old mice received one single krypton (630 nm) laser lesion: 50 microm, 0.05 s, 400 mW. On the following day, every day thereafter for 1 week and every 2-3 days for the following 3 weeks, serial sections throughout the lesion were systematically collected and studied. Immunohistology using specific markers or antibodies for glial fibrillary acidic protein (GFAP) (astrocytes, glia and Muller's cells), von Willebrand (vW) (vascular endothelial cells), TUNEL (cells undergoing caspase dependent apoptosis), PCNA (proliferating cell nuclear antigen) p36, CD4 and F4/80 (infiltrating inflammatory and T cells), DAPI (cell nuclei) and routine histology were carried out. Laser confocal microscopy was also performed on flat mounts. Temporal and spatial observations of the created photocoagulation lesions demonstrate that, after a few hours, activated glial cells within the retinal path of the laser beam express GFAP. After 48 h, GFAP-positive staining was also detected within the choroid lesion center. "Movement" of this GFAP-positive expression towards the lasered choroid was preceded by a well-demarcated and localized apoptosis of the retina outer nuclear layer cells within the laser beam path. Later, death of retinal outer nuclear cells and layer thinning at this site was followed by evagination of the inner nuclear retinal layer. Funneling of the entire inner nuclear and the thinned outer nuclear layers into the choroid lesion center was accompanied by "dragging" of the retinal capillaries. Thus, from days 10 to 14 after krypton laser photocoagulation onward, well-formed blood capillaries (of retinal origin) were observed within the lesion. Only a few of the vW-positive capillary endothelial cells stained also for PCNA p36. In the choroid, dilatation of the vascular bed occurred at the vicinity of the

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

    PubMed Central

    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

    2016-01-01

    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. PMID:26188133

  16. Myeloid-Specific Blockade of Notch Signaling Attenuates Choroidal Neovascularization through Compromised Macrophage Infiltration and Polarization in Mice

    PubMed Central

    Dou, Guo-Rui; Li, Na; Chang, Tian-Fang; Zhang, Ping; Gao, Xiang; Yan, Xian-Chun; Liang, Liang; Han, Hua; Wang, Yu-Sheng

    2016-01-01

    Macrophages have been recognized as an important inflammatory component in choroidal neovascularization (CNV). However, it is unclear how these cells are activated and polarized, how they affect angiogenesis and what the underlining mechanisms are during CNV. Notch signaling has been implicated in macrophage activation. Previously we have shown that inducible disruption of RBP-J, the critical transcription factor of Notch signaling, in adult mice results in enhanced CNV, but it is unclear what is the role of macrophage-specific Notch signaling in the development of CNV. In the current study, by using the myeloid specific RBP-J knockout mouse model combined with the laser-induced CNV model, we show that disruption of Notch signaling in macrophages displayed attenuated CNV growth, reduced macrophage infiltration and activation, and alleviated angiogenic response after laser induction. The inhibition of CNV occurred with reduced expression of VEGF and TNF-α in infiltrating inflammatory macrophages in myeloid specific RBP-J knockout mice. These changes might result in direct inhibition of EC lumen formation, as shown in an in vitro study. Therefore, clinical intervention of Notch signaling in CNV needs to pinpoint myeloid lineage to avoid the counteractive effects of global inhibition. PMID:27339903

  17. Evaluation of fixation one year after perifoveal laser treatment of subfoveal choroidal neovascularization.

    PubMed

    Fasce, F; Brancato, R; Bettin, P; Introini, U; Pece, A

    The natural prognosis of subfoveal neovascularization is severe visual acuity loss. Perifoveal laser photocoagulation is meant to spare a small portion of the central retina so as to possibly preserve foveal fixation. The aim of this retrospective study was to detect the persistence of central fixation and to evaluate the visual function of patients who had undergone perifoveal laser photocoagulation one year before, due to the presence of age-related macular degeneration with subfoveal neovascularization. The visual function was assessed by means of visual acuity (VA) measurement, central perimetry, scanning laser ophthalmoscope (SLO) scotometry and capability of using low-vision aids with success. Twelve eyes of 12 patients, 5 males and 7 females, with mean age 72.6 +/- 9.62 years, were included in the Study Group. Mean VA was 0.22 +/- 0.089 before laser treatment, 0.17 +/- 0.054 one week after laser treatment (p = 0.0152) and 0.13 +/- 0.063 one year after laser treatment (p = 0.045), with a statistically significant reduction of VA overtime (initial-final p = 0.0015). Mean lesion size was 2.12 +/- 0.528 disc diameters on the last follow-up fluorescein angiogram. One year after laser treatment, perimetry showed the persistence of central fixation in 2 eyes, while 10 eyes seemed to have lost it. SLO scotometry revealed central dot stimulus perception in 6 eyes and no central residual in 6 eyes. The SLO fixation plot showed persistence of central fixation also in 1 eye in which static perimetry had not detected it. The preferential retinal locus was located on the upper or upper-right margin of the lesion in 8 of the 9 eyes with paracentral fixation. All patients achieved a useful reading VA using low-vision aids, with 7.16 +/- 6.1 mean magnification power. The eyes with central visual residual on SLO scotometry had a final VA slightly higher than those without central residuals (VA 0.158 +/- 0.03 and 0.098 +/- 0.07, respectively), though the difference was not

  18. Choroidal neovascularization is inhibited via an intraocular decrease of inflammatory cells in mice lacking complement component C3

    PubMed Central

    Tan, Xue; Fujiu, Katsuhito; Manabe, Ichiro; Nishida, Junko; Yamagishi, Reiko; Nagai, Ryozo; Yanagi, Yasuo

    2015-01-01

    In early age-related macular degeneration (AMD), complement component C3 can be observed in drusen, which is the accumulation of material beneath the retinal pigment epithelium. The complement pathways, via the activation of C3, can upregulate the expression of cytokines and their receptors and the recruitment of inflammatory leukocytes, both of which play an important role in the development of choroidal neovascularization (CNV) in exudative AMD. Laser-induced CNV lesions were found to be significantly smaller in C3−/− mice than in wild-type mice. By using flow cytometry, we demonstrated that the proportions of intraocular granulocytes, CD11b+F4/80+Ly6Chi and CD11b+F4/80+Ly6Clo cells, were lower in C3−/− mice than in wild-type mice as early as day 1 after laser injury, and the proportions of granulocytes and three macrophage/monocyte subsets were significantly lower on day 3. In contrast, C3−/− mice had more granulocytes and CD11b+F4/80+Ly6Chi cells in peripheral blood than wild-type mice after injury. Further, the expression levels of Vegfa164 were upregulated in intraocular Ly6Chi macrophages/monocytes of C3−/− mice, but not as much as in wild-type mice. Collectively, our data demonstrate that despite a more pronounced induction of systemic inflammation, inhibition of complement factor C3 suppresses CNV by decreasing the recruitment of inflammatory cells to the lesion. PMID:26507897

  19. Reticular Pseudodrusen: A Risk Factor for Geographic Atrophy in Fellow Eyes of Individuals with Unilateral Choroidal Neovascularization

    PubMed Central

    Finger, Robert P.; Wu, Zhichao; Luu, Chi D.; Kearney, Frances; Ayton, Lauren N.; Lucci, Lucia M; Hubbard, William C; Hageman, Jill L; Hageman, Gregory S.; Guymer, Robyn H.

    2014-01-01

    Purpose To determine whether reticular pseudodrusen (RPD) confer an increased risk of progression to late-stage age-related macular degeneration (AMD) in fellow eyes of those recently diagnosed with unilateral choroidal neovascularization (CNV). Design Retrospective study Participants 200 consecutive participants with CNV secondary to AMD in one eye and no signs of late stage AMD in the fellow eye. Methods Clinical examination and comprehensive retinal imaging including spectral-domain optical coherence tomography (SD-OCT), near-infrared reflectance (NIR), and colour fundus photography at baseline and every follow-up visit. Main Outcome Measures Incidence of geographic atrophy (GA) and CNV in the fellow eye. Results Mean age was 77 (±7) years, and 61% of the cohort were female. 116 (58%) had RPD, 68% had drusen ≥125 μm, 36% pigmentary changes, 10% had both drusen ≥125 μm and pigmentary changes, and 17% had only RPD in their fellow eyes. After a mean follow-up of 2.3 years, 36% developed CNV and 14% GA. Those with RPD developed late-stage AMD more often (61% versus 33.4%, p<0.001), and more often GA (22.4% with RPD versus 2.4% without RPD, p<0.001). RPD was an independent risk factor for the development of GA (hazard ratio (HR) 4.93; p=0.042), but not for CNV (HR 1.19; p=0.500), at least within the follow-up of this study. Both drusen ≥125μm and pigmentary changes at baseline were a significant risk factor for the development of CNV and GA (HR 1.96 – 11.73; p ≤ 0.020). Conclusions RPD appear to confer an increased risk of progression to GA, additive to drusen and pigmentary changes. The presence of RPD needs to be taken into account when discussing a patient's prognosis and planning management. PMID:24518615

  20. Comparative role of intravitreal ranibizumab versus bevacizumab in choroidal neovascular membrane in age-related macular degeneration

    PubMed Central

    Biswas, Partha; Sengupta, Subhrangshu; Choudhary, Ruby; Home, Subhankar; Paul, Ajoy; Sinha, Sourav

    2011-01-01

    Context: Ranibizumab and bevacizumab are used widely for treating patients with choroidal neovascular membrane (CNVM) secondary to age-related macular degeneration (AMD). Aims: To determine and compare the efficacy and safety of intravitreal ranibizumab and bevacizumab in treatment of CNVM due to AMD. Settings and Design: Prospective comparative case series carried out in an eye institute and eye department of a hospital in Kolkata, India. Materials and Methods: One hundred and four eyes with CNVM due to AMD were randomized into two groups. Group A (n=54; 24 occult) received monthly intravitreal ranibizumab injections (0.5 mg in 0.05 ml) and Group B (n=50; 22 occult) received monthly bevacizumab injections (1.25 mg in 0.05 ml) for 3 consecutive months and then as per study criteria. Data analysis done using SPSS software. P-value of <0.05 was considered statistically significant. Results: The mean best corrected visual acuity (BCVA) in the ranibizumab group increased from 58.19 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline to 64 ETDRS letters at month 3 (P<0.001). In bevacizumab group mean BCVA increased from 56.80 to 61.72 ETDRS letters at month 3 (P<0.001). At the end of 18 months, there was no statistically significant difference between groups A and B with respect to change in BCVA (P=0.563) or central macular thickness (CMT; P=0.281), as measured by optical coherence tomography (Stratus OCT 3000). No significant sight-threatening complications developed. Conclusions: Ranibizumab and bevacizumab are equally safe and efficacious in treating CNVM due to AMD. PMID:21586838

  1. The effect of triamcinolone acetonide on laser-induced choroidal neovascularization in mice using a hypoxia visualization bio-imaging probe

    PubMed Central

    Takata, Shinsuke; Masuda, Tomomi; Nakamura, Shinsuke; Kuchimaru, Takahiro; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Nagasawa, Hideko; kizaka-Kondoh, Shinae; Hara, Hideaki

    2015-01-01

    Hypoxic stress is a risk factor of ocular neovascularization. Hypoxia visualization may provide clues regarding the underlying cause of angiogenesis. Recently, we developed a hypoxia-specific probe, protein transduction domain-oxygen-dependent degradation domain-HaloTag-Rhodamine (POH-Rhodamine). In this study, we observed the localization of HIF-1α proteins by immunohistochemistry and the fluorescence of POH-Rhodamine on RPE-choroid flat mounts. Moreover, we compared the localization of POH-Rhodamine with pimonidazole which is a standard reagent for detecting hypoxia. Next, we investigated the effects of triamcinolone acetonide (TAAC) against visual function that was evaluated by recording electroretinogram (ERG) and choroidal neovascularization (CNV) development. Mice were given laser-induced CNV using a diode laser and treated with intravitreal injection of TAAC. Finally, we investigated POH-Rhodamine on CNV treated with TAAC. In this study, the fluorescence of POH-Rhodamine and HIF-1α were co-localized in laser-irradiated sites, and both the POH-Rhodamine and pimonidazole fluorescent areas were almost the same. Intravitreal injection of TAAC restored the reduced ERG b-wave but not the a-wave and decreased the mean CNV area. Furthermore, the area of the POH-Rhodamine-positive cells decreased. These findings indicate that POH-Rhodamine is useful for evaluating tissue hypoxia in a laser-induced CNV model, suggesting that TAAC suppressed CNV through tissue hypoxia improvement. PMID:25927172

  2. Choroidal Neovascularization Is Inhibited in Splenic-Denervated or Splenectomized Mice with a Concomitant Decrease in Intraocular Macrophage

    PubMed Central

    Tan, Xue; Fujiu, Katsuhito; Manabe, Ichiro; Nishida, Junko; Yamagishi, Reiko; Terashima, Yuya; Matsushima, Kouji; Kaburaki, Toshikatsu; Nagai, Ryozo; Yanagi, Yasuo

    2016-01-01

    Purpose To determine the involvement of sympathetic activity in choroidal neovascularization (CNV) using laser-induced CNV in a mouse model. Methods We investigated changes in the proportions of intraocular lymphocytes, granulocytes, and three macrophage subtypes (Ly6Chi, Ly6Cint, and Ly6Clo) after laser injury in mice using flow cytometry, and evaluated CNV lesion size in mice lacking inflammatory cells. Further, we evaluated the lesion size in mice administered the β3 receptor antagonist, splenic-denervated and splenectomized mice. We also assessed changes in the proportions of intraocular macrophages and peripheral blood monocytes in splenic-denervated and splenectomized mice. Lastly, lesion size was compared between splenic-denervated mice with or without adoptive transfer of macrophages following laser injury. After Ly5.1 mice spleen-derived Ly6Chi cells were transferred into Ly5.2 mice, the proportions of intraocular Ly5.1+Ly6Chi cells were compared. Results In WT mice, the proportion of CD4+ T cells recruited into the eye increased progressively from day 3 to day 7 after laser injury, whereas, intraocular CD8+ T cells did not change significantly. Proportions of B220+ cells, granulocytes, and two subtypes of intraocular macrophages (Ly6Chi and Ly6Clo) peaked at day 3 following laser injury. In contrast, Ly6Cint/loCD64+ subtype showed a significantly higher percentage at day 7 after laser injury. There were no differences in lesion size between CD4–/–or Rag2–/–mice and controls, whereas lesion size was significantly reduced in CCR2−/− mice and clodronate liposome-treated mice. CNV lesion area was significantly reduced in mice with β3 blocker treatment, splenic-denervated and splenectomized mice compared with controls. Intraocular Ly6Chi macrophages were also reduced by splenic denervation or splenectomy. Adoptive transfer of spleen-derived Ly6Chi cells increased the lesion size in splenic-denervated mice. Compared with controls, intraocular

  3. Incidence of Choroidal Neovascularization in the Fellow Eye in the Comparison of Age-related Macular Degeneration Treatments Trials

    PubMed Central

    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.

    2013-01-01

    Objective To assess the influence of drug, dosing regimen, and traditional, non-traditional, and genetic risk factors on the incidence of choroidal neovascularization (CNV) in the fellow eye of patients treated for CNV with ranibizumab or bevacizumab. Design Cohort study of patients enrolled in a multicenter randomized clinical trial. Participants Patients with no CNV in the fellow eye at the time of enrollment in the Comparison of Age-related Macular Degeneration Treatments Trials (CATT). Methods Eligibility criteria for the clinical trial required that study eyes have evidence on fluorescein angiography and optical coherence tomography (OCT) 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 three different regimens for dosing over a two-year period. The genotypes for four 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. CATT ophthalmologists examined patients every four weeks through two years and recorded treatment for CNV in the fellow eye. Main Outcome Measures Development of CNV in the fellow eye. Results Among 1185 CATT participants, 727 (61%) had no CNV in the fellow eye at enrollment. At two years, CNV had developed in 75 (20.6%) of 365 patients treated with ranibizumab and 60 (16.6%) of 362 patients treated with bevacizumab (absolute difference 4.0%, 95% confidence interval (−1.7%, 9.6%); p=0.17). The risk ratio for pro re nata (PRN) dosing relative to monthly dosing was 1.1 (95% confidence interval (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

  4. Inhibiting the neuronal isoform of nitric oxide synthase has similar effects on the compensatory choroidal and axial responses to myopic defocus in chicks as does the non-specific inhibitor L-NAME.

    PubMed

    Nickla, Debora L; Damyanova, Petya; Lytle, Grace

    2009-06-01

    In birds, the choroid plays a role in the visual regulation of eye growth, thickening in response to myopic defocus, and thinning in response to hyperopic defocus, in both cases moving the retina towards the image plane. This response is rapid, occurring within hours of the defocus stimulus. These changes are consistently associated with slower changes in the sclera, that result in the appropriate changes in axial elongation, decreasing growth in response to myopic defocus and increasing it in response to hyperopic defocus. The molecular mechanisms underlying the scleral response involve changes in the synthesis of extracellular matrix molecules, however, those underlying the changes in choroidal thickness are not known. However, evidence suggests that it may involve the gaseous signal molecule nitric oxide, as nitric oxide is a potent smooth muscle relaxant, and injections of the non-specific nitric oxide synthase inhibitor L-NAME transiently inhibits the thickening response. Interestingly, it also dis-inhibits ocular growth, in accordance with a mechanistic link between the two responses. If nitric oxide is part of the signal cascade underlying the visual regulation of eye growth, it would be important to ascertain the source of the molecule. As a first step towards doing so, we used various more specific NOS inhibitors and studied their effects on the choroidal and growth responses. Birds (7-12 days old) were fitted with +10 D lenses on one eye. On that day, single intravitreal injections (30 microl) of the following inhibitors were used: nNOS inhibitor N(omega)-propyl-L-arginine (n=12), iNOS inhibitor L-NIL (n=16), eNOS/iNOS inhibitor L-NIO (n=15), non-specific inhibitor L-NMMA (n=30) or physiological saline (n=18). Ocular dimensions were measured using high-frequency A-scan ultrasonography at the start of the experiment, and at 7, 24 and 48 h after. We found that the nNOS inhibitor N(omega)-propyl-L-arginine had the same inhibitory effects on the choroidal

  5. Morphologic Changes in Patient with Drusen and Drusenoid Pigment Epithelial Detachment after Intravitreal Ranibizumab for Choroidal Neovascular Membrane : A Case Report.

    PubMed

    Kim, Sukjin; Oh, Jeongjae; Kim, Kiseok

    2016-01-01

    The authors present a case of morphologic changes of drusen and drusenoid pigment epithelial detachment (DPED) after treating choroidal neovascularization (CNV) using ranibizumab in age-related macular degeneration (AMD). A 71-year-old woman has noticed mild visual acuity deterioration in the right eye for several months. She was presented with some drusen and DPED associated with CNV. This patient was given intravitreal injection of 0.5 mg of ranibizumab five times at monthly intervals for treating CNV. DPED in the temporal and drusen in the superior to macula were diminished, which continued up to 2 months. Intravitreal ranibizumab injection may have influenced with diminishment of drusen and DPED. After 2 months, CNV was recurred. PMID:27014379

  6. Topical Application of a G-Quartet Aptamer Targeting Nucleolin Attenuates Choroidal Neovascularization in a Model of Age-Related Macular Degeneration

    PubMed Central

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

    2015-01-01

    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. PMID:26368850

  7. 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.

  8. Intravitreal anti-vascular endothelial growth factor combined with half-fluence photodynamic therapy for choroidal neovascularization in chronic central serous chorioretinopathy.

    PubMed

    Smretschnig, E; Hagen, S; Glittenberg, C; Ristl, R; Krebs, I; Binder, S; Ansari-Shahrezaei, S

    2016-06-01

    PurposeTo evaluate the results of indocyanine green angiography (ICGA)-guided verteporfin photodynamic therapy (PDT) with half-fluence rate combined with intravitreal application of anti-VEGF in treating choroidal neovascularization (CNV) in chronic central serous chorioretinopathy (CSCR).Patients and methodsIn this retrospective cohort study 17 consecutive patients with secondary CNV due to chronic CSCR had their diagnosis verified with fluorescein angiography (FA) and ICGA at baseline. All eyes received either intravitreal ranibizumab (IVR) or bevacizumab (IVB). On the consecutive day following the initial IVR/IVB treatment, ICGA-guided verteporfin (6 mg/m(2)) PDT with half-fluence rate (25 J/cm(2)) was performed on every patient. IVR or IVB was rescheduled on a pro re nata regimen. Main outcome measures were changes in visual acuity (VA) according to the ETDRS letter score and changes in the central foveal thickness (CFT).ResultsBest-corrected VA at baseline was 65.6 letters (±6.7; n=17) according to the ETDRS letter score. At 12 months, mean ETDRS letter score improved to 71.2 letters (P=0.34). CFT was 309 μm and decreased to 216 μm at month 12 control (P=0.0004). Nine eyes (52.9%) received additional treatment with IVR/IVB due to recurrence of subretinal fluid, with an overall mean number of IVR/IVB treatment of 1.8±3.6 per patient with no systemic side effects during 12 months' follow-up.ConclusionsIVR or IVB combined with ICGA-guided half-fluence PDT with verteporfin is effective in treating CNV in chronic CSCR, with choroidal hyperpermeability in ICGA, resulting in stable vision and significant reduction of CFT. PMID:26965012

  9. Connecting the innate and adaptive immune responses in mouse choroidal neovascularization via the anaphylatoxin C5a and γδT-cells

    PubMed Central

    Coughlin, Beth; Schnabolk, Gloriane; Joseph, Kusumam; Raikwar, Himanshu; Kunchithapautham, Kannan; Johnson, Krista; Moore, Kristi; Wang, Yi; Rohrer, Bärbel

    2016-01-01

    Neovascular age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV). An overactive complement system is associated with AMD pathogenesis, and serum pro-inflammatory cytokines, including IL-17, are elevated in AMD patients. IL-17 is produced by complement C5a-receptor-expressing T-cells. In murine CNV, infiltrating γδT- rather than Th17-cells produce the IL-17 measurable in lesioned eyes. Here we asked whether C5a generated locally in response to CNV recruits IL-17-producing T-cells to the eye. CNV lesions were generated using laser photocoagulation and quantified by imaging; T-lymphocytes were characterized by QRT-PCR. CNV resulted in an increase in splenic IL-17-producing γδT- and Th17-cells; yet in the CNV eye, only elevated levels of γδT-cells were observed. Systemic administration of anti-C5- or anti-C5a-blocking antibodies blunted the CNV-induced production of splenic Th17- and γδT-cells, reduced CNV size and eliminated ocular γδT-cell infiltration. In ARPE-19 cell monolayers, IL-17 triggered a pro-inflammatory state; and splenocyte proliferation was elevated in response to ocular proteins. Thus, we demonstrated that CNV lesions trigger a systemic immune response, augmenting local ocular inflammation via the infiltration of IL-17-producing γδT-cells, which are presumably recruited to the eye in a C5a-dependent manner. Understanding the complexity of complement-mediated pathological mechanisms will aid in the development of an AMD treatment. PMID:27029558

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

    PubMed Central

    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. PMID:27799741

  11. Inhibition of APE1/Ref-1 redox activity rescues human retinal pigment epithelial cells from oxidative stress and reduces choroidal neovascularization

    PubMed Central

    Li, Y.; Liu, X.; Zhou, T.; Kelley, M.R.; Edwards, P.; Gao, H.; Qiao, X.

    2014-01-01

    The effectiveness of current treatment for age related macular degeneration (AMD) by targeting one molecule is limited due to its multifactorial nature and heterogeneous pathologies. Treatment strategy to target multiple signaling pathways or pathological components in AMD pathogenesis is under investigation for better clinical outcome. Inhibition of the redox function of apurinic endonuclease 1/redox factor-1 (APE1) was found to suppress endothelial angiogenesis and promote neuronal cell recovery, thereby may serve as a potential treatment for AMD. In the current study, we for the first time have found that a specific inhibitor of APE1 redox function by a small molecule compound E3330 regulates retinal pigment epithelium (RPEs) cell response to oxidative stress. E3330 significantly blocked sub-lethal doses of oxidized low density lipoprotein (oxLDL) induced proliferation decline and senescence advancement of RPEs. At the same time, E3330 remarkably decreased the accumulation of intracellular reactive oxygen species (ROS) and down-regulated the productions of monocyte chemoattractant protein-1 (MCP-1) and vascular endothelial growth factor (VEGF), as well as attenuated the level of nuclear factor-κB (NF-κB) p65 in RPEs. A panel of stress and toxicity responsive transcription factors that were significantly upregulated by oxLDL was restored by E3330, including Nrf2/Nrf1, p53, NF-κB, HIF1, CBF/NF-Y/YY1, and MTF-1. Further, a single intravitreal injection of E3330 effectively reduced the progression of laser-induced choroidal neovascularization (CNV) in mouse eyes. These data revealed that E3330 effectively rescued RPEs from oxidative stress induced senescence and dysfunctions in multiple aspects in vitro, and attenuated laser-induced damages to RPE–Bruch׳s membrane complex in vivo. Together with its previously established anti-angiogenic and neuroprotection benefits, E3330 is implicated for potential use for AMD treatment. PMID:24624338

  12. Choroid Plexus

    MedlinePlus

    ... spread widely via the cerebrospinal fluid. Choroid plexus papilloma is a rare, benign (noncancerous) tumor. Choroid plexus ... the malignant (cancerous) form of the choroid plexus papilloma. Choroid plexus carcinoma occurs primarily in children. Location ...

  13. Polypoidal choroidal vasculopathy.

    PubMed

    Ciardella, Antonio P; Donsoff, Irene M; Huang, Sheau J; Costa, Danielle L; Yannuzzi, Lawrence A

    2004-01-01

    Polypoidal choroidal vasculopathy was first described as a peculiar hemorrhagic disorder of the macula, characterized by recurrent sub-retinal and sub-retinal pigment epithelium bleeding in middle aged black women. The use of indocyanine green angiography and subsequently of optical coherent tomography has widened our ability to study and understand the pathophysiology of this disorder. The primary abnormality involves the choroidal circulation, and the characteristic lesion is an inner choroidal vascular network of vessels ending in an aneurysmal bulge or outward projection, visible clinically as a reddish orange, spheroid, polyp-like structure. We have also recognized that individuals of African-American and Asian descents are more at risk for developing polypoidal choroidal vasculopathy as the disorder seems to preferentially affect pigmented individuals. However, it has been shown that while that still holds true, patients of other racial backgrounds may be afflicted. Particularly, polypoidal choroidal vasculopathy has been found to be present in about 8-13% of white patients with clinical appearance of exudative age-related macular degeneration. Polypoidal choroidal vasculopathy has also been reported in Irish, French, German, and Italian patients. The natural course of the disease often follows a remitting-relapsing course, and clinically, it is associated with chronic, multiple, recurrent serosanguineous detachments of the retinal pigment epithelium and neurosensory retina with long-term preservation of good vision. Photodynamic treatment appears to be a promising alternative to conventional laser therapy, for the treatment of polypoidal choroidal vasculopathy. In conclusion, polypoidal choroidal vasculopathy seems to be a distinct clinical entity that should be differentiated from other types of choroidal neovascularization associated with age-related macular degeneration and other known choroidal degenerative, inflammatory, and ischemic disorders. PMID

  14. 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

    SciTech Connect

    Toyama, Shingo; Tsuji, Hiroshi; Mizoguchi, Nobutaka; Nomiya, Takuma; Kamada, Tadashi; Tokumaru, Sunao; Mizota, Atsushi; Ohnishi, Yoshitaka; Tsujii, Hirohiko

    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 of 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.

  15. Combined therapy (intravitreal bevacizumab plus verteporfin photodynamic therapy) versus intravitreal bevacizumab monotherapy for choroidal neovascularization due to age-related macular degeneration: a 1-year follow-up study

    PubMed Central

    Saviano, Sandro; Leon, Pia Easter; Mangogna, Alessandro; Tognetto, Daniele

    2016-01-01

    Purpose To assess the efficacy and safety of combined intravitreal bevacizumab and low-fluency-rate photodynamic therapy (PDT) in the treatment of choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) and to compare it with intravitreal bevacizumab monotherapy. Methods A total of 62 eyes of 62 patients with angiographic evidence of CNV were divided into 2 groups: the eyes of one group were treated with a combined therapy of 1 intravitreal bevacizumab injection (1.25 mg) and PDT within 7 days; the eyes of the other group received intravitreal bevacizumab monotherapy. Clinical evidence of complications, best-corrected visual acuity (BVCA) and fluorescein leakage were evaluated. Best-corrected visual acuity and optical coherence tomography (OCT) were tested monthly and followed for 12 months. Results In the combined group the mean BCVA increased from 0.61 logMAR before the treatment to 0.54 logMAR at 12 months’ follow-up. In the monotherapy group the mean BCVA increased from 0.65 logMAR to 0.60 logMAR at 12 months’ follow-up. There was no significant difference in visual acuity outcomes between groups (P > 0.05). In the combined group the mean number of treatments was 1.19 per patient; in the monotherapy group, 5.31 per patient (P < 0.01). Conclusions Combined therapy appears to be an effective option for CNV associated with AMD treatment allowing a significant reduction of intravitreal injections. PMID:27582675

  16. 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

  17. Choroidal osteoma - case reports.

    PubMed

    Khan, N; Rahman, N A; Uddin, M S

    2014-07-01

    Choroidal osteoma is a rare disease. In this article four case histories were described. All were female and young patient. One patient had bilateral and other three had unilateral involvement. They had no family history. One patient reported at eye department in Bangabandhu Sheikh Mujib Medical University (BSMMU) and the other three patients reported in Bangladesh Eye Hospital. Choroidal osteoma is a benign tumor. It is diagnosed by fundoscopy, ocular B-scan ultrasonography, x-ray orbit, FFA, OCT and CT-scan of orbit. Most patients do not require treatment. Hemorrhage on the lesion suggests the presence of sub-retinal neovascularization which are typically treated with laser or intra-vitreal anti-VEGF.

  18. 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

  19. Pediatric genetic macular and choroidal diseases.

    PubMed

    Bergman, Mica Y; Nallasamy, Sudha

    2014-12-01

    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

  20. 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.

  1. [Choroidal melanoma].

    PubMed

    Desjardins, Laurence

    2016-03-01

    Choroidal melanoma is the most common form of eye cancer in adults. Treatments enabling the tumour to be destroyed or removed while preserving the eye socket are mainly based on surgery, proton therapy and brachytherapy. PMID:26944641

  2. Optical Defocus Rapidly Changes Choroidal Thickness in Schoolchildren.

    PubMed

    Wang, Danyang; Chun, Rachel Ka Man; Liu, Manli; Lee, Roger Pak Kin; Sun, Yuan; Zhang, Ting; Lam, Chuen; Liu, Quan; To, Chi Ho

    2016-01-01

    The current study aimed to examine the short-term choroidal response to optical defocus in schoolchildren. Myopic schoolchildren aged 8-16 were randomly allocated to control group (CG), myopic defocus group (MDG) and hyperopic defocus group (HDG) (n = 17 per group). Children in MDG and HDG received additional +3D and -3D lenses, respectively, to their full corrections on the right eyes. Full correction was given to their left eyes, and on both eyes in the CG. Axial length (AXL) and subfoveal choroidal thickness (SFChT) were then measured by spectral domain optical coherence tomography. Children wore their group-specific correction for 2 hours after which any existing optical defocus was removed, and subjects wore full corrections for another 2 hours. Both the AXL and SFChT were recorded hourly for 4 hours. The mean refraction of all subjects was -3.41 ± 0.37D (± SEM). SFChT thinned when exposed to hyperopic defocus for 2 hours but less thinning was observed in response to myopic defocus compared to the control group (p < 0.05, two-way ANOVA). Removal of optical defocus significantly decreased SFChT in the MDG and significantly increased SFChT in the HDG after 1 and 2 hours (mean percentage change at 2-hour; control vs. hyperopic defocus vs. myopic defocus; -0.33 ± 0.59% vs. 3.04 ± 0.60% vs. -1.34 ± 0.74%, p < 0.01). Our results showed short-term exposure to myopic defocus induced relative choroidal thickening while hyperopic defocus led to choroidal thinning in children. This rapid and reversible choroidal response may be an important clinical parameter in gauging retinal response to optical defocus in human myopia. PMID:27537606

  3. Optical Defocus Rapidly Changes Choroidal Thickness in Schoolchildren.

    PubMed

    Wang, Danyang; Chun, Rachel Ka Man; Liu, Manli; Lee, Roger Pak Kin; Sun, Yuan; Zhang, Ting; Lam, Chuen; Liu, Quan; To, Chi Ho

    2016-01-01

    The current study aimed to examine the short-term choroidal response to optical defocus in schoolchildren. Myopic schoolchildren aged 8-16 were randomly allocated to control group (CG), myopic defocus group (MDG) and hyperopic defocus group (HDG) (n = 17 per group). Children in MDG and HDG received additional +3D and -3D lenses, respectively, to their full corrections on the right eyes. Full correction was given to their left eyes, and on both eyes in the CG. Axial length (AXL) and subfoveal choroidal thickness (SFChT) were then measured by spectral domain optical coherence tomography. Children wore their group-specific correction for 2 hours after which any existing optical defocus was removed, and subjects wore full corrections for another 2 hours. Both the AXL and SFChT were recorded hourly for 4 hours. The mean refraction of all subjects was -3.41 ± 0.37D (± SEM). SFChT thinned when exposed to hyperopic defocus for 2 hours but less thinning was observed in response to myopic defocus compared to the control group (p < 0.05, two-way ANOVA). Removal of optical defocus significantly decreased SFChT in the MDG and significantly increased SFChT in the HDG after 1 and 2 hours (mean percentage change at 2-hour; control vs. hyperopic defocus vs. myopic defocus; -0.33 ± 0.59% vs. 3.04 ± 0.60% vs. -1.34 ± 0.74%, p < 0.01). Our results showed short-term exposure to myopic defocus induced relative choroidal thickening while hyperopic defocus led to choroidal thinning in children. This rapid and reversible choroidal response may be an important clinical parameter in gauging retinal response to optical defocus in human myopia.

  4. Optical Defocus Rapidly Changes Choroidal Thickness in Schoolchildren

    PubMed Central

    Liu, Manli; Lee, Roger Pak Kin; Sun, Yuan; Zhang, Ting; Lam, Chuen; Liu, Quan; To, Chi Ho

    2016-01-01

    The current study aimed to examine the short-term choroidal response to optical defocus in schoolchildren. Myopic schoolchildren aged 8–16 were randomly allocated to control group (CG), myopic defocus group (MDG) and hyperopic defocus group (HDG) (n = 17 per group). Children in MDG and HDG received additional +3D and -3D lenses, respectively, to their full corrections on the right eyes. Full correction was given to their left eyes, and on both eyes in the CG. Axial length (AXL) and subfoveal choroidal thickness (SFChT) were then measured by spectral domain optical coherence tomography. Children wore their group-specific correction for 2 hours after which any existing optical defocus was removed, and subjects wore full corrections for another 2 hours. Both the AXL and SFChT were recorded hourly for 4 hours. The mean refraction of all subjects was -3.41 ± 0.37D (± SEM). SFChT thinned when exposed to hyperopic defocus for 2 hours but less thinning was observed in response to myopic defocus compared to the control group (p < 0.05, two-way ANOVA). Removal of optical defocus significantly decreased SFChT in the MDG and significantly increased SFChT in the HDG after 1 and 2 hours (mean percentage change at 2-hour; control vs. hyperopic defocus vs. myopic defocus; -0.33 ± 0.59% vs. 3.04 ± 0.60% vs. -1.34 ± 0.74%, p < 0.01). Our results showed short-term exposure to myopic defocus induced relative choroidal thickening while hyperopic defocus led to choroidal thinning in children. This rapid and reversible choroidal response may be an important clinical parameter in gauging retinal response to optical defocus in human myopia. PMID:27537606

  5. Intrachoroidal Neovascularization in Transgenic Mice Overexpressing Vascular Endothelial Growth Factor in the Retinal Pigment Epithelium

    PubMed Central

    Schwesinger, Catherine; Yee, Charles; Rohan, Richard M.; Joussen, Antonia M.; Fernandez, Antonio; Meyer, Tobias N.; Poulaki, Vassiliki; Ma, Joseph J. K.; Redmond, T. Michael; Liu, Suyan; Adamis, Anthony P.; D’Amato, Robert J.

    2001-01-01

    Choroidal neovascularization in age-related macular degeneration is a frequent and poorly treatable cause of vision loss in elderly Caucasians. This choroidal neovascularization has been associated with the expression of vascular endothelial growth factor (VEGF). In current animal models choroidal neovascularization is induced by subretinal injection of growth factors or vectors encoding growth factors such as VEGF, or by disruption of the Bruch’s membrane/retinal pigment epithelium complex with laser treatment. We wished to establish a transgenic murine model of age-related macular degeneration, in which the overexpression of VEGF by the retinal pigment epithelium induces choroidal neovascularization. A construct consisting of a tissue-specific murine retinal pigment epithelium promoter (RPE65 promoter) coupled to murine VEGF164 cDNA with a rabbit β-globin-3′ UTR was introduced into the genome of albino mice. Transgene mRNA was expressed in the retinal pigment epithelium at all ages peaking at 4 months. The expression of VEGF protein was increased in both the retinal pigment epithelium and choroid. An increase of intravascular adherent leukocytes and vessel leakage was observed. Histopathology revealed intrachoroidal neovascularization that did not penetrate through an intact Bruch’s membrane. These results support the hypothesis that additional insults to the integrity of Bruch’s membrane are required to induce growth of choroidal vessels into the subretinal space as seen in age-related macular degeneration. This model may be useful to screen for inhibitors of choroidal vessel growth. PMID:11238064

  6. [Bilateral choroidal osteoma--a case report].

    PubMed

    Jędrychowska-Jamborska, Justyna; Kulig-Stochmal, Agnieszka; Markiewicz, Anna; Jakubowska, Barbara; Romanowska-Dixon, Bożena

    2014-01-01

    Choroidal osteoma is a an extremely rare (especially located bilaterally), benign, intraocular tumor, the type of choristoma. It occurs between 2-3 decades of life, women are particularly vulnerable. The main complication in 1/3 cases is a subretinal neovascularization which may cause bleeding. The gradually progressive decalcification develops within the tumour over time, which causes atrophy of the retinal pigment epithelium and Bruch's membrane deformity. The article presents a case of a 26-year-old woman with bilateral choroidal osteoma complicated by subretinal hemorrhage; the diagnosis was based on clinical examination (biomicroscopy and indirect ophthalmoscopy) as well as specialised tests including: ultrasonography, optical coherence tomography, and fluorescein angiography.

  7. [Macular serpiginous choroiditis complicated by macular hole].

    PubMed

    Brănişteanu, D; Moraru, Andreea

    2014-01-01

    Macular serpiginouschoroiditis is a rare variant of serpiginous choroiditis characterized by a severe recurrent inflammation of both central choroid and retinal pigment epithelium. Visual prognosis is severe due to subsequent distruction of retinal structures. Permanent central visual loss is the consequence of retinal pigment epithelium hyper or hypoplasia and/or subretinal neovascularization leading to fibrous scarring. This article reports the unusual case of rapid development of a macular hole soon after the onset of characteristic clinical features. Despite anti-inflammatory treatment and successful macular hole surgery the visual function remained significantly impaired by secondary central retinal pigment epithelium changes.

  8. Choroidal melanoma

    PubMed Central

    Singh, Parul; Singh, Abhishek

    2012-01-01

    Choroidal melanoma is the most common primary intra-ocular malignant tumor and second most common site of ten malignant melanoma sites in the body. Current diagnosis of choroidal melanoma is based on both the clinical experience of the specialist and modern diagnostic techniques such as indirect ophthalmoscopy, A- and B-ultrasonography scans, fundus fluorescein angiography, and transillumination. Invasive studies such as fine needle aspiration cytology can have significant morbidity and should only be considered if therapeutic intervention is indicated and diagnosis cannot be established by any other means. Several modes of treatment are available for choroidal melanoma. Multiple factors are taken into account when deciding one approach over other approaches, such as visual acuity of the affected eye, visual acuity of the contralateral eye, tumor size, location, ocular structures involved and presence of metastases. A comprehensive review of literature available in books and indexed journals was done. This article discusses in detail epidemiology, diagnosis, current available treatment options, and prognosis and survival of choroidal melanoma. PMID:22557869

  9. Choroidal osteoma: evidence of progression and decalcification over 20 years.

    PubMed

    Chen, Jennifer; Lee, Lawrence; Gass, J Donald M

    2006-03-01

    Choroidal osteoma is a rare, benign, ossifying tumour of the choroid of unknown aetiology. In contrast to other types of intraocular ossification, choroidal osteoma is found typically in young healthy females in the second or third decades of life with no history of systemic or ocular disease. Choroidal osteoma is a deep, pale yellow lesion with distinct geographic borders at the juxtapapillary or macular region, with branching 'spider' vessels on the surface of the tumour. These features should help differentiate choroidal osteoma from other types of intraocular tumour and the diagnosis can be confirmed with ultrasonography and computerised tomography. Here we report an initially unilateral case of choroidal osteoma, which decalcified over 20 years but during the same period the fellow eye also developed a choroidal osteoma to become a bilateral case. Despite the benign nature of the tumour, vision may be compromised by gradual atrophy of the overlying retina, serous retinal detachment, accumulation of sub-retinal fluid and sub-retinal haemorrhage associated with choroidal neovascularisation. Frequent examinations are recommended for patients with choroidal osteoma, for early detection of a subretinal neovascular membrane and potential treatment with laser photocoagulation.

  10. 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.

  11. A potential therapeutic strategy for inhibition of corneal neovascularization with new anti-VEGF agents.

    PubMed

    Hosseini, Hamid; Nejabat, Mahmood

    2007-01-01

    The factors triggering corneal neovascularization involve various growth factors. The data supporting a causal role for vascular endothelial growth factor (VEGF) in corneal neovascularization are extensive. One possible strategy for treating corneal neovascularization is to inhibit VEGF activity by competitively binding VEGF with a specific neutralizing anti-VEGF antibody. The vireo-retinal service in the recent years enjoyed a high level of success in managing choroidal neovascularization using anti-VEGF strategies. Efficacy and tolerability have been demonstrated for drugs targeting VEGF. We herein hypothesize that topical application of new anti-VEGF agents such as pegaptanib, ranibizumab and bevacizumab are potentially useful for inhibiting corneal neovascularization and restoration of corneal clarity. Further investigations are needed to place these medical treatments alongside corneal neovascularization therapeutics. PMID:17107753

  12. [Consensus on neovascular glaucoma].

    PubMed

    Hamard, P; Baudouin, C

    2000-03-01

    Neovascular glaucoma is a dreadful pathology with a rapid spontaneous evolution responsible for painful and blind eye. The main cause is an anterior neovascular proliferation following a broad retinal ischemia. Early diagnosis and treatment are required in order to maintain a good visual status and a satisfactory IOP control with medical, surgical or cylodestructive procedures. In any case, the treatment of the retinal ischemia has to be performed. One must keep in mind that the most efficient way to avoid the incidence of neovascular glaucoma is a strict control of clinical situations potentially responsible for retinal ischemia, namely VRO in elderly patients and diabetic retinopathy in younger patients. PMID:10740059

  13. Lack of netrin-4 modulates pathologic neovascularization in the eye

    PubMed Central

    Kociok, Norbert; Crespo-Garcia, Sergio; Liang, Yong; Klein, Sabrina V.; Nürnberg, Christina; Reichhart, Nadine; Skosyrski, Sergej; Moritz, Eva; Maier, Anna-Karina; Brunken, William J.; Strauß, Olaf; Koch, Manuel; Joussen, Antonia M.

    2016-01-01

    Netrins are a family of matrix-binding proteins that function as guidance signals. Netrin-4 displays pathologic roles in tumorigenesis and neovascularization. To answer the question whether netrin-4 acts either pro- or anti-angiogenic, angiogenesis in the retina was assessed in Ntn-4−/− mice with oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV), mimicking hypoxia-mediated neovascularization and inflammatory mediated angiogenesis. The basement membrane protein netrin-4 was found to be localised to mature retinal blood vessels. Netrin-4, but not netrin-1 mRNA expression, increased in response to relative hypoxia and recovered to normal levels at the end of blood vessel formation. No changes in the retina were found in normoxic Ntn-4−/− mice. In OIR, Ntn-4−/− mice initially displayed larger avascular areas which recovered faster to revascularization. Ganzfeld electroretinography showed faster recovery of retinal function in Ntn-4−/− mice. Expression of netrin receptors, Unc5H2 (Unc-5 homolog B, C. elegans) and DCC (deleted in colorectal carcinoma), was found in Müller cells and astrocytes. Laser-induced neovascularization in Nnt-4−/− mice did not differ to that in the controls. Our results indicate a role for netrin-4 as an angiogenesis modulating factor in O2-dependent vascular homeostasis while being less important during normal retinal developmental angiogenesis or during inflammatory neovascularization. PMID:26732856

  14. Doxycycline inhibits polarization of macrophages to the proangiogenic M2-type and subsequent neovascularization.

    PubMed

    He, Lizhi; Marneros, Alexander G

    2014-03-21

    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.

  15. [Myopic traction maculopathy - vitreoretinal traction syndrome in high myopic eyes and posterior staphyloma].

    PubMed

    Müller, B; Joussen, A M

    2011-09-01

    The pathology of the posterior pole in high myopic eyes is characterised by scleral thinning and staphyloma associated with structural changes of the retina. Epiretinal membranes and epiretinal traction together with partial separation of the ILM result in myopic foveoschisis and posterior tractional detachment with myopic macular holes. Foveal detachment and retinoschisis in highly myopic eyes may resolve after vitrectomy with ILM peeling: however, there is a considerable risk for the development of macular hole formation. Skleral buckling surgery is currently regaining interest and allows one to reduce the tractional forces in selected cases. While reading visual acuity is usually not regained after macular hole development, prophylactic measures should be considered for the fellow eye. Vitreous surgery might have a rationale as prophylactic treatment for highly myopic eyes at high risk of macular hole development; however, this needs to be weighed against possible surgical complications.

  16. Blind and myopic ants in heterogeneous networks

    NASA Astrophysics Data System (ADS)

    Hwang, S.; Lee, D.-S.; Kahng, B.

    2014-11-01

    The diffusion processes on complex networks may be described by different Laplacian matrices due to heterogeneous connectivity. Here we investigate the random walks of blind ants and myopic ants on heterogeneous networks: While a myopic ant hops to a neighbor node every step, a blind ant may stay or hop with probabilities that depend on node connectivity. By analyzing the trajectories of blind ants, we show that the asymptotic behaviors of both random walks are related by rescaling time and probability with node connectivity. Using this result, we show how the small eigenvalues of the Laplacian matrices generating the two random walks are related. As an application, we show how the return-to-origin probability of a myopic ant can be used to compute the scaling behaviors of the Edwards-Wilkinson model, a representative model of load balancing on networks.

  17. 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

  18. Choroidal volume variations with age, axial length, and sex in healthy subjects: a three-dimensional analysis

    PubMed Central

    Barteselli, Giulio; Chhablani, Jay; El-Emam, Sharif; Wang, Haiyan; Chuang, Janne; Kozak, Igor; Cheng, Lingyun; Bartsch, Dirk-Uwe; Freeman, William R.

    2012-01-01

    -dimensional topography of the choroid and to measure choroidal volume at the posterior pole using manual segmentation. Age and axial length are inversely correlated with choroidal volume, most likely leading to changes in retinal metabolic support in old and high myopic patients. Sexual differences should be considered when interpreting an EDI SD-OCT scan of the choroid. PMID:22921388

  19. Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization.

    PubMed

    Basavarajappa, Halesha D; Lee, Bit; Lee, Hyungjun; Sulaiman, Rania S; An, Hongchan; Magaña, Carlos; Shadmand, Mehdi; Vayl, Alexandra; Rajashekhar, Gangaraju; Kim, Eun-Yeong; Suh, Young-Ger; Lee, Kiho; Seo, Seung-Yong; Corson, Timothy W

    2015-06-25

    Eye diseases characterized by excessive angiogenesis such as wet age-related macular degeneration, proliferative diabetic retinopathy, and retinopathy of prematurity are major causes of blindness. Cremastranone is an antiangiogenic, naturally occurring homoisoflavanone with efficacy in retinal and choroidal neovascularization models and antiproliferative selectivity for endothelial cells over other cell types. We undertook a cell-based structure-activity relationship study to develop more potent cremastranone analogues, with improved antiproliferative selectivity for retinal endothelial cells. Phenylalanyl-incorporated homoisoflavonoids showed improved activity and remarkable selectivity for retinal microvascular endothelial cells. A lead compound inhibited angiogenesis in vitro without inducing apoptosis and had efficacy in the oxygen-induced retinopathy model in vivo.

  20. Strategies for improving early detection and diagnosis of neovascular age-related macular degeneration

    PubMed Central

    Keane, Pearse A; de Salvo, Gabriella; Sim, Dawn A; Goverdhan, Srini; Agrawal, Rupesh; Tufail, Adnan

    2015-01-01

    Treatment of the neovascular form of age-related macular degeneration (AMD) has been revolutionized by the introduction of such agents as ranibizumab, bevacizumab, and aflibercept. As a result, the incidence of legal blindness occurring secondary to AMD has fallen dramatically in recent years in many countries. While these agents have undoubtedly been successful in reducing visual impairment and blindness, patients with neovascular AMD typically lose some vision over time, and often lose the ability to read, drive, or perform other important activities of daily living. Efforts are therefore under way to develop strategies that allow for earlier detection and treatment of this disease. In this review, we begin by providing an overview of the rationale for, and the benefits of, early detection and treatment of neovascular AMD. To achieve this, we begin by providing an overview of the pathophysiology and natural history of choroidal neovascularization, before reviewing the evidence from both clinical trials and “real-world” outcome studies. We continue by highlighting an area that is often overlooked: the importance of patient education and awareness for early AMD detection. We conclude the review by reviewing an array of both established and emerging technologies for early detection of choroidal neovascularization, ranging from Amsler chart testing, to hyperacuity testing, to advanced imaging techniques, such as optical coherence tomography. PMID:25733802

  1. Endothelial microRNA-150 is an intrinsic suppressor of pathologic ocular neovascularization

    PubMed Central

    Liu, Chi-Hsiu; Sun, Ye; Li, Jie; Gong, Yan; Tian, Katherine T.; Evans, Lucy P.; Morss, Peyton C.; Fredrick, Thomas W.; Saba, Nicholas J.; Chen, Jing

    2015-01-01

    Pathologic ocular neovascularization commonly causes blindness. It is critical to identify the factors altered in pathologically proliferating versus normally quiescent vessels to develop effective targeted therapeutics. MicroRNAs regulate both physiological and pathological angiogenesis through modulating expression of gene targets at the posttranscriptional level. However, it is not completely understood if specific microRNAs are altered in pathologic ocular blood vessels, influencing vascular eye diseases. Here we investigated the potential role of a specific microRNA, miR-150, in regulating ocular neovascularization. We found that miR-150 was highly expressed in normal quiescent retinal blood vessels and significantly suppressed in pathologic neovessels in a mouse model of oxygen-induced proliferative retinopathy. MiR-150 substantially decreased endothelial cell function including cell proliferation, migration, and tubular formation and specifically suppressed the expression of multiple angiogenic regulators, CXCR4, DLL4, and FZD4, in endothelial cells. Intravitreal injection of miR-150 mimic significantly decreased pathologic retinal neovascularization in vivo in both wild-type and miR-150 knockout mice. Loss of miR-150 significantly promoted angiogenesis in aortic rings and choroidal explants ex vivo and laser-induced choroidal neovascularization in vivo. In conclusion, miR-150 is specifically enriched in quiescent normal vessels and functions as an endothelium-specific endogenous inhibitor of pathologic ocular neovascularization. PMID:26374840

  2. De novo appearance of a choroidal osteoma in an eye with previous branch retinal vein occlusion.

    PubMed

    Adhi, Mehreen; Bryant, Juanita Sonya; Alwassia, Ahmad A; Chen, Carolyn; Duker, Jay S

    2013-01-01

    This report describes the de novo appearance of a choroidal osteoma occurring 8 years after laser photocoagulation for previous branch retinal vein occlusion (BRVO). A 62-year-old man presented with an asymptomatic yellowish orange lesion in the macula on fundus examination of his left eye during a regular follow-up visit for bilateral BRVO associated with macular edema that had previously been treated with laser photocoagulation. The lesion was observed for 1.5 years until a decrease in vision occurred. Fundus photography revealed a yellow-to-orange, well-defined lesion in the macular region. Fluorescein angiography was consistent with choroidal neovascularization (CNV). Optical coherence tomography and B-scan ultrasonography showed features consistent with choroidal osteoma. This is the first report of the de novo appearance of a choroidal osteoma occurring years after laser photocoagulation for BRVO. CNV developed secondary to the lesion, which was treated with intravitreal bevacizumab, leading to subjective and anatomic improvement.

  3. Increased choroidal mast cells and their degranulation in age-related macular degeneration

    PubMed Central

    Bhutto, Imran A; McLeod, D Scott; Jing, Tian; Sunness, Janet S.; Seddon, Johanna M.; Lutty, Gerard A

    2016-01-01

    Background/Aims Inflammation has been implicated in age-related macular degeneration (AMD). This study investigates the association of mast cells (MCs), a resident choroidal inflammatory cell, with pathological changes in AMD. Methods Human donor eyes included aged controls (n=10), clinically diagnosed with early AMD (n=8), geographic atrophy (GA, n=4), and exudative AMD (n=11). The choroids were excised and incubated alkaline phosphatase (APase; blood vessels) and nonspecific esterase activities (MCs). Degranulated (DG) and nondegranulated (NDG) MCs in four areas of posterior choroid (nasal, nonmacular, paramacular, and submacular) were counted in flat mounts (4∼6 fields/area). Choroids were subsequently embedded in JB-4 and sectioned for histological analyses. Results The number of MCs was significantly increased in all choroidal areas in early AMD (p=0.0006) and in paramacular area in exudative AMD (139.44±55.3 cells/mm2; p=0.0091) and GA (199.08±82.0 cells/mm2; p=0.0019) compared to the aged controls. DG MCs was also increased in paramacular (p=0.001) and submacula choroid (p=0.02) in all forms of AMD. Areas with the greatest numbers of DG MC had loss of choriocapillaris (CC). Sections revealed that the MCs were widely distributed in Sattler's and Haller's layer in the choroidal stroma in aged controls, whereas MCs were frequently found in close proximity to CC in GA and exudative AMD and in choroidal neovascularization (CNV). Conclusion Increased MC numbers and degranulation were observed in all AMD choroids. These results suggest that MC degranulation may contribute to the pathogenesis of AMD: death of CC and RPE and CNV formation. The proteolytic enzymes released from MC granules may result in thinning of AMD choroid. PMID:26931413

  4. Circumscribed Choroidal Hemangioma

    PubMed Central

    Karimi, Saeed; Nourinia, Ramin; Mashayekhi, Arman

    2015-01-01

    Circumscribed choroidal hemangiomas are benign vascular hamartomas without systemic associations. Generally, they are orange-red elevated masses, which are found posterior to the equator. Lesions are usually solitary and unilateral. Overlying subretinal fluid, serous retinal detachment and cystoid macular edema are common findings. Intravenous fluorescein angiography, indocyanine green angiography, ultrasonography, optical coherence tomography and enhanced depth imaging are helpful ancillary tests for diagnosis of circumscribed choroidal hemangiomas. Asymptomatic circumscribed choroidal hemangiomas do not require treatment. For symptomatic lesions with exudative retinal detachment or cystoid macular edema, photodynamic therapy has emerged as the treatment of choice with high rates of tumor regression, subretinal fluid resorption and minimal complications. Lens-sparing external beam radiotherapy, plaque brachytherapy, proton beam therapy, stereotactic radiosurgery, transpupillary thermotherapy, laser photocoagulation and anti-VEGF injections are other treatment modalities. PMID:26730320

  5. Bilateral Presumed Tuberculous Choroiditis

    PubMed Central

    Mohammadi, Naseh; Ghassemi, Fariba; Shojaei, Esfandiar; Moradnejad, Pardis

    2016-01-01

    Purpose: To describe a case of bilateral presumed tuberculous choroiditis which resolved promptly with a short course of antituberculous therapy. Case Report: A 44-year-old lady presented with bilateral visual loss of 8 months’duration. Considering the presence of pan-uveitis, severe macular edema, multifocal leakage on fluorescein angiography, positive tuberculin skin test, and after excluding other diseases, she underwent anti-tuberculous therapy (ATT) for disseminated choroiditis due to presumed ocular tuberculosis. She improved promptly and completely. There were no signs of relapse 18 months after completion of the treatment course. In a young patient with disseminated choroiditis and relatively short duration of symptoms, a course of ATT for 6 months may effectively treat the disease preventing relapse for a considerable period of time. Conclusion: In Presumed Tuberculous chroiditis early diagnosis is crucial for prompt and complete improvement. PMID:27413507

  6. STAT3 activation in circulating monocytes contributes to neovascular age-related macular degeneration

    PubMed Central

    Chen, Mei; Lechner, Judith; Zhao, Jiawu; Toth, Levente; Hogg, Ruth; Silvestri, Giuliana; Kissenpfennig, Adrien; Chakravarthy, Usha; Xu, Heping

    2016-01-01

    Infiltrating macrophages are critically involved in pathogenic angiogenesis such as neovascular age-related macular degeneration (nAMD). Macrophages originate from circulating monocytes and three subtypes of monocyte exist in humans: classical (CD14+CD16-), non-classical (CD14-CD16+) and intermediate (CD14+CD16+) monocytes. The aim of this study was to investigate the role of circulating monocyte in neovascular age-related macular degeneration (nAMD). Flow cytometry analysis showed that the intermediate monocytes from nAMD patients expressed higher levels of CX3CR1 and HLA-DR compared to those from controls. Monocytes from nAMD patients expressed higher levels of phosphorylated Signal Transducer and Activator of Transcription 3 (pSTAT3), and produced higher amount of VEGF. In the mouse model of choroidal neovascularization (CNV), pSTAT3 expression was increased in the retina and RPE/choroid, and 49.24% of infiltrating macrophages express pSTAT3. Genetic deletion of the Suppressor of Cytokine Signalling 3 (SOCS3) in myeloid cells in the LysM-Cre+/-:SOCS3fl/fl mice resulted in spontaneous STAT3 activation and accelerated CNV formation. Inhibition of STAT3 activation using a small peptide LLL12 suppressed laser-induced CNV. Our results suggest that monocytes, in particular the intermediate subset of monocytes are activated in nAMD patients. STAT3 activation in circulating monocytes may contribute to the development of choroidal neovascularisation in AMD. PMID:27009107

  7. Identification of RALDH2 as a Visually Regulated Retinoic Acid Synthesizing Enzyme in the Chick Choroid

    PubMed Central

    Hollaway, Lindsey R.; Lam, Wengtse; Li, Nan; Napoli, Joseph L.

    2012-01-01

    Purpose. All-trans-retinoic acid (atRA) has been implicated in the local regulation of scleral proteoglycan synthesis in vivo. The purpose of the present study was to identify the enzymes involved in the synthesis of atRA during visually guided ocular growth, the cells involved in modulation of atRA biosynthesis in the choroid, and the effect of choroid-derived atRA on scleral proteoglycan synthesis. Methods. Myopia was induced in White leghorn chicks by form deprivation for 10 days, followed by up to 15 days of unrestricted vision (recovery). Expression of atRA synthesizing enzymes was evaluated by semiquantitative qRT-PCR, in situ hybridization, and immunohistochemistry. atRA synthesis was measured in organ cultures of isolated choroids using LC-tandem MS quantification. Scleral proteoglycan synthesis was measured in vitro by the incorporation of 35SO4 in CPC-precipitable glycosaminoglycans. Results. RALDH2 was the predominant RALDH transcript in the choroid (>100-fold that of RALDH3). RALDH2 mRNA was elevated after 12 and 24 hours of recovery (60% and 188%, respectively; P < 0.01). The atRA concentration was significantly higher in cultures of choroids from 24-hour to 15-day recovering eyes than in paired controls (∼195%; P < 0.01). Choroid conditioned medium from recovering choroids inhibited proteoglycan synthesis to 43% of controls (P < 0.02, paired t-test; n = 16) and produced a relative inhibition corresponding to a RA concentration of 7.20 × 10−8 M. Conclusions. The results of this study suggest that RALDH2 is the major retinal dehydrogenase in the chick choroid and is responsible for increased atRA synthesis in response to myopic defocus. PMID:22323456

  8. The phase relationships between the diurnal rhythms in axial length and choroidal thickness and the association with ocular growth rate in chicks.

    PubMed

    Nickla, Debora L

    2006-04-01

    Eyes of young chickens show diurnal oscillations in axial length and choroidal thickness that are out of phase. In eyes responding to myopic defocus induced by prior form deprivation, the two rhythms shift into phase. In order to elucidate the possible role for these rhythms in ocular growth regulation, they were measured under visual conditions that altered ocular growth rate. (1) Form deprivation to myopic defocus. Eyes of chicks were monocularly deprived for 5 days. Diffusers were removed. (2) Myopic defocus to hyperopic defocus. Eyes wore positive lenses for 6 days; lenses were removed. (3) Hyperopic to myopic defocus. Eyes wore negative lenses for 5 days; lenses were removed. Eyes were measured using A-scan ultrasonography at 6-h intervals for 24 h over various cycles. The rhythms shift into phase in eyes slowing their growth in response to myopic defocus in all three conditions. This shift precedes by 1 day the decrease in growth in both lens conditions, and is concomitant with it in recovering eyes. There is a positive correlation between the phase difference and growth rate. In conclusion, there is a consistent association between growth rate and phase relationships of the rhythms in axial elongation and choroidal thickness.

  9. Intraocular microablation of choroidal tissue by a 308 nm AIDA excimer laser for RPE-transplantation in patients with age-related macular degeneration.

    PubMed

    Holz, F G; Bindewald, A; Schutt, F; Specht, H

    2003-04-01

    Age-related macular degeneration (AMD) is the leading cause of legal blindness in the western nations beyond 50 years of age. The most frequent cause for severe visual loss is the growth of neovascular membrances from the choroid into the subretinal space. This usually results in irreversible degeneration of the overlying retina. Surgical removal of the membrane is feasible, however, usually results in functional loss of apposing retinal photoreceptors since retinal pigment epithelial (RPE) cells are removed concurrently due to their tight adherence to the neovascular complex. Therefore, various attempts have been undertaken to fill the resulting RPE cell defect with either heterologous or autologous RPE cell transplants. So far cell survival, function and subsequent visual function has been disappointing. To minimize trauma and resulting dedifferentiation harvesting in the eye and transplantation in whole sheets and without temporary removal from the eyes would be desirable. This may be achieved by isolating grafts consisting of choroid, Bruch's membrance and RPE cells from the peripheral retina and transplantation of this graft under the neurosensory retina after removal of the choroidal neovascularization. However, the choroidal component of such a graft would be expected to interfere with diffusion of metabolites to and from the retina. Therefore, outcome would be expected to be better if the choroidal tissue would be removed before translocation. In preclinical experiments we used a 308 nm UV AIDA excimer laser to microablate choroidal tissue from such a graft in human donor eyes. PMID:12749285

  10. Polymeric materials for neovascularization

    NASA Astrophysics Data System (ADS)

    DeVolder, Ross John

    Revascularization therapies have emerged as a promising strategy to treat various acute and chronic wounds, cardiovascular diseases, and tissue defects. It is common to either administer proangiogenic growth factors, such as vascular endothelial growth factor (VEGF), or transplant cells that endogenously express multiple proangiogenic factors. Additionally, these strategies utilize a wide variety of polymeric systems, including hydrogels and biodegradable plastics, to deliver proangiogenic factors in a sophisticated manner to maintain a sustained proangiogenic environment. Despite some impressive results in rebuilding vascular networks, it is still a challenging task to engineer mature and functional neovessels in target tissues, because of the increasing complexities involved with neovascularization applications. To resolve these challenges, this work aims to design a wide variety of proangiogenic biomaterial systems with tunable properties used for neovascularization therapies. This thesis describes the design of several biomaterial systems used for the delivery of proangiogenic factors in neovascularization therapies, including: an electrospun/electrosprayed biodegradable plastic patch used for directional blood vessel growth (Chapter 2), an alginate-g-pyrrole hydrogel system that biochemically stimulates cellular endogenous proangiogenic factor expression (Chapter 3), an enzyme-catalyzed alginate-g-pyrrole hydrogel system for VEGF delivery (Chapter 4), an enzyme-activated alginate-g-pyrrole hydrogel system with systematically controllable electrical and mechanical properties (Chapter 5), and an alginate-g-pyrrole hydrogel that enables the decoupled control of electrical conductivity and mechanical rigidity and is use to electrically stimulate cellular endogenous proangiogenic factor expression (Chapter 6). Overall, the biomaterial systems developed in this thesis will be broadly useful for improving the quality of a wide array of molecular and cellular based

  11. Corneal Biomechanics Determination in Healthy Myopic Subjects.

    PubMed

    Qiu, Kunliang; Lu, Xuehui; Zhang, Riping; Wang, Geng; Zhang, Mingzhi

    2016-01-01

    Purpose. To determine the corneal biomechanical properties by using the Ocular Response Analyzer™ and to investigate potential factors associated with the corneal biomechanics in healthy myopic subjects. Methods. 135 eyes from 135 healthy myopic subjects were included in this cross-sectional observational study. Cornea hysteresis (CH), corneal resistance factor (CRF), cornea-compensated intraocular pressure (IOPcc), and Goldmann-correlated intraocular pressure (IOPg) were determined with the Reichert Ocular Response Analyzer (ORA). Univariate and multivariate regression analyses were performed to investigate factors associated with corneal biomechanics. Results. The mean CH and CRF were 9.82 ± 1.34 mmHg and 9.64 ± 1.57 mmHg, respectively. In univariate regression analysis, CH was significantly correlated with axial length, refraction, central corneal thickness (CCT), and IOPg (r = -0.27, 0.23, 0.45, and 0.21, resp.; all with p ≤ 0.015), but not with corneal curvature or age; CRF was significantly correlated with CCT and IOPg (r = 0.52 and 0.70, resp.; all with p < 0.001), but not with axial length/refraction, corneal curvature, or age. In multivariate regression analysis, axial length, IOPcc, and CCT were found to be independently associated with CH, while CCT and IOPg were associated with CRF. Conclusions. Both CH and CRF were positively correlated with CCT. Lower CH but not CRF was associated with increasing degree of myopia. Evaluation of corneal biomechanical properties should take CCT and myopic status into consideration. PMID:27525109

  12. Corneal Biomechanics Determination in Healthy Myopic Subjects

    PubMed Central

    Qiu, Kunliang; Lu, Xuehui; Zhang, Riping; Wang, Geng

    2016-01-01

    Purpose. To determine the corneal biomechanical properties by using the Ocular Response Analyzer™ and to investigate potential factors associated with the corneal biomechanics in healthy myopic subjects. Methods. 135 eyes from 135 healthy myopic subjects were included in this cross-sectional observational study. Cornea hysteresis (CH), corneal resistance factor (CRF), cornea-compensated intraocular pressure (IOPcc), and Goldmann-correlated intraocular pressure (IOPg) were determined with the Reichert Ocular Response Analyzer (ORA). Univariate and multivariate regression analyses were performed to investigate factors associated with corneal biomechanics. Results. The mean CH and CRF were 9.82 ± 1.34 mmHg and 9.64 ± 1.57 mmHg, respectively. In univariate regression analysis, CH was significantly correlated with axial length, refraction, central corneal thickness (CCT), and IOPg (r = −0.27, 0.23, 0.45, and 0.21, resp.; all with p ≤ 0.015), but not with corneal curvature or age; CRF was significantly correlated with CCT and IOPg (r = 0.52 and 0.70, resp.; all with p < 0.001), but not with axial length/refraction, corneal curvature, or age. In multivariate regression analysis, axial length, IOPcc, and CCT were found to be independently associated with CH, while CCT and IOPg were associated with CRF. Conclusions. Both CH and CRF were positively correlated with CCT. Lower CH but not CRF was associated with increasing degree of myopia. Evaluation of corneal biomechanical properties should take CCT and myopic status into consideration. PMID:27525109

  13. Transient increases in choroidal thickness are consistently associated with brief daily visual stimuli that inhibit ocular growth in chicks.

    PubMed

    Nickla, Debora L

    2007-05-01

    In chickens, transient changes in choroidal thickness are found in conditions in which the eye is slowing its growth in response to visual episodes that prevent excessive elongation. To test the hypothesis that the choroidal and ocular growth responses are linked, we used a variety of "brief daily" stimuli known to ameliorate the development of myopia and assessed the concurrence of the responses. If the hypothesis is true, they should always be correlated. Form deprivation w/vision or strobe. Diffusers were worn for 5 days and removed for 2h of "vision" each day in: (a) one block of 2-h (n=16); or (b) two 1-h periods (n=10). Strobe. Birds were given 0.5h episodes of 12 Hz strobe at dawn and dusk (12h apart, n=11). Negative lenses w/vision or strobe. Lenses (-10D) were worn for 5 days and removed for 2h of vision each day (n=14). Strobe. Same as above (n=11). Darkness/brief vision or myopic defocus. Birds in constant darkness were given 2 daily 0.5h episodes of light 12h apart (n=6) or one daily 0.5h episode of +10D myopic defocus (n=6) for 4 days. Darkness/"frequent" or "infrequent" myopic defocus. Birds in constant darkness were given frequent (2 min x 14) or infrequent (1 min x 7) episodes of +10D myopic defocus for 4 days. In all experiments a control group had the myopia-inducing treatment but did not receive the visual stimulation. High frequency ultrasonography was done at the start and end of the experiment, and on the last day immediately prior to and 1h after the period of stimulation. Refractive errors were measured using a Hartinger's refractometer at the end of the experiment. We found that in 7 of the 8 conditions the development of myopia was inhibited. Form deprivation: vision or strobe vs control: -1.2 and -1.8 vs -9.8D. Negative lenses: vision or strobe vs control: -1.2 and -4.3 vs -8D. Constant dark: vision or myopic defocus vs control: -0.7 and 1.8 vs -1.8D. Constant dark: frequent myopic defocus vs control: 4.8 vs -0.4D (p<0.05 for all

  14. Postnatal Chick Choroids Exhibit Increased Retinaldehyde Dehydrogenase Activity During Recovery From Form Deprivation Induced Myopia

    PubMed Central

    Harper, Angelica R.; Wang, Xiang; Moiseyev, Gennadiy; Ma, Jian-Xing; Summers, Jody A.

    2016-01-01

    Purpose Increases in retinaldehyde dehydrogenase 2 (RALDH2) transcript in the chick choroid suggest that RALDH2 may be responsible for increases observed in all-trans-retinoic acid (atRA) synthesis during recovery from myopic defocus. The purpose of the present study was to examine RALDH2 protein expression, RALDH activity, and distribution of RALDH2 cells in control and recovering chick ocular tissues. Methods Myopia was induced in White Leghorn chicks for 10 days, followed by up to 15 days of unrestricted vision (recovery). Expression of RALDH isoforms in chick ocular tissues was evaluated by Western blot. Catalytic activity of RALDH was measured in choroidal cytosol fractions using an in vitro atRA synthesis assay together with HPLC quantification of synthesized atRA. Distribution of RALDH2 cells throughout the choroid was evaluated by immunohistochemistry. Results RALDH2 was expressed predominately in the chick choroid (P < 0.001) and increased after 24 hours and 4 days of recovery (76%, 74%, and 165%, respectively; P < 0.05). Activity of RALDH was detected solely in the choroid and was elevated at 3 and 7 days of recovery compared to controls (70% and 48%, respectively; P < 0.05). The number of RALDH2 immunopositive cells in recovering choroids was increased at 24 hours and 4 to 15 days of recovery (P < 0.05) and were concentrated toward the RPE side compared to controls. Conclusions The results of this study suggest that RALDH2 is the major RALDH isoform in the chick choroid and is responsible for the increased RALDH activity seen during recovery. PMID:27654415

  15. Corneal autofluorescence in choroidal melanoma or in choroidal naevus

    PubMed Central

    Muskens, R; Van Best, J A; Bleeker, J; Keunen, J

    2001-01-01

    AIMS—To investigate whether corneal autofluorescence is different in patients with choroidal melanoma or choroidal naevus.
METHODS—Corneal autofluorescence was determined by fluorophotometry in both eyes of 32 patients with a unilateral choroidal melanoma, 32 patients with a unilateral choroidal naevus, and 32 age matched healthy controls. The corneal autofluorescence ratio between affected and contralateral eyes of patients or between randomly selected eyes of healthy controls was calculated.
RESULTS—Mean corneal autofluorescence ratio of patients with a choroidal melanoma was significantly higher than that of healthy controls (mean ratio: 1.09 (SD 0.15) and 1.00 (0.09), respectively, ANOVA p=0.014), and than that of patients with choroidal naevus (mean ratio 0.96 (0.09), p<0.001). Mean ratios of patients with choroidal naevus and healthy controls were not significantly different (p=0.27).
CONCLUSIONS—Corneal autofluorescence ratio of patients with a unilateral choroidal melanoma is increased. This is probably due to an increased flow of glucose through the impaired blood-aqueous barrier in the affected eye, resulting in additional glycation of corneal proteins and hence in increased autofluorescence. The corneal autofluorescence is not increased in patients with a choroidal naevus, because the blood-aqueous barrier is not impaired in the affected eye in these patients. Measurement of corneal autofluorescence is simple, fast, and non-invasive, and might be helpful to distinguish between patients with choroidal melanoma and those with choroidal naevus.

 PMID:11371483

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

    PubMed Central

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

    2015-01-01

    Abstract Purpose: To determine thrombospondin-2 (TSP2) expression and its impact on postnatal retinal vascular development and retinal neovascularization. Methods: 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. Results: 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. Conclusions

  17. 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

  18. 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

  19. Synthesis and Biological Evaluation of Novel Homoisoflavonoids for Retinal Neovascularization

    PubMed Central

    Lee, Hyungjun; Sulaiman, Rania S.; An, Hongchan; Magaña, Carlos; Shadmand, Mehdi; Vayl, Alexandra; Rajashekhar, Gangaraju; Kim, Eun-Yeong; Suh, Young-Ger; Lee, Kiho

    2016-01-01

    Eye diseases characterized by excessive angiogenesis such as wet age-related macular degeneration, proliferative diabetic retinopathy, and retinopathy of prematurity are major causes of blindness. Cremastranone is an anti-angiogenic, naturally occurring homoisoflavanone with efficacy in retinal and choroidal neovascularization models and antiproliferative selectivity for endothelial cells over other cell types. We undertook a cell-based structure-activity relationship study to develop more potent cremastranone analogs, with improved antiproliferative selectivity for retinal endothelial cells. Phenylalanyl-incorporated homoisoflavonoids showed improved activity and remarkable selectivity for retinal microvascular endothelial cells. A lead compound inhibited angiogenesis in vitro without inducing apoptosis, and had efficacy in the oxygen-induced retinopathy model in vivo. PMID:26035340

  20. Optical Coherence Tomography Angiography of Type 2 Neovascularization in Age-Related Macular Degeneration.

    PubMed

    Souied, Eric H; El Ameen, Ala; Semoun, Oudy; Miere, Alexandra; Querques, Giuseppe; Cohen, Salomon Yves

    2016-01-01

    Well-defined choroidal neovascularization, known as type 2 neovascularization (NV) or classic NV, is the least representative phenotype of exudative age-related macular degeneration. Clinical aspects of type 2 NV have been widely described in the literature, and to date fluorescein angiography remains the gold standard for imaging age-related macular degeneration at initial presentation. Optical coherence tomography angiography (OCT-A) can be used to image vessels based on flow characteristics without any dye injection. Type 2 NV can be visualized using OCT-A with very typical patterns. A neovascular membrane appears as either a medusa-shaped complex or a glomerulus-shaped lesion in the outer retina and the choriocapillaris layer. Furthermore, in the choriocapillaris layer, the external borders of the lesion appear as a dark ring in most cases, and one or more central feeder vessels that extend deeply into the more profound choroidal layers are visible. Identification of type 2 NV is easily feasible for any clinician using OCT-A, especially in areas where there are normally no vessels, like in subretinal space, if the interpretation rules are respected. PMID:27023798

  1. Choroidal Structure in Children with Anisohypermetropic Amblyopia Determined by Binarization of Optical Coherence Tomographic Images

    PubMed Central

    Nishi, Tomo; Ueda, Tetsuo; Mizusawa, Yuutaro; Shinomiya, Kayo; Semba, Kentaro; Mitamura, Yoshinori; Sonoda, Shozo; Uchino, Eisuke; Sakamoto, Taiji; Ogata, Nahoko

    2016-01-01

    Purpose To compare the choroidal structure of the subfoveal area in the eyes of children with anisohypermetropic amblyopia to that of the fellow eyes and to age-matched controls using a binarization method of the images obtained by enhanced depth imaging optical coherence tomography (EDI-OCT). Methods This study was performed at Nara Medical University Hospital, Tokushima University Hospital, and Kagoshima University Hospital, Japan. Forty amblyopic eyes with anisohypermetropic amblyopia and their fellow eyes (5.9 ± 2.1 years, mean ± standard deviation), and 103 age-matched controls (6.7 ± 2.4 years) were studied. The control eyes were divided into myopic, emmetropic, and hyperopic eyes. The total choroidal area, luminal area and stromal area of the subfoveal choroid were measured by the binarization method. The luminal/stromal ratio and the axial length of the amblyopic eyes were compared to that of the control eyes. Results The total choroidal area in the amblyopic eyes was significantly larger than that of the fellow eyes (P = 0.005). The luminal/stromal ratio was significantly larger in the amblyopic eyes than that of the fellow eyes (P<0.001) and the control hyperopic eyes (P<0.001). There was a significant negative correlation between the luminal/stromal ratio and the axial length in the control eyes (r = -0.30, P = 0.001), but no significant correlation was found in the amblyopic eyes. Conclusions The choroidal structure of the amblyopic eyes was different from that of the fellow and the control hyperopic eyes. The choroidal changes are related to amblyopia. PMID:27736947

  2. Sustained Delivery of a HIF-1 Antagonist for Ocular Neovascularization

    PubMed Central

    Iwase, Takeshi; Fu, Jie; Yoshida, Tsunehiko; Muramatsu, Daisuke; Miki, Akiko; Hashida, Noriyasu; Lu, Lili; Oveson, Brian; Silva, Raquel Lima e; Seidel, Christopher; Yang, Ming; Connelly, Sheila; Shen, Jikui; Han, Bing; Wu, Mingsheng; Semenza, Gregg L.; Hanes, Justin; Campochiaro, Peter A.

    2013-01-01

    Doxorubicin (DXR) and daunorubicin (DNR) inhibit hypoxia-inducible factor-1 (HIF-1) transcriptional activity by blocking its binding to DNA. Intraocular injections of DXR or DNR suppressed choroidal and retinal neovascularization (NV), but also perturbed retinal function as demonstrated by electroretinograms (ERGs). DXR was conjugated to novel copolymers of branched polyethylene glycol and poly(sebacic acid) (DXR-PSA-PEG3) and formulated into nanoparticles that when placed in aqueous buffer, slowly released small DXR-conjugates. Intraocular injection of DXR-PSA-PEG3 nanoparticles (1 or 10 μg DXR content) reduced HIF-1-responsive gene products, strongly suppressed choroidal and retinal NV, and did not cause retinal toxicity. In transgenic mice that express VEGF in photoreceptors, intraocular injection of DXR-PSA-PEG3 nanoparticles (10 μg DXR content) suppressed NV for at least 35 days. Intraocular injection of DXR-PSA-PEG3 nanoparticles (2.7 mg DXR content) in rabbits resulted in sustained DXR-conjugate release with detectable levels in aqueous humor and vitreous for at least 105 days. This study demonstrates a novel HIF-1-inhibitor-polymer conjugate formulated into controlled-release particles that maximizes efficacy and duration of activity, minimizes toxicity, and provides a promising new chemical entity for treatment of ocular NV. PMID:24126220

  3. Sustained delivery of a HIF-1 antagonist for ocular neovascularization.

    PubMed

    Iwase, Takeshi; Fu, Jie; Yoshida, Tsunehiko; Muramatsu, Daisuke; Miki, Akiko; Hashida, Noriyasu; Lu, Lili; Oveson, Brian; Lima e Silva, Raquel; Seidel, Christopher; Yang, Ming; Connelly, Sheila; Shen, Jikui; Han, Bing; Wu, Mingsheng; Semenza, Gregg L; Hanes, Justin; Campochiaro, Peter A

    2013-12-28

    Doxorubicin (DXR) and daunorubicin (DNR) inhibit hypoxia-inducible factor-1 (HIF-1) transcriptional activity by blocking its binding to DNA. Intraocular injections of DXR or DNR suppressed choroidal and retinal neovascularization (NV), but also perturbed retinal function as demonstrated by electroretinograms (ERGs). DXR was conjugated to novel copolymers of branched polyethylene glycol and poly(sebacic acid) (DXR-PSA-PEG3) and formulated into nanoparticles that when placed in aqueous buffer, slowly released small DXR-conjugates. Intraocular injection of DXR-PSA-PEG3 nanoparticles (1 or 10 μg DXR content) reduced HIF-1-responsive gene products, strongly suppressed choroidal and retinal NV, and did not cause retinal toxicity. In transgenic mice that express VEGF in photoreceptors, intraocular injection of DXR-PSA-PEG3 nanoparticles (10 μg DXR content) suppressed NV for at least 35 days. Intraocular injection of DXR-PSA-PEG3 nanoparticles (2.7 mg DXR content) in rabbits resulted in sustained DXR-conjugate release with detectable levels in aqueous humor and vitreous for at least 105 days. This study demonstrates a novel HIF-1-inhibitor-polymer conjugate formulated into controlled-release particles that maximizes efficacy and duration of activity, minimizes toxicity, and provides a promising new chemical entity for treatment of ocular NV. PMID:24126220

  4. [Diagnostics and treatment of choroidal lymphoma].

    PubMed

    Doycheva, D; Zierhut, M; Süsskind, D; Bartz-Schmidt, K U; Deuter, C

    2015-03-01

    Choroidal lymphoma is a rare disease and can be classified into primary and secondary choroidal lymphomas. Primary choroidal lymphoma is a low-grade extranodal marginal zone B-cell lymphoma and secondary choroidal lymphomas present ocular manifestations of disseminated systemic lymphomas. Typical clinical features of choroidal lymphoma are multifocal, yellow-whitish choroidal infiltrates. The vitreous body is usually clear and cell-free. Choroidal lymphoma has a tendency to extend through the sclera. In contrast to primary choroidal lymphoma, which is more often unilateral, does not show signs of anterior segment involvement and has a slow progression, secondary choroidal lymphoma is more often bilateral, has a rapidly progressive course with anterior segment and vitreous involvement and belongs to the high-grade lymphomas. The definitive diagnosis of choroidal lymphoma can only be confirmed by histopathological examination of biopsy tissue. The choroidal biopsy is the gold standard in the diagnostics of choroidal lymphoma. To date, no standardized treatment for choroidal lymphoma has been established. The treatment modalities include external beam radiotherapy, immunotherapy with rituximab and chemotherapy. The prognosis for survival of primary choroidal lymphoma is usually good. The prognosis of secondary choroidal lymphoma depends on the malignancy grade of systemic lymphoma.

  5. Neutralization of IL-23 depresses experimental ocular neovascularization.

    PubMed

    Cai, Yujuan; Tan, Wei; Shen, Xi; Zhu, Yanji; Gao, Yushuo; Sui, Ailing; Lu, Qing; Zhong, Yisheng; Xie, Bing

    2016-05-01

    Interleukin-23 (IL-23) is a heterodimeric cytokine that consists of p19, a novel subunit, and p40, which is shared by IL-12. IL-23 has been demonstrated to play an important role in autoimmunity and tumor growth. However, the role of IL-23 in ocular neovascularization (NV) diseases remains unclear. In this study, we explored the role of IL-23 in the processing of retinal and choroidal neovascularization (RNV and CNV). We found a significantly higher expression of IL-23 in the retinas with oxygen-induced retinopathy (OIR), and after neutralizing IL-23, the mRNA and protein levels of the angiogenic factors vascular endothelial growth factor receptor (VEGFR)1/FLT-1, VEGFR2/FLK-1, placental growth factor (PIGF), endothelial-specific receptor tyrosine kinase (Tie2), inducible nitric-oxide synthase (iNOS), matrix metalloproteinase (MMP) 2 and MMP9 were significantly down regulated, while the opposite trend was found for the anti-angiogenic molecules chemokine (C-X-C motif) ligand (CXCL) 9 and CXCL10. IL-23 blockade caused less NV in both the RNV and CNV mouse models. In addition, our in vitro assay showed that IL-23 alone is able to increase the ability of endothelial cells to form tubes. Our findings suggest that targeting IL-23 could be a potential therapy for RNV and CNV diseases. PMID:26980350

  6. Myopic random walkers and exclusion processes: Single and multispecies

    NASA Astrophysics Data System (ADS)

    Landman, Kerry A.; Fernando, Anthony E.

    2011-10-01

    A motility mechanism based on a simple exclusion process, where the probability of movement of an agent depends on the number of unoccupied nearest-neighbor sites is considered. Such interacting agents are termed myopic. This problem is an extension of the famous blind or myopic ant in a labyrinth problem. For the interacting agent models considered here, each agent plays the role of an ant in a labyrinth, where the paths of allowed sites though the labyrinth consist of sites not occupied by other agents. We derive a nonlinear diffusion equation for the average occupancy of the discrete agent-based model for myopic agents. In contrast, interacting blind agents have a constant probability of movement to each of their nearest-neighbor sites, giving rise to a linear diffusion equation. Insight into the various terms in the nonlinear diffusion coefficient is obtained from a study of multiple subpopulations of interacting myopic agents, where an advection-diffusion equation for each subpopulation is derived, and from tracking an individual agent within the crowd, where a motility coefficient is extracted. Averaged discrete simulation data compares very well with the solution to the continuum models. We also compare the behavior of myopic and blind agents. The myopic motility mechanism is biologically motivated to emulate information an individual cell gathers from environment cues. The multispecies model developed and investigated here assists with the interpretation of experimental data involving the tracking subpopulations of cells within a total cell population.

  7. Peripapillary choroidal thickness in Chinese children using enhanced depth imaging optical coherence tomography

    PubMed Central

    Wu, Xi-Shi; Shen, Li-Jun; Chen, Ru-Ru; Lyu, Zhe

    2016-01-01

    AIM To evaluate the peripapillary choroidal thickness (PPCT) in Chinese children, and to analyze the influencing factors. METHODS PPCT was measured with enhanced depth imaging optical coherence tomography (EDI-OCT) in 70 children (53 myopes and 17 non-myopes) aged 7 to 18y, with spherical equivalent refractive errors between 0.50 and −5.87 diopters (D). Peripapillary choroidal imaging was performed using circular scans of a diameter of 3.4 mm around the optic disc. PPCT was measured by EDI-OCT in six sectors: nasal (N), superonasal (SN), superotemporal (ST), temporal (T), inferotemporal (IT) and inferonasal (IN), as well as global RNFL thickness (G). RESULTS The mean global PPCT was 165.49±33.76 µm. The temporal, inferonasal, inferotemporal PPCT were significantly thinner than the nasal, superonasal, superotemporal segments PPCT were significantly thinner in the myopic group at temporal, superotemporal and inferotemporal segments. The axial length was significantly associated with the average global (β=−0.419, P=0.014), superonasal (β=−2.009, P=0.049) and inferonasal (β= −2.000, P=0.049) PPCT. The other factors (gender, age, SE) were not significantly associated with PPCT. CONCLUSION PPCT was thinner in the myopic group at temporal, superotemporal and inferotemporal segments. The axial length was found to be negatively correlated to PPCT. We need more further studies about the relationship between PPCT and myopia. PMID:27803863

  8. Breaking barriers: insight into the pathogenesis of neovascular age-related macular degeneration

    PubMed Central

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

    2016-01-01

    Neovascular age-related macular degeneration (AMD) is a leading cause of central visual acuity loss in a growing segment of the population, those over the age of 60 years. Treatment has improved over the last decade, with the availability of agents that inhibit the bioactivity of vascular endothelial growth factor (VEGF), but it is still limited, because of tachyphylaxis and potential risk and toxicity of anti-VEGF agents. The authors have sought to understand the mechanisms of choroidal endothelial cell (CEC) activation and transmigration of the retinal pigment epithelium (RPE) and of RPE barrier dysfunction, events preceding vision-threatening neovascular AMD. The authors developed physiologically relevant human RPE and CEC coculture and transmigration models that have been important in helping to understand causes of events in human neovascular AMD. The authors can control for interactions between these cells and can separately assess activation of signaling pathways in each cell type relevant during CEC transmigration. Using these models, it was found that VEGF, particularly the cell-associated VEGF splice variant VEGF189, accounts for about 40% of CEC transmigration across the RPE. This percentage is in the range of similar reports following clinical inhibition of VEGF in neovascular AMD. RPE VEGF189 working through CEC VEGF receptor 2 activates the small guanosine triphosphatase (GTPase) of the Rho family, Rac1, in CECs, which in turn facilitates CEC transmigration. Conversely, inhibition of Rac1 activity prevents CEC transmigration. Once activated, Rac1 aggregates with subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, resulting in the generation of reactive oxygen species. Activated NADPH oxidase increases choroidal neovascularization in animal models of laser-induced injury. Rac1 is also downstream of the eotaxin-CCR3 pathway, another pathway important in human neovascular AMD. Studies also suggest that active Ras-related protein 1

  9. The Bst locus on mouse chromosome 16 is associated with age-related subretinal neovascularization

    PubMed Central

    Smith, Richard S.; John, Simon W. M.; Zabeleta, Adriana; Davisson, Muriel T.; Hawes, Norman L.; Chang, Bo

    2000-01-01

    Ocular neovascularization is the leading cause of blindness in developed countries and often causes rapid loss of vision in age-related macular degeneration. Acute visual loss is most often due to hemorrhage from new vessels that have extended from the choroid into the subretinal space. Growth of abnormal vessels beneath the retina in this condition is known as subretinal neovascularization (SRN). Age-related animal models of macular degeneration and SRN have not been described. Current animal models of SRN depend on chemical or physical stimuli to initiate growth of subretinal vessels. The genes responsible for age-related human macular degeneration with SRN have not been firmly identified. We report an angiogenic phenotype in Bst/+ mice that is age-related, clinically evident, and resembles human SRN. This represents a spontaneous, genetically determined model of SRN. Bst/+ mice offer the possibility of exploring the molecular mechanisms of SRN without the need for exogenous agents. PMID:10681427

  10. Characteristics of peripheral refractive errors of myopic and non-myopic Chinese eyes.

    PubMed

    Chen, Xiang; Sankaridurg, Padmaja; Donovan, Les; Lin, Zhi; Li, Li; Martinez, Aldo; Holden, Brien; Ge, Jian

    2010-01-01

    Interest in peripheral refractive errors has increased as it was hypothesized that peripheral hypermetropia might provide a stimulus for axial elongation (Smith et al., 2005), this study was to determine relative peripheral refractive errors (RPRE) of the eyes of a group of Chinese children and adults. Central and peripheral (20 degrees , 30 degrees , 40 degrees at nasal, temporal, superior and inferior meridians of retina) refractive errors were obtained from cyclopleged eyes of 40 children and 42 adults with a Shin-Nippon auto-refractor. Only right eyes were considered. Central spherical equivalent (M) was used to classify the eyes as Moderate Myopia (MM, -3.00 < M < or = -6.00D), Low Myopia (LM, -0.50 < or = M < or = -3.00D), Emmetropia (E, -0.50myopic shift. The difference in the profile between the MM and LH group was significant (p<0.05). Also, the RPRE profile for MM group was different between adults and children with adult eyes showing greater amount of hypermetropic shift. Vertically, the RPRE profile of all the refractive error groups showed a myopic shift. Off-axis astigmatism increased and horizontally a shift from 'with the rule' to 'against the rule' astigmatism was observed for all groups. Our observations demonstrated that in Chinese eyes, the myopic group present a hyperopic shift in the periphery, the hypermetropic eye present a myopic shift and the emmetropic eyes present no differences to the fovea, which are similar to those reports in Caucasian eyes. The variations in the RPRE between various refractive error groups can be explained on the basis of eye shape. PMID:19825388

  11. Radiotherapy for choroidal melanoma. An 18-year experience with radon

    SciTech Connect

    Davidorf, F.H.; Pajka, J.T.; Makley, T.A. Jr.; Kartha, M.K.

    1987-03-01

    Twenty-three patients were treated with radon therapy for choroidal melanoma at the Ohio State University Hospitals, Columbus, between 1968 and 1976. We present an 18-year experience, including follow-up of at least eight years, in all those receiving therapy. Three patients (13%) died of metastatic disease. Four patients (17.4%) died of other causes. Sixteen patients (69.6%) were alive, with no signs of metastatic disease. Eight patients subsequently required enucleation due to inadequate tumor response. Of the 15 patients who demonstrated successful tumor destruction and retained their eyes, 13 (86.7%) developed substantial irradiation-induced retinopathy, including hard exudates, telangiectasias, neovascularization, microaneurysms, intraretinal and vitreous hemorrhages, secondary glaucoma, and irradiation-induced cataract. Our long-term results indicate a high incidence of both vascular complications and decreased visual acuity.

  12. Sympathetic ophthalmia complicating helium ion irradiation of a choroidal melanoma

    SciTech Connect

    Fries, P.D.; Char, D.H.; Crawford, J.B.; Waterhouse, W.

    1987-11-01

    Sympathetic ophthalmia was diagnosed 49 months after helium ion irradiation of a left choroidal melanoma. The patient maintained good vision until 18 months after therapy, when she developed neovascular glaucoma. This complication required multiple therapeutic procedures, including topical anti-inflammatory and antiglaucomatous drops, 360 degrees peripheral panretinal cryoblation, and a single 180 degrees application of inferior cyclocryotherapy over a 2 1/2-year period. Four weeks after the cyclocryotherapy, inflammation was noted in both eyes, and, one month later, enucleation of the left sympathogenic eye was performed. Serial histopathologic sections showed a full-thickness, fibrovascular, scleral scar and tantalum marker ring suture without uveal incarceration. Penetrating surgical trauma, a uveal melanoma, and multiple nonpenetrating treatments resulted in the development of sympathetic ophthalmia.

  13. Xanthogranuloma of the choroid plexus

    SciTech Connect

    Pear, B.L.

    1984-08-01

    Uncommon tumefactions known as xanthogranulomas can occur throughout the body. Some appear to develop as benign or malignant neoplasms. An even less familiar xanthogranuloma occurs within the choroid plexus. Most are tiny plaques only a few millimeters in diameter. However, they can present as masses of significant size within the glomus. When large and unilateral, they are included in the differential diagnosis of choroid plexus tumors. A computed tomographic (CT) study of such a tumor is presented.

  14. [Choroidal melanoma - evolution and prognosis].

    PubMed

    Chiruţa, Daria; Stan, Cristina

    2014-01-01

    Choroidal melanoma is the most common primary intraocular malignant tumor. We present the case of a 62 year old patient who was diagnosed with intraocular tumor in his right eye, for about three years. Regarding the fact that the patient refused any kind of treatment during this period, we just had the opportunity to monitor this case. Finally, the diagnosis was choroidal melanoma, confirmed by the histopathological exam.

  15. Chick eyes compensate for chromatic simulations of hyperopic and myopic defocus: evidence that the eye uses longitudinal chromatic aberration to guide eye-growth.

    PubMed

    Rucker, Frances J; Wallman, Josh

    2009-07-01

    Longitudinal chromatic aberration (LCA) causes short wavelengths to be focused in front of long wavelengths. This chromatic signal is evidently used to guide ocular accommodation. We asked whether chick eyes exposed to static gratings simulating the chromatic effects of myopic or hyperopic defocus would "compensate" for the simulated defocus. We alternately exposed one eye of each chick to a sine-wave grating (5 or 2 cycle/deg) simulating myopic defocus ("MY defocus": image focused in front of retina; hence, red contrast higher than blue) and the other eye to a grating of the same spatial frequency simulating hyperopic defocus ("HY defocus": blue contrast higher than red). The chicks were placed in a drum with one eye covered with one grating, and then switched to another drum with the other grating with the other eye covered. To minimize the effects of altered eye-growth on image contrast, we studied only the earliest responses: first, we measured changes in choroidal thickness 45 min to 1 h after one 15-min episode in the drum, then we measured glycosaminoglycans (GAG) synthesis in sclera and choroid (by the incorporation of labeled sulfate in tissue culture) after a day of four 30-min episodes in the drum. The eyes compensated in the appropriate directions: The choroids of the eyes exposed to the HY simulation showed significantly more thinning (less thickening) over the course of the experiment than the choroids of the eyes exposed to the MY simulation (all groups mean:-17 microm; 5 c/d groups: -24 microm; paired t-test (one-tailed): p=0.0006). The rate of scleral GAG synthesis in the eye exposed to the HY simulation was significantly greater than in the eye exposed to the MY simulation (HY/MY ratio=1.20; one sample t-test (one-tailed): p=0.015). There was no significant interaction between the sign of the simulated defocus and either the spatial frequency or the presence of a +3 D lens used to compensate for the 33 cm distance of the drum. Although previous

  16. Heterotypic RPE-choroidal endothelial cell contact increases choroidal endothelial cell transmigration via PI 3-kinase and Rac1

    PubMed Central

    Peterson, Lynda J.; Wittchen, Erika S.; Geisen, Pete; Burridge, Keith; Hartnett, M. Elizabeth

    2008-01-01

    Age-related macular degeneration (AMD) is the major cause of non-preventable blindness. Severe forms of AMD involve breaching of the retinal pigment epithelial (RPE) barrier by underlying choroidal endothelial cells (CECs), followed by migration into, and subsequent neovascularization of the neurosensory retina. However, little is known about the interactions between RPE and CECs and the signaling events leading to CEC transmigration. While soluble chemotactic factors secreted from RPE can contribute to inappropriate CEC transmigration, other unidentified stimuli may play an additional role. Using a coculture model that maintains the natural structural orientation of CECs to the basal aspect of RPE, we show that “contact” with RPE and/or RPE extracellular matrix increases CEC transmigration of the RPE barrier. From a biochemical standpoint, contact between CECs and RPE results in an increase in the activity of the GTPase Rac1 within the CECs; this increase is dependent on upstream activation of PI 3-K and Akt1. To confirm a link between these signaling molecules and increased CEC transmigration, we performed transmigration assays while inhibiting both PI 3-K and Rac1 activity, and observed that both decreased CEC transmigration. We hypothesize that contact between CECs and RPE stimulates a signaling pathway involving PI 3-K, Akt1, and Rac1 that facilitates CEC transmigration across the RPE barrier, an important step in the development of neovascular AMD. PMID:17292356

  17. A Case of Diode Laser Photocoagulation in the Treatment of Choroidal Metastasis of Breast Carcinoma

    PubMed Central

    Lee, Sang Joon; Kim, Soo Young

    2008-01-01

    To report a single case of improvement on choroidal metastasis of breast cancer after laser photocoagulation. A 52-year-old female patient who complained of visual disturbance of the right eye with multiple states of metastasis of breast carcinoma. On initial examination, the right best-corrected visual acuity was 0.63. Right fundoscopy revealed an elevated mass-like lesion temporal to the macule with serous retinal detachment. The mass had a 3.5-disc diameter. A right fluorescein angiogram revealed hypofluorescence during the prearterial and arteriovenous phase and hyperfluorescence during the venous phase. The venous phase showed almost total masking of background choroidal fluorescence at the elevated lesion because of leakage and neovascularization. The patient was treated 4 times by diode laser photocoagulation in addition to chemotherapy. Fifty days after the diode laser treatments, the funduscopy examination and fluorescein angiogram revealed that the serous retinal detachment had been absorbed, the choroid had become flat, the lesion had been reduced in size and hyperfluorescence. The right best-corrected visual acuity was improved to 0.8. Laser photocoagulation appears not to cause any problems for the patient and may be an efficient treatment for patients with choroidal breast carcinoma. PMID:18784448

  18. 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

  19. Tamponade or Filling Effect: Changes of Forces in Myopic Eyes

    PubMed Central

    Morescalchi, Francesco; Romano, Mario R.

    2014-01-01

    Myopia is the most common ocular abnormality. Its high and growing prevalence has contributed to a recent surge in surgical interest in the disorder, since retinal detachment in eyes with high myopia differs from that in emmetropic eyes or eyes with low myopia. The myopic eye, because of its specific anatomy, poses special challenges that need to be overcome to ensure the appropriate use of vitreous substitutes. However, intraocular tamponades have shown great potential for revolutionizing retinal detachment surgery and vitreomacular surgery in general in myopic eyes. We provide an updated review of the clinical use of vitreous substitutes in the myopic eye, paying particular attention to analyzing the ideal function of endotamponade agents and comparing the effects of these agents on the physical and biological properties of the eye. PMID:25101290

  20. Retinoic acid metabolic change in retina and choroid of the guinea pig with lens-induced myopia

    PubMed Central

    Mao, Jun-Feng; Liu, Shuang-Zhen; Dou, Xiu-Qiong

    2012-01-01

    AIM To investigate the role of retinoic acid (RA) and retinaldehyde dehydrogenase-2 (RALDH2) of retina and choroid in the guinea pig lens-induced myopic eyes. METHODS Totally 45 guinea pigs, at age of three weeks, were randomly assigned into three groups: the normal control, the lens-induced group and the recovering group. Out of focus was induced by the -6.00D concave lens on the left eye, and lasted for 15 days. All animals underwent biometric measurement (corneal radius of curvature, refraction and axial length). Subsequently, RA content in the retina and RPE/choriod complex was detected by reversed-phase high-performance liquid chromatography. RALDH2 protein in the retina and RPE/choriod complex was evaluated by the immunohistochemical staining and Western blotting. RESULTS After wearing -6.00D lens for 15 days, axial length of the lens-induced eye extends and myopia was formed, with RA contents increasing in both the neural retina and RPE/choroid complex. Comparing with the lens-induced group, myopic degree significantly relieved, and its RA contents in both the neural retina and RPE/choroid complex decreased in the recovering group. In the normal control, RALDH2 protein was expressed positively in the retinal nerve fiber layer (RNFL), inner plexiform layer (IPL) and lateral border of outer nuclear layer (ONL). Retinal RALDH2 protein increased in the lens-induced group, and was also positive in the outer plexiform layer (OPL). In the recovering group, retinal RALDH2 protein attenuated the expression in the OPL turns to negative. RALDH2 protein was not expressed in the choroid of any group. CONCLUSION RA of retina and chorid participates in the regulation of the lens-induced myopia in guinea pigs, which may be related with retinal RALDH2 protein. PMID:23275899

  1. Morphometry of the myopic optic nerve head using FDOCT

    NASA Astrophysics Data System (ADS)

    Lee, Sieun; Young, Mei; Lebed, Evgeniy; Mackenzie, Paul J.; Beg, Mirza F.; Sarunic, Marinko V.

    2011-03-01

    In this paper we present imaging and morphometric analysis of a myopic Optic Nerve Head (ONH) using an 830nm wavelength Fourier domain optical coherence tomography system. The thinner prelaminar neural tissue and shallower optic cup in the myopic subject allows visualization of the tissue structures such as anterior laminar surface and lamina cribrosa that are often challenging to image due to their depth. From these structures we measured volumetric anatomical parameters and topographical tissue thickness correlated with glaucomatous structural damage in the ONH.

  2. Implanted Microvessels Progress through Distinct Neovascularization Phenotypes

    PubMed Central

    Nunes, Sara S.; Greer, Kevin A.; Stiening, Chad M.; Chen, Helen YS.; Kidd, Kameha R.; Schwartz, Mark A; Sullivan, Chris J.; Rekapally, Harish; Hoying, James B.

    2009-01-01

    We have previously demonstrated that implanted microvessels form a new microcirculation with minimal host-derived vessel investment. Our objective was to define the vascular phenotypes present during neovascularization in these implants and identify post-angiogenesis events. Morphological, functional and transcriptional assessments identified three distinct vascular phenotypes in the implants: sprouting angiogenesis, neovascular remodeling, and network maturation. A sprouting angiogenic phenotype appeared first, characterized by high proliferation and low mural cell coverage. This was followed by a neovascular remodeling phenotype characterized by a perfused, poorly organized neovascular network, reduced proliferation, and re-associated mural cells. The last phenotype included a vascular network organized into a stereotypical tree structure containing vessels with normal perivascular cell associations. In addition, proliferation was low and was restricted to the walls of larger microvessels. The transition from angiogenesis to neovascular remodeling coincided with the appearance of blood flow in the implant neovasculature. Analysis of vascular-specific and global gene expression indicates that the intermediate, neovascular remodeling phenotype is transcriptionally distinct from the other two phenotypes. Therefore, this vascular phenotype likely is not simply a transitional phenotype but a distinct vascular phenotype involving unique cellular and vascular processes. Furthermore, this neovascular remodeling phase may be a normal aspect of the general neovascularization process. Given that this phenotype is arguably dysfunctional, many of the microvasculatures present within compromised or diseased tissues may not represent a failure to progress appropriately through a normally occurring neovascularization phenotype. PMID:19833141

  3. [A new approach for studying the retinal and choroidal circulation].

    PubMed

    Yoneya, Shin

    2004-12-01

    mixed with phospholipid, free cholesterol, esterified cholesterol, and triacrylglycerol were observed with the ICG fundus video system. Both electrophoretic studies showed that ICG bound intensely to HDL and moderately to LDL, and only the solution with phospholipid fluoresced brightly when observed with the ICG fundus video system. 2. Residual fundus ICG fluorescence: Residual fundus fluorescence observed in the late phase of ICG angiography may be delineated differently in normal subjects and in patients with age-related macular degeneration (ARMD). We performed ICG angiography on 8 normal subjects aged below 36 years (8 eyes), 9 normal subjects aged above 62 years (9 eyes), and 21 patients with ARMD aged 50 to 88 years (37 eyes). The intensity and pattern of fluorescence from angiograms obtained in the ultra-late phase, 24 hours after dye injection, was recorded and analyzed. In the ultra-late phase, 95% of ARMD eyes with choroidal neovascularization (CNV) showed geographic hypofluorescent lesions. These hypofluorescent lesions occurred in 73% of ARMD eyes without CN, while age-matched normal subjects had no hypofluorescent lesions. The mean intensity of fluorescence in the normal elder subject group was significantly higher than that seen in the normal younger subject group. These findings may reflect aging change and bio-distribution of lipid on the Bruch-RPE complex. 3. The early dye filling pattern of the choroid: We performed ICG angiography on 10 healthy young volunteers aged 22 to 26 years (23.4+/-1.3; mean+/-standard deviation) using an improved ICG video camera system. ICG (50 mg) dissolved in 2 ml in distilled water was injected through the antecubital vein. Although the choroidal dye filling varied among subjects, it always began in the macular area. In the 10 subjects, initial dye filling had two patterns: reticular (n=8) and flush (n=2). The choroidal circulation filled completely before the retinal circulation did. Bright fluorescence in the macula and

  4. [Neovascular glaucoma--etipathogeny and diagnosis].

    PubMed

    Călugăru, D; Călugăru, M

    2012-01-01

    Neovascular glaucoma is defined as an iris and/or anterior chamber angle neovascularization associated with increased intraocular presure. It is a secondary glaucoma most frequently determined by a severe retinal ischemia. The most common diseases responsible for the development of neovascular glaucoma are diabetic retinopathy, ischemic central retinal vein occlusion and ocular ischemic syndrome; the uncommon causes include ocular radiation, ocular tumors, uveitis and other miscellaneous conditions. Vascular endothelial growth factor is an important and probably predominant agent in the pathogenesis of both intraocular neovascularization and neovascular glaucoma. The evolution of clinical and histopathological changes from predisposing conditions to the occurrence of rubeosis iridis as well as neovacular glaucoma is divided into four grades that is prerubeotic, preglaucomatous, open-angle and angle closure glaucoma stages.

  5. The Choroid and Optical Coherence Tomography

    PubMed Central

    Sezer, Taha; Altınışık, Muhammet; Koytak, İbrahim Arif; Özdemir, Mehmet Hakan

    2016-01-01

    The choroid is the most vascular tissue in the eye and it plays an important role in the pathophysiology of various common chorioretinal diseases such as central serous retinopathy, age-related macular degeneration and degenerative myopia. Quantitative assessment of the choroid has been quite challenging with traditional imaging modalities such as indocyanine green angiography and ultrasonography due to limited resolution and repeatability. With the advent of optical coherence tomography (OCT) technology, detailed visualization of the choroid in vivo is now possible. Measurements of choroidal thickness have also enabled new directions in research to study normal and pathological processes within the choroid. The aim of the present study is to review the current literature on choroidal imaging using OCT. PMID:27800255

  6. In vivo ZW800-microbead imaging of retinal and choroidal vascular leakage in mice.

    PubMed

    Gupta, Isha; Cahoon, Judd; Zhang, Xiaohui; Jones, Alex D; Ahmed, Faisal; Uehara, Hironori; Messenger, Wyatt; Ambati, Balamurali K

    2015-05-01

    The eye is an attractive organ for non-invasive discovery and monitoring of disease progression. Traditionally, fluorescein angiography (FA) and indocyanine green angiography (ICGA) have been used for dynamic evaluation of the retina and its vasculature. However, both fluorescein and indocyanine green (ICG) possess considerable disadvantages. FA is limited to assessing superficial retinal blood flow and often results in an unclear view due to fluorescein leakage. This obscures important pathologies such as neovascularization, ischemia and inflammation. ICG, a near-infrared fluorophore (NIRF), has nonspecific binding, high uptake and retention in tissues, as well as detrimental effects on the hepatobiliary tract. Here, we present a potential contrast agent for imaging ocular vascular permeability with ZW800, a heptamethine indocyanine NIRF, conjugated to polystyrene latex beads (ZW800m). ZW800 is an excellent alternative for near-infrared imaging, as it has excellent contrast, superior clearance, and is amendable to conjugation. ZW800m conjugation is an easy, attractive method of in vivo imaging and real-time tracking of ocular vascular pathologies. ZW800m is readily imaged via commercially available laser ophthalmoscope (SLO, HRA OCT, Spectralis) to assess vascular permeability in the mouse retina and choroid. In Type 1 diabetic Ins2Akita mice, ZW800m was observed in mouse retina but not in wild-type mice. After laser-induced choroidal neovascularization (CNV), ZW800m was observed in mouse choroid but not in control. In both CNV and diabetic mice, ZW800 imaging showed increased hyperfluorescence on ICG modality (ICGA) not seen on FA. Presence of ZW800m in respective tissues was confirmed ex vivo with flatmounts visualized with EVOS 800 nm light cube. ZW800 imaging may be easily employed in the research laboratory.

  7. Cooperation enhanced by moderate tolerance ranges in myopically selective interactions

    NASA Astrophysics Data System (ADS)

    Chen, Xiaojie; Wang, Long

    2009-10-01

    We present a mode of myopically selective interaction to study the evolutionary prisoner’s dilemma game in scale-free networks. Each individual has a reputation-based tolerance range and only tends to interact with the neighbors whose reputation is within its tolerance range. Moreover, its reputation is assessed in response to the interactions in the neighborhood. Interestingly, we show that moderate values of tolerance range can result in the best promotion of cooperation due to the emergence of group selection mechanism. Furthermore, we study the effects of weighting factor in the assessment rule of reputation on the evolution of cooperation. We also show how cooperation evolves in some extended situations, where an interaction stimulus payment is considered for individuals, and where the strategy and reputation of individuals can spread simultaneously. Our results may enhance the understanding of evolutionary dynamics in graph-structured populations where individuals conditionally play with their neighbors according to some myopic selection criteria.

  8. Peripheral refractive errors in myopic, emmetropic, and hyperopic young subjects

    NASA Astrophysics Data System (ADS)

    Seidemann, Anne; Schaeffel, Frank; Guirao, Antonio; Lopez-Gil, Noberto; Artal, Pablo

    2002-12-01

    To gain more insight into the relationship between foveal and peripheral refractive errors in humans, spheres, cylinders, and their axes were binocularly measured across the visual field in myopic, emmetropic, and hyperopic groups of young subjects. Both automated infrared photorefraction (the ``PowerRefractor'' www. plusoptix.de) and a double-pass technique were used because the PowerRefractor provided extensive data from the central 44 deg of the visual field in a very convenient and fast way. Two-dimensional maps for the average cross cylinders and spherical equivalents, as well as for the axes of the power meridians of the cylinders, were created. A small amount of lower-field myopia was detected with a significant vertical gradient in spherical equivalents. In the central visual field there was little difference among the three refractive groups. The established double-pass technique provided complementary data also from the far periphery. At 45 deg eccentricity the double-pass technique revealed relatively more hyperopic spherical equivalents in myopic subjects than in emmetropic subjects [+/-2.73+/-2.85 D relative to the fovea, p<0.01 (+/-standard deviation)] and more myopic spherical equivalents in hyperopic subjects (-3.84+/-2.86 D relative to the fovea, p<0.01). Owing to the pronounced peripheral astigmatism, spherical equivalents (refractions with respect to the plane of the circle of least confusion) became myopic relative to the fovea in all three groups. The finding of general peripheral myopia was unexpected. Its possible roles in foveal refractive development are discussed.

  9. Spectral-Domain Optical Coherence Tomography of Polypoidal Choroidal Vasculopathy Associated With Benign Choroidal Nevus.

    PubMed

    De Salvo, Gabriella; Vaz-Pereira, Sara; Sehmi, Kulwant S; Andrews, Richard M; Sagoo, Mandeep S

    2015-01-01

    Two cases of polypoidal choroidal vasculopathy (PCV) complicating benign choroidal nevus and their tomographic features at spectral-domain optical coherence tomography (SD-OCT) are reported. Two eyes with choroidal nevus and associated subretinal fluid underwent complete ophthalmological examination, SD-OCT, fundus fluorescein angiography, and indocyanine green angiography (ICGA). SD-OCT and ICGA confirmed the diagnosis of PCV in both cases. Ophthalmologists should be aware of this rare combination between choroidal nevus and PCV. If a choroidal nevus presents with subretinal fluid, this does not always herald malignant transformation, and PCV should be ruled out so that the correct treatment can be planned.

  10. Effect of irradiation on neovascularization in rat skinfold chambers: Implications for clinical trials of low-dose radiotherapy for wet-type age-related macular degeneration

    SciTech Connect

    Hori, Katsuyoshi . E-mail: k-hori@idac.tohoku.ac.jp; Saito, Sachiko; Tamai, Makoto

    2004-12-01

    Purpose: Wet-type age-related macular degeneration is a refractory eye disease that involves choroidal neovascularization. Randomized controlled trials of low-dose radiotherapy for this disease performed in Japan showed that, at 12 months of follow-up, visual acuity was significantly well preserved and the neovascular membrane size decreased. Because understanding the effect of irradiation on new vascular networks is an important prerequisite for clinical trials, we used a rat skinfold chamber technique to investigate X-ray-induced changes in neovasculature microcirculation. Methods and materials: Neovascularization was induced in rat skinfold chambers via polyvinyl chloride resin plates. Neovessels were irradiated in a single 10-Gy dose, after which, changes in vascular density, blood velocity, tissue blood flow, and interstitial fluid pressure (IFP), were measured. Results: Vascular density, tissue blood flow, and IFP measurements in resin-induced inflammatory tissue were much higher than those measurements in normal tissue. Although overall blood velocity was low and sluggish or blood-flow stasis occurred in the neovascular network, after a single 10-Gy dose of radiation, the velocity increased, stasis improved markedly, and many dilated vessels narrowed. Thereafter, vascular density, blood flow, and IFP significantly decreased and approached normal values. Conclusion: These findings may help explain clinical results related to radiotherapy-induced changes in neovascular membranes in age-related macular degeneration. Both vascular morphology and vascular function in inflammatory tissue returned to normal, without vessel destruction, after an appropriate radiation dose.

  11. 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

  12. Focal choroidal excavation: a preliminary interpretation based on clinic and review

    PubMed Central

    Liu, Guang-Hui; Lin, Bing; Sun, Xin-Quan; He, Zi-Fang; Li, Ji-Rong; Zhou, Rong; Liu, Xiao-Ling

    2015-01-01

    AIM To describe the clinical and imaging characteristics associated with focal choroidal excavation (FCE), analyze the possible complication, and interpret its probable etiopathogenesis. METHODS Retrospective descriptive case series of 37 eyes of 32 patients with FCE. Findings of spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography, indocyanine green angiography, and clinical features were analyzed. RESULTS All patients were Chinese. Five patients (15.6%) were bilaterally involved. Patients' ages ranged from 7 to 66y. Refractive error ranged between +2.0 D and −11.0 D. Mean best-corrected visual acuity was 0.6 (range, 0.1 to 1.2). Fundus examinations exhibited mild-moderate localized pigmentary disturbances in the corresponding area of 17 eyes. Fluorescein angiography performed in 18 patients showed varying degrees of hyperfluorescence and hypofluorescence related to a range of retinal pigment epithelium (RPE) alterations. Indocyanine green angiography performed in 7 patients showed hypofluorescence at the excavation. SD-OCT demonstrated choroidal excavation in all 37 eyes. Twenty-nine eyes showed a single lesion of FCE, and three eyes showed 2-3 separated lesions. Fifteen eyes showed separation between the photoreceptor tips and RPE consistent with nonconforming FCE. Central serous chorioretinopathy (CSC, n=1) and choroidal neovascularization (CNV, n=1) developed during follow-up. CONCLUSION FCE could be interpreted as congenital focal choroidal dysplasia involving the RPE, choriocapillaris, and photoreceptor associated with the faulty anatomy. The abnormal anatomy of FCE was similar to anatomy at risk of CSC and CNV. PMID:26086000

  13. Choroidal Metastases From Cutaneous Melanoma.

    PubMed

    Mercado, Carmel L; Toy, Brian C; Kistler, Henry B; Moshfeghi, Darius M

    2016-05-01

    A 92-year-old man presented with months of progressive blurry vision, worsening acutely in his right eye. He denied pain, diplopia, or photopsias. His history was significant for multiple myeloma, prostate cancer, and malignant melanoma of his right shoulder treated with local excision. He had local recurrence with hepatic metastasis of the melanoma treated with radiation and chemotherapy. On examination, his visual acuity was counting fingers in the right eye and 20/60 in the left eye. Amsler grid testing demonstrated metamorphopsia in the right eye. Fundus exam of the right and left eyes revealed multiple, elevated, pigmented choroidal lesions, with associated subretinal fluid in the right macula. This appearance is consistent with hematogenous metastasis of cutaneous malignant melanoma to the choroid and associated serous fluid-causing metamorphopsia. The patient was enrolled in a clinical trial combining plasmid IL-12 with pembrolizumab (Keytruda; Merck, Whitehouse Station, NJ). He passed away 2 months after initial presentation to our clinic. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:497.]. PMID:27183558

  14. Causes and treatment of choroidal effusion after glaucoma surgery.

    PubMed

    Bakir, Belal; Pasquale, Louis R

    2014-01-01

    Choroidal effusion is a prevalent and potentially vision-threatening complication following glaucoma surgery. This review article will introduce readers to the anatomy and physiology of choroidal effusion. Evidence from the literature will be reviewed to discuss the prevalence of choroidal effusion after glaucoma surgery. Etiology, clinical presentation, and differential diagnosis of choroidal effusion will be detailed in this review article. Finally, readers will gain insight into methods to prevent and treat choroidal effusion after glaucoma surgery.

  15. Acute transient myopic shift induced by red wine: a case report.

    PubMed

    Liu, Ziyuan; Wang, Wei

    2015-01-01

    This case report described a patient presenting with unilateral transient myopic shift after consuming a lot of red wine. Ultrasound biomicroscopy detected annular shallow ciliary body detachment with supraciliary effusion, as well as a narrow chamber angle. The myopic shift was spontaneously resolved about one week after the onset without any treatment.

  16. [Laser correction of myopia and myopic astigmatism in children--literature review].

    PubMed

    Mrukwa-Kominek, Ewa; Gierek-Ciaciura, Stanisława

    2003-01-01

    Anisometropic myopia and myopic astigmatism are very often refractive error in children. Suitable correction of different vision defects in children might prevent the consequences of amblyopia and lack of development of binocular vision. This article presents the effectiveness of correction in myopia and myopic anisometropia using laser method such as PRK, LASEK and LASIK. It is the literature review. PMID:15049271

  17. Carboxyethylpyrrole oxidative protein modifications stimulate neovascularization: Implications for age-related macular degeneration

    PubMed Central

    Ebrahem, Quteba; Renganathan, Kutralanathan; Sears, Jonathan; Vasanji, Amit; Gu, Xiaorong; Lu, Liang; Salomon, Robert G.; Crabb, John W.; Anand-Apte, Bela

    2006-01-01

    Choroidal neovascularization (CNV), the advanced stage of age-related macular degeneration (AMD), accounts for >80% of vision loss in AMD. Carboxyethylpyrrole (CEP) protein modifications, uniquely generated from oxidation of docosahexaenoate-containing lipids, are more abundant in Bruch’s membrane from AMD eyes. We tested the hypothesis that CEP protein adducts stimulate angiogenesis and possibly contribute to CNV in AMD. Human serum albumin (HSA) or acetyl-Gly-Lys-O-methyl ester (dipeptide) were chemically modified to yield CEP-modified HSA (CEP-HSA) or CEP-dipeptide. The in vivo angiogenic properties of CEP-HSA and CEP-dipeptide were demonstrated by using the chick chorioallantoic membrane and rat corneal micropocket assays. Low picomole amounts of CEP-HSA and CEP-dipeptide stimulated neovascularization. Monoclonal anti-CEP antibody neutralized limbal vessel growth stimulated by CEP-HSA, whereas anti-VEGF antibody was found to only partially neutralize vessel growth. Subretinal injections of CEP-modified mouse serum albumin exacerbated laser-induced CNV in mice. In vitro treatments of human retinal pigment epithelial cells with CEP-dipeptide or CEP-HSA did not induce increased VEGF secretion. Overall, these results suggest that CEP-induced angiogenesis utilizes VEGF-independent pathways and that anti-CEP therapeutic modalities might be of value in limiting CNV in AMD. PMID:16938854

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

    PubMed

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

    2016-01-01

    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. PMID:27137488

  19. Excimer laser surgery for myopia and myopic astigmatism.

    PubMed

    Hadden, O B; Morris, A T; Ring, C P

    1995-08-01

    Photorefractive keratectomy using the Summit Excimer Laser has been carried out on 1333 eyes with myopia or myopic astigmatism which have been followed up for six months or longer. Of those, 607 have been followed up for one year. Of the eyes with myopia or myopic astigmatism of up to 3 dioptres spherical equivalent, at one year 85.6% had unaided vision of 6/6, 97.2% 6/9 or better, and 99.4% 6/12 or better. Of the eyes between -3.25 and -6.00 dioptres spherical equivalent at one year 72.1% achieved 6/6 vision unaided, 88.8% 6/9 or better, and 94.2% 6/12 or better. Of the eyes between -6.25 and -10.00 dioptres, at one year 49.6% achieved 6/6 vision unaided, 76.1% 6/9 or better and 88.0% 6/12 or better. To achieve these figures, 28% of the patients had astigmatic keratotomy, either two or three weeks before photorefractive keratectomy, or at the same time as photorefractive keratectomy. Photorefractive keratectomy is as predictable as radial keratotomy in eyes of under 6 dioptres myopia, but is more predictable than radial keratotomy in higher myopia. Photorefractive keratectomy has the advantages of leaving an eye which is structurally sound, and without diurnal variation of focusing. PMID:8534441

  20. Carbon-ion radiotherapy for locally advanced or unfavorably located choroidal melanoma: A Phase I/II dose-escalation study

    SciTech Connect

    Tsuji, Hiroshi . E-mail: h_tsuji@nirs.go.jp; Ishikawa, Hitoshi; Yanagi, Takeshi; Hirasawa, Naoki; Kamada, Tadashi; Mizoe, Jun-Etsu; Kanai, Tatsuaki; Tsujii, Hirohiko; Ohnishi, Yoshitaka

    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 neovascular 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.

  1. [Corneal neovascularization: epidemiological, physiopathological, and clinical features].

    PubMed

    Benayoun, Y; Casse, G; Forte, R; Dallaudière, B; Adenis, J-P; Robert, P-Y

    2013-09-01

    Corneal neovascularization is defined as the presence of vessels within the normally avascular corneal stroma. This physiopathological process is the consequence of local hyper-expression of pro-angiogenic factors in response to tissue damage. These new vessels (neovessels), initially immature and poorly developed, predispose the cornea to lipid exudation, inflammation, and scarring. Additionally, the influx of vascular cells into the stroma induces a loss of the cornea's immune privilege, resulting in a higher rate of graft rejection. In this literature review, we touch on epidemiological, physiopathological, and clinical aspects of corneal neovascularization, as well as secondary complications.

  2. Host immune cellular reactions in corneal neovascularization

    PubMed Central

    Abdelfattah, Nizar S.; Amgad, Mohamed; Zayed, Amira A

    2016-01-01

    Corneal neovascularization (CNV) is a global important cause of visual impairment. The immune mechanisms leading to corneal heme- and lymphangiogenesis have been extensively studied over the past years as more attempts were made to develop better prophylactic and therapeutic measures. This article aims to discuss immune cells of particular relevance to CNV, with a focus on macrophages, Th17 cells, dendritic cells and the underlying immunology of common pathologies involving neovascularization of the cornea. Hopefully, a thorough understanding of these topics would propel the efforts to halt the detrimental effects of CNV. PMID:27162740

  3. Idiopathic Peripapillary Subretinal Neovascular Membrane in a Young Woman with Recurrence of the Lesion during Pregnancy after Treatment with Intravitreal Bevacizumab

    PubMed Central

    Al-Gharbi, Nasra; Al Abdulsalam, Omar; Al Habash, Ahmed

    2015-01-01

    We report a 27-year-old woman who was diagnosed with idiopathic peripapillary subretinal neovascular membrane (PSRNVM) in her left eye with best-corrected visual acuity (BCVA) of 20/160. She had been treated by three monthly doses of intravitreal bevacizumab (1.25 mg/0.05 ml) at 4-week intervals, which showed a favorable response. The treatment led to regression of the choroidal neovascular membrane (CNVM) with complete resorption of subretinal fluid and improvement of BCVA to 20/25. Subsequently, recurrence of the CNVM was observed during pregnancy (28 months after treatment). To the best of our knowledge, this is the first report of recurrence of idiopathic PSRNVM during pregnancy. PMID:25949086

  4. Neovascularization within porous PEG hydrogels

    NASA Astrophysics Data System (ADS)

    Chiu, Yu-Chieh

    interactions with substrate surfaces. The results presented here describe various techniques that can be used to optimize the design of polymer scaffolds for tissue engineering. Future studies should investigate the optimization of these material techniques for control of neovascularization within PEG hydrogels for tissue engineering applications.

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

    SciTech Connect

    Dunavoelgyi, Roman; Dieckmann, Karin; Gleiss, Andreas; Sacu, Stefan; Kircher, Karl; Georgopoulos, Michael; Georg, Dietmar; Zehetmayer, Martin; Poetter, Richard

    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. 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.

  6. Post-LASIK myopic shift after a trek in the North Pole.

    PubMed

    Fam, Han-Bor; Goh, E-Shawn; Lee, Hung-Ming; Lim, Kooi-Ling

    2005-01-01

    Bilateral laser in situ keratomileusis was performed in a 37-year-old male ethnic Chinese adventurer. Eight weeks postoperatively, the patient made an unassisted trek to the geographic North Pole. After 2 weeks in this environment, a myopic shift of more than -1.50 diopters occurred in both eyes. The myopic shift resolved over 2 months when the patient returned to a tropical climate. Using Orbscan corneal topography, we propose that the myopic shift was attributed to biomechanical changes in the cornea induced by corneal dehydration in the Arctic environment.

  7. Corneal Neovascularization: An Anti-VEGF Therapy Review

    PubMed Central

    Chang, Jin-Hong; Garg, Nitin K.; Lunde, Elisa; Han, Kyu-Yeon; Jain, Sandeep; Azar, Dimitri T.

    2013-01-01

    Corneal neovascularization is a serious condition that can lead to a profound decline in vision. The abnormal vessels block light, cause corneal scarring, compromise visual acuity, and may lead to inflammation and edema. Corneal neovascularization occurs when the balance between angiogenic and antiangiogenic factors is tipped toward angiogenic molecules. Vascular endothelial growth factor (VEGF), one of the most important mediators of angiogenesis, is upregulated during neovascularization. In fact, anti-VEGF agents have efficacy in the treatment of neovascular age-related macular degeneration, diabetic retinopathy, macular edema, neovascular glaucoma, and other neovascular diseases. These same agents have great potential for the treatment of corneal neovascularization. We review some of the most promising anti-VEGF therapies, including bevacizumab, VEGF trap, siRNA, and tyrosine kinase inhibitors. PMID:22898649

  8. Cerebral neovascularization in diabetes: implications for stroke recovery and beyond.

    PubMed

    Ergul, Adviye; Abdelsaid, Mohammed; Fouda, Abdelrahman Y; Fagan, Susan C

    2014-04-01

    Neovascularization is an innate physiologic response by which tissues respond to various stimuli through collateral remodeling (arteriogenesis) and new vessel formation from existing vessels (angiogenesis) or from endothelial progenitor cells (vasculogenesis). Diabetes has a major impact on the neovascularization process but the response varies between different organ systems. While excessive angiogenesis complicates diabetic retinopathy, impaired neovascularization contributes to coronary and peripheral complications of diabetes. How diabetes influences cerebral neovascularization remained unresolved until recently. Diabetes is also a major risk factor for stroke and poor recovery after stroke. In this review, we discuss the impact of diabetes, stroke, and diabetic stroke on cerebral neovascularization, explore potential mechanisms involved in diabetes-mediated neovascularization as well as the effects of the diabetic milieu on poststroke neovascularization and recovery, and finally discuss the clinical implications of these effects. PMID:24496174

  9. Optical microangiography of retina and choroid and measurement of total retinal blood flow in mice

    PubMed Central

    Zhi, Zhongwei; Yin, Xin; Dziennis, Suzan; Wietecha, Tomasz; Hudkins, Kelly L.; Alpers, Charles E.; Wang, Ruikang K

    2012-01-01

    We present a novel application of optical microangiography (OMAG) imaging technique for visualization of depth-resolved vascular network within retina and choroid as well as measurement of total retinal blood flow in mice. A fast speed spectral domain OCT imaging system at 820nm with a line scan rate of 140 kHz was developed to image the posterior segment of eyes in mice. By applying an OMAG algorithm to extract the moving blood flow signals out of the background tissue, we are able to provide true capillary level imaging of the retinal and choroidal vasculature. The microvascular patterns within different retinal layers are presented. An en face Doppler OCT approach [Srinivasan et al., Opt Express 18, 2477 (2010)] was adopted for retinal blood flow measurement. The flow is calculated by integrating the axial blood flow velocity over the vessel area measured in an en face plane without knowing the blood vessel angle. Total retinal blood flow can be measured from both retinal arteries and veins. The results indicate that OMAG has the potential for qualitative and quantitative evaluation of the microcirculation in posterior eye compartments in mouse models of retinopathy and neovascularization. PMID:23162733

  10. Orbital Extension of an Unsuspected Choroidal Melanoma Presumably through an Aqueous Tube Shunt

    PubMed Central

    Kiratli, Hayyam; Koç, İrem; Tarlan, Berçin

    2016-01-01

    Aims To report a patient with unrecognized small macular melanoma, who gradually developed neovascular glaucoma that was treated with an Ahmed valve. We presume that tumor cells gained access to the orbit through this aqueous drainage device. Methods The medical records pertaining to 5 different centers, the results of imaging studies, the clinical course of the patient and histopathological findings were retrospectively reviewed. Results A 61-year-old man presented with a blind and painful proptotic right eye. Retinal hemorrhage had been suspected 3 years earlier and followed accordingly thereafter. Yearly performed MRI studies demonstrated the steady growth of the hemorrhagic lesion/tumor. Meanwhile, he developed neovascular glaucoma first treated unsuccessfully with cyclocryotherapy then with implantation of an Ahmed valve. Right proptosis became evident within a year, and a final MRI study revealed a large retrobulbar mass. Orbital exenteration was performed and histopathological examination showed intraocular and orbital epithelioid cell melanoma. Tumor cells were also found within the reservoir of the Ahmed valve. The patient died of widespread metastases 1 year later. Conclusions Ahmed valve implantation in an eye with unsuspected macular choroidal melanoma may ultimately be associated with extraocular extension and orbital tumor formation. PMID:27239454

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

    SciTech Connect

    Al-Wassia, Rolina; Dal Pra, Alan; Shun, Kitty; Shaban, Ahmed; Corriveau, Christine; Edelstein, Chaim; Deschenes, Jean; Ruo, Russel; Patrocinio, Horacio; Cury, Fabio L.B.; DeBlois, Francois; Shenouda, George

    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, 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.

  12. Angiogenesis of buffalo choroid plexuses: structural and immunocytochemical study.

    PubMed

    Scala, Gaetano; Maruccio, Lucianna

    2012-08-01

    Mammalian choroid plexuses (CPs) are vascularized structures involved in numerous exchange processes that supply nutrients and hormones to the brain, and that remove deleterious compounds and metabolites from the brain. Studies in the adult Mediterranean buffalo have investigated the morphology of CPs using histochemical and immunohistochemical techniques. To date, however, there have been no studies conducted on ruminants regarding this removal process which serves to repair functional vascular damage in the CPs. Each of these vascular repair processes is a very complex and none of these has not yet been completely understood. Then, the aim of the present study is to investigate the morphological processes during angiogenesis in the CPs of healthy adult buffaloes, utilizing transmission electron microscopy (TEM), scanning electron microscopy (SEM), and immunogold-labeling SEM analysis (biomarkers: angiopoietin-2 [Ang-2], vascular endothelial growth factor receptor-3 [VEGFR-3], and CD133). At TEM, the inner surface of the blood capillaries sometimes showed pillar-like cells, which in contact with endothelial cells formed prominences, which in turn formed neo-blood capillaries. With immunogold-labeling SEM analysis, the CP blood capillaries showed Ang-2 and VEGF-3, respectively, in positive particles and spheroid formations. In addition, the external surface of the blood capillaries showed spheroid formations that originated from the neo-vascular capillaries whose terminals formed a capillary network, positive to CD133. On the basis of these results, the following hypothesis can be made, namely, that these CPs are vascular structures which play a fundamental role in maintaining brain homeostasis and self-repairing of functional vascular damage, independently of the presence of rete mirabile in this species. PMID:22434550

  13. Wavefront aberrations in eyes of emmetropic and moderately myopic school children and young adults.

    PubMed

    He, Ji C; Sun, Pei; Held, Richard; Thorn, Frank; Sun, Xiuru; Gwiazda, Jane E

    2002-04-01

    Wavefront aberrations were measured using a psychophysical ray-tracing technique in both eyes of 316 emmetropic and moderately myopic school children and young adults. Myopic subjects were found to have greater mean root mean square (RMS) value of wavefront aberrations than emmetropic subjects. Emmetropic adults had the smallest mean RMS, which remained smaller than the values for myopic adults and children and for emmetropic children both when second order Zernike aberrations (astigmatism) and third order Zernike aberrations were removed. Twenty percent of myopic adults had RMS values greater than values for all of the emmetropic adults, with significantly greater values for Zernike aberrations from second to seventh orders. High amounts of wavefront aberrations, which degrade the retinal image, may play a role in the development of myopia.

  14. Functional and genetic analysis of choroid plexus development in zebrafish

    PubMed Central

    Henson, Hannah E.; Parupalli, Chaithanyarani; Ju, Bensheng; Taylor, Michael R.

    2014-01-01

    The choroid plexus, an epithelial-based structure localized in the brain ventricle, is the major component of the blood-cerebrospinal fluid barrier. The choroid plexus produces the cerebrospinal fluid and regulates the components of the cerebrospinal fluid. Abnormal choroid plexus function is associated with neurodegenerative diseases, tumor formation in the choroid plexus epithelium, and hydrocephaly. In this study, we used zebrafish (Danio rerio) as a model system to understand the genetic components of choroid plexus development. We generated an enhancer trap line, Et(cp:EGFP)sj2, that expresses enhanced green fluorescent protein (EGFP) in the choroid plexus epithelium. Using immunohistochemistry and fluorescent tracers, we demonstrated that the zebrafish choroid plexus possesses brain barrier properties such as tight junctions and transporter activity. Thus, we have established zebrafish as a functionally relevant model to study choroid plexus development. Using an unbiased approach, we performed a forward genetic dissection of the choroid plexus to identify genes essential for its formation and function. Using Et(cp:EGFP)sj2, we isolated 10 recessive mutant lines with choroid plexus abnormalities, which were grouped into five classes based on GFP intensity, epithelial localization, and overall choroid plexus morphology. We also mapped the mutation for two mutant lines to chromosomes 4 and 21, respectively. The mutants generated in this study can be used to elucidate specific genes and signaling pathways essential for choroid plexus development, function, and/or maintenance and will provide important insights into how these genetic mutations contribute to disease. PMID:25426018

  15. De novo Evolution of a Small Choroidal Melanoma

    PubMed Central

    Aleksidze, Nino; Medina, Carlos A.; Singh, Arun D.

    2015-01-01

    Aim To report the evolution of a de novo choroidal melanoma. Method This is a case report of a 22-year-old white male patient who has been undergoing periodic examination for a choroidal ‘freckle’ since 10 years of age. Results In 2007, a fundus photograph of the left eye showed a nondescript area of choroidal hyperpigmentation temporal to the fovea. Progressive growth was observed and, by 2012, the lesion had become well circumscribed and raised. One year later, a 4.5 × 4.5 × 1.5 mm, dome-shaped, pigmented, choroidal mass with subretinal fluid and orange pigmentation was evident. The lesion was classified as a small choroidal melanoma. Six months after plaque radiotherapy, tumor regression with total resolution of the subretinal fluid was documented. Conclusion The distinction between small choroidal melanoma and choroidal nevus is not absolute; therefore, some choroidal melanomas may initially be mislabeled as choroidal nevi because of their small size until continued growth identifies them to be small choroidal melanomas. In our case, the documented growth of the choroidal lesion on each consecutive visit and its high-risk features strongly suggest that it had been a melanoma from the beginning. To our knowledge, this is only the second documented case of a de novo evolution of a small choroidal melanoma. PMID:27231689

  16. Functional and genetic analysis of choroid plexus development in zebrafish.

    PubMed

    Henson, Hannah E; Parupalli, Chaithanyarani; Ju, Bensheng; Taylor, Michael R

    2014-01-01

    The choroid plexus, an epithelial-based structure localized in the brain ventricle, is the major component of the blood-cerebrospinal fluid barrier. The choroid plexus produces the cerebrospinal fluid and regulates the components of the cerebrospinal fluid. Abnormal choroid plexus function is associated with neurodegenerative diseases, tumor formation in the choroid plexus epithelium, and hydrocephaly. In this study, we used zebrafish (Danio rerio) as a model system to understand the genetic components of choroid plexus development. We generated an enhancer trap line, Et(cp:EGFP) (sj2), that expresses enhanced green fluorescent protein (EGFP) in the choroid plexus epithelium. Using immunohistochemistry and fluorescent tracers, we demonstrated that the zebrafish choroid plexus possesses brain barrier properties such as tight junctions and transporter activity. Thus, we have established zebrafish as a functionally relevant model to study choroid plexus development. Using an unbiased approach, we performed a forward genetic dissection of the choroid plexus to identify genes essential for its formation and function. Using Et(cp:EGFP) (sj2), we isolated 10 recessive mutant lines with choroid plexus abnormalities, which were grouped into five classes based on GFP intensity, epithelial localization, and overall choroid plexus morphology. We also mapped the mutation for two mutant lines to chromosomes 4 and 21, respectively. The mutants generated in this study can be used to elucidate specific genes and signaling pathways essential for choroid plexus development, function, and/or maintenance and will provide important insights into how these genetic mutations contribute to disease. PMID:25426018

  17. Risk factors of rhegmatogenous retinal detachment associated with choroidal detachment in Chinese patients

    PubMed Central

    Gu, Yong-Hao; Ke, Gen-Jie; Wang, Lin; Gu, Qi-Hong; Zhou, En-Liang; Pan, Hong-Biao; Wang, Shi-Ying

    2016-01-01

    AIM To comprehensively analyze the risk factors of rhegmatogenous retinal detachment (RRD) associated with choroidal detachment (CD). METHODS A total of 265 eyes of 265 consecutive cases of RRD were retrospectively analyzed. All patients had systemic and ophthalmologic examination. CD was diagnosed by indirect ophthalmoscopy, B-scan ultrasonography, and ultrasound biomicroscope (UBM). Each parameter was compared between patients of RRD and rhegmatogenous retinal detachment associated with choroidal detachment (RRDCD). Logistic regression analysis was used to determine the independent risk factors of CD. RESULTS There were 52 eyes (19.62%) with CD. Pseudophakia was more commonly seen in RRDCD (21.15% vs 6.10%, P=0.002). Intraocular pressure (IOP) was lower (8.60±3.62 vs 12.96±3.55, P<0.001), best-corrected visual acuity was worse [3.00 (2.00 to 3.00) vs 1.92 (1.22 to 3.00), P=0.001], and refractive error was more myopic [-4 (-9 to -2) vs -2 (-6 to 0), P=0.007] in RRDCD. Eyes with RRDCD had larger extent of retinal detachment (P=0.007). In RRDCD, 34.62% of eyes presented with multiple holes (P=0.044) and 25.00% with macular holes (P=0.012), compared with 20.66% and 14.08% in RRD. High myopia (P=0.039), low IOP (P=0.017), and larger extent of retinal detachment (P<0.001) were significant and independent risk factors for developing CD. CONCLUSION For CD in RRD, related factors include BCVA, IOP, lens status, refractive error, extent of retinal detachment, number of holes, and macular hole. Larger extent of retinal detachment, high myopia, and low IOP are significant and independent risk factors. PMID:27500106

  18. Transthyretin represses neovascularization in diabetic retinopathy

    PubMed Central

    Shao, Jun

    2016-01-01

    Purpose The apoptosis of human umbilical vein endothelial cells has been reportedly induced by the protein transthyretin (TTR). In human ocular tissue, TTR is generally considered to be secreted mainly by retinal pigment epithelial cells (hRPECs); however, whether TTR affects the development of neovascularization in diabetic retinopathy (DR) remains unclear. Methods Natural and simulated DR media were used to culture human retinal microvascular endothelial cells (hRECs). Hyperglycemia was simulated by increasing the glucose concentration from 5.5 mM up to 25 mM, while hypoxia was induced with 200 µM CoCl2. To understand the effects of TTR on hRECs, cell proliferation was investigated under natural and DR conditions. Overexpression of TTR, an in vitro wound-healing assay, and a tube formation assay were employed to study the repression of TTR on hRECs. Real-time fluorescence quantitative PCR (qRT-PCR) was used to study the mRNA levels of DR-related genes, such as Tie2, VEGFR1, VEGFR2, Angpt1, and Angpt2. Results The proliferation of hRECs was significantly decreased in the simulated hyperglycemic and hypoxic DR environments. The cells were further repressed by added exogenous or endogenous TTR only under hyperglycemic conditions. The in vitro migration and tube formation processes of the hRECs were inhibited with TTR; furthermore, in the hyperglycemia and hyperglycemia/hypoxia environments, the levels of Tie2 and Angpt1 mRNA were enhanced with exogenous TTR, while those of VEGFR1, VEGFR2, and Angpt1 were repressed. Conclusions In hyperglycemia, the proliferation, migration, and neovascularization of hRECs were significantly inhibited by TTR. The key genes for DR neovascularization, including Tie2, VEGFR1, VEGFR2, Angpt1, and Angpt2, were regulated by TTR. Under DR conditions, TTR significantly represses neovascularization by inhibiting the proliferation, migration and tube formation of hRECs. PMID:27746673

  19. Choroidal Freckling in Pediatric Patients Affected by Neurofibromatosis Type 1.

    PubMed

    Vagge, Aldo; Nelson, Leonard B; Capris, Paolo; Traverso, Carlo Enrico

    2016-09-01

    Greater understanding of choroidal freckling in patients affected by neurofibromatosis type 1 (NF1) has changed the previous belief that choroidal lesions are unusual in eyes with this disease. In fact, the high frequency of freckling suggests that the choroid is a structure commonly affected in patients with NF1. A review of patients aged 16 years or younger was performed. Recent studies using near-infrared reflectance imaging have shown that choroidal freckling frequently occurred in pediatric patients. As a result of these findings, some authors have suggested that choroidal freckling should be considered as a new diagnostic criterion for NF1. [J Pediatr Ophthalmol Strabismus. 2016;53(5):271-274.].

  20. 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.

  1. Chronologic versus Biologic Aging of the Human Choroid

    PubMed Central

    May, Christian Albrecht

    2013-01-01

    Several aspects of chronologic and biologic aging in the human choroid are reviewed from the literature. They often reveal methodological problems for age-dependent changes of the following parameters: choroidal thickness, choroidal pigmentation, choroidal vasculature and blood flow, and choroidal innervation. On reinterpreting some data of studies concerning Bruch's membrane, changes observed at different age points seem more likely to be nonlinear. Concluding from the data presented so far, chronologic aging should not be used as a factor for physiological changes in the human choroid. Longitudinal study designs are necessary to further establish the impact of age. Meanwhile, a more biologic oriented model of aging processes in the choroid should be established, including specified conditions (e.g., light exposure and refractory state). This would help to define more individual strategies for prevention and early stages of a certain defined disease. PMID:24453840

  2. [Retinal vein occlusion management algorithm. Part 3. Neovascular complications].

    PubMed

    Budzinskaya, M V; Mazurina, N K; Egorov, A E; Kuroedov, A V; Loskutov, I A; Plyukhova, A A; Razik, S; Ryabtseva, A A; Simonova, S V

    2015-01-01

    Neovascular complications severity in central/branch retinal vein occlusion (RVO) correlates with the level of occlusion and the degree of retinal perfusion disturbance. Large areas of retinal non-perfusion (more than half of the total retinal area) are associated with the risk for posterior segment neovascularization as high as 33% and for neovascular glaucoma - 45%. Over the past 30 years there has been an evident declining tendency of neovascular complications rates in the natural course of RVO. In ischemic RVO, anterior segment neovascularization is more aggressive than posterior. Neovascular glaucoma usually develops within the first 6 months of disease and correlates with uncontrolled arterial hypertension. Panretinal photocoagulation (PRP) is a standard treatment for anterior and posterior segment neovascularization in RVO patients. Anti-VEGF agents, if used as monotherapy, lead to rapid, however, short-term remission. Combination therapy, that is anti-VEGF injections and PRP, is the most effective. Intravitreal steroids have demonstrated no effect on ocular neovascularization. If PRP cannot be performed and intraocular pressure levels remain high, one should consider glaucoma drainage implant surgery. Preventive measures for neovascular complications that have proved effective so far include regular follow-ups, individually scheduled intravitreal injections, and PRP for large zones of ischemia. PMID:26977729

  3. Myopic decisions under negative emotions correlate with altered time perception

    PubMed Central

    Guan, Shuchen; Cheng, Lu; Fan, Ying; Li, Xianchun

    2015-01-01

    Previous studies have obtained inconsistent findings about emotional influence on inter-temporal choice (IC). In the present study, we first examined the effect of temporary emotional priming induced by affective pictures in a trial-to-trial paradigm on IC. The results showed that negative priming resulted in much higher percentages of trials during which smaller-but-sooner reward (SS%) were chosen compared with positive and neutral priming. Next, we attempted to explore the possible mechanisms underlying such emotional effects. When participants performed a time reproduction task, mean reaction times in negative priming condition were significantly shorter than those in the other two emotional contexts, which indicated that negative emotional priming led to overestimation of time. Moreover, such overestimation was negatively correlated with performance in the IC task. In contrast, temporary changes of emotional contexts did not alter performances in a Go/NoGo task (including commission errors and omission errors). In sum, our present findings suggested that myopic decisions under negative emotions were associated with altered time perception but not response inhibition. PMID:25941508

  4. Microwave plaque thermoradiotherapy for choroidal melanoma.

    PubMed Central

    Finger, P. T.

    1992-01-01

    Microwave thermoradiotherapy was used as a primary treatment for 44 patients with choroidal melanoma. An episcleral dish-shaped microwave antenna was placed beneath the tumour at the time of plaque brachytherapy. While temperatures were measured at the sclera, the tumour's apex was targeted to receive a minimum of 42 degrees C for 45 minutes. In addition, the patients received full or reduced doses of plaque radiotherapy. No patients have been lost to follow-up. Two eyes have been enucleated: one for rubeotic glaucoma, and one for uveitic glaucoma. Though six patients have died, only one death was due to metastatic choroidal melanoma (39 months after treatment). Clinical observations suggest that the addition of microwave heating to plaque radiation therapy of choroidal melanoma has been well tolerated. There has been a 97.7% local control rate (with a mean follow-up of 22.2 months). We have reduced the minimum tumour radiation dose (apex dose) to levels used for thermoradiotherapy of cutaneous melanomas (50 Gy/5000 rad). Within the range of this follow-up period no adverse effects which might preclude the use of this microwave heat delivery system for treatment of choroidal melanoma have been noted. Images PMID:1622949

  5. Nd: YAG Laser Posterior Capsulotomy Rates in Myopic Eyes after Implantation of Capsular Tension Ring

    PubMed Central

    Keles, Sadullah; Kartal, Baki; Apil, Aytekin; Ondas, Osman; Kozan, Betul Dertsiz; Topdagi, Elif; Ekinci, Metin; Ceylan, Erdinc; Baykal, Orhan

    2014-01-01

    Background The aim f this study was to evaluate the effect of capsular tension ring implantation during cataract surgery on the incidence of neodymium: YAG (Nd: YAG) laser posterior capsulotomy in myopic (axial length [AL] ≥25.00 mm) eyes. Material/Methods In this retrospective study, the records of the cases of 117 myopic patients who underwent cataract surgery between January 2004 and January 2011 were reviewed. A total of 153 eyes with an axial length of 25 mm or higher were included in the study with consideration of exclusion criteria mentioned below. Eyes were grouped by presence or lack of capsular tension ring (CTR+ and CTR−, respectively). Results The study included 153 eyes from 107 myopic patients. Hydrophilic acrylic IOL and capsular tension ring (CTR) were implanted in 78 eyes (CTR+ group), and 75 eyes received only the hydrophilic acrylic IOL (CTR− group). Six eyes (7.6%) in CTR+ and 16 eyes (21.3%) in CTR− required Nd: YAG laser capsulotomy within 7 years. The difference between the 2 groups was statistically significant (p=0.021). Conclusions Because CTRs significantly decrease subsequent need for Nd: YAG laser posterior capsulotomy in myopic patients, are very inexpensive, and provide other benefits, our data suggest that the use of CTRs in myopic eyes undergoing cataract surgery with an hydrophilic acrylic IOL implantation is advantageous and should be standard practice. PMID:25132225

  6. The Ahmed Glaucoma Valve in Neovascular Glaucoma (An AOS Thesis)

    PubMed Central

    Netland, Peter A.

    2009-01-01

    Purpose: To evaluate the results of Ahmed glaucoma valve surgery in neovascular glaucoma and control patients. Methods: In this retrospective comparative study, we reviewed 76 eyes of 76 patients, comparing the surgical outcomes in control patients (N=38) to matched neovascular glaucoma patients (N=38). Success was defined as intraocular pressure (IOP) ≥6 mm Hg and ≤21 mm Hg, without further glaucoma surgery, and without loss of light perception. Results: Average follow-up for control and neovascular glaucoma patients was 18.4 and 17.4 months, respectively (P = .550). At last follow-up, mean IOP was 16.2 ± 5.2 mm Hg and 15.5 ± 12.5 mm Hg (P = .115) in control and neovascular glaucoma patients, respectively. Life-table analysis showed a significantly lower success for neovascular glaucoma patients compared with controls (P = .0096), with success at 1 year of 89.2% and 73.1%, at 2 years of 81.8% and 61.9%, and at 5 years of 81.8% and 20.6% for control and neovascular glaucoma eyes, respectively. Cox proportional hazards regression analysis showed neovascular glaucoma as a risk factor for surgical failure (odds ratio, 5.384, 95% CI, 1.22–23.84, P = .027). Although IOP control and complications were comparable between the two groups, visual outcomes were worse in neovascular glaucoma patients, with 9 eyes (23.7%) with neovascular glaucoma compared with no controls losing light perception vision (P = .002). The majority with loss of vision (5 of 9) had successful control of IOP during the postoperative period. Conclusion: Neovascular glaucoma patients have greater risk of surgical failure after Ahmed glaucoma valve surgery compared with controls. Despite improved mean IOP with drainage implants, visual outcomes may be poor, possibly due to progression of underlying disease. PMID:20126506

  7. Choroid Melanoma Metastasis to Spine: A Rare Case Report

    PubMed Central

    Mandaliya, Hiren; Singh, Nandini; George, Sanila; George, Mathew

    2016-01-01

    Metastatic choroid melanoma is a highly malignant disease with a limited life expectancy. The liver is the most common site for metastasis of uveal melanoma followed by lung, bone, skin, and subcutaneous tissue. Metastasis from choroidal melanoma usually occurs within the first five years of treatment for primary tumours. Metastatic choroid melanoma to the spine/vertebrae is extremely rare. We report the first case of spinal metastasis from choroid melanoma in a 61-year-old man who had been treated for primary ocular melanoma three years earlier with radioactive plaque brachytherapy. Synchronously, at the time of metastasis, he was also diagnosed as having a new primary lung adenocarcinoma as well. The only other case reported on vertebral metastasis from malignant melanoma of choroid in literature in which primary choroid melanoma was enucleated. PMID:26989537

  8. 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.

  9. Lonafarnib is a potential inhibitor for neovascularization.

    PubMed

    Sun, Linlin; Xie, Songbo; Peng, Guoyuan; Wang, Jian; Li, Yuanyuan; Qin, Juan; Zhong, Diansheng

    2015-01-01

    Atherosclerosis is a common cardiovascular disease that involves the build-up of plaque on the inner walls of the arteries. Intraplaque neovacularization has been shown to be essential in the pathogenesis of atherosclerosis. Previous studies showed that small-molecule compounds targeting farnesyl transferase have the ability to prevent atherosclerosis in apolipoprotein E-deficient mice, but the underlying mechanism remains to be elucidated. In this study, we found that lonafarnib, a specific inhibitor of farnesyl transferase, elicits inhibitory effect on vascular endothelial capillary assembly in vitro in a dose-dependent manner. In addition, we showed that lonafarnib treatment led to a dose-dependent decrease in scratch wound closure in vitro, whereas it had little effect on endothelial cell proliferation. These data indicate that lonafarnib inhibits neovascularization via directly targeting endothelial cells and disturbing their motility. Moreover, we demonstrated that pharmacological inhibition of farnesyl transferase by lonafarnib significantly impaired centrosome reorientation toward the leading edge of endothelial cells. Mechanistically, we found that the catalytic β subunit of farnesyl transferase associated with a cytoskeletal protein important for the establishment and maintenance of cell polarity. Additionally, we showed that lonafarnib remarkably inhibited the expression of the cytoskeletal protein and interrupted its interaction with farnesyl transferase. Our findings thus offer novel mechanistic insight into the protective effect of farnesyl transferase inhibitors on atherosclerosis and provide encouraging evidence for the potential use of this group of agents in inhibiting plaque neovascularization. PMID:25853815

  10. Carotid intraplaque neovascularization quantification software (CINQS).

    PubMed

    Akkus, Zeynettin; van Burken, Gerard; van den Oord, Stijn C H; Schinkel, Arend F L; de Jong, Nico; van der Steen, Antonius F W; Bosch, Johan G

    2015-01-01

    Intraplaque neovascularization (IPN) is an important biomarker of atherosclerotic plaque vulnerability. As IPN can be detected by contrast enhanced ultrasound (CEUS), imaging-biomarkers derived from CEUS may allow early prediction of plaque vulnerability. To select the best quantitative imaging-biomarkers for prediction of plaque vulnerability, a systematic analysis of IPN with existing and new analysis algorithms is necessary. Currently available commercial contrast quantification tools are not applicable for quantitative analysis of carotid IPN due to substantial motion of the carotid artery, artifacts, and intermittent perfusion of plaques. We therefore developed a specialized software package called Carotid intraplaque neovascularization quantification software (CINQS). It was designed for effective and systematic comparison of sets of quantitative imaging biomarkers. CINQS includes several analysis algorithms for carotid IPN quantification and overcomes the limitations of current contrast quantification tools and existing carotid IPN quantification approaches. CINQS has a modular design which allows integrating new analysis tools. Wizard-like analysis tools and its graphical-user-interface facilitate its usage. In this paper, we describe the concept, analysis tools, and performance of CINQS and present analysis results of 45 plaques of 23 patients. The results in 45 plaques showed excellent agreement with visual IPN scores for two quantitative imaging-biomarkers (The area under the receiver operating characteristic curve was 0.92 and 0.93). PMID:25561454

  11. CREG1 promotes angiogenesis and neovascularization.

    PubMed

    Yan, Chenghui; Fang, Pu; Zhang, Huimin; Tao, Jie; Tian, Xiaoxiang; Li, Yang; Zhang, Jian; Sun, Mingyu; Li, Shaohua; Wang, Hong; Han, Yaling

    2014-01-01

    Angiogenesis has long been considered as an important strategy for ischemic injury. It has been reported that cellular repressor of E1A-stimulated genes (CREG1) promotes human umbilical vein endothelial cell (HUVEC) proliferation, migration, and protects endothelial cell (EC) from apoptosis. However, its potential effect on angiogenesis remains undefined. In the present study, we investigated the role and mechanisms of CREG1 in promoting angiogenesis. We found that adenovirus-transduced CREG1 expression in HUVECs increases EC tube formation in matrigel and promotes neovascularization in matrigel plugs grafted into wild type mice. In addition, adenoviral CREG1 expression enhances filopodia formation, which is accompanied by increased expression of integrin-linked kinase (ILK) and activation of its downstream effector Cdc42. Hindlimb perfusion was significantly reduced after femoral artery ligation in CREG1 heterozygous knockout mice. Finally, adenoviral CREG1 was injected intramuscularly in gastrochemius and partially restores ischemic hindlimb perfusion. Our results demonstrated that CREG1 increases EC filopodia formation and vascular assembly via ILK-Cdc42 activation and promotes neovascularization, which might be a therapeutic target for ischemic injury. PMID:24896341

  12. Current perspectives of herpesviral retinitis and choroiditis.

    PubMed

    Madhavan, H N; Priya, K; Biswas, J

    2004-10-01

    Vision-threatening viral retinitis are primarily caused by members of the herpesvirus family. The biology and molecular characterization of herpesviruses, clinical presentations of retinopathies, pathology and pathogenesis including the host responses, epidemiology and the laboratory methods of aetiological diagnosis of these diseases are described. Clinical syndromes are acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN), cytomegalovirus (CMV) retinitis, multifocal choroiditis and serpiginous choroiditis besides other viral retinopathies. Herpes simplex virus (HSV) retinitis is more common in immunocompetent persons while varicella zoster virus (VZV) affects both immunocompetent and immunosuppressed patients equally. CMV retinitis is most common among patients with AIDS. The currently employed laboratory methods of antigen detection, virus isolation and antibody detection by enzyme linked immuno-sorbent assay (ELISA) have low sensitivity. Polymerase chain reaction (PCR) has increased the value of diagnosis due to its high clinical sensitivity and absolute specificity in detection of herpesviruses in intraocular specimens. PMID:16295367

  13. Current perspectives of herpesviral retinitis and choroiditis.

    PubMed

    Madhavan, H N; Priya, K; Biswas, J

    2004-10-01

    Vision-threatening viral retinitis are primarily caused by members of the herpesvirus family. The biology and molecular characterization of herpesviruses, clinical presentations of retinopathies, pathology and pathogenesis including the host responses, epidemiology and the laboratory methods of aetiological diagnosis of these diseases are described. Clinical syndromes are acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN), cytomegalovirus (CMV) retinitis, multifocal choroiditis and serpiginous choroiditis besides other viral retinopathies. Herpes simplex virus (HSV) retinitis is more common in immunocompetent persons while varicella zoster virus (VZV) affects both immunocompetent and immunosuppressed patients equally. CMV retinitis is most common among patients with AIDS. The currently employed laboratory methods of antigen detection, virus isolation and antibody detection by enzyme linked immuno-sorbent assay (ELISA) have low sensitivity. Polymerase chain reaction (PCR) has increased the value of diagnosis due to its high clinical sensitivity and absolute specificity in detection of herpesviruses in intraocular specimens.

  14. Choroid plexus in developmental and evolutionary perspective

    PubMed Central

    Bill, Brent Roy; Korzh, Vladimir

    2014-01-01

    The blood-cerebrospinal fluid boundary is present at the level of epithelial cells of the choroid plexus. As one of the sources of the cerebrospinal fluid (CSF), the choroid plexus (CP) plays an important role during brain development and function. Its formation has been studied largely in mammalian species. Lately, progress in other model animals, in particular the zebrafish, has brought a deeper understanding of CP formation, due in part to the ability to observe CP development in vivo. At the same time, advances in comparative genomics began providing information, which opens a possibility to understand further the molecular mechanisms involved in evolution of the CP and the blood-cerebrospinal fluid boundary formation. Hence this review focuses on analysis of the CP from developmental and evolutionary perspectives. PMID:25452709

  15. Cigarette Smoking in Indonesia: Examination of a Myopic Model of Addictive Behaviour

    PubMed Central

    Hidayat, Budi; Thabrany, Hasbullah

    2010-01-01

    Using aggregated panel data taken from three waves of the Indonesian Family Life Survey (1993–2000), this article tests the myopic addiction behaviour of cigarette demand. Sensitivity analysis is done by examining a rational addiction behavior of cigarette demand. The results provide support for myopic addiction. The short- and long-run price elasticities of cigarette demand are estimated at −0.28 and −0.73 respectively. Excise taxes are more likely to act as an effective tobacco control in the long-run rather than a major source of government revenue. PMID:20644684

  16. Retinal and Choroidal Folds in Papilledema

    PubMed Central

    Sibony, Patrick A.; Kupersmith, Mark J.; Feldon, Steven E.; Wang, Jui-Kai; Garvin, Mona

    2015-01-01

    Purpose To determine the frequency, patterns, associations, and biomechanical implications of retinal and choroidal folds in papilledema due to idiopathic intracranial hypertension (IIH). Methods Retinal and choroidal folds were studied in patients enrolled in the IIH Treatment Trial using fundus photography (n = 165 study eyes) and spectral-domain optical coherence tomography (SD-OCT; n = 125). We examined the association between folds and peripapillary shape, retinal nerve fiber layer (RNFL) thickness, disc volume, Frisén grade, acuity, perimetric mean deviation, intraocular pressure, intracranial pressure, and refractive error. Results We identified three types of folds in IIH patients with papilledema: peripapillary wrinkles (PPW), retinal folds (RF), and choroidal folds (CF). Frequency, with photos, was 26%, 19%, and 1%, respectively; SD-OCT frequency was 46%, 47%, and 10%. At least one type of fold was present in 41% of patients with photos and 73% with SD-OCT. Spectral-domain OCT was more sensitive. Structural parameters related to the severity of papilledema were associated with PPW and RF, whereas anterior deformation of the peripapillary RPE/basement membrane layer was associated with CF and RF. Folds were not associated with vision loss at baseline. Conclusions Folds in papilledema are biomechanical signs of stress/strain on the optic nerve head and load-bearing structures induced by intracranial hypertension. Folds are best imaged with SD-OCT. The patterns of retinal and choroidal folds are the products of a complex interplay between the degree of papilledema and anterior deformation of the load-bearing structures (sclera and possibly the lamina cribrosa), both modulated by structural geometry and material properties of the optic nerve head. (ClinicalTrials.gov number, NCT01003639.) PMID:26335066

  17. Notch receptors in human choroid plexus tumors.

    PubMed

    Beschorner, R; Waidelich, J; Trautmann, K; Psaras, T; Schittenhelm, J

    2013-08-01

    Notch signaling plays a role in development and formation of the normal choroid plexus (nCP), and in formation of various tumors in humans. Activation of Notch3 has been reported to promote tumor growth in invasive gliomas and to initiate formation of choroid plexus tumors (CPT) in mice. We investigated the expression of all currently known Notch receptors (Notch 1-4) in 55 samples of nCP and 88 CPT, including 61 choroid plexus papillomas (CPP), 22 atypical CPP and 5 choroid plexus carcinomas by immunohistochemistry. Notch expression was semiquantitatively evaluated separately for membranous/cytoplasmic and for nuclear staining. In addition, we examined Her2 expression (EGFR2, Her2/neu, ErbB2, CD340) because of its functional link to Notch signaling. All samples were negative for Notch3. Membranous/cytoplasmic expression of Notch1 (p<0.0001) and Notch4 (p=0.046) was significantly higher, whereas Notch2 expression was significantly lower (p<0.0001) in nCP compared to CPT. Nuclear expression of Notch1, -2 and -4 was significantly higher in CPT compared to nCP (p<0.0001 each). Expression of Notch2 and Notch4 showed a shift from a prevailing membranous/cytoplasmic expression in nCP to a predominant nuclear expression in CPT. Her2 was weakly expressed in 42/84 CPT but only in 2/53 nCP (p=0.0001) and positively correlated with nuclear expression of Notch1, -2 and 4 in CPT. In summary, a shift between membranous/cytoplasmic (non-canonical signaling pathway) and nuclear expression (canonical signaling pathway) of Notch1, -2 and -4 and upregulation of Her2 indicate neoplastic transformation in human CP and may reveal new therapeutic approaches.

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

    SciTech Connect

    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{sup +} 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{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.

  19. 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.

  20. 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.

  1. 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

  2. Corneal Biomechanical Properties in Myopic Eyes Measured by a Dynamic Scheimpflug Analyzer

    PubMed Central

    Wang, Jingyi; Li, Ying; Jin, Yumei; Yang, Xue; Zhao, Chan; Long, Qin

    2015-01-01

    Purpose. To evaluate the corneal biomechanical parameters in myopic and emmetropic eyes using Corneal Visualization Scheimpflug Technology (CorVis ST). Methods. 103 myopic and emmetropic eyes of 103 patients were examined. Corneal biomechanical parameters, axial length, and mean keratometry were measured using CorVis ST, IOL Master, and topography, respectively. Corneal biomechanical properties were compared within four groups. Bivariate correlation analysis was used to assess the relationship between corneal biomechanical parameters and ocular characteristics. Results. Four of ten corneal biomechanical parameters, namely, deformation amplitude (DA), first- and second-applanation time (A1-time, A2-time), and radius at highest concavity (HC radius), were significantly different within the four groups (P < 0.05). In correlation analysis, DA was positively correlated with axial length (r = 0.20, P = 0.04); A2-time was positively correlated with spherical equivalent (SE) (r = 0.24, P = 0.02); HC radius was positively correlated with SE (r = 0.24, P = 0.02) and was negatively correlated with mean keratometry (r = −0.20, P = 0.046) and axial length (r = −0.21, P = 0.03). Conclusions. The corneal refraction-related biomechanical alterations were associated with ocular characteristics. Highly myopic eyes exhibited longer DA and smaller HC radius than do moderately myopic eyes; the eyes with longer axial length tend to have less corneal stiffness and are easier to deform under stress. PMID:26576291

  3. Myopic Loss Aversion: Demystifying the Key Factors Influencing Decision Problem Framing

    ERIC Educational Resources Information Center

    Hardin, Andrew M.; Looney, Clayton Arlen

    2012-01-01

    Advancement of myopic loss aversion theory has been hamstrung by conflicting results, methodological inconsistencies, and a piecemeal approach toward understanding the key factors influencing decision problem framing. A series of controlled experiments provides a more holistic view of the variables promoting myopia. Extending the information…

  4. Angiogenesis and parasitic helminth-associated neovascularization.

    PubMed

    Dennis, Roger D; Schubert, Uwe; Bauer, Christian

    2011-04-01

    Successful metazoan parasitism, among many other factors, requires a supply of nutrients and the removal of waste products. There is a prerequisite for a parasite-defined vasculature. The angiogenic mechanism(s) involved presumably depend on the characteristics of the tissue- and vascular system-dwelling, parasitic helminths. Simplistically, 2 possibilities or a combination of both have been considered in this review. The multifactorial induction of parasitic helminth-associated neovascularization could arise through, either a host-, a parasite- or a host-/parasite-dependent, angiogenic switch. Most studies appear to support the first and third hypotheses, but evidence exists for the intrahepatic cestode Echinococcus multilocularis, the free-living nematode Caenorhabditis elegans and the intravascular trematode Schistosoma mansoni for the second inference. In contrast, the nematode anti-coagulant protein NAPc2 from adult Ancylostoma caninum is also an anti-angiogenic factor. PMID:21232174

  5. Corneal neovascularization and contemporary antiangiogenic therapeutics.

    PubMed

    Hsu, Chih-Chien; Chang, Hua-Ming; Lin, Tai-Chi; Hung, Kuo-Hsuan; Chien, Ke-Hung; Chen, Szu-Yu; Chen, San-Ni; Chen, Yan-Ting

    2015-06-01

    Corneal neovascularization (NV), the excessive ingrowth of blood vessels from conjunctiva into the cornea, is a common sequela of disease insult that can lead to visual impairment. Clinically, topical steroid, argon laser photocoagulation, and subconjunctival injection of bevacizumab have been used to treat corneal NV. Sometimes, the therapies are ineffective, especially when the vessels are large. Large vessels are difficult to occlude and easily recanalized. Scientists and physicians are now dedicated to overcoming this problem. In this article, we briefly introduce the pathogenesis of corneal NV, and then highlight the existing animal models used in corneal NV research-the alkali-induced model and the suture-induced model. Most of all, we review the potential therapeutic targets (i.e., vascular endothelial growth factor and platelet-derived growth factor) and their corresponding inhibitors, as well as the immunosuppressants that have been discovered in recent years by corneal NV studies.

  6. Inhibiting the transient choroidal thickening response using the nitric oxide synthase inhibitor l-NAME prevents the ameliorative effects of visual experience on ocular growth in two different visual paradigms.

    PubMed

    Nickla, Debora L; Wilken, Erika; Lytle, Grace; Yom, Sung; Mertz, James

    2006-08-01

    It is generally accepted that the increase in choroidal thickness in response to myopic defocus in chicks acts to move the retina towards the image plane. It may also constitute part of the signal cascade in the visual regulation of eye growth. To test this, we used the nitric oxide synthase inhibitor l-NAME to inhibit the defocus induced choroidal thickening under two different visual conditions, and looked at the effects on ocular growth rate. Exp. 1: Deprivation/Vision: chicks were monocularly deprived of form vision with translucent diffusers from day 6 to day 9. In the middle of each day the diffusers were removed for 2 h. One group received an intravitreal injection of 30 microl l-NAME (16 micromole; n=12) prior to the vision, a second group received injections of physiological saline (n=11). Exp. 2: Recovery/Vision: chicks were made myopic by form deprivation from day 6 to day 10. On days 11 to 14 the diffusers were removed for 2 h per day for 4 days to allow eyes to "recover" from the myopia. One group received an injection of l-NAME prior to vision (n=8), the other saline (n=6). Refractive errors were measured with a refractometer at the start (days 6 and 11) and end (days 10 and 15, respectively) of both experiments. Ocular dimensions were measured with high frequency A-scan ultrasonography at the start and end, and on the third experimental day immediately before and after the period of vision. Choroidal retinoic acid synthesis was measured by HPLC. Finally, NO production and scleral proteoglycan synthesis were measured in eyes wearing positive lenses 6 and 24h after an injection of l-NAME. l-NAME prevented the transient vision-induced choroidal thickening in both experiments. Furthermore, l-NAME inhibited the protective effect of brief daily vision: eyes became significantly more myopic than saline controls (exp. 1: -9 D vs -2.7D; exp. 2: -0.9 D vs +4.3 D; p<0.005 for both) and grew faster (change in lens-sclera: exp. 1: 295 vs 158 microm; exp. 2: 147

  7. The choroid plexuses and their impact on developmental neurogenesis.

    PubMed

    Johansson, Pia A

    2014-01-01

    During brain development the neural stem cells are regulated by both intrinsic and extrinsic sources. One site of origin of extrinsic regulation is the developing choroid plexuses, primely situated inside the cerebral ventricles. The choroid plexuses are very active in terms of both secretion and barrier function as soon as they appear during development and control the production and contents of cerebrospinal fluid (CSF). This suggests that regulated secretion of signaling molecules from the choroid plexuses into CSF can regulate neural stem cell behavior (as they are in direct contact with CSF) and thereby neurogenesis and brain development. Here, choroid plexus development, particularly with regards to molecular regulation and specification, is reviewed. This is followed by a review and discussion of the role of the developing choroid plexuses in brain development. In particular, recent evidence suggests a region-specific reciprocal regulation between choroid plexuses and the neural stem cells. This is accomplished by site-specific secretion of signaling molecules from the different choroid plexuses into CSF, as well as brain region specific competence of the neural stem cells to respond to the signaling molecules present in CSF. In conclusion, although in its infancy, the field of choroid plexus regulation of neurogenesis has already and will likely continue to shed new light on our understanding of the control and fine-tuning of overall brain development.

  8. The choroid plexuses and their impact on developmental neurogenesis

    PubMed Central

    Johansson, Pia A.

    2014-01-01

    During brain development the neural stem cells are regulated by both intrinsic and extrinsic sources. One site of origin of extrinsic regulation is the developing choroid plexuses, primely situated inside the cerebral ventricles. The choroid plexuses are very active in terms of both secretion and barrier function as soon as they appear during development and control the production and contents of cerebrospinal fluid (CSF). This suggests that regulated secretion of signaling molecules from the choroid plexuses into CSF can regulate neural stem cell behavior (as they are in direct contact with CSF) and thereby neurogenesis and brain development. Here, choroid plexus development, particularly with regards to molecular regulation and specification, is reviewed. This is followed by a review and discussion of the role of the developing choroid plexuses in brain development. In particular, recent evidence suggests a region-specific reciprocal regulation between choroid plexuses and the neural stem cells. This is accomplished by site-specific secretion of signaling molecules from the different choroid plexuses into CSF, as well as brain region specific competence of the neural stem cells to respond to the signaling molecules present in CSF. In conclusion, although in its infancy, the field of choroid plexus regulation of neurogenesis has already and will likely continue to shed new light on our understanding of the control and fine-tuning of overall brain development. PMID:25386116

  9. Effects of vasoactive stimuli on blood flow to choroid plexus

    SciTech Connect

    Faraci, F.M.; Mayhan, W.G.; Williams, J.K.; Heistad, D.D. )

    1988-02-01

    The goal of this study was to examine effects of vasoactive stimuli on blood flow to choroid plexus. The authors used microspheres to measure blood flow to choroid plexus and cerebrum in anesthetized dogs and rabbits. A critical assumption of the microsphere method is that microspheres do not pass through arteriovenous shunts. Blood flow values obtained with simultaneous injection of 15- and 50-{mu}m microspheres were similar, which suggest that shunting of 15-{mu}m microspheres was minimal. Blood flow to choroid plexus under control conditions was 287 {plus minus} 26 (means {plus minus} SE) ml {center dot} min{sup {minus}1} {center dot} 100 g{sup {minus}1} in dogs and 385 {plus minus} 73 ml {center dot} min{sup {minus}1} 100 g{sup {minus}1} in rabbits. Consecutive measurements under control conditions indicated that values for blood flow are reproducible. Adenosine did not alter blood flow to cerebrum but increased blood flow to choroid plexus two- to threefold in dogs and rabbits. Norepinephrine and phenylephrine did not affect blood flow to choroid plexus and cerebrum but decreased blood flow to choroid plexus by {approx} 50%. The authors suggest that (1) the microsphere method provides reproducible valid measurements of blood flow to the choroid plexus in dogs and rabbits and (2) vasoactive stimuli may have profoundly different effects on blood flow to choroid plexus and cerebrum.

  10. A choroid plexus papilloma in an elasmobranch (Squalus acanthias).

    PubMed

    Prieur, D J; Fenstermacher, J D; Guarino, A M

    1976-06-01

    A choroid papilloma in the choroid plexus of the ala of the fourth ventricle in a mature male elasmobranch, Squalus acanthias, was described. This is apparently the first report of a neoplasm of the central nervous system in a member of the class Chondrichthyes. PMID:994222

  11. Neovascular glaucoma after helium ion irradiation for uveal melanoma

    SciTech Connect

    Kim, M.K.; Char, D.H.; Castro, J.L.; Saunders, W.M.; Chen, G.T.; Stone, R.D.

    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 percent of patients had some response with intraocular pressures of 21 mmHg or less to a combination of antiglaucoma treatments.

  12. Choroidal Freckling in Pediatric Patients Affected by Neurofibromatosis Type 1.

    PubMed

    Vagge, Aldo; Nelson, Leonard B; Capris, Paolo; Traverso, Carlo Enrico

    2016-09-01

    Greater understanding of choroidal freckling in patients affected by neurofibromatosis type 1 (NF1) has changed the previous belief that choroidal lesions are unusual in eyes with this disease. In fact, the high frequency of freckling suggests that the choroid is a structure commonly affected in patients with NF1. A review of patients aged 16 years or younger was performed. Recent studies using near-infrared reflectance imaging have shown that choroidal freckling frequently occurred in pediatric patients. As a result of these findings, some authors have suggested that choroidal freckling should be considered as a new diagnostic criterion for NF1. [J Pediatr Ophthalmol Strabismus. 2016;53(5):271-274.]. PMID:27637020

  13. NADPH oxidase 2 plays a role in experimental corneal neovascularization.

    PubMed

    Chan, Elsa C; van Wijngaarden, Peter; Chan, Elsie; Ngo, Darleen; Wang, Jiang-Hui; Peshavariya, Hitesh M; Dusting, Gregory J; Liu, Guei-Sheung

    2016-05-01

    Corneal neovascularization, the growth of new blood vessels in the cornea, is a leading cause of vision impairment after corneal injury. Neovascularization typically occurs in response to corneal injury such as that caused by infection, physical trauma, chemical burns or in the setting of corneal transplant rejection. The NADPH oxidase enzyme complex is involved in cell signalling for wound-healing angiogenesis, but its role in corneal neovascularization has not been studied. We have now analysed the role of the Nox2 isoform of NADPH oxidase in corneal neovascularization in mice following chemical injury. C57BL/6 mice aged 8-14 weeks were cauterized with an applicator coated with 75% silver nitrate and 25% potassium nitrate for 8 s. Neovascularization extending radially from limbal vessels was observed in corneal whole-mounts from cauterized wild type mice and CD31+ vessels were identified in cauterized corneal sections at day 7. In contrast, in Nox2 knockout (Nox2 KO) mice vascular endothelial growth factor-A (Vegf-A), Flt1 mRNA expression, and the extent of corneal neovascularization were all markedly reduced compared with their wild type controls. The accumulation of Iba-1+ microglia and macrophages in the cornea was significantly less in Nox2 KO than in wild type mice. In conclusion, we have demonstrated that Nox2 is implicated in the inflammatory and neovascular response to corneal chemical injury in mice and clearly VEGF is a mediator of this effect. This work raises the possibility that therapies targeting Nox2 may have potential for suppressing corneal neovascularization and inflammation in humans. PMID:26814205

  14. Recurrent Annular Peripheral Choroidal Detachment after Trabeculectomy

    PubMed Central

    Liu, Shaohui; Sun, Lisa L.; Kavanaugh, A. Scott; Langford, Marlyn P.; Liang, Chanping

    2013-01-01

    We report a challenging case of recurrent flat anterior chamber without hypotony after trabeculectomy in a 54-year-old Black male with a remote history of steroid-treated polymyositis, cataract surgery, and uncontrolled open angle glaucoma. The patient presented with a flat chamber on postoperative day 11, but had a normal fundus exam and intraocular pressure (IOP). Flat chamber persisted despite treatment with cycloplegics, steroids, and a Healon injection into the anterior chamber. A transverse B-scan of the peripheral fundus revealed a shallow annular peripheral choroidal detachment. The suprachoroidal fluid was drained. The patient presented 3 days later with a recurrent flat chamber and an annular peripheral choroidal effusion. The fluid was removed and reinforcement of the scleral flap was performed with the resolution of the flat anterior chamber. A large corneal epithelial defect developed after the second drainage. The oral prednisone was tapered quickly and the topical steroid was decreased. One week later, his vision decreased to count fingers with severe corneal stromal edema and Descemet's membrane folds that improved to 20/50 within 24 h of resumption of the oral steroid and frequent topical steroid. The patient's visual acuity improved to 20/20 following a slow withdrawal of the oral and topical steroid. Eight months after surgery, the IOP was 15 mm Hg without glaucoma medication. The detection of a shallow anterior choroidal detachment by transverse B-scan is critical to making the correct diagnosis. Severe cornea edema can occur if the steroid is withdrawn too quickly. Thus, steroids should be tapered cautiously in steroid-dependent patients. PMID:24348402

  15. Pitfalls in colour photography of choroidal tumours

    PubMed Central

    Schalenbourg, A; Zografos, L

    2013-01-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown. PMID:23238442

  16. Pitfalls in colour photography of choroidal tumours.

    PubMed

    Schalenbourg, A; Zografos, L

    2013-02-01

    Colour imaging of fundus tumours has been transformed by the development of digital and confocal scanning laser photography. These advances provide numerous benefits, such as panoramic images, increased contrast, non-contact wide-angle imaging, non-mydriatic photography, and simultaneous angiography. False tumour colour representation can, however, cause serious diagnostic errors. Large choroidal tumours can be totally invisible on angiography. Pseudogrowth can occur because of artefacts caused by different methods of fundus illumination, movement of reference blood vessels, and flattening of Bruch's membrane and sclera when tumour regression occurs. Awareness of these pitfalls should prevent the clinician from misdiagnosing tumours and wrongfully concluding that a tumour has grown.

  17. Telocytes in meninges and choroid plexus.

    PubMed

    Popescu, B O; Gherghiceanu, M; Kostin, S; Ceafalan, L; Popescu, L M

    2012-05-16

    Telocytes (TCs) are a recently identified type of interstitial cells present in a wide variety of organs in humans and mammals (www.telocytes.com). They are characterized by a small cell body, but extremely long cell processes - telopodes (Tp), and a specific phenotype. TCs establish close contacts with blood capillaries, nerve fibers and stem cells. We report here identification of TCs by electron microscopy and immunofluorescence in rat meninges and choroid plexus/subventricular zone, in the vicinity of putative stem cells. The presence of TCs in brain areas involved in adult neurogenesis might indicate that they have a role in modulation of neural stem cell fate.

  18. Choroidal abnormalities and masquerade syndromes confounding the diagnosis of laser-induced eye injuries

    NASA Astrophysics Data System (ADS)

    Hacker, Henry D.; Zwick, Harry; Brown, Jeremiah, Jr.; Dicks, Ronald; Cheramie, Rachel; Stuck, Bruce E.

    2005-04-01

    The diagnosis of a laser-induced eye injury occurring in occupational or military environments is often complicated by confounding symptoms, the possibility of pre-existing pathology, and/or a lack of visual deficits that can be clearly associated with a specific incident. Two recent cases are described that illustrate the importance of a thorough differential diagnosis when coexisting retinal pathologies are present with potentially different (e.g. laser or disease) etiologies. Indocyanine green angiography (ICG) and ocular coherence tomography (OCT) used in combination with standard ophthalmic imaging can provide helpful insights as to the etiology of these lesions. Vascular choroidal abnormalities such as hemangiomas or occult histoplasmosis infection can produce findings that can mimic the leakage that may be evident from neovascular membranes associated with laser injury. Further evaluation with OCT and conventional fluorescein angiography (FA) is helpful to look for the classic signature of retinal disruption and retinal pigment layer changes that are often present in association with laser injury. Furthermore, a careful situational assessment of a potential laser exposure is important to confirm the diagnosis of laser-induced eye injury.

  19. Ciliary body and choroidal melanomas treated by proton beam irradiation. Histopathologic study of eyes

    SciTech Connect

    Seddon, J.M.; Gragoudas, E.S.; Albert, D.M.

    1983-09-01

    Proton beam irradiation resulted in clinical and/or histopathological regression of large ciliary body and choroidal melanomas in three eyes. Enucleations were performed 6 1/2 weeks, five months, and 11 months after irradiation for angle-closure glaucoma from total retinal detachment, increase in retinal detachment, and neovascular glaucoma, respectively. A direct relationship was found between the length of the interval from irradiation to enucleation and the degree of histologic changes. Vascular changes in the tumors included endothelial cell swelling and decreased lumen size, basement membrane thickening, collapse of sinusoidal vessels, and thrombosis of vessels. Although apparently unaltered tumor cells remained, degenerative changes occurred in some melanoma cells, including lipid vacuoles in cytoplasm, pyknotic nuclei, and balloon cell formation. Patchy areas of necrosis and proteinaceous exudate were present. Pigment-laden macrophages were found near tumor vessels and all had a substantial chronic inflammatory infiltrate. The effect of proton beam irradiation on tumor vessels probably plays an important role in uveal melanoma regression.

  20. 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.

  1. Resolution of choroidal neovascularization secondary to punctate inner choroidopathy (PIC) with intravitreal anti-VEGF agents: a case series.

    PubMed

    Mangat, Simran S; Ramasamy, B; Prasad, Som; Walters, Gavin; Mohammed, Moin; Mckibbin, Martin

    2011-01-01

    Case series of four patients with CNVM secondary to PIC treated solely with anti VEGF in three cases and in combination with PDT in the other. This series reveals long term follow up (3 months to 28 months) which is currently not described in the literature.

  2. Fibrosis of the Choroid Plexus Filtration Membrane

    PubMed Central

    Parratt, John D. E.; Kirwan, Paul D.

    2016-01-01

    We report a previously undescribed inflammatory lesion consisting of deposition of activated complement (C3d and C9neo) in association with major histocompatibility complex type II (MHC2)-positive activated microglia in choroid plexus villi exhibiting classical fibrous thickening of the pericapillary filtration membrane. The proportion of villi affected ranged from 5% to 90% in 56 adult subjects with diseases of the CNS and 11 subjects with no preexisting disease of the CNS. In 3 of the 4 children studied, 2% or less of examined villi showed stromal thickening, complement deposition, and the presence of MHC2-positive microglia; in adults, the proportion of villi affected increased with age. Other features of the lesion included loss of capillaries and failure by macrophages to clear extracellular particulate electron-dense material by clathrin-mediated phagocytosis. This choroid plexus lesion may relate pathogenetically to age-related macular degeneration and to Alzheimer disease, 2 other conditions with no known risk factors other than increasing age. All 3 conditions are characterized by the presence of damaged capillaries, inflammatory extracellular aggregates of mixed molecular composition and defective clearance of the deposits by macrophages. PMID:27444353

  3. Gyrate atrophy of choroid and retina.

    PubMed

    Bhaduri, Gautam

    2002-03-01

    Gyrate atrophy of choroid and retina is a rare disorder of autosomal recessive nature. There occurs patchy and progressive atrophy of the choroid and retina at the equatorial region with central area being less affected. Here in this case report, one woman of about 47 years attended at the retina clinic, Tenennt Institute of Ophthalmology, Glasgow University with the history of gradual loss of vision. On fundus examination, sharply defined bizarre shaped atrophic areas of fundus was seen in both the eyes. Velvet like fine granular pigments were present in the macula, the zone of healthy retina and the periphery. The colourless, elongated, glittering crystals were scattered over the dark brown pigments visible through 90 dioptre lens. Bone corpuscles pigments were not found. Fluorescein angiography showed hyperfluorescence in the area of gyrate atrophy. Her plasma ornithine level and plasma tiramine level were 1 90 U mol/l and 357 U mol/l. respectively. A rigid schedule of low protein diet including near total elimination of arginine with supplementation of essential amino acids was advised since the diagnosis was established.

  4. [Bilateral choroidal metastases of kidney carcinoma].

    PubMed

    Galetović, Davor; Bućan, Kajo; Karlica, Dobrila; Lesin, Mladen; Znaor, Ljubo

    2010-07-01

    Metastatic tumors are among the most common intraocular malignancies, and are exclusively localized in the uvea, 88% in the choroids. A 54-year-old male patient was admitted to Urology Department for macrohematuria. A tumor of the left kidney was found. Upon nephrectomy, histopathology indicated papillary carcinoma of the kidney with some focal sarcomatous differentiation. The left suprarenal gland was normal, but one of the regional lymph nodes was invaded. Three years later, the patient was hospitalized again for tumor of the right suprarenal gland and para-aortic tumor. At the same time, the patient complained of visual acuity worsening on the left eye. Fundus examination and fundus photography revealed yellowish subretinal lesions with serous retinal detachment. Metastatic eye lesions may anticipate or follow the diagnosis of kidney carcinoma. All tumors with a tendency of hematogenous metastasizing have a high affinity of metastasizing into the uvea because of its abundant blood flow. Posterior pole is the most common localization; over 40% of lesions are found in macular region, which is attributed to the higher posterior choroidal blood flow and easy macular symptom detection. That is why kidney carcinoma has to be ruled out in all patients with such yellowish subretinal lesions.

  5. Peripheral Defocus and Myopia Progression in Myopic Children Randomly Assigned to Wear Single Vision and Progressive Addition Lenses

    PubMed Central

    Berntsen, David A.; Barr, Christopher D.; Mutti, Donald O.; Zadnik, Karla

    2013-01-01

    Purpose. To determine the effect of progressive addition lenses (PALs) and single vision lenses (SVLs) on peripheral defocus in myopic children, and to compare the effect of myopic versus hyperopic peripheral defocus on foveal myopia progression. Methods. Eighty-four myopic children aged 6 to 11 years with spherical equivalent (SE) cycloplegic autorefraction between −0.75 diopters (D) and −4.50 D were randomly assigned to wear SVLs or PALs. Aberrometry measurements of the eye and spectacles were made centrally, 30° nasally, temporally, and superiorly, and 20° inferiorly on the retina using a Complete Ophthalmic Analysis System for Vision Research (COAS-VR). The association between peripheral defocus and the 1-year change in central myopia was investigated. Results. SVLs caused a hyperopic shift in peripheral defocus at all locations (all P ≤ 0.0003). PALs caused a myopic shift in peripheral defocus in three of four locations measured (all P ≤ 0.01) with the greatest shift superiorly due to the PAL addition (−1.04 ± 0.30 D). Superior retinal defocus when wearing either SVLs or PALs was associated with the 1-year change in central myopia. The adjusted 1-year change in central SE myopia was −0.38 D for children with absolute superior myopic defocus (n = 67) and −0.65 D for children with absolute superior hyperopic defocus (n = 17; difference = 0.27 D; P = 0.002). Conclusions. PALs caused a myopic shift in peripheral defocus. Superior myopic defocus was associated with less central myopia progression. These data support the continued investigation of optical designs that result in peripheral myopic defocus as a potential way to slow myopia progression. (ClinicalTrials.gov number, NCT00335049.) PMID:23838771

  6. Matrilin-1 Is an Inhibitor of Neovascularization*

    PubMed Central

    Foradori, Matthew J.; Chen, Qian; Fernandez, Cecilia A.; Harper, Jay; Li, Xin; Tsang, Paul C. W.; Langer, Robert; Moses, Marsha A.

    2014-01-01

    In the course of conducting a series of studies whose goal was to discover novel endogenous angiogenesis inhibitors, we have purified matrilin-1 (MATN-1) and have demonstrated, for the first time, that it inhibits neovascularization both in vitro and in vivo. Proteins were extracted from cartilage using a 2 m NaCl, 0.01 m HEPES buffer at 4 °C, followed by concentration of the extract. The concentrate was fractionated by size exclusion chromatography, and fractions were then screened for their ability to inhibit capillary endothelial cell (EC) proliferation in vitro. Fractions containing EC inhibitory activity were pooled and further purified by cation exchange chromatography. The resulting fractions from this step were then screened to isolate the antiangiogenic activity in vitro. This activity was identified by tandem mass spectrometry as being MATN-1. Human MATN-1 was cloned and expressed in Pichia pastoris and purified to homogeneity. Purified recombinant MATN-1, along with purified native protein, was shown to inhibit angiogenesis in vivo using the chick chorioallantoic membrane assay by the inhibition of capillary EC proliferation and migration. Finally, using a MATN-1-deficient mouse, we showed that angiogenesis during fracture healing was significantly higher in MATN-1−/− mice compared with the wild type mice as demonstrated by in vivo imaging and by elevated expression of angiogenesis markers including PECAM1, VEGFR, and VE-cadherin. PMID:24692560

  7. Characterization of a Spontaneous Retinal Neovascular Mouse Model

    PubMed Central

    Hasegawa, Eiichi; Sweigard, Harry; Husain, Deeba; Olivares, Ana M.; Chang, Bo; Smith, Kaylee E.; Birsner, Amy E.; D’Amato, Robert J.; Michaud, Norman A.; Han, Yinan; Vavvas, Demetrios G.; Miller, Joan W.; Haider, Neena B.; Connor, Kip M.

    2014-01-01

    Background Vision loss due to vascular disease of the retina is a leading cause of blindness in the world. Retinal angiomatous proliferation (RAP) is a subgroup of neovascular age-related macular degeneration (AMD), whereby abnormal blood vessels develop in the retina leading to debilitating vision loss and eventual blindness. The novel mouse strain, neoretinal vascularization 2 (NRV2), shows spontaneous fundus changes associated with abnormal neovascularization. The purpose of this study is to characterize the induction of pathologic angiogenesis in this mouse model. Methods The NRV2 mice were examined from postnatal day 12 (p12) to 3 months. The phenotypic changes within the retina were evaluated by fundus photography, fluorescein angiography, optical coherence tomography, and immunohistochemical and electron microscopic analysis. The pathological neovascularization was imaged by confocal microscopy and reconstructed using three-dimensional image analysis software. Results We found that NRV2 mice develop multifocal retinal depigmentation in the posterior fundus. Depigmented lesions developed vascular leakage observed by fluorescein angiography. The spontaneous angiogenesis arose from the retinal vascular plexus at postnatal day (p)15 and extended toward retinal pigment epithelium (RPE). By three months of age, histological analysis revealed encapsulation of the neovascular lesion by the RPE in the photoreceptor cell layer and subretinal space. Conclusions The NRV2 mouse strain develops early neovascular lesions within the retina, which grow downward towards the RPE beginning at p15. This retinal neovascularization model mimics early stages of human retinal angiomatous proliferation (RAP) and will likely be a useful in elucidating targeted therapeutics for patients with ocular neovascular disease. PMID:25188381

  8. 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. PMID:27216722

  9. Promising new treatments for neovascular age-related macular degeneration.

    PubMed

    Michels, Stephan; Schmidt-Erfurth, Ursula; Rosenfeld, Philip J

    2006-07-01

    Angiogenesis, the growth of new blood vessels from existing blood vessels, is responsible for vision loss in a variety of ophthalmic diseases. In neovascular age-related macular degeneration (AMD), the leading cause for legal blindness in many industrialised countries, abnormal blood vessels grow in the macula and cause blindness. There are a number of factors important in the angiogenic cascade but VEGF-A has been implicated in recent years as the major factor responsible for neovascular and exudative diseases of the eye. Numerous antiangiogenic drugs are in development but anti-VEGF drugs have shown great promise in treating neovascular AMD and other ocular diseases, and many of these drugs have been adopted from oncology where antiangiogenic therapy is gaining wide acceptance. For the first time in neovascular AMD, anti-VEGF drugs have brought the hope of vision improvement to a significant proportion of patients. This review provides an overview on angiogenic mechanisms, potential antiangiogenic treatment strategies and different antiangiogenic drugs with special focus on neovascular AMD.

  10. Parametric imaging of tumor perfusion and neovascular morphology using ultrasound

    NASA Astrophysics Data System (ADS)

    Hoyt, Kenneth

    2015-03-01

    A new image processing strategy is detailed for the simultaneous measurement of tumor perfusion and neovascular morphology parameters from a sequence of dynamic contrast-enhanced ultrasound (DCE-US) images. A technique for locally mapping tumor perfusion parameters using skeletonized neovascular data is also introduced. Simulated images were used to test the neovascular skeletonization technique and variance (error) of relevant parametric estimates. Preliminary DCE-US image datasets were collected in 6 female patients diagnosed with invasive breast cancer and using a Philips iU22 ultrasound system equipped with a L9-3 MHz transducer and Definity contrast agent. Simulation data demonstrates that neovascular morphology parametric estimation is reproducible albeit measurement error can occur at a lower signal-to-noise ratio (SNR). Experimental results indicate the feasibility of our approach to performing both tumor perfusion and neovascular morphology measurements from DCE-US images. Future work will expand on our initial clinical findings and also extent our image processing strategy to 3-dimensional space to allow whole tumor characterization.

  11. Promising new treatments for neovascular age-related macular degeneration.

    PubMed

    Michels, Stephan; Schmidt-Erfurth, Ursula; Rosenfeld, Philip J

    2006-07-01

    Angiogenesis, the growth of new blood vessels from existing blood vessels, is responsible for vision loss in a variety of ophthalmic diseases. In neovascular age-related macular degeneration (AMD), the leading cause for legal blindness in many industrialised countries, abnormal blood vessels grow in the macula and cause blindness. There are a number of factors important in the angiogenic cascade but VEGF-A has been implicated in recent years as the major factor responsible for neovascular and exudative diseases of the eye. Numerous antiangiogenic drugs are in development but anti-VEGF drugs have shown great promise in treating neovascular AMD and other ocular diseases, and many of these drugs have been adopted from oncology where antiangiogenic therapy is gaining wide acceptance. For the first time in neovascular AMD, anti-VEGF drugs have brought the hope of vision improvement to a significant proportion of patients. This review provides an overview on angiogenic mechanisms, potential antiangiogenic treatment strategies and different antiangiogenic drugs with special focus on neovascular AMD. PMID:16787141

  12. Myopic aberrations: Simulation based comparison of curvature and Hartmann Shack wavefront sensors

    NASA Astrophysics Data System (ADS)

    Basavaraju, Roopashree M.; Akondi, Vyas; Weddell, Stephen J.; Budihal, Raghavendra Prasad

    2014-02-01

    In comparison with a Hartmann Shack wavefront sensor, the curvature wavefront sensor is known for its higher sensitivity and greater dynamic range. The aim of this study is to numerically investigate the merits of using a curvature wavefront sensor, in comparison with a Hartmann Shack (HS) wavefront sensor, to analyze aberrations of the myopic eye. Aberrations were statistically generated using Zernike coefficient data of 41 myopic subjects obtained from the literature. The curvature sensor is relatively simple to implement, and the processing of extra- and intra-focal images was linearly resolved using the Radon transform to provide Zernike modes corresponding to statistically generated aberrations. Simulations of the HS wavefront sensor involve the evaluation of the focal spot pattern from simulated aberrations. Optical wavefronts were reconstructed using the slope geometry of Southwell. Monte Carlo simulation was used to find critical parameters for accurate wavefront sensing and to investigate the performance of HS and curvature sensors. The performance of the HS sensor is highly dependent on the number of subapertures and the curvature sensor is largely dependent on the number of Zernike modes used to represent the aberration and the effective propagation distance. It is shown that in order to achieve high wavefront sensing accuracy while measuring aberrations of the myopic eye, a simpler and cost effective curvature wavefront sensor is a reliable alternative to a high resolution HS wavefront sensor with a large number of subapertures.

  13. Myopic Macular Retinoschisis in Teenagers: Clinical Characteristics and Spectral Domain Optical Coherence Tomography Findings

    PubMed Central

    Sun, Chuan-bin; You, Yong-sheng; Liu, Zhe; Zheng, Lin-yan; Chen, Pei-qing; Yao, Ke; Xue, An-quan

    2016-01-01

    To investigate the morphological characteristics of myopic macular retinoschisis (MRS) in teenagers with high myopia, six male (9 eyes) and 3 female (4 eyes) teenagers with typical MRS identified from chart review were evaluated. All cases underwent complete ophthalmic examinations including best corrected visual acuity (BCVA), indirect ophthalmoscopy, colour fundus photography, B-type ultrasonography, axial length measurement, and spectral-domain optical coherence tomography (SD-OCT). The average age was 17.8 ± 1.5 years, average refractive error was −17.04 ± 3.04D, average BCVA was 0.43 ± 0.61, and average axial length was 30.42 ± 1.71 mm. Myopic macular degenerative changes (MDC) by colour fundus photographs revealed Ohno-Matsui Category 1 in 4 eyes, and Category 2 in 9 eyes. Posterior staphyloma was found in 9 eyes. SD-OCT showed outer MRS in all 13 eyes, internal limiting membrane detachment in 7 eyes, vascular microfolds in 2 eyes, and inner MRS in 1 eye. No premacular structures such as macular epiretinal membrane or partially detached posterior hyaloids were found. Our results showed that MRS rarely occurred in highly myopic teenagers, and was not accompanied by premacular structures, severe MDC, or even obvious posterior staphyloma. This finding indicates that posterior scleral expansion is probably the main cause of MRS. PMID:27294332

  14. Myopic Macular Retinoschisis in Teenagers: Clinical Characteristics and Spectral Domain Optical Coherence Tomography Findings.

    PubMed

    Sun, Chuan-Bin; You, Yong-Sheng; Liu, Zhe; Zheng, Lin-Yan; Chen, Pei-Qing; Yao, Ke; Xue, An-Quan

    2016-01-01

    To investigate the morphological characteristics of myopic macular retinoschisis (MRS) in teenagers with high myopia, six male (9 eyes) and 3 female (4 eyes) teenagers with typical MRS identified from chart review were evaluated. All cases underwent complete ophthalmic examinations including best corrected visual acuity (BCVA), indirect ophthalmoscopy, colour fundus photography, B-type ultrasonography, axial length measurement, and spectral-domain optical coherence tomography (SD-OCT). The average age was 17.8 ± 1.5 years, average refractive error was -17.04 ± 3.04D, average BCVA was 0.43 ± 0.61, and average axial length was 30.42 ± 1.71 mm. Myopic macular degenerative changes (MDC) by colour fundus photographs revealed Ohno-Matsui Category 1 in 4 eyes, and Category 2 in 9 eyes. Posterior staphyloma was found in 9 eyes. SD-OCT showed outer MRS in all 13 eyes, internal limiting membrane detachment in 7 eyes, vascular microfolds in 2 eyes, and inner MRS in 1 eye. No premacular structures such as macular epiretinal membrane or partially detached posterior hyaloids were found. Our results showed that MRS rarely occurred in highly myopic teenagers, and was not accompanied by premacular structures, severe MDC, or even obvious posterior staphyloma. This finding indicates that posterior scleral expansion is probably the main cause of MRS. PMID:27294332

  15. SR and LR Union Suture for the Treatment of Myopic Strabismus Fixus: Is Scleral Fixation Necessary?

    PubMed Central

    Lam, Carol P. S.; Yam, Jason C. S.; Lau, Flora H. S.; Fan, Dorothy S. P.; Wong, C. Y.; Yu, Christopher B. O.; Lau, Winnie W. Y.

    2015-01-01

    Purpose. To evaluate and compare the effectiveness of scleral fixation SR and LR union suture and nonscleral fixation union suture for the treatment of myopic strabismus fixus. Methods. Retrospective review of 32 eyes of 22 patients with myopic strabismus fixus who had undergone union suture of superior rectus (SR) and lateral rectus (LR) with or without scleral fixation, and follow-up longer than 6 months at Hong Kong Eye Hospital from 2006 to 2013. Surgical techniques and outcomes in terms of ocular alignment are analyzed. Results. There is significant overall improvement both in postoperative angle of esodeviation (P < 0.01) and postoperative range of movement (P = 0.042). Comparing between the sclera fixation group (11 eyes) versus nonscleral fixation group (21 eyes), the postoperative horizontal deviation, the postoperative vertical deviation, successful outcome, and the change in horizontal deviation were not significantly different (P > 0.05). Conclusions. Union suture of SR and LR is an effective procedure in correcting myopic strabismus fixus. Fixation of the union suture to the sclera does not improve surgical outcome. PMID:25954751

  16. Treatment of choroid hemangioma with argon laser

    NASA Astrophysics Data System (ADS)

    Yang, Chuanzhu; Song, Man

    1993-03-01

    The treatment effects of 7 cases of choroid hemangioma are reported. Of them, 4 cases were men and 3 cases were women. Ages varied from 34 to 52 years. The mean age was 43 years. All of their eyesight was between 0.01 and 0.4. Six of the seven cases were solitary hemangioma, the other one was Sturge-Weber syndrome. After treatment photography, the color of the hemangioma body gradually got weak and the local presented pigmentation. The results of the fluorescein fundus angiography indicated that the hemangioma body reduced, then got atrophy and fibrosis. In five cases eyesight increased, and it didn't in the other two cases.

  17. A mixed choroid plexus papilloma and ependymoma.

    PubMed

    Lee, Yujin; Kim, Seong Ik; Kim, Seung-Ki; Kim, In One; Park, Sung-Hye

    2016-04-01

    We report a novel case of a mixed choroid plexus papilloma (CPP) and ependymoma with cartilaginous differentiation. This kind of mixed tumor has not been previously reported in the English literature. The patient was a 5-year-old girl, who presented with a 1-week history of fever and numbness of the right lower limb. Magnetic resonance imaging of the brain with gadolinium revealed a heterogeneously enhancing mass in the occipital horn of the left lateral ventricle. Histologically, the tumor showed an intermixed CPP area and a low-grade papillary ependymoma-like area, which was studded with cartilage islands and psammoma bodies. In many foci, direct transition of CPP and ependymoma was observed, but there were no high-grade features. We report this novel case, describe the unique microscopic and immunohistochemical features, and speculate on the pathogenesis. PMID:26670168

  18. Sector iris hemangioma in association with diffuse choroidal hemangioma.

    PubMed

    Shields, Carol L; Atalay, Hatice Tuba; Wuthisiri, Wadakarn; Levin, Alex V; Lally, Sara E; Shields, Jerry A

    2015-02-01

    Two patients referred for iris lesions were found to have sector hemangioma of the iris stroma in contiguity with diffuse choroidal hemangioma. Neither patient had other manifestations of Sturge-Weber syndrome. PMID:25727597

  19. Intravitreal bevacizumab and Ahmed glaucoma valve implantation in patients with neovascular glaucoma

    PubMed Central

    Zhang, Hai-Tao; Yang, Yu-Xin; Xu, Ying-Ying; Yang, Rui-Min; Wang, Bao-Jun; Hu, Jun-Xi

    2014-01-01

    AIM To explore the efficacy of preoperative intravitreal bevacizumab (IVB) injection combined with Ahmed glaucoma valve (AGV) implantation in the treatment of neovascular glaucoma (NVG). METHODS This retrospective study included 35 eyes from 35 patients who underwent preoperative IVB and AGV implantation for treatment of NVG. Findings such as intraocular pressure (IOP) number of anti-glaucoma medications, visual acuity (VA), surgical success rates, and complications were recorded. RESULTS After AGV implantation, IOP was 18.2±4.0 mm Hg, 15.5±3.3 mm Hg and 9.8±2.6 mm Hg at 6, 12 and 36mo, significantly decreased compared with pre-IOP (P<0.01). The number of anti-glaucoma medications was 0.9±0.5, 0.8±0.9 and 0.8±0.6 at 6, 12 and 36mo, significantly decreased compared to pre-treatment (P<0.01). At last visit, there were 19 eyes with stable VA, 4 with VA improvement, 12 with diminished VA and 3 with complete loss light perception. There were 7 cases that failed during 3-year fellow up period. Cumulative probabilities of valve survival by Kaplan-Meier analysis were 82.9%, 74.1% and 71.0% at 12, 24 and 36mo, respectively. Cox stepwise regression analysis found that the survival time was significant associated with the pre-visual acuity <2/400 (P<0.05). Post-operative complications occurred in 8 eyes, of which hyphema presented in 2 eyes, choroidal effusion in 2 eyes. CONCLUSION The procedure of preoperative IVB and AGV implantation should be one of treatments for NVG because of its safety and effectiveness. PMID:25349803

  20. Uncommon presentation of choroid plexus papilloma in an infant

    PubMed Central

    Pandey, Sharad; Sharma, Vivek; Singh, Kulwant; Ghosh, Amrita; Gupta, Praveen Kumar

    2016-01-01

    Choroid plexus tumors are relatively rare primary brain tumors that arise from the epithelial differentiated tissue, majority being well-differentiated papillomas. In adults, fourth ventricle and in children, lateral ventricles are the most common site of these tumors. We reported a case of choroid plexus papilloma in the temporal horn of lateral ventricle in a female child who presented with the uncommon symptoms of sudden intraventricular hemorrhage and multiple episodes of seizure without symptoms of raised intracranial tension. PMID:27195037

  1. 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.

  2. Pigmented choroidal nevus in a child with oculocutaneous albinism.

    PubMed

    Sharma, Priya; Kaliki, Swathi; Peña, Maria Soledad; Shields, Carol L

    2013-04-01

    We report the case of an 8-year-old white girl with albinism and a flat pigmented choroidal lesion in the left eye measuring 0.5 mm in diameter. There was no subretinal fluid, lipofuscin, or drusen. The patient later displayed 10 lightly-pigmented cutaneous nevi on her upper chest, left arm, and right leg at 8 months' follow-up. The choroidal nevus showed minimal change over 2 years. PMID:23352722

  3. Retino-choroidal ischemia in central retinal vein occlusion

    PubMed Central

    Hussain, Nazimul; Hussain, Anjli

    2014-01-01

    A 41-year-old gentleman with insulin dependent diabetes had decreased vision in the right eye due to non-ischemic central retinal vein occlusion with macular edema. One month following intravitreal ranibizumab, he developed retino-choroidal ischemia with further loss of vision. Authors show the fluorescein angiographic transition from non-ischemic central retinal vein occlusion to retino-choroidal ischemia. PMID:25473353

  4. Complement Factor H Expressed by Retinal Pigment Epithelium Cells Can Suppress Neovascularization of Human Umbilical Vein Endothelial Cells: An in vitro Study

    PubMed Central

    Zhang, Yi; Huang, Qing; Tang, Min; Zhang, Junjun; Fan, Wei

    2015-01-01

    Complement factor H (CFH) is one of the most important soluble complement regulatory proteins and is closely associated with age-related macular degeneration (AMD), the leading cause of irreversible central vision loss in the elderly population in developed countries. Our study searches to investigate whether CFH expression is changed in oxidative damaged retinal pigment epithelium (RPE) cells and the role of CFH in the in vitro neovascularization. First, it was confirmed by immunofluorescence staining that CFH was expressed by ARPE-19 cells. CFH mRNA and protein in oxidative (H2O2) damaged ARPE-19 cells were both reduced, as determined by Real-time PCR and Western blotting analysis. Enzyme-linked immunosorbent assay (ELISA) also showed that ARPE-19 cells treated with H2O2 caused an increase in C3a content, which indicates complement activation. Then, wound assays were performed to show that CFH expression suppression promoted human umbilical vein endothelial cell (HUVECs) migration. Thereafter, ARPE-19 cells were transfected with CFH-specific siRNA and CFH knockdown was confirmed with the aid of Real-time PCR, immunofluorescence staining and Western blotting. The ELISA results showed that specific CFH knockdown in ARPE-19 cells activated the complement system. Finally, in vitro matrigel tube formation assay was performed to determine whether change of CFH expression in RPE would affect tube formation by HUVECs. More tubes were formed by HUVECs co-cultured with ARPE-19 cells transfected with CFH specific-siRNA when compared with controls. Our results suggested that RPE cells might be the local CFH source, and RPE cell injuries (such as oxidative stress) may cause CFH expression suppression, which in turn may lead to complement activation and promotion of tube formation by HUVECs. This finding is of importance in elucidating the role of complement in the pathogenesis of ocular neovascularization including choroidal neovascularization. PMID:26091360

  5. CHOROIDAL MORPHOLOGY IN A PATIENT WITH HELLP SYNDROME

    PubMed Central

    Kasai, Ayaka; Sugano, Yukinori; Maruko, Ichiro

    2016-01-01

    Purpose: We report here, the morphological characteristics of the retina and choroid in a patient with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, who was not aware of her pregnancy before visiting our hospital. Methods: Case report. Results: The patient complained of visual disturbances in both eyes for a few days. Extensive serous retinal detachment and hyperreflective foci were observed in both eyes on spectral domain optical coherence tomography (SDOCT). Enhanced depth imaging technique using SDOCT revealed choroidal thickening and unclear choroidal vessel contour. Her blood pressure was 230/168 mmHg. Laboratory data showed hemolysis and liver dysfunction. Obstetrical examination disclosed her pregnancy. She was diagnosed as having HELLP syndrome. Because her general condition improved after prompt Cesarean delivery, the fundus lesions were rapidly resolved with choroidal thinning. Conclusion: The eyes in a patient with HELLP syndrome showed characteristic choroidal morphology. The choroidal morphology shown with SDOCT might be one of the pathognomonic signs for a diagnosis of HELLP syndrome. PMID:26595148

  6. 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

  7. Clinical correlates of common corneal neovascular diseases: a literature review

    PubMed Central

    Abdelfattah, Nizar Saleh; Amgad, Mohamed; Zayed, Amira A; Salem, Hamdy; Elkhanany, Ahmed E; Hussein, Heba; Abd El-Baky, Nawal

    2015-01-01

    A large subset of corneal pathologies involves the formation of new blood and lymph vessels (neovascularization), leading to compromised visual acuity. This article aims to review the clinical causes and presentations of corneal neovascularization (CNV) by examining the mechanisms behind common CNV-related corneal pathologies, with a particular focus on herpes simplex stromal keratitis, contact lenses-induced keratitis and CNV secondary to keratoplasty. Moreover, we reviewed CNV in the context of different types of corneal transplantation and keratoprosthesis, and summarized the most relevant treatments available so far. PMID:25709930

  8. Vision loss without Amsler grid abnormalities in macular subretinal neovascularization.

    PubMed

    Roy, M S

    1985-01-01

    An 87-year-old woman, with known atrophic senile macular degeneration in one eye, had isolated decreased reading ability while Amsler grid testing was normal. This led to the early diagnosis of macular subretinal neovascularization in the other eye. Thus patients at high risk for neovascular macular degeneration should be made aware of possible subtle changes in vision as well as abnormalities in the Amsler grid. Regular visual acuity check and careful biomicroscopic examination of the macula should be part of each follow-up examination.

  9. Outcomes of Proton Radiation Therapy for Peripapillary Choroidal Melanoma at the BC Cancer Agency

    SciTech Connect

    Tran, Eric; Ma, Roy; Paton, Katherine; Blackmore, Ewart; Pickles, Tom

    2012-08-01

    Purpose: To report toxicity, local control, enucleation, and survival rates for patients with peripapillary choroidal melanoma treated with proton therapy in Canada. Methods and Materials: We performed a retrospective analysis of patients with peripapillary choroidal melanoma ({<=}2 mm from optic disc) treated between 1995 and 2007 at the only Canadian proton therapy facility. A prospective database was updated for follow-up information from a chart review. Descriptive and actuarial data are presented. Results: In total, 59 patients were treated. The median age was 59 years. According to the 2010 American Joint Committee on Cancer TNM classification, there were 20 T1 tumors (34%), 28 T2 tumors (48%), and 11 T3 tumors (19%). The median tumor diameter was 11.4 mm, and the median thickness was 3.5 mm. Median follow-up was 63 months. Nineteen patients received 54 cobalt gray equivalents (CGE) and forty patients received 60 CGE, each in 4 fractions. The 5-year actuarial local control rate was 91% (T1, 100%; T2, 93%; and T3, 59%) (p = 0.038). There was a suggestive relationship between local control and dose. The local control rate was 97% with 60 CGE and 83% with 54 CGE (p = 0.106). The metastasis-free survival rate was 82% and related to T stage (T1, 94%; T2, 84%; and T3, 47%) (p < 0.001). Twelve patients died, including eleven with metastases. The 5-year actuarial rate of neovascular glaucoma was 31% (23% for T1-T2 and 68% for T3, p < 0.001), and that of enucleation was 0% for T1, 14% for T2, and 72% for T3 (p < 0.001). Radiation retinopathy (74%) and optic neuropathy (64%) were common within-field effects. Conclusions: Proton therapy provides excellent local control with acceptable toxicity while conserving the globe in 80% of cases. These results are consistent with other single-institution series using proton radiotherapy, and toxicity rates were acceptable. T3 tumors carry a higher rate of both local recurrence and metastasis.

  10. Dosimetric and Late Radiation Toxicity Comparison Between Iodine-125 Brachytherapy and Stereotactic Radiation Therapy for Juxtapapillary Choroidal Melanoma

    SciTech Connect

    Krema, Hatem

    2013-07-01

    Purpose: To compare the dose distributions and late radiation toxicities for {sup 125}I brachytherapy (IBT) and stereotactic radiation therapy (SRT) in the treatment of juxtapapillary choroidal melanoma. Methods: Ninety-four consecutive patients with juxtapapillary melanoma were reviewed: 30 have been treated with IBT and 64 with SRT. Iodine-125 brachytherapy cases were modeled with plaque simulator software for dosimetric analysis. The SRT dosimetric data were obtained from the Radionics XKnife RT3 software. Mean doses at predetermined intraocular points were calculated. Kaplan-Meier estimates determined the actuarial rates of late toxicities, and the log–rank test compared the estimates. Results: The median follow-up was 46 months in both cohorts. The 2 cohorts were balanced with respect to pretreatment clinical and tumor characteristics. Comparisons of radiation toxicity rates between the IBT and SRT cohorts yielded actuarial rates at 50 months for cataracts of 62% and 75% (P=.1), for neovascular glaucoma 8% and 47% (P=.002), for radiation retinopathy 59% and 89% (P=.0001), and for radiation papillopathy 39% and 74% (P=.003), respectively. Dosimetric comparisons between the IBT and SRT cohorts yielded mean doses of 12.8 and 14.1 Gy (P=.56) for the lens center, 17.6 and 19.7 Gy (P=.44) for the lens posterior pole, 13.9 and 10.8 Gy (P=.30) for the ciliary body, 61.9 and 69.7 Gy (P=.03) for optic disc center, and 48.9 and 60.1 Gy (P<.0001) for retina at 5-mm distance from tumor margin, respectively. Conclusions: Late radiation-induced toxicities were greater with SRT, which is secondary to the high-dose exposure inherent to the technique as compared with IBT. When technically feasible, IBT is preferred to treat juxtapapillary choroidal melanoma.

  11. Patterns of tumor initiation in choroidal melanoma.

    PubMed

    Li, W; Judge, H; Gragoudas, E S; Seddon, J M; Egan, K M

    2000-07-15

    This study attempts to document the occurrence of tumors with respect to clock hour location and distance from the macula and to evaluate tumor location in relation to retinal topography and light dose distribution on the retinal sphere. Analysis of patterns of tumor initiation may provide new evidence to clarify the controversy regarding the possible light-related etiology of choroidal melanoma. Incident cases of choroidal and ciliary body melanoma in Massachusetts residents diagnosed between 1984 and 1993 were the basis for analysis. Conventional fundus drawings and photos were used to assess the initiation site of each tumor. The initiation site was defined as the intersect between the largest tumor diameter and the largest perpendicular diameter of the tumor. Initiation sites were recorded using spherical coordinates. The retinal sphere was divided into 61 mutually exclusive sectors defined according to clock hour and anteroposterior distance from the macula. Rates of initiation were computed for each sector, overall, and according to gender and other clinical factors. Results were similar in left and right eyes; therefore, these were combined in analysis. Tumor initiation had a predilection for the macula (P < 0.0001). Overall, no significant clock hour preference was observed (P = 0.63). However, the parafoveal zone showed a strong circular trend (P < 0.01), with highest rates occurring in the temporal region, and the lowest rates occurring in the nasal region. Rates of occurrence in six progressively more anterior concentric zones (designated as the foveal, parafoveal, posterior, peripheral, anterior, and ciliary body zones) were 21.4, 14.2, 12.1, 8.9, 4.5, and 4.3 counts per spherical unit per 1000 eyes, respectively. Concentric zone location did not vary by gender (P = 0.93) or laterality (P = 0.78). However, posterior location was associated with light iris color (P = 0.01). Tumor diameters were largest in the peripheral region of the fundus and smallest

  12. Radiation therapy for neovascular age-related macular degeneration

    PubMed Central

    Petrarca, Robert; Jackson, Timothy L

    2011-01-01

    Antivascular endothelial growth factor (anti-VEGF) therapies represent the standard of care for most patients presenting with neovascular (wet) age-related macular degeneration (neovascular AMD). Anti-VEGF drugs require repeated injections and impose a considerable burden of care, and not all patients respond. Radiation targets the proliferating cells that cause neovascular AMD, including fibroblastic, inflammatory, and endothelial cells. Two new neovascular AMD radiation treatments are being investigated: epimacular brachytherapy and stereotactic radiosurgery. Epimacular brachytherapy uses beta radiation, delivered to the lesion via a pars plana vitrectomy. Stereotactic radiosurgery uses low voltage X-rays in overlapping beams, directed onto the lesion. Feasibility data for epimacular brachytherapy show a greatly reduced need for anti-VEGF therapy, with a mean vision gain of 8.9 ETDRS letters at 12 months. Pivotal trials are underway (MERLOT, CABERNET). Preliminary stereotactic radiosurgery data suggest a mean vision gain of 8 to 10 ETDRS letters at 12 months. A large randomized sham controlled stereotactic radiosurgery feasibility study is underway (CLH002), with pivotal trials to follow. While it is too early to conclude on the safety and efficacy of epimacular brachytherapy and stereotactic radiosurgery, preliminary results are positive, and these suggest that radiation offers a more durable therapeutic effect than intraocular injections. PMID:21311657

  13. Spatially Heterogeneous Choroid Plexus Transcriptomes Encode Positional Identity and Contribute to Regional CSF Production

    PubMed Central

    Lun, Melody P.; Johnson, Matthew B.; Broadbelt, Kevin G.; Watanabe, Momoko; Kang, Young-jin; Chau, Kevin F.; Springel, Mark W.; Malesz, Alexandra; Sousa, André M.M.; Pletikos, Mihovil; Adelita, Tai; Calicchio, Monica L.; Zhang, Yong; Holtzman, Michael J.; Lidov, Hart G.W.; Sestan, Nenad; Steen, Hanno; Monuki, Edwin S.

    2015-01-01

    A sheet of choroid plexus epithelial cells extends into each cerebral ventricle and secretes signaling factors into the CSF. To evaluate whether differences in the CSF proteome across ventricles arise, in part, from regional differences in choroid plexus gene expression, we defined the transcriptome of lateral ventricle (telencephalic) versus fourth ventricle (hindbrain) choroid plexus. We find that positional identities of mouse, macaque, and human choroid plexi derive from gene expression domains that parallel their axial tissues of origin. We then show that molecular heterogeneity between telencephalic and hindbrain choroid plexi contributes to region-specific, age-dependent protein secretion in vitro. Transcriptome analysis of FACS-purified choroid plexus epithelial cells also predicts their cell-type-specific secretome. Spatial domains with distinct protein expression profiles were observed within each choroid plexus. We propose that regional differences between choroid plexi contribute to dynamic signaling gradients across the mammalian cerebroventricular system. PMID:25810521

  14. Rap1 GTPase Inhibits Tumor Necrosis Factor-α-Induced Choroidal Endothelial Migration via NADPH Oxidase- and NF-κB-Dependent Activation of Rac1.

    PubMed

    Wang, Haibo; Fotheringham, Lori; Wittchen, Erika S; Hartnett, M Elizabeth

    2015-12-01

    Macrophage-derived tumor necrosis factor (TNF)-α has been found in choroidal neovascularization (CNV) surgically removed from patients with age-related macular degeneration. However, the role of TNF-α in CNV development remains unclear. In a murine laser-induced CNV model, compared with un-lasered controls, TNF-α mRNA was increased in retinal pigment epithelial and choroidal tissue, and TNF-α colocalized with lectin-stained migrating choroidal endothelial cells (CECs). Inhibition of TNF-α with a neutralizing antibody reduced CNV volume and reactive oxygen species (ROS) level around CNV. In CECs, pretreatment with the antioxidant apocynin or knockdown of p22phox, a subunit of NADPH oxidase, inhibited TNF-α-induced ROS generation. Apocynin reduced TNF-α-induced NF-κB and Rac1 activation, and inhibited TNF-α-induced CEC migration. TNF-α-induced Rac1 activation and CEC migration were inhibited by NF-κB inhibitor Bay11-7082. Overexpression of Rap1a prevented TNF-α-induced ROS generation and reduced NF-κB and Rac1 activation. Activation of Rap1 by 8-(4-chlorophenylthio)adenosine-2'-O-Me-cAMP prevented TNF-α-induced CEC migration and reduced laser-induced CNV volume, ROS generation, and activation of NF-κB and Rac1. These findings provide evidence that active Rap1a inhibits TNF-α-induced CEC migration by inhibiting NADPH oxidase-dependent NF-κB and Rac1 activation and suggests that Rap1a de-escalates CNV development by interfering with ROS-dependent signaling in several steps of the pathogenic process. PMID:26476350

  15. Total ocular, anterior corneal and lenticular higher order aberrations in hyperopic, myopic and emmetropic eyes.

    PubMed

    Philip, Krupa; Martinez, Aldo; Ho, Arthur; Conrad, Fabian; Ale, Jit; Mitchell, Paul; Sankaridurg, Padmaja

    2012-01-01

    Total ocular higher order aberrations and corneal topography of myopic, emmetropic and hyperopic eyes of 675 adolescents (16.9 ± 0.7 years) were measured after cycloplegia using COAS aberrometer and Medmont videokeratoscope. Corneal higher order aberrations were computed from the corneal topography maps and lenticular (internal) higher order aberrations derived by subtraction of corneal aberrations from total ocular aberrations. Aberrations were measured for a pupil diameter of 5mm. Multivariate analysis of variance followed by multiple regression analysis found significant difference in the fourth order aberrations (SA RMS, primary spherical aberration coefficient) between the refractive error groups. Hyperopic eyes (+0.083 ± 0.05 μm) had more positive total ocular primary spherical aberration compared to emmetropic (+0.036 ± 0.04 μm) and myopic eyes (low myopia=+0.038 ± 0.05 μm, moderate myopia=+0.026 ± 0.06 μm) (p<0.05). No difference was observed for the anterior corneal spherical aberration. Significantly less negative lenticular spherical aberration was observed for the hyperopic eyes (-0.038 ± 0.05 μm) than myopic (low myopia=-0.088 ± 0.04 μm, moderate myopia=-0.095 ± 0.05 μm) and emmetropic eyes (-0.081 ± 0.04 μm) (p<0.05). These findings suggest the existence of differences in the characteristics of the crystalline lens (asphericity, curvature and gradient refractive index) of hyperopic eyes versus other eyes.

  16. Risk Factors of Myopic Shift among Primary School Children in Beijing, China: A Prospective Study

    PubMed Central

    Wu, Li-Juan; Wang, You-Xin; You, Qi-Sheng; Duan, Jia-Li; Luo, Yan-Xia; Liu, Li-Juan; Li, Xia; Gao, Qi; Zhu, Hui-Ping; He, Yan; Xu, Liang; Song, Man-Shu; Jonas, Jost B; Guo, Xiu-Hua; Wang, Wei

    2015-01-01

    Objective: To evaluate factors associated with myopic shift among primary school children. Methods: In a one-year prospective school-based study, 5052 children from ten schools were enrolled using a multi-stage random cluster approach. The baseline examination included non-cycloplegic auto-refractometry and questionnaire interview. Measurements were repeated at the follow-up. Results: Among 5052 students at baseline investigated, 4292 students (85.0%) returned for the follow-up examination. The mean refractive error (-1.13±1.57 diopters) had changed -0.52±0.73 diopters from the baseline to the follow-up examination. 2170 (51.0%) had a rate of significant myopic shift (significant myopic shift is defined as the change of spherical equivalent of the refraction ≤ -0.50D between the follow-up and baseline measures). We confirmed that common associated factors (older age, parental myopia, lower refractive status at baseline, shorter reading distance and lower frequency of outdoor activities during class recesses) were associated with greater shift towards myopia. After controlling for age, sex, region of habitation, parental myopia and refractive status at baseline, greater shift towards myopia was independently associated with distance from near-work (OR=1.48 , 95% CI=1.26-1.74, P<0.001) and longer time outdoors for leisure (OR=0.87, 95% CI=0.78-0.97, P<0.013). Conclusion: Greater shift towards myopia was independently associated with modifiable factors (distance from near-work and longer time outdoors for leisure) might suggest that encouraging children to go outside for outdoor activities during class recess and after school may be a promising and feasible intervention against myopia development. PMID:26283882

  17. Gamma Knife Radiosurgery for Choroidal Hemangioma

    SciTech Connect

    Kim, Yun Taek; Kang, Se Woong; Lee, Jung-Il

    2011-12-01

    Purpose: Patients with choroidal hemangioma (CH), a benign ocular hamartoma, frequently presents with visual disturbance as a result of exudative retinal detachment (RD), which originates in subretinal fluid accumulation. We report our experience using the Leksell Gamma Knife in the management of symptomatic CH. Methods and Materials: Seven patients with symptomatic CH (circumscribed form in 3 patients and diffuse form in 4) were treated with the Leksell Gamma Knife at our institution during a 7-year period. All patients presented with exudative RD involving the macula that resulted in severe visual deterioration. The prescription dose to the target margin was 10 Gy in all cases. The mean tumor volume receiving the prescription dose was 536 mm{sup 3} (range, 151-1,057). The clinical data were analyzed in a retrospective fashion after a mean follow-up of 34.4 months (range, 9-76). Results: The resolution of exudative RD was achieved within 6 months, and the visual acuity of the affected eye had improved at the latest follow-up examination (p = .018) in all patients. No recurrence of exudative RD occurred. Thinning of the CHs was observed in most patients; however, symptomatic radiation toxicity had not developed in any of the patients. Conclusion: Symptomatic CHs can be safely and effectively managed with Gamma Knife radiosurgery using a marginal dose of 10 Gy.

  18. Peripapillary choroidal thickness in healthy Turkish subjects

    PubMed Central

    Erbagci, Hulya; Oren, Burak; Okumus, Seydi; Kenan, Serhat; Celemler, Pelin; Erbagci, Ibrahim

    2015-01-01

    Aim The objective of the study reported here was to investigate the normal peripapillary choroidal thickness (CT), measured by enhanced depth imaging optical coherence tomography (EDI-OCT), in healthy Turkish volunteers. Materials and methods In this prospective cross-sectional study, 57 eyes of 57 healthy Turkish subjects were enrolled. Each participant underwent a comprehensive ophthalmic examination and peripapillary CT measurement using EDI-OCT. Results The mean age of the 25 female and 32 male patients in the study was 30.9±10.6 years (range, 18–56 years). The mean peripapillary CT at the superior, inferior, nasal, and temporal sites was 225±57, 183±47, 220±57, and 233±59 μm, respectively. The inferior peripapillary CT value was significantly lower than the peripapillary CT values (P<0.001 for all), whereas no significant differences were found between the superior, nasal, and temporal peripapillary CT values. Conclusion The findings of the study revealed that Turkish people had significantly lower peripapillary CT values in the inferior quadrant than in the superior, nasal, and temporal quadrants. PMID:26257510

  19. A noninvasive eye fixation monitoring system for CyberKnife radiotherapy of choroidal and orbital tumors

    SciTech Connect

    Daftari, I. K.; Petti, P. L.; Larson, D. A.; O'Brien, J. M.; Phillips, T. L.

    2009-03-15

    A new noninvasive monitoring system for fixing the eye has been developed to treat orbital and choroidal tumors with CyberKnife-based radiotherapy. This device monitors the eye during CT/MRI scanning and during treatment. The results of this study demonstrate the feasibility of the fixation light system for CyberKnife-based treatments of orbital and choroidal tumors and supports the idea that larger choroidal melanomas and choroidal metastases could be treated with CyberKnife without implanting fiducial markers.

  20. Evidence of a novel gene HERPUD1 in polypoidal choroidal vasculopathy

    PubMed Central

    Jin, Enzhong; Bai, Yujing; Huang, Lvzhen; Zhao, Min; Zhang, Chunfang; Zhao, Mingwei; Li, Xiaoxin

    2015-01-01

    Polypoidal choroidal vasculopathy (PCV) is an exudative maculopathy, with clinical features distinct from neovascular age-related macular degeneration (nAMD) which is the leading cause of irreversible blindness in the elderly. Our studies focused on the genetic background and function of a novel gene HERPUD1 in PCV. HERPUD1 has been reported to increase the level of amyloid β (Aβ), which is a component of drusen deposits underlying the retinal pigment epithelium (RPE) layer. To verify the genetic functional associations of HERPUD1 with PCV, exome sequencing of HERPUD1 was performed in unrelated Chinese individuals, including nAMD patients, PCV patients and control subjects. Immunohistochemistry assays for HERPUD1 were performed in the subretinal membranes of PCV patients. The relationship between HERPUD1 and amyloid beta precursor was determined using real-time PCR in HERPUD1-overexpressing RPE cells. The gene expression patterns of angiogenesis cytokines and chemokines in both Aβ-treated RPE cells and in Brown Norway rats that received Aβ subretinal injections were determined. We showed that HERPUD1 rs2217332 is significant associated with Chinese PCV, and HERPUD1 was expressed in PCV subretinal membranes. Besides, Plasma Aβ42 protein was significantly higher in PCV patients compared to nAMD and control subjects. Aβ could upregulate angiogenic factors, chemokines and matrix metalloproteinases both in RPE cells and in a rat model of subretinal Aβ injection. The imbalance of the cytokines may be one of the mechanisms for the formation and development of PCV. Our results strongly suggest that HERPUD1 is highly associated with PCV patients. PMID:26823705

  1. Evaluation of Retinal and Choroidal Thickness in Fuchs' Uveitis Syndrome

    PubMed Central

    Ozsutcu, Mustafa

    2016-01-01

    Purpose. We aimed to investigate retinal and choroidal thickness in the eyes of patients with Fuchs' uveitis syndrome (FUS). Methods. Fifteen patients with unilateral FUS and 20 healthy control subjects were enrolled. Spectral domain optical coherence tomography (Spectralis HRA+OCT, 870 nm; Heidelberg Engineering, Heidelberg, Germany) was used to obtain retinal and choroidal thickness measurements. The retinal nerve fiber layer (RNFL) thickness, macular thickness, and choroidal thickness of the eyes with FUS were compared with the unaffected eye and the eyes of healthy control subjects. Results. The mean choroidal thickness at fovea and at each point within the horizontal nasal and temporal quadrants at 500 μm intervals to a distance of 1500 µm from the foveal center was significantly thinner in the affected eye of FUS patients compared with the unaffected eye of FUS patients or the eyes of healthy control subjects. However, there were no significant differences in RNFL or macular thickness between groups. Conclusions. Affected eyes in patients with FUS tend to have thinner choroids as compared to eyes of unaffected fellow eyes and healthy individuals, which might be a result of the chronic inflammation associated with the disease. PMID:27579176

  2. Bilateral Choroidal Metastases from Lung Adenocarcinoma: A Case Report

    PubMed Central

    Ergenc, Hasan; Onmez, Attila; Oymak, Ezgi; Tanriseven, Ramiser; Celik, Erkan; Onmez, Funda Ebru; Tamer, Ali; Baykara, Meltem

    2016-01-01

    The most common malignancy of the eye is metastatic tumors, with choroidal metastases being the majority of them. In women, breast cancer is the most common cause of orbital metastases, and in men, it is lung cancer. Despite the fact that there are efficient treatment options for orbital metastases, the benefit of procedures to detect choroidal metastases is debatable due to the quick progression and poor prognosis of lung cancer. In choroidal metastases resulting from lung cancer, patients are usually presented with decreased sight. Defects in the field of vision, flashes of light and floating bodies generally follow. Treatment options of choroidal metastases include many methods including laser photocoagulation, cryotherapy, chemotherapy, radiotherapy, surgical resection, enucleation and photodynamic therapy. There are reports emphasizing radiotherapy as the most efficient treatment option. In this case report, we sum up the case of a male patient presenting with blurry vision in both eyes, who was subsequently detected to have bilateral choroidal metastatic tumor and was diagnosed with primary lung adenocarcinoma.

  3. Bone Remodeling in Choroidal Osteoma Monitored by Fundus Photography and Spectral-Domain Optical Coherence Tomography

    PubMed Central

    Kamalden, Tengku Ain; Lingam, Gopal; Sundar, Gangadhara

    2014-01-01

    Choroidal osteoma is a benign ossifying tumor of the choroid, consisting of mature bone tissue. It has been described to enlarge and evolve at varying rates over time. Here, we report and quantify the progression of a unilateral choroidal osteoma in a 7-year-old boy by fundus photography, and document tumor remodeling by spectral domain optical coherence tomography images. PMID:27175357

  4. DIFFUSE PERIPAPILLARY CHOROIDAL MELANOMA THAT EVOLVED FROM A SMALL PRESUMED CHOROIDAL NEVUS SUCCESSFULLY TREATED WITH GAMMA KNIFE RADIOTHERAPY

    PubMed Central

    Duker, Jacob S.

    2016-01-01

    Purpose: To report a case of diffuse peripapillary choroidal melanoma which began as a small choroidal nevus and was successfully treated with gamma knife radiotherapy. Methods: Observational case report. Results: A 31-year-old visually asymptomatic man presented for a routine eye examination and was noted to have a small choroidal nevus. Six years later, the lesion had become a diffuse juxtapapillary choroidal melanoma with a thickness of 1.9 mm. Given the peripapillary location of the tumor with involvement of about 6 clock hours of the disk, Leksell Gamma Knife radiotherapy was performed. At 5.5 years after radiation therapy, visual acuity remained 20/20. The lesion thickness had decreased to 1.5 mm, and there was no interval growth of any margins. Conclusion: Small choroidal nevi carry low malignant potential but still deserve photographic documentation when possible with regular follow intervals. Gamma knife radiotherapy can be considered for tumors abutting the optic nerve, especially when plaque radiotherapy may be technically difficult. PMID:26963960

  5. RPE and Choroid Mechanisms Underlying Ocular Growth and Myopia.

    PubMed

    Zhang, Yan; Wildsoet, Christine F

    2015-01-01

    Myopia is the most common type of refractive errors and one of the world's leading causes of blindness. Visual manipulations in animal models have provided convincing evidence for the role of environmental factors in myopia development. These models along with in vitro studies have provided important insights into underlying mechanisms. The key locations of the retinal pigment epithelium (RPE) and choroid make them plausible conduits for relaying growth regulatory signals originating in the retina to the sclera, which ultimately determines eye size and shape. Identifying the key signal molecules and their targets may lead to the development of new myopia control treatments. This section summarizes findings implicating the RPE and choroid in myopia development. For RPE and/or choroid, changes in morphology, activity of ion channels/transporters, as well as in gene and protein expression, have been linked to altered eye growth. Both tissues thus represent potential targets for novel therapies for myopia.

  6. RPE and Choroid Mechanisms Underlying Ocular Growth and Myopia

    PubMed Central

    Zhang, Yan; Wildsoet, Christine F.

    2016-01-01

    Myopia is the most common type of refractive errors and one of the world’s leading causes of blindness. Visual manipulations in animal models have provided convincing evidence for the role of environmental factors in myopia development. These models along with in vitro studies have provided important insights into underlying mechanisms. The key locations of the retinal pigment epithelium (RPE) and choroid make them plausible conduits for relaying growth regulatory signals originating in the retina to the sclera, which ultimately determines eye size and shape. Identifying the key signal molecules and their targets may lead to the development of new myopia control treatments. This section summarizes findings implicating the RPE and choroid in myopia development. For RPE and/or choroid, changes in morphology, activity of ion channels/transporters, as well as in gene and protein expression, have been linked to altered eye growth. Both tissues thus represent potential targets for novel therapies for myopia. PMID:26310157

  7. Laser-induced macular holes demonstrate impaired choroidal perfusion

    NASA Astrophysics Data System (ADS)

    Brown, Jeremiah, Jr.; Allen, Ronald D.; Zwick, Harry; Schuschereba, Steven T.; Lund, David J.; Stuck, Bruce E.

    2003-06-01

    Choroidal perfusion was evaluated following the creation of a laser induced macular hole in a nonhuman primate model. Two Rhesus monkeys underwent macular exposures delivered by a Q-switched Nd:YAG laser. The lesions were evaluated with fluorescein angiography and indocyanine green (ICG) angiography . Each lesion produced vitreous hemorrhage and progressed to a full thickness macular hole. ICG angiography revealed no perfusion of the choriocapillaris beneath the lesion centers. Histopathologic evaluation showed replacement of the choriocapillaris with fibroblasts and connective tissue. Nd:YAG, laser-induced macular holes result in long term impairment of choroidal perfusion at the base of the hole due to choroidal scarring and obliteration of the choriocapillaris.

  8. Follow-up studies of suspicious choroidal nevi.

    PubMed

    Mims, J L; Shields, J A

    1978-09-01

    The fundus photographs and fluorescein angiograms of 255 consecutive cases of choroidal nevi were reviewed. Sixty-one cases (24%) were selected as suspicious on the basis of strict preestablished criteria including greatest single diameter, elevation, degree of disruption of the retinal pigment epithelium, and presence of subretinal fluid. Fifty of these 61 had adequate four-year follow-up. The remaining 194 cases, labeled as nonsuspicious, were usually small, relatively flat, slate-grey nevi which failed to meet the criteria for being suspicious. Of the 50 suspicious choroidal nevi followed four years, five (10%) showed photographic evidence of growth 4 to 30 months after the last examination. In contrast, none of the 194 nonsuspicious cases demonstrated growth. On the basis of these results, recommendations are made for the management of suspicious choroidal nevi.

  9. Massive choroidal hemorrhage associated with low molecular weight heparin therapy.

    PubMed

    Neudorfer, M; Leibovitch, I; Goldstein, M; Loewenstein, A

    2002-04-01

    An 84-year-old woman with unstable angina pectoris was treated with subcutaneous enoxaparine (Clexane) for several days before presenting with severe pain and decreased vision in her left eye. The intraocular pressure was 70 mmHg, and fundus examination showed a pigmented choroidal lesion and associated choroidal and retinal detachment. Ultrasonography was consistent with choroidal hemorrhage, and she was diagnosed as having acute glaucoma secondary to massive subchoroidal hemorrhage. Medical control of the intraocular pressure resulted in a significant clinical improvement. Intraocular hemorrhage and angle-closure glaucoma are rare and previously unreported complications in patients treated with low molecular weight heparin. It is important to be aware of this ocular complication as these drugs are so often used. PMID:11943940

  10. Brightness perception under transient glare conditions with myopic observers wearing contact lenses and spectacles

    NASA Astrophysics Data System (ADS)

    Issolio, Luis; Lopez-Gil, Norberto; Colombo, Elisa M.; Miro, Ignacio

    2001-08-01

    Transient glare reduces the perceived brightness for stimulus luminances within the scotopic-mesopic range. This work studies this effect in myopic observers with lens and spectacles corrections and in one emmetrope. The task of the subject consists of compare brightness of two uniform luminance fields sequentially displayed, one of which had a reference luminance of 1 cd/m2. The reference stimulus was presented under glare condition the angle between the glare source and the lie of sight was 10 degrees. The reference field and he glare source were onset at the same time. Subjects had to report which field was brighter with respect to one another. A YES-NO method with constant stimulus was adopted to determine the perceptual matching luminance. Then duration of each stimulus was 300 msec and the interval between both of them was 1.2 msec. We found the effect of the transient glare is stronger as myopic subjects wear glasses corrections than they wear contact lens and the effect is even less for emmetropic subject with the naked eyes. Results could be explained considering an additional ectoptic light veil due to scattering on the glasses and lens.

  11. Comparison of Subjective Refraction under Binocular and Monocular Conditions in Myopic Subjects.

    PubMed

    Kobashi, Hidenaga; Kamiya, Kazutaka; Handa, Tomoya; Ando, Wakako; Kawamorita, Takushi; Igarashi, Akihito; Shimizu, Kimiya

    2015-07-28

    To compare subjective refraction under binocular and monocular conditions, and to investigate the clinical factors affecting the difference in spherical refraction between the two conditions. We examined thirty eyes of 30 healthy subjects. Binocular and monocular refraction without cycloplegia was measured through circular polarizing lenses in both eyes, using the Landolt-C chart of the 3D visual function trainer-ORTe. Stepwise multiple regression analysis was used to assess the relations among several pairs of variables and the difference in spherical refraction in binocular and monocular conditions. Subjective spherical refraction in the monocular condition was significantly more myopic than that in the binocular condition (p < 0.001), whereas no significant differences were seen in subjective cylindrical refraction (p = 0.99). The explanatory variable relevant to the difference in spherical refraction between binocular and monocular conditions was the binocular spherical refraction (p = 0.032, partial regression coefficient B = 0.029) (adjusted R(2) = 0.230). No significant correlation was seen with other clinical factors. Subjective spherical refraction in the monocular condition was significantly more myopic than that in the binocular condition. Eyes with higher degrees of myopia are more predisposed to show the large difference in spherical refraction between these two conditions.

  12. Effect of accommodation training by stereoscopic movie presentation on myopic youth

    NASA Astrophysics Data System (ADS)

    Sugiura, A.; Takada, H.; Yamamoto, T.; Miyao, M.

    2010-02-01

    The abnormal contraction of ciliary muscles due to the performance of a near visual task for several hours causes various vision problems such as asthenopia and visual loss. However, these problems can be resolved by activating the muscles by alternately repeating negative and positive accommodation. In this study, we have verified the effect of accommodation training that uses the strategy of presenting a stereoscopic movie to myopic youth and measuring the uncorrected distant visual acuity, spherical diopter (SPH), and subjective index of asthenopia obtained using a visual analog scale (VAS). Stereoscopic movies are prepared by using the POWER 3D method (Olympus Visual Communications Co., Ltd.), which reduces the inconsistency between the experienced and the actual senses. Thirty two myopic students aged 20 +/- 1 years (16 males and 16 females) were chosen as the subjects. One group performed the accommodation training for 6 min, and the other group underwent a near visual task during the same period as the control group. We concluded the following from each item of verification: (a) The accommodation training using a stereoscopic movie had temporarily improved visual acuity. (b) This training led to a decrease in asthenopia. (c) The training improved the near-point accommodation function.

  13. Eplerenone in the Treatment of Polypoidal Choroidal Vasculopathy.

    PubMed

    Kapoor, Kapil G; Wagner, Alan L

    2015-01-01

    Overactivation of mineralocorticoid receptor pathways has been implicated in the pathophysiology of central serous chorioretinopathy (CSCR). Recently, mineralocorticoid receptor antagonists such as eplerenone have demonstrated success in treating subretinal fluid in CSCR. This case demonstrates a patient who was initially presumed to have subretinal fluid secondary to CSCR and was started on a trial of oral eplerenone. It quickly became evident that her subretinal fluid was secondary to a peripapillary polypoidal choroidal vasculopathy network, but she demonstrated a significant improvement with oral eplerenone. To the authors' knowledge, this is the first case of eplerenone use to treat polypoidal choroidal vasculopathy.

  14. Giant choroid plexus papilloma of the lateral ventricle in fetus

    PubMed Central

    Verma, Satish Kumar; Satyarthee, Guru Dutta; Sharma, Bhawani Shankar

    2014-01-01

    Choroid plexus papillomas (CPPs) are rare tumors having bimodal distribution. Pediatric CPPs are commonly present in supratentorial compartment and most commonly located in lateral ventricle and usually present at 16-18 months. Authors could find only one case report of fetal choroid plexus papilloma in the literature. In the present case, authors illustrate an unusual presentation of CPP with raised intracranial pressure (ICP) since birth, the need for proper preoperative planning, meticulous surgical technique, and intensive intra operative monitoring for normothermia, fluid-electrolyte balance, and blood replacement for achieving excellent results. PMID:25250084

  15. Neovascular glaucoma in a child: an unusual presentation of medulloepithelioma

    PubMed Central

    Kassa, Enoch; Li, Helen; Sun, Yang

    2014-01-01

    A healthy 12 month old infant without significant medical history presented with left eye redness for one week. Ophthalmic examination showed elevated intraocular pressure with iris neovascularization in the affected eye with increased optic nerve cupping. Scleral depression revealed a ciliary body mass in the supratemporal quadrant. A large, non-pigmented, vascular mass was noted; biopsy results showed multilayered cords, tubules, and sheets resembling primitive medullary epithelium arising from the ciliary body. The patient was diagnosed with medulloepithelioma. The patient underwent enucleation of the affected eye. Medulloepithelioma is a rare but important cause of neovascular glaucoma in the pediatric population. This case will focus on the characteristics of medulloepthelioma and the differential diagnosis for a non-pigmented ciliary body mass in a child.

  16. Mesenchymal-endothelial-transition contributes to cardiac neovascularization

    PubMed Central

    Ubil, Eric; Duan, Jinzhu; Pillai, Indulekha C.L.; Rosa-Garrido, Manuel; Wu, Yong; Bargiacchi, Francesca; Lu, Yan; Stanbouly, Seta; Huang, Jie; Rojas, Mauricio; Vondriska, Thomas M.; Stefani, Enrico; Deb, Arjun

    2014-01-01

    Endothelial cells contribute to a subset of cardiac fibroblasts by undergoing endothelial-to-mesenchymal-transition, but whether cardiac fibroblasts can adopt an endothelial cell fate and directly contribute to neovascularization after cardiac injury is not known. Here, using genetic fate map techniques, we demonstrate that cardiac fibroblasts rapidly adopt an endothelial cell like phenotype after acute ischemic cardiac injury. Fibroblast derived endothelial cells exhibit anatomical and functional characteristics of native endothelial cells. We show that the transcription factor p53 regulates such a switch in cardiac fibroblast fate. Loss of p53 in cardiac fibroblasts severely decreases the formation of fibroblast derived endothelial cells, reduces post infarct vascular density and worsens cardiac function. Conversely, stimulation of the p53 pathway in cardiac fibroblasts augments mesenchymal to endothelial transition, enhances vascularity and improves cardiac function. These observations demonstrate that mesenchymal-to-endothelial-transition contributes to neovascularization of the injured heart and represents a potential therapeutic target for enhancing cardiac repair. PMID:25317562

  17. Optical Coherence Tomography: An Adjunctive Tool for Differentiating between Choroidal Melanoma and Metastasis

    PubMed Central

    Vishnevskia-Dai, Vicktoria; Zur, Dinah; Yaacobi, Shiran; Moroz, Iris; Newman, Hadas; Neudorfer, Meira

    2016-01-01

    Purpose. To investigate the value of optical coherence tomography (OCT) for differentiation between choroidal melanoma and metastasis based on characteristics of the anterior choroidal surface and the chorioretinal interface. Methods. This retrospective observational case series included 29 patients with untreated choroidal melanomas and 21 patients with untreated choroidal metastases. Regularity and lobularity characteristics of the anterior choroidal surface were evaluated in a masked manner. Retinal and retinal pigment epithelium (RPE) findings were documented as well. Results. OCT demonstrated a regular and smooth anterior choroidal surface in 89.7% of the eyes with melanoma and in 47.6% of the eyes with metastasis (p = 0.002; sensitivity = 89.7%; specificity = 52.4%). The anterior choroidal contour was lobulated in 81.0% of the eyes with metastasis versus 17.2% of the eyes with melanoma (p < 0.001; sensitivity = 82.8%; specificity = 81.0%). RPE thickness and neuroretinal characteristics (e.g., retinal thickness, the presence of cysts, and the presence of subretinal fluid) were similar in both choroidal tumors. Conclusion. OCT may serve as a noninvasive adjunctive tool for the differential diagnosis of choroidal tumors. Choroidal melanomas usually demonstrate regular surfaces on OCT, while choroidal metastases usually have an irregular and lobulated surface. PMID:26998354

  18. Optical Coherence Tomography: An Adjunctive Tool for Differentiating between Choroidal Melanoma and Metastasis.

    PubMed

    Vishnevskia-Dai, Vicktoria; Zur, Dinah; Yaacobi, Shiran; Moroz, Iris; Newman, Hadas; Neudorfer, Meira

    2016-01-01

    Purpose. To investigate the value of optical coherence tomography (OCT) for differentiation between choroidal melanoma and metastasis based on characteristics of the anterior choroidal surface and the chorioretinal interface. Methods. This retrospective observational case series included 29 patients with untreated choroidal melanomas and 21 patients with untreated choroidal metastases. Regularity and lobularity characteristics of the anterior choroidal surface were evaluated in a masked manner. Retinal and retinal pigment epithelium (RPE) findings were documented as well. Results. OCT demonstrated a regular and smooth anterior choroidal surface in 89.7% of the eyes with melanoma and in 47.6% of the eyes with metastasis (p = 0.002; sensitivity = 89.7%; specificity = 52.4%). The anterior choroidal contour was lobulated in 81.0% of the eyes with metastasis versus 17.2% of the eyes with melanoma (p < 0.001; sensitivity = 82.8%; specificity = 81.0%). RPE thickness and neuroretinal characteristics (e.g., retinal thickness, the presence of cysts, and the presence of subretinal fluid) were similar in both choroidal tumors. Conclusion. OCT may serve as a noninvasive adjunctive tool for the differential diagnosis of choroidal tumors. Choroidal melanomas usually demonstrate regular surfaces on OCT, while choroidal metastases usually have an irregular and lobulated surface.

  19. Optical Coherence Tomography: An Adjunctive Tool for Differentiating between Choroidal Melanoma and Metastasis.

    PubMed

    Vishnevskia-Dai, Vicktoria; Zur, Dinah; Yaacobi, Shiran; Moroz, Iris; Newman, Hadas; Neudorfer, Meira

    2016-01-01

    Purpose. To investigate the value of optical coherence tomography (OCT) for differentiation between choroidal melanoma and metastasis based on characteristics of the anterior choroidal surface and the chorioretinal interface. Methods. This retrospective observational case series included 29 patients with untreated choroidal melanomas and 21 patients with untreated choroidal metastases. Regularity and lobularity characteristics of the anterior choroidal surface were evaluated in a masked manner. Retinal and retinal pigment epithelium (RPE) findings were documented as well. Results. OCT demonstrated a regular and smooth anterior choroidal surface in 89.7% of the eyes with melanoma and in 47.6% of the eyes with metastasis (p = 0.002; sensitivity = 89.7%; specificity = 52.4%). The anterior choroidal contour was lobulated in 81.0% of the eyes with metastasis versus 17.2% of the eyes with melanoma (p < 0.001; sensitivity = 82.8%; specificity = 81.0%). RPE thickness and neuroretinal characteristics (e.g., retinal thickness, the presence of cysts, and the presence of subretinal fluid) were similar in both choroidal tumors. Conclusion. OCT may serve as a noninvasive adjunctive tool for the differential diagnosis of choroidal tumors. Choroidal melanomas usually demonstrate regular surfaces on OCT, while choroidal metastases usually have an irregular and lobulated surface. PMID:26998354

  20. Secondary glaucoma in CAPN5-associated neovascular inflammatory vitreoretinopathy

    PubMed Central

    Cham, Abdourahman; Bansal, Mayank; Banda, Himanshu K; Kwon, Young; Tlucek, Paul S; Bassuk, Alexander G; Tsang, Stephen H; Sobol, Warren M; Folk, James C; Yeh, Steven; Mahajan, Vinit B

    2016-01-01

    Objective The objective of this study was to review the treatment outcomes of patients with secondary glaucoma in cases of autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), a hereditary autoimmune uveitis due to mutations in CAPN5. Patients and methods A retrospective, observational case series was assembled from ADNIV patients with secondary glaucoma. The main outcome measures were intraocular pressure (IOP), visual acuity, use of antiglaucoma medications, ocular surgeries, and adverse outcomes. Perimetry and optic disk optical coherence tomography (OCT) were also analyzed. Results Nine eyes of five ADNIV patients with secondary glaucoma were reviewed. Each received a fluocinolone acetonide (FA) implant for the management of posterior uveitis. Following implantation, no eyes developed neovascular glaucoma. Five eyes (in patients 1, 2, and 5) required Ahmed glaucoma valve surgery for the management of steroid-responsive glaucoma. Patient 2 also developed angle closure with iris bombe and underwent laser peripheral iridotomy. Patient 4 had both hypotony and elevated IOP that required periodic antiglaucoma medication in the FA-implanted eye. Patient 3 did not develop steroid-response glaucoma in either eye. Optic disk examinations were obscured by fibrosis and better assessed with OCT. Conclusion ADNIV patients show combined mechanism secondary glaucoma best assessed by OCT of the optic disk. The FA implants have reduced uveitic and neovascular glaucoma. Nevertheless, IOP management remains complex due to steroid-response glaucoma, angle closure glaucoma, and hypotony. PMID:27390515

  1. Earliest symptoms caused by neovascular membranes in the macula.

    PubMed

    Fine, A M; Elman, M J; Ebert, J E; Prestia, P A; Starr, J S; Fine, S L

    1986-04-01

    One hundred three patients with neovascular maculopathy and relatively recent vision loss were surveyed to determine the most frequent symptoms and to assess the reliability of the Amsler grid in helping patients to detect early symptoms. Blurred vision and distortion, most often with near vision, were the most frequent first symptoms reported by patients. Of 49 patients who said that they were observing the Amsler grid on a regular basis, only five indicated that the Amsler grid abnormality was the first visual symptom. However, all but five of 49 patients did notice an Amsler grid abnormality during the office examination, suggesting noncompliance as the probable explanation for failure to detect an Amsler grid abnormality earlier. Patients at risk for neovascular maculopathy should be encouraged to assess a variety of visual functions--including reading vision, color saturation, and image clarity--in addition to observing the Amsler grid, in order to help them detect the earliest symptoms of submacular fluid from a potentially treatable neovascular membrane.

  2. One-year visual outcome of small incision lenticule extraction (SMILE) surgery in high myopic eyes: retrospective cohort study

    PubMed Central

    Wu, Wenjing; Wang, Yan; Zhang, Hui; Zhang, Jiamei; Li, Hua; Dou, Rui

    2016-01-01

    Objective To determine whether the long-term visual outcome of small incision lenticule extraction (SMILE) surgery is consistent with the short-term results in high myopic eyes. Design Retrospective cohort study; data collected from 8 August 2011 to 31 August 2015. Setting Single refractive surgery centre. Participants A total of 156 eyes were studied: 65 eyes of 39 subjects (22 female/17 male) in the high myopic group (manifest refraction spherical equivalent (MRSE) ≥−6.0 D), and 91 eyes of 54 subjects (29 female/25 male) in the control group (MRSE <−6.0 D). The inclusion criteria were subjects who had follow-ups after 1 day, 1 week, 1 month, 3, 6 months and 1 year with the manifest refraction, uncorrected and corrected distance visual acuity (UDVA/CDVA). There were no statistically significant differences between the two groups in the subjects' gender, age, or cylindrical dioptre, preoperatively (p=0.835, p=0.055, p=0.341, respectively). Primary and secondary outcome measures UDVA, refractive stability, safety index (postoperative CDVA/preoperative CDVA), and predictability (the percentage of eyes within ±0.50 D). Results In both groups, the 1-year UDVA and safety index were significantly better than results at 1 day (high myopic group: p=0.035, p<0.001; control group: p<0.016, p<0.001); the 1-year predictability showed no significant difference with the short-term results (p=1.00 in both groups). In the high myopic eyes, the 1-year MRSE was significantly worse than the short-term result (p=0.048). To correct it, the added magnitude (D) for the high myopic eyes may equal 0.13×Attempted SE (D)−0.66 D. However, the postoperative MRSE showed no differences from 1 day to 1 year (p=0.612) in the control group. Conclusions The 1-year visual outcomes were better than the short-term results after the SMILE surgery on the visual acuity and safety. However, the high myopic eyes suffered a significant regression at 1 year, which may be

  3. Silent polypoidal choroidal vasculopathy in a patient with angioid streaks.

    PubMed

    Cebeci, Zafer; Bayraktar, Serife; Oray, Merih; Kir, Nur

    2016-01-01

    We present a case of silent polypoidal choroidal vasculopathy (PCV) in a patient with angioid streaks. PCV was detected during a routine ophthalmic examination and confirmed by fluorescein angiography, indocyanine green angiography, and optical coherence tomography. After 2 years of follow-up, the PCV remained silent without any complications. We report this rare coexistence and review literature on this topic. PMID:27463636

  4. A Case of Choroidal Melanoma Metastatic to the Breast

    PubMed Central

    Taran-Munteanu, L.; Hartkopf, A.; Eigentler, T. K.; Vogel, U.; Brucker, S.; Taran, F. A.

    2016-01-01

    A 61-year-old woman developed blurred vision in her left eye in December 2006. A clinical diagnosis of choroidal melanoma was made. The patient underwent excision of the left lens, followed by vitrectomy and stereotactic radiotherapy. She remained systemically healthy until 50 months later when, during a CT scan done for staging purposes, a newly visible lump was noted in the lower quadrant of her left breast. Core needle biopsy of the lesion in the left breast was performed, and histologic examination revealed metastasis from the choroidal melanoma. The patient underwent breast-conserving surgery of the left breast. Definitive histological examination showed clear tumor margins in the resected specimen and one sentinel lymph node without evidence of metastatic cells. Twenty-nine months after surgery, a similar nodule was detected in the upper quadrant of the left breast. Core biopsy again showed metastatic melanoma, and similar breast-conserving surgery was performed. Systemic examination, including magnetic resonance imaging of the head and computed tomography of the pelvis, abdomen, and chest, was done regularly and revealed no significant findings. Solitary breast metastases from choroidal melanoma are extremely rare. Nevertheless, clinicians should be aware of this rare form of metastasis when treating patients with suspicious breast lesions and a history of choroidal melanoma. If solitary metastasis is confirmed, then breast-conserving surgery may be recommended. PMID:27239068

  5. Bilateral Choroidal Metastasis from Non-Small Cell Lung Cancer

    PubMed Central

    Namad, Tariq; Wang, Jiang; Tilton, Annemarie; Abdel Karim, Nagla

    2014-01-01

    Breast and lung cancers are the most common primary neoplasms to manifest with choroidal metastases. The incidence of choroidal metastases from metastatic lung cancer was reported to be 2–6.7%. We report a case of bilateral choroidal metastasis from non-small cell lung cancer. A 59-year-old Caucasian female patient, never a smoker, was diagnosed with stage IV lung adenocarcinoma metastatic to the pleura, bones, and the brain. Her initial scan of the chest showed innumerable soft tissue nodules and mediastinal adenopathy compatible with metastatic disease. Her initial brain MRI showed numerous small enhancing lesions consistent with extensive disease. Unfortunately, during her follow-up visits, she presented with bulge on her left eye. Simultaneously, her follow-up chest scan showed increase in the size of the lung nodules. She continued to have a reasonable performance status at that time, except for mild increase in her dyspnea. The choroidal metastases require a multidisciplinary care and should be among the differential patients with malignancy who present with ocular symptoms. PMID:25295203

  6. Emerging therapies for the treatment of neovascular age-related macular degeneration and diabetic macular edema.

    PubMed

    Emerson, M Vaughn; Lauer, Andreas K

    2007-01-01

    Diabetic macular edema (DME) and choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) are the leading causes of vision loss in the industrialized world. The mainstay of treatment for both conditions has been thermal laser photocoagulation, while there have been recent advances in the treatment of CNV using photodynamic therapy with verteporfin. While both of these treatments have prevented further vision loss in a subset of patients, vision improvement is rare. Anti-vascular endothelial growth factor (VEGF)-A therapy has revolutionized the treatment of both conditions. Pegaptanib, an anti-VEGF aptamer, prevents vision loss in CNV, although the performance is similar to that of photodynamic therapy. Ranibizumab, an antibody fragment, and bevacizumab, a full-length humanized monoclonal antibody against VEGF, have both shown promising results, with improvements in visual acuity in the treatment of both diseases. VEGF trap, a modified soluble VEGF receptor analog, binds VEGF more tightly than all other anti-VEGF therapies, and has also shown promising results in early trials. Other treatment strategies to decrease the effect of VEGF have used small interfering RNA to inhibit VEGF production and VEGF receptor production. Corticosteroids have shown efficacy in controlled trials, including anacortave acetate in the treatment and prevention of CNV, and intravitreal triamcinolone acetonide and the fluocinolone acetonide implant in the treatment of DME. Receptor tyrosine kinase inhibitors, such as vatalanib, inhibit downstream effects of VEGF, and have been effective in the treatment of CNV in early studies. Squalamine lactate inhibits plasma membrane ion channels with downstream effects on VEGF, and has shown promising results with systemic administration. Initial results are also encouraging for other growth factors, including pigment epithelium-derived factor administered via an adenoviral vector. Ruboxistaurin, which decreases protein

  7. Retinal and vitreal neovascularization in retinopathy of prematurity. A scanning electron microscopic study in the kitten.

    PubMed

    Yoneya, S; Tso, M O

    1991-12-01

    The angioarchitecture of vitreal and retinal neovascularizations produced experimentally in the eyes of kittens aged 2 to 9 weeks was studied with scanning electron microscopy. Various forms of new retinal and vitreal vessels were observed depending on topographic locations. Intraretinal neovascularization was observed at the retinal periphery as it grew toward the avascular zone in forms of short vascular buds, aneurysmal outgrowths, and neovascular loops. Posterior or to this frond of neovascularization, intertwining intraretinal telangiectasia was observed. At the posterior pole, capillaries with microaneurysms extended posteriorly toward the deeper layers of the retina from the vascular trunks at the nerve fiber layer. Vitreal neovascularization broke through the internal limiting membrane and exhibited aneurysmal outgrowths, clusters of glomerular swellings, and sinusoidal vascular channels. At the optic disc, vitreous neovascularization took the form of aneurysmal outgrowths and long vascular buds. Vitreal neovascularization showed different characteristics from the intraretinal neovascularization. We hypothesize that the topographic variation of the angioarchitecture of retinal and vitreal neovascularizations depends on the maturity of the vessels and might be related to the hemodynamics at each site. PMID:1726774

  8. Epithelial Thickness Profile Changes Induced by Myopic LASIK as Measured by Artemis Very High-frequency Digital Ultrasound

    PubMed Central

    Reinstein, Dan Z.; Srivannaboon, Sabong; Gobbe, Marine; Archer, Timothy J.; Silverman, Ronald H.; Sutton, Hugo; Coleman, D. Jackson

    2008-01-01

    PURPOSE To characterize changes in the corneal epithelial thickness profile induced by myopic LASIK. METHODS This was a prospective study of 37 eyes of 19 myopic LASIK patients. Eyes were divided into three groups according to sphere in the maximum myopic meridian: low (−1.00 to −4.00 diopters [D]), moderate (−4.25 to −6.00 D), and high myopia (−6.25 to −13.50 D). The epithelial thickness profile was measured by prototype Artemis very high-frequency (VHF) digital ultrasound scanner (ArcScan Inc) across the central 10-mm corneal diameter preoperatively and between 3 and 6 months postoperatively. The epithelial thickness profile was determined by averaging the epithelial thickness within annular bands centered on the corneal vertex. The change in epithelial thickness profile was calculated as the difference between the preoperative and postoperative epithelial thickness profiles. RESULTS The corneal epithelium thickened after myopic LASIK across the central 6 mm with maximum thickening centrally and progressively less thickening centrifugally in low myopia, and a more homogenous thickening in moderate and high myopia within the 5-mm diameter. The mean epithelial thickening at the corneal vertex was 7.41±1.09 μm, 9.29±1.22 μm, and 12.33±1.05 μm for low, moderate, and high myopia, respectively. The rate of epithelial thickening at the corneal vertex per diopter of myopia treated decreased with increasing myopia. CONCLUSIONS Although the magnitude of epithelial thickening increased with increasing ablation depth, in accordance with Barraquer’s Law of Thicknesses, the myopic refractive shift due to epithelial thickness profile changes was paradoxically more significant in low myopia than in high myopia. PMID:19507797

  9. Effect of Myopic Defocus on Visual Acuity after Phakic Intraocular Lens Implantation and Wavefront-guided Laser in Situ Keratomileusis

    PubMed Central

    Kamiya, Kazutaka; Shimizu, Kimiya; Igarashi, Akihito; Kawamorita, Takushi

    2015-01-01

    This study aimed to investigate the effect of myopic defocus on visual acuity after phakic intraocular lens (IOL) implantation and wavefront-guided laser in situ keratomileusis (wfg-LASIK). Our prospective study comprised thirty eyes undergoing posterior chamber phakic IOL implantation and 30 eyes undergoing wfg-LASIK. We randomly measured visual acuity under myopic defocus after cycloplegic and non-cycloplegic correction. We also calculated the modulation transfer function by optical simulation and estimated visual acuity from Campbell & Green’s retinal threshold curve. Visual acuity in the phakic IOL group was significantly better than that in the wfg-LASIK group at myopic defocus levels of 0, –1, and –2 D (p < 0.001, p < 0.001, and p = 0.02, Mann-Whitney U-test), but not at a defocus of –3 D (p = 0.30). Similar results were also obtained in a cycloplegic condition. Decimal visual acuity values at a myopic defocus of 0, −1, −2, and -3 D by optical simulation were estimated to be 1.95, 1.21, 0.97, and 0.75 in the phakic IOL group, and 1.39, 1.11, 0.94, and 0.71 in the wfg-LASIK group, respectively. From clinical and optical viewpoints, phakic IOL implantation was superior to wfg-LASIK in terms of the postoperative visual performance, even in the presence of low to moderate myopic regression. PMID:25994984

  10. Ultrasound imaging of breast tumor perfusion and neovascular morphology.

    PubMed

    Hoyt, Kenneth; Umphrey, Heidi; Lockhart, Mark; Robbin, Michelle; Forero-Torres, Andres

    2015-09-01

    A novel image processing strategy is detailed for simultaneous measurement of tumor perfusion and neovascular morphology parameters from a sequence of dynamic contrast-enhanced ultrasound (DCE-US) images. After normalization and tumor segmentation, a global time-intensity curve describing contrast agent flow was analyzed to derive surrogate measures of tumor perfusion (i.e., peak intensity, time-to-peak intensity, area under the curve, wash-in rate, wash-out rate). A maximum intensity image was generated from these same segmented image sequences, and each vascular component was skeletonized via a thinning algorithm. This skeletonized data set and collection of vessel segments were then investigated to extract parameters related to the neovascular network and physical architecture (i.e., vessel-to-tissue ratio, number of bifurcations, vessel count, average vessel length and tortuosity). An efficient computation of local perfusion parameters was also introduced and operated by averaging time-intensity curve data over each individual neovascular segment. Each skeletonized neovascular segment was then color-coded by these local measures to produce a parametric map detailing spatial properties of tumor perfusion. Longitudinal DCE-US image data sets were collected in six patients diagnosed with invasive breast cancer using a Philips iU22 ultrasound system equipped with a L9-3 transducer and Definity contrast agent. Patients were imaged using US before and after contrast agent dosing at baseline and again at weeks 6, 12, 18 and 24 after treatment started. Preliminary clinical results suggested that breast tumor response to neoadjuvant chemotherapy may be associated with temporal and spatial changes in DCE-US-derived parametric measures of tumor perfusion. Moreover, changes in neovascular morphology parametric measures may also help identify any breast tumor response (or lack thereof) to systemic treatment. Breast cancer management from early detection to therapeutic

  11. Kir7.1 immunoreactivity in canine choroid plexus tumors.

    PubMed

    Choi, Eun Ju; Sloma, Erica A; Miller, Andrew D

    2016-07-01

    Choroid plexus neoplasms are uncommon brain tumors in dogs. Choroid plexus carcinomas often spread diffusely throughout the ventricular system and subarachnoid space and, in aggressive forms, can mimic histologic patterns of other carcinomas, including being embedded in a desmoplastic reaction. Although choroid plexus tumors (CPTs) heterogeneously express pan-cytokeratin, little is known about other markers to identify choroid plexus and their associated tumors. Kir7.1, an inward-rectifier potassium channel, is reported to have high diagnostic utility in human neuropathology to distinguish CPTs from other primary brain tumors and cerebral metastases. To determine Kir7.1 expression in the dog brain, we analyzed the immunoreactivity of Kir7.1 in normal brain, gliomas, ependymomas, CPTs, meningiomas, and carcinomas. In normal brain tissue, the immunostaining was restricted to the choroid plexus where there was robust membrane immunoreactivity along the apical border of the cells with less intense cytoplasmic staining. Similar strong immunoreactivity was detected in 12 of 12 CPTs, whereas 5 of 5 gliomas, 4 of 5 ependymomas, 5 of 5 meningiomas, and 5 of 6 carcinomas had no immunoreactivity. One ependymoma and 1 nasal carcinoma with squamous metaplasia were up to 75% immunopositive, with moderate cytoplasmic and membranous immunoreactivity, but lacking the robust apical immunoreactivity pattern. Analysis for immunoreactivity in a tissue microarray failed to yield any other locations in which immunoreactivity was detected. These results, including the distinctive pattern of immunostaining in CPTs, suggest that Kir7.1 is an excellent marker for CPTs in the dog. PMID:27216721

  12. Choroidal thickness in pregnant women: a cross-sectional study

    PubMed Central

    Liu, Ru; Kuang, Guo-Ping; Luo, Di-Xian; Lu, Xiao-He

    2016-01-01

    AIM To investigate choroidal thickness in pregnant women and compare the measurements with those of normal nonpregnant women. METHODS Using enhanced depth imaging optical coherence tomography (EDI-OCT), choroidal thickness was measured at the fovea and at 1 mm and 3 mm superior, inferior, temporal, and nasal to the fovea in both healthy pregnant women and nonpregnant women. Pearson correlation analysis was performed to evaluate the relationships between subfoveal choroidal thickness (SFCT) and the demographic and ocular parameters. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed-effects model when Meta-analyses were conducted. RESULTS Comparison of choroidal thickness between the groups showed that it was significantly greater in healthy pregnant women's eyes than in normal nonpregnant women's eyes at all locations except at 3 mm superior and 3 mm temporal from the fovea (P<0.05). The mean SFCT was 344.13±50.94 µm in healthy pregnant women's eyes and 315.03±60.57 µm in normal nonpregnant women's eyes, with a statistically significant difference (P=0.008). Pearson correlation analysis showed that age and axial length were significantly related to SFCT in healthy pregnant women, normal nonpregnant women, and all subjects. The results of our cross-sectional study were consistent with the results of the further Meta-analysis, with a pooled weighted mean difference (WMD) of 33.66 µm (95% CI: 26.16 to 41.15) for SFCT. CONCLUSION Our results, along with the comprehensive Meta-analysis, suggest that choroidal thickness in healthy pregnant women is greater than that in normal nonpregnant women. PMID:27588276

  13. [Diagnosis of open-angle glaucoma after myopic excimer laser corneal refractive surgery].

    PubMed

    Wu, Ling-ling

    2013-11-01

    Patients with high myopia are at high risk of glaucoma and are difficult to be discovered at early stage in the case of existing glaucoma. Myopic excimer laser corneal refractive surgery changes the structure of the eye, which makes early glaucoma diagnosis more difficult. Furthermore, refractive surgery may aggravate existing condition of glaucoma. To prevent the exacerbation of glaucoma, it is great important to perform the preoperative glaucoma risk assessment. In this paper, we presented the key diagnostic points of glaucoma assessment before and after excimer laser refractive surgery and discussed the postoperative intraocular pressure measurements and its impact on the diagnosis and treatment of glaucoma including characterization of open angle glaucoma and long-term follow up in patients with high myopia.

  14. Accuracy of Corneal Power Measurements for Intraocular Lens Power Calculation after Myopic Laser In situ Keratomileusis

    PubMed Central

    Helaly, Hany A.; El-Hifnawy, Mohammad A. M.; Shaheen, Mohamed Shafik; Abou El-Kheir, Amr F.

    2016-01-01

    Purpose: To evaluate the accuracy of corneal power measurements for intraocular lens (IOL) power calculation after myopic laser in situ keratomileusis (LASIK). Methods: The study evaluated 45 eyes with a history of myopic LASIK. Corneal power was measured using manual keratometry, automated keratometry, optical biometry, and Scheimflug tomography. Different hypothetical IOL power calculation formulas were performed for each case. Results: The steepest mean K value was measured with manual keratometry (37.48 ± 2.86 D) followed by automated keratometry (37.31 ± 2.83 D) then optical biometry (37.06 ± 2.98 D) followed by Scheimflug tomography (36.55 ± 3.08). None of the K values generated by Scheimflug tomography were steeper than the measurements from the other 3 instruments. Using equivalent K reading (EKR) 4 mm with the Double-K SRK/T formula, the refractive outcome generated 97.8% of cases within ± 2 D, 80.0% of cases within ± 1 D, and 42.2% of cases within ± 0.5 D. The best combination of formulas was “Shammas-PL + Double-K SRK/T formula using EKR 4 mm.” Conclusion: Scheimflug tomography imaging using the Holladay EKR 4 mm improved the accuracy of IOL power calculation in post-LASIK eyes. The best option is a combination of formulas. We recommended the use the combined “Shammas-PL ± Double-K SRK/T formula using EKR 4 mm”h for optical outcomes. PMID:26957851

  15. Angiopoietin-like Protein 2 Is a Multistep Regulator of Inflammatory Neovascularization in a Murine Model of Age-related Macular Degeneration.

    PubMed

    Hirasawa, Manabu; Takubo, Keiyo; Osada, Hideto; Miyake, Seiji; Toda, Eriko; Endo, Motoyoshi; Umezawa, Kazuo; Tsubota, Kazuo; Oike, Yuichi; Ozawa, Yoko

    2016-04-01

    Choroidal neovascularization (CNV) is a pathogenic process of age-related macular degeneration, a vision-threatening disease. The retinal pigment epithelium and macrophages both influence CNV development. However, the underlying mechanisms remain obscure. Here, we focus on Angptl2 (angiopoietin-like protein 2), a cytokine involved in age-related systemic diseases. Angptl2 was originally identified as an adipocytokine and is also expressed in the eye. Using a laser-induced CNV model, we found thatAngptl2KO mice exhibited suppressed CNV development with reduced macrophage recruitment and inflammatory mediator induction. The mediators monocyte chemotactic protein-1, interleukin-1β (Il-1β),Il-6, matrix metalloprotease-9 (Mmp-9), and transforming growth factor-β1 (Tgf-β1) that were up-regulated during CNV development were all suppressed in the retinal pigment epithelium-choroid of CNV models generated in theAngptl2KO mice. Bone marrow transplantation using wild-type and KO mice suggested that both bone marrow-derived and host-derived Angptl2 were responsible for macrophage recruitment and CNV development. Peritoneal macrophages derived fromAngptl2KO mice expressed lower levels of the inflammatory mediators. In the wild-type peritoneal macrophages and RAW264.7 cells, Angptl2 induced the mediators via integrins α4 and β2, followed by the downstream activation of NF-κB and ERK. The activation of NF-κB and ERK by Angptl2 also promoted macrophage migration. Therefore, Angptl2 from focal tissue might trigger macrophage recruitment, and that from recruited macrophages might promote expression of inflammatory mediators including Angptl2 in an autocrine and/or paracrine fashion to facilitate CNV development. Angptl2 might therefore represent a multistep regulator of CNV pathogenesis and serve as a new therapeutic target for age-related macular degeneration.

  16. Choroidal vascularity index as a measure of vascular status of the choroid: Measurements in healthy eyes from a population-based study

    NASA Astrophysics Data System (ADS)

    Agrawal, Rupesh; Gupta, Preeti; Tan, Kara-Anne; Cheung, Chui Ming Gemmy; Wong, Tien-Yin; Cheng, Ching-Yu

    2016-02-01

    The vascularity of the choroid has been implicated in the pathogenesis of various eye diseases. To date, no established quantifiable parameters to estimate vascular status of the choroid exists. Choroidal vascularity index (CVI) may potentially be used to assess vascular status of the choroid. We aimed to establish normative database for CVI and identify factors associated with CVI in healthy eyes. In this population-based study on 345 healthy eyes, choroidal enhanced depth imaging optical coherence tomography scans were segmented by modified image binarization technique. Total subfoveal choroidal area (TCA) was segmented into luminal (LA) and stromal (SA) area. CVI was calculated as the proportion of LA to TCA. Linear regression was used to identify ocular and systemic factors associated with CVI and subfoveal choroidal thickness (SFCT). Subfoveal CVI ranged from 60.07 to 71.27% with a mean value of 65.61 ± 2.33%. CVI was less variable than SFCT (coefficient of variation for CVI was 3.55 vs 40.30 for SFCT). Higher CVI was associated with thicker SFCT, but not associated with most physiological variables. CVI was elucidated as a significant determinant of SFCT. While SFCT was affected by many factors, CVI remained unaffected suggesting CVI to be a more robust marker of choroidal diseases.

  17. Interleukin-17A neutralization alleviated ocular neovascularization by promoting M2 and mitigating M1 macrophage polarization.

    PubMed

    Zhu, Yanji; Tan, Wei; Demetriades, Anna M; Cai, Yujuan; Gao, Yushuo; Sui, Ailing; Lu, Qing; Shen, Xi; Jiang, Chunhui; Xie, Bing; Sun, Xinghuai

    2016-04-01

    Neovascularization (NV), as a cardinal complication of several ocular diseases, has been intensively studied, and research has shown its close association with inflammation and immune cells. In the present study, the role of interleukin-17A (IL-17A) in angiogenesis in the process of ocular NV both in vivo and in vitro was investigated. Also, a paracrine role of IL-17A was demonstrated in the crosstalk between endothelial cells and macrophages in angiogenesis. In the retinas of mice with retinopathy of prematurity, the IL-17A expression increased significantly at postnatal day 15 (P15) and P18 during retinal NV. Mice given IL-17A neutralizing antibody (NAb) developed significantly reduced choroidal NV and retinal NV. Studies on vascular endothelial growth factor (VEGF) over-expressing mice suggested that IL-17A modulated NV through the VEGF pathway. Furthermore, IL-17A deficiency shifted macrophage polarization toward an M2 phenotype during retinal NV with significantly reduced M1 cytokine expression compared with wild-type controls. In vitro assays revealed that IL-17A treated macrophage supernatant gave rise to elevated human umbilical vascular endothelial cell proliferation, tube formation and VEGF receptor 1 and receptor 2 expression. Therefore, IL-17A could potentially serve as a novel target for treating ocular NV diseases. The limitation of this study involved the potential mechanisms, such as which transcription accounted for macrophage polarization and how the subsequent cytokines were modulated when macrophages were polarized. Further studies need to be undertaken to definitively determine the extent to which IL-17A neutralizing anti-angiogenic activity depends on macrophage modulation compared with anti-VEGF treatment.

  18. 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 Central

    Kokame, Gregg T.

    2014-01-01

    Purpose: 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? Methods: 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. Results: 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. Conclusions: 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. PMID:25646029

  19. Segmentation of the macular choroid in OCT images acquired at 830nm and 1060nm

    NASA Astrophysics Data System (ADS)

    Lee, Sieun; Beg, Mirza F.; Sarunic, Marinko V.

    2013-06-01

    Retinal imaging with optical coherence tomography (OCT) has rapidly advanced in ophthalmic applications with the broad availability of Fourier domain (FD) technology in commercial systems. The high sensitivity afforded by FD-OCT has enabled imaging of the choroid, a layer of blood vessels serving the outer retina. Improved visualization of the choroid and the choroid-sclera boundary has been investigated using techniques such as enhanced depth imaging (EDI), and also with OCT systems operating in the 1060-nm wavelength range. We report on a comparison of imaging the macular choroid with commercial and prototype OCT systems, and present automated 3D segmentation of the choroid-scleral layer using a graph cut algorithm. The thickness of the choroid is an important measurement to investigate for possible correlation with severity, or possibly early diagnosis, of diseases such as age-related macular degeneration.

  20. Toxicology of choroid plexus: special reference to metal-induced neurotoxicities.

    PubMed

    Zheng, W

    2001-01-01

    The chemical stability in the brain underlies normal human thinking, learning, and behavior. Compelling evidence demonstrates a definite capacity of the choroid plexus in sequestering toxic heavy metal and metalloid ions. As the integrity of blood-brain and blood-CSF barriers, both structurally and functionally, is essential to brain chemical stability, the role of the choroid plexus in metal-induced neurotoxicities has become an important, yet under-investigated research area in neurotoxicology. Metals acting on the choroid plexus can be categorized into three major groups. A general choroid plexus toxicant can directly damage the choroid plexus structure such as mercury and cadmium. A selective choroid plexus toxicant may impair specific plexus regulatory pathways that are critical to brain development and function, rather than induce massive pathological alteration. The typical examples in this category include lead-induced alteration in transthyretin production and secretion as well as manganese interaction with iron in the choroid plexus. Furthermore, a sequestered choroid plexus toxicant, such as iron, silver, or gold, may be sequestered by the choroid plexus as an essential CNS defense mechanism. Our current knowledge on the toxicological aspect of choroid plexus research is still incomplete. Thus, the future research needs have been suggested to focus on the role of choroid plexus in early CNS development as affected by metal sequestration in this tissue, to explore how metal accumulation alters the capacity of the choroid plexus in regulation of certain essential elements involved in the etiology of neurodegenerative diseases, and to better understand the blood-CSF barrier as a defense mechanism in overall CNS function.

  1. Cataract extraction after brachytherapy for malignant melanoma of the choroid

    SciTech Connect

    Fish, G.E.; Jost, B.F.; Snyder, W.I.; Fuller, D.G.; Birch, D.G. )

    1991-05-01

    Thirteen eyes of 55 consecutive patients treated with brachytherapy for malignant melanoma of the choroid developed postirradiation cataracts. Cataract development was more common in older patients and in patients with larger and more anterior tumors. Eleven eyes had extracapsular cataract extraction and intraocular lens implantation. Initial visual improvement occurred in 91% of eyes, with an average improvement of 5.5 lines. Visual acuity was maintained at 20/60 or better in 55% of the eyes over an average period of follow-up of 24 months (range, 6 to 40 months). These data suggest that, visually, cataract extraction can be helpful in selected patients who develop a cataract after brachytherapy for malignant melanoma of the choroid.

  2. Choroidal coloboma in a case of tay-sachs disease.

    PubMed

    Ahmed, Nasreen Raees; Tripathy, Koushik; Kumar, Vivek; Gogia, Varun

    2014-01-01

    Coloboma as an ocular finding has been documented in various syndromes. Here we have a case of infantile Tay-Sachs disease associated with unilateral choroidal coloboma. To the best of our knowledge, such an association has not been documented in the literature. Whether such an association is a matter of chance or signifies the involvement of ganglioside metabolism in ocular embryogenesis remains to be elucidated.

  3. Prognostic factors of choroidal melanoma in Slovenia, 1986–2008

    PubMed Central

    Budihna, Marjan; Drnovsek-Olup, Brigita; Andrejcic, Katrina Novak; Zupancic, Irena Brovet; Pahor, Dusica

    2016-01-01

    Introduction Choroidal melanoma is the most common primary malignancy of the eye, which frequently metastasizes. The Cancer Registry of Slovenia reported the incidence of choroid melanoma from 1983 to 2009 as stable, at 7.8 cases/million for men and 7.4/million for women. The aim of the retrospective study was to determinate the prognostic factors of survival for choroidal melanoma patients in Slovenia. Patients and methods From January 1986 to December 2008 we treated 288 patients with malignant choroidal melanoma; 127 patients were treated by brachytherapy with beta rays emitting ruthenium-106 applicators; 161 patients were treated by enucleation. Results Patients with tumours thickness < 7.2 mm and base diameter < 16 mm were treated by brachytherapy and had 5- and 10-year overall mortality 13% and 32%, respectively. In enucleated patients, 5- and 10-year mortality was higher, 46% and 69%, respectively, because their tumours were larger. Thirty patients treated by brachytherapy developed local recurrence. Twenty five of 127 patients treated by brachytherapy and 86 of 161 enucleated patients developed distant metastases. Patients of age ≥ 60 years had significantly lower survival in both treatment modalities. For patients treated by brachytherapy the diameter of the tumour base and treatment time were independent prognostic factors for overall survival, for patients treated by enucleation age and histological type of tumour were independent prognosticators. In first few years after either of treatments, the melanoma specific annual mortality rate increased, especially in older patients, and then slowly decreased. Conclusions It seems that particularly younger patients with early tumours can be cured, whereby preference should be given to eyesight preserving brachytherapy over enucleation. PMID:27069456

  4. Leiomyoma of The Ciliary Body and Hemangiopericytoma of the Choroid.

    PubMed

    Tóth, Jeannette; Kerényi Á, Ágnes; Süveges, Ildikó; Futó, Gábor

    1996-01-01

    Two unusual uveal tumors occurring in eyes enucleated for presumed malignant melanoma are discussed. One was a leiomyoma of the ciliary body, affecting a 22-year-old female, the other a hemangiopericytoma of the choroid in an 84-year-old male patient. The latter case is the fourth intraocular hemangiopericytoma reported in the literature to date. The histopathologic diagnosis was confirmed by immunohistochemistry and electron microscopy. PMID:11173593

  5. Choroidal coloboma in a case of tay-sachs disease.

    PubMed

    Ahmed, Nasreen Raees; Tripathy, Koushik; Kumar, Vivek; Gogia, Varun

    2014-01-01

    Coloboma as an ocular finding has been documented in various syndromes. Here we have a case of infantile Tay-Sachs disease associated with unilateral choroidal coloboma. To the best of our knowledge, such an association has not been documented in the literature. Whether such an association is a matter of chance or signifies the involvement of ganglioside metabolism in ocular embryogenesis remains to be elucidated. PMID:25295204

  6. Quantitative polarization and flow evaluation of choroid and sclera by multifunctional Jones matrix optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Sugiyama, S.; Hong, Y.-J.; Kasaragod, D.; Makita, S.; Miura, M.; Ikuno, Y.; Yasuno, Y.

    2016-03-01

    Quantitative evaluation of optical properties of choroid and sclera are performed by multifunctional optical coherence tomography. Five normal eyes, five glaucoma eyes and one choroidal atrophy eye are examined. The refractive error was found to be correlated with choroidal birefringence, polarization uniformity, and flow in addition to scleral birefringence among normal eyes. The significant differences were observed between the normal and the glaucoma eyes, as for choroidal polarization uniformity, flow and scleral birefringence. An automatic segmentation algorithm of retinal pigment epithelium and chorioscleral interface based on multifunctional signals is also presented.

  7. Choroid plexus calcification: clinical, neuroimaging and histopathological correlations in schizophrenia.

    PubMed

    Marinescu, Ileana; Udriştoiu, I; Marinescu, D

    2013-01-01

    Schizophrenia is recognized as a psychiatric disorder that causes the most pronounced disturbances of cognition and social integration. In the etiopathogenesis of the disease, genetic, neurobiological and vascular factors are involved. Functional integrity of the brain can be correlated with the integrity of the blood-brain barrier (BBB), and the dysfunction of this barrier is an indicator that suggests neurodevelopmental abnormalities, injuries of various etiologies and dysfunctions within the small vessels of the brain that disrupt the calcium homeostasis. Neuroimaging shows that in patients with poor evolution, cognitive dysfunction and therapeutic resistance, the presence of choroid plexus calcification associated with hippocampal, frontal, temporoparietal and cerebellar atrophies. Antipsychotics with high capacity to block D2 dopamine receptors (haloperidol model) can aggravate apoptotic mechanisms of the brain areas involved in cognition and disrupts the functional integrity of the BBB due to decreased of choroid plexus blood flow because of the narrowing of cerebral small vessels. Choroid plexus calcification may be a predictive indicator of poor evolution or of a neurodegenerative type. PMID:23771083

  8. Circumscribed choroidal haemangioma mimicking chronic central serous chorioretinopathy.

    PubMed

    Rahman, W; Horgan, N; Hungerford, J

    2013-03-01

    We describe a rare case of bilateral circumscribed choroidal haemangioma in an otherwise healthy male, which mimicked chronic central serous chorioretinopathy (CSCR). A 52-year-old Asian man presented with a one-year history of visual decline in his left eye. The vision in the right eye had been reduced for 15 years. Visual acuity was 6/60 in the right eye and 6/18 in the left eye. Fundus examination of the right eye revealed an area of discoloration with overlying retinal pigment epithelial changes in the macula and evidence of prior surrounding argon laser photocoagulation. The left macula showed a raised choroidal lesion with overlying retinal pigment epithelial changes and associated subretinal fluid. This appearance illustrates how chronic retinal pigment epithelial alterations associated with longstanding subretinal fluid exudation from circumscribed choroidal haemangiomas may mimick the appearance of chronic central serous chorioretinopathy. B-scan ultrasonography, fluorescein angiography, indocyanine green angiography and optical coherence tomography helped to establish the diagnosis. The active lesion in the left eye was treated with verteporfin photodynamic therapy with improvement in vision.

  9. Photodynamic therapy for circumscribed choroidal haemangioma: a case report.

    PubMed

    Bhatt, Chirag; Bandyopadhyay, Samir Kumar; Chatterjee, P K; Paul, R C; Bagchi, S C; Chatterjee, Arkendu

    2011-10-01

    Choroidal haemangioma is a benign tumour with visual acuity diminution due to subretinal fluid accumulation. There are many modalities of treatment of this visually disabling syndrome, some of them being argon laser photocoagulation, cryotherapy, external beam irradiation, proton beam radiotherapy, episcleral plaque radiotherapy and transpupillary thermotherapy. Another new modality of treatment with remarkable success rate is photodynamic therapy. In this modality a photosensitiser is injected intravenously followed by irradiation of a specific wave length for a specified time period. The photosensitiser concentrates within the vascular channels and after irradiation these channels are irreversibly obliterated. A 62 years old female patient of choroidal haemangioma, who presented in eye outpatient department was treated with the standard protocol used for photodynamic therapy. On follow-up of this patient it was found that there was improvement in the visual acuity from 6/12 in the left eye (affected eye) to 6/9. Not only was there an improvement in the visual acuity but there was anatomical improvement too as was evident by regressed cystoid macular oedema and circumscribed choroidal haemangioma. After six months of follow-up there was no leakage of dye with digital fluorescein angiography and indocyanine green.

  10. Prognostic Factor Analysis of Intraocular Pressure with Neovascular Glaucoma.

    PubMed

    Nakano, Satoko; Nakamuro, Takako; Yokoyama, Katsuhiko; Kiyosaki, Kunihiro; Kubota, Toshiaki

    2016-01-01

    Purpose. To perform multivariate analysis for identifying independent predictors of elevated intraocular pressure (IOP) with neovascular glaucoma (NVG), including antivascular endothelial growth factor (VEGF) intravitreal injections. Methods. We retrospectively reviewed 142 NVG patients (181 eyes) with ischemic retinal diseases [proliferative diabetic retinopathy (PDR) in 134 eyes, retinal vein occlusion (RVO) in 29, and ocular ischemic syndrome in 18]. We analyzed age, gender, initial/final LogMAR VA, initial/final IOP, extent of iris and/or angle neovascularization, treatments, preexisting complications, concurrent medications, and follow-up duration. Results. The mean follow-up duration was 23.8 ± 18.8 months. At the final follow-up, 125 (72.3%) eyes had IOP ≤ 21 mmHg. NVG patients with RVO had a higher degree of angle closure and higher IOP. NVG with PDR had better IOP and LogMAR VA. Angle closure had the greatest impact on final IOP. Greater than 90% of patients treated with trabeculectomy with mitomycin C (LEC) had persistent declines in IOP (≤21 mmHg). Stand-alone and combination anti-VEGF therapies were not associated with improved long-term prognosis of IOP. Conclusions. Angle closure was found to have the greatest effect on NVG-IOP prognosis. When target IOP values are not obtained after adequate PRP with or without anti-VEGF, early LEC may improve the prognosis of IOP. PMID:27579175

  11. Nanotechnology in corneal neovascularization therapy--a review.

    PubMed

    Gonzalez, Lilian; Loza, Raymond J; Han, Kyu-Yeon; Sunoqrot, Suhair; Cunningham, Christy; Purta, Patryk; Drake, James; Jain, Sandeep; Hong, Seungpyo; Chang, Jin-Hong

    2013-03-01

    Nanotechnology is an up-and-coming branch of science that studies and designs materials with at least one dimension sized from 1-100 nm. These nanomaterials have unique functions at the cellular, atomic, and molecular levels. The term "nanotechnology" was first coined in 1974. Since then, it has evolved dramatically and now consists of distinct and independent scientific fields. Nanotechnology is a highly studied topic of interest, as nanoparticles can be applied to various fields ranging from medicine and pharmacology, to chemistry and agriculture, to environmental science and consumer goods. The rapidly evolving field of nanomedicine incorporates nanotechnology with medical applications, seeking to give rise to new diagnostic means, treatments, and tools. Over the past two decades, numerous studies that underscore the successful fusion of nanotechnology with novel medical applications have emerged. This has given rise to promising new therapies for a variety of diseases, especially cancer. It is becoming abundantly clear that nanotechnology has found a place in the medical field by providing new and more efficient ways to deliver treatment. Ophthalmology can also stand to benefit significantly from the advances in nanotechnology research. As it relates to the eye, research in the nanomedicine field has been particularly focused on developing various treatments to prevent and/or reduce corneal neovascularization among other ophthalmologic disorders. This review article aims to provide an overview of corneal neovascularization, currently available treatments, and where nanotechnology comes into play.

  12. Prognostic Factor Analysis of Intraocular Pressure with Neovascular Glaucoma

    PubMed Central

    Nakamuro, Takako; Yokoyama, Katsuhiko; Kiyosaki, Kunihiro

    2016-01-01

    Purpose. To perform multivariate analysis for identifying independent predictors of elevated intraocular pressure (IOP) with neovascular glaucoma (NVG), including antivascular endothelial growth factor (VEGF) intravitreal injections. Methods. We retrospectively reviewed 142 NVG patients (181 eyes) with ischemic retinal diseases [proliferative diabetic retinopathy (PDR) in 134 eyes, retinal vein occlusion (RVO) in 29, and ocular ischemic syndrome in 18]. We analyzed age, gender, initial/final LogMAR VA, initial/final IOP, extent of iris and/or angle neovascularization, treatments, preexisting complications, concurrent medications, and follow-up duration. Results. The mean follow-up duration was 23.8 ± 18.8 months. At the final follow-up, 125 (72.3%) eyes had IOP ≤ 21 mmHg. NVG patients with RVO had a higher degree of angle closure and higher IOP. NVG with PDR had better IOP and LogMAR VA. Angle closure had the greatest impact on final IOP. Greater than 90% of patients treated with trabeculectomy with mitomycin C (LEC) had persistent declines in IOP (≤21 mmHg). Stand-alone and combination anti-VEGF therapies were not associated with improved long-term prognosis of IOP. Conclusions. Angle closure was found to have the greatest effect on NVG-IOP prognosis. When target IOP values are not obtained after adequate PRP with or without anti-VEGF, early LEC may improve the prognosis of IOP. PMID:27579175

  13. Vascular Guidance: Microstructural Scaffold Patterning for Inductive Neovascularization

    PubMed Central

    Muller, Daniel; Chim, Harvey; Bader, Augustinus; Whiteman, Matthew; Schantz, Jan-Thorsten

    2011-01-01

    Current tissue engineering techniques are limited by inadequate vascularisation and perfusion of cell-scaffold constructs. Microstructural patterning through biomimetic vascular channels within a polymer scaffold might induce neovascularization, allowing fabrication of large engineered constructs. The network of vascular channels within a frontal-parietal defect in a patient, originating from the anterior branch of the middle meningeal artery, was modeled using computer-aided design (CAD) techniques and subsequently incorporated into polycaprolactone (PCL) scaffolds fabricated using fused deposition modeling (FDM). Bone marrow-derived mesenchymal stem cells (MSCs) were seeded onto the scaffolds and implanted into a rat model, with an arteriovenous bundle inserted at the proximal extent of the vascular network. After 3 weeks, scaffolds were elevated as a prefabricated composite tissue-polymer flap and transferred using microsurgical technique. Histological examination of explanted scaffolds revealed vascular ingrowth along patterned channels, with abundant capillary and connective tissue formation throughout experimental scaffolds, while control scaffolds showed only granulation tissue. All prefabricated constructs transferred as free flaps survived and were viable. We term this concept “vascular guidance,” whereby neovascularization is guided through customized channels in a scaffold. Our technique might potentially allow fabrication of much larger tissue-engineered constructs than current technologies allow, as well as allowing tailored construct fabrication with a patient-specific vessel network based on CT scan data and CAD technology. PMID:21188080

  14. Microcomputed Tomography Characterization of Neovascularization in Bone Tissue Engineering Applications

    PubMed Central

    Young, Simon; Kretlow, James D.; Nguyen, Charles; Bashoura, Alex G.; Baggett, L. Scott; Jansen, John A.; Wong, Mark

    2008-01-01

    Abstract Vasculogenesis and angiogenesis have been studied for decades using numerous in vitro and in vivo systems, fulfilling the need to elucidate the mechanisms involved in these processes and to test potential therapeutic agents that inhibit or promote neovascularization. Bone tissue engineering in particular has benefited from the application of proangiogenic strategies, considering the need for an adequate vascular supply during healing and the challenges associated with the vascularization of scaffolds implanted in vivo. Conventional methods of assessing the in vivo angiogenic response to tissue-engineered constructs tend to rely on a two-dimensional assessment of microvessel density within representative histological sections without elaboration of the true vascular tree. The introduction of microcomputed tomography (micro-CT) has recently allowed investigators to obtain a diverse range of high-resolution, three-dimensional characterization of structures, including renal, coronary, and hepatic vascular networks, as well as bone formation within healing defects. To date, few studies have utilized micro-CT to study the vascular response to an implanted tissue engineering scaffold. In this paper, conventional in vitro and in vivo models for studying angiogenesis will be discussed, followed by recent developments in the use of micro-CT for vessel imaging in bone tissue engineering research. A new study demonstrating the potential of contrast-enhanced micro-CT for the evaluation of in vivo neovascularization in bony defects is described, which offers significant potential in the evaluation of bone tissue engineering constructs. PMID:18657028

  15. Efficacy and Acceptability of Orthokeratology for Slowing Myopic Progression in Children: A Systematic Review and Meta-Analysis

    PubMed Central

    Wen, Daizong; Huang, Jinhai; Chen, Hao; Bao, Fangjun; Savini, Giacomo; Calossi, Antonio; Chen, Haisi; Li, Xuexi; Wang, Qinmei

    2015-01-01

    Background. To evaluate the efficacy and acceptability of orthokeratology for slowing myopic progression in children with a well conducted evidence-based analysis. Design. Meta-analysis. Participants. Children from previously reported comparative studies were treated by orthokeratology versus control. Methods. A systematic literature retrieval was conducted in MEDLINE, EMBASE, Cochrane Library, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The included studies were subjected to meta-analysis using Stata version 10.1. Main Outcome Measures. Axial length change (efficacy) and dropout rates (acceptability) during 2-year follow-up. Results. Eight studies involving 769 subjects were included. At 2-year follow-up, a statistically significant difference was observed in axial length change between the orthokeratology and control groups, with a weighted mean difference (WMD) of −0.25 mm (95% CI, −0.30 to −0.21). The pooled myopic control rate declined with time, with 55, 51, 51, and 41% obtained after 6, 12, 18, and 24 months of treatment, respectively. No statistically significant difference was obtained for dropout rates between the orthokeratology and control groups at 2-year follow-up (OR, 0.79; 95% CI, 0.52 to 1.22). Conclusions. Orthokeratology is effective and acceptable for slowing myopic progression in children with careful education and monitoring. PMID:26221539

  16. Efficacy and Acceptability of Orthokeratology for Slowing Myopic Progression in Children: A Systematic Review and Meta-Analysis.

    PubMed

    Wen, Daizong; Huang, Jinhai; Chen, Hao; Bao, Fangjun; Savini, Giacomo; Calossi, Antonio; Chen, Haisi; Li, Xuexi; Wang, Qinmei

    2015-01-01

    Background. To evaluate the efficacy and acceptability of orthokeratology for slowing myopic progression in children with a well conducted evidence-based analysis. Design. Meta-analysis. Participants. Children from previously reported comparative studies were treated by orthokeratology versus control. Methods. A systematic literature retrieval was conducted in MEDLINE, EMBASE, Cochrane Library, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The included studies were subjected to meta-analysis using Stata version 10.1. Main Outcome Measures. Axial length change (efficacy) and dropout rates (acceptability) during 2-year follow-up. Results. Eight studies involving 769 subjects were included. At 2-year follow-up, a statistically significant difference was observed in axial length change between the orthokeratology and control groups, with a weighted mean difference (WMD) of -0.25 mm (95% CI, -0.30 to -0.21). The pooled myopic control rate declined with time, with 55, 51, 51, and 41% obtained after 6, 12, 18, and 24 months of treatment, respectively. No statistically significant difference was obtained for dropout rates between the orthokeratology and control groups at 2-year follow-up (OR, 0.79; 95% CI, 0.52 to 1.22). Conclusions. Orthokeratology is effective and acceptable for slowing myopic progression in children with careful education and monitoring. PMID:26221539

  17. Involvement of GABA transporters in atropine-treated myopic retina as revealed by iTRAQ quantitative proteomics.

    PubMed

    Barathi, Veluchamy A; Chaurasia, Shyam S; Poidinger, Michael; Koh, Siew Kwan; Tian, Dechao; Ho, Candice; Iuvone, P Michael; Beuerman, Roger W; Zhou, Lei

    2014-11-01

    Atropine, a muscarinic antagonist, is known to inhibit myopia progression in several animal models and humans. However, the mode of action is not established yet. In this study, we compared quantitative iTRAQ proteomic analysis in the retinas collected from control and lens-induced myopic (LIM) mouse eyes treated with atropine. The myopic group received a (-15D) spectacle lens over the right eye on postnatal day 10 with or without atropine eye drops starting on postnatal day 24. Axial length was measured by optical low coherence interferometry (OLCI), AC-Master, and refraction was measured by automated infrared photorefractor at postnatal 24, 38, and 52 days. Retinal tissue samples were pooled from six eyes for each group. The experiments were repeated twice, and technical replicates were also performed for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. MetaCore was used to perform protein profiling for pathway analysis. We identified a total of 3882 unique proteins with <1% FDR by analyzing the samples in replicates for two independent experiments. This is the largest number of mouse retina proteome reported to date. Thirty proteins were found to be up-regulated (ratio for myopia/control > global mean ratio + 1 standard deviation), and 28 proteins were down-regulated (ratio for myopia/control < global mean ratio - 1 standard deviation) in myopic eyes as compared with control retinas. Pathway analysis using MetaCore revealed regulation of γ-aminobutyric acid (GABA) levels in the myopic eyes. Detailed analysis of the quantitative proteomics data showed that the levels of GABA transporter 1 (GAT-1) were elevated in myopic retina and significantly reduced after atropine treatment. These results were further validated with immunohistochemistry and Western blot analysis. In conclusion, this study provides a comprehensive quantitative proteomic analysis of atropine-treated mouse retina and suggests the involvement of GABAergic signaling in the

  18. Accuracy of Intraocular Lens Power Calculation Formulas for Highly Myopic Eyes

    PubMed Central

    Zhang, Yichi; Liang, Xiao Ying; Liu, Shu; Lee, Jacky W. Y.; Bhaskar, Srinivasan; Lam, Dennis S. C.

    2016-01-01

    Purpose. To evaluate and compare the accuracy of different intraocular lens (IOL) power calculation formulas for eyes with an axial length (AL) greater than 26.00 mm. Methods. This study reviewed 407 eyes of 219 patients with AL longer than 26.0 mm. The refractive prediction errors of IOL power calculation formulas (SRK/T, Haigis, Holladay, Hoffer Q, and Barrett Universal II) using User Group for Laser Interference Biometry (ULIB) constants were evaluated and compared. Results. One hundred seventy-one eyes were enrolled. The Barrett Universal II formula had the lowest mean absolute error (MAE) and SRK/T and Haigis had similar MAE, and the statistical highest MAE were seen with the Holladay and Hoffer Q formulas. The interquartile range of the Barrett Universal II formula was also the lowest among all the formulas. The Barrett Universal II formulas yielded the highest percentage of eyes within ±1.0 D and ±0.5 D of the target refraction in this study (97.24% and 79.56%, resp.). Conclusions. Barrett Universal II formula produced the lowest predictive error and the least variable predictive error compared with the SRK/T, Haigis, Holladay, and Hoffer Q formulas. For high myopic eyes, the Barrett Universal II formula may be a more suitable choice. PMID:27119018

  19. The Myopic-Ubpy-Hrs nexus enables endosomal recycling of Frizzled

    PubMed Central

    Pradhan-Sundd, Tirthadipa; Verheyen, Esther M.

    2015-01-01

    Endosomal trafficking of signaling proteins plays an essential role in cellular homeostasis. The seven-pass transmembrane protein Frizzled (Fz) is a critical component of Wnt signaling. Although Wnt signaling is proposed to be regulated by endosomal trafficking of Fz, the molecular events that enable this regulation are not completely understood. Here we show that the endosomal protein Myopic (Mop) regulates Fz trafficking in the Drosophila wing disk by inhibiting the ubiquitination and degradation of Hrs. Deletion of Mop or Hrs results in endosomal accumulation of Fz and therefore reduced Wnt signaling. The in situ proximity ligation assay revealed a strong association between Mop and Hrs in the Drosophila wing disk. Overexpression of Hrs rescues the trafficking defect caused by mop knockdown. Mop aids in the maintenance of Ubpy, which deubiquitinates (and thus stabilizes) Hrs. In the absence of the ubiquitin ligase Cbl, Mop is dispensable. These findings support a previously unknown role for Mop in endosomal trafficking of Fz in Wnt-receiving cells. PMID:26224310

  20. Expression of Sonic hedgehog and retinal opsin genes in experimentally-induced myopic chick eyes.

    PubMed

    Escaño, M F; Fujii, S; Sekiya, Y; Yamamoto, M; Negi, A

    2000-11-01

    The purpose of this study was to evaluate changes in the expression of different genes in chick retinal tissues after induction of experimental myopia and to evaluate the roles of these genes in the regulation of postnatal eye growth and myopia. Form-deprivation using occlusive goggles and hyperopic defocus by negative spectacle lenses were used to induce myopia in hatched chicks. Expression levels of Sonic hedgehog, its receptor complex, and other retinal cell genes were evaluated by semi-quantitative reverse transcription-polymerase chain reaction. Levels of Sonic hedgehog protein were further evaluated by Western blot analysis. The induction of myopia caused significant increase in expression of Sonic hedgehog mRNA and protein and increased expression of blue and red opsin mRNA. In contrast, the expression of mRNA for Sonic hedgehog receptor complex (Patched-Smoothened), rhodopsin, vimentin, green opsin, violet opsin, and HPC-1 were unaffected by the induction of myopia. The increase in expression of Sonic hedgehog in chick retinas in experimentally-induced myopia suggests involvement in the retina control of postnatal eye growth. Furthermore, Sonic hedgehog may influence the expression of blue and red opsins under myopic conditions.

  1. Mild myopic astigmatism corrected by accidental flap complication: a case report.

    PubMed

    Fahed, Daoud C; Fahed, Charbel D

    2009-10-01

    A 35-year-old female presented for laser in-situ keratomileusis (LASIK). Her preoperative eye exam was normal, with a preop refraction of OD -2.50 D Sph +1.25 D Cyl x175 and OS -2.75 D Sph +1.50 D Cyl x165 (cycloplegic and manifest), with 20/20 BCVA OU. The central pachymetry reading was 553 mum in the right eye. Preoperative topography was normal. At the start of the pendular microkeratome path, some resistance was felt, but the microkeratome continued along its path. Upon inspection of the flap, there was a central rectangle of intact epithelium with two mirror-image flaps on both sides. The flap was repositioned and LASIK was discontinued. The cornea healed with two faint thin linear vertical parallel scars at the edge of the pupil. Postoperative inspection of the blade revealed central blunting. One month postoperatively, the uncorrected visual acuity (UCVA) was 20/20. Manifest and cycloplegic refractions were plano. This is an interesting case of accidental flap complication resulting in the correction of mild myopic astigmatism.

  2. Changes in Choroidal Structures in Eyes with Chronic Central Serous Chorioretinopathy after Half-Dose Photodynamic Therapy

    PubMed Central

    Mitamura, Yoshinori; Mori, Terumi; Akaiwa, Kei; Semba, Kentaro; Egawa, Mariko; Mori, Junya; Sonoda, Shozo; Sakamoto, Taiji

    2016-01-01

    Purpose To determine the structural changes in the choroid after half-dose photodynamic therapy (hPDT) in eyes with chronic central serous chorioretinopathy (CSC). Methods This was a retrospective interventional study of 29 eyes of 29 patients who underwent hPDT for chronic CSC with serous retinal detachment (SRD) and were followed for ≥3 months. Enhanced depth imaging optical coherence tomographic (EDI-OCT) images of the subfoveal choroid were converted to binary images. The central choroidal thickness (CCT), the cross sectional subfoveal choroidal area, the hyporeflective and hyperreflective areas of the inner, outer, and whole choroid were determined at the baseline, and at 1, 3, and 12 months after the hPDT. Results The SRDs were resolved in 26 (89.7%) eyes at 3 months after the hPDT. The mean CCT (P = 0.001), the total choroidal area (P = 0.001), and the hypo-reflective area (P = 0.003) of the whole choroid were significantly decreased from the baseline at 3 months. The hyperreflective area of whole choroid was not significantly changed during the study period (P = 0.083). The hyperreflective but not the hyporeflective area of the inner choroid was significantly decreased at 3 months (P = 0.001, P = 1.000, respectively). The hyporeflective but not the hyperreflective area of the outer choroid was significantly decreased at 3 months (P = 0.001, P = 1.000, respectively). Conclusions The hyperreflective area of the inner choroid and hyporeflective area of the outer choroid were significantly decreased after hPDT for chronic CSC. Because the hyperreflective and hyporeflective area correspond to the choroidal stroma and vessels, respectively, the decreased CCT and subfoveal choroidal area after hPDT may be attributed to a decrease in the exudative changes in the inner choroidal stroma and the reduction of the dilation of the outer choroidal vessels. PMID:27636093

  3. Minocycline Inhibits Alkali Burn-Induced Corneal Neovascularization in Mice

    PubMed Central

    Xiao, Ou; Xie, Zhao-lian; Lin, Bin-wu; Yin, Xiao-fang; Pi, Rong-biao; Zhou, Shi-you

    2012-01-01

    The purpose of this study was to investigate the effects of minocycline on alkali burn-induced corneal neovascularization (CNV). A total of 105 mice treated with alkali burns were randomly divided into three groups to receive intraperitoneal injections of either phosphate buffered saline (PBS) or minocycline twice a day (60 mg/kg or 30 mg/kg) for 14 consecutive days. The area of CNV and corneal epithelial defects was measured on day 4, 7, 10, and14 after alkali burns. On day 14, a histopathological examination was performed to assess morphological change and the infiltration of polymorphonuclear neutrophils (PMNs). The mRNA expression levels of vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), basic fibroblast growth factor (bFGF), matrix metalloproteinases (MMPs), interleukin-1α, 1β, 6 (IL-1α, IL-1β, IL-6) were analyzed using real-time quantitative polymerase chain reaction. The expression of MMP-2 and MMP-9 proteins was determined by gelatin zymography. In addition, enzyme-linked immunosorbent assay was used to analyze the protein levels of VEGFR1, VEGFR2, IL-1β and IL-6. Minocycline at a dose of 60 mg/kg or 30 mg/kg significantly enhanced the recovery of the corneal epithelial defects more than PBS did. There were significant decreases of corneal neovascularization in the group of high-dosage minocycline compared with the control group at all checkpoints. On day 14, the infiltrated PMNs was reduced, and the mRNA expression of VEGFR1, VEGFR2, bFGF, IL-1β, IL-6, MMP-2, MMP-9, -13 as well as the protein expression of VEGFR2, MMP-2, -9, IL-1β, IL-6 in the corneas were down-regulated with the use of 60 mg/kg minocycline twice a day. Our results showed that the intraperitoneal injection of minocycline (60 mg/kg b.i.d.) can significantly inhibit alkali burn-induced corneal neovascularization in mice, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors, inflammatory cytokines and MMPs. PMID

  4. Cellular and physiological mechanisms underlying blood flow regulation in the retina choroid in health disease

    PubMed Central

    Kur, Joanna; Newman, Eric A.; Chan-Ling, Tailoi

    2012-01-01

    We review the cellular and physiological mechanisms responsible for the regulation of blood flow in the retina and choroid in health and disease. Due to the intrinsic light sensitivity of the retina and the direct visual accessibility of fundus blood vessels, the eye offers unique opportunities for the non-invasive investigation of mechanisms of blood flow regulation. The ability of the retinal vasculature to regulate its blood flow is contrasted with the far more restricted ability of the choroidal circulation to regulate its blood flow by virtue of the absence of glial cells, the markedly reduced pericyte ensheathment of the choroidal vasculature, and the lack of intermediate filaments in choroidal pericytes. We review the cellular and molecular components of the neurovascular unit in the retina and choroid, techniques for monitoring retinal and choroidal blood flow, responses of the retinal and choroidal circulation to light stimulation, the role of capillaries, astrocytes and pericytes in regulating blood flow, putative signaling mechanisms mediating neurovascular coupling in the retina, and changes that occur in the retinal and choroidal circulation during diabetic retinopathy, age-related macular degeneration, glaucoma, and Alzheimer's disease. We close by discussing issues that remain to be explored. PMID:22580107

  5. A contact Nd:YAG laser to resect large ciliary body and choroidal tumors.

    PubMed

    Peyman, G A; Alghadyan, A; Peace, J H

    1987-10-01

    We used a contact Nd:YAG laser fit with a 0.2-mm diameter sapphire tip to excise a large (5 1/2 clock hour) iris ciliary body-choroidal tumor and a large (15 X 8 X 3 mm) choroidal tumor. The cutting and coagulation action of the laser helped to minimize intraoperative and postoperative hemorrhage.

  6. 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.

  7. Radiation Therapy for Neovascular Age-related Macular Degeneration

    SciTech Connect

    Kishan, Amar U.; Modjtahedi, Bobeck S.; Morse, Lawrence S.; Lee, Percy

    2013-03-01

    In the enormity of the public health burden imposed by age-related macular degeneration (ARMD), much effort has been directed toward identifying effective and efficient treatments. Currently, anti-vascular endothelial growth factor (VEGF) injections have demonstrated considerably efficacy in treating neovascular ARMD, but patients require frequent treatment to fully benefit. Here, we review the rationale and evidence for radiation therapy of ARMD. The results of early photon external beam radiation therapy are included to provide a framework for the sequential discussion of evidence for the usage of stereotactic radiation therapy, proton therapy, and brachytherapy. The evidence suggests that these 3 modern modalities can provide a dose-dependent benefit in the treatment of ARMD. Most importantly, preliminary data suggest that all 3 can be used in conjunction with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF injections required to maintain visual acuity.

  8. Diospyros kaki Extract Inhibits Alkali Burn-Induced Corneal Neovascularization.

    PubMed

    Yang, Sung Jae; Jo, Hyoung; Kim, Kyung-A; Ahn, Hong Ryul; Kang, Suk Woo; Jung, Sang Hoon

    2016-01-01

    The purpose of this study was to evaluate the effect of ethanol extract of Diospyros kaki (EEDK) leaves on corneal neovascularization (CoNV) in rats. One week after the alkali burns in the corneas, the CoNV area coverage in the CoNV-positive control group, 100 mg/kg EEDK group, and 200 mg/kg EEDK group was 43.3% ± 5.5%, 337.7% ± 2.5%, and 27.2% ± 4.3%, respectively. The areas of CoNV in the EEDK-treated groups were significantly different from those of the CoNV group. EEDK significantly attenuated the upregulation of vascular endothelial growth factor, fibroblast growth factor, interleukin-6, and matrix metalloproteinase-2 (MMP-2) protein levels. Orally administrated D. kaki inhibited CoNV development in rats. PMID:26348484

  9. 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.

  10. The choroid plexus response to a repeated peripheral inflammatory stimulus

    PubMed Central

    2009-01-01

    Background Chronic systemic inflammation triggers alterations in the central nervous system that may relate to the underlying inflammatory component reported in neurodegenerative disorders such as multiple sclerosis and Alzheimer's disease. However, it is far from being understood whether and how peripheral inflammation contributes to induce brain inflammatory response in such illnesses. As part of the barriers that separate the blood from the brain, the choroid plexus conveys inflammatory immune signals into the brain, largely through alterations in the composition of the cerebrospinal fluid. Results In the present study we investigated the mouse choroid plexus gene expression profile, using microarray analyses, in response to a repeated inflammatory stimulus induced by the intraperitoneal administration of lipopolysaccharide every two weeks for a period of three months; mice were sacrificed 3 and 15 days after the last lipopolysaccharide injection. The data show that the choroid plexus displays a sustained response to the repeated inflammatory stimuli by altering the expression profile of several genes. From a total of 24,000 probes, 369 are up-regulated and 167 are down-regulated 3 days after the last lipopolysaccharide injection, while at 15 days the number decreases to 98 and 128, respectively. The pathways displaying the most significant changes include those facilitating entry of cells into the cerebrospinal fluid, and those participating in the innate immune response to infection. Conclusion These observations contribute to a better understanding of the brain response to peripheral inflammation and pave the way to study their impact on the progression of several disorders of the central nervous system in which inflammation is known to be implicated. PMID:19922669

  11. Technique for Robotic Stereotactic Irradiation of Choroidal Melanoma.

    PubMed

    Béliveau-Nadeau, Dominic; Callejo, Sonia; Roberge, David

    2016-01-01

    Radiotherapy has a long history in the organ-sparing management of choroidal melanoma. Joining plaque radiotherapy and proton irradiation, stereotactic robotic photon irradiation is a new tool in the radiation oncologist's armamentarium for ocular tumors. The non-coplanar fields with steep dose gradients are well suited to spare uninvolved retina, anterior chamber, and the optic nerve. In our practice, it is the preferred treatment for melanomas that are non-amenable to standard plaque brachytherapy. Since late 2010, we have treated more than 40 patients with our robotic linear accelerator. This case-based technical note outlines the technique used at the University of Montreal, Montreal, Canada. PMID:27226942

  12. Technique for Robotic Stereotactic Irradiation of Choroidal Melanoma

    PubMed Central

    Béliveau-Nadeau, Dominic; Callejo, Sonia

    2016-01-01

    Radiotherapy has a long history in the organ-sparing management of choroidal melanoma. Joining plaque radiotherapy and proton irradiation, stereotactic robotic photon irradiation is a new tool in the radiation oncologist’s armamentarium for ocular tumors. The non-coplanar fields with steep dose gradients are well suited to spare uninvolved retina, anterior chamber, and the optic nerve. In our practice, it is the preferred treatment for melanomas that are non-amenable to standard plaque brachytherapy. Since late 2010, we have treated more than 40 patients with our robotic linear accelerator. This case-based technical note outlines the technique used at the University of Montreal, Montreal, Canada. PMID:27226942

  13. Expression of stanniocalcin in the epithelium of human choroid plexus.

    PubMed

    Franzén, A M; Zhang, K Z; Westberg, J A; Zhang, W M; Arola, J; Olsen, H S; Andersson, L C

    2000-12-29

    Stanniocalcin (STC) is a 28 kD glycoprotein hormone originally found in bony fish in which it regulates calcium/phosphate homeostasis and protects against hypercalcemia. The recently characterized mammalian STC shows about 70% homology with fish STC. The epithelial cells of proximal tubuli in human and rat kidney and brain neurons have been found to express STC. Here we show that the epithelium of the choroid plexus, already at 16 weeks of fetal age, and of plexus papillomas, synthesize and express STC. Our findings suggest that STC may be of importance for the distribution of calcium and phosphate between the cerebrospinal fluid and blood. PMID:11134638

  14. Smart social adaptation prevents catastrophic ecological regime shifts in networks of myopic harvesters

    NASA Astrophysics Data System (ADS)

    Donges, Jonathan; Lucht, Wolfgang; Wiedermann, Marc; Heitzig, Jobst; Kurths, Jürgen

    2015-04-01

    In the anthropocene, the rise of global social and economic networks with ever increasing connectivity and speed of interactions, e.g., the internet or global financial markets, is a key challenge for sustainable development. The spread of opinions, values or technologies on these networks, in conjunction with the coevolution of the network structures themselves, underlies nexuses of current concern such as anthropogenic climate change, biodiversity loss or global land use change. To isolate and quantitatively study the effects and implications of network dynamics for sustainable development, we propose an agent-based model of information flow on adaptive networks between myopic harvesters that exploit private renewable resources. In this conceptual model of a network of socio-ecological systems, information on management practices flows between agents via boundedly rational imitation depending on the state of the resource stocks involved in an interaction. Agents can also adapt the structure of their social network locally by preferentially connecting to culturally similar agents with identical management practices and, at the same time, disconnecting from culturally dissimilar agents. Investigating in detail the statistical mechanics of this model, we find that an increasing rate of information flow through faster imitation dynamics or growing density of network connectivity leads to a marked increase in the likelihood of environmental resource collapse. However, we show that an optimal rate of social network adaptation can mitigate this negative effect without loss of social cohesion through network fragmentation. Our results highlight that seemingly immaterial network dynamics of spreading opinions or values can be of large relevance for the sustainable management of socio-ecological systems and suggest smartly conservative network adaptation as a strategy for mitigating environmental collapse. Hence, facing the great acceleration, these network dynamics should

  15. Decreased choroidal thickness in eyes with secondary angle closure glaucoma. An aetiological factor for deep retinal changes in glaucoma?

    PubMed Central

    Kubota, T.; Jonas, J. B.; Naumann, G. O.

    1993-01-01

    A decreased count of retinal photoreceptors all over the fundus and a loss of retinal pigment epithelium cells mainly in the parapapillary region have been reported to be associated with glaucoma. This study addressed the question whether this cell loss in the deep retinal layers may be connected with a change of the choroidal thickness in glaucomatous eyes. Histological sections of 12 eyes with secondary angle closure glaucoma due to a malignant melanoma of the ciliary body and 20 eyes with a malignant choroidal melanoma and normal intraocular pressure were histomorphometrically evaluated. Before enucleation the intraocular pressure was significantly higher in the glaucoma group compared with the control group. Thickness of the choroid was measured at 12 locations from the posterior pole to the fundus periphery. The choroid was significantly thinner in the glaucoma group than in the control group. The decreased choroidal thickness was mainly due to a diminished choroidal vessel diameter. The differences were more marked at the optic disc border than in the fundus periphery. The decreased choroidal thickness in the glaucomatous eyes suggests a reduced choroidal perfusion. It fits with the reported lack of autoregulation of the choroidal blood circulation. Considering the diminished choroidal thickness especially in the parapapillary region, it may be one among other factors explaining the changes of the deep retinal layers in eyes with glaucoma. It indicates that thinning of the choroid, besides the chorioretinal atrophy in the parapapillary region, should be added to the panoply of histological changes in glaucoma. Images PMID:8343472

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

    PubMed

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

    2015-05-01

    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.

  17. Interleukin-12 inhibits pathological neovascularization in mouse model of oxygen-induced retinopathy

    PubMed Central

    Zhou, Yedi; Yoshida, Shigeo; Kubo, Yuki; Kobayashi, Yoshiyuki; Nakama, Takahito; Yamaguchi, Muneo; Ishikawa, Keijiro; Nakao, Shintaro; Ikeda, Yasuhiro; Ishibashi, Tatsuro; Sonoda, Koh-Hei

    2016-01-01

    Hypoxia-induced retinal neovascularization is a major pathological condition in many vision-threatening diseases. In the present study, we determined whether interleukin (IL)-12, a cytokine that regulates angiogenesis, plays a role in the neovascularization in a mouse model of oxygen-induced retinopathy (OIR). We found that the expressions of the mRNAs of both IL-12p35 and IL-12p40 were significantly reduced in the OIR retinas compared to that of the room air-raised control. The sizes of the avascular areas and neovascular tufts were larger in IL-12p40 knock-out (KO) mice than that in wild type (WT) mice. In addition, an intravitreal injection of recombinant IL-12 reduced both avascular areas and neovascular tufts. IL-12 injection enhanced the expressions of interferon-gamma (IFN-γ) and other downstream chemokines. In an in vitro system, IL-12 had no significant effect on tube formation of human retinal microvascular endothelial cells (HRECs). Moreover, a blockade of IFN-γ suppressed the inhibitory effect of IL-12 on pathological neovascularization. These results suggest that IL-12 plays important roles in inhibiting pathological retinal neovascularization. PMID:27312090

  18. 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

  19. Cathepsin L is required for endothelial progenitor cell-induced neovascularization

    SciTech Connect

    Urbich, Carmen; Heeschen, Christopher; Aicher, Alexandra; Sasaki, Ken-ichiro; Bruhl, Thomas; Hofmann, Wolf K.; Peters, Christoph; Reinheckel, Thomas; Pennacchio, Len A.; Abolmaali, Nasreddin D.; Chavakis, Emmanouil; Zeiher, Andreas M.; Dimmeler, Stefanie

    2004-01-15

    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 sites 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.

  20. Refractive lenticule extraction (ReLEx) through a small incision (SMILE) for correction of myopia and myopic astigmatism: current perspectives

    PubMed Central

    Ağca, Alper; Demirok, Ahmet; Yıldırım, Yusuf; Demircan, Ali; Yaşa, Dilek; Yeşilkaya, Ceren; Perente, İrfan; Taşkapılı, Muhittin

    2016-01-01

    Small-incision lenticule extraction (SMILE) is an alternative to laser-assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) for the correction of myopia and myopic astigmatism. SMILE can be performed for the treatment of myopia ≤−12 D and astigmatism ≤5 D. The technology is currently only available in the VisuMax femtosecond laser platform. It offers several advantages over LASIK and PRK; however, hyperopia treatment, topography-guided treatment, and cyclotorsion control are not available in the current platform. The working principles, potential advantages, and disadvantages are discussed in this review. PMID:27757010

  1. Composition of fluid obtained from choroid plexus tissue isolated in a chamber in situ.

    PubMed

    Miner, L C; Reed, D J

    1972-12-01

    1. A method was developed for isolating a segment of the choroid plexus of the lateral ventricle of the cat brain in a chamber in situ.2. A comparison of electrolyte and protein concentrations in serum, ultrafiltrate of serum, cisterna magna fluid, fluid accumulated in the chamber and fluid collected from the choroid plexus by another technique, demonstrates that the chamber fluid is a secretory product of the choroid plexus.3. The rate of fluid formation in the chamber was 0.4 mul. min(-1) mg(-1) of tissue, a value in good agreement with reports in the literature.4. The observation that the concentration of K(+) in choroid plexus fluid was lower than that in the serum ultrafiltrate suggests that K(+) is regulated by an active transport process at the choroid plexus.5. Significant correlation was found between electrolyte values and the protein content of the chamber fluid. This suggests that plasma is the probable source of the protein in the chamber fluid and that K(+) and probably Ca(2+) and Mg(2+) in c.s.f. are subject to active homoeostatic regulation by the choroid plexus.6. The technique described provides a new opportunity to study in detail the functional characteristics of the choroid plexus.

  2. Choroid plexus of the fourth ventricle: Review and anatomic study highlighting anatomical variations.

    PubMed

    Tubbs, R Shane; Shoja, Mohammadali M; Aggarwal, Anjali; Gupta, Tulika; Loukas, Marios; Sahni, Daisy; Ansari, Shaheryar F; Cohen-Gadol, Aaron A

    2016-04-01

    Relatively few studies have been performed that analyze the morphology of the choroid plexus of the fourth ventricle. Due to the importance of this tissue as a landmark on imaging and during surgical intervention of the fourth ventricle, the authors performed a cadaveric study to better characterize this important structure. The choroid plexus of the fourth ventricle of 60 formalin fixed adult human brains was examined and measured. The horizontal distance from the midline to the lateral most point of the protruding tip of the horizontal limbs was measured. In the majority of the 60 brain specimens, right and left horizontal limbs of the choroid plexus were seen extending from the midline and protruding out of their respective lateral apertures of the fourth ventricle and into the subarachnoid space. However, on 3.3% of sides, there was absence of an extension into the foramen of Luschka and in one specimen, this lack of extension into the foramen of Luschka was bilateral. On two sides, there was discontinuity between the midline choroid plexus and the tuft of choroid just outside the foramen of Luschka. For specimens in which the choroid plexus did protrude through the foramen of Luschka (96.7%), these tufts were located anterior to the flocculus and inferolateral to the facial/vestibulocochlear nerve complex and posterosuperior to the glossopharyngeal/vagal/accessory complex. A thorough understanding of the normal and variant anatomy of the fourth ventricular choroid plexus is necessary for those who operate in, or interpret imaging of, this region.

  3. The p75 neurotrophin receptor localization in blood-CSF barrier: expression in choroid plexus epithelium

    PubMed Central

    2011-01-01

    Background The presence of neurotrophins and their receptors Trk family has been reported in the choroid plexus. High levels of Nerve Growth Factor (NGF), Neurotrophin-4 (NT-4) and TrkB receptor were detected, while nothing was know about p75 neurotrophin receptor (p75NTR) in the choroid plexus epithelial cells. In neurons, p75NTR receptor has a dual function: promoting survival together with TrkA in response to NGF, and inducing apoptotic signaling through p75NTR. We postulated that p75NTR may also affect the survival pathways in the choroid plexus and also undergoes regulated proteolysis with metalloproteases. Results Here, we demonstrated the presence of p75NTR receptor in the choroid plexus epithelial cells. The p75NTR receptor would be involved in cell death mechanisms and in the damaged induced by amyloid beta (Aβ) in the choroid plexus and finally, we propose an essential role of p75NTR in the Aβ transcytosis through out choroid plexus barrier. Conclusions The presence analysis reveals the new localization of p75NTR in the choroid plexus and, the distribution mainly in the cytoplasm and cerebrospinal fluid (CSF) side of the epithelial cells. We propose that p75NTR receptor plays a role in the survival pathways and Aβ-induced cell death. These data suggest that p75NTR dysfunction play an important role in the pathogenesis of brain diseases. The importance and novelty of this expression expands a new role of p75NTR. PMID:21569322

  4. Culture of choroid plexus epithelial cells and in vitro model of blood-CSF barrier.

    PubMed

    Monnot, Andrew D; Zheng, Wei

    2013-01-01

    Chemical homeostasis in the extracellular fluid of the central nervous system (CNS) is maintained by two brain barrier systems, i.e., the blood-brain barrier (BBB) that separates the blood circulation from brain interstitial fluid and the blood-cerebrospinal fluid barrier (BCB) that separates the blood from the cerebrospinal fluid (CSF). The choroid plexus, where the BCB is located, is a polarized tissue, with the basolateral side of the choroidal epithelium facing the blood and the apical microvilli in direct contact with the CSF. The tissue plays a wide range of roles in brain development, aging, nutrient transport, endocrine regulation, and pathogenesis of certain neurodegenerative disorders. This chapter describes two in vitro cultures that have been well established to allow for study of the BCB structure and function. The primary choroidal epithelial cell culture can be established from rat choroid plexus tissue, and a similar immortalized murine choroidal epithelial cell culture known as Z310 cells has also been established. Both cultures display a dominant polygonal morphology, and immunochemical studies demonstrate the presence of transthyretin, a thyroxine transport protein known to be exclusively produced by the choroidal epithelia in the CNS. These cultures have been adapted for use on freely permeable Transwell(®) membranes sandwiched between two culture chambers, facilitating transport studies of various compounds across this barrier in vitro. These choroidal epithelia cultures with the Transwell system will perceivably assist blood-CSF barrier research. PMID:23097098

  5. Culture of choroid plexus epithelial cells and in vitro model of blood-CSF barrier.

    PubMed

    Monnot, Andrew D; Zheng, Wei

    2013-01-01

    Chemical homeostasis in the extracellular fluid of the central nervous system (CNS) is maintained by two brain barrier systems, i.e., the blood-brain barrier (BBB) that separates the blood circulation from brain interstitial fluid and the blood-cerebrospinal fluid barrier (BCB) that separates the blood from the cerebrospinal fluid (CSF). The choroid plexus, where the BCB is located, is a polarized tissue, with the basolateral side of the choroidal epithelium facing the blood and the apical microvilli in direct contact with the CSF. The tissue plays a wide range of roles in brain development, aging, nutrient transport, endocrine regulation, and pathogenesis of certain neurodegenerative disorders. This chapter describes two in vitro cultures that have been well established to allow for study of the BCB structure and function. The primary choroidal epithelial cell culture can be established from rat choroid plexus tissue, and a similar immortalized murine choroidal epithelial cell culture known as Z310 cells has also been established. Both cultures display a dominant polygonal morphology, and immunochemical studies demonstrate the presence of transthyretin, a thyroxine transport protein known to be exclusively produced by the choroidal epithelia in the CNS. These cultures have been adapted for use on freely permeable Transwell(®) membranes sandwiched between two culture chambers, facilitating transport studies of various compounds across this barrier in vitro. These choroidal epithelia cultures with the Transwell system will perceivably assist blood-CSF barrier research.

  6. Inhibition of corneal neovascularization with a nutrient mixture containing lysine, proline, ascorbic acid, and green tea extract.

    PubMed

    Shakiba, Yadollah; Mostafaie, Ali

    2007-10-01

    Corneal neovascularization is a significant, sight-threatening complication of many ocular surface disorders. Various growth factors and proteinases are involved in corneal neovascularization. The data supporting a causal role for vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs) are extensive. Inhibition of VEGF and MMPs is a main strategy for treating corneal neovascularization. Several findings have shown that corneal neovascularization can be reduced by using anti-VEGF and anti-MMPs agents. Efficacy of a nutrient mixture (NM) containing lysine, proline, ascorbic acid, and green tea extract has been demonstrated for reducing VEGF and MMPs secretion by various cells. Moreover, NM can inhibit endothelial cell migration and capillary tube formation. We herein note that topical application of NM is potentially useful for inhibiting corneal neovascularization and restoration of corneal clarity. Further investigations in animal models are needed to place NM alongside corneal neovascularization therapeutics.

  7. Effect of flaxseed on choroid-sclera complex thickness and on LDL oxidation in the sclera, choroid and retina of diet-induced hypercholesterolaemic rabbits.

    PubMed

    Torres, Rogil José de Almeida; Luchini, Andrea; Both, Alessandro Soares; Precoma, Leonardo Brandao; Champoski, Ana Flavia; Schuh, Maynara Leonardi; Torres, Renan Pedro de Almeida; Noronha, Lucia; Pessoa, Bernardo Molinari; Torres, Lucas Antonio de Almeida; Serci, Nicole Francesca de França; Precoma, Dalton Bertolim

    2014-11-14

    The aim of the present study was to evaluate the effect of flaxseed on choroid-sclera complex thickness and on LDL oxidation in the sclera, choroid and retina of diet-induced hypercholesterolaemic rabbits. New Zealand male albino rabbits (n 21) were divided into two groups: group 1 (G1; n 11), fed a hypercholesterolaemic diet, and group 2 (G2; n 10), fed a hypercholesterolaemic diet enriched with flaxseed flour. The serum concentrations of total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol, TAG and fasting blood glucose were determined at the start of the experiment and on the day of killing (8th week). Choroid and sclera samples were subjected to haematoxylin-eosin (HE) staining and histomorphometric and immunohistochemical analyses with the anti-oxidised LDL antibody. Sensory retina samples were subjected to an immunohistochemical analysis with the primary monoclonal nitrotyrosine antibody. At the end of the experiment, a significant increase was observed in TC and LDL-C concentrations in G1 rabbits when compared with G2 rabbits (P= 0·008 and P= 0·02, respectively). HE staining revealed a significant increase in choroid-sclera complex thickness in G1 rabbits when compared with G2 rabbits (P< 0·001). Immunohistochemical analysis of choroid and sclera samples with the anti-oxidised LDL marker revealed a significant increase in immunoreactivity in G1 rabbits when compared with G2 rabbits (P< 0·001). Immunohistochemical analysis of sensory retina samples with the anti-nitrotyrosine marker revealed a significant increase in immunoreactivity in G1 rabbits when compared with G2 rabbits (P= 0·002). Flaxseed reduced the choroid-sclera complex thickness of diet-induced hypercholesterolaemic rabbits and the expression of oxidised LDL in the choroid-sclera complex as well as the expression of nitrotyrosine in the sensory retina.

  8. Acetazolamide-induced cilio-choroidal effusion after cataract surgery: unusual posterior involvement

    PubMed Central

    Malagola, Romualdo; Arrico, Loredana; Giannotti, Rossella; Pattavina, Luigi

    2013-01-01

    Idiosyncratic reactions to a large number of drugs have been reported to cause choroidal detachment and secondary angle-closure glaucoma (ACG). We report a case of bilateral acute ACG and peculiar choroidal effusion following administration of oral acetazolamide immediately after cataract surgery. Few cases of acute secondary ACG with choroidal effusion and anterior shift of the lens-iris diaphragm have been associated with acetazolamide compared with other sulfonamides. As far as we are aware, posterior involvement with retinal folds and papillary edema due to acetazolamide has not been described before. PMID:23378740

  9. Photodynamic therapy for diffuse choroidal hemangioma in a child with Sturge-Weber syndrome.

    PubMed

    Nugent, Ryan; Lee, Lawrence; Kwan, Anthony

    2015-04-01

    Sturge-Weber syndrome is a rare neurocutaneous disorder involving the leptomeninges, skin of the face, and, in 40% of cases, diffuse choroidal hemangioma. We report the case of a 6-year-old girl with Sturge-Weber syndrome and a large diffuse choroidal hemangioma with retinal detachment involving the majority of the retina. The patient underwent photodynamic therapy. The retinal detachment resolved completely within 3 months of treatment. This case represents the youngest patient in the literature to undergo successful treatment with photodynamic therapy for Sturge-Weber syndrome-associated diffuse choroidal hemangioma. PMID:25828818

  10. Biochemical study of prolactin binding sites in Xenopus laevis brain and choroid plexus

    SciTech Connect

    Muccioli, G.; Guardabassi, A.; Pattono, P. )

    1990-03-01

    The occurrence of prolactin binding sites in some brain structures (telencephalon, ventral hypothalamus, myelencephalon, hypophysis, and choroid plexus) from Xenopus laevis (anuran amphibian) was studied by the in vitro biochemical technique. The higher binding values were obtained at the level of the choroid plexus and above all of the hypothalamus. On the bases of hormonal specificity and high affinity, these binding sites are very similar to those of prolactin receptors of classical target tissues as well as of those described by us in other structures from Xenopus. To our knowledge, the present results provide the first demonstration of the occurrence of prolactin specific binding sites in Xenopus laevis choroid plexus cells.

  11. An international collaborative family-based whole genome quantitative trait linkage scan for myopic refractive error

    PubMed Central

    Abbott, Diana; Li, Yi-Ju; Guggenheim, Jeremy A.; Metlapally, Ravikanth; Malecaze, Francois; Calvas, Patrick; Rosenberg, Thomas; Paget, Sandrine; Zayats, Tetyana; Mackey, David A.; Feng, Sheng

    2012-01-01

    Purpose To investigate quantitative trait loci linked to refractive error, we performed a genome-wide quantitative trait linkage analysis using single nucleotide polymorphism markers and family data from five international sites. Methods Genomic DNA samples from 254 families were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel IVb. Quantitative trait linkage analysis was performed on 225 Caucasian families and 4,656 markers after accounting for linkage disequilibrium and quality control exclusions. Two refractive quantitative phenotypes, sphere (SPH) and spherical equivalent (SE), were analyzed. The SOLAR program was used to estimate identity by descent probabilities and to conduct two-point and multipoint quantitative trait linkage analyses. Results We found 29 markers and 11 linkage regions reaching peak two-point and multipoint logarithms of the odds (LODs)>1.5. Four linkage regions revealed at least one LOD score greater than 2: chromosome 6q13–6q16.1 (LOD=1.96 for SPH, 2.18 for SE), chromosome 5q35.1–35.2 (LOD=2.05 for SPH, 1.80 for SE), chromosome 7q11.23–7q21.2 (LOD=1.19 for SPH, 2.03 for SE), and chromosome 3q29 (LOD=1.07 for SPH, 2.05 for SE). Among these, the chromosome 6 and chromosome 5 regions showed the most consistent results between SPH and SEM. Four linkage regions with multipoint scores above 1.5 are near or within the known myopia (MYP) loci of MYP3, MYP12, MYP14, and MYP16. Overall, we observed consistent linkage signals across the SPH and SEM phenotypes, although scores were generally higher for the SEM phenotype. Conclusions Our quantitative trait linkage analyses of a large myopia family cohort provided additional evidence for several known MYP loci, and identified two additional potential loci at chromosome 6q13–16.1 and chromosome 5q35.1–35.2 for myopia. These results will benefit the efforts toward determining genes for myopic refractive error. PMID:22509102

  12. Overload and neovascularization of shoulder tendons in volleyball players

    PubMed Central

    2012-01-01

    Background In overhead sports like volleyball, the onset of a rotator cuff tendinopathy due to functional overload is a common observation. An angiofibroblastic etiopathogenesis has been hypothesized, whereby a greater anaerobic metabolism occurs in critical zones of the tendon with a lower degree of vascularization; this would induce collagen and extracellular matrix degradation, that could then trigger a compensatory neovascularization response. We performed a clinical observational study of 80 elite volleyball players, monitoring the perfusion values of the supraspinatus tendons by oximetry. Results No statistically significant differences were found between the oximetry data and age, sex or years of sports activity, nor when comparing the right and left arm or the dominant and non-dominant arm. A statistically significant difference was found for the dominant arm values in relation to the competitive role, higher values being obtained in outside hitters (62.7%) than middle hitters (53.7%) (p = 0.01), opposite hitters (55.5%) (p = 0.02) and libero players (54.4%) (p = 0.008), whereas there were no differences in setters (56.2%) (p > 0.05). Conclusions The different tendon vascularization values found in players with different roles in the team may be attributed to a response to the specific biomechanical demands posed by the different overhead throwing roles. PMID:22853746

  13. Preterm diagnosis of choristoma and choroidal coloboma in Goldenhar's syndrome.

    PubMed

    Herwig, Martina C; Gembruch, Ulrich; Born, Mark; Gevensleben, Heidrun; Loeffler, Karin U; Müller, Annette M

    2011-01-01

    In addition to general pathological findings characteristic of Goldenhar's syndrome, we report ocular findings in a 22-week-old fetus with hemifacial microsomia, endorsing this diagnosis. After abortion the fetus was examined via a standard paidopathological autopsy including ophthalmopathologic macroscopic and microscopic examination of both eyes. Postmortem findings included left hemifacial microsomia with ipsilateral microtia, atresia of the acoustic meatus, microphthalmia, a ventricular septal defect, and abnormalities of the ribs. Ophthalmopathological examination of the affected microphthalmic eye revealed a scleral choristoma (cartilage), choroidal/retinal pigment epithelium coloboma, and staphyloma. General pathology findings plus the ocular findings allowed the diagnosis of Goldenhar's syndrome. The cartilaginous choristoma present in the patient has previously not been reported in association with this syndrome. A discussion of differential diagnoses is provided, confirming that the ophthalmopathological investigation of fetal eyes can be of great value for classifying syndromes associated with microphthalmia.

  14. Failure of choroidal melanoma to respond to helium ion therapy

    SciTech Connect

    Char, D.H.; Crawford, J.B.; Castro, J.R.; Woodruff, K.H.

    1983-02-01

    Helium ion irradiation is a promising alternative therapy for choroidal melanoma. In short-term follow-up (less than 5 years), more than 90% (18/19) of treated patients demonstrated tumor regression. Researchers had to enucleate five eyes after helium ion therapy either because of continued tumor growth (four patients) or other complications (one patient). Two melanomas continued to grow and seemed to be radioresistant. In two other tumors it retrospectively seemed that the entire lesion was not inside the radiation field. In one patient total retinal detachment and glaucoma developed; enucleation was performed because of a painful eye. Metastatic disease developed in no patients. The treatment failures emphasize that there are a number of unresolved issues regarding the use of charged-particle irradiation in the treatment of melanoma. Further studies must be performed to answer these questions and better delineate the use of these newer forms of therapy.

  15. Surgical treatment of retinal detachment in the choroidal colobomas.

    PubMed

    Corcostegui, B; Güell, J L; García-Arumí, J

    1992-01-01

    Seven eyes from seven patients with retinal detachment and choroidal coloboma (with or without optic disc involvement) were treated. The retinal break was always inside the colobomatous area, except in the cases with evidence of peripheral retinal breaks. In order to produce reattachment of the retina, vitrectomy procedures with removal of posterior hyaloid were used. Drainage of subretinal fluid was performed through the break in the area of the coloboma, with simultaneous fluid-air exchange. Previously undetected retinal breaks were identified by inspecting for the presence of schlieren in the colobomatous area during fluid-air exchange. A peripheral scleral buckle was then applied. Argon laser endophotocoagulation was performed, but when the coloboma involved the optic disc, red krypton endophotocoagulation was used. Retinal reattachment was achieved in all cases.

  16. The prevalence of neovascularity in patients clinically diagnosed with rotator cuff tendinopathy

    PubMed Central

    2009-01-01

    Background Shoulder dysfunction is common and pathology of the rotator cuff tendons and subacromial bursa are considered to be a major cause of pain and morbidity. Although many hypotheses exist there is no definitive understanding as to the origin of the pain arising from these structures. Research investigations from other tendons have placed intra-tendinous neovascularity as a potential mechanism of pain production. The prevalence of neovascularity in patients with a clinical diagnosis of rotator cuff tendinopathy is unknown. As such the primary aim of this pilot study was to investigate if neovascularity could be identified and to determine the prevalence of neovascularity in the rotator cuff tendons and subacromial bursa in subjects with unilateral shoulder pain clinically assessed to be rotator cuff tendinopathy. The secondary aims were to investigate the association between the presence of neovascularity and pain, duration of symptoms, and, neovascularity and shoulder function. Methods Patients with a clinical diagnosis of unilateral rotator cuff tendinopathy referred for a routine diagnostic ultrasound (US) scan in a major London teaching hospital formed the study population. At referral patients were provided with an information document. On the day of the scan (on average, at least one week later) the patients agreeing to participate were taken through the consent process and underwent an additional clinical examination prior to undergoing a bilateral grey scale and colour Doppler US examination (symptomatic and asymptomatic shoulder) using a Philips HDI 5000 Sono CT US machine. The ultrasound scans were performed by one of two radiologists who recorded their findings and the final assessment was made by a third radiologist blinded both to the clinical examination and the ultrasound examination. The findings of the radiologists who performed the scans and the blinded radiologist were compared and any disagreements were resolved by consensus. Results

  17. Implementation studies of ranibizumab for neovascular age-related macular degeneration.

    PubMed

    Bloch, Sara Brandi

    2013-11-01

    The pathogenesis of AMD is associated with age changes plus pathological changes involving oxidative stress and an altered inflammatory response leading to injury of retinal pigment epithelial cells and the adjacent choroidea and photoreceptor cells. AMD is divided into early, intermediate and advanced AMD. The advanced form of AMD is further divided into non-neovascular AMD and neovascular AMD. The diagnosis of neovascular AMD is based on FA and clinical characteristics of the eyes. The CNV lesions are by their growth pattern divided into type 1 CNV lesions, which grow primarily beneath the RPE, and type 2 CNV lesions, which have penetrated the RPE and evolve within the subretinal space. The natural course of neovascular AMD leads to visual disability in a majority of cases within the first years after onset, primarily caused by the development of subfoveal fibrous tissue and atrophy of the RPE. The prognosis of visual acuity in neovascular AMD has been markedly improved by the introduction of an intravitreal administered VEGF inhibitor (ranibizumab) given on a monthly basis. Treatment with ranibizumab for neovascular AMD was introduced in Denmark in 2006 under a fully reimbursed national healthcare plan. Treatment with ranibizumab is given in a variable dosing regimen that varies from the monthly dosing regimen administered in the studies that led to the approval of ranibizumab for neovascular AMD in Europe. The main objectives of this PhD thesis were to evaluate and potentially improve treatment with ranibizumab in a variable OCT guided regimen for neovascular AMD. Another intension of this PhD thesis was to prepare the conditions for future research to further improve the visual prognosis in neovascular AMD treated with anti-VEGF agents. The first study revealed that vision was improved in eyes with active neovascular AMD treated for 1 year in a variable ranibizumab treatment regimen as compared to PDT and the natural course of the disease. We assumed by

  18. Implementation studies of ranibizumab for neovascular age-related macular degeneration.

    PubMed

    Bloch, Sara Brandi

    2013-11-01

    The pathogenesis of AMD is associated with age changes plus pathological changes involving oxidative stress and an altered inflammatory response leading to injury of retinal pigment epithelial cells and the adjacent choroidea and photoreceptor cells. AMD is divided into early, intermediate and advanced AMD. The advanced form of AMD is further divided into non-neovascular AMD and neovascular AMD. The diagnosis of neovascular AMD is based on FA and clinical characteristics of the eyes. The CNV lesions are by their growth pattern divided into type 1 CNV lesions, which grow primarily beneath the RPE, and type 2 CNV lesions, which have penetrated the RPE and evolve within the subretinal space. The natural course of neovascular AMD leads to visual disability in a majority of cases within the first years after onset, primarily caused by the development of subfoveal fibrous tissue and atrophy of the RPE. The prognosis of visual acuity in neovascular AMD has been markedly improved by the introduction of an intravitreal administered VEGF inhibitor (ranibizumab) given on a monthly basis. Treatment with ranibizumab for neovascular AMD was introduced in Denmark in 2006 under a fully reimbursed national healthcare plan. Treatment with ranibizumab is given in a variable dosing regimen that varies from the monthly dosing regimen administered in the studies that led to the approval of ranibizumab for neovascular AMD in Europe. The main objectives of this PhD thesis were to evaluate and potentially improve treatment with ranibizumab in a variable OCT guided regimen for neovascular AMD. Another intension of this PhD thesis was to prepare the conditions for future research to further improve the visual prognosis in neovascular AMD treated with anti-VEGF agents. The first study revealed that vision was improved in eyes with active neovascular AMD treated for 1 year in a variable ranibizumab treatment regimen as compared to PDT and the natural course of the disease. We assumed by

  19. Evaluation of choroidal thickness changes after phacoemulsification surgery

    PubMed Central

    Aslan Bayhan, Seray; Bayhan, Hasan Ali; Muhafiz, Ersin; Kırboğa, Kadir; Gürdal, Canan

    2016-01-01

    Purpose The aim of the study was to analyze the effects of uneventful phacoemulsification surgery on choroidal thickness (CT) using spectral domain optical coherence tomography (SD-OCT). Methods In this prospective study, 38 eyes of 38 patients having phacoemulsification surgery were included. All patients underwent detailed ophthalmologic examination, including preoperative axial length (AXL) measurement with optical biometry and intraocular pressure (IOP) measurement preoperatively and 1 month postoperatively. The CT was measured perpendicularly at the fovea and 1.5 mm temporal, 3.0 mm temporal, 1.5 mm nasal, and 3.0 mm nasal using SD-OCT preoperatively and 1 month postoperatively. Changes in the CT after surgery and correlation of this change with age, AXL, preoperative IOP, and IOP change were evaluated. Results There was a statistically significant increase in the CT at all regions evaluated. This increment was more prominent in the nasal and subfoveal regions. The IOP decreased significantly 1 month after surgery (16.14±4.94 mmHg vs 13.91±4.86 mmHg; P<0.001). The change in IOP was correlated with the CT changes at all regions, whereas age, AXL, and preoperative IOP had no significant correlations with the changes in CT. Conclusion Phacoemulsification surgery may cause significant increase in CT, which is correlated with surgery-induced IOP change in the short term. Long-term follow-up of eyes having phacoemulsification surgery may provide further insight into the effects of cataract surgery on the choroid. PMID:27307699

  20. Transpupillary thermotherapy (TTT) for the treatment of choroidal neovascularisation

    PubMed Central

    Newsom, R; McAlister, J; Saeed, M; McHugh, J

    2001-01-01

    AIM—To assess the effectiveness of transpupillary thermotherapy (TTT) for the treatment of classic and occult choroidal neovascularisation (CNV).
METHOD—In a retrospective, case selected, open label trial 44 eyes of 42 patients with CNV secondary to age related macular degeneration (ARMD) were studied. 44 eyes with angiographically defined CNV were treated with diode laser (810 nm) TTT. Laser beam sizes ranged between 0.8 and 3.0 mm and power settings between 250-750 mW. Treatment was given in one area for 1 minute, the end point being no visible change, or a slight greying of the retina. Outcome was assessed with Snellen visual acuity and clinical examination; in 24/44 patients angiographic follow up was available.
RESULTS—12 predominantly classic CNV and 32 predominantly occult membranes were followed up for a mean of 6.1 months (range 2-19). Mean change in vision for classic membranes was −0.75 (SD 1.75) Snellen lines and occult membranes was −0.66 Snellen lines (2.1) (p>0.05). Predominantly classic membranes were closed in 75% (95% CI: 62.5-87.5) of eyes, remained persistent in 25% (95% CI: 12.5-37.5); no recurrences occurred. Predominantly occult membranes were closed in 78% (95% CI: 70.1-85.3) of eyes, remained persistent in 12.5% (95% CI: 6.6-18.5), and were recurrent in 5.1% (95% CI: 4.2-14.3).
CONCLUSIONS—Transpupillary thermotherapy is a potential treatment for CNV. It is able to close choroidal neovascularisation while maintaining visual function in patients with classic and occult disease. Further trials of TTT are needed to compare this intervention with the natural history and other treatment modalities.

 PMID:11159481

  1. 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. PMID:26957857

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

    PubMed Central

    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. PMID:26957857

  3. Association between choroidal thickness and anterior chamber segment in eyes with narrow or open-angle

    PubMed Central

    Li, Song-Feng; Wu, Ge-Wei; Chen, Chang-Xi; Shen, Ling; Zhang, Zhi-Bao; Gao, Fei; Wang, Ning-Li

    2016-01-01

    AIM To investigate the relationship between choroidal thickness and anterior chamber segment in subjects with eyes with narrow or open-angle. METHODS The subfoveal choroidal thickness was measured with enhanced depth-imaging optical coherence tomography and anterior chamber parameters were measured with ultrasound biomicroscopy in one eye of 23 subjects with open-angle eyes and 38 subjects with narrow-angle eyes. The mean age was 59.52±7.04y for narrow-angle subjects and 60.76±7.23y for open-angle subjects (P=0.514). Multivariate linear regression analysis was performed to assess the association between choroidal thickness and narrow-angle parameters. RESULTS There were no differences in subfoveal choroidal thickness between open- and narrow-angle subjects (P=0.231). Anterior chamber parameters, including central anterior chamber depth, trabecular iris angle, iris thickness 500 µm from the scleral spur (IT500), and ciliary body thickness at 1 mm and 2 mm from the scleral spur (CBT1, CBT2) showed significant differences between the two groups (P<0.05). Subfoveal choroidal thickness showed negative correlation (β=-0.496, P=0.016) only with anterior chamber depth in the open-angle group and with age (β=-0.442, P=0.003) and IT500 (β=-0.399, P=0.008) in the narrow-angle group. However, subfoveal choroidal thickness was not correlated with trabecular iris angle, anterior chamber depth, ciliary body thickness, or central corneal thickness in the narrow-angle group. CONCLUSION Choroidal thickness does not differ in the two groups and has not correlated with anterior chamber parameters in narrow-angle subjects, suggesting a lack of relationship between choroidal thickness and primary angle-closure glaucoma. PMID:27588269

  4. Persistent suppression of ocular neovascularization with intravitreal administration of AAVrh.10 coding for bevacizumab.

    PubMed

    Mao, Yanxiong; Kiss, Szilard; Boyer, Julie L; Hackett, Neil R; Qiu, Jianping; Carbone, Andrew; Mezey, Jason G; Kaminsky, Stephen M; D'Amico, Donald J; Crystal, Ronald G

    2011-12-01

    Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of neovascular age-related macular degeneration and diabetic retinopathy. Bevacizumab, an anti-VEGF monoclonal antibody, is efficacious for these disorders, but requires monthly intravitreal administration, with associated discomfort, cost, and adverse event risk. We hypothesized that a single intravitreal administration of adeno-associated virus (AAV) vector expressing bevacizumab would result in persistent eye expression of bevacizumab and suppress VEGF-induced retinal neovascularization. We constructed an AAV rhesus serotype rh.10 vector to deliver bevacizumab (AAVrh.10BevMab) and assessed its ability to suppress neovascularization in transgenic mice overexpressing human VEGF165 in photoreceptors. Intravitreal AAVrh.10BevMab directed long-term bevacizumab expression in the retinal pigmented epithelium. Treated homozygous mice had reduced levels of neovascularization, with 90±4% reduction 168 days following treatment. Thus, a single administration of AAVrh.10BevMab provides long-term suppression of neovascularization without the costs and risks associated with the multiple administrations required for the current conventional bevacizumab monoclonal drug delivery.

  5. OB protein binds specifically to the choroid plexus of mice and rats.

    PubMed

    Devos, R; Richards, J G; Campfield, L A; Tartaglia, L A; Guisez, Y; van der Heyden, J; Travernier, J; Plaetinck, G; Burn, P

    1996-05-28

    Binding studies were conducted to identify the anatomical location of brain target sites for OB protein, the ob gene product. 125I-labeled recombinant mouse OB protein or alkaline phosphatase-OB fusion proteins were used for in vitro and in vivo binding studies. Coronal brain sections or fresh tissue from lean, obese ob/ob, and obese db/db mice as well as lean and obese Zucker rats were probed to identify potential central OB protein-binding sites. We report here that recombinant OB protein binds specifically to the choroid plexus. The binding of OB protein (either radiolabeled or the alkaline phosphatase-OB fusion protein) and its displacement by unlabeled OB protein was similar in lean, obese ob/ob, and obese db/db mice as well as lean and obese Zucker rats. These findings suggest that OB protein binds with high affinity to a specific receptor in the choroid plexus. After binding to the choroid plexus receptor, OB protein may then be transported across the blood-brain barrier into the cerebrospinal fluid. Alternatively, binding of OB protein to a specific receptor in the choroid plexus may activate afferent neural inputs to the neural network that regulates feeding behavior and energy balance or may result in the clearance or degradation of OB protein. The identification of the choroid plexus as a brain binding site for OB protein will provide the basis for the construction of expression libraries and facilitate the rapid cloning of the choroid plexus OB receptor.

  6. Evaluation of Choroidal Thickness in Patients with Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma

    PubMed Central

    Ozec, Ayse Vural; Dogan, Oznur; Dursun, Feyza Gulac; Toker, Mustafa Ilker; Topalkara, Aysen; Arici, Mustafa Kemal; Erdogan, Haydar

    2016-01-01

    Purpose. To compare the macular and peripapillary choroidal thickness in eyes with pseudoexfoliation (PEX) syndrome and PEX glaucoma with the normal eyes of healthy controls. Materials and Methods. In this prospective study, 30 eyes of 30 patients with PEX syndrome, 28 eyes of 28 patients with PEX glaucoma, and 30 eyes of 30 age-matched healthy subjects were enrolled. Choroidal thicknesses in the macular and peripapillary areas were measured by using spectral domain optical coherence tomography. Results. Gender, age, and axial length did not significantly differ between the groups (all, p > 0.05). The mean values of choroidal thickness in the macular and peripapillary areas (except the superior quadrant) in the patients with PEX syndrome and PEX glaucoma were lower compared with controls (all p < 0.05). The mean values of the macular and peripapillary choroidal thickness in the PEX glaucoma group were lower compared with PEX syndrome group; however this difference was not significant. Conclusions. The findings of this study revealed that macular and peripapillary choroidal thicknesses were decreased in PEX syndrome and PEX glaucoma cases. The role of choroid in the development of glaucomatous damage in patients with PEX syndrome remains unclear. PMID:27403338

  7. Tumor seeding after diagnostic vitrectomy for choroidal metastasis in breast cancer.

    PubMed

    Kung, Ya-Hsin; Wu, Tsung-Tien; Lin, Chia-Shian

    2012-09-01

    Choroidal metastasis is the most common type of intraocular tumor in adults, and in females the most common primary site is the breast. We report a case of unilateral choroidal metastasis with exudative retinal detachment as the initial presentation of recurrent breast cancer, and subsequent ophthalmic metastasis following diagnostic vitrectomy. A 49-year-old woman with a 7-year-history of well-treated bilateral breast cancer had been suffering from blurred vision in the left eye for 1 week. Ocular examination was normal except for superotemporal retinal detachment in the left eye. Neither retinal break nor choroidal mass was seen. The patient received scleral buckling and pneumatic retinopexy without significant improvement. Fluorescein angiography revealed a suspected choroidal metastasis in the left eye, but ocular ultrasonography did not show a visible choroidal mass. Two consecutive diagnostic vitrectomies with cytology could not confirm malignancy. A systemic workup was also negative. Six months later, two tumor masses were noted over two of the sclerotomy wounds of the left eye. Pathology showed adenocarcinoma compatible with invasive ductal carcinoma of the breast. Ocular metastasis may present as infiltrative choroidal lesions with exudative retinal detachment without a visible mass. Invasive procedures, such as fine-needle aspiration biopsy and diagnostic vitrectomy, may risk tumor seeding.

  8. Defining the proteome of human iris, ciliary body, retinal pigment epithelium, and choroid.

    PubMed

    Zhang, Pingbo; Kirby, David; Dufresne, Craig; Chen, Yan; Turner, Randi; Ferri, Sara; Edward, Deepak P; Van Eyk, Jennifer E; Semba, Richard D

    2016-04-01

    The iris is a fine structure that controls the amount of light that enters the eye. The ciliary body controls the shape of the lens and produces aqueous humor. The retinal pigment epithelium and choroid (RPE/choroid) are essential in supporting the retina and absorbing light energy that enters the eye. Proteins were extracted from iris, ciliary body, and RPE/choroid tissues of eyes from five individuals and fractionated using SDS-PAGE. After in-gel digestion, peptides were analyzed using LC-MS/MS on an Orbitrap Elite mass spectrometer. In iris, ciliary body, and RPE/choroid, we identified 2959, 2867, and 2755 nonredundant proteins with peptide and protein false-positive rates of <0.1% and <1%, respectively. Forty-three unambiguous protein isoforms were identified in iris, ciliary body, and RPE/choroid. Four "missing proteins" were identified in ciliary body based on ≥2 proteotypic peptides. The mass spectrometric proteome database of the human iris, ciliary body, and RPE/choroid may serve as a valuable resource for future investigations of the eye in health and disease. The MS proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifiers PXD001424 and PXD002194. PMID:26834087

  9. Evaluation of Choroidal Thickness in Patients with Pseudoexfoliation Syndrome and Pseudoexfoliation Glaucoma.

    PubMed

    Dursun, Ayhan; Ozec, Ayse Vural; Dogan, Oznur; Dursun, Feyza Gulac; Toker, Mustafa Ilker; Topalkara, Aysen; Arici, Mustafa Kemal; Erdogan, Haydar

    2016-01-01

    Purpose. To compare the macular and peripapillary choroidal thickness in eyes with pseudoexfoliation (PEX) syndrome and PEX glaucoma with the normal eyes of healthy controls. Materials and Methods. In this prospective study, 30 eyes of 30 patients with PEX syndrome, 28 eyes of 28 patients with PEX glaucoma, and 30 eyes of 30 age-matched healthy subjects were enrolled. Choroidal thicknesses in the macular and peripapillary areas were measured by using spectral domain optical coherence tomography. Results. Gender, age, and axial length did not significantly differ between the groups (all, p > 0.05). The mean values of choroidal thickness in the macular and peripapillary areas (except the superior quadrant) in the patients with PEX syndrome and PEX glaucoma were lower compared with controls (all p < 0.05). The mean values of the macular and peripapillary choroidal thickness in the PEX glaucoma group were lower compared with PEX syndrome group; however this difference was not significant. Conclusions. The findings of this study revealed that macular and peripapillary choroidal thicknesses were decreased in PEX syndrome and PEX glaucoma cases. The role of choroid in the development of glaucomatous damage in patients with PEX syndrome remains unclear. PMID:27403338

  10. Homoisoflavanone inhibits retinal neovascularization through cell cycle arrest with decrease of cdc2 expression.

    PubMed

    Kim, Jeong Hun; Kim, Ki Hyun; Kim, Jin Hyoung; Yu, Young Suk; Kim, Young-Myeong; Kim, Kyu-Won; Kwon, Ho Jeong

    2007-11-01

    Neovascularization in the eye is the most common cause of blindness in all age groups; retinopathy of prematurity (ROP), diabetic retinopathy, and age-related macular degeneration. Despite current advances in surgical treatments, ROP remains as the most serious problem of vision loss in children. Here, we report that homoisoflavanone, a natural product from Cremastra appendiculata, significantly reduces retinal neovascularization in a mouse model of ROP. Homoisoflavanone inhibited the cell growth of HUVECs, but its cytotoxic effect was not observed in a concentration range of 1-20 microM. HUVECs population gradually increased in G2/M phase and reduced in G0/G1 and S phases after exposure to the compound. Homoisoflavanone decreased the level of cdc2 expression whereas the level of p21WAF1 expression was increased in a dose-dependent manner. These data demonstrate that homoisoflavanone could inhibit retinal neovascularization and be applied in the treatment of other vasoproliferative retinopathies.

  11. Sulodexide inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy

    PubMed Central

    Jo, Hyoung; Jung, Sang Hoon; Kang, Jun; Yim, Hye Bin; Kang, Kui Dong

    2014-01-01

    Sulodexide is a mixed glycosaminoglycan composed of heparin and dermatan sulfate. In this study, the anti-angiogenic effect of sulodexide was investigated using an oxygen-induced retinopathy (OIR) mouse model. The retinas of sham-injected OIR mice (P17) had a distinctive central area of nonperfusion, and this area was significantly decreased in sulodexide-injected mice. The number of neovascular tufts measured by SWIFT_NV and mean neovascular lumen number were significantly decreased in sulodexide-injected mice. Hyperbaric oxygen exposure resulted in increased levels of VEGF, MMP-2 and MMP-9, and when mice were treated with sulodexide, a dose-dependent reduction in VEGF, MMP-2 and MMP-9 levels was observed. Our results clearly demonstrate the anti-angiogenic effect of sulodexide and highlight sulodexide as a candidate supplementary substance to be used for the treatment of ocular pathologies that involve neovascularization. [BMB Reports 2014; 47(11): 637-642] PMID:24602608

  12. Early detection of extrafoveal neovascular membranes by daily central field evaluation.

    PubMed

    Fine, S L

    1985-05-01

    Argon laser photocoagulation can reduce the risk of severe vision loss in patients with age-related macular degeneration, ocular histoplasmosis, and idiopathic neovascularization. Early detection of neovascularization soon after the onset increases the likelihood of identifying patients with a new vessel membrane in a potentially treatable position. Patients with one or both eyes at risk for the development of a new vessel membrane should assess their central visual fields on a daily basis by occluding first one eye and then the other. Any disturbance in distance vision or reading vision or the appearance of distortion in the patient's field or on the Amsler grid should prompt an eye examination at the earliest feasible time, in an effort to detect neovascularization in a treatable position.

  13. Sonic hedgehog: its expression in a healing cornea and its role in neovascularization

    PubMed Central

    Miyamoto, Takeshi; Saika, Shizuya

    2009-01-01

    Purpose To examine if sonic hedgehog (Shh) is involved in tissue neovascularization by using cell culture and an animal cornea. Methods The effects of exogenous Shh (5.0 nM), vascular endothelial growth factor (VEGF), and/or a Shh signal inhibitor (2.5 or 10.0 μM cyclopamine) on vessel-like tube formation of vascular endothelial cells were examined in vitro. The effects of Shh on the expression of angiogenic cytokines in cultured cell types were examined in cultured cells. The expression of Shh and its receptor, Patched 1 (Ptc), was examined in a vascularized mouse cornea during post-alkali burn healing. The effect of exogenous Shh on corneal neovascularization in vivo was assayed using a rat cornea system. The effect of a topical injection of cyclopamine on cauterization-induced corneal neovascularization was then studied. Results Adding Shh promoted vessel-like tube formation of vascular endothelial cells. This effect was counteracted by addition of cyclopamine. Cyclopamine did not affect VEGF-enhanced tube formation. Shh did not affect the expression levels of angiogenic cytokines in cultured cell types. mRNA and protein expression levels of Shh and Ptc were under the detection limit in an uninjured cornea, but Shh but not Ptc was upregulated in a healing, alkali-burned, vascularized cornea. Exogenous Shh promoted neovascularization (NV) formation in vivo in a rat cornea. Topical cyclopmine blocked Gli signaling (blocked translocation of Gli3) and the length of neovascularization in the peripheral cornea post-cauterization as compared with the control vehicle-treated cornea. Conclusions Shh enhances endothelial tube formation independently through VEGF signaling in vitro. Shh signaling is involved in the development of unfavorable corneal neovascularization in animal corneas. PMID:19471603

  14. Lack of association between VAP-1/SSAO activity and corneal neovascularization in a rabbit model.

    PubMed

    Énzsöly, Anna; Markó, Katalin; Tábi, Tamás; Szökő, Éva; Zelkó, Romána; Tóth, Miklós; Petrash, J Mark; Mátyus, Péter; Németh, János

    2013-06-01

    The aim of this study is to determine the efficacy of a potent and specific vascular adhesive protein-1/semicarbazide-sensitive amine oxidase (VAP-1/SSAO) inhibitor, LJP 1207, as a potential antiangiogenic and anti-inflammatory agent in the therapy of corneal neovascularization. Corneal neovascularization was induced with intrastromal suturing in rabbits (n = 20). Topical treatment with VAP-1/SSAO inhibitor LJP 1207 (n = 5, 4 times a day), bevacizumab (n = 5, daily), their combination (n = 5) and vehicle only (n = 5, 4 times a day) were applied postoperatively for 2 weeks. The development and extent of corneal neovascularization were evaluated by digital image analysis. At the end of the observation period, the level of corneal and serum VAP-1/SSAO activity was measured fluorometrically and radiochemically. The corneal VAP-1/SSAO activity was significantly elevated in the suture-challenged vehicle-treated group (3,075 ± 1,009 pmol/mg/h) as compared to unoperated controls (464.2 ± 135 pmol/mg/h, p < 0.001). Treatment with LJP 1207 resulted in slower early phase neovascularization compared to vehicle-treated animals (not significant). At days 7-14, there was no significant difference in the extent of corneal neovascularization between inhibitor- and vehicle-treated corneas, even though inhibitor treatment caused a normalization of corneal VAP-1/SSAO activity (885 ± 452 pmol/mg/h). Our results demonstrate that the significant elevation of VAP-1/SSAO activity due to corneal injury can be prevented with VAP-1/SSAO inhibitor LJP 1207 treatment. However, normalization of VAP-1/SSAO activity in this model does not prevent the development of corneal neovascularization.

  15. Short-Term Topical Bevacizumab in the Treatment of Stable Corneal Neovascularization

    PubMed Central

    Cheng, Sheng-Fu; Dastjerdi, Mohammad H.; Ferrari, Giulio; Okanobo, Andre; Bower, Kraig S.; Ryan, Denise S.; Amparo, Francisco; Stevenson, William; Hamrah, Pedram; Nallasamy, Nambi; Dana, Reza

    2012-01-01

    Purpose To evaluate the safety and efficacy of topical bevacizumab in the treatment of corneal neovascularization (NV). Design Prospective, non-randomized, interventional case series. Methods Setting Institutional, multicenter clinical trial. Study Population Twenty eyes from 20 patients with stable corneal NV. Intervention Procedures Patients were treated with topical 1.0% for 3 weeks and monitored for a total of 24 weeks. Main Outcome Measures Primary outcome measures included: neovascular area, defined as the area of the corneal vessels themselves; vessel caliber, defined as the mean corneal vessel diameter; and invasion area, defined as the fraction of the total cornea into which the vessels extended. The occurrence of ocular and systemic adverse events was closely monitored. Results As compared to the baseline visit, patients exhibited a statistically significant improvement in neovascular area by week 6 (P = .007) and vessel caliber by week 12 (P = .006). At the final visit, neovascular area, vessel caliber, and invasion area were reduced by 47.5%, 36.2%, and 20%, respectively. The decreases in neovascular area and vessel caliber were statistically significant (P < .001 and P = .003, respectively); however, the reduction in invasion area did not reach statistical significance (P = .06). There were no significant changes in the secondary outcomes and there were no adverse events. Conclusions Short-term topical bevacizumab treatment reduced the extent of stable corneal NV as measured by neovascular area and vessel caliber with no associated adverse events. Interestingly, the degree of treatment efficacy was inversely proportional to the baseline invasion area. PMID:22967868

  16. Age-Dependent Morphologic Alterations in the Outer Retinal and Choroidal Thicknesses Using Swept Source Optical Coherence Tomography

    PubMed Central

    2016-01-01

    Purpose To evaluate the age-dependent morphologic alterations in the outer retina and choroid at the macula using swept-source optical coherence tomography (OCT). Methods Thirty eyes (30 normal subjects; average age, 49 years) were examined; five (age range, third-eighth decades of life) had refractive errors of ±2 diopters or less and no fundus abnormalities. An Early Treatment Diabetic Retinopathy Study (ETDRS) map of the outer retinal and choroidal thickness was constructed using swept-source OCT. The outer retinal and choroidal segmentation lines were drawn automatically, partially manually, within 6 millimeters of the macula. Results The mean outer retinal and choroidal thicknesses in the 6-millimeter-diameter circle were 145±13 and 236±68 microns, respectively. The choroidal thickness and age were negatively (r = -0.66, P<0.01) correlated; the outer retinal thickness and age were not correlated (r = -0.16, P = 0.39). The outer retinal and choroidal thicknesses in the ETDRS map were not correlated (r = -0.13, P = 0.49) within 1 millimeter but correlated (r = 0.32, P<0.01) within 6 millimeters. Conclusions The choroid thins with aging. The outer retina remains stable. Outer retina and choroid are correlated in the entire macula except for the center. ETDRS map can be useful for evaluation of the morphologic relationship between the outer retina and choroid. PMID:27467879

  17. Structural Changes of Inner and Outer Choroid in Central Serous Chorioretinopathy Determined by Optical Coherence Tomography

    PubMed Central

    Sonoda, Shozo; Sakamoto, Taiji; Kuroiwa, Nobuhiro; Arimura, Noboru; Kawano, Hiroki; Yoshihara, Naoya; Yamashita, Takehiro; Uchino, Eisuke; Kinoshita, Takamasa; Mitamura, Yoshinori

    2016-01-01

    Purpose To determine the structural changes of the choroid in eyes with central serous chorioretinopathy (CSC) by enhanced depth imaging optical coherence tomography (EDI-OCT). Methods A retrospective comparative study was performed at two academic institutions. Forty eyes with CSC, their fellow eyes, and 40 eyes of age-matched controls were studied. Subfoveal cross sectional EDI-OCT images were recorded, and the hypo reflective and hyperreflective areas of the inner and outer choroid in the EDI-OCT images were separately measured. The images were analyzed by a binarization method to determine the sizes of the hyporeflective and hyperreflective areas. Results In the inner choroid, the hyperreflective area was significantly larger in the CSC eyes (35,640±10,229 μm2) than the fellow eyes (22,908±8,522 μm2) and the control eyes (20,630±8,128 μm2; P<0.01 vs control for both, Wilcoxon signed-rank test). In the outer choroid, the hyporeflective area was significantly larger in the CSC eyes (446,549±121,214 μm2) than the control eyes (235,680±97,352 μm2, P<0.01). The average ratio of the hyporeflective area to the total choroidal area was smaller in the CSC eyes (67.0%) than the fellow eyes (76.5%) and the control eyes (76.7%) in the inner choroid (P<0.01, both). However, the ratio was larger in the CSC eyes (75.2%) and fellow eyes (71.7%) than in the control eyes (64.7%) in the outer choroid (P<0.01, both). Conclusions The larger hyperreflective area in the inner choroid is related to the inflammation and edema of the stroma of the choroid in the acute stage of CSC. The larger hyporeflective areas in the outer choroid is due to a dilatation of the vascular lumens of the larger blood vessels. These are the essential characteristics of eyes with CSC regardless of the onset. PMID:27305042

  18. Imaging polarimetry in patients with neovascular age-related macular degeneration.

    PubMed

    Elsner, Ann E; Weber, Anke; Cheney, Michael C; VanNasdale, Dean A; Miura, Masahiro

    2007-05-01

    Imaging polarimetry was used to examine different components of neovascular membranes in age-related macular degeneration. Retinal images were acquired with a scanning laser polarimeter. An innovative pseudocolor scale, based on cardinal directions of color, displayed two types of image information: relative phases and magnitudes of birefringence. Membranes had relative phase changes that did not correspond to anatomical structures in reflectance images. Further, membrane borders in depolarized light images had significantly higher contrasts than those in reflectance images. The retinal birefringence in neovascular membranes indicates optical activity consistent with molecular changes rather than merely geometrical changes. PMID:17429494

  19. Iterated snowdrift game among mobile agents with myopic expected-reward based decision rule: Numerical and analytical research

    NASA Astrophysics Data System (ADS)

    Zhong, Shiquan; Jia, Ning; Ma, Shoufeng

    2014-11-01

    The iterated spatial game among the mobile population is an interesting problem in the fields of biological, social and economic sciences. Inspired by some recent works, this paper concentrates on the iterated snowdrift game among movable and myopic agents. Two different decision-making schemes, namely the utility-maximum rule and the Fermi rule, are applied and examined. In the former case, cooperation is found to be enhanced by moving velocity with an upper bound. The analytical results of the model are deduced at two extreme cases when agents cannot move or move quickly. In the latter case, the influences of velocity and temptation-to-defect are much more complicated. These results allow a deeper insight of the related model as well as the emergence of cooperation.

  20. A Large-Scale Computational Analysis of Corneal Structural Response and Ectasia Risk in Myopic Laser Refractive Surgery

    PubMed Central

    Dupps, William Joseph; Seven, Ibrahim

    2016-01-01

    Purpose: To investigate biomechanical strain as a structural susceptibility metric for corneal ectasia in a large-scale computational trial. Methods: A finite element modeling study was performed using retrospective Scheimpflug tomography data from 40 eyes of 40 patients. LASIK and PRK were simulated with varied myopic ablation profiles and flap thickness parameters across eyes from LASIK candidates, patients disqualified for LASIK, subjects with atypical topography, and keratoconus subjects in 280 simulations. Finite element analysis output was then interrogated to extract several risk and outcome variables. We tested the hypothesis that strain is greater in known at-risk eyes than in normal eyes, evaluated the ability of a candidate strain variable to differentiate eyes that were empirically disqualified as LASIK candidates, and compared the performance of common risk variables as predictors of this novel susceptibility marker across multiple virtual subjects and surgeries. Results: A candidate susceptibility metric that expressed mean strains across the anterior residual stromal bed was significantly higher in eyes with confirmed ectatic predisposition in preoperative and all postoperative cases (P≤.003). The strain metric was effective at differentiating normal and at-risk eyes (area under receiver operating characteristic curve ≥ 0.83, P≤.002), was highly correlated to thickness-based risk metrics (as high as R2 = 95%, P<.001 for the percent of stromal tissue altered (PSTA)), and predicted large portions of the variance in predicted refractive response to surgery (R2 = 57%, P<.001). Conclusions: This study represents the first large-scale 3-dimensional structural analysis of ectasia risk and provides a novel biomechanical construct for expressing structural risk in refractive surgery. Mechanical strain is an effective marker of known ectasia risk and correlates to predicted refractive error after myopic photoablative surgery.

  1. Peripapillary choroidal thickness in glaucoma measured with optical coherence tomography.

    PubMed

    Ehrlich, Joshua R; Peterson, Jeffrey; Parlitsis, George; Kay, Kristine Y; Kiss, Szilárd; Radcliffe, Nathan M

    2011-03-01

    As choroidal changes have been suggested in glaucoma, we examined peripapillary choroidal thickness (CT) in patients with and without primary open-angle glaucoma (POAG) using spectral-domain optical coherence tomography (SD-OCT). We collected measurements retrospectively on 70 eyes of 70 patients consecutively undergoing SD-OCT. POAG (n = 31) and suspect eyes (n = 39) had two reliable and repeatable Humphrey 24-2 visual fields with glaucoma hemifield test outside or within normal limits, respectively. A 360-degree peripapillary scan was performed using the standard protocol for retinal nerve fiber layer (RNFL) assessment. Using provided software, two independent masked investigators manually segmented CT as the area of visible choroidal vasculature. Agreement between investigators was determined using Lin's concordance correlation coefficient (CCC). A single masked observer determined clock hours of parapapillary atrophy (PPA) and the presence of ßPPA for each optic nerve quadrant. Correlation between RNFL and CT was assessed; two-sample t-tests were used to determine differences in RNFL and CT between POAG and suspect eyes; and linear regression was used to model changes in RNFL and CT. We found that independent measurements of CT by two observers were highly correlated (Lin's CCC for global CT; ρ(c) = 0.93, p < 0.001). RNFL and CT measurements were not significantly correlated for any peripapillary location (|r| ≤ 0.15, p ≥ 0.22). Global CT (ß = -1.94, 95% confidence interval [CI] -2.76, -1.13) but not RNFL thickness (ß = -0.18, 95% CI -0.58, 0.22) decreased significantly with age. Compared to suspect eyes, eyes with POAG had significantly thinner RNFL measurements at all locations (p ≤ 0.005) but CT measurements did not differ between groups for any location (p ≥ 0.13). Adjusting for glaucoma status and age, total (ß = 3.15 95% CI -0.24, 6.53) and ß clock hours of PPA (ß = 1.33, 95% CI -1.72, 4.38) were not significantly

  2. Advances of optical coherence tomography in myopia and pathologic myopia.

    PubMed

    Ng, D S C; Cheung, C Y L; Luk, F O; Mohamed, S; Brelen, M E; Yam, J C S; Tsang, C W; Lai, T Y Y

    2016-07-01

    The natural course of high-axial myopia is variable and the development of pathologic myopia is not fully understood. Advancements in optical coherence tomography (OCT) technology have revealed peculiar intraocular structures in highly myopic eyes and unprecedented pathologies that cause visual impairment. New OCT findings include posterior precortical vitreous pocket and precursor stages of posterior vitreous detachment; peripapillary intrachoroidal cavitation; morphological patterns of scleral inner curvature and dome-shaped macula. Swept source OCT is capable of imaging deeper layers in the posterior pole for investigation of optic nerve pits, stretched and thinned lamina cribrosa, elongated dural attachment at posterior scleral canal, and enlargement of retrobulbar subarachnoid spaces. This has therefore enabled further evaluation of various visual field defects in high myopia and the pathogenesis of glaucomatous optic neuropathy. OCT has many potential clinical uses in managing visual impairing conditions in pathologic myopia. Understanding how retinal nerve fibers are redistributed in axial elongation will allow the development of auto-segmentation software for diagnosis and monitoring progression of glaucoma. OCT is indispensable in the diagnosis of various conditions associated with myopic traction maculopathy and monitoring of post-surgical outcomes. In addition, OCT is commonly used in the multimodal imaging assessment of myopic choroidal neovascularization. Biometry and topography of the retinal layers and choroid will soon be validated for the classification of myopic maculopathy for utilization in epidemiological studies as well as clinical trials. PMID:27055674

  3. In Vivo Choroidal Vascular Lesions in Diabetes on Swept-Source Optical Coherence Tomography.

    PubMed

    Murakami, Tomoaki; Uji, Akihito; Suzuma, Kiyoshi; Dodo, Yoko; Yoshitake, Shin; Ghashut, Rima; Yoza, Rina; Fujimoto, Masahiro; Yoshimura, Nagahisa

    2016-01-01

    Diabetes induces microvascular diseases including diabetic retinopathy and choroidopathy which reciprocally promote the pathogenesis, although optical coherence tomography images of diabetic choroidopathy remains to be documented. Here we evaluated the qualitative characteristics of choroidal vascular lesions in patients with diabetes and their association with diabetic retinopathy on swept-source optical coherence tomography (SS-OCT) images. We retrospectively reviewed 110 consecutive eyes of 110 patients with diabetes and 35 eyes of 35 healthy subjects for whom SS-OCT images (6x6-mm scans centered on the fovea) of sufficient quality were acquired. The curve of chorioretinal sections was flattened using Bruch's membrane as a reference surface, followed by generation of en-face images. We characterized choroidal vascular lesions and evaluated their association with the logarithm of the minimum angle of resolution visual acuity (logMAR VA), retinal and choroidal thicknesses, and diabetic retinopathy severity. En-face SS-OCT images showed unvisualized vessels in Sattler's layer in 33 eyes (30.0%). Focal narrowing was seen in choroidal vessels in Haller's layer in 56 eyes (50.9%). The choroidal vessels ended in the superficial or middle portion of Haller's layer, referred to as vascular stumps, in 20 eyes (18.2%). Diabetic eyes had these findings more frequently than nondiabetic eyes. The subfoveal choroid was thicker in eyes with focal vascular narrowing and vascular stumps than in eyes without such lesions. Vascular stumps in Haller's layer were significantly related to diabetic retinopathy severity, logMAR VA, and central retinal and choroidal thicknesses. These novel findings on SS-OCT images would promote the better understanding of complicated pathogenesis in diabetic retinopathy and choroidopathy. PMID:27479070

  4. In Vivo Choroidal Vascular Lesions in Diabetes on Swept-Source Optical Coherence Tomography

    PubMed Central

    Murakami, Tomoaki; Uji, Akihito; Suzuma, Kiyoshi; Dodo, Yoko; Yoshitake, Shin; Ghashut, Rima; Yoza, Rina; Fujimoto, Masahiro; Yoshimura, Nagahisa

    2016-01-01

    Diabetes induces microvascular diseases including diabetic retinopathy and choroidopathy which reciprocally promote the pathogenesis, although optical coherence tomography images of diabetic choroidopathy remains to be documented. Here we evaluated the qualitative characteristics of choroidal vascular lesions in patients with diabetes and their association with diabetic retinopathy on swept-source optical coherence tomography (SS-OCT) images. We retrospectively reviewed 110 consecutive eyes of 110 patients with diabetes and 35 eyes of 35 healthy subjects for whom SS-OCT images (6x6-mm scans centered on the fovea) of sufficient quality were acquired. The curve of chorioretinal sections was flattened using Bruch’s membrane as a reference surface, followed by generation of en-face images. We characterized choroidal vascular lesions and evaluated their association with the logarithm of the minimum angle of resolution visual acuity (logMAR VA), retinal and choroidal thicknesses, and diabetic retinopathy severity. En-face SS-OCT images showed unvisualized vessels in Sattler’s layer in 33 eyes (30.0%). Focal narrowing was seen in choroidal vessels in Haller’s layer in 56 eyes (50.9%). The choroidal vessels ended in the superficial or middle portion of Haller’s layer, referred to as vascular stumps, in 20 eyes (18.2%). Diabetic eyes had these findings more frequently than nondiabetic eyes. The subfoveal choroid was thicker in eyes with focal vascular narrowing and vascular stumps than in eyes without such lesions. Vascular stumps in Haller’s layer were significantly related to diabetic retinopathy severity, logMAR VA, and central retinal and choroidal thicknesses. These novel findings on SS-OCT images would promote the better understanding of complicated pathogenesis in diabetic retinopathy and choroidopathy. PMID:27479070

  5. Celastrol nanoparticles inhibit corneal neovascularization induced by suturing in rats

    PubMed Central

    Li, Zhanrong; Yao, Lin; Li, Jingguo; Zhang, Wenxin; Wu, Xianghua; Liu, Yi; Lin, Miaoli; Su, Wenru; Li, Yongping; Liang, Dan

    2012-01-01

    Purpose Celastrol, a traditional Chinese medicine, is widely used in anti-inflammation and anti-angiogenesis research. However, the poor water solubility of celastrol restricts its further application. This paper aims to study the effect of celastrol nanoparticles (CNPs) on corneal neovascularization (CNV) and determine the possible mechanism. Methods To improve the hydrophilicity of celastrol, celastrol-loaded poly(ethylene glycol)-block-poly(ɛ-caprolactone) nanopolymeric micelles were developed. The characterization of CNPs was measured by dynamic light scattering and transmission electron microscopy analysis. Celastrol loading content and release were assessed by ultraviolet-visible analysis and high performance liquid chromatography, respectively. In vitro, human umbilical vein endothelial cell proliferation and capillary-like tube formation were assayed. In vivo, suture-induced CNV was chosen to evaluate the effect of CNPs on CNV in rats. Immunohistochemistry for CD68 assessed the macrophage infiltration of the cornea on day 6 after surgery. Real-time quantitative reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were used to evaluate the messenger ribonucleic acid and protein levels, respectively, of vascular endothelial growth factor, matrix metalloproteinase 9, and monocyte chemoattractant protein 1 in the cornea. Results The mean diameter of CNPs with spherical shape was 48 nm. The celastrol loading content was 7.36%. The release behavior of CNPs in buffered solution (pH 7.4) showed a typical two-phase release profile. CNPs inhibited the proliferation of human umbilical vein endothelial cells in a dose-independent manner and suppressed the capillary structure formation. After treatment with CNPs, the length and area of CNV reduced from 1.16 ± 0.18 mm to 0.49 ± 0.12 mm and from 7.71 ± 0.94 mm2 to 2.29 ± 0.61 mm2, respectively. Macrophage infiltration decreased significantly in the CNP-treated corneas. CNPs reduced

  6. [Preliminary results of treatment with aflibercept].

    PubMed

    Blăjan, Codruta; Nicula, D; Rusu, Ioana

    2014-01-01

    The paper presents the first results concerning the Aflibercept (Eylea) treatment, the last antiVEGF approved for treatment of the age related macular degeneration (AMD), neovascular form and for macular edema due to the central retinal vein occlusion. The treatment was applied to patients presenting AMD, ME and other diseases: myopic and idiopatic choroidal neovascularisation, central serous choroidopathy (CSC) or diabetic macular edema (DME). The results were good: improvement of the visual acuity, resolution of the intraretinal fluids and macular edema. Although we did not notice major side-effects, resistance or tachyphylaxis, we noticed some recurrences.

  7. Application of Intravitreal Bevacizumab for Circumscribed Choroidal Hemangioma

    PubMed Central

    Sagong, Min; Lee, Junyeop

    2009-01-01

    We report 3 cases of circumscribed choroidal hemangioma (CCH) effectively managed with intravitreal bevacizumab. One patient (case 1) who had recurrent CCH (1.6 mm in thickness) with prior laser photocoagulation was treated with intravitreal bevacizumab alone. Two patients (case 2 and 3) who had CCH (2.4 mm and 2.2 mm in thickness, respectively) with recent visual impairment were treated with bevacizumab followed by photodynamic therapy (PDT). Ophthalmic evaluations included visual acuity, ophthalmoscopic examination, fluorescein angiography, ultrasonography, and optical coherence tomography. Patients were followed up for 6-9 months. After therapy, all patients showed improved visual acuity due to complete resorption of subretinal fluid and macular edema. Ultrasonography demonstrated a reduction of the thickness of CCH in case 1 and complete regression of the lesions in case 2 and 3. No patient showed tumor recurrence. Intravitreal bevacizumab, alone or in combination therapy with PDT, may be a useful alternative for the treatment of symptomatic CCH with subretinal fluid. PMID:19568366

  8. An evaluation of cognitive disorders after anterior choroidal artery infarction.

    PubMed

    Rousseaux, Marc; Cabaret, Maryline; Serafi, Rawabi; Kozlowski, Odile

    2008-09-01

    Anterior choroidal artery infarction (AChAI) can be the source of aphasia and spatial neglect, but we have no idea of the other possible cognitive disorders. Here, we investigated these disorders in a relatively large cohort of AChAI patients. Twenty patients with relatively recent infarction (left side: 13; mean delay = 47.4 days; 10 men; mean age = 59.6; mean education level, EL = 10.3) were included. We assessed nonspatial attention (alertness, Go Nogo, divided attention and visual vigilance from the computerized test TEA), spatial attention (bell test), language (BDAE) orientation (time, place), short-term memory (forward and backward digit spans, spatial span), executive functioning (WCST, TMT A and B, categorial evocation), delayed memory (Buschke verbal test, Rey figure test), and retrograde memory (questionnaire on famous events). The performance level was compared with that of 20 control subjects matched in age and EL. AChAI patients were impaired in several tests of attention (slowness, increase in omission and error rate), executive functioning (TMT B; categorical evocation) and delayed memory. Conversely, we found preservation of spatial attention, language, orientation, short-term memory, WCST, and retrograde memory. In conclusion, at the secondary phase post-stroke, these patients can present with moderate disorders of attention, memory and executive functioning, which are clearly less severe than what is usually observed following thalamic or cortical lesions. PMID:18575919

  9. Treatment Outcomes in Patients with Polypoidal Choroidal Vasculopathy

    PubMed Central

    Sayman Muslubaş, Işıl; Hocaoğlu, Mümin; Arf, Serra; Özdemir, Hakan; Karaçorlu, Murat

    2016-01-01

    Objectives: To report outcomes of photodynamic therapy (PDT) and combined therapy with PDT and intravitreal bevacizumab (IVB) in patients with polypoidal choroidal vasculopathy (PCV). Materials and Methods: Thirty-four eyes of 31 patients with subfoveal PCV were evaluated. Nine eyes were treated with PDT and 25 eyes treated with combined therapy of PDT and IVB. All eyes had a follow-up period of at least 12 months. In this retrospective study the demographic features, best corrected visual acuity, fundus color photography, optical coherence tomography, fluorescein angiography and indocyanine green angiography of the 34 eyes were evaluated. Results: Visual acuity improved but did not change significantly in the patients treated with PDT and combined PDT+IVB therapy (p=0.149; p=0.087). Although the mean central foveal thickness decreased in both groups, there was no statistically significant difference between groups (p=0.98). The polypoidal lesions regressed in 6 (66.7%) of 9 eyes in the PDT monotherapy group and 16 (64%) of 25 eyes in the PDT+IVB combined therapy group. Conclusion: Both PDT and a combined therapy of PDT and IVB yielded successful outcomes in patients with PCV. PMID:27800252

  10. Role of PTFE Patch Saphenoplasty in Reducing Neovascularization and Recurrence in Varicose Veins.

    PubMed

    Vashist, M G; Singhal, Nitin; Verma, Manish; Sen, Jyotsana

    2015-12-01

    Varicose veins have a high recurrence rate following surgery. Besides poor surgical technique, majority of these recurrences are attributable to neovascularization after both primary and repeat surgery. Authors have studied the effectiveness of a polytetrafluoroethylene (PTFE) patch interposition between the ligated vein stump and the overlying soft tissue at saphenofemoral junction in decreasing recurrence of varicose veins after initial surgery. Study was conducted on 50 patients of varicose veins with saphenofemoral junction incompetence. Patients were randomly divided into two groups, group A and group B alternately. In group A, standard surgical procedure was done followed by PTFE patch application. In group B, same surgical procedure was applied as in group A, with the exception of PTFE patch application. Patients in both groups were given similar postoperative care. A full venous duplex ultrasound assessment was performed in all the patients postoperatively. Neovascularization was observed in five patients (20 %) of group B, while it was not seen in any of the patients in group A at 1-year follow-up. This difference in neovascularization across the two groups was found to be statistically significant with a p value of 0.0251. Hence, authors concluded that patch saphenoplasty helps in reducing recurrence in varicose veins by decreasing neovascularization at saphenofemoral junction.

  11. Differences in spectral absorption properties between active neovascular macular degeneration and mild age related maculopathy.

    PubMed

    Balaskas, Konstantinos; Nourrit, Vincent; Dinsdale, Michelle; Henson, David B; Aslam, Tariq

    2013-05-01

    This study examines the differences in spectral absorption properties between the maculae of patients with active neovascular macular degeneration and those with early age related maculopathy (ARM). Patients attending for management of neovascular age related macular degeneration (AMD) underwent multispectral imaging with a system comprising of a modified digital fundus camera coupled with a 250-W tungsten-halogen lamp and a liquid crystal fast-tuneable filter. Images were obtained at 8 wavelengths between 496 and 700 nm. Aligned images were used to generate a DLA (differential light absorption, a measure of spectral absorption properties) map of the macular area. DLA maps were generated for both eyes of 10 sequential patients attending for anti-vascular endothelial growth factor injections. Each of these patients had active leaking neovascular AMD in one eye and early ARM or milder disease in the fellow eye. Eyes with neovascular AMD demonstrated lower average levels of DLA compared with their fellow eyes with early ARM (p=0.037, t test). The significant difference in DLA demonstrates the potential of multispectral imaging for differentiating the two pathologies non-invasively. PMID:23137662

  12. Inhibition of corneal neovascularization by recombinant adenovirus-mediated sFlk-1 expression

    SciTech Connect

    Yu Hui; Wu Jihong; Li Huiming; Wang Zhanli; Chen Xiafang; Tian Yuhua; Yi Miaoying; Ji Xunda; Ma Jialie; Huang Qian

    2007-10-05

    The interaction of vascular endothelial growth factor (VEGF) and its receptors (Flt-1, Flk-1/KDR) is correlated with neovascularization in the eyes. Therefore, blocking the binding of VEGF and the corresponding receptor has become critical for inhibiting corneal neovascularization. In this study, we have expressed the cDNA for sFlk-1 under the control of cytomegalovirus immediate-early promoter (CMV) from an E1/partial E3 deleted replication defective recombinant adenovirus, and Ad.sflk-1 expression was determined by Western blotting. We have shown that conditioned media from Ad.sflk-1-infected ARPE-19 cells significantly reduced VEGF-induced human umbilical vein endothelial cells (HUVEC) and murine endothelial cells (SVEC) proliferation in vitro compared with the control vector. In vivo, adenoviral vectors expressing green fluorescent protein alone (Ad.GFP) were utilized to monitor gene transfer to the cornea. Moreover, in the models of corneal neovascularization, the injection of Ad.sflk-1 (10{sup 8} PFU) into the anterior chamber could significantly inhibit angiogenic changes compared with Ad.null-injected and vehicle-injected models. Immunohistochemical analysis showed that corneal endothelial cells and corneal stroma of cauterized rat eyes were efficiently transduced and expressed sFlk-1. These results not only support that adenoviral vectors are capable of high-level transgene expression but also demonstrate that Ad.sflk-1 gene therapy might be a feasible approach for inhibiting the development of corneal neovascularization.

  13. [Prenatal screening for cysts of choroid plexus. Evolution and interpretation of 30 cases].

    PubMed

    Rebaud, A; Chardon, C; Rebaud, M F; Berland, M

    1992-01-01

    The authors report thirty cases in which they diagnosed a cyst of the choroid plexus antenatally between the 18th and the 36th week of amenorrhoea (mean 21 weeks). Choroid plexus cysts show up in some pictures as round or oval cysts clearly visible in the region of the choroid plexus. They appear in the lateral cerebral ventricles. They frequently occur between the 15th and 25th week of amenorrhoea (0.6 to 2.5% of pregnancies), unilaterally or bilaterally (46%) either on the right of left side and varying in size (3 to 20 mm). These characteristics do not influence the way they evolve. If a single choroid plexus cyst is found a control ultrasound should be carried out four weeks later. 96% of them have disappeared by the end of the second trimester; but if they do persist in the third trimester (4%) they are not necessarily pathological. On the other hand if a choroid plexus cyst is associated with some other morphological biometric abnormality antenatal chromosome testing should be carried out because trisomy 18 is more common in this situation (4.8%) than in the general population.

  14. 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.

  15. Fundus Autofluorescence, Optical Coherence Tomography, and Electroretinogram Findings in Choroidal Sclerosis

    PubMed Central

    Hwang, John C.; Kim, David Y.; Chou, Chai Lin; Tsang, Stephen H.

    2010-01-01

    Purpose To describe fundus autofluorescence, optical coherence tomography, and electroretinogram findings in choroidal sclerosis. Methods Retrospective case series. Eight eyes of four patients with choroidal sclerosis were evaluated with fundus autofluorescence, optical coherence tomography, and electroretinogram testing. Results In all eight eyes, fundus autofluorescence imaging revealed hypofluorescent placoid lesions corresponding to areas of chorioretinal atrophy seen on stereo biomicroscopy. Prominent hyperfluorescent linear markings underlying regions of atrophic disease were observed in all eyes, likely representative of normal choroidal vessel autofluorescence. In two eyes, fundus autofluorescence revealed punctate hypofluorescent lesions in the fovea that were not visualized on biomicroscopy. In one eye, fundus autofluorescence identified a central island of preserved retinal pigment epithelium that was not appreciated on ophthalmoscopic examination. Optical coherence imaging was significant for loss of choroidal fine tubular structures, retinal pigment epithelium, and outer nuclear layer in regions of chorioretinal atrophy. Full-field electroretinogram testing demonstrated generalized rod-cone dysfunction in all patients with a lower b- to a- wave ratio in two patients. Conclusion Fundus autofluorescence and optical coherence tomography are noninvasive diagnostic adjunct that can aid in the diagnosis of choroidal sclerosis. Fundus autofluorescence may be a more sensitive marker of disease extent and progression than clinical exam alone. Electroretinogram testing can result in an electronegative maximal response. PMID:20224472

  16. Progression of Cutaneous Vitiligo in a Patient with Large Posterior Choroidal Melanoma: A Case Report

    PubMed Central

    Ding, Angela; Elizalde, Javier; Barraquer, Rafael Ignacio

    2015-01-01

    Background/Aims The aim of our study was to report a case of progression of cutaneous vitiligo after large posterior choroidal melanoma diagnosis. Methods The clinical history, fundus findings and histopathological features suggest the diagnosis of cutaneous vitiligous progression after a diagnosis of large posterior choroidal melanoma. Results A 30-year-old female, with a personal history of cutaneous vitiligo for 12 years, was diagnosed with choroidal melanoma 18 months previously. The cutaneous vitiligo had progressed over her back, body and arms during the preceding 3 years. She refused treatment because she was in her 28th week of pregnancy. When she came to our clinic her visual symptoms had worsened, and the fundus examination showed a melanocytic choroidal mass. After confirming that there was no extraocular extension, she was treated with enucleation. A histopathological study confirmed the choroidal melanoma diagnosis. Conclusion The association between the progression of vitiligo and the diagnosis of uveal melanoma could be considered a good prognostic factor, as has been described in cases of cutaneous melanoma. A longer follow-up of these patients will allow us to confirm this association. PMID:27354983

  17. Decreased FOXJ1 expression and its ciliogenesis programme in aggressive ependymoma and choroid plexus tumours.

    PubMed

    Abedalthagafi, Malak S; Wu, Michael P; Merrill, Parker H; Du, Ziming; Woo, Terri; Sheu, Shu-Hsien; Hurwitz, Shelley; Ligon, Keith L; Santagata, Sandro

    2016-03-01

    Well-differentiated human cancers share transcriptional programmes with the normal tissue counterparts from which they arise. These programmes broadly influence cell behaviour and function and are integral modulators of malignancy. Here, we show that the master regulator of motile ciliogenesis, FOXJ1, is highly expressed in cells along the ventricular surface of the human brain. Strong expression is present in cells of the ependyma and the choroid plexus as well as in a subset of cells residing in the subventricular zone. Expression of FOXJ1 and its transcriptional programme is maintained in many well-differentiated human tumours that arise along the ventricle, including low-grade ependymal tumours and choroid plexus papillomas. Anaplastic ependymomas as well as choroid plexus carcinomas show decreased FOXJ1 expression and its associated ciliogenesis programme genes. In ependymomas and choroid plexus tumours, reduced expression of FOXJ1 and its ciliogenesis programme are markers of poor outcome and are therefore useful biomarkers for assessing these tumours. Transitions in ciliogenesis define distinct differentiation states in ependymal and choroid plexus tumours with important implications for patient care. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:26690880

  18. Decreased prevalence of asymptomatic choroidal metastasis in disseminated breast and lung cancer: argument against screening

    PubMed Central

    Barak, A; Neudorfer, M; Heilweil, G; Merimsky, O; Lowenstein, A; Inbar, M; Yaal‐Hahoshen, N

    2007-01-01

    Aim To determine the frequency of visually asymptomatic choroidal metastases in patients with disseminated breast and lung carcinomas in order to establish optimal patient management policies. Methods All patients with confirmed metastatic disease treated in our institution between January 2002 and December 2003 were invited to undergo a funduscopic examination and a B‐scan ultrasound evaluation. Results Of the 169 study participants, 77 had breast cancer (64 with metastases in one organ and 13 with multiple‐organ involvement) and 92 had lung cancer (85 with metastases in one organ and 7 with multiple‐organ involvement). No patient with metastatic breast cancer and two patients with metastatic lung disease (each with multiple‐organ involvement) were found to have choroidal metastases. The choroidal metastases were detected by both the funduscopic and ultrasound examinations. Conclusions The 2.17% incidence of choroidal metastasis in disseminated lung cancer and the 0% incidence in disseminated breast cancer speaks against the practicality of screening for early detection of choroidal metastasis among these patients, even though it would lead to early implementation of appropriate, often vision saving, therapeutic management. Its low incidence probably testifies to progress achieved by enhanced systemic oncological treatment policies that have been introduced into routine patient management over the past few years. PMID:16943227

  19. 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

  20. Neovascularization in the pulmonary endothelium is regulated by the endosome: Rab4-mediated trafficking and p18-dependent signaling.

    PubMed

    Chichger, Havovi; Braza, Julie; Duong, Huetran; Stark, Myranda; Harrington, Elizabeth O

    2015-10-01

    Neovascularization, the formation of new blood vessels, requires multiple processes including vascular leak, migration, and adhesion. Endosomal proteins, such as Rabs, regulate trafficking of key signaling proteins involved in neovascularization. The novel endosome protein, p18, enhances vascular endothelial (VE)-cadherin recycling from early endosome to cell junction to improve pulmonary endothelial barrier function. Since endothelial barrier integrity is vital in neovascularization, we sought to elucidate the role for endosome proteins p18 and Rab4, Rab7, and Rab9 in the process of vessel formation within the pulmonary vasculature. Overexpression of wild-type p18 (p18(wt)), but not the nonendosomal-binding mutant (p18(N39)), significantly increased lung microvascular endothelial cell migration, adhesion, and both in vitro and in vivo tube formation. Chemical inhibition of mTOR or p38 attenuated the proneovascularization role of p18(wt). Similar to the effect of p18(wt), overexpression of prorecycling wild-type (Rab4(WT)) and endosome-anchored (Rab4(Q67L)) Rab4 enhanced neovascularization processes, whereas molecular inhibition of Rab4, by using the nonendosomal-binding mutant (Rab4(S22N)) attenuated VEGF-induced neovascularization. Unlike p18, Rab4-induced neovascularization was independent of mTOR or p38 inhibition but was dependent on p18 expression. This study shows for the first time that neovascularization within the pulmonary vasculature is dependent on the prorecycling endocytic proteins Rab4 and p18.

  1. Exacerbated corneal inflammation and neovascularization in the HO-2 null mice is ameliorated by biliverdin

    PubMed Central

    Bellner, Lars; Vitto, Marco; Patil, Kiran A.; Dunn, Michael W.; Regan, Raymond; Laniado-Schwartzman, Michal

    2008-01-01

    Heme oxygenase (HO-1 and HO-2) represents an intrinsic cytoprotective and anti-inflammatory system based on its ability to modulate leukocyte migration and to inhibit expression of inflammatory cytokines and proteins. HO-2 deletion leads to unresolved corneal inflammation and chronic inflammatory complications including ulceration, perforation and neovascularization. We examined the consequences of HO-2 deletion on hemangiogenesis and lymphangiogenesis in the model of suture-induced inflammatory neovascularization. A 8.0 silk suture was placed at the corneal apex of wild type and HO-2 null mice. Neovascularization was assessed by vital microscopy and quantified by image analysis. Hemangiogenesis and lymphangiogenesis were determined by immunofluorescence staining using anti-CD31 and anti-LYVE-1 antibodies, respectively. Inflammation was quantified by histology and myeloperoxidase activity. The levels of HO-1 expression and inflammatory cytokines were determined by real time PCR and ELISA, respectively. Corneal sutures produced a consistent inflammatory response and a time-dependent neovascularization. The response in HO-2 null mice was associated with a greater increase compared to the wild type in the number of leukocytes (827600±129000 vs. 294500±57510; p<0.05), neovessels measured by vital microscopy (21.91±1.05 vs. 12.77±1.55 mm; p<0.001) 4 days after suture placement. Hemangiogenesis but not lymphangiogenesis was more pronounced in HO-2 null mice compared to wild type mice. Induction of HO-1 in sutured corneas was greatly attenuated in HO-2 null corneas and treatment with biliverdin diminished the exaggerated inflammatory and neovascular response in HO-2 null mice. The demonstration that the inflammatory responses, including expression of proinflammatory proteins, inflammatory cell influx and hemangiogenesis are exaggerated in HO-2 knockout mice strongly supports the notion that the HO system is critical for controlling the inflammatory and neovascular

  2. Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease.

    PubMed

    Kur, Joanna; Newman, Eric A; Chan-Ling, Tailoi

    2012-09-01

    We review the cellular and physiological mechanisms responsible for the regulation of blood flow in the retina and choroid in health and disease. Due to the intrinsic light sensitivity of the retina and the direct visual accessibility of fundus blood vessels, the eye offers unique opportunities for the non-invasive investigation of mechanisms of blood flow regulation. The ability of the retinal vasculature to regulate its blood flow is contrasted with the far more restricted ability of the choroidal circulation to regulate its blood flow by virtue of the absence of glial cells, the markedly reduced pericyte ensheathment of the choroidal vasculature, and the lack of intermediate filaments in choroidal pericytes. We review the cellular and molecular components of the neurovascular unit in the retina and choroid, techniques for monitoring retinal and choroidal blood flow, responses of the retinal and choroidal circulation to light stimulation, the role of capillaries, astrocytes and pericytes in regulating blood flow, putative signaling mechanisms mediating neurovascular coupling in the retina, and changes that occur in the retinal and choroidal circulation during diabetic retinopathy, age-related macular degeneration, glaucoma, and Alzheimer's disease. We close by discussing issues that remain to be explored.

  3. Potential anti-angiogenic role of Slit2 in corneal neovascularization.

    PubMed

    Han, Xi; Zhang, Ming-Chang

    2010-06-01

    Slits are large secreted proteins critical for axon guidance and neuronal precursor cell migration in nervous system. Evidence suggests that classical neuronal guidance cues also regulate vascular development. Our objective was to investigate whether neuronal guidance cue Slit2 and Roundabout (Robo) receptors are involved in corneal neovascularization (NV). Corneal NV model in rats was induced by implantation of agarose-coated gelfoam pellets containing basic fibroblast growth factor (bFGF) into corneal stroma. Differential expression of Slit2 and Robo1-4 between normal and neovascularized cornea was detected by real-time RT-PCR and visualized by immunohistochemistry and in situ hybridization. Primary human umbilical vein endothelial cells (HUVECs) were harvested and their expression of Robo1-4 was detected by RT-PCR. Recombinant human Slit2 protein was prepared and the effect of it on the migration of vascular endothelial cells was examined using cell migration assay. Agarose-coated gelfoam pellets were able to induce well-localized and reproducible corneal NV model. A significant down-regulation of Slit2 and a strong up-regulation of Robo1 and Robo4 were seen in neovascularized cornea when compared with normal cornea (P < 0.05). Slit2, Robo1 and Robo4 were throughout the epithelium in normal cornea and markedly weak or absent in epithelium in neovascularized cornea, with Robo1 and Robo4 being prominent in vascular endothelial cells invading the stroma. Primary HUVECs were confirmed to express both Robo1 and Robo4 receptors and their migration was inhibited by Slit2 (P < 0.05). This is the first study to assess the association between Slit2 and corneal NV. Our findings suggest that the interaction of Slit2 with Robo1 and Robo4 receptors plays an essential role in inhibiting pathological neovascular processes of the cornea and may represent a new therapeutic target for corneal NV.

  4. Ocular neovascularization in eyes with a central retinal artery occlusion or a branch retinal artery occlusion

    PubMed Central

    Mason, John O; Patel, Shyam A; Feist, Richard M; Albert, Michael A; Huisingh, Carrie; McGwin, Gerald; Thomley, Martin L

    2015-01-01

    Purpose To investigate the ocular neovascularization (ONV) rate in eyes with a branch retinal artery occlusion (BRAO) or a central retinal artery occlusion (CRAO), and to study factors that may influence the ONV rate secondary to CRAO. Methods This was a retrospective case series of consecutive patients (286 total eyes: 83 CRAOs and 203 BRAOs) who were diagnosed with a retinal artery occlusion from 1998 to 2013 at the Retina Consultants of Alabama and University of Alabama at Birmingham, Birmingham, AL, USA. Generalized estimating equations were used to evaluate the association between hypothesized risk factors and ONV development. Results Twelve (14.5%) of the 83 eyes with a CRAO developed ONV. Eleven of 12 eyes (91.7%) had iris neovascularization, ten of 12 eyes (83.3%) had neovascular glaucoma, and two of 12 eyes (16.7%) had neovascularization of the optic disc. The average time for ONV development secondary to CRAO was 30.7 days, ranging from the date of presentation to 137 days. Only two (<1.0%) of the 203 eyes with a BRAO developed iris neovascularization. Diabetes mellitus type 2 was a risk factor for ONV development following a CRAO with an adjusted odds ratio of 5.2 (95% confidence interval: 1.4–19.8) (P=0.02). Conclusion ONV is an important complication of CRAO and is a less-frequent complication of BRAO. Patients with a CRAO, especially those with diabetes mellitus type 2, should be closely monitored for the first 6 months for ONV. PMID:26089631

  5. Topical and subcutaneous alpha-interferon fails to suppress corneal neovascularization.

    PubMed

    Nguyen, N; Goldberg, M; Pico, J; Kim, W; Abbott, R L; Levy, B

    1995-03-01

    Corneal neovascularization is a potentially blinding complication of a variety of corneal disorders. alpha-Interferon has been shown to inhibit endothelial cell migration and proliferation. It has been used successfully in the treatment of pediatric pulmonary hemangioma and hairy cell leukemia. This study was undertaken to evaluate the effect of topical and subcutaneous (s.c.) alpha-interferon on corneal neovascularization. Corneal neovascularization was induced in 40 male New Zealand white rabbits by placing silk sutures (7.0) bilaterally in each rabbit eye at the 3 and 9 o'clock positions of the cornea, 3 mm from the limbus. Animals were randomized into two main treatment groups for topical (group 1) and s.c. (group 2) administration of interferon. Group 1 (n = 24) was then randomized into four subgroups and treated daily with topical doses of (a) rabbit specific alpha-interferon; (b) alpha-interferon plus 1% prednisolone acetate; (c) 1% prednisolone acetate; and (d) buffered phosphate control. Group 2 (n = 16) was randomized into two subgroups that received s.c. injections every other day of (a) alpha-interferon and (b) phosphate buffer. Rate of corneal neovascularization was documented photographically, with the end-point being the arrival of vessels at the suture for each group. The results of this study indicated that at the concentration and dosing regimens we used, neither topical nor s.c. alpha-interferon inhibits the rate of corneal vascular growth significantly when compared with our phosphate buffered solution control group (p = 0.88 and p = 0.84, respectively). Prednisolone acetate appeared to be the most effective in inhibiting corneal neovascularization (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Enhanced anti-angiogenic effect of a deletion mutant of plasminogen kringle 5 on neovascularization.

    PubMed

    Cai, Weibin; Ma, Jianfang; Li, Chaoyang; Yang, Zhonghan; Yang, Xia; Liu, Wei; Liu, Zuguo; Li, Mintao; Gao, Guoquan

    2005-12-15

    Kringle 5 (K5), a proteolytic fragment of plasminogen, has been proved to be an angiogenic inhibitor. Previously, we have evaluated the effect of K5 on the vascular leakage and neovascularization in a rat model of oxygen-induced retinopathy. In this study, we expressed K5 and a deletion mutant of K5 (K5 mutant) in a prokaryocyte expression system and purified them by affinity chromatography. K5 mutant was generated by deleting 11 amino acids from K5 while retaining the three disulfide bonds. The anti-angiogenic activity of intact K5 and K5 mutant were compared in endothelial cells and retinal neovascularization rat model. K5 mutant inhibited the proliferation of primary human retinal capillary endothelial cells (HRCEC) in a concentration-dependent manner, with an apparent EC50 of approximate 35 nmol/L, which is twofold more potent than intact K5. In the even higher concentration range, K5 mutant did not inhibit pericytes from the same origin of HRCEC, which suggested an endothelial cell-specific inhibition. K5 mutant had no effect on normal liver cells and Bel7402 hepatoma cells even at high concentration range either. Intravitreal injection of the K5 and mutant in the oxygen-induced retinopathy rat model both resulted in significantly fewer neovascular tufts and nonperfusion area than controls with PBS injection, as shown by fluorescein angiography. Furthermore, K5 mutant exhibited more strong inhibition effect on neovascularization than intact K5 by quantification of vascular cells. These results suggest that this K5 deletion mutant is a more potent angiogenic inhibitor than intact K5 and may have therapeutic potential in the treatment of those disorders with neovascularization, such as solid tumor, diabetic retinopathy, age-related macular degeneration, rheumatoid arthritis, and hyperplasia of prostate. PMID:16167344

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

    SciTech Connect

    Vavilala, Divya Teja; O’Bryhim, Bliss E.; Ponnaluri, V.K. Chaithanya; White, R. Sid; Radel, Jeff; Symons, R.C. Andrew; Mukherji, Mridul

    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. 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.

  8. Age-related structural abnormalities in the human retina-choroid complex revealed by two-photon excited autofluorescence imaging.

    PubMed

    Han, Meng; Giese, Guenter; Schmitz-Valckenberg, Steffen; Bindewald-Wittich, Almut; Holz, Frank G; Yu, Jiayi; Bille, Josef F; Niemz, Markolf H

    2007-01-01

    The intensive metabolism of photoreceptors is delicately maintained by the retinal pigment epithelium (RPE) and the choroid. Dysfunction of either the RPE or choroid may lead to severe damage to the retina. Two-photon excited autofluorescence (TPEF) from endogenous fluorophores in the human retina provides a novel opportunity to reveal age-related structural abnormalities in the retina-choroid complex prior to apparent pathological manifestations of age-related retinal diseases. In the photoreceptor layer, the regularity of the macular photoreceptor mosaic is preserved during aging. In the RPE, enlarged lipofuscin granules demonstrate significantly blue-shifted autofluorescence, which coincides with the depletion of melanin pigments. Prominent fibrillar structures in elderly Bruch's membrane and choriocapillaries represent choroidal structure and permeability alterations. Requiring neither slicing nor labeling, TPEF imaging is an elegant and highly efficient tool to delineate the thick, fragile, and opaque retina-choroid complex, and may provide clues to the trigger events of age-related macular degeneration.

  9. Characterization of Choroidal Layers in Normal Aging Eyes Using Enface Swept-Source Optical Coherence Tomography

    PubMed Central

    Mullins, Robert F.; Baumal, Caroline R.; Mohler, Kathrin J.; Kraus, Martin F.; Liu, Jonathan; Badaro, Emmerson; Alasil, Tarek; Hornegger, Joachim; Fujimoto, James G.; Duker, Jay S.; Waheed, Nadia K.

    2015-01-01

    Purpose To characterize qualitative and quantitative features of the choroid in normal eyes using enface swept-source optical coherence tomography (SS-OCT). Methods Fifty-two eyes of 26 consecutive normal subjects were prospectively recruited to obtain multiple three-dimensional 12x12mm volumetric scans using a long-wavelength high-speed SS-OCT prototype. A motion-correction algorithm merged multiple SS-OCT volumes to improve signal. Retinal pigment epithelium (RPE) was segmented as the reference and enface images were extracted at varying depths every 4.13μm intervals. Systematic analysis of the choroid at different depths was performed to qualitatively assess the morphology of the choroid and quantify the absolute thicknesses as well as the relative thicknesses of the choroidal vascular layers including the choroidal microvasculature (choriocapillaris, terminal arterioles and venules; CC) and choroidal vessels (CV) with respect to the subfoveal total choroidal thickness (TC). Subjects were divided into two age groups: younger (<40 years) and older (≥40 years). Results Mean age of subjects was 41.92 (24-66) years. Enface images at the level of the RPE, CC, CV, and choroidal-scleral interface were used to assess specific qualitative features. In the younger age group, the mean absolute thicknesses were: TC 379.4μm (SD±75.7μm), CC 81.3μm (SD±21.2μm) and CV 298.1μm (SD±63.7μm). In the older group, the mean absolute thicknesses were: TC 305.0μm (SD±50.9μm), CC 56.4μm (SD±12.1μm) and CV 248.6μm (SD±49.7μm). In the younger group, the relative thicknesses of the individual choroidal layers were: CC 21.5% (SD±4.0%) and CV 78.4% (SD±4.0%). In the older group, the relative thicknesses were: CC 18.9% (SD±4.5%) and CV 81.1% (SD±4.5%). The absolute thicknesses were smaller in the older age group for all choroidal layers (TC p=0.006, CC p=0.0003, CV p=0.03) while the relative thickness was smaller only for the CC (p=0.04). Conclusions Enface SS-OCT at

  10. Effect of timolol on sub-foveal choroidal blood flow using laser Doppler flowmetry

    NASA Astrophysics Data System (ADS)

    Palanisamy, Nithiyanantham; Rovati, Luigi; Cellini, Mauro; Gizzi, Corrado; Strobbe, Ernesto; Campos, Emilio; Riva, Charles E.

    2011-03-01

    Laser Doppler flowmetry (LDF) is a technique used to measure relative average velocity, number and flux (number times velocity) of red blood cells in vessels or capillaries. In this study, the effect of topical timolol on the choroidal circulation was investigated in 12 healthy subjects. Maximum velocity of red blood cells and volumetric blood flow rate in sub-foveal choroids are determined in each eye just before instillation of drops and then every 30 min upto 2 hours. Average intraocular pressure (IOP) decreased significantly in the timolol-treated eyes compared to that of placebo-treated eyes. Nevertheless no significant differences in choroidal blood hemodynamic between timolol and placebo-treated eyes were observed.

  11. Choroidal rupture and optic nerve injury with equipment designated as 'child-safe'.

    PubMed

    Petrarca, Robert; Saldana, Manuel

    2012-01-01

    Blunt ocular trauma from a child's plastic foam-covered toy baseball bat caused traumatic optic neuropathy and choroidal rupture in a 9-year-old child. The examination revealed a visual acuity of 6/60, a relative afferent pupillary defect, optic nerve swelling, commotio retinae and retinal haemorrhages. There was no orbital fracture or intraorbital haematoma on CT scanning. Optical coherence tomography showed macular oedema and disruption of the retinal pigment epithelium and Bruch's membrane. The child was admitted for intravenous methylprednisolone and discharged on topical steroid treatment. At 1 month follow-up, visual acuity had improved to 6/12. Optic nerve swelling had resolved and the fundus had two crescent-shaped choroidal rupture scars. Choroidal rupture and optic neuropathy can be secondary to indirect trauma, and even when the mechanism of injury is with a piece of equipment designated as suitable for children, serious ocular injury can occur. PMID:22927278

  12. Choroidal rupture and optic nerve injury with equipment designated as 'child-safe'.

    PubMed

    Petrarca, Robert; Saldana, Manuel

    2012-01-01

    Blunt ocular trauma from a child's plastic foam-covered toy baseball bat caused traumatic optic neuropathy and choroidal rupture in a 9-year-old child. The examination revealed a visual acuity of 6/60, a relative afferent pupillary defect, optic nerve swelling, commotio retinae and retinal haemorrhages. There was no orbital fracture or intraorbital haematoma on CT scanning. Optical coherence tomography showed macular oedema and disruption of the retinal pigment epithelium and Bruch's membrane. The child was admitted for intravenous methylprednisolone and discharged on topical steroid treatment. At 1 month follow-up, visual acuity had improved to 6/12. Optic nerve swelling had resolved and the fundus had two crescent-shaped choroidal rupture scars. Choroidal rupture and optic neuropathy can be secondary to indirect trauma, and even when the mechanism of injury is with a piece of equipment designated as suitable for children, serious ocular injury can occur.

  13. Effects of Dorzolamide on Choroidal Blood Flow, Ciliary Blood Flow, and Aqueous Production in Rabbits

    PubMed Central

    Reitsamer, Herbert A.; Bogner, Barbara; Tockner, Birgit; Kiel, Jeffrey W.

    2015-01-01

    Purpose To determine the effects of topical dorzolamide (a carbonic anhydrase inhibitor) on choroidal and ciliary blood flow and the relationship between ciliary blood flow and aqueous flow. Methods The experiments were performed in four groups of pentobarbital-anesthetized rabbits treated with topical dorzolamide (2%, 50 μL). In all groups, intraocular pressure (IOP) and mean arterial pressure (MAP) at the eye level were measured continuously by direct cannulation. In group 1, aqueous flow was measured by fluorophotometry before and after dorzolamide treatment. In group 2, aqueous flow was measured after dorzolamide at normal MAP and while MAP was held constant at 80, 55, or 40 mm Hg with occluders on the aorta and vena cava. In group 3, the same MAP levels were used, and ciliary blood flow was measured transsclerally by laser Doppler flowmetry (LDF). In group 4, choroidal blood flow was measured by LDF with the probe tip positioned in the vitreous over the posterior pole during ramp increases and decreases in MAP before and after dorzolamide. Results Dorzolamide lowered IOP by 19% (P < 0.01) and aqueous flow by 17% (P < 0.01), and increased ciliary blood flow by 18% (P < 0.01), which was associated with a significant reduction in ciliary vasculature resistance (−7%, P < 0.01). Dorzolamide shifted the relationship between ciliary blood flow and aqueous flow downward relative to the previously determined control relationship in the rabbit. Dorzolamide did not alter choroidal blood flow, choroidal vascular resistance, or the choroidal pressure flow relationship. Conclusions Acute topical dorzolamide is a ciliary vasodilator and has a direct inhibitory effect on aqueous production, but it does not have a detectable effect on choroidal hemodynamics at the posterior pole in the rabbit. PMID:19182250

  14. OB protein binds specifically to the choroid plexus of mice and rats.

    PubMed Central

    Devos, R; Richards, J G; Campfield, L A; Tartaglia, L A; Guisez, Y; van der Heyden, J; Travernier, J; Plaetinck, G; Burn, P

    1996-01-01

    Binding studies were conducted to identify the anatomical location of brain target sites for OB protein, the ob gene product. 125I-labeled recombinant mouse OB protein or alkaline phosphatase-OB fusion proteins were used for in vitro and in vivo binding studies. Coronal brain sections or fresh tissue from lean, obese ob/ob, and obese db/db mice as well as lean and obese Zucker rats were probed to identify potential central OB protein-binding sites. We report here that recombinant OB protein binds specifically to the choroid plexus. The binding of OB protein (either radiolabeled or the alkaline phosphatase-OB fusion protein) and its displacement by unlabeled OB protein was similar in lean, obese ob/ob, and obese db/db mice as well as lean and obese Zucker rats. These findings suggest that OB protein binds with high affinity to a specific receptor in the choroid plexus. After binding to the choroid plexus receptor, OB protein may then be transported across the blood-brain barrier into the cerebrospinal fluid. Alternatively, binding of OB protein to a specific receptor in the choroid plexus may activate afferent neural inputs to the neural network that regulates feeding behavior and energy balance or may result in the clearance or degradation of OB protein. The identification of the choroid plexus as a brain binding site for OB protein will provide the basis for the construction of expression libraries and facilitate the rapid cloning of the choroid plexus OB receptor. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8643634

  15. Chronic lead exposure alters transthyretin concentration in rat cerebrospinal fluid: the role of the choroid plexus.

    PubMed

    Zheng, W; Shen, H; Blaner, W S; Zhao, Q; Ren, X; Graziano, J H

    1996-08-01

    The choroid plexus, which is responsible for the maintenance of the biochemical milieu of the cerebrospinal fluid (CSF), avidly sequesters Pb. In order to test the hypothesis that chronic Pb exposure may impair choroid plexus function, male weanling Sprague-Dawley rats were exposed to Pb in drinking water at doses of 0, 50, or 250 micrograms Pb/ml (as Pb acetate) for 30, 60, or 90 days. The function of the choroid plexus was assessed as reflected by CSF concentrations of transthyretin (TTR, a major CSF protein manufactured by brain choroid plexus) and CSF essential metal ions (Ca2+, Mg2+, K+, and Na+). TTR concentrations were determined by radioimmunoassay using a monospecific rabbit anti-rat TTR polyclonal antibody, and CSF metal ions analyzed by flame atomic absorption spectrophotometry. Two-way ANOVA of CSF TTR concentrations revealed highly significant dose (p < 0.0001), time (p < 0.0223), and dose-by-time effects (p < 0.0379). Moreover, the percentage of reduction of CSF TTR was directly correlated with Pb concentrations in the choroid plexus (r = 0.703, p < 0.05). Pb exposure significantly increased CSF concentrations of Mg2+, but did not markedly altered CSF concentrations of Ca2+, K+, and Na+. Histopathologic examination under the light microscope did not show distinct alterations of plexus structure in Pb-treated rats. Since TTR is responsible for transport of thyroid hormones to the developing brain, we postulate that the depression of choroid plexus TTR production (and/or secretion) by Pb may impair brain development in young animals by depriving the CNS of thyroid hormones. PMID:8806863

  16. Response of choroidal blood flow to carbogen breathing in smokers and non-smokers

    PubMed Central

    Wimpissinger, B; Resch, H; Berisha, F; Weigert, G; Schmetterer, L; Polak, K

    2004-01-01

    Aim: To investigate a potential difference in ocular vascular reactivity during carbogen breathing in optic nerve head, choroid, and retina between healthy smokers and non-smokers. Methods: 25 (13 smokers and 12 non-smokers) healthy male volunteers participated in this observer masked, two cohort study. During inhalation of carbogen (5% CO2 and 95% O2) over 10 minutes measurements were taken using laser Doppler flowmetry to assess submacular choroidal and optic nerve head blood flow, laser interferometry to assess fundus pulsation amplitudes, and retinal vessel analyser (RVA) to assess retinal vessel diameters. Results: At baseline choroidal blood flow was higher (p = 0.018, ANOVA) in smokers than in non-smokers. During administration of carbogen the response in choroidal blood flow was significantly different between the two groups: there was an increase in non-smokers after carbogen breathing (p = 0.048) compared with relatively stable blood flow in smokers (p = 0.049 between groups, ANOVA). A similar response pattern was seen for fundus pulsation amplitude, which increased notably after carbogen breathing in non-smokers but not in smokers (p<0.001 between groups, ANOVA). Optic nerve head blood flow and retinal vessel diameters were reduced in both groups to a comparable degree during carbogen breathing. Conclusion: The study indicated abnormal choroidal vascular reactivity in chronic smokers. These early haemodynamic changes may be related to the increased risk to smokers of developing ocular vascular diseases. The specific mechanisms underlying abnormal choroidal vascular reactivity in chronic smokers remain to be characterised. PMID:15148211

  17. OB protein binds specifically to the choroid plexus of mice and rats.

    PubMed

    Devos, R; Richards, J G; Campfield, L A; Tartaglia, L A; Guisez, Y; van der Heyden, J; Travernier, J; Plaetinck, G; Burn, P

    1996-05-28

    Binding studies were conducted to identify the anatomical location of brain target sites for OB protein, the ob gene product. 125I-labeled recombinant mouse OB protein or alkaline phosphatase-OB fusion proteins were used for in vitro and in vivo binding studies. Coronal brain sections or fresh tissue from lean, obese ob/ob, and obese db/db mice as well as lean and obese Zucker rats were probed to identify potential central OB protein-binding sites. We report here that recombinant OB protein binds specifically to the choroid plexus. The binding of OB protein (either radiolabeled or the alkaline phosphatase-OB fusion protein) and its displacement by unlabeled OB protein was similar in lean, obese ob/ob, and obese db/db mice as well as lean and obese Zucker rats. These findings suggest that OB protein binds with high affinity to a specific receptor in the choroid plexus. After binding to the choroid plexus receptor, OB protein may then be transported across the blood-brain barrier into the cerebrospinal fluid. Alternatively, binding of OB protein to a specific receptor in the choroid plexus may activate afferent neural inputs to the neural network that regulates feeding behavior and energy balance or may result in the clearance or degradation of OB protein. The identification of the choroid plexus as a brain binding site for OB protein will provide the basis for the construction of expression libraries and facilitate the rapid cloning of the choroid plexus OB receptor. PMID:8643634

  18. Choroidal Vascularity Index (CVI) - A Novel Optical Coherence Tomography Parameter for Monitoring Patients with Panuveitis?

    PubMed Central

    Agrawal, Rupesh; Salman, Mohammed; Tan, Kara-Anne; Karampelas, Michael; Sim, Dawn A.; Keane, Pearse A.; Pavesio, Carlos

    2016-01-01

    Purpose To compute choroidal vascularity index (CVI) using an image binarization tool on enhanced depth imaging (EDI)-optical coherence tomography (OCT) scans as a non-invasive optical tool to monitor progression in panuveitis and to investigate the utility of volumetric data from EDI-OCT scans using custom image analysis software. Materials and Methods In this retrospective cohort study, segmented EDI-OCT scans of both eyes in 19 patients with panuveitis were taken at baseline and at 3-month follow-up and were compared with EDI-OCT scans of normal eyes. Subfoveal choroidal area was segmented into luminal (LA) and stromal interstitial area (SA). Choroidal vascularity index (CVI) was defined as the proportion of LA to the total circumscribed subfoveal choroidal area (TCA). Results The mean choroidal thickness was 265.5±100.1μm at baseline and 278.4±102.6μm at 3 months follow up (p = 0.06). There was no statistically significant difference in TCA between study and control eyes (p = 0.08). CVI in the control group was 66.9±1.5% at baseline and 66.4±1.5% at follow up. CVI was 74.1±4.7% at baseline and 69.4±4.8% at 3 months follow up for uveitic eyes (p<0.001). The % change in CVI was 6.2 ±3.8 (4.3 to 8.0) for uveitic eyes, which was significantly higher from % change in CVI for control eyes (0.7±1.1, 0.2 to 1.3, p<0.001). Conclusion The study reports composite OCT-derived parameters and CVI as a possible novel tool in monitoring progression in panuveitis. CVI may be further validated in larger studies as a novel optical tool to quantify choroidal vascular status. PMID:26751702

  19. Choroidal responses in microgravity. (SLS-1, SLS-2 and hindlimb-suspension experiments).

    PubMed

    Gabrion, J; Herbute, S; Oliver, J; Maurel, D; Davet, J; Clavel, B; Gharib, C; Fareh, J; Fagette, S; Nguyen, B

    1995-01-01

    Fluid and electrolyte shifts occurring during human spaceflight have been reported and investigated at the level of blood, cardiovascular and renal responses. Very few data were available concerning the cerebral fluid and electrolyte adaptation to microgravity, even in animal models. It is the reason why we developed several studies focused on the effects of spaceflight (SLS-1 and SLS-2 programs, carried on NASA STS 40 and 56 missions, which were 9- and 14-day flights, respectively), on structural and functional features of choroid plexuses, organs which secrete 70-90% of cerebrospinal fluid (CSF) and which are involved in brain homeostasis. Rats flown aboard space shuttles were sacrificed either in space (SLS-2 experiment, on flight day 13) or 4-8 hours after landing (SLS-1 and SLS-2 experiments). Quantitative autoradiography performed by microdensitometry and image analysis, showed that lateral and third ventricle choroid plexuses from rats flown for SLS-1 experiment demonstrated an increased number (about x 2) of binding sites to natriuretic peptides (which are known to be involved in mechanisms regulating CSF production). Using electron microscopy and immunocytochemistry, we studied the cellular response of choroid plexuses, which produce cerebrospinal fluid (CSF) in brain lateral, third and fourth ventricles. We demonstrated that spaceflight (SLS-2 experiment, inflight samples) induces changes in the choroidal cell structure (apical microvilli, kinocilia organization, vesicle accumulation) and protein distribution or expression (carbonic anhydrase II, water channels,...). These observations suggested a loss of choroidal cell polarity and a decrease in CSF secretion. Hindlimb-suspended rats displayed similar choroidal changes. All together, these results support the hypothesis of a modified CSF production in rats during long-term (9, 13 or 14 days) adaptations to microgravity.

  20. Altered choroid plexus gene expression in major depressive disorder

    PubMed Central

    Turner, Cortney A.; Thompson, Robert C.; Bunney, William E.; Schatzberg, Alan F.; Barchas, Jack D.; Myers, Richard M.; Akil, Huda; Watson, Stanley J.

    2014-01-01

    Given the emergent interest in biomarkers for mood disorders, we assessed gene expression in the choroid plexus (CP), the region that produces cerebrospinal fluid (CSF), in individuals with major depressive disorder (MDD). Genes that are expressed in the CP can be secreted into the CSF and may be potential biomarker candidates. Given that we have previously shown that fibroblast growth factor family members are differentially expressed in post-mortem brain of subjects with MDD and the CP is a known source of growth factors in the brain, we posed the question whether growth factor dysregulation would be found in the CP of subjects with MDD. We performed laser capture microscopy of the CP at the level of the hippocampus in subjects with MDD and psychiatrically normal controls. We then extracted, amplified, labeled, and hybridized the cRNA to Illumina BeadChips to assess gene expression. In controls, the most highly abundant known transcript was transthyretin. Moreover, half of the 14 most highly expressed transcripts in controls encode ribosomal proteins. Using BeadStudio software, we identified 169 transcripts differentially expressed (p < 0.05) between control and MDD samples. Using pathway analysis we noted that the top network altered in subjects with MDD included multiple members of the transforming growth factor-beta (TGFβ) pathway. Quantitative real-time PCR (qRT-PCR) confirmed downregulation of several transcripts that interact with the extracellular matrix in subjects with MDD. These results suggest that there may be an altered cytoskeleton in the CP in MDD subjects that may lead to a disrupted blood-CSF-brain barrier. PMID:24795602

  1. Study of the blood-aqueous barrier in choroidal melanoma.

    PubMed Central

    Castella, A P; Bercher, L; Zografos, L; Egger, E; Herbort, C P

    1995-01-01

    AIMS--Aqueous flare was used to determine the frequency and amount of blood-aqueous barrier breakdown and correlate it with tumour variables. METHODS--Aqueous flare was analysed prospectively by laser flare photometry in 139 consecutive patients seen in the oncology unit for choroidal melanoma. Both eyes of patients were examined with a laser flare cell meter in a standard fashion. RESULTS--Mean flare difference between healthy and tumour eyes was 3.01 (SD 2.5) photons per millisecond (ph/ms) in 32 cases of small melanomas (p < 0.0001), 10.74 (13.9) ph/ms in 92 cases of medium and large melanomas (p < 0.0001), and 19.23 (11.8) ph/ms in 15 cases of very large melanomas (p < 0.0001). This mean differential flare was significantly higher in medium and large than in small melanomas (p < 0.002) and in very large melanomas than in medium and large melanomas (p < 0.028). A difference of > or = 7 ph/ms between affected and healthy eyes was noted in 70 of 139 melanomas (50.4%). It was found in 3/32 small melanomas (9.4%), in 53/92 medium and large melanomas (57.6%), and in 14/15 very large melanomas (93.3%). CONCLUSION--Multiple linear regression analysis showed that flare was most strongly correlated with tumour volume (r = 0.43; p < 0.0001) and tumour height (r = 0.41; p < 0.0008). PMID:7742283

  2. Investigation of the choroidal thickness in patients with hypothyroidism

    PubMed Central

    Ulaş, Fatih; Dogan, Ümit; Dikbaş, Oğuz; Çelebi, Serdal; Keleş, Asena

    2015-01-01

    Purpose: The effect of hypothyroidism on the choroidal thickness (CT) was investigated in patients with subclinical hypothyroidism and overt hypothyroidism, and biochemically and clinically euthyroid patients receiving levothyroxine treatment. The patients were compared with healthy subjects. Materials and Methods: One eye of 71 hypothyroid and 22 healthy subjects between 20 and 40 years of age were included in this study. CT measurements were taken at the fovea and at 2 points that were 1500 μm nasal and temporal to the fovea using spectral-domain optical coherence tomography. Independent sample t-test's and was used for statistical analysis of the data. Results: The CT was significantly thicker in hypothyroid patients compared to healthy subjects (P values were 0.013 for subfoveal, 0.015 for temporal and 0.020 for nasal segments). The intraocular pressure (IOP) and body mass index (BMI) were also significantly higher in hypothyroid patients (P values were 0.021 and 0.003, respectively). There was not a statistically significant difference in the BMI and IOP measurements between healthy subjects and euthyroid patients (P > 0.05). However, there was a statistically significant difference in the subfoveal, temporal and nasal CT measurements between healthy subjects and euthyroid patients (P values were 0.006, 0.031 and 0.013, respectively). Conclusions: All subgroups of hypothyroid patients had thicker CT compared to healthy subjects. Euthyroid patients receiving levothyroxine treatment had lower IOP, BMI levels, and serum lipid levels than patients with subclinical hypothyroidism and overt hypothyroidism. PMID:25971170

  3. "Tasting" the cerebrospinal fluid: Another function of the choroid plexus?

    PubMed

    Tomás, J; Santos, C R A; Quintela, T; Gonçalves, I

    2016-04-21

    The choroid plexus (CP) located in brain ventricles, by forming the interface between the blood and the cerebrospinal fluid (CSF) is in a privileged position to monitor the composition of these body fluids. Yet, the mechanisms involved in this surveillance system remain to be identified. The taste transduction pathway senses some types of molecules, thereby evaluating the chemical content of fluids, not only in the oral cavity but also in other tissues throughout the body, such as some cell types of the airways, the gastrointestinal tract, testis and skin. Therefore, we hypothesized that the taste transduction pathway could also be operating in the CP to assess the composition of the CSF. We found transcripts for some taste receptors (Tas1r1, Tas1r2, Tas1r3, Tas2r109 and Tas2r144) and for downstream signaling molecules (α-Gustducin, Plcβ2, ItpR3 and TrpM5) that encode this pathway, and confirmed the expression of the corresponding proteins in Wistar rat CP explants and in the CP epithelial cells (CPEC). The functionality of the T2R receptor expressed in CP cells was assessed by calcium imaging, of CPEC stimulated with the bitter compound D-Salicin, which elicited a rise in the intracellular Ca(2+). This effect was diminished in the presence of the bitter receptor blocker Probenecid. In summary, we described the expression of the taste-related components involved in the transduction signaling cascade in CP. Taken together, our results suggest that the taste transduction pathway in CPEC makes use of T2R receptors in the chemical surveillance of the CSF composition, in particular to sense bitter noxious compounds. PMID:26850994

  4. Myopic Shift and Outdoor Activity among Primary School Children: One-Year Follow-Up Study in Beijing

    PubMed Central

    Guo, Yin; Liu, Li Juan; Xu, Liang; Tang, Ping; Lv, Yan Yun; Feng, Yi; Meng, Meng; Jonas, Jost B.

    2013-01-01

    Purpose To assess whether a change in myopia related oculometric parameters of primary school children in Beijing was associated with indoors and outdoors activity. Methods The longitudinal school-based study included school children who were examined in 2011 and who were re-examined in 2012. The children underwent a comprehensive eye examination including ocular biometry by optical low-coherence reflectometry and non-cycloplegic refractometry. Parents and children had a detailed interview including questions on time spent indoors and outdoors. Results Out of 681 students examined at baseline, 643 (94.4%) returned for follow-up examination. Within the one-year period, mean time spent daily outdoors increased by 0.4±0.9 hours, mean axial length by 0.26±0.49 mm, the ratio of axial length divided by anterior corneal curvature (AL/CC) by 0.03±0.06, and myopic refractive error by −0.06±0.89 diopters. In multivariate analysis, elongation of axial length was significantly associated with less total time spent outdoors (P = 0.02; standardized coefficient beta −0.12) and more time spent indoors with studying (P = 0.007; beta: 0.14) after adjustment for maternal myopia (P = 0.02; beta: 0.12). An increase in AL/CC was significantly associated with less time spent outdoors (P = 0.01; beta:−0.12) after adjustment for paternal myopia (P = 0.003; beta: 0.15) and if region of habitation was excludedors for leisure (P = 0.006; beta:−0.13), with less total time spent outdoors (P = 0.04; beta:−0.10), or with more time spent i. An increase in myopic refractive error, after adjustment for age, was significantly associated with less time spent outdo ndoors with studying (P = 0.005; beta: 0.13). Conclusions A change in oculometric parameters indicating an increase in myopia was significantly associated with less time spent outdoors and more time spent indoors in school children in Greater Beijing within a study period of one year. Our study

  5. Single-Step Transepithelial PRK vs Alcohol-Assisted PRK in Myopia and Compound Myopic Astigmatism Correction.

    PubMed

    Kaluzny, Bartlomiej J; Cieslinska, Iwona; Mosquera, Samuel A; Verma, Shwetabh

    2016-02-01

    Transepithelial photorefractive keratectomy (tPRK), where both the epithelium and stroma are removed in a single-step, is a relatively new procedure of laser refractive error correction. This study compares the 3-month results of myopia and compound myopic astigmatism correction by tPRK or conventional alcohol-assisted PRK (aaPRK).This prospective, nonrandomized, case-control study recruited 148 consecutive patients; 93 underwent tPRK (173 eyes) and 55 aaPRK (103 eyes). Refractive results, predictability, safety, and efficacy were evaluated during the 3-month follow-up. The main outcome measures were uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and mean refractive spherical equivalent (MRSE).Mean preoperative MRSE was -4.30 ± 1.72 D and -4.33 ± 1.96 D, respectively (P = 0.87). The 3-month follow-up rate was 82.1% in the tPRK group (n = 145) and 86.4% in aaPRK group (n = 90), P = 0.81. Postoperative UDVA was 20/20 or better in 97% and 94% of eyes, respectively (P = 0.45). In the tPRK and aaPRK groups, respectively, 13% and 21% of eyes lost 1 line of CDVA, and 30% and 31% gained 1 or 2 lines (P = 0.48). Mean postoperative MRSE was -0.14 ± 0.26 D in the tPRK group and -0.12 ± 0.20 D in the aaPRK group (P = 0.9). The correlation between attempted versus achieved MRSE was equally high in both groups.Single-step transepithelial PRK and conventional PRK provide very similar results 3 months postoperatively. These procedures are predictable, effective, and safe for correction of myopia and compound myopic astigmatism.

  6. Agreement between clinical history method, Orbscan IIz, and Pentacam in estimating corneal power after myopic excimer laser surgery.

    PubMed

    Lekhanont, Kaevalin; Nonpassopon, Manachai; Wannarosapark, Khemruetai; Chuckpaiwong, Varintorn

    2015-01-01

    The purpose of this study was to investigate the agreement between the clinical history method (CHM), Orbscan IIz, and Pentacam in estimating corneal power after myopic excimer laser surgery. Fifty five patients who had myopic LASIK/PRK were recruited into this study. One eye of each patient was randomly selected by a computer-generated process. At 6 months after surgery, postoperative corneal power was calculated from the CHM, Orbscan IIz total optical power at the 3.0 and 4.0 mm zones, and Pentacam equivalent keratometric readings (EKRs) at 3.0, 4.0, and 4.5 mm. Statistical analyses included multilevel models, Pearson's correlation test, and Bland-Altman plots. The Orbscan IIz 3.0-mm and 4.0 mm total optical power, and Pentacam 3.0-mm, 4.0-mm, and 4.5-mm EKR values had strong linear positive correlations with the CHM values (r = 0.90-0.94, P = <0.001, for all comparisons, Pearson's correlation). However, only Pentacam 3.0-mm EKR was not statistically different from CHM (P = 0.17, multilevel models). The mean 3.0- and 4.0-mm total optical powers of the Orbscan IIz were significantly flatter than the values derived from CHM, while the average EKRs of the Pentacam at 4.0 and 4.5 mm were significantly steeper. The mean Orbscan IIz 3.0-mm total optical power was the lowest keratometric reading compared to the other 5 values. Large 95% LoA was observed between each of these values, particularly EKRs, and those obtained with the CHM. The width of the 95% LoA was narrowest for Orbscan IIz 3.0-mm total optical power. In conclusion, the keratometric values extracted from these 3 methods were disparate, either because of a statistically significant difference in the mean values or moderate agreement between them. Therefore, they are not considered equivalent and cannot be used interchangeably.

  7. A case of choroidal osteoma in a 10-year-old child

    PubMed Central

    Behera, Madhusmita; Das, Manmath Kumar

    2015-01-01

    Choroidal osteoma is a rare, benign tumor, usually diagnosed in healthy adult women in their second or third decade of life. Though its etiology and pathogenesis are unclear, it is usually diagnosed due to its typical clinical features of yellowish-orange colored subretinal lesion at posterior pole and a dense echogenic plaque persisting even in lower gains on B-scan ultrasonography. Mostly unilateral (79%), the median age of diagnosis is 26 years. It is relatively rare in children. We report a case of choroidal osteoma in a 10-year-old boy. PMID:26586966

  8. Defining response to anti-VEGF therapies in neovascular AMD.

    PubMed

    Amoaku, W M; Chakravarthy, U; Gale, R; Gavin, M; Ghanchi, F; Gibson, J; Harding, S; Johnston, R L; Kelly, S P; Kelly, S; Lotery, A; Mahmood, S; Menon, G; Sivaprasad, S; Talks, J; Tufail, A; Yang, Y

    2015-06-01

    The introduction of anti-vascular endothelial growth factor (anti-VEGF) has made significant impact on the reduction of the visual loss due to neovascular age-related macular degeneration (n-AMD). There are significant inter-individual differences in response to an anti-VEGF agent, made more complex by the availability of multiple anti-VEGF agents with different molecular configurations. The response to anti-VEGF therapy have been found to be dependent on a variety of factors including patient's age, lesion characteristics, lesion duration, baseline visual acuity (VA) and the presence of particular genotype risk alleles. Furthermore, a proportion of eyes with n-AMD show a decline in acuity or morphology, despite therapy or require very frequent re-treatment. There is currently no consensus as to how to classify optimal response, or lack of it, with these therapies. There is, in particular, confusion over terms such as 'responder status' after treatment for n-AMD, 'tachyphylaxis' and 'recalcitrant' n-AMD. This document aims to provide a consensus on definition/categorisation of the response of n-AMD to anti-VEGF therapies and on the time points at which response to treatment should be determined. Primary response is best determined at 1 month following the last initiation dose, while maintained treatment (secondary) response is determined any time after the 4th visit. In a particular eye, secondary responses do not mirror and cannot be predicted from that in the primary phase. Morphological and functional responses to anti-VEGF treatments, do not necessarily correlate, and may be dissociated in an individual eye. Furthermore, there is a ceiling effect that can negate the currently used functional metrics such as >5 letters improvement when the baseline VA is good (ETDRS>70 letters). It is therefore important to use a combination of both the parameters in determining the response.The following are proposed definitions: optimal (good) response is defined as when there

  9. High-order myopic coronagraphic phase diversity (COFFEE) for wave-front control in high-contrast imaging systems.

    PubMed

    Paul, B; Mugnier, L M; Sauvage, J-F; Dohlen, K; Ferrari, M

    2013-12-30

    The estimation and compensation of quasi-static aberrations is mandatory to reach the ultimate performance of high-contrast imaging systems. COFFEE is a focal plane wave-front sensing method that consists in the extension of phase diversity to high-contrast imaging systems. Based on a Bayesian approach, it estimates the quasi-static aberrations from two focal plane images recorded from the scientific camera itself. In this paper, we present COFFEE's extension which allows an estimation of low and high order aberrations with nanometric precision for any coronagraphic device. The performance is evaluated by realistic simulations, performed in the SPHERE instrument framework. We develop a myopic estimation that allows us to take into account an imperfect knowledge on the used diversity phase. Lastly, we evaluate COFFEE's performance in a compensation process, to optimize the contrast on the detector, and show it allows one to reach the 10(-6) contrast required by SPHERE at a few resolution elements from the star. Notably, we present a non-linear energy minimization method which can be used to reach very high contrast levels (better than 10(7) in a SPHERE-like context).

  10. Q-value customized ablation (custom-Q) versus wavefront optimized ablation for primary myopia and myopic astigmatism.

    PubMed

    Tawfik, Ahmed; Eid, Ahmed Mostafa; Hasanen, Rabei; Moftah, Ismail A N

    2014-04-01

    Comparison between treatment with wavefront optimized and custom-Q laser-assisted in situ keratomileusis (LASIK) ablations. Our study included 400 eyes of 200 patients divided into two equal groups. All patients were treated for myopia and myopic astigmatism with LASIK. The first group was treated with wavefront optimized ablation and the second group with custom-Q ablation. They were examined preoperatively and postoperatively to assess asphericity, image quality, and other classical outcome parameters. The wavefront optimized ablation group comprised 200 eyes with a mean spherical equivalent refraction (SE) of -5.2188 diopters (D) (range: -1.15 to -10.50 D); the mean Q-value changed from 0.30 preoperatively to 0.06 postoperatively. The custom-Q ablation group also comprised 200 eyes with a mean SE of -5.1575 D (range: -1.35 to -9.00 D); the mean Q-value changed from 0.32 preoperatively to 0.03 postoperatively. A statistically significant difference in postoperative change in Q-values (P = 0.02) and in postoperative visual acuity (P = 0.42) between the two groups was noted. There was no difference between the two groups regarding refractive correction. There was a marginally significant change in BSCVA (best spectacle-corrected visual acuity) between the two groups, and less impairment in the corneal asphericity in the custom-Q group.

  11. Treatment for neovascular age related macular degeneration: The state of the art.

    PubMed

    Eandi, Chiara M; Alovisi, Camilla; De Sanctis, Ugo; Grignolo, Federico M

    2016-09-15

    With the introduction in the clinical practice of drugs inhibiting vascular endothelial growth factor (VEGF) the visual outcomes of patients with neovascular age related macular degeneration (AMD) dramatically improved. Since 2006 repeated intravitreal injections of anti-VEGF became the standard of care for the treatment of neovascular AMD. This review provides an overview of available data form clinical trials supporting the use of anti-VEGF molecules for the treatment of this condition. Several questions remain open, in particular the regimen of treatment, the frequency of injection, the safety of the different drugs, and the poor response to the treatment in some cases. Therefore, new agents and alternative delivery are currently under evaluation. PMID:26948315

  12. Subfoveal Choroidal Thickness and Glaucoma. The Beijing Eye Study 2011

    PubMed Central

    Wang, Ya Xing; Xu, Liang; Shao, Lei; Zhang, Ya Qin; Yang, Hua; Da Wang, Jin; Jonas, Jost B.; Wei, Wen Bin

    2014-01-01

    Purpose To examine subfoveal choroidal thickness (SFCT) in eyes with glaucoma, using enhanced depth imaging spectral domain optical coherence tomography. Methods The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years (range: 50–93 years). A detailed ophthalmic examination was performed including spectral-domain optical coherence tomography (SD-OCT) with enhanced depth imaging for measurement of SFCT, and assessment of fundus photographs for presence of glaucoma. In addition, the group of patients with chronic angle-closure glaucoma (ACG) from the Beijing Eye Study (n = 37) was merged with a group of patients with chronic ACG from the Tongren hospital (n = 52). Results Assessments of SFCT and glaucoma were available for 3232 (93.2%) subjects. After adjusting for age, axial length, gender, anterior chamber and lens thickness, SFCT was not significantly associated with presence of glaucoma (P = 0.08; regression coefficient B:−15.7). As a corollary, in logistic regression analysis with adjustment for age, axial length and intraocular pressure, presence of glaucoma was not significantly associated with SFCT (P = 0.20). If only open-angle glaucoma was considered, multivariate analysis revealed no significant association between SFCT and presence of open-angle glaucoma (P = 0.44). As a corollary, in logistic regression analysis, open-angle glaucoma was not significantly associated with SFCT (P = 0.91). In a similar manner if only ACG was taken into account, SFCT was not significantly associated with the presence of ACG (P = 0.27) in multivariate analysis. As a corollary in binary regression analysis, presence of ACG was not significantly associated with SFCT (P = 0.27). Conclusions In multivariate analysis with adjustment for age, axial length, gender, anterior chamber and lens thickness, neither OAG nor ACG was associated with an abnormal SFCT. PMID:25210857

  13. Developmentally Regulated Production of meso-Zeaxanthin in Chicken Retinal Pigment Epithelium/Choroid and Retina

    PubMed Central

    Gorusupudi, Aruna; Shyam, Rajalekshmy; Li, Binxing; Vachali, Preejith; Subhani, Yumna K.; Nelson, Kelly; Bernstein, Paul S.

    2016-01-01

    Purpose meso-Zeaxanthin is a carotenoid that is rarely encountered in nature outside of the vertebrate eye. It is not a constituent of a normal human diet, yet this carotenoid comprises one-third of the primate macular pigment. In the current study, we undertook a systematic approach to biochemically characterize the production of meso-zeaxanthin in the vertebrate eye. Methods Fertilized White Leghorn chicken eggs were analyzed for the presence of carotenoids during development. Yolk, liver, brain, serum, retina, and RPE/choroid were isolated, and carotenoids were extracted. The samples were analyzed on C-30 or chiral HPLC columns to determine the carotenoid composition. Results Lutein and zeaxanthin were found in all studied nonocular tissues, but no meso-zeaxanthin was ever detected. Among the ocular tissues, the presence of meso-zeaxanthin was consistently observed starting at embryonic day 17 (E17) in the RPE/choroid, several days before its consistent detection in the retina. If RPE/choroid of an embryo was devoid of meso-zeaxanthin, the corresponding retina was always negative as well. Conclusions This is the first report of developmentally regulated synthesis of meso-zeaxanthin in a vertebrate system. Our observations suggest that the RPE/choroid is the primary site of meso-zeaxanthin synthesis. Identification of meso-zeaxanthin isomerase enzyme in the developing chicken embryo will facilitate our ability to determine the biochemical mechanisms responsible for production of this unique carotenoid in other higher vertebrates, such as humans. PMID:27082300

  14. Ruthenium-106 Plaque Therapy for Diffuse Choroidal Hemangioma in Sturge-Weber Syndrome

    PubMed Central

    Kubicka-Trząska, Agnieszka; Kobylarz, Joanna; Romanowska-Dixon, Bożena

    2011-01-01

    Diffuse choroidal hemangiomas associated with Sturge-Weber syndrome (SWS) are classically treated with external beam radiotherapy (EBR), but there are a few reports usually of single cases indicating the usefulness of plaque therapy. We present our observations on two cases of diffuse choroidal hemangiomas with exudative retinal detachment associated with SWS treated with Ruthenium-106 plaque therapy. Outcomes included best-corrected visual acuity (BCVA) and regression in tumor thickness measured by ultrasonography. The initial BCVA of the affected eyes was counting fingers at 1 meter and light projection. Pretreatment tumors thickness was 3.5 mm and 4.7 mm. In a follow-up period of 18–24 months, significant reduction in thickness of choroidal hemangiomas up to 1.2 mm and 1.4 mm with prompt resolution of exudative retinal detachment was observed. BCVA achieved 20/200 and 20/400, respectively. The findings in this paper indicate that Ruthenium-106 plaque therapy is effective in treatment of diffuse choroidal hemangiomas associated with SWS. PMID:22606475

  15. Grossly calcified choroid plexus concealing foramen of Monro meningiomas as an unusual cause of obstructive hydrocephalus

    PubMed Central

    Kawaguchi, Tomohiro; Fujimura, Miki; Tominaga, Teiji

    2016-01-01

    Various intraventricular tumors can present with calcifications; however, the choroid plexus can also have physiological calcifications. This is the first case report of meningiomas located at the bilateral foramen of Monro (FOM), concealed by a grossly calcified choroid plexus, presenting with obstructive hydrocephalus. A 60-year-old woman with disturbed consciousness was admitted by ambulance. Head computed tomography revealed significantly high-density lesions that smoothly extended from the choroid plexus of the lateral ventricles to the third ventricle. They occupied both sides of the FOM, resulting in obstructive hydrocephalus. The diagnostic endoscopic biopsy was performed using a flexible neuroendoscopic system, and an egg shell-like grossly calcified choroid plexus was found to smoothly extend toward the FOM. Resection was not selected because the calcified lesions had tightly adhered to the veins and fornix; therefore, the patient underwent ventriculo-peritoneal shunting. The lesions were histologically identified as psammomatous meningiomas with low proliferation potential (the Ki-67 labeling index was lower than 1%). She was discharged 10 days after surgery without neurological deficits. As calcifications can have tumoral and nontumoral origins, we considered neuroendoscopic exploration to be essential in order to achieve an accurate diagnosis and select optimal management. PMID:26889294

  16. Extensive choroidal infarction in a case of mixed essential cryoglobulinaemia in a postpartum female.

    PubMed

    Takkar, Brijesh; Azad, Shorya Vardhan; Kumar, Uma; Venkatesh, Pradeep

    2016-01-01

    A case of mixed essential cryoglobulinaemia resulting in massive choroidal infarction and irreversible vision loss in a postpartum female is discussed. Cryoglobulinaemia can rarely involve ocular vessels and, in this case, was adjunctive to mild hypertension in causing acute choroidopathy. Although the systemic condition of the patient improved after steroids and immunosuppressive agents, the visual loss was permanent. PMID:27637276

  17. [Ultrastructure of melanocytes from retina and choroid of the Pacific salmon].

    PubMed

    Zagal'skaia, E O

    2001-01-01

    The ultrastructure of the retina and choroid cells in three species of the Pacific salmon, Oncohrynchus gorbuscha, O. keta and O. masou, was studied. The structure of retina pigment cells is similar in all the three species, only a small difference was found in the percentage of lengthened and rounded forms of melanosomes. Melanocytes of the masu salmon differ also in the structure of their nuclei. The pigment cells of choroid differ from those of retina by a more extended form of melanosomes and by the presence of less rounded melanosomes. In the chum salmon retina we found electron lucent "contact vesicles", whose assignment is open to discussion. In retina pigment cells of the masu salmon smolts ready for migration, the activity of Golgi appararus rises, mitochondria and mature melanosomes increase in number. The choroid pigment cells are slightly swollen, their processes more often and deeper penetrate into the walls of vessels, down to the endothelium. Results of the experiment with the application of an artificial magnetic field (AMF) have shown that the retina and choroid pigment cells in the masu salmon fry react to the field of a certain direction. The phenomenon of magnetosensitivity of pigment cells is discussed in addition to their possible involvement in magnetoreception.

  18. The Impact of Chronic Tobacco Smoking on Retinal and Choroidal Thickness in Greek Population

    PubMed Central

    Moschos, Marilita M.; Nitoda, Eirini; Laios, Konstantinos; Ladas, Dimitrios S.; Chatziralli, Irini P.

    2016-01-01

    Aim. To investigate the effect of more than 25-year cigarette smoking on choroidal and retinal thickness, using spectral domain optical coherence tomography (SD-OCT). Methods. Thirty-one smokers and 25 age- and sex-matched nonsmokers, serving as control group, were submitted to slit-lamp biomicroscopy and dilated fundoscopy, SD-OCT, measurements of intraocular pressure (IOP), central corneal thickness (CCT), and axial length (AL). Heidelberg Spectralis was used to calculate choroidal thickness (CT), ganglion cell complex (GCC), outer retina layers (ORL), and macular thicknesses (MT). Results. The smokers' group consisted of 17 males and 14 females with mean age of 57.8 ± 4.5 years, while the controls' group consisted of 14 males and 11 females with mean age of 68.0 ± 4.1 years. CT and GCC thicknesses were significantly reduced in smokers compared to control group. The differences in thicknesses of ORL were marginally significant between two groups. The measurements of MT, IOP, CCT, and AL had the same distributions between smokers and nonsmokers. Conclusions. Tobacco smoking seems to result in thinner choroid and retina compared to nonsmokers. This is the first study in literature that investigates the anatomical effect of smoking for more than 25 years on the choroid and retina. PMID:26885247

  19. Multimodal Imaging Evaluations of Focal Choroidal Excavations in Eyes with Central Serous Chorioretinopathy

    PubMed Central

    Chen, Zhi-Qing; Wang, Wei

    2016-01-01

    Purpose. To investigate the prevalence and characteristics of focal choroidal excavation (FCE) concurrent with central serous chorioretinopathy (CSC)