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Sample records for ocular choroidal neovascularization

  1. Choroidal neovascularization secondary to ocular penetration during retrobulbar anesthesia and its treatment

    PubMed Central

    Dikci, Seyhan; Yılmaz, Turgut; Gök, Zarife Ekici; Demirel, Soner; Genç, Oğuzhan

    2017-01-01

    Retrobulbar anesthesia is still used before ocular surgery; however, it has various complications including ocular penetration. The penetration/perforation of the globe can cause complications such as endophthalmitis, retinal detachment, and scotoma. Choroidal neovascularization (CNV) is rarely seen, following choroidal rupture in penetrating eye injuries. Here, we present a patient who underwent a pars plana vitrectomy for vitreous hemorrhage secondary to ocular penetration during a retrobulbar injection for cataract surgery. This patient later developed CNV at the penetration site during follow-up. Physicians should remember that CNV can occur as an unusual late complication of ocular penetration during retrobulbar anesthesia.

  2. Multiple Intravitreal Ranibizumab Injections for Persistant Choroidal Neovascularization Associated with Presumed Ocular Histoplasmosis Syndrome

    PubMed Central

    Yılmaz, Turgut; Dikci, Seyhan; Genç, Oğuzhan; Mutlu, Kayhan

    2017-01-01

    Presumed ocular histoplasmosis syndrome (POHS) is a clinical entity that is characterized by small, round, discrete, macular or mid peripheral atrophic (punched out) chorioretinal lesions (histo spots), peripapillary scarring, choroidal neovascularization (CNV), and the absence of anterior uveitis and vitritis. Diagnosis of this disorder is based upon characteristic clinical findings and a positive histoplasmin skin test or residence in an endemic region for Histoplasma capsulatum. There is no active systemic disease during diagnosis of POHS. Disciform scarring and macular CNV secondary to POHS is a well-known complication which leads to loss of visual acuity or visual disturbance. Without therapy, the visual prognosis in these patients is unfavorable. Submacular surgery, radiation, steroids, photodynamic therapy, and most recently anti-vascular endothelial growth factor therapy are current therapeutic options for this condition. We report a case with persistent CNV secondary to POHS in a middle-aged woman with moderate myopia and the clinical course of treatment with multiple intravitreal ranibizumab (Lucentis®, Novartis) injections.

  3. 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

  4. Topical ocular delivery to laser-induced choroidal neovascularization by dual internalizing RGD and TAT peptide-modified nanoparticles

    PubMed Central

    Chu, Yongchao; Chen, Ning; Yu, Huajun; Mu, Hongjie; He, Bin; Hua, Hongchen; Wang, Aiping; Sun, Kaoxiang

    2017-01-01

    A nanoparticle (NP) was developed to target choroidal neovascularization (CNV) via topical ocular administration. The NPs were prepared through conjugation of internalizing arginine-glycine-aspartic acid RGD (iRGD; Ac-CCRGDKGPDC) and transactivated transcription (TAT) (RKKRRQRRRC) peptide to polymerized ethylene glycol and lactic-co-glycolic acid. The iRGD sequence can specifically bind with integrin αvβ3, while TAT facilitates penetration through the ocular barrier. 1H nuclear magnetic resonance and high-performance liquid chromatography demonstrated that up to 80% of iRGD and TAT were conjugated to poly(ethylene glycol)– poly(lactic-co-glycolic acid). The resulting particle size was 67.0±1.7 nm, and the zeta potential of the particles was −6.63±0.43 mV. The corneal permeation of iRGD and TAT NPs increased by 5.50- and 4.56-fold compared to that of bare and iRGD-modified NPs, respectively. Cellular uptake showed that the red fluorescence intensity of iRGD and TAT NPs was highest among primary NPs and iRGD- or TAT-modified NPs. CNV was fully formed 14 days after photocoagulation in Brown Norway (BN) rats as shown by optical coherence tomography and fundus fluorescein angiography analyses. Choroidal flat mounts in BN rats showed that the red fluorescence intensity of NPs followed the order of iRGD and TAT NPs > TAT-modified NPs > iRGD-modified NPs > primary NPs. iRGD and TAT dual-modified NPs thus displayed significant targeting and penetration ability both in vitro and in vivo, indicating that it is a promising drug delivery system for managing CNV via topical ocular administration. PMID:28260884

  5. Perspectives of choroidal neovascularization therapy.

    PubMed

    Caputo, M; Zirpoli, H; Di Benedetto, R; De Nadai, K; Tecce, M F

    2011-02-01

    Vision loss secondary to Choroidal Neovascularization (CNV) is becoming a major disease condition in developed world. CNV is typically secondary to Age-related Macular Degeneration (AMD) and these conditions are major, and also substantially increasing, causes of blindness among aged people. Several therapeutic options are currently available to treat CNV with variable efficacy on disease progress. Among existing treatments there are laser photocoagulation, photodynamic therapies, local corticosteroids and, more recently, the use of anti-angiogenic factors. Although by these treatments very effective results are obtained and their further improvement is still possible, it is also reasonable and necessary to look for more successful and definitive alternatives. The research in this direction is already very active and it can be expected that applications of the more recent molecular technologies will bring important advances also for CNV. These will likely regard the use of gene therapy and of new target specific factors. Gene therapies methodologies are rapidly becoming closer to current clinical use and, since the eye is a particularly favourable organ for drug delivery, their ocular use is probably going to be among the first successful applications of these techniques. In addition to its specific technology, gene therapy requires the knowledge of specific genes to be modulated to adequately affect pathogenesis and progression of the disease in which has to be applied. This will also be true for the use of novel target specific drugs such as antibodies and other molecules able to affect cellular factors and pathways also related to disease development. For this reason, a major direction of future CNV therapies will be the identification of specific gene, gene products, metabolic pathways and metabolites related to the disease. This information, in addition to be suitable for gene and target specific therapies, will also allow the development of new procedures to

  6. Inflammatory choroidal neovascular membrane after healed tuberculous choroidal granuloma

    PubMed Central

    Lodhi, Sikander A. K.; Saifuddin, Khadija; Devulapally, Santhosh

    2017-01-01

    Objective: To present a case of choroidal granuloma masquerading as intraocular tumor that healed on anti-tuberculous treatment but led to the development of inflammatory choroidal neovascular membrane (CNVM). Method: A 42-year-old female patient with past history of hysterectomy presented with diminution of vision in the right eye. Fundus examination in the right eye showed a yellowish white choroidal mass with associated bullous retinal detachment superotemporal to fovea. Left eye fundus was normal. Fundus flourescein angiography showed early and late hyperflourescence with late pooling in serous detachments. Complete systemic evaluation did not yield a clue to diagnosis. Positron emission tomography scan (PET scan) showed enlarged lymph nodes in cervical, mediastinal and peritoneal regions. Lymph node biopsy showed caseating granulomas. Results: The granuloma subsided and a scar formed 5 months after starting anti-tuberculous treatment with improvement in vision. Six months later, the vision deteriorated again with the development of a choroidal neovascular membrane (CNVM) at the margin of the scar. The CNVM resolved and all the signs of activity subsided after giving intravitreal antivascular endothelial growth factor (anti-VEGF) injections. Conclusions: Making a diagnosis of tuberculous granuloma in a case of choroidal mass lesion is a challenge. PET scan helps in identifying metabolically active lymph nodes appropriate for biopsy. Healed scars of tuberculous choroid lesions should be followed closely to detect the development of CNVM. PMID:28293535

  7. CCR3 and choroidal neovascularization.

    PubMed

    Li, Yiwen; Huang, Deqiang; Xia, Xin; Wang, Zhengying; Luo, Lingyu; Wen, Rong

    2011-02-15

    Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly in industrialized countries. The "wet" AMD, characterized by the development of choroidal neovacularization (CNV), could result in rapid and severe loss of central vision. The critical role of vascular endothelial growth factor A (VEGF-A) in CNV development has been established and VEGF-A neutralization has become the standard care for wet AMD. Recently, CCR3 was reported to play an important role in CNV development and that CCR3 targeting was reported to be superior to VEGF-A targeting in CNV suppression. We investigated the role of CCR3 in CNV development using the Matrigel induced CNV and found that in both rats and mice, CNV was well-developed in the control eyes as well as in eyes treated with CCR3 antagonist SB328437 or CCR3 neutralizing antibodies. No statistically significant difference in CNV areas was found between the control and SB328437 or CCR3-ab treated eyes. Immunostaining showed no specific expression of CCR3 in or near CNV. In contrast, both VEGF-A neutralizing antibodies and rapamycin significantly suppressed CNV. These results indicate that CCR3 plays no significant role in CNV development and question the therapeutic approach of CCR3 targeting to suppress CNV. On the other hand, our data support the therapeutic strategies of VEGF-A and mTOR (mammalian target of rapamycin) targeting for CNV.

  8. Risk of choroidal neovascularization among the uveitides

    PubMed Central

    Baxter, Sally L.; Pistilli, Maxwell; Pujari, Siddharth S.; Liesegang, Teresa L.; Suhler, Eric B.; Thorne, Jennifer E.; Foster, C. Stephen; Jabs, Douglas A.; Levy-Clarke, Grace A.; Nussenblatt, Robert B.; Rosenbaum, James T.; Kempen, John H.

    2013-01-01

    Purpose To evaluate the risk, risk factors, and visual impact of choroidal neovascularization (CNV) in uveitis cases. Design Retrospective cohort study Methods Standardized medical record review at five tertiary centers. Results Among 15,137 uveitic eyes (8,868 patients), CNV was rare in the cases of anterior or intermediate uveitis. Among the 4,041 eyes (2,307 patients) with posterior or panuveitis, 81 (2.0%) presented with CNV. Risk factors included posterior uveitis in general and specific uveitis syndromes affecting the outer retina/retinal pigment epithelium (RPE)/choroid interface. Among the 2,364 eyes (1,357 patients) with posterior or panuveitis and free of CNV at the time of cohort entry, the cumulative two-year incidence of CNV was 2.7% (95% confidence interval (95%CI): 1.8-3.5%). Risk factors for incident CNV included currently active inflammation (adjusted HR [aHR] 2.13, 95%CI: 1.26-3.60), preretinal neovascularization (aHR 3.19, 95%CI: 1.30-7.80), and prior diagnosis of CNV in the contralateral eye (aHR 5.79, 95%CI: 2.77-12.09). Among specific syndromes, the incidence was greater in Vogt-Koyanagi-Harada Syndrome (aHR 3.37, 95%CI: 1.52-7.46), and punctate inner choroiditis (aHR 8.67, 95%CI: 2.83-26.54). Incident CNV was associated with two lines’ loss of visual acuity (+0.19 logMAR units, 95%CI: 0.079–0.29) from the preceding visit. Conclusions CNV is an uncommon complication of uveitis associated with visual impairment, which more commonly occurs in forms affecting the outer retina/RPE/choroid interface, during periods of inflammatory activity, in association with preretinal neovascularization, and in second eyes of patients with unilateral CNV. Because CNV is treatable, a systematic approach to early detection in high-risk patients may be appropriate. PMID:23795984

  9. Choroidal detachment and ocular hypotony: CT evaluation

    SciTech Connect

    Mafee, M.F.; Peyman, G.A.

    1984-12-01

    The computed tomographic (CT) findings in 20 patients with hemorrhagic choroidal detachment, serous choroidal detachment and/or ocular hypotony are described. Hemorrhagic choroidal detachment appeared as an area of high attenuation that was usually localized, uniformly hyperdense, and not position-dependent. Serous choroidal detachment appeared as a convex, thick line of increased density within the vitreous cavity. Inflammatory choroidal detachment produces a diffuse intrauveal and suprachoroidal accumulation of high-density, position-dependent fluid, and uveoscleral thickening and enhancement, which in cross section resembles a ring. CT has proved valuable in localizing and differentiating serous or hemorrhagic choroidal detachment and uveoscleral infolding.

  10. A Simple Optical Coherence Tomography Quantification Method for Choroidal Neovascularization

    PubMed Central

    Sulaiman, Rania S.; Quigley, Judith; Qi, Xiaoping; O'Hare, Michael N.; Grant, Maria B.; Boulton, Michael E.

    2015-01-01

    Abstract Purpose: Therapeutic efficacy is routinely assessed by measurement of lesion size using flatmounted choroids and confocal microscopy in the laser-induced choroidal neovascularization (L-CNV) rodent model. We investigated whether optical coherence tomography (OCT) quantification, using an ellipsoid volume measurement, was comparable to standard ex vivo evaluation methods for this model and whether this approach could be used to monitor treatment-related lesion changes. Methods: Bruch's membrane was ruptured by argon laser in the dilated eyes of C57BL/6J mice, followed by intravitreal injections of anti-VEGF164 or vehicle, or no injection. In vivo OCT images were acquired using Micron III or InVivoVue systems at 7, 10, and/or 14 days post-laser and neovascular lesion volume was calculated as an ellipsoid. Subsequently, lesion volume was compared to that calculated from confocal Z-stack images of agglutinin-stained choroidal flatmounts. Results: Ellipsoid volume measurement of orthogonal 2-dimensional OCT images obtained from different imaging systems correlated with ex vivo lesion volumes for L-CNV (Spearman's ρ=0.82, 0.75, and 0.82 at days 7, 10, and 14, respectively). Ellipsoid volume calculation allowed temporal monitoring and evaluation of CNV lesions in response to antivascular endothelial growth factor treatment. Conclusions: Ellipsoid volume measurements allow rapid, quantitative use of OCT for the assessment of CNV lesions in vivo. This novel method can be used with different OCT imaging systems with sensitivity to distinguish between treatment conditions. It may serve as a useful adjunct to the standard ex vivo confocal quantification, to assess therapeutic efficacy in preclinical models of CNV, and in models of other ocular diseases. PMID:26060878

  11. Treatment of choroidal neovascularization in high myopia.

    PubMed

    Montero, Javier A; Ruiz-Moreno, Jose M

    2010-05-01

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

  12. Optical Coherence Tomography Angiography Study of Choroidal Neovascularization Associated With Focal Choroidal Excavation.

    PubMed

    Chawla, Rohan; Mittal, Kanhaiya; Vohra, Rajpal

    2016-10-01

    The authors report the use of optical coherence tomography angiography (OCTA) (DRI OCT Triton; Topcon, Tokyo, Japan) to localize, characterize, and confirm the presence of a choroidal neovascular membrane in a patient of focal choroidal excavation (FCE) with recent-onset metamorphopsia and visual blurring. En face OCTA images just above the level of the retinal pigment epithelium-Bruch's membrane complex typically showed the presence of a glomerulus-like neovascular network with an adjacent dark area suggestive of a Type 2 choroidal neovascularization (CNV). OCTA was found to be a very useful, noninvasive, and quick imaging modality to detect secondary CNV formation in a case of FCE. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:969-971.].

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

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  14. 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

  15. Retinal and choroidal neovascularization in a transgenic mouse model of sickle cell disease.

    PubMed Central

    Lutty, G. A.; McLeod, D. S.; Pachnis, A.; Costantini, F.; Fabry, M. E.; Nagel, R. L.

    1994-01-01

    A complication of sickle cell disease is proliferative retinopathy. We investigated the eyes from a transgenic mouse model of sickle cell disease (alpha H beta S[beta MDD] type) to determine if pathological changes occurred in their retinas and choroids. One retina from each animal was processed by flat-embedding adenosine diphosphatase-reacted retinas in glycol methacrylate. The fellow eye from each animal was embedded whole in glycol methacrylate for histopathological analysis of all ocular structures. Retinal vascular occlusions resulted in nonperfused areas of retina and arterio-venous anastomoses. Intra- and extraretinal neovascularization was observed adjacent to nonperfused areas. Retinal pigmented lesions were formed by the migration of retinal pigment epithelial cells into sensory retina, often ensheathing choroidal neovascularization. The incidence of this bilateral chorioretinopathy was 30% in animals older than 15 months of age. The ocular histopathological changes we observed in the mouse model mimicked many aspects of human proliferative sickle cell retinopathy. Furthermore, this is the first genetically derived animal model for chorio-retinal neovascularization. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7519831

  16. CD200R signaling inhibits pro-angiogenic gene expression by macrophages and suppresses choroidal neovascularization

    PubMed Central

    Horie, Shintaro; Robbie, Scott J.; Liu, Jian; Wu, Wei-Kang; Ali, Robin R.; Bainbridge, James W.; Nicholson, Lindsay B.; Mochizuki, Manabu; Dick, Andrew D.; Copland, David A.

    2013-01-01

    Macrophages are rapidly conditioned by cognate and soluble signals to acquire phenotypes that deliver specific functions during inflammation, wound healing and angiogenesis. Whether inhibitory CD200R signaling regulates pro-angiogenic macrophage phenotypes with the potential to suppress ocular neovascularization is unknown. CD200R-deficient bone marrow derived macrophages (BMMΦ) were used to demonstrate that macrophages lacking this inhibitory receptor exhibit enhanced levels of Vegfa, Arg-1 and Il-1β when stimulated with PGE2 or RPE-conditioned (PGE2-enriched) media. Endothelial tube formation in HUVECs was increased when co-cultured with PGE2-conditioned CD200R−/− BMMΦ, and laser-induced choroidal neovascularization was enhanced in CD200R-deficient mice. In corroboration, signaling through CD200R results in the down-regulation of BMMΦ angiogenic and pro-inflammatory phenotypes. Translational potential of this pathway was investigated in the laser-induced model of choroidal neovascularization. Local delivery of a CD200R agonist mAb to target myeloid infiltrate alters macrophage phenotype and inhibits pro-angiogenic gene expression, which suppresses pathological angiogenesis and CNV development. PMID:24170042

  17. Optical coherence tomography angiography in pediatric choroidal neovascularization

    PubMed Central

    Veronese, Chiara; Maiolo, Chiara; Huang, David; Jia, Yali; Armstrong, Grayson W.; Morara, Mariachiara; Ciardella, Antonio P.

    2016-01-01

    Purpose To report two cases of pediatric choroidal neovascularization (CNV) and the associated neo-vascular and retinal findings identified on Optical Coherence Tomography Angiography (OCTA) imaging. Methods A 14-year-old boy with handheld laser-induced maculopathy-related CNV and a 13-year-old boy with idiopathic CNV were evaluated with visual acuity testing, slit-lamp exam, fundus photography, fluorescein angiography, indocyanine green angiography, spectral domain optical coherence tomography, and OCTA. Results Macular CNV were identified in both pediatric patients using OCTA imaging. The first case demonstrated a classic pediatric type II CNV with a “tree-like” pattern and a single vessel in-growth site, while the second case demonstrated a type I CNV with a “glomerular” pattern. Conclusion Distinct choroidal neovascular patterns were visualized in these two cases of pediatric CNV when compared to adult subtypes. OCTA is a noninvasive imaging modality capable of evaluating and characterizing pediatric CNV and their associated vascular patterns. PMID:27990495

  18. 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.

  19. Improved assessment of laser-induced choroidal neovascularization.

    PubMed

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

    2010-12-01

    The primary objective of this study was to develop and evaluate new methods of analyzing laser-induced choroidal neovascularization (CNV), in order to make recommendations for improving the reporting of experimental CNV in the literature. Six laser burns of sufficient power to rupture Bruch's membrane were concentrically placed in each eye of 18 adult Norway rats. Eyes received intravitreal injections of either triamcinolone acetonide, ketorolac, or balanced salt solution (BSS). Fluorescein angiography (FA) was performed 2 and 3 weeks after injection, followed by choroidal flat mount preparation. Vascular leakage on FAs and vascular budding on choroidal mounts were quantified by measuring either the cross-sectional area of each CNV lesion contained within the best-fitting polygon using Adobe Photoshop (Lasso Technique or Quick Selection Technique), or the area of bright pixels within a lesion using Image-Pro Plus. On choroidal mounts, the Lasso Technique and Image-Pro Plus detected a significant difference in lesion size between either ketorolac or triamcinolone when compared to BSS, while the Quick Selection Technique did not (Lasso Technique, 0.78 and 0.64; Image-Pro Plus, 0.77 and 0.65). On FA, the Lasso Technique and Quick Selection Technique detected a significant difference in lesion size between either ketorolac or triamcinolone when compared to BSS, while Image-Pro Plus did not (Lasso Tool, 0.81 and 0.54; Quick Selection Tool, 0.76 and 0.57). Choroidal mounts and FA are both valuable for imaging experimental CNV. Adobe Photoshop and Image-Pro Plus are both able to detect subtle differences in CNV lesion size, when images are not manipulated. The combination of choroidal mounts and FA provides a more comprehensive assessment of CNV anatomy and physiology.

  20. Long-term remission of myopic choroidal neovascular membrane after treatment with ranibizumab: a case report

    PubMed Central

    2009-01-01

    Introduction Myopia has become a big public health problem in certain parts of the world. Sight-threatening complications like choroidal neovascularisation membranes occur in up to 10% of pathological myopia, and natural history studies show a trend towards progressive visual loss. There are long-term financial and quality-of-life implications in this group of patients, and treatment strategies should aim for long-term preservation of vision. Case presentation A 56-year-old Caucasian woman presented with a best-corrected visual acuity of 6/6-1 in her right eye and 6/24 in her left. Fundal examination revealed pathological myopia in both eyes and an elevated lesion associated with pre-retinal haemorrhage in the left macula. Ocular coherence tomography and fundus fluorescein angiogram confirmed a subfoveal classic choroidal neovascularisation membrane. The patient decided to proceed with intravitreal ranibizumab (0.5 mg) therapy. One month after treatment, best-corrected visual acuity improved to 6/12 in her left eye, with complete resolution subretinal fluid on ocular coherence tomography. After three months, best-corrected visual acuity further improved to 6/9, which was maintained up to 16 months post-treatment. Conclusion We suggest intravitreal ranibizumab as an alternative treatment for long-term remission of myopic choroidal neovascular membrane. It also suggests that myopic choroidal neovascularisation membranes may require fewer treatments to achieve sustained remission. Furthermore, this could serve as a feasible long-term management option if used in conjunction with ocular coherence tomography. PMID:19946560

  1. A Mouse Model for Laser-induced Choroidal Neovascularization.

    PubMed

    Shah, Ronil S; Soetikno, Brian T; Lajko, Michelle; Fawzi, Amani A

    2015-12-27

    The mouse laser-induced choroidal neovascularization (CNV) model has been a crucial mainstay model for neovascular age-related macular degeneration (AMD) research. By administering targeted laser injury to the RPE and Bruch's membrane, the procedure induces angiogenesis, modeling the hallmark pathology observed in neovascular AMD. First developed in non-human primates, the laser-induced CNV model has come to be implemented into many other species, the most recent of which being the mouse. Mouse experiments are advantageously more cost-effective, experiments can be executed on a much faster timeline, and they allow the use of various transgenic models. The miniature size of the mouse eye, however, poses a particular challenge when performing the procedure. Manipulation of the eye to visualize the retina requires practice of fine dexterity skills as well as simultaneous hand-eye-foot coordination to operate the laser. However, once mastered, the model can be applied to study many aspects of neovascular AMD such as molecular mechanisms, the effect of genetic manipulations, and drug treatment effects. The laser-induced CNV model, though useful, is not a perfect model of the disease. The wild-type mouse eye is otherwise healthy, and the chorio-retinal environment does not mimic the pathologic changes in human AMD. Furthermore, injury-induced angiogenesis does not reflect the same pathways as angiogenesis occurring in an age-related and chronic disease state as in AMD. Despite its shortcomings, the laser-induced CNV model is one of the best methods currently available to study the debilitating pathology of neovascular AMD. Its implementation has led to a deeper understanding of the pathogenesis of AMD, as well as contributing to the development of many of the AMD therapies currently available.

  2. 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

  3. RAGE Regulates Immune Cell Infiltration and Angiogenesis in Choroidal Neovascularization

    PubMed Central

    McVicar, Carmel; Ward, Michael; Colhoun, Liza; Quinn, Michael; Bierhaus, Angelika; Xu, Heping; Stitt, Alan W.

    2014-01-01

    Purpose RAGE regulates pro-inflammatory responses in diverse cells and tissues. This study has investigated if RAGE plays a role in immune cell mobilization and choroidal neovascular pathology that is associated with the neovascular form of age-related macular degeneration (nvAMD). Methods RAGE null (RAGE−/−) mice and age-matched wild type (WT) control mice underwent laser photocoagulation to generate choroidal neovascularization (CNV) lesions which were then analyzed for morphology, S100B immunoreactivity and inflammatory cell infiltration. The chemotactic ability of bone marrow derived macrophages (BMDMs) towards S100B was investigated. Results RAGE expression was significantly increased in the retina during CNV of WT mice (p<0.001). RAGE−/− mice exhibited significantly reduced CNV lesion size when compared to WT controls (p<0.05). S100B mRNA was upregulated in the lasered WT retina but not RAGE−/− retina and S100B immunoreactivity was present within CNV lesions although levels were less when RAGE−/− mice were compared to WT controls. Activated microglia in lesions were considerably less abundant in RAGE−/− mice when compared to WT counterparts (p<0.001). A dose dependent chemotactic migration was observed in BMDMs from WT mice (p<0.05–0.01) but this was not apparent in cells isolated from RAGE−/− mice. Conclusions RAGE-S100B interactions appear to play an important role in CNV lesion formation by regulating pro-inflammatory and angiogenic responses. This study highlights the role of RAGE in inflammation-mediated outer retinal pathology. PMID:24586862

  4. Suppression of Experimental Choroidal Neovascularization by Curcumin in Mice

    PubMed Central

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

    2012-01-01

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

  5. Ocular Sarcoidosis Limited to Retinal Vascular Ischemia and Neovascularization

    PubMed Central

    Dyer, Gawain; Shaikh, Saad

    2016-01-01

    A 59-year-old Caucasian male experienced progressive vision loss secondary to retinal vascular ischemia and neovascularization. At no time did he present with uveitis or vasculitis, and his serology tests were all negative. He was soon after diagnosed with sarcoidosis by hilar lymph node lung biopsy. Our patient demonstrates an atypical presentation of ocular sarcoidosis, manifesting solely as neovascularization and retinal vascular ischemia. Ophthalmologists should consider proliferative sarcoid retinopathy in patients with neovascularization. PMID:27928517

  6. Attenuation of Choroidal Neovascularization by Histone Deacetylase Inhibitor

    PubMed Central

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

    2015-01-01

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

  7. Segmentation of choroidal neovascularization in fundus fluorescein angiograms.

    PubMed

    Abdelmoula, Walid M; Shah, Syed M; Fahmy, Ahmed S

    2013-05-01

    Choroidal neovascularization (CNV) is a common manifestation of age-related macular degeneration (AMD). It is characterized by the growth of abnormal blood vessels in the choroidal layer causing blurring and deterioration of the vision. In late stages, these abnormal vessels can rupture the retinal layers causing complete loss of vision at the affected regions. Determining the CNV size and type in fluorescein angiograms is required for proper treatment and prognosis of the disease. Computer-aided methods for CNV segmentation is needed not only to reduce the burden of manual segmentation but also to reduce inter- and intraobserver variability. In this paper, we present a framework for segmenting CNV lesions based on parametric modeling of the intensity variation in fundus fluorescein angiograms. First, a novel model is proposed to describe the temporal intensity variation at each pixel in image sequences acquired by fluorescein angiography. The set of model parameters at each pixel are used to segment the image into regions of homogeneous parameters. Preliminary results on datasets from 21 patients with Wet-AMD show the potential of the method to segment CNV lesions in close agreement with the manual segmentation.

  8. Inhibitory role of adiponectin peptide I on rat choroidal neovascularization

    PubMed Central

    Lyzogubov, Valeriy V.; Tytarenko, Ruslana G.; Bora, Nalini S.; Bora, Puran S.

    2013-01-01

    Age-related macular degeneration (AMD) is a leading cause of central blindness in elderly population. Wet type of AMD is characterized by extensive growth of new vessels. One of the effective strategies to treat wet AMD is to limit the choroidal neovascularization (CNV). We studied effect of adiponectin peptide I (APNpI) on new vessel growth in laser-induced rat model of wet AMD and on rat choroidal endothelial cell (CEC) culture. CNV size and vessel density was investigated by microscopy. Immunohistochemical staining (IHC) for Von Willebrand Factor (vWF), APN, APN receptors 1 (AdipoR1), 2 (AdipoR2), VEGF, VEGF receptor 2 (VEGF-R2), proliferating cell nuclear antigen (PCNA) was performed in CNV area. The mRNA expression of VEGF and VEGF-R2 in RPE-choroid was investigated by RT-PCR and real-time PCR. APNpI inhibited area of CNV by 4 fold, number of vWF positive vessels by 99% and area of subretinal tissue by 40%. The expression of VEGF and VEGF-R2 at mRNA and protein levels were decreased after APNpI treatment in vivo. Proliferative index (PCNA) was 5 fold less in laser spots of APNpI treated rats compared to controls. In conclusion, APNpI inhibited formation of new vessels in rat model of CNV by decreasing VEGF, VEGF-R2 expression and cell proliferation. Thus, APNpI may have potential therapeutic use for AMD treatment since it significantly inhibited CNV. PMID:22633972

  9. Spontaneous Regression of Choroidal Neovascularization in a Patient with Pattern Dystrophy

    PubMed Central

    Goleni, Flamur; Livir-Rallatos, Gerasimos; Livir-Rallatos, Charalampos; Zafirakis, Panagiotis; Allen Fishman, Gerald

    2016-01-01

    Purpose. To present a case of a patient with pattern dystrophy (PD) associated choroidal neovascularization (CNV) that resolved spontaneously without treatment. Methods. A 69-year-old male patient was referred to our unit, for evaluation of a recent visual loss (metamorphopsias) in his left eye. Fundus examination, fundus autofluorescence imaging, and fluorescein angiography showed a choroidal neovascular membrane in his left eye. Since visual acuity was satisfactory the patient elected observation. Clinical examination and OCT testing were repeated at 6 and 12 months after presentation. Results. Visual acuity remained stable at the level of 0.9 (baseline BCVA) during the follow-up period (12 months). Repeat OCT testing showed complete spontaneous regression of the choroidal neovascular membrane without evidence of intra- or subretinal fluid in both follow-up visits. Conclusions. Spontaneous regression of choroidal neovascularization can occur in patients with retinal dystrophies and associated choroidal neovascular membranes. The decision to treat or observe these patients relies strongly on the presenting visual acuity, since, in isolated instances, spontaneous resolution of choroidal neovascularization may occur. PMID:27847664

  10. 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

  11. Idiopathic polypoidal choroidal vasculopathy in Thai patients with clinical and angiographic choroidal neovascularization

    PubMed Central

    Bhoomibunchoo, Chavakij; Yospaiboon, Yosanan; Thoongsuwan, Somanus; Rojanaporn, Duangnate; Watanachai, Nawat; Jirarattanasopa, Pichai; Wongcumchang, Nattapon; Amphornphruet, Atchara; Vongkulsiri, Sritatath; Arayangkoon, Eakkachai

    2017-01-01

    Objective This study aimed to study the prevalence and characteristics of idiopathic polypoidal choroidal vasculopathy (IPCV) in Thai patients with clinical and angiographic choroidal neovascularization (CNV). Patients and methods A consecutive case study of 140 patients presenting with CNV was conducted in nine large referral eye centers throughout Thailand. The demographic data, fundus photographs, fundus fluorescein angiography and indocyanine green angiography of the patients were analyzed. Results Of 129 patients with clinical and angiographic CNV, IPCV was diagnosed in 100 patients (77.52%), idiopathic CNVs in 16 patients (12.40%) and age-related macular degeneration (AMD) in 12 patients (9.30%). Of the 107 eyes with IPCV, 90 eyes (84.11%) had both branching venous networks (BVNs) and polypoidal lesions. Most IPCV patients (93%) had unilateral involvement and were at a younger age than AMD patients. In all, 79 eyes (73.83%) had lesions found in the macular area, 14 eyes (13.08%) in the temporal to vascular arcades, ten eyes (9.35%) in the peripapillary area and four eyes (3.74%) in both macular and peripapillary areas. The clinical manifestations of IPCV at presentation were categorized into two patterns. There were 95 eyes (88.79%) of a hemorrhagic pattern and 12 eyes (11.21%) of an exudative pattern. Conclusion IPCV is the most common macular disease in Thai patients with CNV. Most IPCVs have both BVNs and polypoidal lesions located in the macular area and present with a hemorrhagic pattern. PMID:28223776

  12. Objective Area Measurement Technique for Choroidal Neovascularization from Fluorescein Angiography

    PubMed Central

    Guthrie, Micah J.; Osswald, Christian R.; Valio, Nicole L.; Mieler, William F.; Kang-Mieler, Jennifer J.

    2014-01-01

    The purpose of this study was to develop a non-biased method of quantitatively measuring choroidal neovascularization (CNV) areas based on late-phase fluorescein angiography (FA) images. Experimental CNV was induced in Long Evans rats by laser disruption of the Bruch’s membrane. FA was performed weekly for 5 weeks. Multi-Otsu thresholding (MOT) was used to quantify CNV in late-phase FA images from both experimental rodent CNV and wet age-related macular degeneration patients (wAMD). Images were automatically thresholded into three levels based on the image histogram, with the highest level containing CNV. To determine the technique’s ability to quantify CNV areas, rats were given either triamcinolone acetonide or dexamethasone sodium phosphate to treat CNV and compared to untreated rats. The rat CNV lesion areas measured from 5-week histology sections from each treatment group were compared to areas measured from the corresponding FA images. MOT was able to detect statistical decreases in rodent CNV area in the treatment groups versus control from weeks 3 through 5. The ratio of CNV area measured from histology to area measured from FA images was not statistically different between groups. Finally, to determine the usefulness of MOT on pathological morphologies of CNV, MOT was performed on late-phase FA images from patients with classic and diffuse CNV. The technique was able to segment classical CNV in wAMD patients, but performed poorly with diffuse CNV. MOT provides a robust, objective, and quantifiable area measurement of CNV lesion area in both experimentally-induced and pathological CNV. The results indicate that MOT could be a useful research tool in helping evaluate the effects of therapeutics on CNV growth. PMID:24316422

  13. 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

  14. Chorioretinal Coloboma Complications: Retinal Detachment and Choroidal Neovascular Membrane

    PubMed Central

    Hussain, Rehan M.; Abbey, Ashkan M.; Shah, Ankoor R.; Drenser, Kimberly A.; Trese, Michael T.; Capone, Antonio

    2017-01-01

    Purpose: To report the chorioretinal coloboma, and its association with increased risk of retinal detachment (RD) and choroidal neovascularization (CNV). Methods: This retrospective case series included eyes with chorioretinal coloboma diagnosed between 1995 and 2014 with a focus on RD and CNV as related complications. Cases of CNV were managed with laser photocoagulation or intravitreal injection of bevacizumab. For eyes with CNV, therapeutic success was defined as resolution of the subretinal hemorrhage on fundus examination and resolution of the subretinal and intraretinal fluid on optical coherence tomography (OCT). For eyes with RD, anatomic success following surgical intervention was defined as attachment of the retina at the last follow-up visit. Results: Fifty-one eyes of 31 patients with chorioretinal coloboma were identified for review. Bilateral chorioretinal coloboma was present in 64.5% of subjects. RD developed in 15 eyes (29.4%). Among 15 eyes with RD, 4 eyes (27%) had retinal breaks identified within the coloboma, 5 eyes (33%) had retinal breaks outside the coloboma, 2 eyes (13%) showed retinal breaks both inside and outside the coloboma, and in 4 eyes (27%) the causative retinal break was not localized. The overall rate of anatomic success after RD repair was 85.7%. CNV developed in 7 eyes (13.7%) and was located along the margin of the coloboma in all cases. CNV was bilateral in 2 of the 5 affected individuals (40%). Conclusion: RD and CNV were present in a high percentage of eyes with chorioretinal coloboma in these series. The frequent finding of retinal breaks outside the coloboma bed suggests that vitreoretinal interface abnormalities may play a role in development of RD in these eyes. PMID:28299000

  15. 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.

  16. Local Production of the Alternative Pathway Component Factor B Is Sufficient to Promote Laser-Induced Choroidal Neovascularization

    PubMed Central

    Schnabolk, Gloriane; Coughlin, Beth; Joseph, Kusumam; Kunchithapautham, Kannan; Bandyopadhyay, Mausumi; O'Quinn, Elizabeth C.; Nowling, Tamara; Rohrer, Bärbel

    2015-01-01

    Purpose. Complement factor B (CFB) is a required component of the alternative pathway (AP) of complement, and CFB polymorphisms are associated with age-related macular degeneration (AMD) risk. Complement factor B is made in the liver, but expression has also been detected in retina and retinal pigment epithelium (RPE)-choroid. We investigated whether production of CFB by the RPE can promote AP activation in mouse choroidal neovascularization (CNV). Methods. Transgenic mice expressing CFB under the RPE65 promoter were generated and crossed onto factor B-deficient (CFB-KO) mice. Biological activity was determined in vitro using RPE monolayers and in vivo using laser-induced CNV. Contribution of systemic CFB was investigated using CFB-KO reconstituted with CFB-sufficient serum. Results. Transgenic mice (CFB-tg) expressed CFB in RPE-choroid; no CFB was detected in serum. Cultured CFB-tg RPE monolayers secreted CFB apically and basally upon exposure to oxidative stress that was biologically active. Choroidal neovascularization sizes were comparable between wild-type and CFB-tg mice, but significantly increased when compared to lesions in CFB-KO mice. Injections of CFB-sufficient serum into CFB-KO mice resulted in partial reconstitution of systemic AP activity and significantly increased CNV size. Conclusions. Mouse RPE cells express and secrete CFB sufficient to promote RPE damage and CNV. This further supports that local complement production may regulate disease processes; however, the reconstitution experiments suggest that additional components may be sequestered from the bloodstream. Understanding the process of ocular complement production and regulation will further our understanding of the AMD disease process and the requirements of a complement-based therapeutic. PMID:25593023

  17. 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

  18. 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.

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

    PubMed Central

    Ijeri, Raghavendra; Beladiya, Gautam; Bhomaj, Sharad

    2016-01-01

    Tick typhus causes hemorrhagic lesions over the skin. Retina also shows hemorrhages and exudates. Many cases have been reported in western literature about this condition. To our best of knowledge, this is the first case report of tick typhus in India which was also associated with inflammatory choroidal neovascularization. PMID:27905346

  20. 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

  1. VEGF-production by CCR2-dependent macrophages contributes to laser-induced choroidal neovascularization.

    PubMed

    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

  2. [Neovascularization in ocular tissues: mechanisms and role of proangiogenic and antiangiogenic factors].

    PubMed

    Nowak, Jerzy Z; Wiktorowska-Owczarek, Anna

    2004-01-01

    Blood vessel growth and stability are under precise control of an array of pro- and anti-angiogenic factors. Under physiological conditions, actions of particular regulatory factors, as well as their mutual interactions are harmonized and balanced. Disruption of the balance between these pro- and anti-angiogenic factors is characteristic of many vascular diseases, including those occurring within the eye. Functional dominancy of proangiogenic factors (e.g., vascular endothelial growth factor, VEGF) over antiangiogenic ones (e.g., pigment epithelium-derived growth factor, PEDF), which may occur under ischemic conditions, may initiate the process of retinal or choroidal neovascularization, representing a major threat to the eyesight. This article presents and discusses current ideas concerning molecular and cellular processes underlying aberrant growth on new blood vessels in ocular tissues, in relation to microvascular ocular complications associated mainly (but not only), with diabetes mellitus, age-related macular degeneration (AMD), and retinopathy of prematurity (ROP). This review also surveys latest achievements in the field of clinically more effective future therapeutic strategies, including gene therapy applicable to the neovascular eye diseases.

  3. The anti-angiogenic role of discoidin domain receptor 2 (DDR2) in laser-induced choroidal neovascularization.

    PubMed

    Zhu, Tong; Zhu, Jie; Bu, Xin; Zhao, Hu; Zhang, Shuya; Chang, Yuan; Li, Rong; Yao, Libo; Wang, Yusheng; Su, Jin

    2015-02-01

    Choroidal neovascularization (CNV), an aberrant growth of blood vessels in the choroid layer of the eye, is a major cause of vision loss. In view of our recent finding that discoidin domain receptor 2 (DDR2), a collagen-binding receptor tyrosine kinase, is involved in control of vascular endothelial activity and tumor angiogenesis, the present study aims to investigate whether and how DDR2 affects the pathogenesis of CNV. We initially found that a spontaneous DDR2 mutant mouse colony (slie) exhibited enhanced amplitude of laser-induced CNV. The inhibitory role of DDR2 in CNV development was further confirmed by experiments through intravitreous injection of DDR2 small interference RNA (siRNA) or DDR2-expressing adenovirus. Quantitative real-time polymerase chain reaction (qPCR) and immunoblot analysis showed that DDR2 regulates the expression of several major pro-angiogenic factors in the laser-injured choroid as well as in retinal pigment epithelium (RPE) cells. In addition, it was demonstrated that the CNV-induced increases in the phosphorylation levels of Akt and mTOR were affected by the upregulation or downregulation of DDR2. Thus, the data from this study for the first time revealed that DDR2 negatively regulates the development of experimental CNV in vivo, which may provide a novel target for preventing human pathological ocular neovascularization. Key messages: DDR2 does not affect retinal development. DDR2 inhibits laser-induced CNV. DDR2 regulates angiogenic factor expression in CNV lesion as well as in RPE cells. DDR2 is involved in modulation of CNV-induced activation of PI3K pathway.

  4. 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

  5. Visible-Light Optical Coherence Tomography Angiography for Monitoring Laser-Induced Choroidal Neovascularization in Mice

    PubMed Central

    Shah, Ronil S.; Soetikno, Brian T.; Yi, Ji; Liu, Wenzhong; Skondra, Dimitra; Zhang, Hao F.; Fawzi, Amani A.

    2016-01-01

    Purpose This study sought to determine the earliest time-point at which evidence of choroidal neovascularization (CNV) could be detected with visible-light optical coherence tomography angiography (vis-OCTA) in a mouse model of laser-induced CNV. Methods Visible light-OCTA was used to study laser-induced CNV at different time-points after laser injury to monitor CNV development and measure CNV lesion size. Measurements obtained from vis-OCTA angiograms were compared with histopathologic measurements from isolectin-stained choroidal flatmounts. Results Choroidal neovascularization area measurements between the vis-OCTA system and isolectin-stained choroidal flatmounts were significantly different in area for days 2 to 4 postlaser injury, and were not significantly different in area for days 5, 7, and 14. Choroidal neovascularization area measurements taken from the stained flatmounts were larger than their vis-OCTA counterparts for all time-points. Both modalities showed a similar trend of CNV size increasing from the day of laser injury until a peak of day 7 postlaser injury and subsequently decreasing by day 14. Conclusions The earliest vis-OCTA can detect the presence of aberrant vessels in a mouse laser-induced CNV model is 5 days after laser injury. Visible light-OCTA was able to visualize the maximum of the CNV network 7 days postlaser injury, in accordance with choroidal flatmount immunostaining. Visible light-OCTA is a reliable tool in both detecting the presence of CNV development, as well as accurately determining the size of the lesion in a mouse laser-induced CNV model. PMID:27409510

  6. 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

  7. Lymphocytic Microparticles Modulate Angiogenic Properties of Macrophages in Laser-induced Choroidal Neovascularization

    PubMed Central

    Tahiri, Houda; Omri, Samy; Yang, Chun; Duhamel, François; Samarani, Suzanne; Ahmad, Ali; Vezina, Mark; Bussières, Martin; Vaucher, Elvire; Sapieha, Przemyslaw; Hickson, Gilles; Hammamji, Karim; Lapointe, Réjean; Rodier, Francis; Tremblay, Sophie; Royal, Isabelle; Cailhier, Jean-François; Chemtob, Sylvain; Hardy, Pierre

    2016-01-01

    Pathological choroidal neovascularization (CNV) is the common cause of vision loss in patients with age-related macular degeneration (AMD). Macrophages possess potential angiogenic function in CNV. We have demonstrated that human T lymphocyte-derived microparticles (LMPs) exert a potent antiangiogenic effect in several pathological neovascularization models. In this study, we investigated the alteration of proangiogenic properties of macrophages by LMPs treatment in vitro and in vivo models. LMPs regulated the expression of several angiogenesis-related factors in macrophages and consequently stimulated their antiangiogenic effects evidenced by the suppression of the proliferation of human retinal endothelial cells in co-culture experiments. The involvement of CD36 receptor in LMPs uptake by macrophages was demonstrated by in vitro assays and by immunostaining of choroidal flat mounts. In addition, ex vivo experiments showed that CD36 mediates the antiangiogenic effect of LMPs in murine and human choroidal explants. Furthermore, intravitreal injection of LMPs in the mouse model of laser-induced CNV significantly suppressed CNV in CD36 dependent manner. The results of this study suggested an ability of LMPs to alter the gene expression pattern of angiogenesis-related factors in macrophages, which provide important information for a new therapeutic approach for efficiently interfering with both vascular and extravascular components of CNV. PMID:27874077

  8. Lymphocytic Microparticles Modulate Angiogenic Properties of Macrophages in Laser-induced Choroidal Neovascularization.

    PubMed

    Tahiri, Houda; Omri, Samy; Yang, Chun; Duhamel, François; Samarani, Suzanne; Ahmad, Ali; Vezina, Mark; Bussières, Martin; Vaucher, Elvire; Sapieha, Przemyslaw; Hickson, Gilles; Hammamji, Karim; Lapointe, Réjean; Rodier, Francis; Tremblay, Sophie; Royal, Isabelle; Cailhier, Jean-François; Chemtob, Sylvain; Hardy, Pierre

    2016-11-22

    Pathological choroidal neovascularization (CNV) is the common cause of vision loss in patients with age-related macular degeneration (AMD). Macrophages possess potential angiogenic function in CNV. We have demonstrated that human T lymphocyte-derived microparticles (LMPs) exert a potent antiangiogenic effect in several pathological neovascularization models. In this study, we investigated the alteration of proangiogenic properties of macrophages by LMPs treatment in vitro and in vivo models. LMPs regulated the expression of several angiogenesis-related factors in macrophages and consequently stimulated their antiangiogenic effects evidenced by the suppression of the proliferation of human retinal endothelial cells in co-culture experiments. The involvement of CD36 receptor in LMPs uptake by macrophages was demonstrated by in vitro assays and by immunostaining of choroidal flat mounts. In addition, ex vivo experiments showed that CD36 mediates the antiangiogenic effect of LMPs in murine and human choroidal explants. Furthermore, intravitreal injection of LMPs in the mouse model of laser-induced CNV significantly suppressed CNV in CD36 dependent manner. The results of this study suggested an ability of LMPs to alter the gene expression pattern of angiogenesis-related factors in macrophages, which provide important information for a new therapeutic approach for efficiently interfering with both vascular and extravascular components of CNV.

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

    PubMed

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

    1992-01-01

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

  10. 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

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

    PubMed Central

    Mansour, Ahmad M.; Al Kahtani, Eman; Zegarra, Hernando; 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. PMID:25147732

  12. 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.

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

    PubMed Central

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

    2012-01-01

    The purpose of this report is to evaluate the efficacy and safety of combined intravitreal injection of bevacizumab and intravitreal triamcinolone acetonide (IVTA) for recurrent inflammatory choroidal neovascular membrane (CNVM). It was a prospective interventional study of a young female, who was a known case of Vogt-Koyanagi-Harada syndrome. She presented with an inflammatory choroidal neovascualar membrane and signs of panuveitis in the right eye. She underwent a complete ophthalmic examination. She was given intravitreal injection of bevacizumab and IVTA at different sites. There was complete regression of CNVM and ocular inflammation within a week. After six months, she had recurrence of CNVM in the same eye, which was treated similarly. There was a complete resolution of CNVM and ocular inflammation after the combination therapy and systemic steroids, until one year of follow-up. No serious systemic or ocular adverse events were noted. Combination therapy appears to be an effective and safe method in the management of recurrent inflammatory CNVM. PMID:23202396

  14. Analysis of Scleral Feeder Vessel in Myopic Choroidal Neovascularization Using Optical Coherence Tomography Angiography

    PubMed Central

    Louzada, Ricardo Noguera; Ferrara, Daniela; Novais, Eduardo Amorim; Moult, Eric; Cole, Emily; Lane, Mark; Fujimoto, James; Duker, Jay S.; Baumal, Caroline R.

    2017-01-01

    To describe the appearance of a scleral-derived feeder vessel in a highly myopic eye with secondary choroidal neovascularization (CNV) as visualized on both en face high-speed swept-source (SS) optical coherence tomography angiography (OCTA) prototype, and a commercially available spectral-domain (SD) OCTA, with the corresponding en face and cross-sectional structural OCT images. In this case report, a 60-year-old white male presented with high myopia and secondary CNV in the right eye, previously treated with anti-vascular endothelial growth factor, and was imaged on both SD-OCT and SS-OCT. The neovascular complex could be visualized on both devices. Structural en face SS-OCT images demonstrated a large choroidalscleral feeder vessel that was not visualized with SD-OCT. The authors concluded that structural en face SS-OCT better visualizes scleral feeder vessel compared to SD-OCT due to the longer wavelength (~1,050 nm) with increased choroidal penetration and decreased sensitivity roll-off in the SS-OCT system. PMID:27759864

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

    PubMed

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

    2015-09-01

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

  16. 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

  17. 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.

  18. 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.

  19. Topical Antiangiogenic SRPK1 Inhibitors Reduce Choroidal Neovascularization in Rodent Models of Exudative AMD

    PubMed Central

    Gammons, Melissa V.; Fedorov, Oleg; Ivison, David; Du, Chunyun; Clark, Tamsyn; Hopkins, Claire; Hagiwara, Masatoshi; Dick, Andrew D.; Cox, Russell; Harper, Steven J.; Hancox, Jules C.; Knapp, Stefan; Bates, David O.

    2013-01-01

    Purpose. Exudative AMD (wet AMD) is treated by monthly injection into the eye of anti-VEGF proteins. VEGF is alternatively spliced to produce numerous isoforms that differ in angiogenic activity. Serine-rich protein kinase-1 (SRPK1) has been identified as a regulator of pro-angiogenic VEGF splicing by phosphorylating serine-rich splicing factor-1 (SRSF1), which binds to VEGF pre-mRNA. We tested the hypothesis that topical (eye drop) SRPK1-selective inhibitors could be generated that reduce pro-angiogenic isoforms, and prevent choroidal neovascularization in vivo. Methods. Novel inhibitors were tested for SRPK inhibition in vitro, pro-angiogenic VEGF production in RPE cells by PCR and ELISA, and for inhibition of choroidal neovascularisation in mice and rats. Results. A novel disubstituted furan inhibitor was selective for the SRPK family of kinases and reduced expression of pro-angiogenic but not antiangiogenic VEGF isoforms. This inhibitor and previously identified SRPK inhibitors significantly reduced choroidal neovascularisation in vivo. Topical administration of SRPK inhibitors dose-dependently blocked CNV with an EC50 of 9 μM. Conclusions. These results indicate that novel SRPK1 selective inhibitors could be a potentially novel topical (eye drop) therapeutic for wet AMD. PMID:23887803

  20. 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

  1. Lipopolysaccharide Promotes Choroidal Neovascularization by Up-Regulation of CXCR4 and CXCR7 Expression in Choroid Endothelial Cell

    PubMed Central

    Feng, Yi-fan; Guo, Hua; Yuan, Fei; Shen, Min-qian

    2015-01-01

    Stromal cell-derived factor-1 (SDF-1) has been confirmed to participate in the formation of choroidal neovascularization (CNV) via its two receptors: CXC chemokine receptors 4 (CXCR4) and CXCR7. Previous studies have indicated that the activation of Toll-like receptors (TLRs) by lipopolysaccharide (LPS) might elevate CXCR4 and/or CXCR7 expression in tumor cells, enhancing the response to SDF-1 to promote invasion and cell dissemination. However, the impact of LPS on the CXCR4 and CXCR7 expression in endothelial cells and subsequent pathological angiogenesis formation remains to be elucidated. The present study shows that LPS enhanced the CXCR4 and CXCR7 expression via activation of the TLR4 pathway in choroid-retinal endothelial (RF/6A) cells. In addition, the transcriptional regulation of CXCR4 and CXCR7 by LPS was found to be mediated by phosphorylation of the extracellular signal-related kinase (ERK) 1/2 and activation of nuclear factor kappa B (NF-κB) signaling pathways, which were blocked by ERK- or NF-κB-specific inhibitors. Furthermore, the increased CXCR4 and CXCR7 expression resulted in increased SDF-1-induced RF/6A cells proliferation, migration and tube formation. In vivo, LPS-treated rat had significantly higher mRNA levels of CXCR4 and CXCR7 expression and lager laser-induced CNV area than vehicle-treated rat. SDF-1 blockade with a neutralizing antibody attenuated the progression of CNV in LPS-treated rat after a single intravitreal injection. Altogether, these results demonstrated that LPS might influence CNV formation by enhancing CXCR7 and CXCR7 expression in endothelial cells, possibly providing a new perspective for the treatment of CNV-associated diseases. PMID:26288180

  2. What ocular and systemic variables affect choroidal circulation in healthy eyes

    PubMed Central

    Iwase, Takeshi; Yamamoto, Kentaro; Kobayashi, Misato; Ra, Eimei; Murotani, Kenta; Terasaki, Hiroko

    2016-01-01

    Abstract The aim of the study was to investigate the relationship between choroidal blood flow and systemic and ocular variables in patients with healthy eyes. In this prospective cross-sectional study, we examined 241 eyes of 241 healthy Japanese subjects (92 males and 149 females; mean age, 37.8 ± 17.0 years). The mean blur rate, a measure of the relative blood flow of the choroid, was determined using laser speckle flowgraphy. The total cross-sectional choroidal, luminal, and stromal areas of the choroid were determined by the binarization method. We investigated the correlation between choroidal MBR and systemic and ocular variables. Choroidal mean blur rate correlated with age (r = −0.385, P < 0.001) and choroidal thickness (r = 0.264, P < 0.001). The choroidal area correlated with choroidal mean blur rate (r = 0.374, P < 0.001), age (r = −0.184, P = 0.004), axial length (r = −0.251, P < 0.001), and choroidal thickness (r = 0.468, P < 0.001). The luminal area correlated with choroidal mean blur rate (r = 0.403, P < 0.001), age (r = −0.244, P < 0.001), axial length (r = −0.218, P = 0.001), and choroidal thickness (r = 0.435, P < 0.001). On multiple stepwise regression analyses, age (β = −0.321, P < 0.001) and luminal area (β = 0.320, P < 0.001), heart rate (β = 0.136, P = 0.018), and mean ocular perfusion pressure (β = 0.126, P = 0.045) were independent factors indicating the choroidal mean blur rate. Furthermore, axial length (β = −0.352, P < 0.001), choroidal mean blur rate (β = 0.273, P < 0.001), age (β = −0.247, P < 0.001), gender (β = −0.226, P < 0.001), and mean ocular perfusion pressure (β = 0.193, P = 0.002) were independent factors indicating the luminal area. The choroidal blood flow positively correlated with the luminal area and negatively correlating with age. In addition, the luminal area was negative correlated with age. It is suggested that aging causes a

  3. Identification of Chlamydia pneumoniae within human choroidal neovascular membranes secondary to age-related macular degeneration.

    PubMed

    Kalayoglu, Murat V; Bula, Deisy; Arroyo, Jorge; Gragoudas, Evangelos S; D'Amico, Donald; Miller, Joan W

    2005-11-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in the United States, and increasing evidence suggests that it is an inflammatory disease. The prokaryotic obligate intracellular pathogen Chlamydia pneumoniae is emerging as a novel risk factor in cardiovascular disease, and recent sero-epidemiological data suggest that C. pneumoniae infection is also associated with AMD. In this study, we examined choroidal neovascular membrane (CNV) tissue from patients with neovascular AMD for the presence of C. pneumoniae and determined whether the pathogen can dysregulate the function of key cell types in ways that can cause neovascular AMD. Nine CNV removed from patients with neovascular AMD were examined for the presence of C. pneumoniae by immunohistochemistry (IHC) and polymerase chain reaction (PCR); in addition, we performed PCR on nine non-AMD eyes, and IHC on five non-AMD CNV, seven non-AMD eyes, and one internal limiting membrane specimen. Finally, human monocyte-derived macrophages and retinal pigment epithelial (RPE) cells were exposed to C. pneumoniae and assayed in vitro for the production of pro-angiogenic immunomodulators (VEGF, IL-8, and MCP-1). C. pneumoniae was detected in four of nine AMD CNV by IHC and two of nine AMD CNV by PCR, induced VEGF production by human macrophages, and increased production of IL-8 and MCP-1 by RPE cells. In contrast, none of the 22 non-AMD specimens showed evidence for C. pneumoniae. These data indicate that a pathogen capable of inducing chronic inflammation and pro-angiogenic cytokines can be detected in some AMD CNV, and suggest that infection may contribute to the pathogenesis of AMD.

  4. 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

  5. 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

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

    PubMed

    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

  7. Topical Application of PPADS Inhibits Complement Activation and Choroidal Neovascularization in a Model of Age-Related Macular Degeneration

    PubMed Central

    Birke, Kerstin; Lipo, Erion; Birke, Marco T.; Kumar-Singh, Rajendra

    2013-01-01

    Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly. AMD patients have elevated levels of membrane attack complex (MAC) in their choroidal blood vessels and retinal pigment epithelium (RPE). MAC forms pores in cell membranes. Low levels of MAC result in an elevation of cytokine release such as vascular endothelial growth factor (VEGF) that promotes the formation of choroidal neovascularization (CNV). High levels of MAC result in cell lysis and RPE degeneration is a hallmark of advanced AMD. The current standard of care for CNV associated with wet AMD is intravitreal injection of anti-VEGF molecules every 4 to 12 weeks. Such injections have significant side effects. Recently, it has been found that membrane pore-forming proteins such as α-haemolysin can mediate their toxic effects through auto- and paracrine signaling and that complement-induced lysis is amplified through ATP release followed by P2X receptor activation. We hypothesized that attenuation of P2X receptor activation may lead to a reduction in MAC deposition and consequent formation of CNV. Hence, in this study we investigated topical application of the purinergic P2X antagonist Pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) as a potential treatment for AMD. We found that 4.17 µM PPADS inhibited formation of HUVEC master junctions and master segments by 74.7%. In a human complement mediated cell lysis assay, 104 µM PPADS enabled almost complete protection of Hepa1c1c7 cells from 1% normal human serum mediated cell lysis. Daily topical application of 4.17 mM PPADS for 3 days attenuated the progression of laser induced CNV in mice by 41.8% and attenuated the deposition of MAC at the site of the laser injury by 19.7%. Our data have implications for the future treatment of AMD and potentially other ocular disorders involving CNV such as angioid streaks, choroidal rupture and high myopia. PMID:24130789

  8. Management of Myopic Choroidal Neovascularization: Focus on Anti-VEGF Therapy.

    PubMed

    Teo, Kelvin Yi Chong; Ng, Wei Yan; Lee, Shu Yen; Cheung, Chui Ming Gemmy

    2016-07-01

    Myopic choroidal neovascularization (mCNV) is the second most common form of CNV after age-related macular degeneration (AMD). It is a sight-threatening complication of pathologic myopia (PM) and often affects patients in their working years causing significant impact on quality of life. Previous therapies such as photodynamic therapy with verteporfin have shown limited success. Due to the similarities in pathogenesis of mCNV and AMD CNV, anti-vascular endothelial growth factor therapy (anti-VEGF), which has so far been the mainstay of treatment for AMD CNV, has been shown to be effective in the treatment of mCNV and has become the first-line treatment of choice. This article aims to examine briefly the epidemiology and pathophysiology of mCNV, as well as review the evidence for efficacy, safety, and clinical use of anti-VEGF treatment for mCNV.

  9. Geographic Atrophy and Choroidal Neovascularization in the Same Eye: A Review.

    PubMed

    Kaszubski, Patrick; Ben Ami, Tal; Saade, Celine; Smith, R Theodore

    2016-01-01

    Geographic atrophy (GA) and choroidal neovascularization (CNV), the two late forms of age-related macular degeneration, are generally considered two distinct entities. However, GA and CNV can occur simultaneously in the same eye, with GA usually occurring first. The prevalence of this combined entity is higher in histological studies than in clinical studies. No distinct systemic or genetic risk characteristics are associated with the combined GA/CNV entity, although on clinical examination and retinal imaging it can feature drusen or subretinal drusenoid deposits. GA and CNV may exist within the spectrum of a single disease, or they may be two very different diseases. Therapy with antivascular endothelial growth factor (anti-VEGF) is often successful for CNV, but some evidence suggests increased rates of GA development in eyes treated with anti-VEGF. In this article, we review the current literature regarding the epidemiology, clinical presentation, and treatment options for patients with the combined GA/CNV entity.

  10. Combined choroidal neovascularization and hypopituitarism in a patient with homozygous mutation in methylenetetrahydrofolate reductase gene

    PubMed Central

    Aydogdu, Aydogan; Haymana, Cem; Baskoy, Kamil; Durukan, Ali H.; Ozgur, Gokhan; Azal, Omer

    2014-01-01

    We report a case of choroidal neovascularization (CNV) secondary to methylenetetrahydrofolate reductase (MTHFR) gene mutation in a 20-year-old male patient with hypopituitarism. Treatment with three consecutive injections of intravitreal ranibizumab (anti-vascular endothelial growth factor) resulted in significant improvement of the patient's vision and the appearance of the macula. A search of the literature produced no previously reported case of MTHFR gene mutation associated both CNV and possibly hypopituitarism. With hormone replacement therapy of hypopituitarism, acetyl salicylic acid 100 mg/day also was started. The patient was clinically stable both for CNV and other thromboembolic disorders over a 6-month follow-up and also 1-year follow-up period. PMID:24672570

  11. Drusen complement components C3a and C5a promote choroidal neovascularization

    PubMed Central

    Nozaki, Miho; Raisler, Brian J.; Sakurai, Eiji; Sarma, J. Vidya; Barnum, Scott R.; Lambris, John D.; Chen, Yali; Zhang, Kang; Ambati, Balamurali K.; Baffi, Judit Z.; Ambati, Jayakrishna

    2006-01-01

    Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrialized nations, affecting 30–50 million people worldwide. The earliest clinical hallmark of AMD is the presence of drusen, extracellular deposits that accumulate beneath the retinal pigmented epithelium. Although drusen nearly always precede and increase the risk of choroidal neovascularization (CNV), the late vision-threatening stage of AMD, it is unknown whether drusen contribute to the development of CNV. Both in patients with AMD and in a recently described mouse model of AMD, early subretinal pigmented epithelium deposition of complement components C3 and C5 occurs, suggesting a contributing role for these inflammatory proteins in the development of AMD. Here we provide evidence that bioactive fragments of these complement components (C3a and C5a) are present in drusen of patients with AMD, and that C3a and C5a induce VEGF expression in vitro and in vivo. Further, we demonstrate that C3a and C5a are generated early in the course of laser-induced CNV, an accelerated model of neovascular AMD driven by VEGF and recruitment of leukocytes into the choroid. We also show that genetic ablation of receptors for C3a or C5a reduces VEGF expression, leukocyte recruitment, and CNV formation after laser injury, and that antibody-mediated neutralization of C3a or C5a or pharmacological blockade of their receptors also reduces CNV. Collectively, these findings establish a mechanistic basis for the clinical observation that drusen predispose to CNV, revealing a role for immunological phenomena in angiogenesis and providing therapeutic targets for AMD. PMID:16452172

  12. Systemic, Ocular and Genetic Risk Factors for Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy in Singaporeans

    PubMed Central

    Cheung, Chui Ming Gemmy; Laude, Augustinus; Yeo, Ian; Tan, Shu-Pei; Fan, Qiao; Mathur, Ranjana; Lee, Shu Yen; Chan, Choi Mun; Tan, Gavin; Lim, Tock Han; Cheng, Ching-Yu; Wong, Tien Yin

    2017-01-01

    To examine the association of systemic, ocular and genetic risk factors in neovascular age-related macular degeneration (nAMD) in a large cohort of Asian patients, and to further compare risk factors between those with typical AMD and polypoidal choroidal vasculoapthy (PCV) subtypes. We recruited 456 cases and 1,824 controls matched for age, gender and ethnicity. Data on systemic and ocular risk factors were collected on questionnaires. In a subgroup of subjects, we included genetic data on four AMD-associated single nucleotide polymorphisms (SNPs). Risk factors for nAMD and subtypes were analyzed. Systemic risk factors for nAMD included older age, male gender, higher BMI and higher HDL-cholesterol. Ocular risk factors included pseudophakic and shorter axial length. Risk factors common to both typical AMD and PCV subtypes included age, BMI and HDL-cholesterol. Shorter axial length was only associated with PCV, while male gender and pseudophakia were only associated with typical AMD. In the subgroup with genotype data, ARMS2 rs10490924 and CFH rs800292 were associated with nAMD. None of the risk factors were significantly different between PCV and typical AMD. Systemic, ocular and genetic risk factors were largely similar for typical AMD and PCV subtypes in this Asian population based in Singapore. PMID:28120909

  13. Idiopathic Multifocal Choroiditis

    PubMed Central

    Tavallali, Ali; Yannuzzi, Lawrence A.

    2016-01-01

    Idiopathic multifocal choroiditis (MFC) and/or punctate inner choroidopathy (PIC) describe a chronic progressive bilateral inflammatory chorioretinopathy that predominantly affect healthy myopic white women with no known associated systemic or ocular diseases. The principal sites of involvement are the retinal pigment epithelium (RPE) and outer retinal spaces; the choroid is not affected during the active phase of the disease. Idiopathic MFC with atrophy is a recently described variant. Although there is no generally accepted standard treatment, anti-inflammatory and anti-VEGF (vascular endothelial growth factor) agents are necessary in the acute stage to control the inflammation and choroidal neovascularization (CNV). PMID:27994812

  14. Bilateral choroidal neovascularization associated with optic nerve head drusen treated by antivascular endothelial growth factor therapy

    PubMed Central

    Delas, Barbara; Almudí, Lorena; Carreras, Anabel; Asaad, Mouafk

    2012-01-01

    Objective To report a good clinical outcome in a patient with bilateral choroidal neovascularization (CNV) associated with optic nerve head drusen (ONHD) treated with intravitreal ranibizumab injection. Methods A 12-year-old girl was referred for loss of right eye vision detected in a routine check-up. Best-corrected visual acuity (BCVA) was hand movements in the right eye and 0.9 in the left eye. Funduscopy revealed the presence of superficial and buried bilateral ONHD, which was confirmed by ultrasonography and computed tomography, and the study was completed with perimetry. The presence of bilateral CNV, active in the right eye, was observed and subsequently confirmed using fluorescein angiography and optical coherence tomography. Results Treatment with two consecutive injections of intravitreal ranibizumab resulted in inactivation of the neovascular membrane with subretinal fluid reabsorption and improved right eye BCVA. After 12 months’ follow-up, this was 20/60 and stable. Conclusion Although there are no published studies of safety in children, antiangiogenic therapy for CNV secondary to ONHD may be useful and safe. A search of the literature produced only one previously reported case of ONHD-associated CNV treated with antivascular endothelial growth factor alone. PMID:22368440

  15. 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

  16. Block copolymers encapsulated poly (aryl benzyl ether) dendrimer silicon (IV) phthalocyanine for in vivo and in vitro photodynamic efficacy of choroidal neovascularization

    NASA Astrophysics Data System (ADS)

    Wang, Xiongwei; Chen, Kuizhi; Huang, Zheng; Peng, Yiru

    2015-03-01

    A novel series of poly (aryl benzyl ether) dendrimer silicon phthalocyanines loaded block copolymers ethoxypoly(ethylene glycol)-poly (lactic-co-glycolic acid) (MPEG-PLGA)were formed. The time-dependent intracellular uptake of nanoparticles in HUVECs cells increased as they were incorporated into nanoparticles. With its highly effective selective accumulation on choroidal neovascularization(CNV). This treatment resulted in a efficacious choroidal neovascularization (CNV) occlusion with minimal unfavorable phototoxicity.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. Effect of cytokeratin 17 on retinal pigment epithelium degeneration and choroidal neovascularization

    PubMed Central

    Shen, Yi; Zhuang, Pei; Xiao, Tao; Chiou, George CY

    2016-01-01

    AIM To study the effects of cytokeratin 17 (CK17) on sodium iodate (NaIO3) induced rat retinal pigment epithelium (RPE) degeneration, laser induced rat choroidal neovascularization (CNV), and oxidative stress of human retinal pigment epithelium cells (ARPE-19) and human umbilical vein endothelial cell (HUVEC). METHODS Thirty 8-week-old male Brown Norway rats were randomly divided into 3 groups, 10 rats in control group treated with solvent alone; 10 rats in NaIO3 group treated with solvent and 35 mg/kg NaIO3 injection through hypoglossal vein and 10 rats in CK17+NaIO3 group treated with 1% CK17 eye drop 3 times a day for 1wk before and 4wk after NaIO3 injection. RPE function was measured with c-wave of electroretinogram (ERG). Another 20 rats were randomly divided into 2 groups. Of them 10 rats in CK17 group were anesthetized to receive Nd:YAG laser and given 1% CK17 eye drop before same as above; 10 rats in control were received Nd:YAG and treated with solvent. The development of choroidal neovascularization (CNV) was determined by fundus fluorescein angiography (FFA) performed on 4wk after laser. Methylthiazoly tetrazolium (MTT) assay was used to study effect of CK17 on various oxidants induced injury in ARPE-19 and HUVEC in vitro. RESULTS Four weeks after NaIO3 injection, the c-wave amplitude of ERG was 0.393±0.02 V in the control group, 0.184±0.018 V in NaIO3 group and 0.3±0.01 V in CK17+NaIO3 group. There was a significant reversal of the c-wave by CK17 as compared to NaIO3 group (P<0.01). Four weeks after laser, the size of the CNV lesion was 2.57±0.27 mm2 in control group and 1.64±0.08 mm2 in CK17 group. The lesion size significantly diminished in CK17 group (P<0.01). The in vitro results showed CK17 also reversed the various oxidants induced injuries in ARPE-19 at the dose of 100 µg/mL and enhanced the injury in HUVECs at different concentrations. CONCLUSION CK17 can significantly protect RPE from NaIO3 induced degeneration in vivo and in vitro and

  2. Intravitreal aflibercept for the treatment of choroidal neovascularization associated with pathologic myopia: a pilot study

    PubMed Central

    Korol, Andrii R; Zadorozhnyy, Oleg S; Naumenko, Volodymyr O; Kustryn, Taras B; Pasyechnikova, Nataliya V

    2016-01-01

    Purpose To determine the efficacy of intravitreal aflibercept injections for the treatment of patients with choroidal neovascularization (CNV) associated with pathologic myopia. Methods In this uncontrolled, prospective cohort study, 31 eyes of 30 consecutive patients affected by CNV associated with pathologic myopia were treated with intravitreal aflibercept (2 mg) as needed following two initial monthly doses and observed over a 12-month follow-up period. The primary endpoint was change in best-corrected visual acuity (BCVA) at month 12, while central retinal thickness (CRT) on optical coherence tomography (OCT), neovascularization activity on fluorescein angiography, the number of aflibercept injections administered, and safety were examined as secondary endpoints. Results Patients received a mean of 2.6 intravitreal aflibercept injections over the 12-month study period. Compared with baseline, BCVA improved significantly at all time points (P<0.05). Mean (standard deviation [SD]) decimal BCVA was 0.2 (0.1) at baseline and 0.35 (0.16) at month 12. The greatest improvement in BCVA was seen within the first 2 months (P=0.01). Mean (SD) CRT on OCT decreased from 285 (62) µm at baseline to 227 (42) µm (P=0.01) at month 12. There was a continuous decrease in mean CRT on OCT over time. No cases of endophthalmitis, uveitis, stroke, or retinal detachment were noted. No patient demonstrated an intraocular pressure >20 mmHg during any study visit. Conclusion The 12-month results of intravitreal aflibercept for myopic CNV using an as-needed regimen were positive, showing benefits in visual and anatomic outcomes and an acceptable tolerability profile. PMID:27853350

  3. Detection of heat shock protein 70 in choroidal neovascular membranes secondary to age related macular degeneration

    PubMed Central

    2011-01-01

    Background Heat shock proteins are acute phase proteins that are upregulated in inflammation or following thermal stress. We analyzed the presence of the heat shock protein 70 (Hsp 70) in choroidal neovascular (CNV) membranes secondary to AMD after treatment with verteporphin photodynamic therapy (PDT) or transpupillary thermo therapy (TTT) to determine whether treatment correlated with the presence of Hsp70. Results CNV membranes were removed by pars plana vitrectomy (ppV) and subretinal extraction. The membranes were analysed by light microscopy and the presence of Hsp 70 was examined using histochemistry. HeLa Cells served as controls. Of the 14 membranes analysed 11 were Hsp70 positive and 3 negative. In the no pre-treatment group of 8 membranes 6 were Hsp70 positive and 2 negative; in the PTD group all 4 membranes were positive and in the TTT group 1 membrane was positive and 1 membrane was negative for Hsp70. Conclusion Hsp70 is present in the most CNV membranes secondary to AMD. Pre-treatment of the membrane with PTD or TTT does not appear to influence the expression of Hsp70. PMID:21477309

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. Choroid, Haller's, and Sattler's Layer Thickness in Intermediate Age-Related Macular Degeneration With and Without Fellow Neovascular Eyes

    PubMed Central

    Esmaeelpour, Marieh; Ansari-Shahrezaei, Siamak; Glittenberg, Carl; Nemetz, Susanne; Kraus, Martin F.; Hornegger, Joachim; Fujimoto, James G.; Drexler, Wolfgang; Binder, Susanne

    2014-01-01

    Purpose. To analyze choroidal, Sattler's, and Haller's layer thickness maps in age-related macular degeneration (AMD) patients having eyes with bilateral large drusen and pigment changes (intermediate AMD), in patients having intermediate AMD eyes with neovascular fellow eyes (nAMD), and in healthy subjects using three-dimensional (3D) 1060-nm optical coherence tomography (OCT). Methods. Automatically generated choroidal thickness (ChT), retinal thickness, and Sattler's and Haller's layer thickness maps were statistically analyzed in 67 subjects consisting of intermediate AMD (n = 21), intermediate AMD (n = 22) with fellow nAMD eyes (n = 22), and healthy eyes (n = 24) with no age and axial eye length difference between groups of eyes (P > 0.05, ANOVA). Eyes were imaged by a prototype high-speed (60,000 A-scans/s) spectral-domain 3D 1060-nm OCT over a 36° × 36° field of view. Results. The mean ± SD (μm) subfoveal ChT for healthy subjects and for bilateral intermediate AMD, unilateral intermediate AMD, and their nAMD fellow eyes was 259 ± 95 and 222 ± 98, 149 ± 60, and 171 ± 78, respectively. Choroidal thickness maps demonstrated significant submacular thinning in unilateral intermediate AMD in comparison to healthy and bilateral intermediate AMD eyes (P < 0.001, ANOVA, post hoc P < 0.001 and P < 0.05, respectively). Sattler's and Haller's layers were thinnest in intermediate AMDs that presented with nAMD fellow eyes (Kruskal-Wallis test P < 0.01). For the choroid and its sublayers, there was no difference between the intermediate AMD eyes and their fellow nAMD eyes (paired testing, P < 0.05). Conclusions. The 3D 1060-nm OCT choroidal imaging visualized significant changes in choroidal, Sattler's, and Haller's layer thickness in relation to the progression of AMD. This may be important for understanding the choroidopathy in the pathophysiology of AMD. PMID:25052997

  9. The HIF-1 antagonist acriflavine: visualization in retina and suppression of ocular neovascularization.

    PubMed

    Zeng, Mingbing; Shen, Jikui; Liu, Yuanyuan; Lu, Lucy Yang; Ding, Kun; Fortmann, Seth D; Khan, Mahmood; Wang, Jiangxia; Hackett, Sean F; Semenza, Gregg L; Campochiaro, Peter A

    2017-04-01

    Acriflavine, a fluorescent drug previously used for bacterial and trypanosomal infections, reduces hypoxia-inducible factor-1 (HIF-1) and HIF-2 transcriptional activity. In mice with oxygen-induced ischemic retinopathy, intraocular or intraperitoneal injections of acriflavine caused dose-dependent suppression of retinal neovascularization (NV) and significantly reduced expression of HIF-1-responsive genes. Intraocular injection of 100 ng caused inner retina fluorescence within 1 h that was seen throughout the entire retina between 1 and 5 days, and at 7 days after injection, strongly suppressed choroidal NV at Bruch's membrane rupture sites. After suprachoroidal injection of 300 ng in rats, there was retinal fluorescence in the quadrant of the injection at 1 h that spread throughout the entire retina and choroid by 1 day, was detectable for 5 days, and dramatically reduced choroidal NV 14 days after rupture of Bruch's membrane. After topical administration of acriflavine in mice, fluorescence was seen in the retina and retinal pigmented epithelium within 5 min and was detectable for 6-12 h. Administration of 0.5% drops to the cornea twice a day significantly reduced choroidal NV in mice. Electroretinographic b-wave amplitudes were normal 7 days after intravitreous injection of 100 ng of acriflavine in mice, showed mild threshold reductions at highest stimulus intensities after injection of 250 ng, and more extensive changes after injection of 500 ng. These data provide additional evidence for an important role for HIF-1 in retinal and choroidal NV and suggest that acriflavine can target HIF-1 through a variety of modes of administration and has good potential to provide a novel therapy for retinal and choroidal vascular diseases.

  10. Focal Choroidal Excavation

    PubMed Central

    Cebeci, Zafer; Bayraktar, Şerife; Oray, Merih; Kır, Nur

    2016-01-01

    Focal choroidal excavation is a choroidal pit that can be detected by optical coherence tomography. Central serous chorioretinopathy, choroidal neovascularization and polypoidal choroidal vasculopathy are pathologies associated with focal choroidal excavation. In this article, we present the follow-up and treatment outcomes of three eyes of two patients with focal choroidal excavation. PMID:28050329

  11. Focal Choroidal Excavation.

    PubMed

    Cebeci, Zafer; Bayraktar, Şerife; Oray, Merih; Kır, Nur

    2016-12-01

    Focal choroidal excavation is a choroidal pit that can be detected by optical coherence tomography. Central serous chorioretinopathy, choroidal neovascularization and polypoidal choroidal vasculopathy are pathologies associated with focal choroidal excavation. In this article, we present the follow-up and treatment outcomes of three eyes of two patients with focal choroidal excavation.

  12. Small Molecular-Sized Artesunate Attenuates Ocular Neovascularization via VEGFR2, PKCα, and PDGFR Targets

    PubMed Central

    Zong, Yao; Yuan, Yongguang; Qian, Xiaobing; Huang, Zhen; Yang, Wei; Lin, Leilei; Zheng, Qishan; Li, Yujie; He, Huining; Gao, Qianying

    2016-01-01

    Ocular neovascularization (NV) is the primary cause of blindness in many ocular diseases. Large molecular weight anti- vascular endothelial growth factor (VEGF) protein drugs, such as Avastin and Lucentis, have saved the vision of millions. However, approximately 20–30% of patients respond poorly to anti-VEGF treatment. We found that artesunate (ART), a small molecular derivative of artemisinin, had a significant inhibitory effect on ocular NV by downregulating the expression of VEGFR2, PKCα, and PDGFR. ART significantly inhibited retinal NV in rabbits and macular edema in monkeys with greater anterior chamber penetrability and more durable efficacy than Avastin. Our pilot study showed that intravitreal injection of 80 μg ART significantly inhibited iris and corneal NV in a severe retinal detachment case. Our results suggest that ART might be a potential persistent small-molecule drug to manage ocular NV via multi-targets. PMID:27480521

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

    PubMed Central

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

    2017-01-01

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

  14. Mechanism for laser-induced neovascularization in rat choroid: Accumulation of integrin α chain-positive cells and their ligands

    PubMed Central

    Nakajima, Takeshi; Hirata, Masayuki; Shearer, Thomas R.

    2014-01-01

    Purpose Inhibitors binding to integrins α5 and αv are antiangiogenic in models of choroidal neovascularization (CNV). However, a comprehensive understanding of the accumulation of integrin α isoform-positive cells, their ligands, and associations is limited. The purpose of the present study was to examine the localization of integrin α chain-positive cells and their extracellular matrix (ECM) ligands in the RPE/choroid after laser injury. Methods CNV, observed with fluorescein isothiocyanate (FITC)-labeled isolectin, was produced in Brown Norway rats with a 532 nm green laser. Localization of α5 and αv integrins and their ligands was performed with immunohistochemistry in consecutive cryosections. To test the binding specificity between the integrin α chains and ECM ligands, an in vitro cell adhesion assay was performed using retinal endothelial cells and specific antibodies. Results Angiogenesis was observed on day 7 after laser injury in choroidal flat mounts and cryosections. The number of integrin α5- and αv-positive cells markedly increased at day 3 and then gradually decreased, but was still elevated on day 14. One day after laser treatment, α integrin ligands fibronectin (FN) and vitronectin (VN) were markedly increased, and localized closely to integrins in the laser-injured regions. FN decreased on day 7, but was still retained until 14 days. In contrast, VN disappeared. Cell adhesion assays showed specific association of integrin α5 to FN, and integrin αv to VN. Conclusions Laser-induced choroidal injury increased FN and VN, followed by accumulation of integrin α5- and αv-positive cells. The interaction between integrin α chain-positive cells and their specific ligands FN and VN may be important steps leading to CNV. PMID:24959065

  15. 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

  16. Optical Coherence Tomography Angiography Demonstration of Choroidal Neovascularization in Malattia Leventinese.

    PubMed

    Corbelli, Eleonora; Corvi, Federico; Carnevali, Adriano; Querques, Lea; Zucchiatti, Ilaria; Bandello, Francesco; Querques, Giuseppe

    2016-06-01

    In a case of Malattia Leventinese, optical coherence tomography angiography led to the diagnosis of type 1 neovascularization, despite absence of evidence on conventional dye-based angiography. The authors hypothesize that, at least in some cases, accumulation of subretinal fluid in Malattia Leventinese could be due to a subretinal pigment epithelium (RPE) neovascular component rather than creation of hydrophobic barrier at the RPE and Bruch's membrane. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:602-604.].

  17. Inhibition of new vessel growth in mouse model of laser-induced choroidal neovascularization by adiponectin peptide II

    PubMed Central

    Lyzogubov, Valeriy V.; Tytarenko, Ruslana G.; Thotakura, Sushma; Viswanathan, Tito; Bora, Nalini S.; Bora, Puran S.

    2012-01-01

    We have investigated the effect of adiponectin (APN) peptide II on new vessel growth in mouse model of choroidal neovascularization (CNV) or wet type age-related macular degeneration (AMD). Mice were injected intraperitoneally with APN peptide II, control peptide, or PBS on day 1–7 or day 5–14. APN, AdipoR1, PCNA, and VEGF localization was investigated using confocal microscopy, immunohistochemistry, and RT-PCR. APN peptide II decreased the relative area of FITC-dextran perfused vessels by 4-fold, PCNA expression by 3-fold, and the number of PCNA stained HUVEC and MAVEC cells by 38 and 46%, respectively. We concluded that APN peptide II inhibits CNV size on days 7 and 14 by inhibiting the proliferation of endothelial cells in vivo and in vitro. APN peptide II may have therapeutic potential to inhibit CNV or wet AMD. PMID:19422927

  18. 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.

  19. A RANDOMIZED PILOT STUDY OF SYSTEMIC IMMUNOSUPPRESSION IN THE TREATMENT OF AGE-RELATED MACULAR DEGENERATION WITH CHOROIDAL NEOVASCULARIZATION

    PubMed Central

    Nussenblatt, Robert B.; Byrnes, Gordon; Sen, H. Nida; Yeh, Steven; Faia, Lisa; Meyerle, Catherine; Wroblewski, Keith; Li, Zhuqing; Liu, Baoying; Chew, Emily; Sherry, Patti R.; Friedman, Penelope; Ferris, Frederick

    2011-01-01

    Background Age-related macular degeneration remains the leading cause of irreversible blindness in the United States and the developed world. Intravitreal injections of anti–vascular endothelial growth factor (VEGF) medications have become standard of care for the treatment of the wet form of the disease. Recent reports have demonstrated an association with various immune factors. We aimed to investigate the effect of immunosuppressive therapy in the clinical course of the wet form of the disease. We compared anti-VEGF therapy plus one of three systemic immunosuppressive therapies versus anti-VEGF therapy alone for recurrent choroidal neovascularization associated with age-related macular degeneration. Methods This was a pilot, Phase I/II, prospective, randomized, unmasked, single-center trial. Patients with subretinal exudation secondary to recurrent choroidal neovascularization associated with age-related macular degeneration were included in the study. Patients were randomized to 1 of 3 systemic arms immunosuppressive agents (daclizumab, rapamycin, or infliximab) for 6 months plus intraocular anti-VEGF therapy if indicated, compared with a group who received only anti-VEGF therapy if indicated. Results The number of anti-VEGF injections per group, visual acuity, retinal thickness, and safety measures were assessed in all groups. Thirteen patients were randomized; comparing anti-VEGF injections before and during the study, a decrease in the number of injections from 0.73 injections per month to 0.42 for daclizumab and from 0.67 to 0.34 for sirolimus was seen, while no apparent decrease was seen for either infliximab or observation. Visual acuities were maintained in all groups. Conclusion These preliminary data suggest that some immunosuppressive agents given systemically can alter the clinical course of the wet form of the disease and support the notion that more definitive clinical trials of immune mediation of age-related macular degeneration are indicated

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

    PubMed Central

    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. PMID:25573059

  1. Antiproliferative, Apoptotic, and Autophagic Activity of Ranibizumab, Bevacizumab, Pegaptanib, and Aflibercept on Fibroblasts: Implication for Choroidal Neovascularization

    PubMed Central

    Lytvynchuk, Lyubomyr; Sergienko, Andrii; Lavrenchuk, Galina; Petrovski, Goran

    2015-01-01

    Purpose. Choroidal neovascularization (CNV) is one of the most common complications of retinal diseases accompanied by elevated secretion of vascular endothelial growth factor (VEGF). Intravitreal anti-VEGFs (ranibizumab, bevacizumab, pegaptanib, and aflibercept) can suppress neovascularization, decrease vascular permeability and CNV size, and, thereby, improve visual function. The antiproliferative, apoptotic, and autophagic effect of anti-VEGF drugs on fibroblasts found in CNVs has not been yet explored. Methods. Concentration-dependent cellular effects of the four anti-VEGFs were examined in L929 fibroblasts over a 5-day period. The cell survival, mitotic and polykaryocytic indices, the level of apoptosis and autophagy, and the cellular growth kinetics were all assessed. Results. The anti-VEGFs could inhibit the survival, mitotic activity, and proliferation as well as increase the cellular heterogeneity, apoptosis, and autophagy of the fibroblasts in a dose-dependent manner. Cellular growth kinetics showed ranibizumab to be less aggressive, but three other anti-VEGFs showed higher antiproliferative and apoptotic activity and expressed negative cellular growth kinetics. Conclusions. The antiproliferative, apoptotic, and autophagic activity of anti-VEGFs upon fibroblasts may explain the cellular response and the etiology of CNV involution in vivo and serve as a good study model for CNV in vitro. PMID:26491557

  2. Choroidal tuberculoma in a patient with ocular Behçet disease.

    PubMed

    Atmaca, Leyla; Yalçindağ, F Nilüfer; Ciledağ, Aydin

    2012-02-01

    Behçet disease is a chronic relapsing inflammatory disease affecting many different organs. Ocular involvement is quite common in the course of Behçet disease and is frequently manifested by bilateral panuveitis and retinal vasculitis. Medications such as corticosteroids and immunosuppressive agents are used to reduce inflammation in patients with posterior or panuveitis. Chronic immunosuppression is a risk factor for systemic infections. We report a case of choroidal tuberculoma associated with tuberculosis in a patient with ocular Behçet disease. A 25-year-old female with known ocular Behçet disease contracted tuberculosis 3 months earlier. She had been receiving methotrexate and oral steroids. Funduscopy of the left eye revealed a choroidal tuberculoma located superonasally to the optic disc. Fluorescein angiography showed a central area of hypofluorescence surrounded by a hyperfluorescent zone. Since she was already receiving antituberculosis treatment combined with oral steroids, the same treatment was continued. Diagnosis of the other diseases that may cause uveitis in patients with Behçet disease should not be missed. This is especially important since immunosuppressive drugs, that cause an increased incidence of systemic infections, are the common treatment of choice for patients with Behçet disease.

  3. 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

  4. Comparison Between Spectral-Domain and Swept-Source Optical Coherence Tomography Angiographic Imaging of Choroidal Neovascularization

    PubMed Central

    Miller, Andrew R.; Roisman, Luiz; Zhang, Qinqin; Zheng, Fang; Rafael de Oliveira Dias, Joao; Yehoshua, Zohar; Schaal, Karen B.; Feuer, William; Gregori, Giovanni; Chu, Zhongdi; Chen, Chieh-Li; Kubach, Sophie; An, Lin; Stetson, Paul F.; Durbin, Mary K.; Wang, Ruikang K.; Rosenfeld, Philip J.

    2017-01-01

    Purpose The purpose of this study was to compare imaging of choroidal neovascularization (CNV) using swept-source (SS) and spectral-domain (SD) optical coherence tomography angiography (OCTA). Methods Optical coherence tomography angiography was performed using a 100-kHz SS-OCT instrument and a 68-kHz SD-OCTA instrument (Carl Zeiss Meditec, Inc.). Both 3 × 3- and 6 × 6-mm2 scans were obtained on both instruments. The 3 × 3-mm2 SS-OCTA scans consisted of 300 A-scans per B-scan at 300 B-scan positions, and the SD-OCTA scans consisted of 245 A-scans at 245 B-scan positions. The 6 × 6-mm2 SS-OCTA scans consisted of 420 A-scans per B-scan at 420 B-scan positions, and the SD-OCTA scans consisted of 350 A-scans and 350 B-scan positions. B-scans were repeated four times at each position in the 3 × 3-mm2 scans and twice in the 6 × 6-mm2 scans. Choroidal neovascularization was excluded if not fully contained within the 3 × 3-mm2 scans. The same algorithm was used to detect CNV on both instruments. Two graders outlined the CNV, and the lesion areas were compared between instruments. Results Twenty-seven consecutive eyes from 23 patients were analyzed. For the 3 × 3-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.17 and 1.01 mm2, respectively (P = 0.047). For the 6 × 6-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.24 and 0.74 mm2 (P = 0.003). Conclusions The areas of CNV tended to be larger when imaged with SS-OCTA than with SD-OCTA, and this difference was greater for the 6 × 6-mm2 scans. PMID:28273316

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

    PubMed

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

    2015-01-01

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

  6. 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

  7. SIRT1 mediated inhibition of VEGF/VEGFR2 signaling by Resveratrol and its relevance to choroidal neovascularization

    PubMed Central

    Zhang, Huiming; He, Shikun; Spee, Christine; Ishikawa, Keijiro; Hinton, David R.

    2015-01-01

    SIRT1, a NAD+ dependent histone deacetylase, has been shown to act as a key regulator of angiogenesis. The purpose of this study was to determine the effects of resveratrol (RSV, a SIRT1 activator) on the vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathway and to establish its relevance to choroidal neovascularization (CNV), a blinding complication of age-related macular degeneration. Western blot and ELISA assay showed that RSV inhibited hypoxia-inducible factor (HIF)-1α accumulation and VEGF secretion induced by cobalt chloride (CoCl2) through SIRT1 in human retinal pigment epithelial (hRPE) cells. Furthermore, RSV down-regulated VEGFR2 phosphorylation and activation induced by VEGF in endothelial cells via SIRT1. Thus, the inhibitory effect of RSV on the HIF-1α\\VEGF\\ VEGFR2 signaling axis is mediated, at least in part, through SIRT1. The results suggest that targeting SIRT1 could have therapeutic potential for the treatment of CNV. PMID:26174951

  8. ICG videoangiography at very low light level of choroidal neovascularization and of central serous choroidopathy

    NASA Astrophysics Data System (ADS)

    Longobardi, Giuseppe; Ciamberlini, Claudio; Guarnieri, Vittorio; Panzardi, G.; Donati, M. C.

    1996-01-01

    ICG videoangiography has widely demonstrated its importance as an investigation method in several ocular pathologies. By means of an optoelectronic system developed by the authors, many cases of age related macular degeneration and central serous coroidopathy affecting patients of different ages have been investigated. The analysis of the eye fundus infrared-light images obtained allows the clinician to draw medical conclusions otherwise not obtainable with traditional visible-light techniques. A comprehensive survey and discussion of the most significant cases are presented.

  9. PKR promotes choroidal neovascularization via upregulating the PI3K/Akt signaling pathway in VEGF expression

    PubMed Central

    Zhu, Manhui; Liu, Xiaojuan; Wang, Shengcun; Miao, Jin; Wu, Liucheng; Yang, Xiaowei; Wang, Ying; Kang, Lihua; Li, Wendie; Cui, Chen; Sang, Aimin

    2016-01-01

    Purpose The aim of this study was to investigate the functions of dsRNA-activated protein kinase (PKR) in choroidal neovascularization (CNV) and related signaling pathways in the production of vascular endothelial growth factor (VEGF). Methods A chemical hypoxia model of in vitro RF/6A cells, a rhesus choroid-retinal endothelial cell line, was established by adding cobalt chloride (CoCl2) to the culture medium. PKR, phosphophosphatidylinositol 3-kinase (p-PI3K), phosphoprotein kinase B (p-Akt), and VEGF protein levels in RF/6A cells were detected with western blotting. PKR siRNA and the PI3K inhibitor LY294002 were used to evaluate the roles of the PKR and PI3K signaling pathways in VEGF expression with western blotting. In an ARPE-19 (RPE cell line) and RF/6A cell coculture system, proliferation, migration, and tube formation of RF/6A cells under hypoxic conditions were measured with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), Transwell, and Matrigel Transwell assays, respectively. In vivo CNV lesions were induced in C57BL/6J mice using laser photocoagulation. The mice were euthanized in a timely manner, and the eyecups were dissected from enucleated eyes. PKR, p-PI3K, p-Akt, and VEGF protein levels in tissues were detected with western blotting. To evaluate the leakage area, fundus fluorescein angiography and choroidal flat mount were performed on day 7 after intravitreal injection of an anti-PKR monoclonal antibody. Results The in vitro RF/6A cell chemical hypoxia model showed that PKR expression was upregulated in parallel with p-PI3K, p-Akt, and VEGF expression, peaking at 12 h. PKR siRNA downregulated PKR, p-PI3K, p-Akt, and VEGF expression. In addition, the PI3K inhibitor LY294002 greatly decreased the p-PI3K, p-Akt, and VEGF protein levels, but PKR expression was unaffected, indicating that Akt was a downstream molecule of PKR that upregulated VEGF expression. In the ARPE-19 (RPE cell line) and RF/6A cell coculture system, PKR si

  10. A Sema3C Mutant Resistant to Cleavage by Furin (FR-Sema3C) Inhibits Choroidal Neovascularization

    PubMed Central

    Toledano, Shira; Lu, Huayi; Palacio, Agustina; Ziv, Keren; Kessler, Ofra; Schaal, Shlomit; Neufeld, Gera; Barak, Yoreh

    2016-01-01

    In age-related macular degeneration (AMD), abnormal sub retinal choroidal neovascularization (CNV) is a major cause of blindness. FR-sema3C is a point mutated form of semaphorin-3C that is resistant to cleavage by furin like pro-protein convertases (FPPC). We have found in previous work that FR-sema3C functions as an anti-angiogenic factor. In this study we investigated the possible use of FR-sema3C as an inhibitor of CNV. FR-sema3C inhibits VEGF as well as PDGF-BB signal transduction in endothelial cells and to less extent bFGF induced signal transduction using a mechanism that does not depend upon the binding of VEGF like the drugs that are currently the mainstay treatment for AMD. CNV was induced in eyes of C57 black mice by laser photocoagulation. Intravitreal injection of FR-Sema3C or aflibercept (VEGF-trap) was then used to inhibit CNV formation. Invading choroidal vessels were visualized a week later by injection of FITC-dextran into the circulation, followed by the measurement of the area of the invading blood vessels. Injection of 0.1 μg FR-Sema3C inhibited CNV by 55% (P<0.01) and was as effective as 5 μg aflibercept. FR-sema3C did not display any adverse effects on retinal function following its injection into eyes of healthy mice as assessed by optokinetic reflex (OKR) and Electro-retinogram (ERG) criteria. Furthermore, FR-sema3C did not induce apoptosis in the retina as determined by TUNEL nor was there any discernable structural damage to the retina as assessed by several immuno-histochemical criteria. Our results suggest that FR-sema3C could perhaps be used for the treatment of AMD, and that it may perhaps be of benefit to patients that do not respond well to current treatments relying on VEGF sequestering agents. PMID:28036336

  11. Treatment Satisfaction and Well-Being in Patients with Myopic Choroidal Neovascularization Treated with Ranibizumab in the REPAIR Study

    PubMed Central

    Amoaku, Winfried M.; Gale, Richard P.; Lotery, Andrew J.; Menon, Geeta; Sivaprasad, Sobha; Petrillo, Jennifer; Quinn, Jennifer

    2015-01-01

    The Ranibizumab for the Treatment of Choroidal Neovascularisation (CNV) Secondary to Pathological Myopia (PM): an Individualized Regimen (REPAIR) trial was a prospective study exploring the efficacy and safety of intravitreal ranibizumab 0.5 mg using an individualized treatment regimen over 12 months. The current study investigated the impact of treatment with ranibizumab as needed (pro re nata [PRN]) on individuals with myopic choroidal neovascularization (mCNV) in the REPAIR study, using patient-reported outcome measures (PROMs) for treatment satisfaction and well-being. This study included 65 adults with mCNV and a best-corrected visual acuity (BCVA) letter score of 24–78 in the study eye. Patients completed the Macular Disease Treatment Satisfaction Questionnaire (MacTSQ) at months 1, 6 and 12, and the 12-item Well-Being Questionnaire (W-BQ12) at baseline and months 1, 6 and 12. Subgroup analyses investigated the relationship between PROM scores and treatment in the better- or worse-seeing eye (BSE/WSE), number of injections received, baseline BCVA, BCVA improvement and age. Pearson correlations between change in BCVA, MacTSQ scores and W-BQ12 scores were calculated. The main outcome measures were treatment satisfaction measured with the MacTSQ (score 0–72) and well-being measured with the W-BQ12 (score 0–36). Treatment satisfaction significantly increased over the study period (p = 0.0001). Mean MacTSQ scores increased by 9.7 and 10.0 in patients treated in their WSE and BSE, respectively. Treatment satisfaction was highest in individuals receiving only one injection at month 1; however, by month 12, scores were similar across injection subgroups. Patients aged 68 years or older had the highest MacTSQ scores. Well-being scores also significantly increased over the study period (p = 0.03). Mean W-BQ12 scores increased by 1.7 in patients treated in their WSE and by 2.1 in patients treated in their BSE. Individuals aged 40 years or younger had the greatest

  12. GENE TRANSFER FOR THE TREATMENT OF NEOVASCULAR OCULAR DISEASE (AN AMERICAN OPHTHALMOLOGICAL SOCIETY THESIS)

    PubMed Central

    Stout, John Timothy

    2006-01-01

    Purpose As vasoproliferative diseases account for a substantial fraction of worldwide blindness and share the activation of the angiogenic pathway as a common etiology, the expression of antiangiogenic proteins offers a promising means of treatment. This study was designed to develop viral vectors, harboring angiostatic genes, for the study and treatment of experimental proliferative ocular disease. A variety of methods (in vitro, ex vivo tissue, and in vivo) were employed to model the process of proliferation and test the effectiveness of these reagents. Methods Antiangiogenic genes included single genes as well as hybrid genes that fused the active elements of different genes. Genes studied included the soluble vascular endothelial growth factor receptor (sKDR), soluble neuropilin (sNRP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), plasminogen gene fragments (Kringle 1-3, 1-4, and 1-5), and soluble receptors for advanced glycosylation end products (sRAGE) genes, as well as the Endo:Ang, MIG:IP10, and Endo:Kringle5 fusion genes. All genes were cloned into a lentiviral vector system and were used to produce replication deficient lentiviral particles. These viral particles were used to transduce a variety of ocular cells and tissues to test viral transfer efficiency and transgene expression. In vivo systems were employed to explore the potential of these genes as antiangiogenic agents in models of corneal and retinal neovascular disease. Results Recombinant lentiviral particles, capable of transducing cell lines germane to eye disease (ocular endothelial, epithelial, and fibroblast cells), were successfully produced. These vectors were demonstrated to be effective in long-term transformation of cells and tissues. In vivo experiments confirmed that at least three different potentially angiostatic genes were successful in aborting the angiogenic process in the ocular models tested. Conclusions Lentiviral vectors are a viable means to deliver angiostatic genes

  13. Immunotherapy for choroidal neovascularization in a laser-induced mouse model simulating exudative (wet) macular degeneration

    NASA Astrophysics Data System (ADS)

    Bora, Puran S.; Hu, Zhiwei; Tezel, Tongalp H.; Sohn, Jeong-Hyeon; Kang, Shin Goo; Cruz, Jose M. C.; Bora, Nalini S.; Garen, Alan; Kaplan, Henry J.

    2003-03-01

    Age-related macular degeneration (AMD) is the leading cause of blindness after age 55 in the industrialized world. Severe loss of central vision frequently occurs with the exudative (wet) form of AMD, as a result of the formation of a pathological choroidal neovasculature (CNV) that damages the macular region of the retina. We tested the effect of an immunotherapy procedure, which had been shown to destroy the pathological neovasculature in solid tumors, on the formation of laser-induced CNV in a mouse model simulating exudative AMD in humans. The procedure involves administering an Icon molecule that binds with high affinity and specificity to tissue factor (TF), resulting in the activation of a potent cytolytic immune response against cells expressing TF. The Icon binds selectively to TF on the vascular endothelium of a CNV in the mouse and pig models and also on the CNV of patients with exudative AMD. Here we show that the Icon dramatically reduces the frequency of CNV formation in the mouse model. After laser treatment to induce CNV formation, the mice were injected either with an adenoviral vector encoding the Icon, resulting in synthesis of the Icon by vector-infected mouse cells, or with the Icon protein. The route of injection was i.v. or intraocular. The efficacy of the Icon in preventing formation of laser-induced CNV depends on binding selectively to the CNV. Because the Icon binds selectively to the CNV in exudative AMD as well as to laser-induced CNV, the Icon might also be efficacious for treating patients with exudative AMD.

  14. Gene Transfer of Prolyl Hydroxylase Domain 2 Inhibits Hypoxia-inducible Angiogenesis in a Model of Choroidal Neovascularization.

    PubMed

    Takei, Anna; Ekström, Malena; Mammadzada, Parviz; Aronsson, Monica; Yu, Ma; Kvanta, Anders; André, Helder

    2017-02-10

    Cellular responses to hypoxia are mediated by the hypoxia-inducible factors (HIF). In normoxia, HIF-α proteins are regulated by a family of dioxygenases, through prolyl and asparagyl hydroxylation, culminating in proteasomal degradation and transcriptional inactivation. In hypoxia, the dioxygenases become inactive and allow formation of HIF transcription factor, responsible for upregulation of hypoxia genes. In ocular neoangiogenic diseases, such as neovascular age-related macular degeneration (nAMD), hypoxia seems pivotal. Here, we investigate the effects of HIF regulatory proteins on the hypoxia pathway in retinal pigment epithelium (RPE) cells, critically involved in nAMD pathogenesis. Our data indicates that, in ARPE-19 cells, prolyl hydroxylase domain (PHD)2 is the most potent negative-regulator of the HIF pathway. The negative effects of PHD2 on the hypoxia pathway were associated with decreased HIF-1α protein levels, and concomitant decrease in angiogenic factors. ARPE-19 cells stably expressing PHD2 impaired angiogenesis in vitro by wound healing, tubulogenesis, and sprouting assays, as well as in vivo by iris-induced angiogenesis. Gene transfer of PHD2 in vivo resulted in mitigation of HIF-mediated angiogenesis in a mouse model of nAMD. These results may have implications for the clinical treatment of nAMD patients, particularly regarding the use of gene therapy to negatively regulate neoangiogenesis.

  15. Gene Transfer of Prolyl Hydroxylase Domain 2 Inhibits Hypoxia-inducible Angiogenesis in a Model of Choroidal Neovascularization

    PubMed Central

    Takei, Anna; Ekström, Malena; Mammadzada, Parviz; Aronsson, Monica; Yu, Ma; Kvanta, Anders; André, Helder

    2017-01-01

    Cellular responses to hypoxia are mediated by the hypoxia-inducible factors (HIF). In normoxia, HIF-α proteins are regulated by a family of dioxygenases, through prolyl and asparagyl hydroxylation, culminating in proteasomal degradation and transcriptional inactivation. In hypoxia, the dioxygenases become inactive and allow formation of HIF transcription factor, responsible for upregulation of hypoxia genes. In ocular neoangiogenic diseases, such as neovascular age-related macular degeneration (nAMD), hypoxia seems pivotal. Here, we investigate the effects of HIF regulatory proteins on the hypoxia pathway in retinal pigment epithelium (RPE) cells, critically involved in nAMD pathogenesis. Our data indicates that, in ARPE-19 cells, prolyl hydroxylase domain (PHD)2 is the most potent negative-regulator of the HIF pathway. The negative effects of PHD2 on the hypoxia pathway were associated with decreased HIF-1α protein levels, and concomitant decrease in angiogenic factors. ARPE-19 cells stably expressing PHD2 impaired angiogenesis in vitro by wound healing, tubulogenesis, and sprouting assays, as well as in vivo by iris-induced angiogenesis. Gene transfer of PHD2 in vivo resulted in mitigation of HIF-mediated angiogenesis in a mouse model of nAMD. These results may have implications for the clinical treatment of nAMD patients, particularly regarding the use of gene therapy to negatively regulate neoangiogenesis. PMID:28186209

  16. Migraine causes retinal and choroidal structural changes: evaluation with ocular coherence tomography.

    PubMed

    Reggio, Ester; Chisari, Clara G; Ferrigno, Giulia; Patti, Francesco; Donzuso, Giulia; Sciacca, Giorgia; Avitabile, Teresio; Faro, Salvatore; Zappia, Mario

    2017-03-01

    Few studies have evaluated whether the retina is involved in migraine through the evaluation of retinal nerve fiber layer (RNFL) examined with ocular coherence tomography (OCT) with conflicting results. Aim of this case-control study is to evaluate the retina and the choroid in migraine. Patients having migraine with aura (MwA) or without aura (MoA) and chronic migraine (CM) were evaluated. Age- and sex-matched normal subjects were selected as healthy controls (HC). Patients and HC were examined with OCT. RNFL, ganglion cell layer (GCL), foveal thickness (FT), choroidal thickness (CT) and total macular volume (TMV) were calculated for right eyes (RE) and left eyes (LE). Seventy-seven patients (62 women; 80.5%), 21 MoA, 12 MwA, 44 CM and 42 HC were enrolled in the study. Patients compared to HC had a significant reduction of RNFL (RE: 91.2 ± 9.2 vs 99.3 ± 7.5 μm; p < 0.001. LE: 93.3 ± 8.7 vs 100.2 ± 6.5 μm; p < 0.001). GCL (RE: 80.6 ± 6.4 vs 86.9 ± 2.1 μm; p < 0.0001. LE: 81.5 ± 5.7 vs 87.1 ± 2.6 μm; p < 0.0001) and CT (RE: 286.4 ± 31.4 vs 333.2 ± 3.1 μm; p < 0.0001. LE: 287.2 ± 31.6 vs 334.5 ± 4.1 μm; p < 0.0001) were thinner in patients compared to HC. Moreover, CM showed reduction of RNFL and of GCL compared to the other migraineurs. Finally, we found a significant inverse correlation between RNFL thickness and total number of headache attacks per months. Our data suggest the involvement of retina and choroid in migraineurs, especially in the CM group. Although migraine is an episodic and recurrent disease, its chronic nature might cause permanent structural abnormalities involving not only the brain, but also the retina.

  17. Sox4 regulates choroid fissure closure by limiting Hedgehog signaling during ocular morphogenesis

    PubMed Central

    Wen, Wen; Pillai-Kastoori, Lakshmi; Wilson, Stephen G.; Morris, Ann C.

    2015-01-01

    SoxC transcription factors play critical roles in many developmental processes, including neurogenesis, cardiac formation, and skeletal differentiation. In vitro and in vivo loss-of-function studies have suggested that SoxC genes are required for oculogenesis, however the mechanism was poorly understood. Here, we have explored the function of the SoxC factor Sox4 during zebrafish eye development. We show that sox4a and sox4b are expressed in the forebrain and periocular mesenchyme adjacent to the optic stalk during early eye development. Knockdown of sox4 in zebrafish resulted in coloboma, a structural malformation of the eye that is a significant cause of pediatric visual impairment in humans, in which the choroid fissure fails to close. Sox4 morphants displayed altered proximo-distal patterning of the optic vesicle, including expanded pax2 expression in the optic stalk, as well as ectopic cell proliferation in the retina. We show that the abnormal ocular morphogenesis observed in Sox4-deficient zebrafish is caused by elevated Hedgehog (Hh) signaling, and this is due to increased expression of the Hh pathway ligand Indian hedgehog b (ihhb). Consistent with these results, coloboma in sox4 morphants could be rescued by pharmacological treatment with the Hh inhibitor cyclopamine, or by co-knockdown of ihhb. Conversely, overexpression of sox4 reduced Hh signaling and ihhb expression, resulting in cyclopia. Finally, we demonstrate that sox4 and sox11 have overlapping, but not completely redundant, functions in regulating ocular morphogenesis. Taken together, our data demonstrate that Sox4 is required to limit the extent of Hh signaling during eye development, and suggest that mutations in SoxC factors could contribute to the development of coloboma. PMID:25557621

  18. Automated Quantitation of Choroidal Neovascularization: A Comparison Study Between Spectral-Domain and Swept-Source OCT Angiograms

    PubMed Central

    Zhang, Qinqin; Chen, Chieh-Li; Chu, Zhongdi; Zheng, Fang; Miller, Andrew; Roisman, Luiz; Rafael de Oliveira Dias, Joao; Yehoshua, Zohar; Schaal, Karen B.; Feuer, William; Gregori, Giovanni; Kubach, Sophie; An, Lin; Stetson, Paul F.; Durbin, Mary K.; Rosenfeld, Philip J.; Wang, Ruikang K.

    2017-01-01

    Purpose To compare the lesion sizes of choroidal neovascularization (CNV) imaged with spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) and measured using an automated detection algorithm. Methods Patients diagnosed with CNV were imaged by SD-OCTA and SS-OCTA systems using 3 × 3-mm and 6 × 6-mm scans. The complex optical microangiography (OMAGC) algorithm was used to generate the OCTA images. Optical coherence tomography A datasets for imaging CNV were derived by segmenting from the outer retina to 8 μm below Bruch's membrane. An artifact removal algorithm was used to generate angiograms free of retinal vessel projection artifacts. An automated detection algorithm was developed to quantify the size of the CNV. Automated measurements were compared with manual measurements. Measurements from SD-OCTA and SS-OCTA instruments were compared as well. Results Twenty-seven eyes from 23 subjects diagnosed with CNV were analyzed. No significant differences were detected between manual and automatic measurements: SD-OCTA 3 × 3-mm (P = 0.61, paired t-test) and 6 × 6-mm (P = 0.09, paired t-test) scans and the SS-OCTA 3 × 3-mm (P = 0.41, paired t-test) and 6 × 6-mm (P = 0.16, paired t-test) scans. Bland-Altman analyses were performed to confirm the agreement between automatic and manual measurements. Mean lesion sizes were significantly larger for the SS-OCTA images compared with the SD-OCTA images: 3 × 3-mm scans (P = 0.011, paired sample t-test) and the 6 × 6-mm scans (P = 0.021, paired t-test). Conclusions The automated algorithm measurements of CNV were in agreement with the hand-drawn measurements. On average, automated SS-OCTA measurements were larger than SD-OCTA measurements and consistent with the results from using hand-drawn measurements. PMID:28273317

  19. 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

  20. Panretinal photocoagulation for radiation-induced ocular ischemia

    SciTech Connect

    Augsburger, J.J.; Roth, S.E.; Magargal, L.E.; Shields, J.A.

    1987-08-01

    We present preliminary findings on the effectiveness of panretinal photocoagulation in preventing neovascular glaucoma in eyes with radiation-induced ocular ischemia. Our study group consisted of 20 patients who developed radiation-induced ocular ischemia following cobalt-60 plaque radiotherapy for a choroidal or ciliary body melanoma. Eleven of the 20 patients were treated by panretinal photocoagulation shortly after the diagnosis of ocular ischemia, but nine patients were left untreated. In this non-randomized study, the rate of development of neovascular glaucoma was significantly lower (p = 0.024) for the 11 photocoagulated patients than for the nine who were left untreated.

  1. Ocular Response of Choroidal Melanoma With Monosomy 3 Versus Disomy 3 After Iodine-125 Brachytherapy

    SciTech Connect

    Marathe, Omkar S.; Wu, Jeffrey; Lee, Steve P.; Yu Fei; Burgess, Barry L.; Leu Min; Straatsma, Bradley R.; McCannel, Tara A.

    2011-11-15

    Purpose: To report the ocular response of choroidal melanoma with monosomy 3 vs. disomy 3 after {sup 125}I brachytherapy. Methods and Materials: We evaluated patients with ciliochoroidal melanoma managed with fine needle aspiration biopsy immediately before plaque application for {sup 125}I brachytherapy between January 1, 2005 and December 31, 2008. Patients with (1) cytopathologic diagnosis of melanoma, (2) melanoma chromosome 3 status identified by fluorescence in situ hybridization, and (3) 6 or more months of follow-up after brachytherapy were sorted by monosomy 3 vs. disomy 3 and compared by Kruskal-Wallis test. Results: Among 40 ciliochoroidal melanomas (40 patients), 15 had monosomy 3 and 25 had disomy 3. Monosomy 3 melanomas had a median greatest basal diameter of 12.00 mm and a median tumor thickness of 6.69 mm before brachytherapy; at a median of 1.75 years after brachytherapy, median thickness was 3.10 mm. Median percentage decrease in tumor thickness was 48.3%. Disomy 3 melanomas had a median greatest basal diameter of 10.00 mm and median tumor thickness of 3.19 mm before brachytherapy; at a median of 2.00 years after brachytherapy, median tumor thickness was 2.37 mm. The median percentage decrease in tumor thickness was 22.7%. Monosomy 3 melanomas were statistically greater in size than disomy 3 melanomas (p < 0.001) and showed a greater decrease in tumor thickness after brachytherapy (p = 0.006). Conclusion: In this study, ciliochoroidal melanomas with monosomy 3 were significantly greater in size than disomy 3 melanoma and showed a significantly greater decrease in thickness at a median of 1.75 years after brachytherapy. The greater decrease in monosomy 3 melanoma thickness after brachytherapy is consistent with other malignancies in which more aggressive pathology has been shown to be associated with a greater initial response to radiotherapy.

  2. Unrelenting Ocular Pain as a Masquerading Symptom of Occult Choroidal Metastasis

    PubMed Central

    Deaner, Jordan D.; Pointdujour-Lim, Renelle; Say, Emil Anthony T.; Shields, Carol L.

    2017-01-01

    Purpose To report a case of chronic eye pain as a presenting feature of choroidal metastasis from lung cancer. Methods We report the case of a 58-year-old Caucasian woman with stage IV lung adenocarcinoma presenting with an 8-month history of left eye pain and blurred vision. Results The patient had previously consulted 14 ophthalmologists with varying diagnoses including posterior scleritis and trigeminal neuralgia. Visual acuity at presentation was 20/20 in the right eye and 20/80 in the left eye. Examination of the right eye was normal, while the left eye showed ill-defined flat yellow discoloration of the choroid with overlying shifting subretinal fluid. Ultrasonography demonstrated a dense choroidal thickening measuring 2.6 mm in size and showing subretinal fluid. Enhanced depth imaging optical coherence tomography revealed choroidal thickening with a ‘lumpy bumpy’ surface topography consistent with a metastatic choroidal tumor presumably from the patient's lung adenocarcinoma. Fine needle aspiration biopsy followed by treatment was recommended, but the patient declined and later succumbed to metastatic disease. Conclusion We present a case of chronic eye pain associated with diffuse choroidal thickening from metastatic lung adenocarcinoma that was previously unrecognized and misdiagnosed. This case emphasizes the importance of recognizing pain as a presenting symptom of choroidal metastasis. PMID:28275605

  3. Intravitreal Poly(L-lactide) Microparticles Sustain Retinal and Choroidal Delivery of TG-0054, a Hydrophilic Drug Intended for Neovascular Diseases

    PubMed Central

    Shelke, Namdev B; Kadam, Rajendra; Tyagi, Puneet; Rao, Vidhya R; Kompella, Uday B.

    2012-01-01

    While poorly soluble drugs such as corticosteroids sustain drug delivery in the vitreous humor by virtue of slow dissolution, macromolecules such as antibodies and their fragments sustain their levels due to their slow clearance. However, currently there are no approaches to sustain the delivery of well water soluble small molecule drugs in the vitreous. In this study we optimized a PLA microparticle formulation for sustained intravitreal delivery of TG-0054, a well water soluble anti-angiogenic drug that is of potential value in treating choroid neovascularization. After determining the influence of process parameters on particle size and drug loading, spherical microparticles syringeable through a 27 G needle, with a mean diameter of 7.6 μm, 10% w/w TG-0054 loading, sustained in vitro drug release for at least 6 months, and low residual organic solvent content (~ 1 ppb/mg) were prepared. Microparticles as well as drug solution were assessed for their in vivo drug delivery over 3 months following intravitreal injection in New Zealand white rabbits. Drug levels in the microparticle dosed eyes at 3 months were 43.7 ± 16.2, 243 ± 42.6, 62.8 ± 22.6 μg/g vitreous, retina, and choroid-RPE, respectively, and similar to levels at one month. Intravitreal injection of plain drug solution resulted in significantly lower amounts of drug in the dosed eye, with the levels being 0.8 ± 0.5, 2.7 ± 2.8, and 4.9± 4.2 μg/g in vitreous, retina, and choroid-RPE, respectively, at one month, with no detectable drug at three months. Although surface degradation was evident, microparticles maintained their spherical structure during the 6 months in vitro study and the 3 months in vivo study, with the vitreal particle retention at 1 and 3 months being 60% and 27%, respectively. Thus, PLA microparticles capable of sustaining retinal and choroidal delivery of TG-0054 for three to six months were developed. PMID:22888471

  4. Change in choroidal thickness after intravitreal aflibercept in pretreated and treatment-naive eyes for neovascular age-related macular degeneration

    PubMed Central

    Mazaraki, Kyriaki; Fassnacht-Riederle, Heidi; Blum, Robert; Becker, Matthias; Michels, Stephan

    2015-01-01

    Aim Evaluation of effects of intravitreal aflibercept therapy on choroidal thickness (CT) in neovascular age-related macular degeneration. Methods Retrospective cohort study evaluating the change in CT following a loading dose of three intravitreal aflibercept injections at 4 weeks interval. Pretreated and treatment-naive eyes as well as untreated fellow eyes were evaluated at five retinal locations (subfoveal, 300 and 2500 µm nasal and temporal to the fovea) using spectral domain optical coherence tomography prior to and 4 weeks after a loading dose of three intravitreal aflibercept injections. Results A total of 84 treated eyes (61 pretreated, 23 treatment naive) and 48 fellow eyes were enrolled into the study. Treatment-naive and pretreated eyes showed a significant reduction in CT at all retinal locations. The effect was more pronounced in treatment-naive eyes. In the pretreated group, the mean reduction in CT was greatest at 2500 µm temporal to the fovea at 10.7 µm compared with 22.4 at 300 µm nasal to the fovea in the treatment-naive group. Only the fellow eyes in the treatment-naive group showed a significant CT reduction 12 weeks after initiation of therapy to the partner eye. Conclusions Aflibercept induces a reduction in CT in treatment-naive and pretreated eyes with neovascular age-related macular degeneration. There is some evidence of a systemic effect of aflibercept reflected by CT reduction in untreated fellow eyes. PMID:25877895

  5. 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

  6. Stereotactic radiotherapy in neovascular age-related macular degeneration: Real-life efficacy and morphological evaluation of the outer retina-choroid complex.

    PubMed

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

    2016-12-01

    Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address in this retrospective analysis.Patients who met the INTREPID criteria for best responders were eligible for SRT. A total of 32 eyes of 32 patients were treated. Thereafter, patients were examined monthly for 12 months and received pro re nata IVI of aflibercept or ranibizumab. Outcome measures were: mean number of injections, best-corrected visual acuity, and morphological changes of the outer retina-choroid complex as well as patient safety.Mean number of IVI decreased by almost 50% during the 12 months after SRT compared to the year before, whereas visual acuity increased by one line (logMAR). Morphological evaluation showed that most changes affect outer retinal layers.Stereotactic radiotherapy significantly reduced IVI retreatment in nAMD patients under real-life circumstances. Therefore, SRT might be the first step to stop visual loss as a result of IVI undertreatment, which is a major risk.

  7. Natural product inhibitors of ocular angiogenesis

    PubMed Central

    Sulaiman, Rania S.; Basavarajappa, Halesha D.; Corson, Timothy W.

    2014-01-01

    Natural products are characterized by high chemical diversity and biochemical specificity; therefore, they are appealing as lead compounds for drug discovery. Given the importance of angiogenesis to many pathologies, numerous natural products have been explored as potential anti-angiogenic drugs. Ocular angiogenesis underlies blinding eye diseases such as retinopathy of prematurity (ROP) in children, proliferative diabetic retinopathy (DR) in adults of working age, and age-related macular degeneration (AMD) in the elderly. Despite the presence of effective therapy in many cases, these diseases are still a significant health burden. Anti-VEGF biologics are the standard of care, but may cause ocular or systemic side effects after intraocular administration and patients may be refractory. Many anti-angiogenic compounds inhibit tumor growth and metastasis alone or in combination therapy, but a more select subset of them has been tested in the context of ocular neovascular diseases. Here, we review the promise of natural products as anti-angiogenic agents, with a specific focus on retinal and choroidal neovascularization. The multifunctional curcumin and the chalcone isoliquiritigenin have demonstrated promising anti-angiogenic effects in mouse models of DR and choroidal neovascularization (CNV) respectively. The homoisoflavanone cremastranone and the flavonoid deguelin have been shown to inhibit ocular neovascularization in more than one disease model. The isoflavone genistein and the flavone apigenin on the other hand are showing potential in the prevention of retinal and choroidal angiogenesis with long-term administration. Many other products with antiangiogenic potential in vitro such as the lactone withaferin A, the flavonol quercetin, and the stilbenoid combretastatin A4 are awaiting investigation in different ocular disease relevant animal models. These natural products may serve as lead compounds for the design of more specific, efficacious, and affordable

  8. Intravitreal triamcinolone with transpupillary therapy for subfoveal choroidal neovascularization in age related macular degeneration. A randomized controlled pilot study [ISRCTN74123635

    PubMed Central

    Agurto-Rivera, Ricardo; Diaz-Rubio, Jose; Torres-Bernal, Luis; Macky, Tamer A; Colina-Luquez, Juner; Papa-Oliva, Gabriela; Jager, Rama D; Martinez-Jardon, Susana; Fromow-Guerra, Jans; Quiroz-Mercado, Hugo

    2005-01-01

    Background To assess the effect of intravitreal triamcinolone acetonide (iTA) as an adjunctive treatment to transpupillary therapy (TTT) for new subfoveal choroidal neovascular membranes (CNV) in age-related macular degeneration (AMD). Methods This prospective randomized controlled pilot study comprised 26 patients scheduled to receive TTT, due to either absent indications for photodynamic therapy or financial issues. Patients were assigned into; Group A (n = 14) received TTT alone and Group B (n = 12) received iTA (4 mg) followed by TTT within one week. Follow ups were at 2 weeks, and 1, 3 and 6 months for; best-corrected visual acuity (BCVA) by ETDRS chart at 4 meters, intraocular pressures (IOP), fluorescein angiography (FAG), and central foveal thickness by optical coherence tomography (OCT). Results All 26 patients completed 6 months of follow ups. The average age for both groups was 74 years. Occult CNV formed 64% and 41%; classis/predominately classic 21% and 16.6%; and minimally classic 15% and 42.4% of group A and B respectively. At baseline; the mean BCVA was 0.045 for group A and 0.04 for group B; mean CNV size was 6.15 disc diameter (DD) and 2.44 DD; mean OCT foveal thickness was 513 um and 411 um for group A and B respectively with no statistical differences (P = 0.8, 0.07, and 0.19). At six months the proportion of patients gained ≥ 1 lines was 14% and 25% (P = 0.136) and stabilization was 86% and 66% (P = 0.336); the mean size of the CNV was 5.63 DD and 2.67 DD (P = 0.162); rate of CNV closure was 64% and 83% (P = 0.275); and the mean OCT central foveal thickness was 516.36 um and 453.67 um (P = 0.341), for group A and B respectively. Conclusion The use of iTA as an adjunctive to TTT for new subfoveal CNV in AMD showed a tendency towards better functional results. However due to the small sample size of the study a statistically significant results could not be reached. PMID:16309554

  9. Choroidal neovascularization analyzed on ultra-high speed swept source optical coherence tomography angiography compared to spectral domain optical coherence tomography angiography

    PubMed Central

    Novais, Eduardo A.; Adhi, Mehreen; Moult, Eric M.; Louzada, Ricardo N.; Cole, Emily D.; Husvogt, Lennart; Lee, ByungKun; Dang, Sabin; Regatieri, Caio V. S.; Witkin, André J.; Baumal, Caroline R.; Hornegger, Joachim; Jayaraman, Vijaysekhar; Fujimoto, James G; Duker, Jay S.; Waheed, Nadia K.

    2016-01-01

    Purpose To compare visualization of choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) using an ultra-high speed swept-source (SS)-optical coherence tomography angiography (OCTA) prototype versus a spectral-domain (SD)-OCTA device. Design Comparative analysis of diagnostic instruments. Methods Patients were prospectively recruited to be imaged on SD-OCT and SS-OCT devices on the same day. The SD-OCT device employed is the RTVue Avanti that operates at ~840nm wavelength and 70,000 A-scans/second. The SS-OCT device used is an ultra-high speed long-wavelength prototype that operates at ~1050nm wavelength and 400,000 A-scans/second. Two observers independently measured the CNV area on OCTA en face images from the two devices using ImageJ. The non-parametric Wilcoxon signed-rank test was used to compare area measurements and p-values of <0.05 were considered statistically significant. Results Fourteen eyes from 13 patients were enrolled. The CNV in 11 eyes (78.6%) were classified as type-1, 2 eyes (14.3%) as type-2, and 1 eye (7.1%) as mixed type. Total CNV area measured using SS-OCT and SD-OCT 3mm × 3mm OCTA were 0.949 ± 1.168mm2 and 0.340 ± 0.301mm2, respectively (p=0.001). For the 6mm × 6mm OCTA the total CNV area using SS-OCT and SD-OCT were 1.218 ± 1.284mm2 and 0.604 ± 0.597mm2, respectively (p=0.0019). The field of view did not significantly affect the measured CNV area (p=0.19 and p=0.18 for SS-OCT and SD-OCT respectively). Conclusion SS-OCTA yielded significantly larger CNV areas than SD-OCTA. It is possible that SS-OCTA is better able to demarcate the full extent of CNV vasculature. PMID:26851725

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

    PubMed Central

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

    2017-01-01

    We report a case of a Caucasian female who developed active polypoidal choroidal vasculopathy (PCV) at the edge of a stable choroidal nevus and was successfully treated with verteporfin photodynamic therapy. No active polyp was detectable on indocyanine green angiography 2 years after treatment, and good vision was maintained. Indocyanine green angiography is a useful investigation to diagnose PCV and may be underutilized. Unlike treatment of choroidal neovascularization secondary to choroidal nevus, management of PCV secondary to nevus may not require intravitreal anti-vascular endothelial growth factor therapy. Photodynamic monotherapy may be an effective treatment of secondary PCV. PMID:28243154

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

    PubMed

    Dong, Ling-Feng; Yao, Jin; Wang, Xiao-Qun; Shan, Kun; Yang, Hong; Yan, Biao; Jiang, Qin

    2015-10-02

    Ocular angiogenesis is an important pathologic character of several ocular diseases, such as retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration (AMD). Inhibition of ocular angiogenesis has great therapeutic value for treating these dieses. Here we show that lenalidomide, an anti-tumor drug, has great anti-angiogenic potential in ocular diseases. Lenalidomide inhibits retinal endothelial cell viability in normal and pathological condition, and inhibits VEGF-induced endothelial cell migration and tube formation in vitro. Moreover, lenalidomide inhibits ocular angiogenesis in vivo through the reduction of angiogenesis- and inflammation-related protein expression. Collectively, lenalidomide is a promising drug for treating ocular angiogenesis through its anti-proliferative and anti-inflammatory property.

  12. Ocular axial length and choroidal thickness in newly hatched chicks and one-year-old chickens fluctuate in a diurnal pattern that is influenced by visual experience and intraocular pressure changes.

    PubMed

    Papastergiou, G I; Schmid, G F; Riva, C E; Mendel, M J; Stone, R A; Laties, A M

    1998-02-01

    Low coherence laser Doppler interferometry (LDI) allows high precision measurements of the axial length of the eye and of the thickness of the individual layers of the ocular fundus. Here, we used LDI to monitor diurnal changes in these dimensions in eyes of newly hatched chicks and one-year-old chickens with normal or altered visual input. In chicks and chickens with normal visual experience, axial eye length displays diurnal fluctuations increasing during the light phase. Choroidal thickness also exhibits a diurnal pattern, shrinking during the day and expanding during the night. Retinal thickness does not vary. Based on the pressure compliance of the enucleated chick eye, the diurnal intraocular pressure (IOP) fluctuation could contribute both to the increase in axial length and to daytime choroidal shrinkage. Following deprivation of form vision by unilateral goggle wear, occluded chick eyes demonstrate enhanced axial elongation. Diurnal fluctuations in axial length but not in choroidal thickness are temporarily disrupted. The retina of form deprived eyes thins approximately 10% in five days. In contralateral eyes, the diurnal patterns of both axial length and choroidal thickness fluctuations are also disrupted. Following occluder removal in chicks, choroidal thickness increases for several days during both the light and dark phase, leading to its overall expansion. Retinal thickness returns to baseline. When deprived of form vision for five days, the eyes of year-old chickens do not exhibit measurable axial elongation. Diurnal patterns of fluctuation in axial length and choroidal thickness are however disrupted. After goggle removal, axial length fluctuation is restored to normal, but the diurnal choroidal thickness pattern is inverted. In contralateral eyes, choroidal thickness exhibits normal diurnal fluctuations both during and after form vision deprivation. In conclusion, axial length and choroidal thickness fluctuations are influenced by visual experience

  13. Molecular Pathogenesis of Retinal and Choroidal Vascular Diseases

    PubMed Central

    Campochiaro, Peter A.

    2015-01-01

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

  14. Cysteine-rich protein 61 (CCN1) and connective tissue growth factor (CCN2) at the crosshairs of ocular neovascular and fibrovascular disease therapy.

    PubMed

    Yan, Lulu; Chaqour, Brahim

    2013-12-01

    The vasculature forms a highly branched network investing every organ of vertebrate organisms. The retinal circulation, in particular, is supported by a central retinal artery branching into superficial arteries, which dive into the retina to form a dense network of capillaries in the deeper retinal layers. The function of the retina is highly dependent on the integrity and proper functioning of its vascular network and numerous ocular diseases including diabetic retinopathy, age-related macular degeneration and retinopathy of prematurity are caused by vascular abnormalities culminating in total and sometimes irreversible loss of vision. CCN1 and CCN2 are inducible extracellular matrix (ECM) proteins which play a major role in normal and aberrant formation of blood vessels as their expression is associated with developmental and pathological angiogenesis. Both CCN1 and CCN2 achieve disparate cell-type and context-dependent activities through modulation of the angiogenic and synthetic phenotype of vascular and mesenchymal cells respectively. At the molecular level, CCN1 and CCN2 may control capillary growth and vascular cell differentiation by altering the composition or function of the constitutive ECM proteins, potentiating or interfering with the activity of various ligands and/or their receptors, physically interfering with the ECM-cell surface interconnections, and/or reprogramming gene expression driving cells toward new phenotypes. As such, these proteins emerged as important prognostic markers and potential therapeutic targets in neovascular and fibrovascular diseases of the eye. The purpose of this review is to highlight our current knowledge and understanding of the most recent data linking CCN1 and CCN2 signaling to ocular neovascularization bolstering the potential value of targeting these proteins in a therapeutic context.

  15. Ocular histoplasmosis syndrome.

    PubMed

    Diaz, Rocio I; Sigler, Eric J; Rafieetary, Mohammad R; Calzada, Jorge I

    2015-01-01

    Ocular histoplasmosis syndrome (OHS) is a chorioretinal disorder with a distinct fundus appearance that is commonly found in regions endemic for Histoplasma capsulatum. Choroidal neovascularization (CNV) secondary to OHS is considered one of the principal causes of central vision loss among young adults in endemic areas. Although there is no consensus regarding its pathogenesis, evidence points to Histoplasma capsulatum as the most probable etiology. Once considered an intractable hemorrhagic maculopathy, CNVs are now treatable. Extrafoveal CNVs are successfully treated with laser photocoagulation. Subfoveal and juxtafoveal CNVs are managed with anti-vascular endothelial growth factor therapy, photodynamic therapy, or a combination of both. Modern imaging technologies such as spectral-domain optical coherence tomography have improved our diagnostic abilities, making it easier to monitor disease activity and CNV regression. We review the epidemiology, pathogenesis, clinical manifestations, differential diagnosis, and current treatment of this disease.

  16. Peripapillary subretinal neovascularization and serous macular detachment. Association with congenital optic nerve pits.

    PubMed

    Borodic, G E; Gragoudas, E S; Edward, W O; Brockhurst, R J

    1984-02-01

    Congenital anomalous disc changes were associated with acquired macular detachment and peripapillary choroidal neovascularization in two cases. The anomalous disc changes resembled optic nerve pits. In one case, the peripapillary choroidal neovascularization was treated with argon laser photocoagulation, with subsequent reattachment of the macula and considerable improvement in the visual acuity. Although the pathogenesis of macular detachment occurring with optic nerve pits is usually not disclosed by fluorescein angiography, leakage from choroidal neovascularization can occur with this congenital defect and may contribute to the formation of a neurosensory macular detachment. If found, choroidal neovascularization may represent a remedial cause for visual loss in a condition with an otherwise poor prognosis.

  17. Neuropilin 1 Involvement in Choroidal and Retinal Neovascularisation

    PubMed Central

    Fernández-Robredo, Patricia; Sim, Dawn A.; Fruttiger, Marcus

    2017-01-01

    Purpose Inhibiting VEGF is the gold standard treatment for neovascular age-related macular degeneration (AMD). It is also effective in preventing retinal oedema and neovascularisation (NV) in diabetic retinopathy (DR) and retinal vein occlusions (RVO). Neuropilin 1 (Nrp1) is a co-receptor for VEGF and many other growth factors, and therefore a possible alternative drug target in intra ocular neovascular disease. Here we assessed choroidal and retinal NV in an inducible, endothelial specific knock out model for Nrp1. Methods Crossing Nrp1 floxed mice with Pdgfb-CreERT2 mice produced tamoxifen-inducible, endothelial specific Nrp1 knock out mice (Nrp1ΔEC) and Cre-negative, control littermates. Cre-recombinase activity was confirmed in the Ai3(RCL-EYFP) reporter strain. Animals were subjected to laser-induced CNV (532 nm) and spectral domain-optical coherence tomography (SD-OCT) was performed immediately after laser and at day 7. Fluorescein angiography (FA) evaluated leakage and postmortem lectin staining in flat mounted RPE/choroid complexes was also used to measure CNV. Furthermore, retinal neovascularisation in the oxygen induced retinopathy (OIR) model was assessed by immunohistochemistry in retinal flatmounts. Results In vivo FA, OCT and post-mortem lectin staining showed a statistically significant reduction in leakage (p<0.05), CNV volume (p<0.05) and CNV area (p<0.05) in the Nrp1ΔEC mice compared to their Cre-negative littermates. Also the OIR model showed reduced retinal NV in the mutant animals compared to wild types (p<0.001). Conclusion We have demonstrated reduced choroidal and retinal NV in animals that lack endothelial Nrp1, confirming a role of Nrp1 in those processes. Therefore, Nrp1 may be a promising drug target for neovascular diseases in the eye. PMID:28107458

  18. 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.

  19. THE MULTIFUNCTIONAL CHOROID

    PubMed Central

    Nickla, Debora L.; Wallman, Josh

    2010-01-01

    slowing of ocular elongation, and attempts to decouple the choroidal and scleral changes have largely failed, it seems that the thickening of the choroid may be mechanistically linked to the scleral synthesis of macromolecules, and thus may play an important role in the homeostatic control of eye growth, and, consequently, in the etiology of myopia and hyperopia. PMID:20044062

  20. 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

  1. [Choroidal neovascularisation in a patient with choroidal osteoma visualized by OCT angiography].

    PubMed

    Mihailovic, N; Alnawaiseh, M; Merté, R-L; Eter, N

    2016-11-04

    We present the case of a 38-year-old Asian patient who reported vision loss of her left eye since 4 weeks. The funduscopy showed a choroidal tumor in the papillomacular bundle, which could be identified as a choroidal osteoma with secondary choroidal neovascularization (CNV). OCT angiography (OCT-A) detected abnormal flow in the choriocapillaris; the osteoma showed no flow in the OCT angiogram of the choroid level. Therefore, OCT-A can be a helpful adjuvant for diagnosis of CNV secondary to choroidal osteoma.

  2. Comparative study between a spectral domain and a high-speed single-beam swept source OCTA system for identifying choroidal neovascularization in AMD

    NASA Astrophysics Data System (ADS)

    Told, R.; Ginner, L.; Hecht, A.; Sacu, S.; Leitgeb, R.; Pollreisz, A.; Schmidt-Erfurth, U.

    2016-12-01

    This comparative study between a SD- and SS-OCTA system for visualizing neovascular patterns in AMD, also assessed the influence of cataract on OCTA imaging. 25 eyes with active CNV (AMD) were documented by FA, ICGA and SD-OCT. Two OCTA devices were used: A custom built SS-OCTA (1050 nm, 400,000 A-scans/s, 5 × 5 mm, no image segmentation); AngioVue (OptoVue, CA, USA) SD-OCTA (840 nm, 70.000 A-scans/s, 3 × 3 mm, SSADA technology). Two retina experts graded CNV types and vascular patterns. Cataract influence on OCTA image quality was reported for the superficial retinal plexus (6 eyes). The SS-OCTA prototype showed more CNV lesions compared to the SD-OCTA system (p = 0.01). Overall sensitivity of SD- and SS-OCTA systems to detect CNV lesions was.32 and.68, respectively. The SS-OCTA system was able to detect discrete lesion characteristics better than the SD-OCTA. No significant difference was found in the ability to identify CNV in treatment-naïve eyes. There was no significant influence of cataract. The SS-OCTA prototype detected CNV-associated vascular patterns more reliably than the SD-OCTA system. This is attributed to the SS-OCTA system’s longer center wavelength and higher A-scan rate yielding higher definition and contrast of small neovascular structures. The SS-OCTA system used showed no advantage regarding cataract influence.

  3. Comparative study between a spectral domain and a high-speed single-beam swept source OCTA system for identifying choroidal neovascularization in AMD.

    PubMed

    Told, R; Ginner, L; Hecht, A; Sacu, S; Leitgeb, R; Pollreisz, A; Schmidt-Erfurth, U

    2016-12-05

    This comparative study between a SD- and SS-OCTA system for visualizing neovascular patterns in AMD, also assessed the influence of cataract on OCTA imaging. 25 eyes with active CNV (AMD) were documented by FA, ICGA and SD-OCT. Two OCTA devices were used: A custom built SS-OCTA (1050 nm, 400,000 A-scans/s, 5 × 5 mm, no image segmentation); AngioVue (OptoVue, CA, USA) SD-OCTA (840 nm, 70.000 A-scans/s, 3 × 3 mm, SSADA technology). Two retina experts graded CNV types and vascular patterns. Cataract influence on OCTA image quality was reported for the superficial retinal plexus (6 eyes). The SS-OCTA prototype showed more CNV lesions compared to the SD-OCTA system (p = 0.01). Overall sensitivity of SD- and SS-OCTA systems to detect CNV lesions was.32 and.68, respectively. The SS-OCTA system was able to detect discrete lesion characteristics better than the SD-OCTA. No significant difference was found in the ability to identify CNV in treatment-naïve eyes. There was no significant influence of cataract. The SS-OCTA prototype detected CNV-associated vascular patterns more reliably than the SD-OCTA system. This is attributed to the SS-OCTA system's longer center wavelength and higher A-scan rate yielding higher definition and contrast of small neovascular structures. The SS-OCTA system used showed no advantage regarding cataract influence.

  4. Comparative study between a spectral domain and a high-speed single-beam swept source OCTA system for identifying choroidal neovascularization in AMD

    PubMed Central

    Told, R.; Ginner, L.; Hecht, A.; Sacu, S.; Leitgeb, R.; Pollreisz, A.; Schmidt-Erfurth, U.

    2016-01-01

    This comparative study between a SD- and SS-OCTA system for visualizing neovascular patterns in AMD, also assessed the influence of cataract on OCTA imaging. 25 eyes with active CNV (AMD) were documented by FA, ICGA and SD-OCT. Two OCTA devices were used: A custom built SS-OCTA (1050 nm, 400,000 A-scans/s, 5 × 5 mm, no image segmentation); AngioVue (OptoVue, CA, USA) SD-OCTA (840 nm, 70.000 A-scans/s, 3 × 3 mm, SSADA technology). Two retina experts graded CNV types and vascular patterns. Cataract influence on OCTA image quality was reported for the superficial retinal plexus (6 eyes). The SS-OCTA prototype showed more CNV lesions compared to the SD-OCTA system (p = 0.01). Overall sensitivity of SD- and SS-OCTA systems to detect CNV lesions was.32 and.68, respectively. The SS-OCTA system was able to detect discrete lesion characteristics better than the SD-OCTA. No significant difference was found in the ability to identify CNV in treatment-naïve eyes. There was no significant influence of cataract. The SS-OCTA prototype detected CNV-associated vascular patterns more reliably than the SD-OCTA system. This is attributed to the SS-OCTA system’s longer center wavelength and higher A-scan rate yielding higher definition and contrast of small neovascular structures. The SS-OCTA system used showed no advantage regarding cataract influence. PMID:27917889

  5. [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.

  6. Choroid Plexus

    MedlinePlus

    ... Learning Subscribe for e-updates Please leave this field empty Choroid Plexus SHARE Home > Brain Tumor Information > Types of Tumors These tumors arise from brain tissue called the “choroid plexus.” They commonly invade nearby ...

  7. Targeting VE-PTP activates TIE2 and stabilizes the ocular vasculature

    PubMed Central

    Shen, Jikui; Frye, Maike; Lee, Bonnie L.; Reinardy, Jessica L.; McClung, Joseph M.; Ding, Kun; Kojima, Masashi; Xia, Huiming; Seidel, Christopher; Silva, Raquel Lima e; Dong, Aling; Hackett, Sean F.; Wang, Jiangxia; Howard, Brian W.; Vestweber, Dietmar; Kontos, Christopher D.; Peters, Kevin G.; Campochiaro, Peter A.

    2014-01-01

    Retinal and choroidal neovascularization (NV) and vascular leakage contribute to visual impairment in several common ocular diseases. The angiopoietin/TIE2 (ANG/TIE2) pathway maintains vascular integrity, and negative regulators of this pathway are potential therapeutic targets for these diseases. Here, we demonstrated that vascular endothelial-protein tyrosine phosphatase (VE-PTP), which negatively regulates TIE2 activation, is upregulated in hypoxic vascular endothelial cells, particularly in retinal NV. Intraocular injection of an anti–VE-PTP antibody previously shown to activate TIE2 suppressed ocular NV. Furthermore, a small-molecule inhibitor of VE-PTP catalytic activity (AKB-9778) activated TIE2, enhanced ANG1-induced TIE2 activation, and stimulated phosphorylation of signaling molecules in the TIE2 pathway, including AKT, eNOS, and ERK. In mouse models of neovascular age-related macular degeneration, AKB-9778 induced phosphorylation of TIE2 and strongly suppressed NV. Ischemia-induced retinal NV, which is relevant to diabetic retinopathy, was accentuated by the induction of ANG2 but inhibited by AKB-9778, even in the presence of high levels of ANG2. AKB-9778 also blocked VEGF-induced leakage from dermal and retinal vessels and prevented exudative retinal detachments in double-transgenic mice with high expression of VEGF in photoreceptors. These data support targeting VE-PTP to stabilize retinal and choroidal blood vessels and suggest that this strategy has potential for patients with a wide variety of retinal and choroidal vascular diseases PMID:25180601

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

    PubMed

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

    2015-05-01

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

  9. 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

  10. [Ocular fundus disease in China: the current situation, progression, and issues to be resolved].

    PubMed

    Xu, Xun

    2014-11-01

    Ocular fundus disease is an important cause of blindness in China today. It has been a serious threat to people's health and quality of life. After unremitting efforts of generations, we have made remarkable achievements in the prevention, diagnosis, and treatment of ocular fundus disease. We have achieved many breakthroughs and progressions in the investigations of diabetic retinopathy, choroidal neovascularization, pediatric fundus disease, and other major diseases. And weare gradually standardizing imaging data management, new drug development procedures, and multi-center clinical trials. In the future, we need to further standardize the clinical diagnosis and treatment, to accelerate the basic research of serious and rare diseases, and to improve the overall level in the field of ocular fundus disease in China, so as to enhance our international influence in ophthalmology.

  11. Slit-Robo signaling in ocular angiogenesis.

    PubMed

    Chen, Haoyu; Zhang, Mingzhi; Tang, Shibo; London, Nyall R; Li, Dean Y; Zhang, Kang

    2010-01-01

    Slit-Robo signaling was firstly discovered as a major repellent pathway at the midline of the central nervous system. Intense investigation found that this pathway also plays an important role in other biological process including angiogenesis. Robo4 is the vascular endothelial cell specific member of Robo family. It was found that Slit-Robo signaling can inhibit endothelial cell migration, tube formation and vascular permeability. Slit-Robo signaling also plays an important role in embryonic and tumor angiogenesis. In animal model of ocular angiogenesis, addition of Slit inhibited laser induced choroidal neovascularization, oxygen induced retinopathy and VEGF induced retinal permeability in a Robo4 dependent manner. Recent data demonstrates that Robo1 and Robo4 form a heterodimer in endothelial cells, The role of this heterodimer in counteracting VEGF signaling is unknown. Further investigation is required to better understand Slit-Robo signaling and develop novel therapy for angiogenesis.

  12. 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.

  13. Peripapillary choroidal thickness in healthy Chinese subjects

    PubMed Central

    2013-01-01

    Background To evaluate the peripapillary choroidal thickness of a healthy Chinese population, and to determine its influencing factors. Methods A total of 76 healthy volunteers (76 eyes) without ophthalmic or systemic symptoms were enrolled. Choroidal scans (360-degree 3.4 mm diameter peripapillary circle scans) were obtained for all eyes using enhanced depth imaging spectral-domain optical coherence tomography. Choroid thickness was measured at the temporal, superotemporal, superior, superonasal, nasal, inferonasal, inferior, and inferotemporal segments. Results The average peripapillary choroidal thicknesses were 165.03 ± 40.37 μm. Inferonasal, inferior, and inferotemporal thicknesses were significantly thinner than temporal, superotemporal, superior, superonasal, nasal thicknesses (p < 0.05). No statistically significant difference was found among inferonasal, inferior, and inferotemporal thicknesses. The average peripapillary choroidal thickness decreased linearly with age (β = −1.33, 95% CI −1.98, -0.68, P < 0.001). No correlation was noted between average choroidal thickness and other factors (gender, refractive error, axial length, average retinal nerve fiber layer thickness, intraocular pressure, diastolic blood pressure, systolic blood pressure, mean blood pressure, diastolic ocular perfusion pressure, systolic ocular perfusion pressure, and mean ocular perfusion pressure). Conclusions The inferonasal, inferior, inferotemporal peripapillary choroidal thicknesses were significantly thinner than temporal, superotemporal, superior, superonasal, and nasal thicknesses. A thinner peripapillary choroid is associated with increasing age. PMID:23758729

  14. Ocular phototherapy.

    PubMed

    Singh, A D

    2013-02-01

    Phototherapy can be translated to mean 'light or radiant energy-induced treatment.' Lasers have become the exclusive source of light or radiant energy for all applications of phototherapy. Depending on the wavelength, intensity, and duration of exposure, tissues can either absorb the energy (photocoagulation, thermotherapy, and photodynamic therapy (PDT)) or undergo ionization (photodisruption). For phototherapy to be effective, the energy has to be absorbed by tissues or more specifically by naturally occurring pigment (xanthophyll, haemoglobin, and melanin) within them. In tissues or tumours that lack natural pigment, dyes (verteporphin, Visudyne) with narrow absorption spectrum can be injected intravenously that act as focal absorbent of laser energy after they have preferentially localized within the tumour. Ocular phototherapy has broad applications in treatment of ocular tumours. Laser photocoagulation, thermotherapy, and PDT can be delivered with low rates of complications and with ease in the outpatient setting. Review of the current literature suggests excellent results when these treatments are applied for benign tumours, particularly for vascular tumours such as circumscribed choroidal haemangioma. For primary malignant tumours, such as choroidal melanoma, thermotherapy, and PDT do not offer local tumour control rates that are equivalent or higher than those achieved with plaque or proton radiation therapy. However, for secondary malignant tumours (choroidal metastases), thermotherapy and PDT can be applied as a palliative treatment. Greater experience is necessary to fully comprehend risks, comparative benefits, and complication of ocular phototherapy of ocular tumours.

  15. Polymerase chain reaction for Mycobacterium tuberculosis DNA detection from ocular fluids in patients with various types of choroiditis in a referral eye center in India

    PubMed Central

    Biswas, Jyotirmay; Kazi, Mohmmad Salman; Agarwal, Vishvesh Ashokkumar; Alam, Md. Shahid; Therese, K Lily

    2016-01-01

    Aims: The aim of this study was to detect Mycobacterium tuberculosis (MTB) DNA with polymerase chain reaction (PCR) in aqueous or vitreous samples of patients suffering from choroiditis presumed to be infectious origin. Settings and Design: Hospital-based, retrospective case–control study. Subjects and Methods: In all, forty eyes of forty patients with choroiditis divided into two groups – Group A (serpiginous-like choroiditis, ampiginous choroiditis, multifocal choroiditis) and Group B (choroidal abscess, miliary tuberculosis (TB), choroidal tubercle) were analyzed retrospectively. In 27 controls (patients without uveitis undergoing phacoemulsification), anterior chamber aspirate was done and sample subjected to real-time PCR. Patients underwent nested PCR for MTB using IS6110 and MPB64 primers from aqueous (n = 39) or vitreous (n = 1). All patients underwent detailed ophthalmological examination by slit-lamp biomicroscopy, fundus examination by indirect ophthalmoscopy, and fundus photograph and fundus fluorescein angiography if required. Statistical Analysis: Positive results of PCR for MTB within the group and between two groups were statistically analyzed using Chi-square test. Results: There were 25 males and 15 females. Mean age at presentation was 34.66 years (range, 14–62). PCR positivity rates were 41.3% (n = 12/29) and 81.82% (n = 9/11) in Groups A and B, respectively. No controls had PCR-positive result. Comparison of PCR positivity rates showed statistically significant difference between Groups A and B (P = 0.028). Systemic TB was detected in 57.14% (n = 12/21) of all PCR-positive cases (Group A - 33.3%, n = 4/12; Group B - 88.9%, n = 8/9). Systemic antitubercular treatment (ATT) for 9 months and oral steroids were successful in resolution of choroiditis in all PCR-positive patients (n = 21) without disease recurrence. Conclusions: Eyes with choroiditis of suspected/presumed tubercular origin should be subjected to PCR for diagnosis of TB and

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

    PubMed Central

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

    2015-01-01

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

  17. The choroid as a sclera growth regulator.

    PubMed

    Summers, Jody A

    2013-09-01

    Emmetropization is a vision dependent mechanism that attempts to minimize refractive error through coordinated growth of the cornea, lens and sclera such that the axial length matches the focal length of the eye. It is generally accepted that this visually guided eye growth is controlled via a cascade of locally generated chemical events that are initiated in the retina and ultimately cause changes in scleral extracellular matrix (ECM) remodeling which lead to changes in eye size and refraction. Of much interest, therefore, are the molecular mechanisms that underpin emmetropization and visually guided ocular growth. The choroid, a highly vascularized layer located between the retina and the sclera is uniquely situated to relay retina-derived signals to the sclera to effect changes in ECM synthesis and ocular size. Studies initiated by Josh Wallman clearly demonstrate that the choroid plays an active role in emmetropization, both by modulation of its thickness to adjust the retina to the focal plane of the eye (choroidal accommodation), and well as through the release of growth factors that have the potential to regulate scleral extracellular matrix remodeling. His discoveries prompted numerous investigations on the molecular composition of the choroid and changes in gene expression associated with visually guided ocular growth. This article will review molecular and functional studies of the choroid to provide support for the hypothesis that the choroid is a source of sclera growth regulators that effect changes in ocular growth in response to visual stimuli.

  18. [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.

  19. Ocular hemodynamics during isometric exercise.

    PubMed

    Kiss, B; Dallinger, S; Polak, K; Findl, O; Eichler, H G; Schmetterer, L

    2001-01-01

    The autoregulatory capacity of the human retina is well documented, but the pressure-flow relationship of the human choroid is still a matter of controversy. Recent data, using laser Doppler flowmetry to measure choroidal blood flow, indicate that the choroid has some autoregulatory potential, whereas most data using other techniques for the assessment of choroidal hemodynamics indicate that the choroidal pressure-flow curve is linear. We used a new laser interferometric technique to characterize choroidal blood flow during isometric exercise. Twenty healthy subjects performed squatting for 6 min during normocapnia and during inhalation of 5% CO2 and 95% air. Ocular fundus pulsation amplitude, flow velocities in the ophthalmic artery, intraocular pressure, and systemic hemodynamics were measured in 2-min intervals. To gain information on choroidal blood flow fundus pulsation amplitude was corrected for changes in flow pulsatility using data from the ophthalmic artery and for changes in pulse rate. Ocular perfusion pressure was calculated from mean arterial pressure and intraocular pressure. The ocular pressure-flow relationship was calculated by sorting data according to ascending ocular perfusion pressure values. In a pilot study in 6 healthy subjects comparable ocular pressure flow relationships were obtained when choroidal blood flow was assessed with the method described above and with laser Doppler flowmetry. In the main study isometric exercise caused a significant increase in mean arterial pressure (56%, P < 0.001), pulse rate (84%, P < 0.001), and intraocular pressure (37%, P 0.004), but decreased fundus pulsation amplitude (-36%, P < 0.001). Significant deviations from baseline choroidal blood flow were observed only at ocular perfusion pressures >69% during normocapnia and 70% during hypercapnia. Our data indicate that during isometric exercise the choroid has a high capacity to keep blood flow constant despite changes in perfusion pressure and that this

  20. Enucleation versus plaque irradiation for choroidal melanoma

    SciTech Connect

    Straatsma, B.R.; Fine, S.L.; Earle, J.D.; Hawkins, B.S.; Diener-West, M.; McLaughlin, J.A.

    1988-07-01

    The Collaborative Ocular Melanoma Study (COMS) is an international, multicenter-controlled study. The organization includes an Executive Committee, Steering Committee, 6 Central Units, 32 Clinical Centers, and a Data and Safety Monitoring Committee. Scientifically, the COMS consists of (1) a randomized trial of patients with medium choroidal melanoma treated with enucleation versus iodine-125 plaque irradiation, (2) a randomized trial of patients with large choroidal melanoma treated with enucleation versus preenucleation external beam irradiation and enucleation, and (3) a prospective observational study of patients with small choroidal melanoma to determine whether a randomized trial of treatment is appropriate. In design and conduct of the COMS, special consideration is given to biostatistics and sample size considerations, iodine-125 plaque irradiation of choroidal melanoma, and coordinated ocular melanoma research. Recruitment is in progress. However, the pool of eligible patients is limited and the COMS needs the continued support and cooperation of ophthalmologists throughout the United States and Canada.

  1. 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

  2. [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.

  3. BMP9/ALK1 inhibits neovascularization in mouse models of age-related macular degeneration

    PubMed Central

    Ntumba, Kalonji; Akla, Naoufal; Oh, S. Paul; Eichmann, Anne; Larrivée, Bruno

    2016-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in aging populations of industrialized countries. The drawbacks of inhibitors of vascular endothelial growth factor (VEGFs) currently used for the treatment of AMD, which include resistance and potential serious side-effects, require the identification of new therapeutic targets to modulate angiogenesis. BMP9 signaling through the endothelial Alk1 serine-threonine kinase receptor modulates the response of endothelial cells to VEGF and promotes vessel quiescence and maturation during development. Here, we show that BMP9/Alk1 signaling inhibits neovessel formation in mouse models of pathological ocular angiogenesis relevant to AMD. Activating Alk1 signaling in laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR) inhibited neovascularization and reduced the volume of vascular lesions. Alk1 signaling was also found to interfere with VEGF signaling in endothelial cells whereas BMP9 potentiated the inhibitory effects of VEGFR2 signaling blockade, both in OIR and laser-induced CNV. Together, our data show that targeting BMP9/Alk1 efficiently prevents the growth of neovessels in AMD models and introduce a new approach to improve conventional anti-VEGF therapies. PMID:27517154

  4. Gene Therapies for Neovascular Age-Related Macular Degeneration.

    PubMed

    Pechan, Peter; Wadsworth, Samuel; Scaria, Abraham

    2014-12-18

    Pathological neovascularization is a key component of the neovascular form (also known as the wet form) of age-related macular degeneration (AMD) and proliferative diabetic retinopathy. Several preclinical studies have shown that antiangiogenesis strategies are effective for treating neovascular AMD in animal models. Vascular endothelial growth factor (VEGF) is one of the main inducers of ocular neovascularization, and several clinical trials have shown the benefits of neutralizing VEGF in patients with neovascular AMD or diabetic macular edema. In this review, we summarize several preclinical and early-stage clinical trials with intraocular gene therapies, which have the potential to reduce or eliminate the repeated intravitreal injections that are currently required for the treatment of neovascular AMD.

  5. 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

  6. 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.

  7. 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

  8. Natural course of symptomatic focal choroidal excavation.

    PubMed

    Pierro, Luisa; Casalino, Giuseppe; Introini, Ugo; Gagliardi, Marco; Sergenti, Jessica; Cascavilla, Maria Lucia; Bandello, Francesco

    2015-01-01

    A 32-year-old man was referred to the authors' department for nonspecified macular dystrophy with persistent metamorphopsia in the right eye diagnosed 10 years before and followed using optical coherence tomography. The patient underwent a comprehensive ocular examination, including multimodal imaging evaluation and electrofunctional testing. The diagnosis was consistent with nonconforming focal choroid excavation. Over 10 years, no complications occurred, visual acuity was stable, and optical coherence tomography showed no progression of the lesion during follow-up. In this case, nonconforming symptomatic focal choroid excavation was a nonprogressive condition with good long-term visual outcome.

  9. Polypoidal Choroidal Vasculopathy in Asians

    PubMed Central

    Wong, Chee Wai; Wong, Tien Y.; Cheung, Chui Ming Gemmy

    2015-01-01

    Age related macular degeneration (AMD) in Asians has been suggested to differ from their Western counterparts in terms of epidemiology, pathogenesis, clinical presentation and treatment. In particular, polypoidal choroidal vasculopathy (PCV) appears to be the predominant subtype of exudative AMD in Asian populations, in contrast to choroidal neovascularization secondary to AMD (CNV-AMD) in Western populations. Epidemiological data on PCV has been largely limited to hospital-based studies and there are currently no data on the incidence of PCV. Similarities and differences in risk factor profile between PCV and CNV-AMD point to some shared pathogenic mechanisms but also differential underlying mechanisms leading to the development of each phenotype. Serum biomarkers such as CRP, homocysteine and matrix metalloproteinases suggest underlying inflammation, atherosclerosis and deranged extracellular matrix metabolism as possible pathogenic mechanisms. In addition, recent advances in genome sequencing have revealed differences in genetic determinants of each subtype. While the standard of care for CNV-AMD is anti-vascular endothelial growth factor (VEGF) therapy, photodynamic therapy (PDT) has been the mainstay of treatment for PCV, although long-term visual prognosis remains unsatisfactory. The optimal treatment for PCV requires further clarification, particularly with different types of anti-VEGF agents and possible benefits of reduced fluence PDT. PMID:26239448

  10. Choroidal Round Hyporeflectivities in Geographic Atrophy

    PubMed Central

    De Vitis, Luigi Antonio; Carnevali, Adriano; Rabiolo, Alessandro; Querques, Lea; Bandello, Francesco; Querques, Giuseppe

    2016-01-01

    Purpose In geographic atrophy (GA), choroidal vessels typically appear on structural optical coherence tomography (OCT) as hyperreflective round areas with highly reflective borders. We observed that some GA eyes show choroidal round hyporeflectivities with highly reflective borders beneath the atrophy, and futher investigated the charcteristcs by comparing structural OCT, indocyanine green angiography (ICGA) and OCT angiography (OCT-A). Methods Round hyporeflectivities were individuated from a pool of patients with GA secondary to non-neovascular age-related macular degeneration consecutively presenting between October 2015 and March 2016 at the Medical Retina & Imaging Unit of the University Vita-Salute San Raffaele. Patients underwent a complete ophthalmologic examination including ICGA, structural OCT and OCT-A. The correspondence between choroidal round hyporeflectivities beneath GA on structural OCT and ICGA and OCT-A imaging were analyzed. Results Fifty eyes of 26 consecutive patients (17 females and 9 males; mean age 76.8±6.2 years) with GA were included. Twenty-nine round hyporeflectivities have been found by OCT in choroidal layers in 21 eyes of 21 patients (42.0%; estimated prevalence of 57.7%). All 29 round hyporeflectivities showed constantly a hyperreflective border and a backscattering on structural OCT, and appeared as hypofluorescent in late phase ICGA and as dark foci with non detectable flow in the choroidal segmentation of OCT-A. Interestingly, the GA area was greater in eyes with compared to eyes without round hyporeflectivities (9.30±5.74 and 5.57±4.48mm2, respectively; p = 0.01). Conclusions Our results suggest that most round hyporeflectivities beneath GA may represent non-perfused or hypo-perfused choroidal vessels with non-detectable flow. PMID:27880806

  11. Surgical implantation of steroids with antiangiogenic characteristics for treating neovascular age-related macular degeneration

    PubMed Central

    Geltzer, Arthur; Turalba, Angela; Vedula, Satyanarayana S

    2014-01-01

    Background Neovascular age-related macular degeneration (AMD) is associated with rapid vision loss due to choroidal neovascularization (CNV), leakage, and scarring. Steroids have gained attention in their role for the treatment of neovascular AMD for their antiangiogenic and anti-inflammatory properties. Objectives This review aims to examine effects of steroids with antiangiogenic properties in the treatment of neovascular AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 11), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2012), EMBASE (January 1980 to November 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to November 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 21 November 2012. Selection criteria We included randomized controlled clinical trials of intra- and peri-ocular antiangiogenic steroids in people diagnosed with neovascular AMD. Data collection and analysis Two authors independently screened abstracts and full-text articles, assessed risk of bias in the included trials, and extracted data. We did not conduct a meta-analysis. Main results We included three trials after screening a total of 1503 abstracts and 21 full-text articles. The three trials included a total of 809 participants. One trial compared different doses of acetonide anecortave acetate with placebo, a second trial compared triamcinolone acetonide versus placebo, and the third trial compared anecortave acetate against photodynamic therapy (PDT). We did not conduct a

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

    PubMed

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

    2007-05-01

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

  13. 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.

  14. 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.

  15. 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

  16. Aflibercept for neovascular age-related macular degeneration

    PubMed Central

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

    2016-01-01

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

  17. Optical coherence tomography findings in ocular argyrosis.

    PubMed

    Rahimy, Ehsan; Beardsley, Robert; Ferrucci, Steven; Ilsen, Pauline; Sarraf, David

    2013-11-25

    A 68-year-old Caucasian man with a remote history of daily colloidal silver ingestion presented for ophthalmic examination in which he was noted to have a distinct slate gray skin discoloration. Funduscopy revealed confluent perimacular drusenoid deposits bilaterally, most of which localized at the level of or anterior to the inner segment ellipsoid band by optical coherence tomography (OCT) imaging. Enhanced depth imaging OCT demonstrated marked choroidal thinning. Fluorescein angiogram displayed a dark or silent choroid. Confirmatory serum silver levels were found to be markedly elevated. This report describes a unique geographic maculopathy with large drusenoid deposits anterior to the ellipsoid layer and severe choroidal thinning in association with ocular argyrosis.

  18. [Recent advances of clinical and basic studies of ocular fundus diseases in China in the last five years].

    PubMed

    Li, Xiao-xin; Zhao, Ming-wei; Yu, Wen-zhen

    2005-08-01

    In the last 5 years, a great progress in the clinical treatment and basic research of ocular fundus diseases in China has been obtained. An abundance of clinical experience and a great deal of research data have been accumulated. In the field of clinical work, the photodynamic therapy (PDT) and transpupillary thermotherapy (TTT) of choroidal neovascular membrane have been established gradually in China. A rapid progress has been achieved in the vitreous surgery, intraocular injection of triamcinolone acetonide for treating macular edema, radial optic neurotomy (RON) for treating central retinal vein occlusion, the multi-access prevention and management of retinopathy of prematurity and intraocular tumor, and the update of the techniques and equipments for vitreous and retinal surgeries, etc. In the field of laboratory work, Chinese scientists achieved lasting and great progress in many fields: diabetic retinopathy, retinoblastoma, proliferative vitreoretinopathy, retinal pigment epithelial cells, retinal transplantation, gene therapy of ocular fundus diseases, etc. All of these achievements implied that both the clinical work and basic research of ocular fundus diseases in China have approached international advanced technology, while some fields have achieved the international advanced level.

  19. Choroidal tuberculoma as a presenting sign of tuberculosis

    PubMed Central

    Arej, Nicolas; Fadlallah, Ali; Chelala, Elias

    2016-01-01

    Choroidal tuberculoma is a rare ocular form of tuberculosis (TB) that raises both a diagnostic and a therapeutical challenge, especially when occurring without other manifestations of the disease. This study reports the case of a 27-year-old woman who had a unilateral drop of vision (20/100) with ocular pain. Her fundus examination revealed an elevated juxtapapillary choroidal mass measuring 892 µm in diameter, as calculated by optical coherence tomography (OCT), and associated with a serous retinal detachment involving the macula. The diagnosis of choroidal tuberculoma was established by positive QuantiFERON-TB and tuberculin skin test. Laboratory and imaging workup ruled out pulmonary and systemic TB as well as other possible etiologies. Antituberculosis therapy was started and led to an improved visual acuity (20/30) and a shrinkage of the tuberculoma to a diameter of 499 µm at 3 months. This is one of the few reported cases of solitary choroidal tuberculoma in a patient with no other sign of TB. It sheds light on the place of OCT in the diagnosis and follow-up of the choroidal mass, in terms of measuring the size of the mass and revealing the associated serous retinal detachment and the distinctive “contact sign” between the neurosensory retina and the retinal pigment epithelium (RPE)–choriocapillaris layer surmounting the tuberculoma. PMID:27956845

  20. Vitelliform focal choroidal excavation.

    PubMed

    Or, Chris; Forooghian, Farzin

    2014-05-30

    Focal choroidal excavations (FCE) are characterized by foveal or perifoveal choroid excavations seen on optical coherence tomography (OCT). The authors report a case of FCE associated with a vitelliform lesion within the excavation. A case of FCE associated with a small vitelliform lesion has been described previously, but the larger extent of the vitelliform lesion observed in the current case has not been previously reported. This may represent a novel category of FCE, vitelliform focal choroidal excavation, in which deposition of vitelliform material is associated with its development.

  1. 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

  2. Automatic segmentation of choroidal thickness in optical coherence tomography

    PubMed Central

    Alonso-Caneiro, David; Read, Scott A.; Collins, Michael J.

    2013-01-01

    The assessment of choroidal thickness from optical coherence tomography (OCT) images of the human choroid is an important clinical and research task, since it provides valuable information regarding the eye’s normal anatomy and physiology, and changes associated with various eye diseases and the development of refractive error. Due to the time consuming and subjective nature of manual image analysis, there is a need for the development of reliable objective automated methods of image segmentation to derive choroidal thickness measures. However, the detection of the two boundaries which delineate the choroid is a complicated and challenging task, in particular the detection of the outer choroidal boundary, due to a number of issues including: (i) the vascular ocular tissue is non-uniform and rich in non-homogeneous features, and (ii) the boundary can have a low contrast. In this paper, an automatic segmentation technique based on graph-search theory is presented to segment the inner choroidal boundary (ICB) and the outer choroidal boundary (OCB) to obtain the choroid thickness profile from OCT images. Before the segmentation, the B-scan is pre-processed to enhance the two boundaries of interest and to minimize the artifacts produced by surrounding features. The algorithm to detect the ICB is based on a simple edge filter and a directional weighted map penalty, while the algorithm to detect the OCB is based on OCT image enhancement and a dual brightness probability gradient. The method was tested on a large data set of images from a pediatric (1083 B-scans) and an adult (90 B-scans) population, which were previously manually segmented by an experienced observer. The results demonstrate the proposed method provides robust detection of the boundaries of interest and is a useful tool to extract clinical data. PMID:24409381

  3. Automatic segmentation of choroidal thickness in optical coherence tomography.

    PubMed

    Alonso-Caneiro, David; Read, Scott A; Collins, Michael J

    2013-01-01

    The assessment of choroidal thickness from optical coherence tomography (OCT) images of the human choroid is an important clinical and research task, since it provides valuable information regarding the eye's normal anatomy and physiology, and changes associated with various eye diseases and the development of refractive error. Due to the time consuming and subjective nature of manual image analysis, there is a need for the development of reliable objective automated methods of image segmentation to derive choroidal thickness measures. However, the detection of the two boundaries which delineate the choroid is a complicated and challenging task, in particular the detection of the outer choroidal boundary, due to a number of issues including: (i) the vascular ocular tissue is non-uniform and rich in non-homogeneous features, and (ii) the boundary can have a low contrast. In this paper, an automatic segmentation technique based on graph-search theory is presented to segment the inner choroidal boundary (ICB) and the outer choroidal boundary (OCB) to obtain the choroid thickness profile from OCT images. Before the segmentation, the B-scan is pre-processed to enhance the two boundaries of interest and to minimize the artifacts produced by surrounding features. The algorithm to detect the ICB is based on a simple edge filter and a directional weighted map penalty, while the algorithm to detect the OCB is based on OCT image enhancement and a dual brightness probability gradient. The method was tested on a large data set of images from a pediatric (1083 B-scans) and an adult (90 B-scans) population, which were previously manually segmented by an experienced observer. The results demonstrate the proposed method provides robust detection of the boundaries of interest and is a useful tool to extract clinical data.

  4. Effects of Exercise on the Structure and Circulation of Choroid in Normal Eyes

    PubMed Central

    Mori, Junya; Okuda, Natsuki; Imaizumi, Hiroko; Iwasaki, Masanori; Shimizu, Miho; Miyamoto, Hirotomo; Akaiwa, Kei; Semba, Kentaro; Sonoda, Shozo; Sakamoto, Taiji; Mitamura, Yoshinori

    2016-01-01

    Aims To determine the effects of dynamic exercise on the circulation and the luminal and stromal areas of the choroid in normal eyes. Methods This was a prospective interventional study of 38 eyes of 38 normal subjects enrolled by invitation. The systolic and diastolic blood pressures, heart rate, intraocularpressure, mean ocular perfusion pressure (MOPP), choroidal blood velocity, and enhanced depth imaging optical coherence tomographic (EDI-OCT) images were recorded before, and immediately after mild dynamic exercise. The same measurements were recorded after 10 min of rest. The choroidal blood velocity was measured bylaser speckle flowgraphy, and the mean blur rate was used for the evaluations. The horizontal EDI-OCT images of the subfoveal choroid were converted to binary images. The central choroidal thickness (CCT), total cross sectional choroidal area, luminal areas, stromal areas, and the ratio of luminal area to total choroidal area (L/C ratio) were determined from these images. Results The systolic and diastolic blood pressures, heart rate, MOPP, and the mean blur rate were significantly increased immediately after the exercise and significantly decreased 10 minutes after the exercise. There wereno significant changes in the mean CCT, the mean total choroidal area, the mean luminal and stromal areas, and the mean L/C ratio after the exercise. Conclusions Our results suggest that a rest period is needed before measurements of blood flow velocity but not necessary for the EDI-OCT imaging to determine the choroidal thickness and area. PMID:27973598

  5. 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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:26868048

  7. 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

  8. 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

  9. The effect of allergic rhinitis with positive skin prick test on choroidal thickness.

    PubMed

    Yenigun, Alper; Elbay, Ahmet; Dogan, Remzi; Ozturan, Orhan; Ozdemir, Mehmet Hakan

    2017-03-06

    Allergic rhinitis is an inflammatory disease that develops through immunoglobulin E in the rhino-ocular mucosa due to allergy. The main symptoms are runny nose, nasal congestion, sneezing and itchy nose. This study was designed to investigate the effect of allergic rhinitis on choroidal thickness. This study was planned as a case-control study. This study performed in a tertiary referral center. The study included 61 patients with allergic rhinitis and 35 healthy subjects. Patients in both groups underwent skin prick test. In allergic rhinitis patients and healthy persons; subfoveal, temporal and nasal choroidal thickness measurement was performed. The choroidal thicknesses were measured without pupil dilation using the Spectralis Optical Coherence Tomography. In the subfoveal and temporal region, choroidal tissue was followed up significantly thicker in allergic rhinitis patients statistically compared to healthy persons (p = 0.031, p = 0.049). However, no significant difference was followed up between the nasal choroidal thickness measurements statistically (p = 0.54). Runny nose (67.2%), sneeze (65.5%), stuffiness (62.2%), itching of the nose (40.9%), and nasal discharge (21.3%) complaints were observed significantly higher in the group having allergic rhinitis. The effect of allergic rhinitis on choroidal thickness were assessed and compared with the control group. Our study revealed that there was significant association between increased choroidal thickness and allergic rhinitis. Allergic sensitivity may play an important role in increased choroidal thickness.

  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. Clinicopathologic correlation of retinal to choroidal venous collaterals of the optic nerve head.

    PubMed

    Schatz, H; Green, W R; Talamo, J H; Hoyt, W F; Johnson, R N; McDonald, H R

    1991-08-01

    An optic nerve meningioma developed in an elderly woman and was followed for 13 years until her death. The optic nerve was initially normal. Over time it became swollen and then atrophic and developed retinal venous to choroidal venous collaterals. Five hundred serial sections were prepared through the optic nerve and for approximately 1.5 mm superiorly and inferiorly to the optic nerve to trace the course of the collaterals that were seen ophthalmoscopically and angiographically in the optic nerve head. This clinicopathologic study shows clearly that the abnormal channels are, in fact, retinal venous to choroidal venous collaterals (bypass channels). Four collaterals extended around the end of Bruch's membrane at the optic nerve head. Two more collaterals extended through the retinal pigment epithelium to become continuous with a subretinal pigment epithelial neovascular membrane, the vessels of which connected with the choroidal vessels through a defect in Bruch's membrane.

  12. Choroid plexus taurine transport.

    PubMed

    Keep, R F; Xiang, J

    1996-04-09

    The putative osmoregulatory agent, taurine, is lost from the brain during hypo-osmotic stress or ischemia, but the regulatory mechanisms involved in this loss have not been fully elucidated. In this study, we have examined taurine transport by the isolated rat choroid plexus, one element of the brain-blood interface, and examined how it may be regulated as part of brain volume regulation. Choroid plexus taurine uptake was Na- and Cl-dependent with a Vmax and Km of 6.5 +/- 0.3 pmol/mg/min and 232 +/- 33 microM. The latter is substantially greater than the normal CSF taurine concentration and this may be important in removing taurine released into the CSF during parenchymal cell swelling. Taurine uptake also appears calmodulin dependent as it was reduced by 84 and 91% in the presence of 25 microM trifluoperazine and 100 microM W-7, two calmodulin inhibitors. Taurine efflux from choroid plexus was stimulated by trifluoperazine, taurine, and hypo-osmotic stress. The latter two effects were reduced by niflumic acid, suggesting that taurine and hypo-osmotic stress act on the same pathway. The stimulation of efflux by hypo-osmotic stress decreased with time, whereas the effect of external taurine was sustained. If this efflux pathway is involved in the movement of taurine from choroid plexus to blood, these results suggest that changes in extracellular taurine may be more important than the direct effect of hypo-osmolality in the long-term loss of taurine from the brain.

  13. Choroidal rupture and optic nerve injury with equipment designated as 'child-safe'.

    PubMed

    Petrarca, Robert; Saldana, Manuel

    2012-08-27

    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.

  14. Extensive choroidal infarction in a case of mixed essential cryoglobulinaemia in a postpartum female.

    PubMed

    Takkar, Brijesh; Azad, Shorya Vardhan; Kumar, Uma; Venkatesh, Pradeep

    2016-09-16

    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.

  15. Ocular Rosacea

    MedlinePlus

    ... Staff Ocular rosacea is inflammation that causes redness, burning and itching of the eyes. It often develops ... symptoms of ocular rosacea may include: Dry eyes Burning or stinging in the eyes Itchy eyes Grittiness ...

  16. Paradoxical Worsening of Tubercular Serpiginous-Like Choroiditis after Initiation of Antitubercular Therapy

    PubMed Central

    Esen, Ebru; Sızmaz, Selçuk; Kunt, Zeynep; Demircan, Nihal

    2016-01-01

    In this study, a case with tubercular choroiditis showing severe macular edema and progression of choroidal lesions following initiation of antitubercular treatment is presented and the management of posterior uveitis associated with tuberculosis is evaluated. A 40-year-old female patient was admitted with decreased vision in her right eye and her fundoscopic examination revealed serpiginous choroiditis. It was learned from her medical history that she had taken antitubercular therapy 9 years ago. Mantoux tuberculin skin test showed an area of induration measuring 15 mm and a positive interferon-gamma release assay was documented. Additionally, sequelae lesions due to previous tubercular infection were remarkable on her chest imaging. By excluding other causes of uveitis, the patient was considered presumed ocular tuberculosis and a full standard course of 4-drug antitubercular therapy was initiated. On the seventh day of the treatment existing choroidal lesions showed progression, new foci of choroiditis appeared and severe macular edema occurred. After adding systemic corticosteroid to the treatment, the macular edema resolved and choroidal lesions began to inactivate. In patients with tubercular choroiditis, continued progression may develop after initiation of antitubercular therapy. This paradoxical worsening is thought to be a hyperacute immunologic reaction occurring against antigen load released after antitubercular therapy. This phenomenon may be suppressed by the addition of systemic corticosteroids to the treatment. PMID:28058156

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

    PubMed

    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.

  18. 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

  19. 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

  20. [Association of ocular inflammation and innate immune response].

    PubMed

    Sonoda, Koh-Hei

    2008-03-01

    Immune response has been divided into innate immunity and acquired immunity. We focused on the role of innate immunity during the formation of uveitis and choroidal neovascularization (CNV)-related diseases. To carry out a comprehensive analysis of ocular inflammatory responses in patients with uveitis, vitreous fluid was analyzed using a microbead-based multiplex ELIZA system. We found that cytokines which were related with innate immunity were elevated, but cytokines which were related with acquired immunity were not. We also found that the role of IL-17 was to produce Th17 cells in the chronic phase of experimental uveitis. Next, we investigated the role of the natural killer (NK) T cells which restrict CD1 and participate in the innate immune response in laser-induced experimental CNV. We studied the CNV formation in two independent NK T cell-deficient strains of mice, CD1 knockout (KO) mice and Jalpha18 KO mice, and found that both KO mice showed significant reduction of the effects of experimental CNV. After laser treatment, both CD1 KO mice and Jalpha18 KO mice showed a decrease in the expression of vascular endothelial growth factor (VEGF) expression in retina and choroid. Interestingly, intravitreous inoculation of a galactosylceramide (alphaGalCer), which is the ligand of NK Tcells, inhibited CNV in C57BL6 mice. Collectively, we conclude that NK T cells play an important role in forming CNV as one of the inducers of VEGS. Because NK T cells bear the potential to regulate immune response, alphaGalCer might activate NK T cells differently to produce angiostatic factors and have a therapeutic potential in vivo. During the clinical process of CNV-related diseases, not only CNV formation, but also subretinal scarring is thought to be another important step. We thus established the experimental model of subretinal scaring by injecting peritoneal exudating macrophases into the subretinal space. This scaring was inhibited by inoculation of anti-IL-6 antibody and

  1. Regulation of signaling events involved in the pathophysiology of neovascular AMD.

    PubMed

    Wang, Haibo; Hartnett, M Elizabeth

    2016-01-01

    Neovascular age-related macular degeneration (AMD) is a complex disease in which an individual's genetic predisposition is affected by aging and environmental stresses, which trigger signaling pathways involving inflammation, oxidation, and/or angiogenesis in the RPE cells and choroidal endothelial cells (CECs), to lead to vision loss from choroidal neovascularization. Antiangiogenic therapies have greatly improved clinical outcomes in the last decade; however, vision improves in less than half of patients treated for neovascular AMD, and treatments remain inadequate for atrophic AMD. Many studies focus on genetic predisposition or the association of outcomes in trials of human neovascular AMD but are unable to evaluate the effects between different cell types involved in AMD and the signaling events that take place to cause pathologic biologic events. This manuscript complements other reviews in that it describes what is known generally in human AMD studies and clinical trials testing methods to inhibit vascular endothelial growth factor (VEGF inhibitors) and presents pathologic signaling events that develop in two important cell types, the RPE cells and the CECs, when stimulated by stresses or placed into conditions similar to what is currently understood to occur in neovascular AMD. This manuscript complements other reviews by discussing signaling events that are activated by cell-cell or cell-matrix interactions. These considerations are particularly important when considering growth factors, such as VEGF, which are important in physiologic and pathologic processes, or GTPases that are present but active only if GTP bound. In either case, it is essential to understand the role of signaling activation to distinguish what is pathologic from what is physiologic. Particularly important is the essential role of activated Rac1 in CEC transmigration of the RPE monolayer, an important step in blindness associated with neovascular AMD. Other concepts discussed include

  2. Systemic viral infections and their retinal and choroidal manifestations.

    PubMed

    Yoser, S L; Forster, D J; Rao, N A

    1993-01-01

    Viruses are one of the most common causes of infections involving the posterior segment of the eye. Such infections can occur either on a congenital or an acquired basis, and may affect primarily the retina or the choroid. Congenital cytomegalovirus (CMV) and rubella infections may result in retinitis. CMV retinitis is also the most common cause of acquired viral retinitis, primarily because of the acquired immunodeficiency syndrome (AIDS). Other types of viral retinitis, such as those caused by herpes simplex or herpes zoster, can occur in immunocompromised or immunocompetent individuals. Retinitis or choroiditis caused by viruses such as measles, influenza, Epstein-Barr virus, and Rift Valley fever virus, typically occurs subsequent to an acute viral systemic illness. The systemic and ocular manifestations, as well as the histopathology, laboratory tests, differential diagnoses, and treatment regimens for each of the individual viruses are discussed in detail.

  3. Photochemical Thrombosis Of Retinal And Choroidal Vessels Using Rose Bengal

    NASA Astrophysics Data System (ADS)

    Lewis, Mary Lou; Winward, Kirk; Watson, Brant D.; Hernandez, Eleut

    1989-09-01

    Rose bengal is an effective photosensitizing agent which interacts with argon green light to induce photochemical thrombosis of irradiated vessels. We used focal, low energy irradiation to occlude retinal and choroidal vessels in both albino and pigmented rabbits. Immediately after intravenous injection of rose bengal at concentrations of 10 and 20 mg/kg, irradiation was performed via a slit lamp-delivered argon green laser (514.5 nm) with the aid of fundus contact lens. In 11 eyes, arteries were treated with 50-100 interrupted bursts of 75u spot size at 0.2 sec and 40-100 mW (9 choroidal vessels, serous elevation of the retina, and disc neovascularization. In eight eyes choroidal vessels were irradiated with 10-20 mW, 15-60 sec, 500u spot size (31 choroidal vessels. There was minimal damage to surrounding tissue. Control eyes in all three groups irradiated utilizing the same parameters, but without rose bengal, demonstrated no evidence of thermal injury.

  4. 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

  5. Ocular manifestations in systemic lupus erythematosus.

    PubMed

    Silpa-archa, Sukhum; Lee, Joan J; Foster, C Stephen

    2016-01-01

    Systemic lupus erythematosus (SLE) can involve many parts of the eye, including the eyelid, ocular adnexa, sclera, cornea, uvea, retina and optic nerve. Ocular manifestations of SLE are common and may lead to permanent blindness from the underlying disease or therapeutic side effects. Keratoconjunctivitis sicca is the most common manifestation. However, vision loss may result from involvement of the retina, choroid and optic nerve. Ocular symptoms are correlated to systemic disease activity and can present as an initial manifestation of SLE. The established treatment includes prompt systemic corticosteroids, steroid-sparing immunosuppressive drugs and biological agents. Local ocular therapies are options with promising efficacy. The early recognition of disease and treatment provides reduction of visual morbidity and mortality.

  6. Ocular lesions and experimental choline deficiency.

    PubMed

    Ossani, Georgina P; Pelayes, David; Diaz, María L; Lago, Nestor R; Fariña, Silvia L; Monserrat, Alberto J; Zarate, Jorge O

    2006-01-01

    Previous studies have shown ocular haemorrhages in choline-deficient rats. The aim of this paper is to study further the relationship between ocular and renal lesions and biochemical alterations in rats fed a choline-deficient diet. Fifty one weanling male Wistar rats, were divided into two groups. Thirty one of them were fed a choline-deficient diet and the rest was fed a choline-supplemented diet ad libitum. Animals from both groups were killed between the fifth and the eighth day. Urea, creatinine and homocysteine concentrations in blood were determined. Eyes were used for light microscopy study; high resolution light microscopy and the study of the retina as "rétine a plat". Kidneys were studied by light microscopy. Choline-supplemented rats did not show ocular or renal lesion. Choline-deficient rats that showed renal lesions, tubular or cortical necrosis, did not always have ocular changes. There were no ocular changes in the only choline-deficient rat without renal lesion. The ocular changes consisted mainly in haemorrhage in both cameras and ciliary and vitreous bodies. Correlations between ocular and renal lesion (r = 0.72, p < 0.0001, CI 95%: 0.48-0.86); ocular lesion and creatinine (r = 0.86, p < 0.0001, Cl 95%: 0.72-0.93) and ocular lesion and urea (r = 0.70, p < 0.0001, Cl 95%: 0.44-0.85) were positive. Choline-deficiency induces ocular haemorrhagic lesions after the development of renal necrosis. The ocular pathology could be due to the immaturity of the ocular vasculature at this age. The hyaloid, choroid and retinal system are involved.

  7. Choroidal thickness in diabetic patients of Indian ethnicity

    PubMed Central

    Sudhalkar, Aditya; Chhablani, Jay Kumar; Venkata, Amarnath; Raman, Rajiv; Rao, P Srinivasa; Jonnadula, Ganesh Babu

    2015-01-01

    Purpose: To evaluate choroidal thickness (CT) change in various grades of diabetic retinopathy (DR) in comparison to age-matched healthy subjects. Methods: This prospective observational study included 227 eyes of 125 subjects with diabetes (study group: 58 females) and 197 eyes of 110 age-matched healthy subjects (control group: 66 females). Collected data included age, gender, duration of diabetes, glycemic control, comprehensive ocular examination, fundus photography, and CT measurement on spectral domain ocular coherence tomography using enhanced depth imaging. Results: Mean age in the study group was 57.0 ± 9.37 years (43–73 years). The mean age was 41.48 ± 5.43 years in the control group. Subjects with diabetes with (252.8 ± 55.6 microns) and without (261.71 ± 51.8 microns) retinopathy had significantly thinner choroids when compared to the control group (281.7 ± 47.7 microns; P = 0.032). Seventy-four of 227 eyes did not have any evidence of DR, 89 eyes had features of nonproliferative diabetic retinopathy (NPDR), and 33 eyes had treatment naïve proliferative diabetic retinopathy (PDR). Thirty-one PDR eyes had received previous laser photocoagulation. Subjects with diabetes without retinopathy had a greater subfoveal choroidal thickness (SFCT) than subjects with diabetes with retinopathy (P < 0.001). Eyes with PDR (243.9 ± 56.2 microns) had thinner SFCT than those with NPDR (238.98 ± 111.23 microns). There was no difference in the SFCT between treated (laser photocoagulation done; 251.784 ± 103.72 microns) and treatment naïve PDR (258.405 ± 89.47 microns, P = 0.23). Conclusions: Control eyes had greater SFCT compared to subjects with diabetes, with and without retinopathy. The thinning progressed with increasing severity of DR. Choroidal thinning may contribute to DR pathogenesis. PMID:26862096

  8. Anti-vascular endothelial growth factor for neovascular age-related macular degeneration

    PubMed Central

    Solomon, Sharon D.; Lindsley, Kristina; Vedula, Satyanarayana S.; Krzystolik, Magdalena G.; Hawkins, Barbara S.

    2014-01-01

    Background Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to neovascular AMD accounts for most AMD-related severe vision loss. Anti-vascular endothelial growth factor (anti-VEGF) agents, injected intravitreally, aim to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, improve vision. Objectives To investigate: (1) the ocular and systemic effects of, and quality of life associated with, intravitreally injected anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) for the treatment of neovascular AMD compared with no anti-VEGF treatment; and (2) the relative effects of one anti-VEGF agent compared with another when administered in comparable dosages and regimens. Search methods We searched Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2014), EMBASE (January 1980 to March 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2014), the metaRegister of Controlled Trials (mRCT) (www.controlledtrials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 27 March 2014. Selection criteria We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or a control treatment (e.g., sham treatment or photodynamic therapy). All trials followed participants for at least one year. Data collection

  9. [Ocular allergies].

    PubMed

    Messmer, E M

    2005-05-01

    Recent developments indicate that ocular allergy is more than an IgE-mediated allergic conjunctivitis. Ocular allergy is a disease affecting the entire ocular surface including conjunctiva, lids, cornea, lacrimal gland and tear film. Besides an IgE-mediated reaction, a complex chronic inflammation is involved in the pathogenesis of many ocular allergies. According to their pathogenesis and clinical picture, ocular allergies are classified into mild forms, such as seasonal and perennial allergic conjunctivitis as well as giant papillary conjunctivitis, and chronic, potentially blinding forms such as atopic keratoconjunctivitis and vernal keratoconjunctivitis. New therapeutics act on the entire inflammatory process or try to modulate the allergic reaction early and specifically. The association with non-ocular allergic symptoms requires an interdisciplinary approach.

  10. Growing Hemorrhagic Choroidal Fissure Cyst

    PubMed Central

    Gelal, Fazıl; Gurkan, Gokhan; Feran, Hamit

    2016-01-01

    Choroidal fissure cysts are often incidentally discovered. They are usually asymptomatic. The authors report a case of growing and hemorrhagic choroidal fissure cyst which was treated surgically. A 22-year-old female presented with headache. Cranial MRI showed a left-sided choroidal fissure cyst. Follow-up MRI showed that the size of the cyst had increased gradually. Twenty months later, the patient was admitted to our emergency department with severe headache. MRI and CT showed an intracystic hematoma. Although such cysts usually have a benign course without symptoms and progression, they may rarely present with intracystic hemorrhage, enlargement of the cyst and increasing symptomatology. PMID:26962426

  11. Delayed Patchy Choroidal Filling in the Comparison of Age-related Macular Degeneration Treatment Trials (CATT)

    PubMed Central

    Gewaily, Dina Y.; Grunwald, Juan E.; Pistilli, Maxwell; Ying, Gui-Shuang; Maguire, Maureen G.; Daniel, Ebenezer; Ostroff, Candace P.; Fine, Stuart L.

    2015-01-01

    Purpose To determine the relationship between delayed patchy choroidal filling and morphologic and functional outcomes among eyes treated with ranibizumab or bevacizumab. Design Cohort study. Methods Comparison of Age-related Macular Degeneration Treatment Trials participants were randomly assigned to ranibizumab or bevacizumab on a monthly or as needed schedule. Presence of delayed patchy choroidal filling and morphologic and functional outcomes were evaluated among eyes with gradeable fluorescein angiography at baseline (N=973) and at one year (N=860) eyes. Results Delayed filling was present in 75 (7.7%) of 973 eyes at baseline. Eyes with incident delayed filling at one year (23 (2.9%) of 798) showed a mean decrease of 1.7 letters in visual acuity, whereas eyes without incident delayed filling had a mean improvement of 8.1 letters (Δ=−9.8 [−15.8, −3.9], p<0.01). Eyes with incident delayed filling had a larger increase in mean total lesion area of choroidal neovascularization (3.00 mm2) than eyes without incident delayed filling (0.56 mm2, Δ=2.4 [0.4, 4.4], p=0.02). The proportion with incident delayed filling at one year was similar among eyes treated with ranibizumab (10 (2.4%) of 413) or bevacizumab (13 (3.3%) of 385, p=0.53) and among eyes treated monthly (12 (3.1%) of 388) or as needed (11 (2.7%) of 410, p=0.83). Conclusions Delayed patchy choroidal filling was uncommon at baseline. Although only a small percentage of eyes developed delayed filling during the first year of anti-vascular endothelial growth factor treatment, these eyes had worse visual acuity and a larger increase in total lesion area of choroidal neovascularization. PMID:24949820

  12. Distribution and Quantification of Choroidal Macrophages in Human Eyes With Age-Related Macular Degeneration

    PubMed Central

    McLeod, D. Scott; Bhutto, Imran; Edwards, Malia M.; Silver, Rachel E.; Seddon, Johanna M.; Lutty, Gerard A.

    2016-01-01

    Purpose Increasing evidence suggests a role for macrophages in the pathogenesis of age-related macular degeneration (AMD). This study examined choroidal macrophages and their activation in postmortem eyes from subjects with and without AMD. Methods Choroids were incubated with anti-ionized calcium-binding adapter molecule 1 (anti-IBA1) to label macrophages, anti-human leukocyte antigen-antigen D-related (anti-HLA-DR) as a macrophage activation marker, and Ulex europaeus agglutinin lectin to label blood vessels. Whole mounts were imaged using confocal microscopy. IBA1- and HLA-DR–positive (activated) cells were counted in submacula, paramacula, and nonmacula, and cell volume and sphericity were determined using computer-assisted image analysis. Results In aged control eyes, the mean number of submacular IBA1+ and HLA-DR+ macrophages was 433/mm2 and 152/mm2, respectively. In early AMD eyes, there was a significant increase in IBA1+ and HLA-DR+ cells in submacula compared to those in controls (P = 0.0015 and P = 0.008, respectively). In eyes with neovascular AMD, there were significantly more HLA-DR+ cells associated with submacular choroidal neovascularization (P = 0.001). Mean cell volume was significantly lower (P ≤ 0.02), and sphericity was significantly higher (P ≤ 0.005) in all AMD groups compared to controls. Conclusions The average number of IBA1+ macrophages in submacular and paramacular choroid was significantly higher in early/intermediate AMD compared to that in aged controls. HLA-DR+ submacular macrophages were significantly increased in all stages of AMD, and they were significantly more round and smaller in size in the submacular AMD choroid, suggesting their activation. These findings support the concept that AMD is an inflammatory disease. PMID:27802514

  13. 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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-09-03

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

  16. 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

  17. Technique for Robotic Stereotactic Irradiation of Choroidal Melanoma.

    PubMed

    Béliveau-Nadeau, Dominic; Callejo, Sonia; Roberge, David

    2016-04-21

    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.

  18. 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

  19. 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

  20. Open-source algorithm for automatic choroid segmentation of OCT volume reconstructions

    NASA Astrophysics Data System (ADS)

    Mazzaferri, Javier; Beaton, Luke; Hounye, Gisèle; Sayah, Diane N.; Costantino, Santiago

    2017-02-01

    The use of optical coherence tomography (OCT) to study ocular diseases associated with choroidal physiology is sharply limited by the lack of available automated segmentation tools. Current research largely relies on hand-traced, single B-Scan segmentations because commercially available programs require high quality images, and the existing implementations are closed, scarce and not freely available. We developed and implemented a robust algorithm for segmenting and quantifying the choroidal layer from 3-dimensional OCT reconstructions. Here, we describe the algorithm, validate and benchmark the results, and provide an open-source implementation under the General Public License for any researcher to use (https://www.mathworks.com/matlabcentral/fileexchange/61275-choroidsegmentation).

  1. 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.

  2. [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.

  3. Ocular drug development--future directions.

    PubMed

    Sherris, David

    2007-01-01

    Technology has caught up with retinal diseases of neovasculature. Work with anti-cancer, anti-angiogenic agents has fueled the way for ocular therapeutics. The market size for age-related macular degeneration and diabetic retinopathy is huge. Fifteen million people in the United States alone have age-related macular degeneration with 2 million new cases each year (1). About 20.8 million people in the United States have diabetes. Of those, 14.6 million are diagnosed and 6.2 million are undiagnosed (2). Of patients who have had type 1 diabetics for more than 20 years, 50% will have proliferative diabetic retinopathy (3). Between 60% and 80% of type 2 diabetics will manifest retinopathy after 15 years, and 20% will progress to proliferative retinopathy after 25 years of duration (4). Big pharma and biotech were complacent in developing drugs capable of having effect on ocular neovascular diseases even though technologies were available, at least on the research level, long before there was serious activity to bring such technologies to the clinic. Finally, over the last three years, triple digit million dollar business development deals have been consummated, mostly for VEGF-A targeted modalities. Such biodollar partnerships were the eye openers which have now led to a concerted action to develop ocular drugs to combat ocular neovascularization. Anti-VEGF-A technologies do not constitute the whole story. Agents with broader activity, activity that occurs later down the angiogenic pathway and those drugs which are capable to synergize with anti-VEGF-A technologies will dominate the next wave in ocular diseases of neovascularization and will lead the next round of significant business development deals.

  4. 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.

  5. 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.

  6. 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

  7. Sulodexide inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy.

    PubMed

    Jo, Hyoung; Jung, Sang Hoon; Kang, Jun; Yim, Hye Bin; Kang, Kui Dong

    2014-11-01

    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.

  8. Indocyanine Green Angiographic Findings of Obscure Choroidal Abnormalities in Neurofibromatosis

    PubMed Central

    Byun, Yong Soo

    2012-01-01

    We report two cases of choroidal neurofibromatosis, detected with the aid of indocyanine green angiography (ICGA) in patients with neurofibromatosis (NF)-1, otherwise having obscure findings based on ophthalmoscopy and fluoresceine angiography (FA). In case 1, the ophthalmoscopic exam showed diffuse bright or yellowish patched areas with irregular and blunt borders at the posterior pole. The FA showed multiple hyperfluorescent areas at the posterior pole in the early phase, which then showed more hyperfluorescence without leakage or extent in the late phase. The ICGA showed diffuse hypofluorescent areas in both the early and late phases, and the deep choroidal vessels were also visible. In case 2, the fundus showed no abnormal findings, and the FA showed weakly hypofluorescent areas with indefinite borders in both eyes. With the ICGA, these areas were more hypofluorescent and had clear borders. Choroidal involvement in NF-1 seems to occur more than expected. In selected cases, ICGA is a useful tool to be utilized when an ocular examination is conducted in a patient that has no definite findings based on the ophthalmoscope, B-scan, or FA tests. PMID:22670083

  9. Ocular Sarcoidosis

    PubMed Central

    Pasadhika, Sirichai; Rosenbaum, James T

    2015-01-01

    Sarcoidosis is one of the leading causes of inflammatory eye disease. Ocular sarcoidosis can involve any part of the eye and its adnexal tissues, and may cause uveitis, episcleritis/scleritis, eyelid abnormalities, conjunctival granuloma, optic neuropathy, lacrimal gland enlargement and orbital inflammation. Glaucoma and cataract can be complications from inflammation itself or adverse effects from therapy. Ophthalmic manifestations can be isolated, or associated with other organ involvement. Patients with ocular sarcoidosis can present with a wide range of clinical presentations and severity. Multi-disciplinary approaches are required to achieve the best treatment outcomes for both ocular and systemic manifestations. PMID:26593141

  10. Diffuse villous hyperplasia of choroid plexus.

    PubMed

    Iplikcioglu, A C; Bek, S; Gökduman, C A; Bikmaz, K; Cosar, M

    2006-06-01

    Diffuse villous hyperplasia of choroid plexus (DVHCP) is a rare condition which is characterized by the presence of diffuse enlargement of the entire choroid plexus throughout the length of the choroidal fissure and overproduction of CSF. The diagnosis of diffuse villous hyperplasia of choroid plexus can be established by the MR demonstration of diffusely large, contrast enhanced choroid plexus in the cases of overproduction hydrocephalus. Although some authors recommend choroid plexus excision or coagulation, ventriculo-atrial shunt insertion is a simple and effective treatment modality in cases of diffuse villous hyperplasia of the choroid plexus. In this report we present a case of diffuse villous hyperplasia of the choroid plexus and a short review of the literature. To our knowledge, in the CT and MRI era only 5 cases of DVHCP cases have been reported.

  11. Indocyanine green angiography for examining the normal ocular fundus in dogs.

    PubMed

    Wakaiki, Shinsuke; Maehara, Seiya; Abe, Reona; Tsuzuki, Keiko; Igarashi, Osamu; Saito, Akihiko; Itoh, Norihiko; Yamashita, Kazuto; Izumisawa, Yasuharu

    2007-05-01

    In dogs, a variety of diseases of the retina and choroid have been reported, either separately or concomitantly; however, the canine choroid is difficult to evaluate by veterinary techniques currently available. Indocyanine green (ICG) angiography is widely used in human ophthalmology, but has not been investigated for use in canine ophthalmology. The aim of this study was to apply a new approach to ICG angiography and compare the resulting angiograms with fluorescein (FLUO) angiograms of the ocular fundus in dogs. With a fundus camera equipped with an infrared-sensitive charged coupled device (CCD), we performed angiography on eight healthy beagles under inhalation anesthesia. ICG angiography enabled clear visualization of the choroidal vasculature, whereas FLUO angiography showed only the retinal vessels. At 8.4 +/- 3.6 sec after administration of ICG dye into the cephalic vein, the choroidal arteries could be seen extending radially from the optic disc, then the choroidal veins became apparent at 10.2 +/- 4.1 sec, coursing alongside the choroidal arteries. Gradual fading of the choroidal vessels began 13.2 +/- 2.2 min after the dye was administered, and overall diffuse fluorescence of the fundus appeared. Diffuse fluorescence of the fundus continued after the choroidal vessels and optic disc faded at about 58.3 +/- 5.3 min from administration of the dye. In conclusion, ICG angiography provides clear resolution and is reliable and simple, thus offering promise as a diagnostic aid for clinical evaluation of the choroid in dogs.

  12. Focal choroidal excavation associated with polypoidal choroidal vasculopathy.

    PubMed

    Say, Emil Anthony T; Jani, Pooja D; Appenzeller, Matthew F; Houghton, Odette M

    2013-01-01

    A 48-year-old woman presented with blurred vision in her right eye for 6 weeks. Visual acuity was 20/300 and 20/25 in the right and left eyes, respectively. Fundus examination showed subretinal hemorrhage in the superonasal macula in the right eye, whereas the left eye was normal. Fluorescein angiography showed blocked fluorescence from hemorrhage and a round distinct hypofluorescent spot along the inferotemporal arcade. Indocyanine green angiography revealed hyperfluorescent tubular and aneurysmal dilatations consistent with polypoidal choroidal vasculopathy in the superior macula. Spectral-domain optical coherence tomography showed retinal pigment epithelial irregularities and detachment. Scans through the round area of hypofluorescence revealed a conforming focal choroidal excavation and thinning of the underlying choriocapillaries. Because the pathogenesis of focal choroidal excavation is currently unclear, the authors propose the possibility of an acquired etiology related to loss of choriocapillaries from perfusion abnormalities as evidenced here.

  13. Vascular basophilia in ocular and orbital tumors.

    PubMed

    Stowe, G C; Zakov, Z N; Albert, D M; Smith, T R; Sang, D N; Craft, J L

    1979-10-01

    The occurrence of vascular basophilia in ocular tumors has been a selective histologic feature of retinoblastomas. We recently observed a metastatic oat-cell carcinoma to the choroid which also demonstrated such a vascular hematoxyphilia. Histologic review of a variety of ocular and orbital metastatic carcinomas failed to yield a similar basophilic pattern. Examination of 100 consecutive retinoblastomas for vascular basophilia revealed an incidence of 6.0%. Similar material was not seen in any of 125 melanomas, including 10 with areas of necrosis. Histochemical studies showed the basophilic material to be DNA, and electron microscopy revealed the nuclear debris of pyknotic tumor cells to be continuous with identical material surrounding the adjacent blood vessels. The pathogenesis of vascular deposition of DNA in these two ocular tumors remains unclear. This finding most likely represents a form of tumor activity requiring comparatively healthy blood vessels to adequately precipitate liberated nucleic acids being filtered from the necrotic and degenerating tumor tissue.

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

    PubMed

    Mertz, J R; Wallman, J

    2000-04-01

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

  15. Quantitative reflection spectroscopy at the human ocular fundus

    NASA Astrophysics Data System (ADS)

    Hammer, Martin; Schweitzer, Dietrich

    2002-01-01

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

  16. Gender Differences in Ocular Blood Flow

    PubMed Central

    Schmidl, Doreen; Garhöfer, Gerhard; Popa-Cherecheanu, Alina

    2015-01-01

    Gender medicine has been a major focus of research in recent years. The present review focuses on gender differences in the epidemiology of the most frequent ocular diseases that have been found to be associated with impaired ocular blood flow, such as age-related macular degeneration, glaucoma and diabetic retinopathy. Data have accumulated indicating that hormones have an important role in these diseases, since there are major differences in the prevalence and incidence between men and pre- and post-menopausal women. Whether this is related to vascular factors is, however, not entirely clear. Interestingly, the current knowledge about differences in ocular vascular parameters between men and women is sparse. Although little data is available, estrogen, progesterone and testosterone are most likely important regulators of blood flow in the retina and choroid, because they are key regulators of vascular tone in other organs. Estrogen seems to play a protective role since it decreases vascular resistance in large ocular vessels. Some studies indicate that hormone therapy is beneficial for ocular vascular disease in post-menopausal women. This evidence is, however, not sufficient to give any recommendation. Generally, remarkably few data are available on the role of sex hormones on ocular blood flow regulation, a topic that requires more attention in the future. PMID:24892919

  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. 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.

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

    PubMed Central

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

    2014-01-01

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

  20. Rabies: ocular pathology.

    PubMed Central

    Haltia, M; Tarkkanen, A; Kivelä, T

    1989-01-01

    Ocular pathology in the first European case of human bat-borne rabies is described. The patient was a 30-year-old bat scientist who seven weeks after bat bite developed neurological symptoms and died 23 days later. Rabies virus antigens were detected in brain smears. After extensive virological studies the virus turned out to be a rabies-related virus, closely resembling the Duvenhage virus isolated from bats in South Africa in 1980. By light microscopy focal chronic inflammatory infiltration of the ciliary body and of the choroid was found. PAS-positive exudate was seen in the subretinal and in the outer plexiform layers of the retina, and retinal veins showed endothelial damage and perivascular inflammation. Many of the retinal ganglion cells were destroyed. The presence of rabies-related viral antigen in the retinal ganglion cells was shown by positive cytoplasmic immunofluorescence, though electron microscopy failed to identify definite viral structures in the retina. By immunohistochemistry glial fibrillary acidic protein was observed in the Müller's cells, which are normally negative for this antigen but express it as a reactive change when the retina is damaged. Synaptophysin, a constituent of presynaptic vesicles of normal retinal neurons, was not detected in the retina. Images PMID:2920157

  1. Nanoparticles in the ocular drug delivery

    PubMed Central

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

    2013-01-01

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

  2. Ocular Pathology.

    PubMed

    Bauer, Bianca S

    2015-08-01

    Although not comprehensive of all ocular conditions in the equine species, this article concentrates on various ophthalmic conditions observed in the horse where laboratory diagnostics are recommended. The importance of laboratory diagnostic testing cannot be underestimated with equine ophthalmic disease. In many cases, laboratory diagnostics can aid in obtaining an early diagnosis and determining appropriate therapy, which in turn, can provide a better prognosis. In unfortunate cases where ocular disease results in a blind, painful eye necessitating enucleation, light microscopic evaluation is imperative to determine or confirm the cause of the blindness and provide a prognosis for the contralateral eye.

  3. Ocular toxocariasis.

    PubMed

    Arevalo, J Fernando; Espinoza, Juan V; Arevalo, Fernando A

    2013-01-01

    Ocular toxocariasis is an uncommon worldwide parasitic infection that affects mostly children and is found in both rural and metropolitan areas. In many parts of the world, parasitic infections of the eye are a major cause of blindness. The diagnosis of toxocariasis is essentially clinical, based on the lesion morphology and supportive laboratory data such as serum enzyme-linked immunosorbent assay (ELISA) titers and ELISA Toxocara titers on aqueous humor; other diagnostic methods are imaging studies including optical coherence tomography, fluorescein angiography, computed tomography, and ocular ultrasound. Treatment is directed at complications arising from intraocular inflammation and vitreous membrane traction. Early vitrectomy may be of value both diagnostically and therapeutically.

  4. Laser interferometric investigations of pulsatile choroidal blood flow: review and new results on the validity of the technique

    NASA Astrophysics Data System (ADS)

    Schmetterer, Leopold F.; Wolzt, M.

    1998-07-01

    A short overview of currently available ocular blood flow techniques is given. We have recently introduced a laser interferometric technique for the measurement of ocular fundus pulsation. The eye is illuminated by a single mode laser beam which is reflected at the anterior corneal surface and the fundus. The two re-emitted waves produce interference fringes from which distance changes between cornea and retina during the cardiac cycle can be calculated. These rhythmic changes in corneo-retinal distance are caused by the arterial pulsatile inflow of blood, which increases the ocular volume. The fundus pulsation amplitude (FPA) is the maximum distance change between cornea and retina during the cardiac cycle and is taken as a relative measure of pulsatile choroidal blood flow. The high reproducibility and the high sensitivity of the method are discussed. In addition, the present article reviews comparative measurement with other techniques for the assessment of choroidal blood flow, which validates the method. Furthermore, we present new data on a comparison of color Doppler imaging in the posterior ciliary arteries and laser interferometric measurement of FPA. Applications of laser interferometric measurement of FPA to study the physiology, the pharmacology, and the pathophysiology of the choroidal circulation are reviewed. In conclusion, FPA can be taken as a relative measure of pulsatile choroidal blood flow. The technique is particularly suitable for pharmacodynamic studies.

  5. Characterization of the choroidal mast cell.

    PubMed Central

    Godfrey, W A

    1987-01-01

    The experimental studies performed on nonpigmented rat choroids and the review of the important literature covered in this thesis seem to justify the following statements: 1. Mast cells are present in the choroid in significant numbers. 2. Mast cell numbers vary considerably from one individual to another and from one location in the choroid to another. 3. The major concentration of mast cells in the uvea is in the posterior choroid. 4. The mast cells of the choroid have a preferential location along arterial vessels. 5. Choroidal mast cell population density apparently decreases with senescence. 6. Mast cell products are present in sufficient quantity to exert substantial effects on physiologic, immunologic, and inflammatory responses in the choroid. 7. Choroidal mast cell products are released with appropriate stimulation and share some properties with the connective-tissue mast cell. 8. Choroidal mast cell demonstrate enough differences to suggest that a local differentiation may be present and may represent a locally controlled modulating effect for choroidal physiologic, immunologic, and inflammatory reactions. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 11 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16 FIGURE 17 PMID:3328921

  6. 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.

  7. 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

  8. 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

  9. Endoplasmic Reticulum Stress in Age-Related Macular Degeneration: Trigger for Neovascularization

    PubMed Central

    Salminen, Antero; Kauppinen, Anu; Hyttinen, Juha MT; Toropainen, Elisa; Kaarniranta, Kai

    2010-01-01

    Age-related macular degeneration (AMD) can be classified into two main categories: the atrophic, dry form and the exudative, wet form. The crucial difference between dry and wet AMD is the development of choroidal neovascularization in wet AMD. One fundamental cause of the neovascularization is the increased expression of VEGF (vascular endothelial growth factor) in retinal pigment epithelial cells. Progression of AMD is linked to augmentation of cellular stress, for example, oxidative stress, proteotoxic stress, inflammation and hypoxia. All these conditions can trigger stress in endoplasmic reticulum (ER), which maintains protein quality control in cells. ER stress induces the unfolded protein response (UPR) via IRE1 (inositol-requiring protein-1), PERK (protein kinase RNA-like ER kinase) and ATF6 (activating transcription factor-6) transducers. UPR signaling is a double-edged sword, that is, it can restore cellular homeostasis as far as possible, but ultimately may lead to chronic, overwhelming stress that can cause apoptotic cell death. Interestingly, ER stress is a well-known inducer of angiogenesis in cancer. Moreover, stress conditions associated with the progress of AMD can induce the expression of VEGF. We discuss the role of ER stress in the regulation of neovascularization and the conversion of dry AMD to its wet, detrimental counterpart. PMID:20683548

  10. [Ocular ischemic syndrome--a case report].

    PubMed

    Zemba, M; Avram, Corina Ioana; Ochinciuc, Uliana; Stamate, Alina Cristina; Camburu, Raluca Lăcrămioara

    2013-01-01

    Ocular ischemic syndrome, also known as hypoperfusion/ hypotensive retinopathy or as ischemic oculopathy is a rare ocular disease determined by chronic arterial hypoperfusion through central retinal artery, posterior and anterior ciliary arteries. It is bilateral in 20% of the cases. Most often it appears due to severe occlusion of the carotid arteries (ICA, MCA>ECA), described in 1963 by Kearns and Hollenhorst. Occasionally it can be determined by the obstruction of ophtalmic artery or some arterities (Takayasu, giant cell arteritis). The risk factors are: age between 50-80 years, males (M:F = 2:1), arterial hypertension, diabetes, coronary diseases (5% of the cases develop ocular ischemic syndrome), vascular stroke, hemodialysis. The case we present is of an 63 years old man known with primary arterial hypertension, hypercholesterolemia, diabetes type 2 non insulin dependent and diagnosticated with ischemic cerebral stroke and bilateral obstruction of internal carotid arteries in march 2010, who is presenting for visual impairment in both eyes. The imaging investigations show important carotid occlusion and at the ophthalmologic evaluation there are ocular hypertension and rubeosis iridis at the right eye, optic atrophy at both eyes (complete in the right eye and partial in the left eye), with superior altitudinal visual field defect in left eye. The following diagnosis was established: Chronic ocular ischemic syndrome in both eyes with Neovascular glaucoma at the right eye, Anterior ischemic optic neuropathy at the left eye and laser panphotocoagulation at the right eye was started.

  11. Blunt ocular trauma secondary to "war games".

    PubMed

    Mamalis, N; Monson, M C; Farnsworth, S T; White, G L

    1990-11-01

    "War games" are gaining popularity in the western United States. These recreational contests involve members of one team attempting to shoot their opponents with high-velocity dye or paint pellets fired from air guns. Unfortunately, serious eye injuries occur when participants do not use protective eye wear. We report a case of severe blunt ocular trauma resulting in a hyphema, choroidal rupture, and retinal and vitreal hemorrhage secondary to a paint pellet striking an unprotected eye. This injury resulted in a significant visual defect in this patient.

  12. 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

  13. Spontaneous Necrosis of Choroidal Melanoma

    PubMed Central

    Thareja, Shalini; Rashid, Alia; Grossniklaus, Hans E.

    2014-01-01

    Background/Aims The purpose of this study was to examine the clinical presentations and pathological features of spontaneously necrotic choroidal melanomas. Methods The clinical and histological features of patients who underwent enucleation for uveal melanoma from 1989 to 2012 at Emory University and were found to have spontaneously necrotic choroidal melanomas were retrospectively analyzed. Results A total of 6 cases were identified. All cases had 90-100% tumor necrosis and also exhibited marked ischemic necrosis of the iris and ciliary body; 5 of 6 cases exhibited marked ischemic necrosis of the retina. The tumor consisted of melanoma ghost cells often surrounded by a zone of pigmented macrophages. Thrombi were not found in any of the cases. All of the tumors in our cases were centered around the equatorial choroid and 2 extended into the ciliary body. One of the cases exhibited a wedge-shaped infarct in a lateral aspect of the tumor. In most of the cases, microscopic areas of intact tumor cells were present in the peripheries of the tumors. Conclusions Spontaneous necrosis may occur in uveal melanoma. We believe that this occurs secondary to tumor hypoxia in the center of the tumor, followed by secondary inflammation, generalized ischemia and finally complete tumor necrosis. PMID:27175363

  14. Ocular metastases

    PubMed Central

    Cohen, V M L

    2013-01-01

    The eye is a rare site for disseminated malignancy because of the absence of a lymphatic system. Metastases to the ocular structures occur by haematogenous spread and therefore the parts of the eye with the best vascular supply are most likely to be affected. Many patients with Stage 4 carcinomatosis (distal metastatic spread) already have a history of a previous primary cancer. However, this is not always the case for lung cancer as this can metastasise early to the uveal tract and therefore the ophthalmologist may be the first to discover the presence of terminal metastatic disease. Broadly speaking, treatment options are focused on improving the patients' quality of life if visual acuity is threatened. Long-term side effects of treatment need to be considered as systemic cancer treatments and therefore patient life expectancy is improving. In this manuscript, presented at the Cambridge symposium 2012, the diagnosis and challenges involved in the management of ocular metastases are presented. PMID:23222564

  15. Stereotactic radiotherapy in neovascular age-related macular degeneration

    PubMed Central

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

    2016-01-01

    Abstract Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address in this retrospective analysis. Patients who met the INTREPID criteria for best responders were eligible for SRT. A total of 32 eyes of 32 patients were treated. Thereafter, patients were examined monthly for 12 months and received pro re nata IVI of aflibercept or ranibizumab. Outcome measures were: mean number of injections, best-corrected visual acuity, and morphological changes of the outer retina-choroid complex as well as patient safety. Mean number of IVI decreased by almost 50% during the 12 months after SRT compared to the year before, whereas visual acuity increased by one line (logMAR). Morphological evaluation showed that most changes affect outer retinal layers. Stereotactic radiotherapy significantly reduced IVI retreatment in nAMD patients under real-life circumstances. Therefore, SRT might be the first step to stop visual loss as a result of IVI undertreatment, which is a major risk. PMID:28033280

  16. Airbag-Associated Severe Blunt Eye Injury Causes Choroidal Rupture and Retinal Hemorrhage: A Case Report

    PubMed Central

    Wang, Shih Hao; Lim, Chen Chee; Teng, Yu Ti

    2017-01-01

    A case of choroidal rupture caused by airbag-associated blunt eye trauma and complicated with massive subretinal hemorrhage and vitreous hemorrhage that was successfully treated with intravitreal injection of expansile gas and bevacizumab is presented. A 53-year-old man suffered from loss of vision in his right eye due to blunt eye trauma by a safety airbag after a traffic accident. On initial examination, the patient had no light perception in his right eye. Dilated ophthalmoscopy revealed massive subretinal hemorrhage with macular invasion and faint vitreous hemorrhage. We performed intravitreal injection of pure sulfur hexafluoride twice for displacement, after which visual acuity improved to 0.03. For persistent subretinal hemorrhage and suspicion of choroidal neovascularization (CNV), intravitreal bevacizumab (1.25 mg/0.05 mL) injection was administered. After 3 weeks, the visual acuity of his right eye recovered to 0.4. For early-stage choroidal rupture-induced subretinal hemorrhage and complications of suspected CNV, intravitreal injection of expandable gas and intraocular injection of antiangiogenesis drugs seem to be an effective treatment. PMID:28203191

  17. 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.

  18. Corticosteroids for ocular toxoplasmosis

    PubMed Central

    Jasper, Smitha; Vedula, Satyanarayana S; John, Sheeja S; Horo, Saban; Sepah, Yasir J; Nguyen, Quan Dong

    2014-01-01

    Background Ocular infestation with Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea and consequently lead to complications such as glaucoma, cataract, and posterior synechiae. Objectives The objective of this systematic review was to assess the effects of adjunctive use of corticosteroids for ocular toxoplasmosis. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to October 2012), EMBASE (January 1980 to October 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We searched the reference lists of included studies for any additional studies not identified by the electronic searches. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 11 October 2012. Selection criteria We planned to include randomized and quasi-randomized controlled trials. Eligible trials would have enrolled participants of any age who were immunocompetent and were diagnosed with active ocular toxoplasmosis. Included trials would have compared anti-parasitic therapy plus corticosteroids versus anti-parasitic therapy alone, or different doses or times of initiation of corticosteroids. Data collection and analysis Two authors independently screened titles and abstracts retrieved from the electronic searches. We retrieved full-text articles of studies categorized as ‘unsure’ or ‘include’ after review of the abstracts. Two authors independently reviewed each full-text article. Discrepancies were

  19. Morphologic Characteristics of Choroid in the Major Choroidal Thickening Diseases, Studied by Optical Coherence Tomography

    PubMed Central

    Kang, Se Woong; Woo, Se Joon; Ryoo, Na-Kyung; Kim, Sang Jin; Han, Gyule

    2016-01-01

    We investigated morphologic features of choroid in the choroidal thickening diseases, including central serous chorioretinopathy (CSC), polypoidal choroidal vasculopathy (PCV), and Vogt-Koyanagi-Harada disease (VKH), by a novel tomographic classification system of the choroid. This cross-sectional study involved 30 patients with active CSC, 30 patients with active PCV, and 27 patients with active VKH, and 30 normal controls. Utilizing enhanced depth imaging optical coherence tomography, we classified the morphology of the choroid into five categories: 1) Standard (S), 2) Dilated outer layer and Attenuated inner layer (DA), 3) Darkened (D), 4) Marbled (M), and 5) Pauci-Vascular (PV) types. Additional tomographic characteristics of the choroid such as choroidal vascular dilation, convolution, scleral invisibility, and choroidal hyper- or hypo-thickening were identified as well. The distribution of five choroidal tomographic morphology and additional tomographic characteristics in each group were analyzed. The DA type was observed in the CSC group more frequently than in the normal control group (53.3% vs 3.3%, P < 0.001). Additional tomographic characteristics, such as choroidal vascular dilation (76.7%), and choroidal hyper-thickening (36.7%), were more prevalent in the CSC group than in the control group. The PCV group showed higher prevalence of DA type (33.3% vs. 3.3%, P = 0.006) than the control group. The VKH group showed a significantly higher frequency of the D type (63.0%), convolution (40.7%), and scleral invisibility (70.4%) than controls (0% for all three findings). In conclusion, CSC and PCV shared common morphologic characteristics of choroid, including dilated outer vascular layer and focally attenuated innermost layer. Dense hypo-reflectivity and convolution of choroid were the specific tomographic markers for acute VKH. A new tomographic classification system of choroid may provide discrimination ability and insight into major pachychoroidopathies

  20. Choroidal osteoma: acoustic shadowing and reduplication echoes.

    PubMed

    Abramson, D H; Servodidio, C A; Poole, T A; Budinger, K

    1996-12-01

    A 27-year-old woman had a curious choroidal mass of 12 years duration in her right eye. Interesting ultrasonic findings of a choroidal osteoma, including acoustic shadowing and reduplication echoes on A-scan and B-scan are presented. Ophthalmic nurses can assist in performing ophthalmic examinations and in reinforcing regular follow-up examinations for these patients.

  1. Vascular tumors of the choroid and retina.

    PubMed

    Shanmugam, P Mahesh; Ramanjulu, Rajesh

    2015-02-01

    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.

  2. Bietti crystalline dystrophy and choroidal neovascularisation.

    PubMed

    Gupta, B; Parvizi, S; Mohamed, M D

    2011-02-01

    Bietti crystalline dystrophy is a rare autosomal recessive condition characterised by the presence of crystals in the retina and is followed by retinal and choroidal degeneration. We present a novel finding of juxtafoveal choroidal neovascularisation in Bietti crystalline dystrophy and demonstrate a spectral domain optical coherence tomography image of this disorder.

  3. 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

  4. Systemic Hypertension, Headache, and Ocular Hemodynamics: A New Hypothesis

    PubMed Central

    Gupta, Vinod Kumar

    2006-01-01

    The association between systemic hypertension and headache remains controversial and its pathophysiologic basis is uncertain. A rather characteristic early-morning pulsating headache is commonly seen in hypertensive patients, and a recent meta-analysis supports the link between these 2 entities. Epidemiologic evidence has paradoxically suggested a negative association between hypertension and headache. Unpredictable clinical association between severe hypertension and headache indicates that another cranial perfusion-related variable exerts a critical role. Neuroanatomically, head and neck pain primarily involves the ophthalmic division of the trigeminal nerve (V1). A link between systemic hypertension, pulsatile choroidal blood flow (CBF), and intraocular pressure (IOP) has been established. I propose that a trait ocular sympathetic hypofunction permits rapid episodic ocular choroidal overperfusion that stretches the ocular globe in the cohort of hypertensive patients with headache. Rapid distension of the pain-sensitive corneoscleral envelope can stimulate corneoscleral and iridial pain-sensitive V1 nerve endings and generate headache. Ocular tamponade function physiologically limits choroidal overperfusion. A higher basal IOP in some patients with moderate-to-severe hypertension may dampen pulsatile CBF and account for the negative epidemiologic link between sustained systemic hypertension and headache. Besides activation of the baroreceptor reflex, the association of hypalgesia with hypertension probably involves activation of the vasopressin-endorphin adaptive system consequent to mechanical stimulation of V1. The analogy between hypertensive headache and angle-closure glaucoma is rather limited because typical ocular and visual signs and symptoms of angle-closure glaucoma are not seen in hypertension-related headache. Hypertensive crises, including those associated with pheochromocytoma, are not accompanied by attacks of angle-closure glaucoma. Glaucoma is

  5. 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.

  6. 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.

  7. Ocular dispersion

    NASA Astrophysics Data System (ADS)

    Hammer, Daniel X.; Noojin, Gary D.; Thomas, Robert J.; Stolarski, David J.; Rockwell, Benjamin A.; Welch, Ashley J.

    1999-06-01

    Spectrally resolved white-light interferometry (SRWLI) was used to measure the wavelength dependence of refractive index (i.e., dispersion) for various ocular components. The accuracy of the technique was assessed by measurement of fused silica and water, the refractive indices of which have been measured at several different wavelengths. The dispersion of bovine and rabbit aqueous and vitreous humor was measured from 400 to 1100 nm. Also, the dispersion was measured from 400 to 700 nm for aqueous and vitreous humor extracted from goat and rhesus monkey eyes. For the humors, the dispersion did not deviate significantly from water. In an additional experiment, the dispersion of aqueous and vitreous humor that had aged up to a month was compared to freshly harvested material. No difference was found between the fresh and aged media. An unsuccessful attempt was also made to use the technique for dispersion measurement of bovine cornea and lens. Future refinement may allow measurement of the dispersion of cornea and lens across the entire visible and near-infrared wavelength band. The principles of white- light interferometry including image analysis, measurement accuracy, and limitations of the technique, are discussed. In addition, alternate techniques and previous measurements of ocular dispersion are reviewed.

  8. Analysis of the Serum Lipid Profile in Polypoidal Choroidal Vasculopathy

    PubMed Central

    Li, Miaoling; Zhang, Xiongze; Liao, Nanying; Ye, Baikang; Peng, Yuting; Ji, Yuying; Wen, Feng

    2016-01-01

    Polypoidal choroidal vasculopathy (PCV), the predominant subtype of neovascular age-related macular degeneration in the Asian population, is associated with genetic polymorphism of lipid metabolism. In this study, we performed the untargeted lipidomics approach of ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) to reveal the potential discriminating lipid profile of PCV patients in serum (21 PCV patients and 19 age-matched controls). Unsupervised principal component, supervised orthogonal partial least squares analysis, correlation analysis, and heatmap analysis were performed with the data obtained by UPLC-MS. Forty–one discriminating metabolites were identified. Receiver operating characteristic curve analysis, pathway analysis and functional analysis were performed subsequently, and platelet-activating factor (PAF) was further selected as the key indicator of the distinct lipid metabolism in PCV patients. Finally, the serum level of PAF was validated by enzyme-linked immunosorbent assay, which is significantly higher in PCV patients compared to controls (65 PCV patients and 63 age-matched controls, p < 0.0001), consistent with the UPLC-MS analysis. Our results suggested that PAF is considered as the major indicator of the distinct lipid metabolism in PCV patients. PMID:27910906

  9. Unilateral Glaucoma Associated with Conjunctival Angioma and Choroidal Thickening without Facial Angioma

    PubMed Central

    Saeedi, Osamah J.; Chang, Luke Y.; Arora, Karun S.; Jampel, Henry D.; Quigley, Harry A.

    2016-01-01

    We report a case of a suspected Sturge–Weber syndrome variant diagnosed at the age of 58 with the help of enhanced depth imaging spectral-domain ocular coherence tomography (EDI-SDOCT). A 58-year-old female with unilateral glaucoma was suspected to have choroidal vascular lesion, conjunctival angioma, and no facial port-wine stain who presented to the clinic with bleb dysesthesia many years after trabeculectomy. EDI-SDOCT was performed and revealed markedly increased choroidal thickness in the affected eye. EDI-SDOCT may be helpful in diagnosing Sturge–Weber variants without facial involvement and may aid in the investigation of the pathogenesis of this disease. PMID:27555719

  10. Open-source algorithm for automatic choroid segmentation of OCT volume reconstructions

    PubMed Central

    Mazzaferri, Javier; Beaton, Luke; Hounye, Gisèle; Sayah, Diane N.; Costantino, Santiago

    2017-01-01

    The use of optical coherence tomography (OCT) to study ocular diseases associated with choroidal physiology is sharply limited by the lack of available automated segmentation tools. Current research largely relies on hand-traced, single B-Scan segmentations because commercially available programs require high quality images, and the existing implementations are closed, scarce and not freely available. We developed and implemented a robust algorithm for segmenting and quantifying the choroidal layer from 3-dimensional OCT reconstructions. Here, we describe the algorithm, validate and benchmark the results, and provide an open-source implementation under the General Public License for any researcher to use (https://www.mathworks.com/matlabcentral/fileexchange/61275-choroidsegmentation). PMID:28181546

  11. [Evaluation of antiangiogenic treatment results in choroidal neovascularization related to pathological myopia].

    PubMed

    Carvalho, Beatriz; Freitas-Costa, Paulo; Pinheiro-Costa, João; Falcão, Manuel; Carneiro, Ângela; Falcão-Reis, Fernando

    2014-01-01

    Introdução: A neovascularização coroideia associada à miopia patológica é uma das principais causas de perda de visão central e irreversível em indivíduos jovens. Os objetivos deste estudo são avaliar os resultados a longo prazo do tratamento antiangiogénico, com ranibizumab e/ou bevacizumab, na neovascularização coroideia associada à miopia patológica e caraterizar os fatores preditivos dos resultados funcionais e anatómicos obtidos.Material e Métodos: Avaliámos os resultados de 84 olhos de 81 doentes com neovascularização coroideia miópica, dos quais 84 (100%) completaram 12 meses de seguimento, 67 (79,8%) 24 meses de seguimento, 54 (64,3%) 36 meses de seguimento, 29 (34,5%) 48 meses de seguimento e 15 (16,7%) 60 meses de seguimento. Procedemos à recolha de dados relativos à melhor acuidade visual corrigida em escala ETDRS, espessura foveal na tomografia de coerência óptica e caraterísticas da angiografia fluoresceínica, inicial e após tratamento.Resultados: As melhorias na melhor acuidade visual corrigida e na espessura foveal foram significativas para todos os tempos de seguimento (p < 0,05). A média da melhor acuidade visual corrigida inicial era de 43,7 ± 20,1 letras e da espessura foveal inicial de 304,8 ± 127,9μm. As médias da melhor acuidade visual corrigida foram de 55,6 ± 18,5, 52,1 ± 22,3, 52,1 ± 22,6, 50,3 ± 23,8 e 47,8 ± 24,5 para os 12, 24, 36, 48 e 60 meses de tratamento, respetivamente. As médias das espessuras foveais foram de 209,7 ± 86,2, 190,6 ± 76,1, 174,7 ± 60,6, 189,8 ± 96,7 e 159,4 ± 73,3 para os mesmos tempos de seguimento. Apenas a melhor acuidade visual corrigida inicial foi preditiva de melhores resultados na melhor acuidade visual corrigida final (p < 0,001).Discussão/Conclusão: As injecções intravítreas de anti-VEGF em doentes com neovascularização coroideia miópica cursam com uma melhoria funcional e anatómica significativa e sustentada no tempo. Ensaios clínicos randomizados com follow-up mais extenso são necessários para comprovar a eficácia sustentada destes agentes.

  12. Alectinib for choroidal metastasis in a patient with crizotinib-resistant ALK rearranged positive non-small cell lung cancer.

    PubMed

    Okuma, Yusuke; Tanaka, Yuichiro; Kamei, Tina; Hosomi, Yukio; Okamura, Tatsuru

    2015-01-01

    Choroidal metastasis is rare in cancer patients. Small molecules of molecular targeted agents for lung cancer with actionable mutations were reported to be palliated for symptoms caused by choroidal metastasis. Visual disturbance by choroidal metastasis significantly decreases quality of life during the patient's remaining lifespan; therefore, radiotherapy or laser photocoagulation is proposed with consensus. However, improvement in survival with matched molecular targeted agents for oncogenic driver mutations reminds us to also be concerned with late treatment toxicities. A 30-year-old female patient previously treated with crizotinib harboring ALK rearranged non-small cell lung cancer complained of visual disturbance, fever, and bone pains undergoing anti-PD-1 antibody treatment. A decreased proportion of ALK fusion was demonstrated by fluorescence in situ hybridization in liver metastasis compared to the primary site in a chemo-naïve state. She was diagnosed with low vision, choroidal metastasis and retinal detachment. Therefore, she started alectinib treatment and both her ocular and systemic symptoms were palliated in a week. Later, she temporarily discontinued alectinib because of skin rash although the choroidal metastasis and retinal detachment resolved and she regained low vision completely at 2 weeks. She obtained partial response with alectinib for more than 5 months after recovering from skin rash.

  13. Multivalent nanoparticles bind the retinal and choroidal vasculature.

    PubMed

    Hennig, Robert; Ohlmann, Andreas; Staffel, Janina; Pollinger, Klaus; Haunberger, Alexandra; Breunig, Miriam; Schweda, Frank; Tamm, Ernst R; Goepferich, Achim

    2015-12-28

    The angiotensin II receptor type 1 (AT1R), which is expressed in blood vessels of the posterior eye, is of paramount significance in the pathogenesis of severe ocular diseases such as diabetic retinopathy and age-related macular degeneration. However, small molecule angiotensin receptor blockers (ARBs) have not proven to be a significant therapeutic success. We report here on a nanoparticle system consisting of ARB molecules presented in a multivalent fashion on the surface of quantum dots (Qdots). As a result of the multivalent receptor binding, nanoparticles targeted cells with high AT1R expression and inhibited their angiotensin receptor signaling with an IC50 of 3.8 nM while showing only minor association to cells with low AT1R expression. After intravenous injection into the tail vein of mice, multivalent nanoparticles accumulated in retinal and choroidal blood vessels of the posterior eye. At the same time, multivalent ligand display doubled the Qdot concentration in the blood vessels compared to non-targeted Qdots. Remarkably, ARB-targeted Qdots showed no pronounced accumulation in AT1R-expressing off-target tissues such as the kidney. Following systemic application, this multivalent targeting approach has the potential to amplify AT1R blockade in the eye and concomitantly deliver a therapeutic payload into ocular lesions.

  14. Changes in choroidal thickness after prophylactic iridectomy in primary angle closure suspect eyes using enhanced depth imaging optical coherence tomography

    PubMed Central

    Wang, Wei; Zhou, Minwen; Huang, Wenbin; Gao, Xinbo; Zhang, Xiulan

    2015-01-01

    Purpose: The aim of the present study was to evaluate the effect of surgical peripheral iridectomy (SPI) on choroidal thickness in primary angle-closure suspect (PACS) eyes. Materials and Methods: This was a prospective observational case series of 30 subjects with PACS. Ocular biometry was performed before SPI (baseline) and then 1 week later. Choroid was imaged by enhanced depth imaging optical coherence tomography (EDI-OCT). The choroidal thickness of the subfoveal area at 1 and 3 mm diameter around the fovea was determined. Central anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD), and axial length (AL) were measured by A-scan ultrasound. Parameters were compared before SPI (baseline) and 1 week later. Results: Thirty eyes of 30 patients with mean age of 61.53 ± 7.98 years were studied. There was no significant difference in the choroidal thickness at all macular locations before and after SPI (all P > 0.05). Mean subfoveal choroidal thickness was 279.61 μm ± 65.50 μm before and 274.54 μm ± 63.36 μm after SPI (P = 0.308). There was also no significant change in central ACD, LT, VCD, and LT after SPI (all P > 0.05). Conclusions: SPI does not appear to alter choroidal thickness in PACS eyes, as assessed using EDI-OCT. Long-term follow-up of PACS eyes treated with SPI may provide further insight into the effects of this treatment modality on the choroid. PMID:26654999

  15. Cystic choroid plexus papilloma in the cavum septum pellucidum.

    PubMed

    Tuchman, Alexander; Kalhorn, Stephen P; Mikolaenko, Irina; Wisoff, Jeffrey H

    2009-12-01

    A choroid plexus papilloma is a rare CNS neoplasm arising from the neuroepithelial lining of the choroid plexus. A third ventricular location of a choroid plexus papilloma is rare compared with the more common sites in the lateral and fourth ventricles. Cystic choroid plexus papilloma represents an infrequent subtype that may present diagnostic ambiguity. The authors present a case of cystic choroid plexus papilloma within a cavum septum pellucidum that radiographically mimicked neurocysticercosis.

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

    PubMed Central

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

    2016-01-01

    Ocular neovascularisation underlies blinding eye diseases such as retinopathy of prematurity, proliferative diabetic retinopathy, and wet age-related macular degeneration. These diseases cause irreversible vision loss, and provide a significant health and economic burden. Biologics targeting vascular endothelial growth factor (VEGF) are the major approach for treatment. However, up to 30% of patients are non-responsive to these drugs and they are associated with ocular and systemic side effects. Therefore, there is a need for small molecule ocular angiogenesis inhibitors to complement existing therapies. We examined the safety and therapeutic potential of SH-11037, a synthetic derivative of the antiangiogenic homoisoflavonoid cremastranone, in models of ocular neovascularisation. SH-11037 dose-dependently suppressed angiogenesis in the choroidal sprouting assay ex vivo and inhibited ocular developmental angiogenesis in zebrafish larvae. Additionally, intravitreal SH-11037 (1 μM) significantly reduced choroidal neovascularisation (CNV) lesion volume in the laser-induced CNV mouse model, comparable to an anti-VEGF antibody. Moreover, SH-11037 synergised with anti-VEGF treatments in vitro and in vivo. Up to 100 μM SH-11037 was not associated with signs of ocular toxicity and did not interfere with retinal function or pre-existing retinal vasculature. SH-11037 is thus a safe and effective treatment for murine ocular neovascularisation, worthy of further mechanistic and pharmacokinetic evaluation. PMID:27148944

  17. Effects of dynamic exercise and its intensity on ocular blood flow in humans.

    PubMed

    Hayashi, Naoyuki; Ikemura, Tsukasa; Someya, Nami

    2011-10-01

    Visual performance is impaired when the ocular blood flow decreases, indicating that ocular blood flow plays a role in maintaining visual performance during exercise. We examined the ocular blood flow response to incremental cycling exercise to test the hypothesis that ocular blood flow is relatively stable during dynamic exercise because of its autoregulatory nature. The blood flow in the inferior and superior temporal retinal arterioles (ITRA and STRA, respectively) and retinal and choroidal vessels (RCV), mean arterial pressure, and heart rate (HR) were measured at rest and during leg cycling in nine young and healthy subjects (26 ± 5 years, mean ± SD). Ocular blood flow was measured by laser speckle flowmetry. The exercise intensity was incremented by 30 W every 3 min until the subject was unable to maintain a position appropriate for measuring ocular blood flow. Blood flow data obtained during cycling exercise were categorized based on HR as follows: <100, 100-120, and >120 bpm. Blood flow in the RCV increased with the exercise intensity: by 16 ± 8, 32 ± 13, and 40 ± 19% from baseline, respectively. However, blood flow and vascular conductance in the ITRA and STRA did not change significantly with exercise. These findings demonstrate for the first time that ocular blood flow increases in the retina and choroid, but not in the arterioles, with increasing exercise intensity during dynamic exercise.

  18. Vascular Endothelial Growth Factor/Vascular Permeability Factor Is Temporally and Spatially Correlated with Ocular Angiogenesis in a Primate Model

    PubMed Central

    Miller, Joan W.; Adamis, Anthony P.; Shima, David T.; D'Amore, Patricia A.; Moulton, Rachel S.; O'Reilly, Michael S.; Folkman, Judah; Dvorak, Harold F.; Brown, Lawrence F.; Berse, Brygida; Yeo, Tet-Kin; Yeo, Kiang-Teck

    1994-01-01

    Ischemia often precedes neovascularization. Inocular neovascularization, such as occurs in diabetic retinopathy, a diffusible angiogenic factor has been postulated to be produced by ischemicretina and to lead to neovascularization of theretina, optic nerve, or iris. However, no angiogenic factor has been conclusively identified that satisfies this hypothesis. Vascular endothelial growth factor/vascular permeability factor, hereafter referred to as VEGF, is a likely candidate for an ocular angiogenic factor because it is a secreted mitogen, specific for endothelial cells, and is upregulated by hypoxia. We investigated the association of VEGF with the development of experimental iris neovascularization in the cynomolgus monkey. Following theproduction of retinal ischemia by laser occlusion of all branch retinal veins, VEGF was increased in the aqueous fluid, and the aqueous VEGF levels changed synchronously and proportionally with the severity of iris neovascularization. Northern analysis and in situ hybridization revealed that VEGF messenger RNA is upregulated in the ischemic retina. These observations support the hypothesis that ocular neovascularization is regulated by a diffusible factor and identify VEGF as a likely candidate for a retina-derived vascular permeability and angiogenesis factor in vivo. ImagesFigure 2Figure 4Figure 5 PMID:7521577

  19. 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.

  20. Preliminary studies of the effects of vascular adhesion protein-1 inhibitors on experimental corneal neovascularization.

    PubMed

    Enzsöly, Anna; Dunkel, Petra; Récsán, Zsuzsa; Gyorffy, Hajnalka; Tóth, Jeanette; Marics, Gábor; Bori, Zoltán; Tóth, Miklós; Zelkó, Romána; Di Paolo, Maria Luisa; Mátyus, Péter; Németh, János

    2011-07-01

    Vascular adhesion protein-1 (VAP-1) controls the adhesion of lymphocytes to endothelial cells and is upregulated at sites of inflammation. Moreover, it expresses amine oxidase activity, due to the sequence identity with semicarbazide-sensitive amine oxidase. Recent studies indicate a significant role for VAP-1 in neovascularization, besides its contribution to inflammation. Pathological blood vessel development in severe ocular diseases (such as diabetes, age-related macula degeneration, trauma and infections) might lead to decreased visual acuity and finally to blindness, yet there is no clear consensus as to its appropriate treatment. In the present case study, the effects of two VAP-1 inhibitors on experimentally induced corneal neovascularization in rabbits were compared with the effects of a known inhibitor of angiogenesis, bevacizumab, an anti-vascular endothelial growth factor antibody. In accordance with recent literature data, the results of the preliminary study reported here indicate that the administration of VAP-1 inhibitors is a potentially valuable therapeutic option in the treatment of corneal neovascularization.

  1. Influence of ranibizumab treatment on the extracellular matrix in patients with neovascular age-related macular degeneration

    PubMed Central

    Nita, Małgorzata; Michalska-Małecka, Katarzyna; Mazurek, Urszula; Kimsa, Małgorzata; Strzałka-Mrozik, Barbara; Grzybowski, Andrzej; Romaniuk, Dorota

    2014-01-01

    Background We know the influence of the intravitreal anti-vascular endothelial growth factor (VEGF) injections on the choroidal neovascularization in the course of exudative age-related macular degeneration (AMD). However, the influence of the ranibizumab therapy in question on the extracellular matrix (ECM) remains unknown. We aimed to estimate the influence of Lucentis intravitreal injections on the gene expression of structural components of the extracellular matrix in patients with neovascular AMD. Material/Methods Patients with subfoveal localization of neovascularization in AMD, which was clinically active and observed using optical coherence tomography, were treated with ranibizumab (0.5 mg/0.05 mL) in accordance with the PrONTO scheme. Total RNA was extracted from peripheral blood mononuclear cells, and an oligonucleotide microarray technique enabled comparison of the expression level of genes encoding collagens, elastin, and laminins in AMD patients compared to control subjects. Results After 3 intravitreal injections of ranibizumab (Lucentis), COL1A1 and COL6A1 genes showed increased expression, whereas decreased expression mainly occurred for the following genes: COL4A5, COL11A1, COL4A6, LAMB4, and LAMC2. Conclusions Anti-VEGF local therapy influences the gene expression of structural components of the ECM as measured from blood samples. The loading dose of ranibizumab for the retina changes the expression of collagen and laminin genes, but does not influence the expression of the elastin gene. PMID:24866589

  2. [Advance studies of Slit-Robo signal pathway and its roles in ocular neovascularisation].

    PubMed

    Kong, Yichun; Zhao, Kanxing

    2014-05-01

    The migration and patterning of axons and blood vessels share similar guidance mechanisms. Slits and their Roundabout (Robo) receptors were initially characterized as repulsive guidance cues for neuronal axons and mediate the migration of neuronal precursor cells during neural development. In recent years, the research of Slit/Robo signal pathway on neovascularization has become one of hot topics. This review will focus on the role of Slit/Robo signal pathway in ocular neovascularization to promote the research of Slit/Robo signaling on ophthalmology.

  3. Presumed choroidal metastasis of Merkel cell carcinoma

    SciTech Connect

    Small, K.W.; Rosenwasser, G.O.; Alexander, E. III; Rossitch, G.; Dutton, J.J. )

    1990-05-01

    Merkel cell carcinoma is a rare skin tumor of neural crest origin and is part of the amine precursor uptake and decarboxylase system. It typically occurs on the face of elderly people. Distant metastasis is almost uniformly fatal. Choroidal metastasis, to our knowledge, has not been described. We report a patient with Merkel cell carcinoma who had a synchronous solid choroidal tumor and a biopsy-proven brain metastasis. Our 56-year-old patient presented with a rapidly growing, violaceous preauricular skin tumor. Computed tomography of the head disclosed incidental brain and choroidal tumors. Light and electron microscopy of biopsy specimens of both the skin and the brain lesions showed Merkel cell carcinoma. Ophthalmoscopy, fluorescein angiography, and A and B echography revealed a solid choroidal mass. The brain and skin tumors responded well to irradiation. A radioactive episcleral plaque was applied subsequently to the choroidal tumor. All tumors regressed, and the patient was doing well 28 months later. To our knowledge this is the first case of presumed choroidal metastasis of Merkel cell carcinoma.

  4. Cytokines in neovascular age-related macular degeneration: fundamentals of targeted combination therapy.

    PubMed

    de Oliveira Dias, João Rafael; Rodrigues, Eduardo Büchele; Maia, Mauricio; Magalhães, Octaviano; Penha, Fernando Marcondes; Farah, Michel Eid

    2011-12-01

    The neovascular form of age-related macular degeneration (AMD), called wet-AMD or choroidal neovascularisation, begins with damage to the outer retinal cells and retinal pigment epithelium (RPE), which elicits a cascade of inflammatory and angiogenic responses leading to neovascularisation under the macula. Studies showed that oxidative damage, chronic inflammation of the RPE and complement misregulation work at different steps of this disease. After established neovascularisation, several pro- and antiangiogenic agents start to play an important role. Vascular endothelial growth factors (VEGFs) are the most specific and potent regulators of angiogenesis, which are inhibited by intravitreal injections of ranibizumab, bevacizumab, VEGF Trap, pegaptanib sodium and other agents under investigation. Pigment epithelium-derived factor, on the other hand, shows neuroprotective and antiangiogenic activities. Hepatocyte growth factor (HGF) has a mitogenic effect on a wide range of epithelial and endothelial cells, and it is inhibited by an anti-HGF monoclonal antibody. Platelet-derived growth factor is a potent chemoattractant and mitogen for both fibroblasts and retinal RPE cells, which has been inhibited experimentally by VEGF Trap and human anti-platelet-derived growth factor-D monoclonal antibody. Fibroblast growth factor-2 has pleiotropic effects in different cell and organ systems, and it is blocked by anti-FGF antibodies, with a greater benefit regarding antiangiogenesis when combined treatment with anti-VEGF is performed. Tumour necrosis factor alpha is expressed in the retina and the choroid, and its blockade in choroidal neovascularisation includes the use of monoclonals such as infliximab. This paper reviews the most important cytokines involved in the pathogenesis of wet-AMD, with emphasis on potential combined therapies for disease control.

  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. Predictive role of gene polymorphisms affecting thrombin-generation pathway in variable efficacy of photodynamic therapy for neovascular age-related macular degeneration.

    PubMed

    Parmeggiani, Francesco; Gemmati, Donato; Costagliola, Ciro; Sebastiani, Adolfo; Incorvaia, Carlo

    2009-01-01

    Age-related macular degeneration (AMD) represents the leading cause of central blindness in developed countries. The majority of severe vision loss occurs in the neovascular form of AMD, generally characterized by the presence of choroidal neovascularization (CNV) beneath the fovea. Photodynamic therapy with verteporfin (PDT-V) and drugs acting against vascular endothelial growth factor are the most commonly employed treatments for AMD-related subfoveal CNV. The combined use of both these strategies is the most promising therapeutic approach towards this harmful disease. The therapeutic action of PDT-V depends to a photochemical perturbation of thrombo-coagulative processes within CNV. Predictive correlations between peculiar coagulation-balance gene polymorphisms and different levels of post-PDT-V benefit have been recently documented in Caucasian patients with neovascular AMD. Particularly, heterozygous A-allele carriers of factor V Leiden 1691 or prothrombin 20210 gene are characterized by a greater possibility to exhibit clinical benefit after PDT-V. Both mutations induce thrombophilia increasing the thrombin generation in plasma and, thus, they can consistently intensify the photothrombotic phase of the therapeutic CNV occlusion. In prospect, considering the different individual susceptibility to PDT-V, a preoperative assessment of the genotypic thrombophilic background could optimize the eligibility criteria of this intriguing treatment. This review summarizes some of the recent published patents on treatment of neovascular AMD, with a particular attention to PDT-V application in combined therapeutic modalities.

  7. Automated choroidal segmentation method in human eye with 1050nm optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Liu, Cindy; Wang, Ruikang K.

    2014-02-01

    Choroidal thickness (ChT), defined as the distance between the retinal pigment epithelium (RPE) and the choroid-sclera interface (CSI), is highly correlated with various ocular disorders like high myopia, diabetic retinopathy, and central serous chorioretinopathy. Long wavelength Optical Coherence Tomography (OCT) has the ability to penetrate deep to the CSI, making the measurement of the ChT possible. The ability to accurately segment the CSI and RPE is important in extracting clinical information. However, automated CSI segmentation is challenging due to the weak boundary in the lower choroid and inconsistent texture with varied blood vessels. We propose a K-means clustering based automated algorithm, which is effective in segmenting the CSI and RPE. The performance of the method was evaluated using 531 frames from 4 normal subjects. The RPE and CSI segmentation time was about 0.3 seconds per frame, and the average time was around 0.5 seconds per frame with correction among frames, which is faster than reported algorithms. The results from the proposed method are consistent with the manual segmentation results. Further investigation includes the optimization of the algorithm to cover more OCT images captured from patients and the increase of the processing speed and robustness of the segmentation method.

  8. Electrophysiological changes after 360° retinotomy and macular translocation for subfoveal choroidal neovascularisation in age related macular degeneration

    PubMed Central

    Luke, C.; Aisenbrey, S.; Luke, M.; Marzella, G.; Bartz-Schmidt, K. U.; Walter, P.

    2001-01-01

    AIM—To evaluate electrophysiological changes after 360° retinotomy and macular translocation for subfoveal choroidal neovascularisation in patients with age related macular degeneration (AMD).
METHODS—A consecutive series of 32 patients suffering from subfoveal choroidal neovascularisation secondary to AMD underwent 360° retinotomy and macular translocation. The ERG served as the main parameter of the study and was recorded 1 day before the translocation surgery and no earlier than 4 weeks after the silicone oil removal.
RESULTS—The scotopic ERG amplitudes were significantly reduced after translocation surgery. Depending on the applied flash luminance the mean b-wave amplitude reduction of the scotopic ERG varied between 67% (0.2 cd.s/m2) and 74% (0.03 cd.s/m2). The a-waves and b-waves of the saturating light response decreased significantly by 46% and 59%, respectively. The photopic a-wave and b-wave amplitudes were significantly lower after the translocation surgery resulting in a mean reduction of 27% and 43%, respectively.
CONCLUSIONS—Although macular translocation may provide the potential of preserving and even restoring vision in patients with subfoveal choroidal neovascular membranes secondary to AMD the present study indicates that a significant electrophysiological decrease is caused by surgical procedures associated with this technique. Further research is necessary to clarify if certain modifications of the surgical procedure are able to substantially reduce the neuroretinal trauma.

 PMID:11466247

  9. Identical Choroid Plexus Cysts in Monozygotic Monochorionic Twins.

    PubMed

    Qureshi, Adnan I; Degenhardt, Jan; Axt-Fliedner, Roland; Kohl, Thomas

    2016-01-01

    Choroid plexus cysts have been infrequently reported with chromosomal abnormalities.Isolated choroid plexus cysts in a monozygotic twin pair hints to a genetically determined pathway as a possible cause.

  10. Ocular involvement in acute febrile neutrophilic dermatosis (Sweet syndrome): new cases and review of the literature.

    PubMed

    Gottlieb, Chloe C; Mishra, Aditya; Belliveau, Dan; Green, Peter; Heathcote, J Godfrey

    2008-01-01

    Sweet syndrome (acute febrile neutrophilic dermatosis) is a dermatologic disorder with accompanying features of systemic inflammation. It is commonly associated with conjunctivitis, but a variety of types of ocular inflammation have been reported. The ocular manifestations of Sweet syndrome include periorbital and orbital inflammation, dacryoadenitis, conjunctivitis, episcleritis, scleritis, limbal nodules, peripheral ulcerative keratitis, iritis, glaucoma, and choroiditis. The ocular inflammation appears concurrently with skin lesions. An overview of Sweet syndrome is presented with a review of cases in the literature describing ocular involvement. We report two additional cases of ocular involvement, one with conjunctivitis and a second with iritis, peripheral ulcerative keratitis, and episcleritis. Of the 20 cases, half were bilateral. Thirteen cases occurred in the setting of classical or idiopathic Sweet syndrome and seven in association with malignancy. Biopsies of ocular tissue were infrequent, but, in the seven cases where ocular tissue was analyzed, the histopathology was similar to that of the cutaneous lesions. The ocular complications of Sweet syndrome resolved with systemic administration of corticosteroid or cyclosporine. Topical ocular steroid treatment was frequently used in conjunction with oral steroid but may not have been valuable.

  11. 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

  12. Choroidal and skin metastases from colorectal cancer

    PubMed Central

    Ha, Joo Young; Oh, Edward Hynseung; Jung, Moon Ki; Park, Song Ee; Kim, Ji Tak; Hwang, In Gyu

    2016-01-01

    Choroidal and skin metastasis of colon cancer is rare. In women, the frequency of cutaneous metastasis from colon cancer as the primary lesion in is 9% and skin metastasis occurs in 0.81% of all colorectal cancers. We report a patient with colonic adenocarcinoma who presented with visual disorder in her right eye and scalp pain as her initial symptoms. Contrast-enhance orbital magnetic resonance imaging with fat suppression revealed an infrabulbar mass, and skin biopsy of the posterior parietal scalp confirmed adenocarcinoma. These symptoms were diagnosed as being caused by choroidal and skin metastases of colonic adenocarcinoma. We started palliative chemotherapy with oral capecitabine (1000 mg/m2, twice a day, on days 1-14) every 3 wk, which was effective at shrinking the brain masses and improving the visual disorder. This is the first report that capecitabine is effective at reducing a choroidal and cutaneous metastatic lesion from right-sided colorectal cancer. PMID:27920486

  13. Ocular hemodynamic effects of nitrovasodilators in healthy subjects.

    PubMed

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

    2010-01-01

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

  14. Ocular surface temperature in age-related macular degeneration.

    PubMed

    Sodi, Andrea; Matteoli, Sara; Giacomelli, Giovanni; Finocchio, Lucia; Corvi, Andrea; Menchini, Ugo

    2014-01-01

    Background. The aim of this study is to investigate the ocular thermographic profiles in age-related macular degeneration (AMD) eyes and age-matched controls to detect possible hemodynamic abnormalities, which could be involved in the pathogenesis of the disease. Methods. 32 eyes with early AMD, 37 eyes with atrophic AMD, 30 eyes affected by untreated neovascular AMD, and 43 eyes with fibrotic AMD were included. The control group consisted of 44 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, diabetes mellitus, and a body temperature higher than 37.5°C. A total of 186 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The ocular surface temperature (OST) of three ocular points was calculated by means of an image processing technique from the infrared images. Two-sample t-test and one-way analysis of variance (ANOVA) test were used for statistical analyses. Results. ANOVA analyses showed no significant differences among AMD groups (P value >0.272). OST in AMD patients was significantly lower than in controls (P > 0.05). Conclusions. Considering the possible relationship between ocular blood flow and OST, these findings might support the central role of ischemia in the pathogenesis of AMD.

  15. Ocular Surface Temperature in Age-Related Macular Degeneration

    PubMed Central

    Sodi, Andrea; Giacomelli, Giovanni; Corvi, Andrea; Menchini, Ugo

    2014-01-01

    Background. The aim of this study is to investigate the ocular thermographic profiles in age-related macular degeneration (AMD) eyes and age-matched controls to detect possible hemodynamic abnormalities, which could be involved in the pathogenesis of the disease. Methods. 32 eyes with early AMD, 37 eyes with atrophic AMD, 30 eyes affected by untreated neovascular AMD, and 43 eyes with fibrotic AMD were included. The control group consisted of 44 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, diabetes mellitus, and a body temperature higher than 37.5°C. A total of 186 eyes without pupil dilation were investigated by infrared thermography (FLIR A320). The ocular surface temperature (OST) of three ocular points was calculated by means of an image processing technique from the infrared images. Two-sample t-test and one-way analysis of variance (ANOVA) test were used for statistical analyses. Results. ANOVA analyses showed no significant differences among AMD groups (P value >0.272). OST in AMD patients was significantly lower than in controls (P > 0.05). Conclusions. Considering the possible relationship between ocular blood flow and OST, these findings might support the central role of ischemia in the pathogenesis of AMD. PMID:25436140

  16. Effects of exercise on ocular physiology and disease.

    PubMed

    Gale, Jesse; Wells, Anthony P; Wilson, Graham

    2009-01-01

    Regular exercise is a healthy lifestyle choice with numerous benefits to general health. Ophthalmologists may face questions of the benefits or risks of exercise to eyes. Here the effects of acute exertion and regular physical activity on ocular physiology and disease are reviewed. Intraocular pressure is transiently reduced by dynamic exercise. For the great majority of patients exercise is beneficial to the eyes by reducing risk of central retinal vein occlusion and neovascular age-related macular degeneration, and by improving control of systemic hypertension and diabetes. Ophthalmologists should be advocates of regular exercise with appropriate eye protection.

  17. [Diagnostic Approaches to Suspected Choroidal Melanoma].

    PubMed

    Girbardt, C; Rehak, M; Wiedemann, P

    2017-03-10

    Whenever funduscopy reveals possible choroidal melanoma, all available information must be gathered to either confirm or exclude the diagnosis. Well-defined funduscopic criteria are available, which can already lead to a high degree of diagnostic certainty. Additional technical examinations can be used to exclude possible differential diagnoses. In cases where no clear diagnosis can be established, it is possible to take a biopsy or to watch and wait in order to observe possible growth. Whenever the diagnosis of a choroidal melanoma is established, cancer staging has to be performed in order to search for possible metastases.

  18. Evaluation of Subfoveal Choroidal Thickness in Internal Carotid Artery Stenosis

    PubMed Central

    Akçay, Betül İlkay Sezgin; Kardeş, Esra; Maçin, Sultan; Ünlü, Cihan; Özgürhan, Engin Bilge; Maçin, Aydın; Bozkurt, Tahir Kansu; Ergin, Ahmet; Surmeli, Reyhan

    2016-01-01

    Purpose. To evaluate the relationship between internal carotid artery (ICA) stenosis and subfoveal choroidal thickness (SFCT) in the elderly population. Methods. A total of 42 eyes of 21 patients with more than 70% ICA stenosis (Group 1) on one side and less than 70% stenosis (Group 2) on the other side were recruited for this study. ICA stenosis was diagnosed using both the B-mode and Doppler ultrasound. The two groups were compared in terms of the percentage of stenosis, SFCT measurements, intraocular pressure, ocular perfusion pressure, refractive error, and peak systolic velocity. Eyes were examined with the RTVue-100 OCT device by the EDI-OCT technique. Results. The mean age of the patients was 71.9 ± 10.8 years. The mean percentage of ICA stenosis was 74 ± 4.9% in Group 1 and 47.5 ± 7.7% in Group 2. The mean SFCT was 231.9 ± 44.6 μm in Group 1 and 216.2 ± 46.8 μm in Group 2, which was significantly lower (P = 0.028). A statistically significant positive correlation was found between the percentage of internal carotid artery stenosis and SFCT (r = 0896, P = 0.001). Conclusions. Compensatory SFCT increase can be seen in ipsilateral internal carotid artery stenosis greater than 70%. PMID:26989500

  19. Increased ocular blood flow and /sup 125/I-albumin permeation in galactose-fed rats: inhibition by sorbinil

    SciTech Connect

    Tilton, R.G.; Chang, K.; Weigel, C.; Eades, D.; Sherman, W.R.; Kilo, C.; Williamson, J.R.

    1988-06-01

    125I-Albumin permeation and blood flow (assessed with 15 micron, 85Sr-labelled microspheres) were determined in the retina, choroid, anterior uvea, and brain of male Sprague-Dawley rats fed diets containing 50% dextrin (control) or 50% galactose. Blood flow was increased in the retina, choroid, and anterior uvea but not in the brain of rats fed galactose for 3 weeks and 3 months versus controls, and was normalized by sorbinil (an inhibitor of aldose reductase) in the 3-week group. After 8 months of galactose feeding, blood flow was reduced to normal levels in the retina and was slightly below normal in the choroid; blood flow remained elevated in the anterior uvea but was significantly lower than that observed at 3 weeks and at 3 months. In rats fed galactose for 8 months, sorbinil completely normalized blood flow in the choroid, and decreased, but did not normalize, blood flow in the anterior uvea. 125I-Albumin permeation was increased in the retina, choroid, and anterior uvea of rats fed 50% galactose for 3 weeks, 3 months, and 8 months versus controls, but was unchanged in the brain. Sorbinil normalized 125I-albumin permeation in all three ocular tissues in 8-month galactose-fed rats. Polyol levels were increased significantly in all three ocular tissues of 3-week galactose-fed rats; sorbinil markedly decreased, but did not normalize, polyol levels in all three tissues.

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

    PubMed

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

    2017-03-01

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

  1. Enlargement of choroid plexus in complex regional pain syndrome.

    PubMed

    Zhou, Guangyu; Hotta, Jaakko; Lehtinen, Maria K; Forss, Nina; Hari, Riitta

    2015-09-21

    The choroid plexus, located in brain ventricles, has received surprisingly little attention in clinical neuroscience. In morphometric brain analysis, we serendipitously found a 21% increase in choroid plexus volume in 12 patients suffering from complex regional pain syndrome (CRPS) compared with age- and gender-matched healthy subjects. No enlargement was observed in a group of 8 patients suffering from chronic pain of other etiologies. Our findings suggest involvement of the choroid plexus in the pathogenesis of CRPS. Since the choroid plexus can mediate interaction between peripheral and brain inflammation, our findings pinpoint the choroid plexus as an important target for future research of central pain mechanisms.

  2. The complex interaction between ocular perfusion pressure and ocular blood flow - relevance for glaucoma.

    PubMed

    Schmidl, Doreen; Garhofer, Gerhard; Schmetterer, Leopold

    2011-08-01

    Glaucoma is an optic neuropathy of unknown origin. The most important risk factor for the disease is an increased intraocular pressure (IOP). Reducing IOP is associated with reduced progression in glaucoma. Several recent large scale trials have indicated that low ocular perfusion pressure (OPP) is a risk factor for the incidence, prevalence and progression of the disease. This is a strong indicator that vascular factors are involved in the pathogenesis of the disease, a hypothesis that was formulated 150 years ago. The relation between OPP and blood flow to the posterior pole of the eye is, however, complex, because of a phenomenon called autoregulation. Autoregulatory processes attempt to keep blood flow constant despite changes in OPP. Although autoregulation has been observed in many experiments in the ocular vasculature the mechanisms underlying the vasodilator and vasoconstrictor responses in face of changes in OPP remain largely unknown. There is, however, recent evidence that the human choroid regulates its blood flow better during changes in blood pressure induced by isometric exercise than during changes in IOP induced by a suction cup. This may have consequences for our understanding of glaucoma, because it indicates that blood flow regulation is strongly dependent not only on OPP, but also on the level of IOP itself. Indeed there is data indicating that reduction of IOP by pharmacological intervention improves optic nerve head blood flow regulation independently of an ocular vasodilator effect.

  3. 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.

  4. Beyond the Cherry-Red Spot: Ocular Manifestations of Sphingolipid-mediated Neurodegenerative and Inflammatory Disorders

    PubMed Central

    Stone, Donald U.; Mandal, Nawajes A.

    2013-01-01

    Sphingolipids are a ubiquitous membrane lipid present in every cell and found most abundantly in neural tissues. Disorders such as Tay Sachs or Niemann Pick disease are the most familiar examples of dysfunction in sphingolipid metabolism and are typically associated with neurodegeneration and ocular findings such as blindness. More recently, the role of bioactive sphingolipids has been established in a multitude of cellular events, including cell survival, growth, senescence and apoptosis, inflammation, and neovascularization. We discuss our current knowledge and understanding of sphingolipid metabolism and signaling in the pathogenesis of ocular diseases. PMID:24011710

  5. Does tropicamide affect choroidal blood flow in humans? a laser Doppler flowmetry study

    NASA Astrophysics Data System (ADS)

    Palanisamy, Nithiyanantham; Riva, Charles E.; Rovati, Luigi; Cellini, Mauro; Gizzi, Corrado; Strobbe, Ernesto; Campos, Emilio C.

    2012-03-01

    The measurement of blood flow in the ocular fundus is of scientific and clinical interest. Investigating ocular blood flow in the choroid may be important to understand the pathogenesis of numerous ocular diseases, such as glaucoma or agerelated macular degeneration (AMD). Laser Doppler flowmetry (LDF) was applied to measure relative velocity, volume and flux of red blood cells in the tissues of human eye. Its main application lies in the possibility of assessing alterations in blood flow early in the course of diseases. The purpose of the present study was to investigate the effect of pupil dilatation with one drop of 1% tropicamide on blood flow in the foveal region of the choroid of the human fundus. The blood flow parameters were measured in 24 eyes during 30 minutes (one measurement in every 3 minutes) after the application of the drop. Since the Doppler parameters depend on the scattering geometry, which may change as the pupil dilates; an artificial pupil of 4mm in diameter was placed directly in front the eye. Following the administration of tropicamide the mean pupil diameter was increased from 3.29 mm to 8.25 mm (P<0.0001, Paired student t-test). In comparison to the baseline values, the data shows no significant increases were observed in velocity, volume, and flow with 4 mm artificial pupil (0.2%, 1.3%, 0.8% respectively) and a statistically significant increases were observed without artificial pupil (10.7%, 13.9%, 12.8% respectively) following the application of tropicamide.

  6. Responsiveness of eyes with polypoidal choroidal vasculopathy with choroidal hyperpermeability to intravitreal ranibizumab

    PubMed Central

    2013-01-01

    Background To determine the role played by vascular endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV) based on an interventional immunology theory. Methods Eyes with PCV were divided in a masked fashion into those with choroidal hyperpermeability (HP group) and those with normal choroidal permeability (NP group) based on the indocyanine green angiograms. The inter-rater agreement rate was evaluated using Fleiss’ kappa. Patients were treated by intravitreal ranibizumab (IVB). The central choroidal thickness and central foveal thickness (CFT) at the baseline and 7 days after the treatment were measured by optical coherence tomography. Results Among the 57 consecutive eyes diagnosed with PCV, 42 eyes of 42 patients met the inclusion criteria (21 eyes/HP group vs 21 eyes /NP group). Central choroidal thickness in HP group was significantly thicker than that in the NP group (P < .001, Mann–Whitney U test). The inter-rater agreement was high with a Fleiss’ kappa = 0.95, P < .0001. The percentage reduction in the CFT in HP group (14.0%) was significantly less than that in NP group (20.4%; P = .013, Mann–Whitney U test). Conclusions Eyes with PCV that are associated with choroidal hyper-permeability may not be strongly associated with VEGF-related pathology, and may not respond favorably to anti-VEGF monotherapy. PMID:23962072

  7. Choroidal melanoma clinically simulating a retinal angioma.

    PubMed

    Shields, J A; Joffe, L; Guibor, P

    1978-01-01

    An amelanotic fundus lesion in a 35-year-old man was associated with a dilated retinal vessel, thus suggesting the diagnosis of retinal angioma. Fluorescein angiography and B-scan ultrasonography were not diagnostic, but a radioactive phosphorus uptake test suggested the lesion was malignant. The enucleated globe showed a malignant choroidal melanoma drained by a large retinal vein.

  8. 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

  9. Photoacoustic detection of neovascularities in skin graft

    NASA Astrophysics Data System (ADS)

    Yamazaki, Mutsuo; Sato, Shunichi; Saitoh, Daizo; Ishihara, Miya; Okada, Yoshiaki; Ashida, Hiroshi; Obara, Minoru

    2005-04-01

    We previously proposed a new method for monitoring adhesion of skin graft by measuring photoacoustic (PA) signal originated from the neovascularities. In this study, immunohistochemical staining (IHC) with CD31 antibody was performed for grafted skin tissue to observe neovascularity, and the results were compared with PA signals. We also used a laser Doppler imaging (LDI) to observe blood flow in the grafted skin, and sensitivity of PA measurement and that of LDI were compared. In rat autograft models, PA signals were measured for the grafted skin at postgrafting times of 0-48 h. At 6 h postgrafting, PA signal was observed in the skin depth region of 500-600 mm, while the results of IHC showed that angiogenesis occurred at the depth of about 600 mm. Depths at which PA signal and angiogenesis were observed decreased with postgrafting time. These indicate that the PA signal observed at 6 h postgrafting originated from the neovascularities in the skin graft. Results of LDI showed no blood-originated signal before 48 h postgrafting. These findings suggest that PA measurement is effective in monitoring the adhesion of skin graft in early stage after transplantation.

  10. Ocular disease and driving.

    PubMed

    Wood, Joanne M; Black, Alex A

    2016-09-01

    As the driving population ages, the number of drivers with visual impairment resulting from ocular disease will increase given the age-related prevalence of ocular disease. The increase in visual impairment in the driving population has a number of implications for driving outcomes. This review summarises current research regarding the impact of common ocular diseases on driving ability and safety, with particular focus on cataract, glaucoma, age-related macular degeneration, hemianopia and diabetic retinopathy. The evidence considered includes self-reported driving outcomes, driving performance (on-road and simulator-based) and various motor vehicle crash indices. Collectively, this review demonstrates that driving ability and safety are negatively affected by ocular disease; however, further research is needed in this area. Older drivers with ocular disease need to be aware of the negative consequences of their ocular condition and in the case where treatment options are available, encouraged to seek these earlier for optimum driving safety and quality of life benefits.

  11. Risk factors of a reduced response to ranibizumab treatment for neovascular age-related macular degeneration – evaluation in a clinical setting

    PubMed Central

    2013-01-01

    Background To identify risk factors for being a “reduced responder” to ranibizumab treatment in a clinical setting in patients with neovascular age-related macular degeneration. Methods This retrospective study included 165 eyes of 165 consecutive patients with choroidal neovascularisation secondary to neovascular, age-related macular degeneration. Eyes were treated with three intravitreal injections of ranibizumab, followed by PRN (pro re nata) dosing thereafter. All patients were reevaluated every four weeks and then followed for six months. Reduced responders were defined as patients with a loss in visual acuity of at least 1 visual acuity line at the last follow-up and/or persistent intraretinal or subretinal fluid or detectable choroidal neovascularisation at the last follow-up, compared to baseline. Results Overall, 58 out of 165 eyes (35.2%) were considered to be reduced responders to treatment at the end of follow-up. The initial CNV size at baseline was correlated with the risk of being a reduced responder at the end of follow-up (p = 0.017). Conclusion We identified the initial lesion size as a predictor for a reduced response to treatment in this study. Patients with a large initial lesion size should be thoroughly informed about the possible poorer response to the intravitreal treatment. PMID:24359591

  12. Numerical Modeling of Ocular Dysfunction in Space

    NASA Technical Reports Server (NTRS)

    Nelson, Emily S.; Mulugeta, Lealem; Vera, J.; Myers, J. G.; Raykin, J.; Feola, A. J.; Gleason, R.; Samuels, B.; Ethier, C. R.

    2014-01-01

    Upon introduction to microgravity, the near-loss of hydrostatic pressure causes a marked cephalic (headward) shift of fluid in an astronaut's body. The fluid shift, along with other factors of spaceflight, induces a cascade of interdependent physiological responses which occur at varying time scales. Long-duration missions carry an increased risk for the development of the Visual Impairment and Intracranial Pressure (VIIP) syndrome, a spectrum of ophthalmic changes including posterior globe flattening, choroidal folds, distension of the optic nerve sheath, kinking of the optic nerve and potentially permanent degradation of visual function. In the cases of VIIP found to date, the initial onset of symptoms occurred after several weeks to several months of spaceflight, by which time the gross bodily fluid distribution is well established. We are developing a suite of numerical models to simulate the effects of fluid shift on the cardiovascular, central nervous and ocular systems. These models calculate the modified mean volumes, flow rates and pressures that are characteristic of the altered quasi-homeostatic state in microgravity, including intracranial and intraocular pressures. The results of the lumped models provide initial and boundary data to a 3D finite element biomechanics simulation of the globe, optic nerve head and retrobulbar subarachnoid space. The integrated set of models will be used to investigate the evolution of the biomechanical stress state in the ocular tissues due to long-term exposure to microgravity.

  13. Thermography in ocular inflammation

    PubMed Central

    Kawali, Ankush A

    2013-01-01

    Background and Objectives: The purpose of this study was to evaluate ocular inflammatory and non-inflammatory conditions using commercially available thermal camera. Materials and Methods: A non-contact thermographic camera (FLIR P 620) was used to take thermal pictures of seven cases of ocular inflammation, two cases of non-inflammatory ocular pathology, and one healthy subject with mild refractive error only. Ocular inflammatory cases included five cases of scleritis, one case of postoperative anterior uveitis, and a case of meibomian gland dysfunction with keratitis (MGD-keratitis). Non-inflammatory conditions included a case of conjunctival benign reactive lymphoid hyperplasia (BRLH) and a case of central serous chorio-retinopathy. Thermal and non-thermal photographs were taken, and using analyzing software, the ocular surface temperature was calculated. Results: Patient with fresh episode of scleritis revealed high temperature. Eyes with MGD-keratitis depicted lower temperature in clinically more affected eye. Conjunctival BRLH showed a cold lesion on thermography at the site of involvement, in contrast to cases of scleritis with similar clinical presentation. Conclusion: Ocular thermal imaging is an underutilized diagnostic tool which can be used to distinguish inflammatory ocular conditions from non-inflammatory conditions. It can also be utilized in the evaluation of tear film in dry eye syndrome. Its applications should be further explored in uveitis and other ocular disorders. Dedicated “ocular thermographic” camera is today's need of the hour. PMID:24347863

  14. Effects of Dorzolamide on Retinal and Choroidal Blood Flow in the DBA/2J Mouse Model of Glaucoma

    PubMed Central

    Chandra, Saurav; Muir, Eric R.; Deo, Kaiwalya; Kiel, Jeffrey W.; Duong, Timothy Q.

    2016-01-01

    Purpose To test the hypothesis that acute topical dorzolamide (DZ) decreases intraocular pressure (IOP) and increases retinal and choroidal blood flow in the DBA/2J mouse model of glaucoma. Methods Retinal and choroidal blood flow were measured in 4- and 9-month-old DBA/2J mice, and 4-month C57BL/6 (control) mice under isoflurane anesthesia using magnetic resonance imaging. Ocular blood flow was measured at baseline, and 1 and 2 hours after topical dorzolamide. Intraocular pressure was measured using a rebound tonometer in a subset of animals at the same time points. Results Baseline IOP in the 4-month-old DBA/2J mice and C57BL/6 mice was not significantly different (P > 0.05), and IOP in both groups was less than in the 9-month-old DBA/2J mice (P < 0.05 for both). Compared to baseline, dorzolamide reduced IOP at 1 and 2 hours after dorzolamide in the 4- (P < 0.05) and 9-month-old (P < 0.01) DBA/2J mice, but not in the C57BL/6J mice (P > 0.05). Baseline retinal blood flow was lower in the 4-month and 9-month-old DBA/2J mice compared with the 4-month-old C57BL/6J mice (P < 0.05). Baseline choroidal blood flow in the 9-month-old DBA/2J mice was less than in the C57BL/6J mice (P < 0.05). Compared with baseline, both retinal and choroidal blood flow increased at 1-hour post-dorzolamide and remained elevated 2 hours later in the 9-month-old DBA/2J mice (P < 0.05). Conclusions Dorzolamide lowers IOP and raises retinal and choroidal blood flow in older DBA/2J mice, consistent with the study hypothesis. PMID:26934140

  15. Effects of photocoagulation on ocular blood flow in patients with severe non-proliferative diabetic retinopathy

    PubMed Central

    Kobayashi, Misato; Yamamoto, Kentaro; Ra, Eimei; Terasaki, Hiroko

    2017-01-01

    Purpose To investigate ocular blood flow and correlations between ocular blood flow and variables in patients with severe non-proliferative diabetic retinopathy (S-NPDR) following panretinal photocoagulation (PRP). Methods In this retrospective, cross-sectional study, the blood flow on the optic nerve head (ONH) and choroid was assessed with laser speckle flowgraphy (LSFG) using the mean blur rate (MBR) in 76 eyes of 76 patients with S-NPDR who underwent PRP, 39 eyes of 39 patients with S-NPDR who did not undergo PRP, and 71 eyes of 71 normal subjects. The correlation between MBR and variables, including visual acuity (VA) and choroidal area determined by binarization method, was analyzed. Results The mean age was 62.9 ± 11.9 years in the S-NPDR with PRP eyes, 55.6 ± 11.4 years in the S-NPDR without PRP eyes, and 60.3 ± 11.1 years in the normal subject eyes. The ONH MBR in vessel and tissue areas and the choroidal MBR were significantly lower in the S-NDR with PRP group than in the other groups (p < 0.001, p < 0.001, and p < 0.001, respectively). The luminal and the stromal areas were significantly smaller in the S-NDR with PRP group than in the other groups (p < 0.001 and p < 0.001, respectively). LogMAR best corrected visual acuity (BCVA) exhibited significant negative correlation with the ONH MBR in vessel (r = −0.386, p < 0.001), tissue (r = −0.348, p < 0.001), and the choroid MBR (r = −0.339, p = 0.002) in the S-NDR with PRP group. Stepwise multiple regression analysis demonstrated that BCVA was a common independent factor associated with the ONH MBR in vessel, tissue, and the choroidal MBR in the S-NDR with PRP group. Conclusions ONH and choroid MBR in addition to choroidal component, including the luminal area, were significantly lower in eyes of patients with S-NPDR after PRP compared with no PRP and normal subjects group. This could suggest that the significantly reduced ocular blood flow in PRP-treated S-NPDR eyes correlated with long

  16. Predictors of anti-VEGF treatment response in neovascular age-related macular degeneration.

    PubMed

    Finger, Robert P; Wickremasinghe, Sanjeewa S; Baird, Paul N; Guymer, Robyn H

    2014-01-01

    Currently available evidence on predictors of anti-vascular endothelial growth factor (VEGF) treatment response in neovascular age-related macular degeneration was reviewed. No meta-analysis of results is possible because of a lack of controlled and randomized trials, varying treatment regimes and outcome measures used, as well as suboptimal reporting. For genetic factors, most evidence to date has been generated for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), and VEGF-A genes. Just under half of the SNPs assessed in the CFH gene and 15% of the SNPs assessed in the VEGF gene were found to be associated with visual outcomes or the number of injections required during follow-up. Some evidence suggests association of worse treatment outcomes as well as a younger age at treatment onset with an increasing number of risk alleles in known risk genes (CFH and ARMS2/HTRA1) and polymorphisms in the VEGF-A gene. Clinical factors such as higher age, a better visual acuity (VA), a larger choroidal neovascularization (CNV) lesion at baseline, and a delay between symptom onset and initiation of treatment of more than 3 weeks also impact outcomes. Conversely, a worse acuity at baseline predicted more gain in vision. Overall, patients presenting with good acuity at baseline were more likely to have good VA at follow up, but the gain afforded by treatment was impacted by a ceiling effect. Most available evidence suggests a strong association of clinical factors such as age, baseline VA, and CNV lesion size with anti-VEGF treatment outcomes. No behavioral factors such as smoking influence treatment outcomes. Based on the studies conducted so far, the evidence suggests that underlying genotype of known AMD risk associated genes or of the VEGF-A gene have a limited effect, whereas presenting clinical factors appear to be more important in determining treatment outcomes.

  17. Topical, Aqueous, Clear Cyclosporine Formulation Design for Anterior and Posterior Ocular Delivery

    PubMed Central

    Cholkar, Kishore; Gilger, Brian C.; Mitra, Ashim K.

    2015-01-01

    Purpose: The main objective of this study was to optimize cyclosporine (CsA) nanomicellar solution and study in vivo ocular CsA tissue distribution with a topical drop. Methods: An optimized blend of hydrogenated castor oil-40 and octoxynol-40 was prepared to entrap CsA within nanomicelles. In vivo studies were conducted in New Zealand White albino rabbits with topical drop instillation. Results: Average size of CsA-loaded nanomicelles was approximately 22.4 nm. Ocular tissue CsA quantification with single and multiple dosing revealed that CsA levels followed as cornea → iris-ciliary body → aqueous humor → lens. Cyclosporine levels were also found to be in the following order: conjunctiva → sclera → retina/choroid → vitreous humor. High CsA level was detected in retina/choroid (53.7 ng/g tissue). Conclusions: Ocular tissue CsA distribution studies revealed high CsA concentrations in anterior ocular tissues. Moreover, it appears that nanomicelles are transported through a conjunctival–scleral pathway and deliver CsA to the retina/choroid. Results suggest polymeric blend to be a safe carrier for anterior and posterior ocular tissues. Translational Relevance: This study has significant translational relevance, disclosing results that suggest that aqueous nanomicellar approach can provide high corneal and conjunctival CsA concentrations. Aqueous nanomicelles can deliver high drug concentrations not only to anterior but also to back of the eye tissues, including retina. This article provides a platform for noninvasive back of the eye drug delivery with topical eye drops. Aqueous CsA nanomicelles have no perceptible toxicity such as cell membrane damage or cytotoxicity to corneal and retinal pigment epithelial cells. Clear aqueous nanomicellar solution can be translated to human conditions for keratoconjunctivitis sicca and other anti-inflammatory conditions. PMID:25964868

  18. Spectral imaging of the human ocular fundus

    NASA Astrophysics Data System (ADS)

    Truitt, Paul Wiley

    between types of drusen. The mean spectral curves of the normal anatomical tissue showed a strong correlation with fundus pigmentation for classes greatly affected by melanin with significantly less correlation for classes not affected by melanin. Inter-subject variability was greatly reduced in the melanin-normalized curves. The simple piece-wise linear model captured the first order shape properties of the spectral curves and the first three principle components of the model coefficients produced good and consistent class separation. Conclusion. High-resolution spectral imaging of the ocular fundus produces features that are useful in separating fundus tissue classes for classification and visualization. Images at wavelengths in excess of 600 nm allow non-invasive visualization of the important choroidal circulation. The data further suggest spectral features that can be used to detect macular edema pre-clinically and spectral features that can be used to detect macular edema pre-clinically and quantitatively classify drusen sub-types.

  19. The Use of Microperimetry to Detect Functional Progression in Non-Neovascular Age-Related Macular Degeneration: A Systematic Review.

    PubMed

    Wong, Evan N; Chew, Avenell L; Morgan, William H; Patel, Praveen J; Chen, Fred K

    2017-01-01

    We reviewed the current literature on the ability of microperimetry to detect non-neovascular age-related macular degeneration (AMD) disease progression. The index test was retinal sensitivity measurement assessed by microperimetry and comparators were other functional measures (best-corrected and low-luminance visual acuities, and fixation stability) and structural parameters [retinal thickness, choroidal thickness, and area of geographic atrophy (GA) determined by color fundus photographs, short-wave or near-infrared fundus autofluorescence]. The reference standard was area of GA. The literature search was conducted in January 2016 and included MEDLINE, EMBASE, the Cochrane Library, Biosis, Science Citation Index, ProQuest Health and Medicine, CINAHL, and Highwire Press. We included 6 studies that enrolled 41 eyes with intermediate AMD (from a single study) and 80 eyes with GA secondary to AMD. Retinal sensitivity measured by microperimetry was the only functional measure that consistently detected progression in each cohort. Insufficient reported data precluded meta-analysis. Various microperimetry parameters were used to assess cohort-level change in retinal sensitivity, but the methods of analysis have yet to mature in complexity in comparison with established glaucoma field progression analysis. Microperimetry-assessed retinal sensitivity measurement may be more sensitive in detecting progression than other functional measures in non-neovascular AMD. However, the lack of standardized testing protocol and methods of progression analysis hindered comparison. Harmonization of testing protocol and development of more robust methods of analyzing raw microperimetric data will facilitate clinical implementation of this valuable retinal assessment tool.

  20. Foxc1 and Foxc2 in the Neural Crest Are Required for Ocular Anterior Segment Development

    PubMed Central

    Seo, Seungwoon; Chen, Lisheng; Liu, Wenzhong; Zhao, Demin; Schultz, Kathryn M.; Sasman, Amy; Liu, Ting; Zhang, Hao F.; Gage, Philip J.; Kume, Tsutomu

    2017-01-01

    Purpose The large Forkhead (Fox) transcription factor family has essential roles in development, and mutations cause a wide range of ocular and nonocular disease. One member, Foxc2 is expressed in neural crest (NC)-derived periocular mesenchymal cells of the developing murine eye; however, its precise role in the development, establishment, and maintenance of the ocular surface has yet to be investigated. Methods To specifically delete Foxc2 from NC-derived cells, conditional knockout mice for Foxc2 (NC-Foxc2−/−) were generated by crossing Foxc2F mice with Wnt1-Cre mice. Similarly, we also generated compound NC-specific mutations of Foxc2 and a closely related gene, Foxc1 (NC-Foxc1−/−;NC-Foxc2−/−) in mice. Results Neural crest-Foxc2−/− mice show abnormal thickness in the peripheral-to-central corneal stroma and limbus and displaced pupils with irregular iris. The neural crest-specific mutation in Foxc2 also leads to ectopic neovascularization in the cornea, as well as impaired ocular epithelial cell identity and corneal conjunctivalization. Compound, NC-specific Foxc1; Foxc2 homozygous mutant mice have more severe defects in structures of the ocular surface, such as the cornea and eyelids, accompanied by significant declines in the expression of another key developmental factor, Pitx2, and its downstream effector Dkk2, which antagonizes canonical Wnt signaling. Conclusions The neural crest-Foxc2 mutation is associated with corneal conjunctivalization, ectopic corneal neovascularization, and disrupted ocular epithelial cell identity. Furthermore, Foxc2 and Foxc1 cooperatively function in NC-derived mesenchymal cells to ensure proper morphogenesis of the ocular surface via the regulation of Wnt signaling. Together, Foxc2 is required in the NC lineage for mesenchymal-epithelial interactions in corneal and ocular surface development. PMID:28253399

  1. IL-23-independent induction of IL-17 from γδT cells and innate lymphoid cells promotes experimental intraocular neovascularization.

    PubMed

    Hasegawa, Eiichi; Sonoda, Koh-Hei; Shichita, Takashi; Morita, Rimpei; Sekiya, Takashi; Kimura, Akihiro; Oshima, Yuji; Takeda, Atsunobu; Yoshimura, Takeru; Yoshida, Shigeo; Ishibashi, Tatsuro; Yoshimura, Akihiko

    2013-02-15

    Choroidal neovascularization (CNV) is a characteristic of age-related macular degeneration. Genome-wide association studies have provided evidence that the immune system is involved in the pathogenesis of age-related macular degeneration; however, the role of inflammatory cytokines in CNV has not been established. In this study, we demonstrated that IL-17 had a strong potential for promoting neovascularization in a vascular endothelial growth factor-independent manner in laser-induced experimental CNV in mice. Infiltrated γδT cells and Thy-1(+) innate lymphoid cells, but not Th17 cells, were the main sources of IL-17 in injured eyes. IL-23 was dispensable for IL-17 induction in the eye. Instead, we found that IL-1β and high-mobility group box 1 strongly promoted IL-17 expression by γδT cells. Suppression of IL-1β and high-mobility group box 1, as well as depletion of γδT cells, reduced IL-17 levels and ameliorated experimental CNV. Our findings suggest the existence of a novel inflammatory cytokine network that promotes neovascularization in the eye.

  2. Ocular circulatory responses to exhaustive exercise in humans.

    PubMed

    Ikemura, Tsukasa; Hayashi, Naoyuki

    2012-09-01

    It is unclear whether exhaustive dynamic exercise increases ocular blood flow, although we have reported that submaximal exercise increases ocular blood flow. We hypothesized that ocular blood flow decreases at exhaustion, since exhaustion causes hyperventilation, which induces a reduction in PaCO(2). To test this hypothesis, ocular blood flow, blood pressure, and respiratory measurements were made in 12 healthy male subjects during cycle ergometer exercise at 75% of maximal heart rate, until exhaustion. Blood flows in the retinal and choroidal vasculature (RCV), the superior temporal retinal arteriole (STRA), and the superior nasal retinal arteriole (SNRA) were measured with the aid of laser-speckle flowgraphy every 3 min during the exercise. The conductance index (CI) in the ocular vasculature was calculated by dividing the blood flow by the mean arterial pressure (MAP). The mean arterial partial pressure of CO(2) (PaCO(2)) was estimated from tidal volume and end-tidal CO(2) partial pressure. MAP significantly increased from the resting baseline throughout the exercise, while PaCO(2) was significantly decreased at exhaustion and during the recovery period. By 6 min after the onset of exercise, blood flow velocity in the RCV significantly increased by 32 ± 6% (mean ± SD) from the resting baseline value. At exhaustion, blood flow velocity in the RCV did not differ significantly from the resting baseline value, and the STRA blood flow was significantly decreased by 13 ± 4%. The CIs in the RCV, STRA, and SNRA were significantly decreased compared to baseline at exhaustion. These findings suggest that ocular blood flow is increased by submaximal exercise, whereas it is suppressed by the hypocapnia associated with exhaustion.

  3. Polarisation-sensitive OCT is useful for evaluating retinal pigment epithelial lesions in patients with neovascular AMD

    PubMed Central

    Schütze, Christopher; Teleky, Katharina; Baumann, Bernhard; Pircher, Michael; Götzinger, Erich; Hitzenberger, Christoph K; Schmidt-Erfurth, Ursula

    2016-01-01

    Background/aims To examine the reproducibility of lesion dimensions of the retinal pigment epithelium (RPE) in neovascular age-related macular degeneration (AMD) with polarisation-sensitive optical coherence tomography (PS-OCT), specifically imaging the RPE. Methods Twenty-six patients (28 eyes) with neovascular AMD were included in this study, and examined by a PS-OCT prototype. Each patient was scanned five times at a 1-day visit. The PS-OCT B-scan located closest to the macular centre presenting with RPE atrophy was identified, and the longitudinal diameter of the lesion was quantified manually using AutoCAD 2008. This procedure was followed for the identical B-scan position in all five scans per eye and patient. Reproducibility of qualitative changes in PS-OCT was evaluated. Interobserver variability was assessed. Results were compared with intensity-based spectral-domain OCT (SD-OCT) imaging. Results Mean variability of all atrophy lesion dimensions was 0.10 mm (SD±=0.06 mm). Coefficient of variation (SD±/mean) was 0.06 on average (SD±=0.03). Interobserver variability assessment showed a mean difference of 0.02 mm across all patients regarding RPE lesion size evaluation (paired t test: p=0.38). Spearman correlation coefficient was r=0.98, p<0.001. Results revealed a good overall reproducibility of ∼90%. PS-OCT specifically detected the RPE in all eyes compared with conventional intensity-based SD-OCT that was not capable to clearly identify RPE atrophy in 25 eyes (89.3%, p<0.01). Conclusions PS-OCT offers good reproducibility of RPE atrophy assessment in neovascular AMD, and may be suitable for precise RPE evaluation in clinical practice. PS-OCT unambiguously identifies RPE changes in choroidal neovascularisation compared with intensity-based SD-OCT that does not identify the RPE status reliably. PMID:26183936

  4. Choroid plexus acinar adenoma: a case report.

    PubMed

    Rembao-Bojórquez, Daniel; Vega, Rosalba; Bermúdez-Maldonado, Luis; Gutiérrez, Ramón; Salinas, Citlaltepetl; Tena-Suck, Martha

    2007-06-01

    Mucus-secreting adenomas or acinar adenoma of the choroid plexus are very rare. We report the case of a 79-year-old male with a 3-year history of occipital headaches with vomiting, ataxia and cerebellar signs. He was first seen due to difficulty while walking. He was admitted to the hospital with significant tumor expansion and clinical deterioration. CT and MRI revealed obstructive hydrocephalus secondary to a large fourth ventricular cyst mass, which enhanced markedly on contrast administration. Pathological findings were consistent with an acinar choroid plexus adenoma. The tumor was attached to the ependymal lining and was strongly adhered to the walls and floor of the IV ventricle. Post-operative bleeding complicated partial removal of this tumor. The patient died 6 h after surgery.

  5. 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

  6. 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.

  7. Choroid plexus cyst in a dog.

    PubMed

    Galano, Heather R; Platt, Simon R; Neuwirth, Lisa; Quist, Charlotte F; de Lahunta, Alexander

    2002-01-01

    A 6-year-old male Doberman Pinscher had a 2-month history of dysequilibrium. Lesion localization was determined to be the cerebellomedullary pontine angle. In computed tomographic images, a well-defined, circular, hypoattenuating mass was visible at the cerebellomedullary pontine angle. The lesion, which was isoattenuating to cerebrospinal fluid, was 4 x 8 mm in diameter. Peripheral ring enhancement was evident after contrast medium administration. A choroid plexus cyst was diagnosed histopathologically.

  8. 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

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

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita L.

    2011-01-01

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

  10. Effect of trapping vascular endothelial growth factor-A in a murine model of dry eye with inflammatory neovascularization

    PubMed Central

    Kwon, Jin Woo; Choi, Jin A; Shin, Eun Young; La, Tae Yoon; Jee, Dong Hyun; Chung, Yeon Woong; Cho, Yang Kyung

    2016-01-01

    AIM To evaluate whether trapping vascular endothelial growth factor A (VEGF-A) would suppress angiogenesis and inflammation in dry eye corneas in a murine corneal suture model. METHODS We established two groups of animals, one with non-dry eyes and the other with induced dry eyes. In both groups, a corneal suture model was used to induce inflammation and neovascularization. Each of two groups was again divided into three subgroups according to the treatment; subgroup I (aflibercept), subgroup II (dexamethasone) and subgroup III (phosphate buffered saline, PBS). Corneas were harvested and immunohistochemical staining was performed to compare the extents of neovascularization and CD11b+ cell infiltration. Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and VEGF-A in the corneas. RESULTS Trapping VEGF-A with aflibercept resulted in significantly decreased angiogenesis and inflammation compared with the dexamethasone and PBS treatments in the dry eye corneas (all P<0.05), but with no such effects in non-dry eyes. The anti-inflammatory and anti-angiogenic effects of VEGF-A trapping were stronger than those of dexamethasone in both dry eye and non-dry eye corneas (all P<0.05). The levels of RNA expression of VEGF-A, TNF-alpha, and IL-6 in the aflibercept subgroup were significantly decreased compared with those in the PBS subgroup in the dry eye group. CONCLUSION Compared with non-dry eye corneas, dry eye corneas have greater amounts of inflammation and neovascularization and also have a more robust response to anti-inflammatory and anti-angiogenic agents after ocular surface surgery. Trapping VEGF-A is effective in decreasing both angiogenesis and inflammation in dry eye corneas after ocular surface surgery. PMID:27990354

  11. 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).

  12. Advanced drug delivery and targeting technologies for the ocular diseases

    PubMed Central

    Barar, Jaleh; Aghanejad, Ayuob; Fathi, Marziyeh; Omidi, Yadollah

    2016-01-01

    Introduction: Ocular targeted therapy has enormously been advanced by implementation of new methods of drug delivery and targeting using implantable drug delivery systems (DDSs) or devices (DDDs), stimuli-responsive advanced biomaterials, multimodal nanomedicines, cell therapy modalities and medical bioMEMs. These technologies tackle several ocular diseases such as inflammation-based diseases (e.g., scleritis, keratitis, uveitis, iritis, conjunctivitis, chorioretinitis, choroiditis, retinitis, retinochoroiditis), ocular hypertension and neuropathy, age-related macular degeneration and mucopolysaccharidosis (MPS) due to accumulation of glycosaminoglycans (GAGs). Such therapies appear to provide ultimate treatments, even though much more effective, yet biocompatible, noninvasive therapies are needed to control some disabling ocular diseases/disorders. Methods: In the current study, we have reviewed and discussed recent advancements on ocular targeted therapies. Results: On the ground that the pharmacokinetic and pharmacodynamic analyses of ophthalmic drugs need special techniques, most of ocular DDSs/devices developments have been designed to localized therapy within the eye. Application of advanced DDSs such as Subconjunctival insert/implants (e.g., latanoprost implant, Gamunex-C), episcleral implant (e.g., LX201), cationic emulsions (e.g., Cationorm™, Vekacia™, Cyclokat™), intac/punctal plug DDSs (latanoprost punctal plug delivery system, L-PPDS), and intravitreal implants (I-vitaion™, NT-501, NT- 503, MicroPump, Thethadur, IB-20089 Verisome™, Cortiject, DE-102, Retisert™, Iluvein™ and Ozurdex™) have significantly improved the treatment of ocular diseases. However, most of these DDSs/devices are applied invasively and even need surgical procedures. Of these, use of de novo technologies such as advanced stimuli-responsive nanomaterials, multimodal nanosystems (NSs)/nanoconjugates (NCs), biomacromolecualr scaffolds, and bioengineered cell therapies

  13. CCR3 is a therapeutic and diagnostic target for neovascular age-related macular degeneration

    PubMed Central

    Takeda, Atsunobu; Baffi, Judit Z.; Kleinman, Mark E.; Cho, Won Gil; Nozaki, Miho; Yamada, Kiyoshi; Kaneko, Hiroki; Albuquerque, Romulo J.C.; Dridi, Sami; Saito, Kuniharu; Raisler, Brian J.; Budd, Steven J.; Geisen, Pete; Munitz, Ariel; Ambati, Balamurali K.; Green, Martha G.; Ishibashi, Tatsuro; Wright, John D.; Humbles, Alison A.; Gerard, Craig J.; Ogura, Yuichiro; Pan, Yuzhen; Smith, Justine R.; Grisanti, Salvatore; Hartnett, M. Elizabeth; Rothenberg, Marc E.; Ambati, Jayakrishna

    2009-01-01

    Age-related macular degeneration (AMD), a leading cause of blindness worldwide, is as prevalent as cancer in industrialized nations. Most blindness in AMD results from invasion of the retina by choroidal neovascularization (CNV). We report that the eosinophil/mast cell chemokine receptor CCR3 is specifically expressed in CNV endothelial cells in humans with AMD, and that, despite the expression of its ligands eotaxin-1, -2, and -3, neither eosinophils nor mast cells are present in human CNV. Genetic or pharmacological targeting of CCR3 or eotaxins inhibited injury-induced CNV in mice. CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation as it occurred in mice lacking eosinophils or mast cells and was independent of macrophage and neutrophil recruitment. CCR3 blockade was more effective at reducing CNV than vascular endothelial growth factor-A (VEGF-A) neutralization, which is currently in clinical use, and, unlike VEGF-A blockade, not toxic to the mouse retina. In vivo imaging with CCR3-targeting quantum dots located spontaneous CNV invisible to standard fluorescein angiography in mice before retinal invasion. CCR3 targeting might reduce vision loss due to AMD through early detection and therapeutic angioinhibition. PMID:19525930

  14. Submacular hemorrhage in neovascular age-related macular degeneration: A synthesis of the literature.

    PubMed

    Stanescu-Segall, Dinu; Balta, Florian; Jackson, Timothy L

    2016-01-01

    Large submacular hemorrhage, an uncommon manifestation of neovascular age-related macular degeneration, may also occur with idiopathic polypoidal choroidal vasculopathy. Submacular hemorrhage damages photoreceptors owing to iron toxicity, fibrin meshwork contraction, and reduced nutrient flux, with subsequent macular scarring. Clinical and experimental studies support prompt treatment, as tissue damage can occur within 24 hours. Without treatment the natural history is poor, with a mean final visual acuity (VA) of 20/1600. Reported treatments include retinal pigment epithelial patch, macular translocation, pneumatic displacement, intravitreal or subretinal tissue plasminogen activator, intravitreal anti-vascular endothelial growth factor (VEGF) drugs, and combinations thereof. In the absence of comparative studies, we combined eligible studies to assess the VA change before and after each treatment option. The greatest improvement occurred after combined pars plana vitrectomy, subretinal tissue plasminogen activator, intravitreal gas, and anti-vascular endothelial growth factor treatment, with VA improving from 20/1000 to 20/400. The best final VA occurred using combined intravitreal tissue plasminogen activator, gas, and anti-vascular endothelial growth factor therapy, with VA improving from 20/200 to 20/100. Both treatments had an acceptable safety profile, but most studies were small, and larger randomized controlled trials are needed to determine both safety and efficacy.

  15. HTRA1 variant confers similar risks to geographic atrophy and neovascular age-related macular degeneration.

    PubMed

    Cameron, D Joshua; Yang, Zhenglin; Gibbs, Daniel; Chen, Haoyu; Kaminoh, Yuuki; Jorgensen, Adam; Zeng, Jiexi; Luo, Ling; Brinton, Eric; Brinton, Gregory; Brand, John M; Bernstein, Paul S; Zabriskie, Norman A; Tang, Shibo; Constantine, Ryan; Tong, Zongzhong; Zhang, Kang

    2007-05-02

    Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy (GA) and choroidal neovascularization (wet AMD), represent two types of degenerative processes in the macula that lead to loss of central vision. Soft confluent drusen, characterized by deposits in macula without visual loss are considered a precursor of advanced AMD. A single nucleotide polymorphism, rs11200638, in the promoter of HTRA1 has been shown to increases the risk for wet AMD. However, its impact on soft confluent drusen and GA or the relationship between them is unclear. To better understand the role the HTRA1 polymorphism plays in AMD subtypes, we genotyped an expanded Utah population with 658 patients having advanced AMD or soft confluent drusen and 294 normal controls and found that the rs11200638 was significantly associated with GA. This association remains significant conditional on LOC387715 rs10490924. In addition, rs11200638 was significantly associated with soft confluent drusen, which are strongly immunolabeled with HTRA1 antibody in an AMD eye with GA similar to wet AMD. Two-locus analyses were performed for CFH Y402H variant at 1q31 and the HTRA1 polymorphism. Together CFH and HTRA1 risk variants increase the odds of having AMD by more than 40 times. These findings expand the role of HTRA1 in AMD. Understanding the underlying molecular mechanism will provide an important insight in pathogenesis of AMD.

  16. Suppression of Retinal Neovascularization in vivo by Inhibition of Vascular Endothelial Growth Factor (VEGF) Using Soluble VEGF-Receptor Chimeric Proteins

    NASA Astrophysics Data System (ADS)

    Aiello, Lloyd Paul; Pierce, Eric A.; Foley, Eliot D.; Takagi, Hitoshi; Chen, Helen; Riddle, Lavon; Ferrara, Napoleone; King, George L.; Smith, Lois E. H.

    1995-11-01

    The majority of severe visual loss in the United States results from complications associated with retinal neovascularization in patients with ischemic ocular diseases such as diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. Intraocular expression of the angiogenic protein vascular endothelial growth factor (VEGF) is closely correlated with neovascularization in these human disorders and with ischemia-induced retinal neovascularization in mice. In this study, we evaluated whether in vivo inhibition of VEGF action could suppress retinal neovascularization in a murine model of ischemic retinopathy. VEGF-neutralizing chimeric proteins were constructed by joining the extracellular domain of either human (Flt) or mouse (Flk) high-affinity VEGF receptors with IgG. Control chimeric proteins that did not bind VEGF were also used. VEGF-receptor chimeric proteins eliminated in vitro retinal endothelial cell growth stimulation by either VEGF (P < 0.006) or hypoxic conditioned medium (P < 0.005) without affecting growth under nonstimulated conditions. Control proteins had no effect. To assess in vivo response, animals with bilateral retinal ischemia received intravitreal injections of VEGF antagonist in one eye and control protein in the contralateral eye. Retinal neovascularization was quantitated histologically by a masked protocol. Retinal neovascularization in the eye injected with human Flt or murine Flk chimeric protein was reduced in 100% (25/25; P < 0.0001) and 95% (21/22; P < 0.0001) of animals, respectively, compared to the control treated eye. This response was evident after only a single intravitreal injection and was dose dependent with suppression of neovascularization noted after total delivery of 200 ng of protein (P < 0.002). Reduction of histologically evident neovascular nuclei per 6-um section averaged 47% ± 4% (P < 0.001) and 37% ± 2% (P < 0.001) for Flt and Flk chimeric proteins with maximal inhibitory effects of 77% and 66

  17. Hemosideric heterochromia iridum in malignant melanoma of the choroid.

    PubMed

    Awan, K J

    1975-08-01

    A case is reported in which hyperchromic heterochromia iridum developed due to blood staining of an eye with malignant melanoma of the choroid in which massive hemorrhage developed. It is suggested that a possibility of the malignant melanoma of the choroid be kept in mind where hemosiderin deposits are suspected to be the cause of heterochromia but no intraocular iron foreign body is present.

  18. 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

  19. 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.

  20. Long-Term Changes in Subfoveal Choroidal Thickness After Cataract Surgery

    PubMed Central

    Yilmaz, Tolga; Karci, Ayse Aslihan; Yilmaz, İhsan; Yilmaz, Ahu; Yildirim, Yusuf; Sakalar, Yildirim Bayezit

    2016-01-01

    Background Cataract surgery is associated with the development of late-onset age-related macular degeneration (AMD). The pathogenic mechanism is still not fully established. The purpose of this study was to evaluate the possible changes in central macula thickness (CMT) and subfoveal choroid thickness (SCT) after uneventful cataract surgery. Material/Methods A total of 65 eyes of 65 patients who underwent phacoemulsification and intracapsular lens implantation were included in this prospective study. Patients had not undergone previous ocular surgery and had no other ocular abnormality. CMT and SCT were measured at baseline and postoperatively at week 1 and months 1, 3, 6 and 12 via spectral domain optical cohorence tomography (SD-OCT). Results CMT was 252.4±27.6 μm (mean ±SD) preoperatively, then 253.5±29.8, 256.1±28.7, 257.4±27.2, 253.18±23.7, and 252.8±21.7 μm at postoperative week 1 and postoperative months 1, 3, 6, and 12, respectively. There were insignificant changes in CMT, and it returned to baseline at six months after surgery (all p>0.05). SCT was 237.4±21.6 μm preoperatively, and 240.5±24.8, 241.2±25.7, 242.7±26.3, 243.1±24.2, and 244.2±21.4 μm at postoperative week 1 and postoperative months 1, 3, 6, and 12, respectively. Although there was an increase in SCT during follow-up, the difference between preoperative and postoperative values was not significant (p>0.05). Conclusions Uncomplicated phacoemulsification induces subclinical changes in CMT, probably due to the inflammatory insult of surgery, and CMT returns to baseline value. There were slight, insignificant increases in choroid thickness during follow-up, and this did not return to baseline during follow-up. Changes in the choroid after cataract surgery may provide clues to the development of late-onset AMD. PMID:27158971

  1. THE ELECTRON MICROSCOPY OF THE CHOROID PLEXUS

    PubMed Central

    Maxwell, David S.; Pease, Daniel C.

    1956-01-01

    1. The choroid plexus of the rat has been studied in detail by electron microscopy. Samples from the frog, rabbit, and cat have also been examined without noting significant differences. 2. The surface of the ependymal epithelium is covered by pedicels of variable size. There is reason for thinking of these structures as labile. They may actually pinch off and contribute to the secretory product. In any case, the surface area is vastly increased by their presence. Polypoid border seems an apt term to apply to this type of surface. 3. There is also a great expansion of the basal surface of ependymal cells. In the vicinity of cell junctions this surface is deeply infolded, and continuous with elaborate interdigitations of the lateral intercellular surfaces. Analogous infolding of the basal cell surface is known to exist in other epithelia also noted for their water transport (kidney tubules, salivary gland, and ciliary body). 4. Pretreatment of rats with diamox, an agent known to block cerebro-spinal fluid production, did not produce an important morphological change in the features of the ependyma, or any other part of the choroid plexus. 5. Capillaries of the choroid plexus have a very attenuated endothelium. This is seen to be fenestrated. It is thought this probably represents the condition in life, and is not simply a fixation artefact. 6. Pial cells tend to interpose sheets of cytoplasm between the capillaries and ependyma. The sheets are not continuous, however, and so would not constitute a serious diffusion barrier. These cells belong to the reticuloendothelial system, and undergo shape changes, and probably increase in number, when the system is stimulated by the repeated injection of trypan blue. PMID:13357511

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. What Is an Ocular Migraine?

    MedlinePlus

    ... When to seek help What is an ocular migraine? Is it a sign of something serious? Answers ... the other which might have more–serious complications. Migraine aura involving your vision In some cases, ocular ...

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

    PubMed

    Nickla, Debora L; Totonelly, Kristen

    2016-05-01

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

  8. Ocular complications of boxing

    PubMed Central

    Bianco, M; Vaiano, A; Colella, F; Coccimiglio, F; Moscetti, M; Palmieri, V; Focosi, F; Zeppilli, P; Vinger, P

    2005-01-01

    Objectives: To investigate the prevalence of ocular injuries in a large population of boxers over a period of 16 years, in particular, the most severe lesions that may be vision threatening. Methods: Clinical records of the medical archive of the Italian Boxing Federation were analysed. A total of 1032 boxers were examined from February 1982 to October 1998. A complete ophthalmological history was available for 956, who formed the study population (a total of 10 697 examinations). The following data were collected: age when started boxing; duration of competitive boxing career (from the date of the first bout); weight category; a thorough ocular history. The following investigations were carried out: measurement of visual acuity and visual fields, anterior segment inspection, applanation tonometry, gonioscopy, and examination of ocular fundus. Eighty age matched healthy subjects, who had never boxed, formed the control group. Results: Of the 956 boxers examined, 428 were amateur (44.8%) and 528 professional (55.2%). The median age at first examination was 23.1 (4.3) years (range 15–36). The prevalence of conjunctival, corneal, lenticular, vitreal, ocular papilla, and retinal alterations in the study population was 40.9% compared with 3.1% in the control group (p⩽0.0001). The prevalence of serious ocular findings (angle, lens, macula, and peripheral retina alterations) was 5.6% in boxers and 3.1% in controls (NS). Conclusions: Boxing does not result in a higher prevalence of severe ocular lesions than in the general population. However, the prevalence of milder lesions (in particular with regard to the conjunctiva and cornea) is noteworthy, justifying the need for adequate ophthalmological surveillance. PMID:15665199

  9. Ocular manifestations of Sturge–Weber syndrome: pathogenesis, diagnosis, and management

    PubMed Central

    Mantelli, Flavio; Bruscolini, Alice; La Cava, Maurizio; Abdolrahimzadeh, Solmaz; Lambiase, Alessandro

    2016-01-01

    Sturge–Weber syndrome has been included in the group of phakomatoses that is characterized by hamartomas involving the brain, skin, and eyes. The characteristic facial port-wine stain, involving the first branch of the trigeminal nerve and the embryonic vasculature distribution in this area, leads to several ocular complications of the anterior segment and can involve the eyelids and conjunctiva. The posterior segment of the eyes is also affected with diffuse choroidal hemangiomas. However, the most frequent ocular comorbidity is glaucoma with a prevalence rate ranging from 30%–70%. Glaucoma is related to anterior chamber malformations, high episcleral venous pressure (EVP), and changes in ocular hemodynamics. Glaucoma can be diagnosed at birth, but the disease can also develop during childhood and in adults. The management of glaucoma in Sturge–Weber syndrome patients is particularly challenging because of early onset, frequently associated severe visual field impairment at the time of diagnosis, and unresponsiveness to standard treatment. Several surgical approaches have been proposed, but long-term prognosis for both intraocular pressure control and visual function remains unsatisfactory in these patients. Choroidal hemangiomas may also lead to visual impairment thorough exudative retinal detachment and macular edema. Treatment of exudative hemangioma complications is aimed at destructing the tumor or decreasing tumor leakage. PMID:27257371

  10. Small-interfering RNAs (siRNAs) as a promising tool for ocular therapy

    PubMed Central

    Guzman-Aranguez, A; Loma, P; Pintor, J

    2013-01-01

    RNA interference (RNAi) can be used to inhibit the expression of specific genes in vitro and in vivo, thereby providing an extremely useful tool for investigating gene function. Progress in the understanding of RNAi-based mechanisms has opened up new perspectives in therapeutics for the treatment of several diseases including ocular disorders. The eye is currently considered a good target for RNAi therapy mainly because it is a confined compartment and, therefore, enables local delivery of small-interfering RNAs (siRNAs) by topical instillation or direct injection. However, delivery strategies that protect the siRNAs from degradation and are suitable for long-term treatment would be help to improve the efficacy of RNAi-based therapies for ocular pathologies. siRNAs targeting critical molecules involved in the pathogenesis of glaucoma, retinitis pigmentosa and neovascular eye diseases (age-related macular degeneration, diabetic retinopathy and corneal neovascularization) have been tested in experimental animal models, and clinical trials have been conducted with some of them. This review provides an update on the progress of RNAi in ocular therapeutics, discussing the advantages and drawbacks of RNAi-based therapeutics compared to previous treatments. PMID:23937539

  11. Central retinal artery occlusion following laser treatment for ocular ischemic aortic arch syndrome

    PubMed Central

    Shah, Payal J.; Ellis, Brian; DiGiovine, Lauren R.; Hogg, Jeffery P.; Leys, Monique J.

    2015-01-01

    Objective: Ocular ischemic syndrome is a rare blinding condition generally caused by disease of the carotid artery. We describe a 69-year-old female with a 50 pack-year smoking history with aortic arch syndrome causing bilateral ocular ischemic syndrome. Methods: The patient presented with progressive visual loss and temple pain. Slit lamp biomicroscopy revealed bilateral iris neovascularization. This finding prompted a cardiovascular work up. Panretinal photocoagulation with retrobulbar block was performed in the right eye. Results: A temporal artery biopsy was negative. The carotid duplex ultrasound showed only a 1–39% stenosis. MRA revealed a more proximal occlusion of the aortic branch for which she underwent subclavian carotid bypass surgery. At the one month follow up, the right eye suffered profound vision loss secondary to a central retinal artery occlusion. Conclusion: Ocular neovascularization may be one of the clinical manifestations of aortic arch syndrome. This case also illustrates the limitations of relying solely on carotid duplex ultrasound testing. We caution against overly aggressive panretinal photocoagulation utilizing retrobulbar anesthesia. PMID:27625958

  12. Ocular involvement of brucellosis.

    PubMed

    Bazzazi, Nooshin; Yavarikia, Alireza; Keramat, Fariba

    2013-01-01

    A 29-year-old male diagnosed with brucellosis a week earlier was referred to the ophthalmology clinic with visual complaints. On examination, visual acuity was 20/25, he had conjunctival injection on slit lamp examination. There was also bilateral optic disk swelling plus retinal hyperemia (optic disc hyperemia and vascular tortuosity) and intraretinal hemorrhage on funduscopy. The patient was admitted and treated with cotrimoxazole, rifampin, doxycycline and prednisolone for 2 months. Ocular manifestations subsided gradually within 6 months after treatment. Brucellosis can affect the eye and lead to serious ocular complications. Early diagnosis and prompt treatment should be considered in endemic areas.

  13. Correction of ocular dystopia.

    PubMed

    Janecka, I P

    1996-04-01

    The purpose of this study was to examine results with elective surgical correction of enophthalmos. The study was a retrospective assessment in a university-based referral practice. A consecutive sample of 10 patients who developed ocular dystopia following orbital trauma was examined. The main outcome measures were a subjective evaluation by patients and objective measurements of patients' eye position. The intervention was three-dimensional orbital reconstruction with titanium plates. It is concluded that satisfactory correction of enophthalmos and ocular dystopia can be achieved with elective surgery using titanium plates. In addition, intraoperative measurements of eye position in three planes increases the precision of surgery.

  14. Irradiation of the posterior ocular segment with the neodymium-YAG laser in its free-running mode

    SciTech Connect

    Fankhauser, F.; Kwasniewska, S.; van der Zypen, E.

    1985-09-01

    A neodymium-YAG laser, operating in its free-running mode with pulse durations of 10 to 20 ms, was used to treat 63 cases of choroidal and retinal diseases. These cases included diabetic background retinopathies, thrombosis of the central retinal vein or branch retinal vein, neovascular membranes under the pigment epithelium, and retinal breaks or degenerations of the peripheral retina. Because the number of diabetic retinopathies (24) and their average follow-up time (25.5 months) are insufficient for the evaluation of irradiation effects, no definite statement as to the merits of this energy modality in such cases can be made. The irradiation of infarcted retina was followed by extensive atrophy of the involved area. No secondary glaucoma was observed during a follow-up period of 16.4 months. The irradiation in four cases of neovascular subretinal membranes was followed by disappearance of the membranes. However, relapse later occurred in all four cases. The irradiation of eight retinal breaks resulted in solid scar tissue. Two choroidal melanomas were destroyed and did not recur during a follow-up period of 22 months.

  15. Ocular rosacea: a dermatologic perspective.

    PubMed

    Webster, Guy; Schaller, Martin

    2013-12-01

    As many as 50% of patients given the diagnosis of cutaneous rosacea also have ocular rosacea. Conservative figures indicate that approximately 10 million patients are affected by ocular rosacea in the United States alone. Despite this prevalence, ocular symptoms of rosacea are often improperly diagnosed, particularly when they occur in the absence of skin involvement.

  16. MRI findings of choroid plexus tumors in the cerebellum.

    PubMed

    Zhang, Ti-Jiang; Yue, Qiang; Lui, Su; Wu, Qi-Zhu; Gong, Qi-Yong

    2011-01-01

    Choroid plexus tumors (CPTs) are uncommon primary intracranial tumors. Here, we describe two patients with CPTs of the cerebellum: one had a choroid plexus papilloma located in the left cerebellar hemisphere that presented as an irregular, lobulated and solid-cystic mass, whereas the other had a choroid plexus carcinoma that exhibited a poorly defined, mixed-intensity mass associated with invasion of adjacent brain parenchyma. Contrast-enhanced MR imaging showed prominent heterogeneous enhancement. CPTs should be considered in the differential diagnosis for irregular, heterogeneous and intensely enhancing masses that occur in the cerebellum.

  17. Ectopic presacral choroid plexus cyst in a neonate.

    PubMed

    Gross, Eitan; Koplewitz, Benjamin Z; Arbell, Dan; Fellig, Jakob; Udassin, Raphael

    2009-05-01

    An unusual case of a presacral ectopic choroid plexus cyst in a neonate is described. After birth, a soft lump was noticed at the left buttock. Imaging studies including sonography and magnetic resonance imaging demonstrated a presacral cystic lesion extending to the buttocks, composed of several septated cystic masses with no connection to the spinal canal or rectum. After total resection, the tumor was diagnosed as an ectopic choroid plexus cyst. To our knowledge, this is the first case report in the English literature of a presacral ectopic choroid plexus cyst.

  18. Clinical Findings, Follow-up and Treatment Results in Patients with Ocular Rosacea

    PubMed Central

    Kılıç Müftüoğlu, İlkay; Aydın Akova, Yonca

    2016-01-01

    Objectives: To report the clinical features, treatment options and complications in patients with ocular rosacea. Materials and Methods: The records of 48 eyes of 24 patients with ocular rosacea were retrospectively reviewed. Patients’ ocular signs and symptoms were scored between 1 and 4 points according to disease severity; tear film break-up time (BUT) and Schirmer’s test results were recorded before and after the treatment. Preservative-free artificial tears, topical antibiotic eye drops/ointments, short-term topical corticosteroids, topical 0.05% cyclosporine and oral doxycycline treatment were applied as a standard therapy to all patients. Additional treatments were given as needed. Complications were recorded. Results: Twenty-four patients with a mean age of 48.5±35.4 (32-54) years were followed for a mean 15±9.4 (8-36) months. Ocular findings included meibomitis in 100% of cases, anterior blepharitis in 83% (40 eyes), punctate keratopathy in 67% (32 eyes), chalazia in 50% (24 eyes), corneal neovascularization in 50% (24 eyes) and subepithelial infiltrates in 16.6% (8 eyes). Significant improvement of symptoms and clinical findings were achieved in all patients with treatment. The increases in Schirmer’s test and BUT were 3.3±1.5 and 4.5±2.8, respectively (p<0.05). Descemetocele and small corneal perforation occurred in 2 eyes; re-epithelialization was achieved in both eyes with tissue adhesive application (1 eye) and additional amniotic membrane transplantation (1 eye). Four eyes of three patients showed significant regression of corneal neovascularization with topical bevacizumab therapy. Conclusion: Ocular rosacea may present with a variety of ophthalmic signs. It is possible to control the ophthalmic disease with appropriate therapeutic modalities including topical corticosteroids, topical cyclosporine and systemic doxycycline. PMID:27800249

  19. Light activated liposomes: Functionality and prospects in ocular drug delivery.

    PubMed

    Lajunen, Tatu; Nurmi, Riikka; Kontturi, Leena; Viitala, Lauri; Yliperttula, Marjo; Murtomäki, Lasse; Urtti, Arto

    2016-12-28

    Ocular drug delivery, especially to the retina and choroid, is a major challenge in drug development. Liposome technology may be useful in ophthalmology in enabling new routes of delivery, prolongation of drug action and intracellular drug delivery, but drug release from the liposomes should be controlled. For that purpose, light activation may be an approach to release drug at specified time and site in the eye. Technical advances have been made in the field of light activated drug release, particularly indocyanine green loaded liposomes are a promising approach with safe materials and effective light triggered release of small and large molecules. This review discusses the liposomal drug delivery with light activated systems in the context of ophthalmic drug delivery challenges.

  20. A simplified technique for in situ excision of cornea and evisceration of retinal tissue from human ocular globe.

    PubMed

    Parekh, Mohit; Ferrari, Stefano; Di Iorio, Enzo; Barbaro, Vanessa; Camposampiero, Davide; Karali, Marianthi; Ponzin, Diego; Salvalaio, Gianni

    2012-06-12

    Enucleation is the process of retrieving the ocular globe from a cadaveric donor leaving the rest of the globe undisturbed. Excision refers to the retrieval of ocular tissues, especially cornea, by cutting it separate from the ocular globe. Evisceration is the process of removing the internal organs referred here as retina. The ocular globe consists of the cornea, the sclera, the vitreous body, the lens, the iris, the retina, the choroid, muscles etc (Suppl. Figure 1). When a patient is suffering from corneal damage, the cornea needs to be removed and a healthy one must be transplanted by keratoplastic surgeries. Genetic disorders or defects in retinal function can compromise vision. Human ocular globes can be used for various surgical procedures such as eye banking, transplantation of human cornea or sclera and research on ocular tissues. However, there is little information available on human corneal and retinal excision, probably due to the limited accessibility to human tissues. Most of the studies describing similar procedures are performed on animal models. Research scientists rely on the availability of properly dissected and well-conserved ocular tissues in order to extend the knowledge on human eye development, homeostasis and function. As we receive high amount of ocular globes out of which approximately 40% (Table 1) of them are used for research purposes, we are able to perform huge amount of experiments on these tissues, defining techniques to excise and preserve them regularly. The cornea is an avascular tissue which enables the transmission of light onto the retina and for this purpose should always maintain a good degree of transparency. Within the cornea, the limbus region, which is a reservoir of the stem cells, helps the reconstruction of epithelial cells and restricts the overgrowth of the conjunctiva maintaining corneal transparency and clarity. The size and thickness of the cornea are critical for clear vision, as changes in either of them

  1. [Ocular Manifestations in Sarcoidosis].

    PubMed

    Walscheid, K; Tappeiner, C; Heiligenhaus, A

    2016-05-01

    Sarcoidosis is an inflammatory multi-organ disease of unknown pathogenesis, characterised by non-necrotising granulomata. Sarcoidosis predominantly manifests in the lung, but any other organ may be affected. Ocular involvement is present in about 25 to 50 % of patients. The most common ocular manifestation is uveitis, especially of the anterior eye segment. If ocular sarcoidosis is suspected, interdisciplinary assessment of the patient is mandatory, including laboratory tests, chest X-ray, assessment by a specialist in internal medicine and, ideally, histological evidence of granuloma formation in a tissue specimen. Other (infectious) causes of granulomatous inflammation need to be excluded, especially tuberculosis or syphilis. For the ophthalmological assessment, detection of granulomatous lesions is of particular importance, especially by visualising chorioretinal granuloma by fluorescein and indocyanin green angiography. Cystoid macular oedema and glaucoma are the most frequent complications limiting visual acuity. Corticosteroids, which can be administered either locally or systemically, are the mainstay of therapy. Depending on the clinical course and the development of ocular complications, systemic steroid-sparing immunosuppressive medication may be indicated.

  2. Ocular Screening System

    NASA Technical Reports Server (NTRS)

    1985-01-01

    An ocular screening system designed for safe, convenient screening of large groups was developed at Marshall Space Flight Center, leading to the formation of Medical Sciences Corporation. The system identifies visual defects accurately and inexpensively, and includes a photorefractor telephoto lens and an electronic flash. Medical Sciences Corporation is using the device to test at schools, industrial plants, etc.

  3. 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.

  4. 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.

  5. Update of choroidal imaging techniques: Past, present and future.

    PubMed

    Ruiz-Medrano, J; Flores-Moreno, I; Gutierrez-Bonet, R; Chhablani, J; Ruiz-Moreno, J M

    2017-03-01

    The choroid is the middle layer of the eye, a very vascular and pigmented tissue, with its role in several ophthalmological pathologies already having been clearly established. But it was not until the last few years that we have been able to reliably and precisely measure and quantify its shape and thickness. Ultrasound technology and indocyanine green angiography were the first techniques used for the study of the choroid, and they still maintain their use and clinical indications for the diagnosis and management of several pathologies. But it was the advent of optical coherence tomography that was the greatest breakthrough in choroidal imaging. In this chapter, the past, current and future image modalities for the study of the choroid will be discussed, with special focus on optical coherence tomography and its latest developments.

  6. 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.

  7. 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.

  8. Severe iritis and choroidal effusion following selective laser trabeculoplasty.

    PubMed

    Kim, Danny Y; Singh, Anna

    2008-01-01

    A patient with uncontrolled primary open-angle glaucoma underwent selective laser trabeculoplasty and developed a significant anterior chamber reaction, shallow anterior chamber, and choroidal effusion. Common complications associated with selective laser trabeculoplasty include conjunctival injection, mild anterior chamber reaction, and post-treatment intraocular pressure elevation. The authors believe this is the first reported case of severe iritis and choroidal effusion following selective laser trabeculoplasty.

  9. Schistosomotic choroiditis. I. Funduscopic changes and differential diagnosis.

    PubMed Central

    Oréfice, F.; Simal, C. J.; Pittella, J. E.

    1985-01-01

    This paper presents the results of biomicroscopy and funduscopy on five patients with hepatosplenic schistosomiasis mansoni. Fluorescein angioretinography was performed on two patients. All cases showed yellowish white multiple billateral nodules of various sizes, located in the choroidal plane. The nature and differential diagnosis of these nodules is discussed, and the suggestion is made that they represent cases of schistosomotic nodular choroiditis. Images PMID:3994946

  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. Visual Function and Its Relationship with Severity of Early, and Activity of Neovascular, Age-Related Macular Degeneration

    PubMed Central

    Loughman, James; Sabour-Pickett, Sarah; Nolan, John M.; Klein, Barbara; Klein, Ronald; Beatty, Stephen

    2017-01-01

    Purpose To investigate the relationship between visual function and severity of early age-related macular degeneration (AMD) and activity of neovascular (nv-) AMD. Methods The following data was collected from 66 eyes of 66 subjects with early AMD and 47 eyes of 47 subjects with active nv-AMD: corrected distance visual acuity (CDVA); contrast sensitivity (CS); glare disability (GD); and retinotopic ocular sensitivity (ROS) of the central 5° of the retina, by microperimetry. Fundus photographic grading of early AMD was performed in a masked fashion. Mean foveal thickness (MFT) was measured by spectral domain optical coherence tomography in patients with nv-AMD. Results In subjects with early AMD, there was an inverse and statistically significant relationship between measures of ROS within the central 5° of retina (including fixation) and severity of early AMD (p=0.01). In eyes with active nv-AMD, an inverse and statistically significant relationship was observed between measures of MFT and measures of ROS at the central 5° of retina (r=-0.34; p=0.02). No other measures, including CDVA, were significantly related to severity of early AMD, or to MFT in nv-AMD. Conclusion Although ROS was cross-sectionally associated with disease severity, and inversely related to MFT, an important determinant of need-to-treat in cases of nv-AMD, further research is required to determine the appropriateness of ROS for monitoring early and active neovascular forms of this disease.

  12. Ocular delivery of macromolecules

    PubMed Central

    Kim, Yoo-Chun; Chiang, Bryce; Wu, Xianggen; Prausnitz, Mark R.

    2014-01-01

    Biopharmaceuticals are making increasing impact on medicine, including treatment of indications in the eye. Macromolecular drugs are typically given by physician-administered invasive delivery methods, because non--invasive ocular delivery methods, such as eye drops, and systemic delivery, have low bioavailability and/or poor ocular targeting. There is a need to improve delivery of biopharmaceuticals to enable less-invasive delivery routes, less-frequent dosing through controlled-release drug delivery and improved drug targeting within the eye to increase efficacy and reduce side effects. This review discusses the barriers to drug delivery via various ophthalmic routes of administration in the context of macromolecule delivery and discusses efforts to develop controlled-release systems for delivery of biopharmaceuticals to the eye. The growing number of macromolecular therapies in the eye needs improved drug delivery methods that increase drug efficacy, safety and patient compliance. PMID:24998941

  13. Progress in measurement of ocular blood flow and relevance to our understanding of glaucoma and age-related macular degeneration.

    PubMed

    Harris, A; Chung, H S; Ciulla, T A; Kagemann, L

    1999-09-01

    New technologies have facilitated the study of the ocular circulation. These modalities and analysis techniques facilitate very precise and comprehensive study of retinal, choroidal, and retrobulbar circulations. These techniques include: 1. Vessel caliber assessment; 2. Scanning laser ophthalmoscopic fluorescein angiography and indocyanine green angiography to image and evaluate the retinal circulation and choroidal circulation respectively; 3. Laser Doppler flowmetry and confocal scanning laser Doppler flowmetry to measure blood flow in the optic nerve head and retinal capillary beds; 4. Ocular pulse measurement; and 5. color Doppler imaging to measure blood flow velocities in the central retinal artery, the ciliary arteries and the ophthalmic artery. These technique have greatly enhanced the ability to quantify ocular perfusion defects in many disorders, including glaucoma and age-related macular degeneration, two of the most prevalent causes of blindness in the industrialized world. Recently it has become clear, in animal models of glaucoma, that retinal ganglion cells die via apoptosis. The factors that initiate apoptosis in these cells remain obscure, but ischemia may play a central role. Patients with either primary open-angle glaucoma or normal-tension glaucoma experience various ocular blood flow deficits. With regard to age-related macular degeneration, the etiology remains unknown although some theories include primary retinal pigment epithelial senescence, genetic defects such as those found in the ABCR gene which is also defective in Stargardt's disease and ocular perfusion abnormalities. As the choriocapillaris supplies the metabolic needs of the retinal pigment epithelium and the outer retina, perfusion defect in the choriocapillaris could account for some of the physiologic and pathologic changes in AMD. Vascular defects have been identified in both nonexudative and exudative AMD patients using new technologies. This paper is a comprehensive update

  14. 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

  15. Ocular sparganosis from Assam

    PubMed Central

    Nath, Reema; Gogoi, Rajendra Nath

    2015-01-01

    Sparganosis is caused by plerocercoid larvae of the Pseudophyllidea tapeworms of the genus Spirometra. Though prevalent in East Asian and south east Asian countries like China, Japan, Korea, Taiwan, Vietnam, Thailand; yet very few cases are reported from India. We report a case of migrating sub-conjunctival ocular sparganosis mimicking scleritis which later on developed into orbital cellulitis from Dibrugarh, Assam, North-eastern part of India. This case is reported for its rarity. PMID:25709957

  16. Human ocular anatomy.

    PubMed

    Kels, Barry D; Grzybowski, Andrzej; Grant-Kels, Jane M

    2015-01-01

    We review the normal anatomy of the human globe, eyelids, and lacrimal system. This contribution explores both the form and function of numerous anatomic features of the human ocular system, which are vital to a comprehensive understanding of the pathophysiology of many oculocutaneous diseases. The review concludes with a reference glossary of selective ophthalmologic terms that are relevant to a thorough understanding of many oculocutaneous disease processes.

  17. 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.

  18. Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration.

    PubMed

    Parmeggiani, Francesco; Costagliola, Ciro; Semeraro, Francesco; Romano, Mario R; Rinaldi, Michele; Gallenga, Carla Enrica; Serino, Maria Luisa; Incorvaia, Carlo; D'Angelo, Sergio; De Nadai, Katia; Dell'Omo, Roberto; Russo, Andrea; Gemmati, Donato; Perri, Paolo

    2015-08-20

    Macular degenerations represent leading causes of central blindness or low vision in developed countries. Most of these severe visual disabilities are due to age-related macular degeneration (AMD) and pathologic myopia (PM), both of which are frequently complicated by subfoveal choroidal neovascularization (CNV). Photodynamic therapy with verteporfin (PDT-V) is still employed for CNV treatment in selected cases or in combined regimen. In Caucasian patients, the common polymorphism G185T of factor XIII-A gene (FXIII-A-G185T; rs5985) has been described as predictor of poor angiographic CNV responsiveness to PDT-V. Nevertheless, the prognostic implications of this pharmacogenetic determinant on long-term visual outcome after a PDT-V regimen have not been evaluated. We retrospectively selected Caucasian patients presenting with treatment-naive CNV and receiving standardized PDT-V protocol for two years. The study population included patients affected by subfoveal CNV secondary to AMD or PM. We assessed the correlations between the polymorphic allele T of FXIII-A-G185T and: (1) total number of photodynamic treatments; and (2) change in visual acuity from baseline to the end of the follow-up period. Considering a total study population of 412 patients with neovascular AMD or PM, the carriers of 185 T-allele of FXIII-A (GT or TT genotype) received a higher number of photodynamic treatments than patients without it (GG wild-type genotype) (p < 0.01; mean number of PDT-V: 5.51 vs. 3.76, respectively). Moreover, patients with 185 T-allele of FXIII-A had a more marked worsening of visual acuity at 24 months than those with the GG-185 wild genotype (p < 0.01; mean difference in logMAR visual acuity: 0.22 vs. 0.08, respectively). The present findings show that the G185T polymorphism of the FXIII-A gene is associated with significant differences in the long-term therapeutic outcomes of patients treated with standardized PDT-V protocol. The comprehensive appraisal of both anti

  19. 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

  20. 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.

  1. Ocular injuries in automobile crashes.

    PubMed

    Huelke, D F; O'Day, J; Barhydt, W H

    1982-01-01

    Tempered windshields commonly used in Europe have been shown to be related to the relatively high incidence of ocular injuries. Although windshields of the High Penetration Resistant (HPR) type in cars in North America are not at all significantly involved in ocular injuries, still about 50 % of the injuries of the eye area are caused by glass. The HPR windshield probably is the main reason for the relatively low occurrence of ocular injuries in United States crashes compared to these injuries reported from countries with tempered windshields. No ocular injuries were observed among belted occupants in this study. It appears that the increased use of lap-shoulder belts would decrease the likelihood of occupant contact with the windshield, mirrors, roof support, steering wheel, and instrument panel- about two thirds of the occupant contacts related to ocular injury- and thus reduce the incidence of ocular injuries leading to decreased vision.

  2. Choroidal Thickness and Choroidal Vessel Density in Nonexudative Age-Related Macular Degeneration Using Swept-Source Optical Coherence Tomography Imaging

    PubMed Central

    Zheng, Fang; Gregori, Giovanni; Schaal, Karen B.; Legarreta, Andrew D.; Miller, Andrew R.; Roisman, Luiz; Feuer, William J.; Rosenfeld, Philip J.

    2016-01-01

    Purpose To analyze the relationship between choroidal thickness and the distribution of choroidal blood vessels in eyes with nonexudative AMD. Methods Eyes with a diagnosis of nonexudative AMD were imaged using a prototype 100-kHz swept-source (SS) optical coherence tomography (OCT) instrument (Carl Zeiss Meditec, Dublin, CA, USA) with a central wavelength of 1050 nm. We used an OCT cube scan pattern consisting of 512 × 512 A-scans over a 12 × 12 mm retinal area. The eyes were partitioned into two groups based on the presence or absence of reticular pseudodrusen (RPD). All scans were segmented using an automated algorithm. In addition, five eyes from each of the two groups were randomly chosen for manual segmentation. Binary choroidal vessels maps were generated from suitable OCT choroidal slabs, and the relationship between the density of large choroidal vessels and choroidal thickness was analyzed using an Early Treatment Diabetic Retinopathy Study–like target centered on the fovea. Results Twenty-five eyes were enrolled in each group. The automated algorithm produced accurate choroidal thickness maps with an average difference between the manual and automated segmentations of 13.7 μm. There was a significant and stable correlation between choroidal thickness and choroidal vessel density across the two groups. Both average choroidal thickness and vessel density were significantly lower in eyes with RPD. Conclusions Our fully automated choroidal segmentation algorithm was able to capture the different patterns of choroidal thickness over a wide area. Choroidal thickness has a clear relationship with the density of large choroid vessels in our sample, irrespective of the presence or absence of RPD. PMID:27849311

  3. A Mystery of Bilateral Annular Choroidal and Exudative Retinal Detachment with No Systemic Involvement: Is It Part of Vogt-Koyanagi-Harada Disease Spectrum or a New Entity?

    PubMed

    Elaraoud, Ibrahim; Andreatta, Walter; Jiang, Li; Damer, Kenan; Al-Ibrahim, Jalil

    2017-01-01

    A 65-year-old Caucasian male presented to the eye emergency department with bilateral significant visual loss. He was otherwise healthy with no significant past medical history. Ophthalmic history was significant for chronic open-angle glaucoma, for which the patient was using latanoprost once daily to both eyes. There was no preceding history of trauma or ocular surgery and the patient was emmetropic. Two weeks prior to his presentation, he reported a headache, which settled spontaneously. Slit-lamp examination demonstrated bilateral keratic precipitates, bilateral significantly shallow anterior chamber, and bilaterally normal intraocular pressures of 16 mm Hg. Fundal examination was significant for bilateral 360-degree choroidal detachments with exudative retinal detachment involving the maculae. These findings were confirmed using wide-field fundus photography, B-scan ultrasonography, and optical coherence tomography. Fundus fluorescein angiography did not reveal any evidence of retinal vasculitis. Indocyanine green chorioangiography of the posterior pole showed multiple areas of focal choroidal hypoperfusion. Extensive systemic investigation demonstrated no infectious, neoplastic, or inflammatory cause, and the patient did not complain of any systemic symptoms. Treatment with high-dose intravenous methylprednisolone was administered and this brought about complete resolution of both choroidal and retinal detachments, with partial visual recovery.

  4. A Mystery of Bilateral Annular Choroidal and Exudative Retinal Detachment with No Systemic Involvement: Is It Part of Vogt-Koyanagi-Harada Disease Spectrum or a New Entity?

    PubMed Central

    Elaraoud, Ibrahim; Andreatta, Walter; Jiang, Li; Damer, Kenan; Al-Ibrahim, Jalil

    2017-01-01

    A 65-year-old Caucasian male presented to the eye emergency department with bilateral significant visual loss. He was otherwise healthy with no significant past medical history. Ophthalmic history was significant for chronic open-angle glaucoma, for which the patient was using latanoprost once daily to both eyes. There was no preceding history of trauma or ocular surgery and the patient was emmetropic. Two weeks prior to his presentation, he reported a headache, which settled spontaneously. Slit-lamp examination demonstrated bilateral keratic precipitates, bilateral significantly shallow anterior chamber, and bilaterally normal intraocular pressures of 16 mm Hg. Fundal examination was significant for bilateral 360-degree choroidal detachments with exudative retinal detachment involving the maculae. These findings were confirmed using wide-field fundus photography, B-scan ultrasonography, and optical coherence tomography. Fundus fluorescein angiography did not reveal any evidence of retinal vasculitis. Indocyanine green chorioangiography of the posterior pole showed multiple areas of focal choroidal hypoperfusion. Extensive systemic investigation demonstrated no infectious, neoplastic, or inflammatory cause, and the patient did not complain of any systemic symptoms. Treatment with high-dose intravenous methylprednisolone was administered and this brought about complete resolution of both choroidal and retinal detachments, with partial visual recovery. PMID:28203189

  5. Sox11 Is Required to Maintain Proper Levels of Hedgehog Signaling during Vertebrate Ocular Morphogenesis

    PubMed Central

    Pillai-Kastoori, Lakshmi; Wen, Wen; Wilson, Stephen G.; Strachan, Erin; Lo-Castro, Adriana; Fichera, Marco; Musumeci, Sebastiano A.; Lehmann, Ordan J.; Morris, Ann C.

    2014-01-01

    Ocular coloboma is a sight-threatening malformation caused by failure of the choroid fissure to close during morphogenesis of the eye, and is frequently associated with additional anomalies, including microphthalmia and cataracts. Although Hedgehog signaling is known to play a critical role in choroid fissure closure, genetic regulation of this pathway remains poorly understood. Here, we show that the transcription factor Sox11 is required to maintain specific levels of Hedgehog signaling during ocular development. Sox11-deficient zebrafish embryos displayed delayed and abnormal lens formation, coloboma, and a specific reduction in rod photoreceptors, all of which could be rescued by treatment with the Hedgehog pathway inhibitor cyclopamine. We further demonstrate that the elevated Hedgehog signaling in Sox11-deficient zebrafish was caused by a large increase in shha transcription; indeed, suppressing Shha expression rescued the ocular phenotypes of sox11 morphants. Conversely, over-expression of sox11 induced cyclopia, a phenotype consistent with reduced levels of Sonic hedgehog. We screened DNA samples from 79 patients with microphthalmia, anophthalmia, or coloboma (MAC) and identified two novel heterozygous SOX11 variants in individuals with coloboma. In contrast to wild type human SOX11 mRNA, mRNA containing either variant failed to rescue the lens and coloboma phenotypes of Sox11-deficient zebrafish, and both exhibited significantly reduced transactivation ability in a luciferase reporter assay. Moreover, decreased gene dosage from a segmental deletion encompassing the SOX11 locus resulted in microphthalmia and related ocular phenotypes. Therefore, our study reveals a novel role for Sox11 in controlling Hedgehog signaling, and suggests that SOX11 variants contribute to pediatric eye disorders. PMID:25010521

  6. Visual performance in patients with neovascular age-related macular degeneration undergoing treatment with intravitreal ranibizumab.

    PubMed

    Sabour-Pickett, Sarah; Loughman, James; Nolan, John M; Stack, Jim; Pesudovs, Konrad; Meagher, Katherine A; Beatty, Stephen

    2013-01-01

    Purpose. To assess visual function and its response to serial intravitreal ranibizumab (Lucentis, Genentech) in patients with neovascular age-related macular degeneration (nv-AMD). Methods. Forty-seven eyes of 47 patients with nv-AMD, and corrected distance visual acuity (CDVA) logMAR 0.7 or better, undergoing intravitreal injections of ranibizumab, were enrolled into this prospective study. Visual function was assessed using a range of psychophysical tests, while mean foveal thickness (MFT) was determined by optical coherence tomography (OCT). Results. Group mean (±sd) MFT reduced significantly from baseline (233 (±59)) to exit (205 (±40)) (P = 0.001). CDVA exhibited no change between baseline and exit visits (P = 0.48 and P = 0.31, resp.). Measures of visual function that did exhibit statistically significant improvements (P < 0.05 for all) included reading acuity, reading speed, mesopic and photopic contrast sensitivity (CS), mesopic and photopic glare disability (GD), and retinotopic ocular sensitivity (ROS) at all eccentricities. Conclusion. Eyes with nv-AMD undergoing intravitreal ranibizumab injections exhibit improvements in many parameters of visual function. Outcome measures other than CDVA, such as CS, GD, and ROS, should not only be considered in the design of studies investigating nv-AMD, but also in treatment and retreatment strategies for patients with the condition.

  7. Visual Performance in Patients with Neovascular Age-Related Macular Degeneration Undergoing Treatment with Intravitreal Ranibizumab

    PubMed Central

    Loughman, James; Nolan, John M.; Stack, Jim; Pesudovs, Konrad; Meagher, Katherine A.; Beatty, Stephen

    2013-01-01

    Purpose. To assess visual function and its response to serial intravitreal ranibizumab (Lucentis, Genentech) in patients with neovascular age-related macular degeneration (nv-AMD). Methods. Forty-seven eyes of 47 patients with nv-AMD, and corrected distance visual acuity (CDVA) logMAR 0.7 or better, undergoing intravitreal injections of ranibizumab, were enrolled into this prospective study. Visual function was assessed using a range of psychophysical tests, while mean foveal thickness (MFT) was determined by optical coherence tomography (OCT). Results. Group mean (±sd) MFT reduced significantly from baseline (233 (±59)) to exit (205 (±40)) (P = 0.001). CDVA exhibited no change between baseline and exit visits (P = 0.48 and P = 0.31, resp.). Measures of visual function that did exhibit statistically significant improvements (P < 0.05 for all) included reading acuity, reading speed, mesopic and photopic contrast sensitivity (CS), mesopic and photopic glare disability (GD), and retinotopic ocular sensitivity (ROS) at all eccentricities. Conclusion. Eyes with nv-AMD undergoing intravitreal ranibizumab injections exhibit improvements in many parameters of visual function. Outcome measures other than CDVA, such as CS, GD, and ROS, should not only be considered in the design of studies investigating nv-AMD, but also in treatment and retreatment strategies for patients with the condition. PMID:23533703

  8. 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

  9. Effect of intraocular pressure (IOP) and choroidal circulation on controlled episcleral drug delivery to retina/vitreous.

    PubMed

    Li, Jie; Lan, Bifei; Li, Xiaoli; Sun, Shumao; Lu, Ping; Cheng, Lingyun

    2016-12-10

    Transscleral drug delivery may become a safe alternative to the intravitreal injection for chronic retinal diseases such as age-related macular degeneration or diabetic macular edema. However, the drug delivered onto the sclera subjects to vigorous clearance by episcleral and choroidal circulation; in addition, the penetration from episclera to retina needs to overcome counter-directional ocular fluid current driven by intraocular pressure (IOP) as well as unfavorable drug disposition exerted by drug transporters before the drug reach retina. It is imperative to understand these processes and quantitate their influence for efficient designing of a sustained formulation or device to achieve efficient transscleral drug delivery. The current study was focused on the effects of intraocular pressure (IOP) and choroidal circulation on transscleral drug delivery using triamcinolone acetonide (TA) as a model drug. Rabbit eye IOP was modulated through cannulation in ex vivo study or through cryopexy of ciliary body in vivo studies before subtenon TA injection or episcleral TA-film implantation. In a subgroup of the rabbit eyes, localized choroid atrophy was induced by cryopexy before TA-film implantation. Each condition had a concurrent control group. The vitreous TA concentration was quantitated by ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC/MS/MS). The vitreous TA concentration was compared between the study and control groups for effect of IOP or choroid circulation. For ex vivo studies, higher IOP was a significant effect against TA penetration from episclera towards vitreous. TA was 8.5±5ng/mL in receptor chamber with a cross pressure of 50mmHg versus 15.9±10ng/mL with the cross pressure of 5mmHg; p=0.001, t-test. A multivariate regression demonstrated each mmHg of IOP increase would result in 3ng/mL lower concentration in the receptor chamber. Similar IOP effect was also identified in a 3-hour study using euthanized rabbit

  10. 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

  11. Pharmacologic synergism of ocular ketorolac and systemic caffeine citrate in rat oxygen-induced retinopathy

    PubMed Central

    Aranda, Jacob V.; Cai, Charles L.; Ahmad, Taimur; Bronshtein, Vadim; Sadeh, Jonathan; Valencia, Gloria B.; Lazzaro, Douglas R.; Beharry, Kay D.

    2016-01-01

    Background: Caffeine or ketorolac decrease the risk of retinopathy of prematurity and may act synergistically to improve beneficial effect. Combination of caffeine (Caff) and ketorolac (Keto) to prevent oxygen-induced retinopathy was studied. Methods: Newborn rats exposed to room air (RA) or intermittent hypoxia (IH) consisting of 12% O2 during hyperoxia (50% O2) from birth (P0) had single daily IP injections of Caff from P0-P13 or saline; and/or ocular Keto (Acuvail, 0.45% ophthalmic solution) administered subcutaneously over the eyes from P5-P7. Pups were studied at P14 or placed in RA for recovery from IH (IHR) until P21. Eyes were examined for neovascularization, histopathology, growth factors, and VEGF-signaling genes. Results: Severe retinal damage noted during IHR in the untreated groups evidenced by hemorrhage, neovascularization, and oxygen-induced retinopathy (OIR) pathologies were prevented with Keto/Caff treatment. Keto and/or Caff treatment in IH also promoted retinal neural development evidenced by eye opening (92%, P < 0.001 vs. 31% in the placebo-treated IH group). No corneal pathologies were noted with Keto. Conclusion. Caff or Keto given individually reduced retinal neovascularization, but the two drugs given together prevented severe OIR. PMID:27438224

  12. TGF-β1 enhances SDF-1-induced migration and tube formation of choroid-retinal endothelial cells by up-regulating CXCR4 and CXCR7 expression.

    PubMed

    Feng, Yi-fan; Yuan, Fei; Guo, Hua; Wu, Wei-zhong

    2014-12-01

    Stromal derived factor (SDF)-1 has been confirmed to regulate angiogenesis in choroidal neovascularization formation via its two receptors, CXC chemokine receptors 4 (CXCR4) and 7 (CXCR7). Previous studies found that there is cross-talk between the transforming growth factor beta (TGF-β) and SDF-1 pathways in some types of immune or tumor cells, but much less is known about this interaction in endothelial cells. This study investigated the effects of TGF-β1 on CXCR4 and CXCR7 expression as well as SDF-1-induced migration and tube formation in choroid-retinal endothelial (RF/6A) cells. RF/6A cells were treated with recombinant TGF-β1 at various concentrations and time points. Real-time PCR and Western blotting were used to examine the mRNA and protein levels of CXCR4 and CXCR7. In addition, transwell migration and Matrigel tube formation analyses were performed to investigate the role of TGF-β1 pretreatment in SDF-1-induced RF/6A cell migration and tube formation. Our results showed that treatment with recombinant human TGF-β1 enhanced the CXCR4 and CXCR7 levels in time- and dose-dependent manners. The increased CXCR4 and CXCR7 expression resulted in increased SDF-1-induced RF/6A cell migration and tube formation. In addition, the transcriptional regulation of CXCR4 and CXCR7 by TGF-β1 was found to be mediated by phosphorylation of the extracellular signal-related kinase1/2 pathway. Altogether, these results demonstrate that a cross-talk exists between the TGF-β1 and SDF-1 pathways in choroid-retinal endothelial cells, reflecting a novel molecular mechanism that explains the pro-angiogenic effects of TGF-β1 and possibly provides new perspectives for the treatment of CNV-associated diseases.

  13. Dendrimer based nanotherapeutics for ocular drug delivery

    NASA Astrophysics Data System (ADS)

    Kambhampati, Siva Pramodh

    PAMAM dendrimers are a class of well-defined, hyperbranched polymeric nanocarriers that are being investigated for ocular drug and gene delivery. Their favorable properties such as small size, multivalency and water solubility can provide significant opportunities for many biologically unstable drugs and allows potentially favorable ocular biodistribution. This work exploits hydroxyl terminated dendrimers (G4-OH) as drug/gene delivery vehicles that can target retinal microglia and pigment epithelium via systemic delivery with improved efficacy at much lower concentrations without any side effects. Two different drugs Triamcinolone acetonide (TA) and N-Acetyl Cysteine (NAC) conjugated to G4-OH dendrimers showed tailorable sustained release in physiological relevant solutions and were evaluated in-vitro and in-vivo. Dendrimer-TA conjugates enhanced the solubility of TA and were 100 fold more effective at lower concentrations than free TA in its anti-inflammatory activity in activated microglia and in suppressing VEGF production in hypoxic RPE cells. Dendrimers targeted activated microglia/macrophages and RPE and retained for a period of 21 days in I/R mice model. The relative retention of intravitreal and intravenous dendrimers was comparable, if a 30-fold intravenous dose is used; suggesting intravenous route targeting retinal diseases are possible with dendrimers. D-NAC when injected intravenously attenuated retinal and choroidal inflammation, significantly reduced (˜73%) CNV growth at early stage of AMD in rat model of CNV. A combination therapy of D-NAC + D-TA significantly suppressed microglial activation and promoted CNV regression in late stages of AMD without causing side-effects. G4-OH was modified with linker having minimal amine groups and incorporation of TA as a nuclear localization enhancer resulted in compact gene vectors with favorable safety profile and achieved high levels of transgene expression in hard to transfect human retinal pigment

  14. Clinical application of digital indocyanine green angiography in choroidal neurofibromatosis.

    PubMed

    Rescaldani, C; Nicolini, P; Fatigati, G; Bottoni, F G

    1998-01-01

    Indocyanine green angiography (ICGA) was used to investigate 2 cases of type 1 systemic neurofibromatosis that had appeared at birth with café-au-lait skin spots, gradually developing into multiple cutaneous neurofibromas. Patients underwent periodical visual acuity examinations, the fundus was checked and fluorescein angiography (FA) was done; all findings appeared extremely stable. In 1995 these 2 patients underwent ICGA to check for pathological choroidal involvement. In both cases the initial examination stages showed multiple extensive areas of hypofluorescence, their morphology and extension coinciding with the retinal pigment epithelium (RPE) lesions shown by FA and by ophthalmoscopic examination. In later stages the hypofluorescent areas became smaller, generally shrinking to small isolated dots in the middle of the original areas. These initially hypofluorescent areas appeared to be due to slow focal choroidal filling caused by deep alterations to the walls of the choroidal arterioles induced by the disease. Chronic hypoperfusion of the choriocapillaris results in impairment of the overlying RPE, causing it to atrophy. The late hypofluorescent areas could be either persistent nonperfused lobules of choriocapillaris or neurofibromatose choroidal nodules. ICGA examination showed that the FA lesions described in the literature as choroidal nodules are in fact alterations to the RPE secondary to areas of hypoperfusion in the choriocapillaris.

  15. 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

  16. Ultrastructural changes in the melanocytes of aging human choroid.

    PubMed

    Nag, Tapas Chandra

    2015-12-01

    Retinal pigment epithelial cells as well as choroidal melanocytes (CM) possess melanin granules. The former show clear, age-related changes (formation of lipofuscin granules with a concomitant decrease in melanin content); however, data on changes in the CM with aging are fairly limited. We examined CM in human macular and mid-peripheral areas by light- and transmission electron microscopy in 50-94 year-old donor eyes (N=12). Unlike in the choroid of lower ages, the melanocytes from aging choroid (>75 years) showed partial fusion of about 8-15 melanosomes, forming rosettes-like structures. Besides, there was evidence of emptiness in cytoplasm caused by the loss of melanosomes in aged CM, as was confirmed by quantification in macular part of choroid. In advanced aged eyes (85-94-year-old), the CM possessed many lipid droplets as well as irregular lipofuscin granules, the latter had a tendency to fuse with melanosomes, as happens in aged retinal pigment epithelium. Macrophages in their cytoplasm contained abundant irregular as well as clumped melanosomes of variable size, suggesting that damaged granules/melanocytes are cleared by these phagocytes. These obvious changes in the CM are likely to make the choroid prone to damage by visible light.

  17. Bilateral Choroidal Metastases from Endobronchial Carcinoid Treated with Somatostatin Analogues

    PubMed Central

    De Bruyn, Deborah; Lamont, Jan; Vanderstraeten, Erik; Van Belle, Simon; Platteau, Elise; De Zaeytijd, Julie; Hoornaert, Kristien P.

    2016-01-01

    Objective: To describe a patient with bilateral multifocal choroidal metastases from an endobronchial carcinoid treated with a somatostatin analogue. Method: A 60-year-old woman presenting with photopsia in the left eye underwent an extensive ophthalmic examination, including fluorescein angiography, OCT and ultrasound. Results: Fundoscopy revealed a small retinal tear in the left eye, for which she received laser treatment. In addition, choroidal masses were detected in both eyes. Her medical history of a pneumectomy for a bronchial carcinoid six years earlier together with recent elevated chromogranin A blood levels prompted a diagnosis of choroidal metastases. Subsequently, a Gallium-68 DOTANOC positron emitting tomography/computer tomography scan revealed a spinal cord metastasis and mediastinal as well as mesenterial lymph node invasion. Systemic treatment with Sandostatin®, a somatostatin analogue was started. Up until two years after the initial presentation and treatment, these choroidal lesions remained stable without any signs of growth. Conclusion: Endobronchial carcinoid tumors have an indolent nature and long-term follow-up is recommended for early detection of metastases. Although treatment with somatostatin analogues rarely induces complete tumor regression, tumor stabilization and prevention of symptoms related to hormone secretion is achieved. This well-tolerated systemic treatment provides a worthy alternative treatment for choroidal metastasis compared to classic radiotherapy without any risk of radiation or laser-related visual loss. PMID:27843513

  18. 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.

  19. Relationship between neovascularization and clinical severity in Achilles tendinopathy in 556 paired measurements.

    PubMed

    De Jonge, S; Warnaars, J L F; De Vos, R J; Weir, A; van Schie, H T M; Bierma-Zeinstra, S M A; Verhaar, J A N; Tol, J L

    2014-10-01

    Neovascularization is frequently observed in tendinopathy. Previous studies have focused on the role of neovascularization in Achilles tendinopathy, but have been conducted in small series. It is still unclear whether the degree of neovascularization is related to severity of symptoms. The purpose was to study the relationship between ultrasonographic neovascularization and clinical severity in patients with Achilles tendinopathy. In this prospective cohort study, data on 127 patients (141 tendons) were assembled from databases of three clinical trials. All patients followed an eccentric exercise program. The Öhberg neovascularization score (0-4+) and Victorian Institute of Sports Assessment-Achilles (VISA-A) score (split into domains: pain, function and activity) were collected during baseline and follow-up. The relationship between neovascularization and VISA-A score was calculated. At baseline, 107 tendons (76%) showed some degree of neovascularization. In 556 coupled measurements, neovascularization was weakly related to the VISA-A score [Exp (B) 1.017, 95% confidence interval (CI), 1.007-1.026]. No significant relationship was found between neovascularization and the pain domain (P = 0.277) and the activity domain (P = 0.283), but there was between neovascularization and the function domain of the VISA-A score [Exp (B) = 1.067, 95% CI 1.018-1.119]. In conclusion, neovascularization in Achilles tendinopathy is weakly related to clinical severity, mainly based on the function domain of the VISA-A score.

  20. Outcomes of Proton Beam Radiotherapy for Large Non-Peripapillary Choroidal and Ciliary Body Melanoma at TRIUMF and the BC Cancer Agency

    PubMed Central

    Weber, Britta; Paton, Katherine; Ma, Roy; Pickles, Tom

    2015-01-01

    Background and Purpose To report outcomes and toxicity after proton beam radiotherapy for non-peripapillary choroidal and ciliary body melanoma considered unsuitable for other eye-sparing therapies. Materials and Methods: An existing database of 77 patients with non-peripapillary tumors treated at TRIUMF, Canada, including patient, tumor, and treatment characteristics, was updated with ocular complications and follow-up status from chart reviews. Results Most of the patients had large tumors: 61% were T3/T4 tumors (AJCC classification), while 48% were large by the Collaborative Ocular Melanoma Study classification. The median thickness was 7.1 mm, and the ciliary body was involved in 35%. After 5 and 10 years, the actuarial ocular tumor control rate was 85 and 85%, metastasis-free survival was 72 and 57%, overall survival was 77 and 63%, the enucleation rate was 22 and 22%, and complete blindness was found in 38 and 38%, respectively. On univariate analysis, patients with ciliary body involvement had significantly worse metastasis-free survival and overall survival rates compared to patients without ciliary body involvement (p < 0.001). Conclusions Proton therapy for large anteriorly located tumors resulted in acceptable ocular tumor control and survival rates. The risk of blindness and severe toxicity requiring enucleation was low, and a substantial proportion of patients maintained useful vision. PMID:27171272

  1. Ocular medications in children.

    PubMed

    Wallace, D K; Steinkuller, P G

    1998-11-01

    Many ocular medications are used by pediatricians or ophthalmologists caring for pediatric patients. Topical antibiotics are commonly prescribed for bacterial conjunctivitis, nasolacrimal duct obstructions, and ophthalmia neonatorum. Many new antiallergy eye drops are now available for the treatment of seasonal (hay fever) conjunctivitis. Dilating eye drops and antiglaucoma medications are generally used or prescribed by ophthalmologists, but pediatricians must be aware of their potentially serious systemic side effects. Before initiating treatment, physicians should evaluate the risks and benefits of ophthalmic medications, establish minimum dosages necessary to achieve a therapeutic benefit, and monitor children for local and systemic side effects.

  2. [Ocular biometry using Orbscan].

    PubMed

    Touzeau, O; Allouch, C; Borderie, V; Laroche, L

    2005-06-01

    Orbscan is a recent optical device that combines the Placido disk of the videokeratoscope and a scanning slit. The scanning slit measures the elevation of both the corneal surface (anterior and posterior) and the anterior iris-lens surface. Biometric measures of the anterior segment such as corneal thickness, anterior chamber depth, corneal diameter, and iridocorneal angle are obtained using spatial coordinates of various ocular surfaces. Orbscan is not only a corneal topograph but a versatile device capable of measuring the biometry of the anterior segment of the eye.

  3. Ocular surface tumors

    PubMed Central

    Othman, Ihab Saad

    2009-01-01

    Tumors of the conjunctiva and cornea comprise a large and varied spectrum of conditions. These tumors are grouped into two major categories of congenital and acquired lesions. The acquired lesions are further subdivided based on origin of the mass into surface epithelial, mucoepidermoid, melanocytic, vascular, fibrous, neural, histiocytic, myxoid, myogenic, lipomatous, lymphoid, leukemic, metastatic and secondary tumors. Ocular surface tumors include a variety of neoplasms originating from squamous epithelium, melanocytic tumors and lymphocytic resident cells of the conjunctival stroma. In this review, we highlight clinical features of these lesions, important diagnostic and investigative tools and standard care of management. PMID:21234217

  4. Ocular oxygen consumption during vitreoperfusion in the cat.

    PubMed Central

    Blair, N P

    2000-01-01

    PURPOSE: Little is known about the total ocular oxygen consumption rate (QO2) in human diseases. Reductions in QO2 may indicate the amount of tissue loss produced by conditions such as retinal ischemia. We sought a method to estimate QO2 that eventually could be used in patients during vitrectomy surgery. METHODS: We performed vitreoperfusion (perfusion of the vitreous cavity after vitrectomy) in 22 cat eyes with no ocular blood flow. The solution contained nutrients and a high partial pressure of oxygen (PO2). In 8 eyes we placed an oxygen electrode on the sclera, choroid, or outer retina to evaluate oxygen delivery from the vitreoperfusion solution (group 1). In 8 eyes the retinas were undisturbed (group 2), and in 6 eyes we excised the retinas (group 3). In groups 2 and 3 we estimated QO2 from the temporal decline of PO2 in the vitreoperfusion solution according to a pharmacokinetic model. RESULTS: Group 1 demonstrated oxygenation of the entire retina. The means and standard deviations of QO2 were 3.2 +/- 0.8 and 0.4 +/- 0.7 microL/min in groups 2 and 3, respectively, the difference being the retinal contribution, 88%. In group 2, metabolism accounted for an average of 82% of the oxygen loss from the vitreoperfusion solution, whereas flow and diffusion accounted for 13% and 5%, respectively. CONCLUSIONS: Ocular oxygen consumption can be estimated by means of vitreoperfusion. Further developments may allow measurements in patients during vitreous surgery to clarify the pathophysiology of their diseases and assess the amount of retinal tissue that has been lost. Images FIGURE 2 PMID:11190030

  5. Ocular Effects of Sulfur Mustard and Therapeutic Approaches: A Review.

    PubMed

    Panahi, Yunes; Rajaee, Seyyed Mahdi; Sahebkar, Amirhossein

    2017-01-20

    Sulfur mustard (SM) is a strong blistering, highly reactive, lipophilic chemical war agent that causes injury in different organs including the skin, eyes and respiratory tract. The Eyes are especially susceptible to the consequences of SM poisoning because of the aqueous and mucosal nature of conjunctiva and cornea. DNA alkylation and depletion of glutathione, are the most important mechanisms of SM action in the eye injuries. Acute clinical symptoms are including decrease in visual acuity, dryness, photophobia, blepharospasm, conjunctivitis and complaints of foreign body sensation and soreness that gradually progress to severe ocular pain. Corneal abrasions, ulcerations, vesication and perforations are common corneal consequences in SM injured victims. Appearance of chronic symptoms has been reported as chronic inflammation of the corneal and conjunctival vasculature, ischemia, lipid and cholesterol deposition, scarring in cornea, corneal thinning, opacification and perforation of the cornea, limbal stem cell deficiency (LSCD) and neovascularization. Different medical and surgical protocols have been documented in the management of SM-induced ocular injuries, including preservative-free artificial tears, topical steroids and antibiotic, mydriatic, antiglaucoma drops, therapeutic contact lenses, dark glasses and punctal plugs/cauterization, N-acetylcysteine, tarsorrhaphy, amniotic membrane transplantation, stem cell transplantation and corneal transplantation. New drugs such as resolvin E1, topical form of essential fatty acids, thymosin β4, 43 amino-acid polypeptides, topical form of curcumin, newly formulated artificial tears, diquafosol, rebamipide, tretinoin and oral uridineseems to be beneficial in the management of ocular lesion associated with sulfur mustard poisoning. Further studies are needed to approve these drugs in SM victims. This article is protected by copyright. All rights reserved.

  6. Combined 60° Wide-Field Choroidal Thickness Maps and High-Definition En Face Vasculature Visualization Using Swept-Source Megahertz OCT at 1050 nm

    PubMed Central

    Mohler, Kathrin J.; Draxinger, Wolfgang; Klein, Thomas; Kolb, Jan Philip; Wieser, Wolfgang; Haritoglou, Christos; Kampik, Anselm; Fujimoto, James G.; Neubauer, Aljoscha S.; Huber, Robert; Wolf, Armin

    2015-01-01

    Purpose To demonstrate ultrahigh-speed swept-source optical coherence tomography (SS-OCT) at 1.68 million A-scans/s for choroidal imaging in normal and diseased eyes over a ∼60° field of view. To investigate and correlate wide-field three-dimensional (3D) choroidal thickness (ChT) and vascular patterns using ChT maps and coregistered high-definition en face images extracted from a single densely sampled Megahertz-OCT (MHz-OCT) dataset. Methods High-definition, ∼60° wide-field 3D datasets consisting of 2088 × 1024 A-scans were acquired using a 1.68 MHz prototype SS-OCT system at 1050 nm based on a Fourier-domain mode-locked laser. Nine subjects (nine eyes) with various chorioretinal diseases or without ocular pathology are presented. Coregistered ChT maps, choroidal summation maps, and depth-resolved en face images referenced to either the retinal pigment epithelium or the choroidal–scleral interface were generated using manual segmentation. Results Wide-field ChT maps showed a large inter- and intraindividual variance in peripheral and central ChT. In only four of the nine eyes, the location with the largest ChT was coincident with the fovea. The anatomy of the large lumen vessels of the outer choroid seems to play a major role in determining the global ChT pattern. Focal ChT changes with large thickness gradients were observed in some eyes. Conclusions Different ChT and vascular patterns could be visualized over ∼60° in patients for the first time using OCT. Due to focal ChT changes, a high density of thickness measurements may be favorable. High-definition depth-resolved en face images are complementary to cross sections and thickness maps and enhance the interpretation of different ChT patterns. PMID:26431482

  7. Mapping Murine Corneal Neovascularization and Weight Loss Virulence Determinants in the Herpes Simplex Virus 1 Genome and the Detection of an Epistatic Interaction between the UL and IRS/US Regions

    PubMed Central

    Lee, Kyubin; Kolb, Aaron W.; Larsen, Inna; Craven, Mark

    2016-01-01

    ABSTRACT Herpes simplex virus 1 (HSV-1) most commonly causes recrudescent labial ulcers; however, it is also the leading cause of infectious blindness in developed countries. Previous research in animal models has demonstrated that the severity of HSV-1 ocular disease is influenced by three main factors: host innate immunity, host immune response, and viral strain. We have previously shown that mixed infection with two avirulent HSV-1 strains (OD4 and CJ994) results in recombinants with a wide range of ocular disease phenotype severity. Recently, we developed a quantitative trait locus (QTL)-based computational approach (vQTLmap) to identify viral single nucleotide polymorphisms (SNPs) predicted to influence the severity of the ocular disease phenotypes. We have now applied vQTLmap to identify HSV-1 SNPs associated with corneal neovascularization and mean peak percentage weight loss (MPWL) using 65 HSV-1 OD4-CJ994 recombinants. The vQTLmap analysis using Random Forest for neovascularization identified phenotypically meaningful nonsynonymous SNPs in the ICP4, UL41 (VHS), UL42, UL46 (VP11/12), UL47 (VP13/14), UL48 (VP22), US3, US4 (gG), US6 (gD), and US7 (gI) coding regions. The ICP4 gene was previously identified as a corneal neovascularization determinant, validating the vQTLmap method. Further analysis detected an epistatic interaction for neovascularization between a segment of the unique long (UL) region and a segment of the inverted repeat short (IRS)/unique short (US) region. Ridge regression was used to identify MPWL-associated nonsynonymous SNPs in the UL1 (gL), UL2, UL4, UL49 (VP22), UL50, and ICP4 coding regions. The data provide additional insights into virulence gene and epistatic interaction discovery in HSV-1. IMPORTANCE Herpes simplex virus 1 (HSV-1) typically causes recurrent cold sores; however, it is also the leading source of infectious blindness in developed countries. Corneal neovascularization is critical for the progression of blinding ocular

  8. MRI in ocular drug delivery

    PubMed Central

    Li, S. Kevin; Lizak, Martin J.; Jeong, Eun-Kee

    2008-01-01

    Conventional pharmacokinetic methods for studying ocular drug delivery are invasive and cannot be conveniently applied to humans. The advancement of MRI technology has provided new opportunities in ocular drug-delivery research. MRI provides a means to non-invasively and continuously monitor ocular drug-delivery systems with a contrast agent or compound labeled with a contrast agent. It is a useful technique in pharmacokinetic studies, evaluation of drug-delivery methods, and drug-delivery device testing. Although the current status of the technology presents some major challenges to pharmaceutical research using MRI, it has a lot of potential. In the past decade, MRI has been used to examine ocular drug delivery via the subconjunctival route, intravitreal injection, intrascleral injection to the suprachoroidal space, episcleral and intravitreal implants, periocular injections, and ocular iontophoresis. In this review, the advantages and limitations of MRI in the study of ocular drug delivery are discussed. Different MR contrast agents and MRI techniques for ocular drug-delivery research are compared. Ocular drug-delivery studies using MRI are reviewed. PMID:18186077

  9. [Radiation therapy in simultaneous choroidal and brain metastases].

    PubMed

    Conill, C; Jorcano, S; Planas, I; Marruecos, J; Casas, F; Fontenla, J R

    2005-09-01

    Choroidal metastases from lung cancer can be the initial clinical manifestation of metastasic disease, although they generally coexist with at least two more metastasic sites. The most common symptom is decreased vision, however 20% of brain metastases can present with visual alterations. A differential diagnosis within brain metastases and/or choroidal is necessary. We present the case of a patient with lung cancer and decreased vision who was diagnosed as simultaneous choroidal and brain metastases. Radiation therapy (20Gy/5fractions) significantly improves decreased vision. This case shows that, although life expectancy of patients with metastasic lung cancer is short, an adequate diagnosis and treatment, can improve the quality of life of those patients.

  10. Choroid plexus in the central nervous system: biology and physiopathology.

    PubMed

    Strazielle, N; Ghersi-Egea, J F

    2000-07-01

    Choroid plexuses (CPs) are localized in the ventricular system of the brain and form one of the interfaces between the blood and the central nervous system (CNS). They are composed of a tight epithelium responsible for cerebrospinal fluid secretion, which encloses a loose connective core containing permeable capillaries and cells of the lymphoid lineage. In accordance with its peculiar localization between 2 circulating fluid compartments, the CP epithelium is involved in numerous exchange processes that either supply the brain with nutrients and hormones, or clear deleterious compounds and metabolites from the brain. Choroid plexuses also participate in neurohumoral brain modulation and neuroimmune interactions, thereby contributing greatly in maintaining brain homeostasis. Besides these physiological functions, the implication of choroid plexuses in pathological processes is increasingly documented. In this review, we focus on some of the novel aspects of CP functions in relation to brain development, transfer of neuro-humoral information, brain/immune system interactions, brain aging, and cerebral pharmaco-toxicology.

  11. Neuroendoscopic removal of large choroid plexus cyst: a case report.

    PubMed

    Jeon, Jin Ho; Lee, Sang Weon; Ko, Jun Kyeong; Choi, Byeong Gwan; Cha, Seung Heon; Song, Geun Seong; Choi, Chang Hwa

    2005-04-01

    Choroid plexus cysts (CPCs) are the most common neuroepithelial cysts, occurring in more than 50% of some autopsy series. They are typically small and asymptomatic and are discovered incidentally in older patients, usually in the trigone of the lateral ventricle. Symptomatic CPCs (usually exceptionally large, 2-8 cm) are rare. The authors report a case of large symptomatic choroid plexus cyst, located in the trigone of the right lateral ventricle in a 26-yr-old man who presented with headache and vomiting. The patient underwent endoscopic removal through a burr hole placed 3 cm from the midline and just behind the hair line. The histological examination of the cyst wall was consistent with choroid epithelium. Despite of postoperative intraventricular hemorrhage and catheter infection, he discharged home without neurologic deficits. The endoscopic fenestration rather than excision should be considered as the first surgical procedure because the goal of treatment is shrinkage of the cyst until normal cerebrospinal fluid flow is restored.

  12. Development of the choroid plexus and blood-CSF barrier

    PubMed Central

    Liddelow, Shane A.

    2015-01-01

    Well-known as one of the main sources of cerebrospinal fluid (CSF), the choroid plexuses have been, and still remain, a relatively understudied tissue in neuroscience. The choroid plexus and CSF (along with the blood-brain barrier proper) are recognized to provide a robust protective effort for the brain: a physical barrier to impede entrance of toxic metabolites to the brain; a “biochemical” barrier that facilitates removal of moieties that circumvent this physical barrier; and buoyant physical protection by CSF itself. In addition, the choroid plexus-CSF system has been shown to be integral for normal brain development, central nervous system (CNS) homeostasis, and repair after disease and trauma. It has been suggested to provide a stem-cell like repository for neuronal and astrocyte glial cell progenitors. By far, the most widely recognized choroid plexus role is as the site of the blood-CSF barrier, controller of the internal CNS microenvironment. Mechanisms involved combine structural diffusion restraint from tight junctions between plexus epithelial cells (physical barrier) and specific exchange mechanisms across the interface (enzymatic barrier). The current hypothesis states that early in development this interface is functional and more specific than in the adult, with differences historically termed as “immaturity” actually correctly reflecting developmental specialization. The advanced knowledge of the choroid plexus-CSF system proves itself imperative to understand a range of neurological diseases, from those caused by plexus or CSF drainage dysfunction (e.g., hydrocephalus) to more complicated late-stage diseases (e.g., Alzheimer's) and failure of CNS regeneration. This review will focus on choroid plexus development, outlining how early specializations may be exploited clinically. PMID:25784848

  13. Retinal and choroidal oxygen saturation of the optic nerve head in open-angle glaucoma subjects by multispectral imaging

    PubMed Central

    Li, Gai-yun; Al-wesabi, Samer abdo; Zhang, Hong

    2016-01-01

    Abstract The aim of this study was to determine whether differences exist in oxygen supply to the optic nerve head (ONH) from the retinal and choroidal vascular layers in patients with primary open angle glaucoma (POAG) using multispectral imaging (MSI).This ia an observational, cross-sectional study. Multispectral images were acquired from 38 eyes of 19 patients with POAG, and 42 healthy eyes from 21 matched volunteers with Annidis’ RHA multispectral digital ophthalmoscopy. Superficial and deeper oxygen saturation of the optic disc was represented by the mean gray scale values on the retinal and choroidal oxy-deoxy maps, respectively. Statistical analysis was performed to detect differences in ONH oxygen saturation between the 2 groups. Oxygen saturation levels in the eyes of POAG patients with severe glaucoma were compared to those of fellow eyes from the same subjects. Linear correlation analysis was performed to assess the association between ONH oxygen saturation and systemic and ocular parameters. No statistical difference was found in retinal and choroidal oxygen saturation between the POAG and control groups. In the glaucoma patients, retinal oxygen saturation was lower for eyes with worse visual fields than in those with good visual fields (t = 4.009, P = 0.001). In POAG patients, retinal oxygen saturation was dependent on mean defect of visual field and retinal nerve fiber layer thickness (RNFLT) (r = 0.511, 0.504, P = 0.001, 0.001, respectively), whereas the choroid vasculature oxygen saturation was inversely related to RNFLT (r = −0.391, P = 0.015). An age-dependent increase in retinal oxygen saturation was found for both the POAG and control groups (r = 0.473, 0.410, P = 0.007, 0.003, respectively). MSI revealed a significant correlation between functional and structural impairments in glaucoma and retinal oxygen saturation. MSI could provide objective assessments of perfusion impairments of the glaucomatous ONH

  14. Retinal and choroidal oxygen saturation of the optic nerve head in open-angle glaucoma subjects by multispectral imaging.

    PubMed

    Li, Gai-Yun; Al-Wesabi, Samer Abdo; Zhang, Hong

    2016-12-01

    The aim of this study was to determine whether differences exist in oxygen supply to the optic nerve head (ONH) from the retinal and choroidal vascular layers in patients with primary open angle glaucoma (POAG) using multispectral imaging (MSI).This ia an observational, cross-sectional study.Multispectral images were acquired from 38 eyes of 19 patients with POAG, and 42 healthy eyes from 21 matched volunteers with Annidis' RHA multispectral digital ophthalmoscopy. Superficial and deeper oxygen saturation of the optic disc was represented by the mean gray scale values on the retinal and choroidal oxy-deoxy maps, respectively. Statistical analysis was performed to detect differences in ONH oxygen saturation between the 2 groups. Oxygen saturation levels in the eyes of POAG patients with severe glaucoma were compared to those of fellow eyes from the same subjects. Linear correlation analysis was performed to assess the association between ONH oxygen saturation and systemic and ocular parameters.No statistical difference was found in retinal and choroidal oxygen saturation between the POAG and control groups. In the glaucoma patients, retinal oxygen saturation was lower for eyes with worse visual fields than in those with good visual fields (t = 4.009, P = 0.001). In POAG patients, retinal oxygen saturation was dependent on mean defect of visual field and retinal nerve fiber layer thickness (RNFLT) (r = 0.511, 0.504, P = 0.001, 0.001, respectively), whereas the choroid vasculature oxygen saturation was inversely related to RNFLT (r = -0.391, P = 0.015). An age-dependent increase in retinal oxygen saturation was found for both the POAG and control groups (r = 0.473, 0.410, P = 0.007, 0.003, respectively).MSI revealed a significant correlation between functional and structural impairments in glaucoma and retinal oxygen saturation. MSI could provide objective assessments of perfusion impairments of the glaucomatous ONH. This is a

  15. Ocular surface reconstruction update.

    PubMed

    Shimmura, Shigeto; Tsubota, Kazuo

    2002-08-01

    Ocular surface reconstruction (OSR) is now a standard procedure in the treatment of severe ocular surface disorders. The past few years have revealed the long-term results of patients who were operated on during the early stages of OSR development, and we now have a more realistic view of the benefits and limits of the procedure. On the other hand, further understanding of the physiologic role played by the amniotic membrane (AM) has opened doors to further refined techniques in treating these patients. This review will introduce some of the major contributions made during the past years in the advancement of OSR. Clinically, we are at a stage of reviewing the pros and cons of the various transplantation techniques. Identification of factors crucial for a successful OSR procedure will further improve surgical results. Basic researchers are on the verge of identifying the so-called limbal stem cells, and further understanding of AM physiology will lead the way to tissue engineering techniques as another alternative in OSR surgery.

  16. Ocular surface temperature.

    PubMed

    Efron, N; Young, G; Brennan, N A

    1989-09-01

    A wide-field color-coded infra-red imaging device was applied to the measurement of i) the temperature profile across the ocular surface and ii) the temporal stability of central corneal temperature, on 21 subjects. The thermographs showed a pattern of ellipsoidal isotherms (major axis horizontal) approximately concentric about a temperature apex (coldest point) which was slightly inferior to the geometric center of the cornea (GCC). The GCC had a mean temperature (+/- SD) of 34.3 +/- 0.7 degrees C (range 32.8 to 35.4 degrees C). Temperature increased towards the periphery of the cornea with the limbus being 0.45 degrees C warmer than the GCC (p less than 0.0001). Following a blink, the GCC cooled at a mean (+/- SD) rate of 0.033 +/- 0.024 degrees C/s (p less than 0.0001) over the first 15s. Subjects whose corneas cooled more slowly following a blink demonstrated a greater capacity to avoid blinking for a prolonged period (p less than 0.05). This improved method of measuring ocular surface temperature has important applications in modeling corneal physiology and pathology.

  17. Nonhuman Primate Ocular Biometry

    PubMed Central

    Augusteyn, Robert C.; Maceo Heilman, Bianca; Ho, Arthur; Parel, Jean-Marie

    2016-01-01

    Purpose To examine ocular growth in nonhuman primates (NHPs) from measurements on ex vivo eyes. Methods We obtained NHP eyes from animals that had been killed as part of other studies or because of health-related issues. Digital calipers were used to measure the horizontal, vertical, and anteroposterior globe diameters as well as corneal horizontal and vertical diameters of excised globes from 98 hamadryas baboons, 551 cynomolgus monkeys, and 112 rhesus monkeys, at ages ranging from 23 to 360 months. Isolated lens sagittal thickness and equatorial diameter were measured by shadowphotogrammetry. Wet and fixed dry weights were obtained for lenses. Results Nonhuman primate globe growth continues throughout life, slowing toward an asymptotic maximum. The final globe size scales with negative allometry to adult body size. Corneal growth ceases at around 20 months. Lens diameter increases but thickness decreases with increasing age. Nonhuman primate lens wet and dry weight accumulation is monophasic, continuing throughout life toward asymptotic maxima. The dry/wet weight ratio reaches a maximum of 0.33. Conclusions Nonhuman primate ocular globe and lens growth differ in several respects from those in humans. Although age-related losses of lens power and accommodative amplitude are similar, lens growth and properties are different indicating care should be taken in extrapolating NHP observations to the study of human accommodation. PMID:26780314

  18. [A symptomatic choroid plexus cyst in the lateral ventricle].

    PubMed

    Darmoul, M; Zemmel, I; Bouhaouala, M H; Haouat, S; Khaldi, M; Zbiba, M

    1999-03-01

    Choroid plexus cyst is generally small and a relatively common finding at autopsy. Huge and symptomatic cysts are rare. Few cases are reported in the literature. We report one case of symptomatic choroid plexus cyst of the right lateral ventricle in a six month baby who presented with epilepsy. Cerebral CT scan and MRI showed a large cyst in the right lateral ventricle compressing the adjacent structures. Total removal of the cyst has been performed by a parieto-temporal approach. The course was uneventful.

  19. Ultrasonic localization of choroidal detachment associated with flat anterior chamber.

    PubMed

    Portney, G L; Kohl, J W

    1975-01-01

    In postoperative patients with flat anterior chambers and small pupils or dense media, A-scan and B-scan ultrasonography can be useful tools in establishing the proper etiologic diagnosis. By searching for the presence of a choroidal detachment and determining its full location, complete drainage of the suprachoroidal fluid can be accomplished satisfactorily should this form of surgical intervention become necessary. If sufficient evidence of a choroidal detachment is not found, then therapy can be more assuredly directed at relief of pupillary block or reduction of excessive fistulization, other causes of a flat chamber.

  20. Treatment Results in Serpiginous Choroiditis and Multifocal Serpiginoid Choroiditis Associated with Latent Tuberculosis

    PubMed Central

    Oray, Merih; Zakiev, Zaur; Çağatay, Tülin; Tuğal-Tutkun, İlknur

    2017-01-01

    Objectives: To compare the results of systemic antitubercular therapy (ATT) and immunomodulatory therapy (IMT) in patients with serpiginous choroiditis (SC) or multifocal serpiginoid choroiditis (MSC). Materials and Methods: The clinical records of 28 patients with SC and MSC were reviewed. Patients were divided into 2 groups according to the treatment applied. Group 1 included 12 patients with MSC and 5 with SC treated with ATT and corticosteroid (CS); group 2 included 9 patients with MSC and 2 with SC treated with conventional IMT, interferon alpha-2a, and/or CS monotherapy. Results: In group 1, clinical remission was achieved in 12/12 MSC and 3/5 SC (total 15/17) patients with administration of ATT for 1 year. Two patients (1 SC, 1 MSC) had reactivation 2 and 7 months after cessation of ATT. Two patients with recurrence after completion of ATT and 2 patients resistant to ATT received IMT ± CS therapy. In group 2, clinical remission was achieved in 7/9 MSC and 2/2 SC (total 9/11) patients after 1 year of treatment. Recurrent inflammation was observed in 2 MSC patients 2 and 112 months after initiation of therapy, but responded well to local/systemic CS or IMT modification, and clinical remission was achieved in 7.8±4.3 months. Cumulative dose of CS was higher in group 2 (p=0.057). Nine of 12 MSC patients treated with ATT and 4/9 MSC patients treated with IMT achieved remission (p=0.203). One of 5 SC patients treated with ATT and 2/2 SC patients treated with IMT achieved remission (p=0.142). Conclusion: Although a statistically significant result could not be achieved in this small case series, our results suggest that ATT may be an appropriate first choice in the treatment of MSC associated with latent tuberculosis, and may be administered in patients with SC who are unresponsive to IMT.

  1. Ocular involvement in pemphigus vulgaris.

    PubMed

    Akhyani, Maryam; Keshtkar-Jafari, Alireza; Chams-Davatchi, Cheyda; Lajevardi, Vahide; Beigi, Sara; Aghazadeh, Nessa; Rayati Damavandi, Maede; Arami, Shabnam

    2014-07-01

    Pemphigus vulgaris (PV) is an autoimmune disorder affecting the skin and mucous membranes. Ocular involvement in PV has been reported but its prevalence and clinical characteristics are not well defined. This prospective cross-sectional study of 103 PV patients was designed to determine the prevalence, clinical types and epidemiological trends of ocular involvement in a population of Iranian patients with PV. Ocular involvement was present in 17 (16.5%) patients. Conjunctivitis was the most prevalent type of ocular involvement (9/17, 52.9%), followed by erosion of the palpebral conjunctiva (7/17, 41.2%). Erosion of the bulbar conjunctiva was noted in only one patient (5.9%). The most commonly reported symptoms were eye irritation (76.5%) and redness (76.5%). No significant relation was found between ocular involvement and disease activity (partial remission or relapse). Mucoid discharge was significantly more common in patients with conjunctival erosions as compared to patients with conjunctivitis (P = 0.038). We conclude that ocular involvement is not rare in PV; 16.5% of PV patients develop ocular disease independent of the disease activity and extension. Conjunctivitis is the most common type of involvement, however, palpebral conjunctival erosion is more frequent than previously realized.

  2. High-resolution photoacoustic imaging of ocular tissues.

    PubMed

    Silverman, Ronald H; Kong, Fanting; Chen, Y C; Lloyd, Harriet O; Kim, Hyung Ham; Cannata, Jonathan M; Shung, K Kirk; Coleman, D Jackson

    2010-05-01

    Optical coherence tomography (OCT) and ultrasound (US) are methods widely used for diagnostic imaging of the eye. These techniques detect discontinuities in optical refractive index and acoustic impedance, respectively. Because these both relate to variations in tissue density or composition, OCT and US images share a qualitatively similar appearance. In photoacoustic imaging (PAI), short light pulses are directed at tissues, pressure is generated due to a rapid energy deposition in the tissue volume and thermoelastic expansion results in generation of broadband US. PAI thus depicts optical absorption, which is independent of the tissue characteristics imaged by OCT or US. Our aim was to demonstrate the application of PAI in ocular tissues and to do so with lateral resolution comparable to OCT. We developed two PAI assemblies, both of which used single-element US transducers and lasers sharing a common focus. The first assembly had optical and 35-MHz US axes offset by a 30 degrees angle. The second assembly consisted of a 20-MHz ring transducer with a coaxial optics. The laser emitted 5-ns pulses at either 532 nm or 1064 nm, with spot sizes at the focus of 35 microm for the angled probe and 20 microm for the coaxial probe. We compared lateral resolution by scanning 12.5 microm diameter wire targets with pulse/echo US and PAI at each wavelength. We then imaged the anterior segment in whole ex vivo pig eyes and the choroid and ciliary body region in sectioned eyes. PAI data obtained at 1064 nm in the near infrared had higher penetration but reduced signal amplitude compared to that obtained using the 532 nm green wavelength. Images were obtained of the iris, choroid and ciliary processes. The zonules and anterior cornea and lens surfaces were seen at 532 nm. Because the laser spot size was significantly smaller than the US beamwidth at the focus, PAI images had superior resolution than those obtained using conventional US.

  3. Ocular leech infestation

    PubMed Central

    Lee, Yueh-Chang; Chiu, Cheng-Jen

    2015-01-01

    This case report describes a female toddler with manifestations of ocular leech infestation. A 2-year-old girl was brought to our outpatient clinic with a complaint of irritable crying after being taken to a stream in Hualien 1 day previous, where she played in the water. The parents noticed that she rubbed her right eye a lot. Upon examination, the girl had good fix and follow in either eye. Slit-lamp examination showed conjunctival injection with a moving dark black–brown foreign body partly attached in the lower conjunctiva. After applying topical anesthetics, the leech, measuring 1 cm in length, was extracted under a microscope. The patient began using topical antibiotic and corticosteroid agents. By 1 week after extraction, the patient had no obvious symptoms or signs, except for a limited subconjunctival hemorrhage, and no corneal/scleral involvement was observed. PMID:25784786

  4. Ocular Screening System

    NASA Technical Reports Server (NTRS)

    1987-01-01

    Used to detect eye problems in children through analysis of retinal reflexes, the system incorporates image processing techniques. VISISCREEN's photorefractor is basically a 35 millimeter camera with a telephoto lens and an electronic flash. By making a color photograph, the system can test the human eye for refractive error and obstruction in the cornea or lens. Ocular alignment problems are detected by imaging both eyes simultaneously. Electronic flash sends light into the eyes and the light is reflected from the retina back to the camera lens. Photorefractor analyzes the retinal reflexes generated by the subject's response to the flash and produces an image of the subject's eyes in which the pupils are variously colored. The nature of a defect, where such exists, is identifiable by atrained observer's visual examination.

  5. Sports related ocular injuries.

    PubMed

    Mishra, Avinash; Verma, Ashok K

    2012-07-01

    Every year > 600,000 sports and recreation related eye injuries occur, out of which roughly 13,500 of these result in permanent loss of sight. Up to 90% of these sports related eye injuries are preventable by using adequate eye protection equipment. Protective eyewear is made of polycarbonate, a highly impact-resistant plastic which is now easily available as prescription and non-prescription eyewear and all players should be encouraged to use them. The medical officers by educating their patients regarding the risks of eye injuries in various sports and the confirmed benefits of using protective equipment have the potential to prevent injury to over thousands of eyes every year. The medical fraternity can also play a very important role in educating the coaches, parents, and children and thus put an end to unnecessary blindness and vision loss from sports related ocular injuries, therefore ensuring a lifetime of healthy vision.

  6. Photorefractor ocular screening system

    NASA Technical Reports Server (NTRS)

    Richardson, John R. (Inventor); Kerr, Joseph H. (Inventor)

    1987-01-01

    A method and apparatus for detecting human eye defects, particularly detection of refractive error is presented. Eye reflex is recorded on color film when the eyes are exposed to a flash of light. The photographs are compared with predetermined standards to detect eye defects. The base structure of the ocular screening system is a folding interconnect structure, comprising hinged sections. Attached to one end of the structure is a head positioning station which comprises vertical support, a head positioning bracket having one end attached to the top of the support, and two head positioning lamps to verify precise head positioning. At the opposite end of the interconnect structure is a camera station with camera, electronic flash unit, and blinking fixation lamp, for photographing the eyes of persons being evaluated.

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

    PubMed Central

    2013-01-01

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

  8. Ocular anomaly in Atlantic midshipman Porichthys plectrodon (Batrachoidiformes: Batrachoididae) from the Mississippi Canyon, north-central Gulf of Mexico.

    PubMed

    Womble, M R; Bullard, S A

    2016-02-01

    The first record of an ocular anomaly in Atlantic midshipman Porichthys plectrodon (Batrachoidiformes: Batrachoididae) is reported from a specimen captured in the Mississippi Canyon. The anomalous specimen was bilaterally anophthalmic and the nape and dorsum were darkly pigmented but alizarin staining and histology revealed a complete eye embedded within the cranium beneath a markedly thickened dermal component of the cornea, along with seemingly minor elaboration of the choroid rete between the cornea and lens. Aetiology is indeterminate and beyond the scope of the study materials but barotrauma, infectious disease and previous wounding are doubtful.

  9. Ocular complications of diabetes mellitus

    PubMed Central

    Sayin, Nihat; Kara, Necip; Pekel, Gökhan

    2015-01-01

    Diabetes mellitus (DM) is a important health problem that induces ernestful complications and it causes significant morbidity owing to specific microvascular complications such as, retinopathy, nephropathy and neuropathy, and macrovascular complications such as, ischaemic heart disease, and peripheral vasculopathy. It can affect children, young people and adults and is becoming more common. Ocular complications associated with DM are progressive and rapidly becoming the world’s most significant cause of morbidity and are preventable with early detection and timely treatment. This review provides an overview of five main ocular complications associated with DM, diabetic retinopathy and papillopathy, cataract, glaucoma, and ocular surface diseases. PMID:25685281

  10. Ocular myasthenia gravis: A review

    PubMed Central

    Nair, Akshay Gopinathan; Patil-Chhablani, Preeti; Venkatramani, Devendra V; Gandhi, Rashmin Anilkumar

    2014-01-01

    Myasthenia gravis (MG) is a disease that affects the neuro-muscular junction resulting in classical symptoms of variable muscle weakness and fatigability. It is called the great masquerader owing to its varied clinical presentations. Very often, a patient of MG may present to the ophthalmologist given that a large proportion of patients with systemic myasthenia have ocular involvement either at presentation or during the later course of the disease. The treatment of ocular MG involves both the neurologist and ophthalmologist. Thus, the aim of this review was to highlight the current diagnosis, investigations, and treatment of ocular MG. PMID:25449931

  11. Ocular manifestations of feline herpesvirus.

    PubMed

    Andrew, S E

    2001-03-01

    Feline herpesvirus-1 (FHV-1) infection is ubiquitous in the domestic cat population worldwide. The most common clinical ocular manifestations of infection with FHV-1 are conjunctivitis and keratitis. This paper reviews the pathogenesis of feline herpesvirus-1 and discusses the various clinical ocular manifestations, diagnostic techniques and treatment of FHV-1-induced diseases. Ocular manifestations include: conjunctivitis, keratitis, stromal keratitis, keratoconjunctivitis sicca, ophthalmia neonatorium, symblepharon, corneal sequestrum, eosinophilic keratitis and anterior uveitis. Diagnostic techniques discussed include: virus isolation, fluorescent antibody testing, serum neutralising titers, ELISA and polymerase chain reaction. Various therapies are also discussed.

  12. X-Linked ocular albinism; Nettleship-Falls ocular albinism.

    PubMed

    Booth, Alexandria V; Soldano, Anthony C; Levine, Jonathan; Pomeranz, Miriam

    2008-05-15

    A 39-year-old man with foveal hypoplasia, nystagmus, and decreased visual acuity was found to have multiple, cutaneous, hypopigmented macules. Macromelanosomes were demonstrated in normal skin on histopathologic examination. The patient's constellation of findings along with a strong X-linked inheritance pattern in family members led to the diagnosis of X-linked ocular albinism, which is an uncommon condition that is characterized by congenital nystagmus, iris translucency, hypopigmentation of the ocular fundus, strabismus, foveal hypoplasia, photophobia, and impaired vision.

  13. 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. PMID:27625938

  14. Neovascular glaucoma treatment with extraction of anterior chamber fibrovascular tissue.

    PubMed

    Nadal, Jeroni; Carreras, Elisa; Kudsieh, Bachar; Canut, Maribel

    2013-08-01

    The use of antibody to vascular endothelial growth factor to treat neovascular glaucoma yields good anatomic results in most cases. However, this type of glaucoma can cause angle closure with decompensation of intraocular pressure secondary to fibrovascular tissue contraction in the anterior chamber. Our surgical technique treats the cause by removing the anterior chamber fibrous complex after administration of antibody to vascular endothelial growth factor, thus restoring the chamber angle.

  15. 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

  16. A new role for cofilin in retinal neovascularization

    PubMed Central

    Kumar, Raj; Janjanam, Jagadeesh; Singh, Nikhlesh K.; Rao, Gadiparthi N.

    2016-01-01

    ABSTRACT Pak1 plays an important role in several cellular processes, including cell migration, but its role in pathological angiogenesis is not known. Here, we have determined its role in pathological retinal angiogenesis using an oxygen-induced retinopathy (OIR) model. VEGFA induced phosphorylation of Pak1 and its effector cofilin in a manner that was dependent on time as well as p38MAPKβ (also known as MAPK11) in human retinal microvascular endothelial cells (HRMVECs). Depletion of the levels of any of these molecules inhibited VEGFA-induced HRMVEC F-actin stress fiber formation, migration, proliferation, sprouting and tube formation. In accordance with these observations, hypoxia induced Pak1 and cofilin phosphorylation with p38MAPKβ being downstream to Pak1 and upstream to cofilin in mouse retina. Furthermore, Pak1 deficiency abolished hypoxia-induced p38MAPKβ and cofilin phosphorylation and abrogated retinal endothelial cell proliferation, tip cell formation and neovascularization. In addition, small interfering RNA (siRNA)-mediated downregulation of p38MAPKβ or cofilin levels in the wild-type mouse retina also diminished endothelial cell proliferation, tip cell formation and neovascularization. Taken together, these observations suggest that, although the p38MAPKβ–Pak1–cofilin axis is required for HRMVEC migration, proliferation, sprouting and tubulogenesis, Pak1–p38MAPKβ–cofilin signaling is also essential for hypoxia-induced mouse retinal endothelial cell proliferation, tip cell formation and neovascularization. PMID:26857814

  17. Characterization of a Mouse Model of Hyperglycemia and Retinal Neovascularization

    PubMed Central

    Rakoczy, Elizabeth P.; Rahman, Ireni S. Ali; Binz, Nicolette; Li, Cai-Rui; Vagaja, Nermina N.; de Pinho, Marisa; Lai, Chooi-May

    2010-01-01

    One of the limitations of research into diabetic retinopathy is the lack of suitable animal models. To study how the two important factors—hyperglycemia and vascular endothelial growth factor—interact in diabetic retinopathy, the Akimba mouse (Ins2AkitaVEGF+/−) was generated by crossing the Akita mouse (Ins2Akita) with the Kimba mouse (VEGF+/+). C57Bl/6 and the parental and Akimba mouse lines were characterized by biometric measurements, histology, immunohistochemistry, and Spectralis Heidelberg retinal angiography and optical coherence tomography. The Akimba line not only retained the characteristics of the parental strains, such as developing hyperglycemia and retinal neovascularization, but developed higher blood glucose levels at a younger age and had worse kidney-body weight ratios than the Akita line. With aging, the Akimba line demonstrated enhanced photoreceptor cell loss, thinning of the retina, and more severe retinal vascular pathology, including more severe capillary nonperfusion, vessel constriction, beading, neovascularization, fibroses, and edema, compared with the Kimba line. The vascular changes were associated with major histocompatibility complex class II+ cellular staining throughout the retina. Together, these observations suggest that hyperglycemia resulted in higher prevalences of edema and exacerbated the vascular endothelial growth factor-driven neovascular and retinal changes in the Akimba line. Thus, the Akimba line could become a useful model for studying the interplay between hyperglycemia and vascular endothelial growth factor and for testing treatment strategies for potentially blinding complications, such as edema. PMID:20829433

  18. Topical Ranibizumab as a Treatment of Corneal Neovascularization

    PubMed Central

    Ferrari, Giulio; Dastjerdi, Mohammad H.; Okanobo, Andre; Cheng, Sheng-Fu; Amparo, Francisco; Nallasamy, Nambi; Dana, Reza

    2014-01-01

    Purpose To examine the effect of topical ranibizumab on clinically stable corneal neovascularization (NV). Methods This was a prospective, open-label, monocentric, uncontrolled, non-comparative study. Ten eyes of 9 patients with corneal NV received topical ranibizumab (1%) 4 times a day for 3 weeks with a follow-up of 16 weeks. The main corneal neovascularization outcome measures were: neovascular area (NA), the area occupied by the corneal neovessels; vessel caliber (VC), the mean diameter of the corneal neovessels; and invasion area (IA), the fraction of the total cornea area covered by the vessels. This study was conducted at the Massachusetts Eye and Ear Infirmary, Boston, MA, USA. Results Statistically significant decreases in NA (55.3%, P<0.001), which lasted through 16 weeks, and VC (59%, P<0.001), which continued to improve up to week 16, were observed after treatment. No significant decrease was observed in IA (12.3%, P=0.49). There was no statistically significant change in visual acuity or intraocular pressure. No adverse events ascribed to the treatment were noted. Conclusions Topical application of ranibizumab is effective in reducing the severity of corneal NV in the context of established corneal NV, mostly through decrease in VC rather than IA. PMID:23407316

  19. miR-146a is upregulated during retinal pigment epithelium (RPE)/choroid aging in mice and represses IL-6 and VEGF-A expression in RPE cells

    PubMed Central

    Hao, Yi; Zhou, Qinbo; Ma, Jing; Zhao, Yun; Wang, Shusheng

    2016-01-01

    Purpose MicroRNA-146a (miR-146a) has been proposed as a marker for age-associated inflammation, or “inflammaging”, acting as a negative regulator of cellular senescence and pro-inflammatory signaling pathways. However, the regulation and function of miR-146 during ocular aging remains unclear. Here we propose that miR-146 is regulated during aging of the retina and choroid, and functions in retinal pigment epithelial (RPE) cells to regulate key genes involved in inflammation and angiogenesis. Methods The expression of miR-146a and miR-146b was examined in the neuroretina and RPE/choroid in mice aged from 2 months to 24 months. Then, the effect of synthetic miR-146a mimetic on IL-6 and VEGF-A expression was analyzed in RPE cells treated with and without TNF-α. Results miR-146a and miR-146b was upregulated during aging of RPE/choroid but not neuroretina, supporting tissue-specific regulation of aging-related miRNAs in retinal tissues. Overexpression of miR-146a by miRNA mimics inhibited VEGF-A and TNF-α-induced IL-6 expression. Conclusions Elevation of miR-146a and miR-146b in the aging RPE/choroid but not neuroretina suggests a role for miRNAs in inflammaging in the RPE/choroid. miR-146a overexpression inhibits the expression IL-6 and VEGF-A in the RPE cells, supporting a negative feedback regulation mechanism by which inflammatory pathways may be dysregulated in RPE during aging. PMID:27917303

  20. Assessment of therapeutic options for reducing alkali burn-induced corneal neovascularization and inflammation.

    PubMed

    Bakunowicz-Łazarczyk, Alina; Urban, Beata

    2016-03-01

    This article aims to review and provide the current knowledge of the possibilities of topical treatment of corneal neovascularization due to alkali burns, evidenced by laboratory experiments, in vitro studies, and clinical trials published in the specialized literature. Authors present clinically relevant treatment of corneal neovascularization used in clinical practice, potential antiangiogenic topical therapeutics against corneal neovascularization, which are under investigation, and anti-angiogenic gene-therapy.

  1. Ocular tropism of respiratory viruses.

    PubMed

    Belser, Jessica A; Rota, Paul A; Tumpey, Terrence M

    2013-03-01

    Respiratory viruses (including adenovirus, influenza virus, respiratory syncytial virus, coronavirus, and rhinovirus) cause a broad spectrum of disease in humans, ranging from mild influenza-like symptoms to acute respiratory failure. While species D adenoviruses and subtype H7 influenza viruses are known to possess an ocular tropism, documented human ocular disease has been reported following infection with all principal respiratory viruses. In this review, we describe the anatomical proximity and cellular receptor distribution between ocular and respiratory tissues. All major respiratory viruses and their association with human ocular disease are discussed. Research utilizing in vitro and in vivo models to study the ability of respiratory viruses to use the eye as a portal of entry as well as a primary site of virus replication is highlighted. Identification of shared receptor-binding preferences, host responses, and laboratory modeling protocols among these viruses provides a needed bridge between clinical and laboratory studies of virus tropism.

  2. [Ocular changes in dialysis patients].

    PubMed

    Popa, M; Nicoară, S

    2000-01-01

    The study analyzes the ocular aspects in patients receiving hemodialysis, in order to define the importance of the ophthalmological exam as prognosis and follow-up parameter. The prospective study includes 84 patients with renal insufficiency who received hemodialysis between 1994-1998. The ocular aspects and their connection with the dialysis and the basic disease are described and analyzed. The most important were the retinal vascular complications: hypertensive retinopathy, anterior optic ischaemic neuropathy, central retinal artery occlusion, diabetic retinopathy.

  3. 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

  4. Ocular toxicity of targeted therapies.

    PubMed

    Renouf, Daniel J; Velazquez-Martin, Juan P; Simpson, Rand; Siu, Lillian L; Bedard, Philippe L

    2012-09-10

    Molecularly targeted agents are commonly used in oncology practice, and many new targeted agents are currently being tested in clinical trials. Although these agents are thought to be more specific and less toxic then traditional cytotoxic chemotherapy, they are associated with a variety of toxicities, including ocular toxicity. Many of the molecules targeted by anticancer agents are also expressed in ocular tissues. We reviewed the literature for described ocular toxicities associated with both approved and investigational molecularly targeted agents. Ocular toxicity has been described with numerous approved targeted agents and also seems to be associated with several classes of agents currently being tested in early-phase clinical trials. We discuss the proposed pathogenesis, monitoring guidelines, and management recommendations. It is important for oncologists to be aware of the potential for ocular toxicity, with prompt recognition of symptoms that require referral to an ophthalmologist. Ongoing collaboration between oncologists and ocular disease specialists is critical as the use of molecularly targeted agents continues to expand and novel targeted drug combinations are developed.

  5. Changes in Choroidal Thickness follow the RNFL Changes in Leber’s Hereditary Optic Neuropathy

    PubMed Central

    Borrelli, Enrico; Triolo, Giacinto; Cascavilla, Maria Lucia; La Morgia, Chiara; Rizzo, Giovanni; Savini, Giacomo; Balducci, Nicole; Nucci, Paolo; Giglio, Rosa; Darvizeh, Fatemeh; Parisi, Vincenzo; Bandello, Francesco; Sadun, Alfredo A.; Carelli, Valerio; Barboni, Piero

    2016-01-01

    Leber’s hereditary optic neuropathy (LHON) is typically characterized by vascular alterations in the acute phase. The aim of this study was to evaluate choroidal changes occurring in asymptomatic, acute and chronic stages of LHON. We enrolled 49 patients with LHON, 19 with Dominant Optic Atrophy (DOA) and 22 healthy controls. Spectral Domain-Optical Coherence Tomography (SD-OCT) scans of macular and peripapillary regions were performed in all subjects, to evaluate macular and peripapillary choroidal thickness, and retinal nerve fiber layer (RNFL) thicknes. Macular and peripapillary choroidal thicknesses were significantly increased in the acute LHON stage. On the contrary, macular choroidal thickness was significantly reduced in the chronic stage. Furthermore, peripapillary choroidal thickness was decreased in chronic LHON and in DOA. Both RNFL and choroid had the same trend (increased thickness, followed by thinning), but RNFL changes preceded those affecting the choroid. In conclusion, our study quantitatively demonstrated the involvement of the choroid in LHON pathology. The increase in choroidal thickness is a feature of the LHON acute stage, which follows the thickening of RNFL. Conversely, thinning of the choroid is the common outcome in chronic LHON and in DOA. PMID:27853297

  6. Galectin-3 Inhibition by a Small-Molecule Inhibitor Reduces Both Pathological Corneal Neovascularization and Fibrosis

    PubMed Central

    Chen*, Wei-Sheng; Cao, Zhiyi; Leffler, Hakon; Nilsson, Ulf J.; Panjwani, Noorjahan

    2017-01-01

    Purpose Corneal neovascularization and scarring commonly lead to significant vision loss. This study was designed to determine whether a small-molecule inhibitor of galectin-3 can inhibit both corneal angiogenesis and fibrosis in experimental mouse models. Methods Animal models of silver nitrate cautery and alkaline burn were used to induce mouse corneal angiogenesis and fibrosis, respectively. Corneas were treated with the galectin-3 inhibitor, 33DFTG, or vehicle alone and were processed for whole-mount immunofluorescence staining and Western blot analysis to quantify the density of blood vessels and markers of fibrosis. In addition, human umbilical vein endothelial cells (HUVECs) and primary human corneal fibroblasts were used to analyze the role of galectin-3 in the process of angiogenesis and fibrosis in vitro. Results Robust angiogenesis was observed in silver nitrate–cauterized corneas on day 5 post injury, and markedly increased corneal opacification was demonstrated in alkaline burn–injured corneas on days 7 and 14 post injury. Treatment with the inhibitor substantially reduced corneal angiogenesis and opacification with a concomitant decrease in α-smooth muscle actin (α-SMA) expression and distribution. In vitro studies revealed that 33DFTG inhibited VEGF-A–induced HUVEC migration and sprouting without cytotoxic effects. The addition of exogenous galectin-3 to corneal fibroblasts in culture induced the expression of fibrosis-related proteins, including α-SMA and connective tissue growth factor. Conclusions Our data provide proof of concept that targeting galectin-3 by the novel, small-molecule inhibitor, 33DFTG, ameliorates pathological corneal angiogenesis as well as fibrosis. These findings suggest a potential new therapeutic strategy for treating ocular disorders related to pathological angiogenesis and fibrosis. PMID:28055102

  7. Human ocular biometry☆

    PubMed Central

    Augusteyn, Robert C.; Nankivil, Derek; Mohamed, Ashik; Maceo, Bianca; Pierre, Faradia; Parel, Jean-Marie

    2012-01-01

    The aim of this study was to examine growth of the human eye globe and cornea from early in gestation to late in adult life. Globe antero-posterior length, horizontal and vertical diameters, corneal horizontal and vertical (white to white) diameters and posterior pole to limbus distances were measured using digital calipers (±0.01 mm) in 541 postmortem eyes. Additional pre- and postnatal data for some of the dimensions were obtained from the literature. All dimensions examined increase rapidly during prenatal development but postnatal growth differs. Growth of globe antero-posterior length, vertical and horizontal diameters as well as corneal vertical and horizontal diameters stops within 1 year after birth. Logistic analysis is consistent with an asymptotic prenatal growth mode and no further growth after its completion around 1 year after birth. Horizontal and vertical globe diameters are the same at all ages but the corneal horizontal diameter is always larger than the vertical diameter. No differences could be detected between males and females in any of the ocular dimensions. Globe and corneal growth take place primarily during the prenatal growth mode and dimensions reach their maxima, shortly after birth. It is suggested that cessation of a growth stimulating signal at birth marks the end of the prenatal growth mode and that the small increases over the next year are due to cells already stimulated. Male and female eyes of the same age have the same globe and cornea dimensions. PMID:22819768

  8. 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.

  9. Is Spectral-Domain Optical Coherence Tomography Essential for Flexible Treatment Regimens with Ranibizumab for Neovascular Age-Related Macular Degeneration?

    PubMed Central

    Ozkaya, Abdullah; Agca, Alper; Ozgurhan, Engin Bilge; Karakucuk, Yalcin; Yazici, Ahmet Taylan; Demirok, Ahmet

    2013-01-01

    Purpose. To evaluate the ability of spectral-domain optical coherence tomography to detect subtle amounts of retinal fluid when the choroidal neovascularization is detected as inactive via time-domain optical coherence tomography and clinical examination in neovascular age-related macular degeneration (nAMD) patients. Methods. Forty-nine eyes of 49 patients with nAMD after ranibizumab treatment were included in this cross-sectional, prospective study. All patients were imaged with TD-OCT and SD-OCT at the same visit one month after a ranibizumab injection. The presence of subretinal, intraretinal, and subretinal pigment epithelium fluid (subRPE) in SD-OCT was evaluated; also mean central retinal thickness (CRT) and the rate of vitreoretinal surface disorders detected via the two devices were evaluated. Results. The mean CRT via TD-OCT and SD-OCT was 218.1 ± 51.3 and 325.7 ± 78.8 microns. Sixteen patients (32.6%) showed any kind of retinal fluid via SD-OCT. In detail, 8 patients (16.3%) showed subretinal fluid, 10 patients (20.4%) showed intraretinal fluid, and 3 patients (6.1%) showed SubRPE fluid. The ability of detecting vitreoretinal surface disorders was comparable between the two devices, except vitreomacular traction. Conclusion. SD-OCT is essential for the nAMD patients who are on an as-needed treatment regimen with ranibizumab. Only TD-OCT and clinical examination may cause insufficient treatment in this group of patients. PMID:24324880

  10. [Steroid induced ocular hypertension and glaucoma].

    PubMed

    Călugăru, D; Călugăru, M

    2009-01-01

    Steroid induced ocular hypertension and glaucoma represent iatrogenic changes of pharmacogenic nature. They are mainly due to exogenous steroids following ocular periocular, intravitreal and systemic administration. Elevated ocular pressure is brought about by structural trabecular changes as well as obstruction of the outflow ways of the aqueous humor localized within the trabecular juxtacanalicular area. Although mostly raised ocular pressure spontaneously descends to basal values after ceasing the steroid therapy, progressive optic nerve damages and glaucomatous visual field defects may occur. Therapy of steroid induced ocular hypertension and glaucoma is similar to that of ocular hypertension and primary open-angle glaucoma.

  11. Mathematical modeling of laser-induced transsclerar ocular hyperthermia

    NASA Astrophysics Data System (ADS)

    Comander, Jason I.; Parel, Jean-Marie A.; Robinson, David S.; Manns, Fabrice; Denham, David B.; Rol, Pascal O.; Murray, Timothy G.

    1996-05-01

    Choroidal melanoma is the most common primary malignant ocular tumor, yet none of the several available treatments is wholly successful. One therapy recently tried in humans was transpupillary thermotherapy. In this procedure, an 810 nm wavelength laser beam passes through the cornea, aqueous, lens, and vitreous to be absorbed by the tumor in the back of the eye. The results of transpupillary thermotherapy were encouraging, but in some patients only the anterior portion of the tumor was necrosed while the center and posterior portions remained viable. The new treatment modality proposed in this study is similar in concept to transpupillary thermotherapy, but we propose to apply the laser energy through the sclera onto the posterior portion of the tumor, known as the tumor bed. At infrared wavelengths, sclera has excellent transmission characteristics, while most ocular tumors are mildly absorbing. Some of the laser energy is absorbed in the posterior portion of the tumor, but some transmission of the energy through the tumor allows the anterior portion of the tumor to be heated as well. In qualitative terms, this scheme sounds appealing, but it is not yet known whether it will fulfill the quantitative requirements required to achieve the appropriate biological response -- that is, raising the temperature of the tumor to the level which causes cell necrosis (greater than or equal to 43 degrees Celsius) for the appropriate amount of time, without causing photocoagulation of the tumor (approximately equal to 60 degrees Celsius) or damage to the sclera (approximately equal to 55 degrees Celsius). The calculation of temperature distribution is a complicated matter, however, because the actual result of a rise in temperature happens only after the applied laser light has undergone several physical processes.

  12. 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.

  13. Novel micelle carriers for cyclosporin A topical ocular delivery: in vivo cornea penetration, ocular distribution and efficacy studies.

    PubMed

    Di Tommaso, Claudia; Bourges, Jean-Louis; Valamanesh, Fatemeh; Trubitsyn, Gregory; Torriglia, Alicia; Jeanny, Jean-Claude; Behar-Cohen, Francine; Gurny, Robert; Möller, Michael

    2012-06-01

    Cornea transplantation is one of the most performed graft procedures worldwide with an impressive success rate of 90%. However, for "high-risk" patients with particular ocular diseases in addition to the required surgery, the success rate is drastically reduced to 50%. In these cases, cyclosporin A (CsA) is frequently used to prevent the cornea rejection by a systemic treatment with possible systemic side effects for the patients. To overcome these problems, it is a challenge to prepare well-tolerated topical CsA formulations. Normally high amounts of oils or surfactants are needed for the solubilization of the very hydrophobic CsA. Furthermore, it is in general difficult to obtain ocular therapeutic drug levels with topical instillations due to the corneal barriers that efficiently protect the intraocular structures from foreign substances thus also from drugs. The aim of this study was to investigate in vivo the effects of a novel CsA topical aqueous formulation. This formulation was based on nanosized polymeric micelles as drug carriers. An established rat model for the prevention of cornea graft rejection after a keratoplasty procedure was used. After instillation of the novel formulation with fluorescent labeled micelles, confocal analysis of flat-mounted corneas clearly showed that the nanosized carriers were able to penetrate into all corneal layers. The efficacy of a 0.5% CsA micelle formulation was tested and compared to a physiological saline solution and to a systemic administration of CsA. In our studies, the topical CsA treatment was carried out for 14 days, and the three parameters (a) cornea transparency, (b) edema, and (c) neovascularization were evaluated by clinical observation and scoring. Compared to the control group, the treated group showed a significant higher cornea transparency and significant lower edema after 7 and 13 days of the surgery. At the end point of the study, the neovascularization was reduced by 50% in the CsA-micelle treated

  14. Alternative Dose for Choroidal Melanoma Treated With an Iodine-125 Radioactive Plaque: A Single-Institution Retrospective Study

    SciTech Connect

    Saconn, Paul A.; Gee, Christopher J.; Greven, Craig M.; McCoy, Thomas P.; Ekstrand, Kenneth E.; Greven, Kathryn M.

    2010-11-01

    Purpose: The Collaborative Ocular Melanoma Study (COMS) established iodine-125 plaque brachytherapy as an accepted standard treatment for medium-size choroidal melanoma. In the COMS, the prescription dose was 85 Gy. This is a retrospective review of our outcomes in patients treated with lower doses than those used in the COMS. Methods and Materials: From 1990 to 2004, 62 patients were treated with iodine-125 plaque brachytherapy for choroidal melanoma. COMS eye plaques were used with dose prescribed to the apex of the tumor. The median and average dose rates at the tumor apex were 63.5 cGy/h and 62.7 cGy/h, respectively. The median and average total doses were 63.0 Gy and 62.5 Gy (range, 56-69 Gy), respectively. The median and mean durations of implant were 100.0 hours and 101.1 hours (range, 71-165 hours). Results: Median follow-up time was 58.2 months. The 5-year outcomes including overall survival, disease-free survival, cause-specific survival, local failure, secondary enucleation rate, and visual acuity (VA) <20/200 were estimated using the Kaplan-Meier method. Overall, there were 7 local failures, 4 distant failures, and 10 secondary enucleations (6 due to local failure and 4 due to treatment complications). Univariate analysis was performed to identify significant prognostic factors associated with disease-free survival (baseline VA in tumor eye, tumor shape), cause-specific survival (diabetic retinopathy), local failure (none found), secondary enucleation rate (diabetic retinopathy, basal tumor dimension) and VA <20/200 (diabetic retinopathy, tumor shape, age, retinal detachment, treatment depth, and history of vision-limiting condition). Conclusions: Our survival and local control outcomes are comparable to those of the COMS. However, VA at 5 years seems to be better. Lower doses of radiation could potentially lead to better visual outcomes.

  15. 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.

  16. Bilateral choroidal excavation in best vitelliform macular dystrophy.

    PubMed

    Parodi, Maurizio Battaglia; Zucchiatti, Ilaria; Fasce, Francesco; Bandello, Francesco

    2014-02-14

    Focal choroidal excavation (FCE) has recently been described as one or more localized areas of choroidal excavation on spectral-domain optical coherence tomography (SD-OCT). The authors describe a case of bilateral FCE in Best vitelliform macular dystrophy (VMD). SD-OCT revealed FCE in both eyes characterized by interruption of the internal segment-outer segment junction and the presence of subretinal hyporeflective space. This is the first report describing bilateral FCE in a distinct macular disorder and specifically with VMD. Future investigations are warranted to ascertain the involvement of other macular dystrophies with atrophic evolution and the impact of FCE on the clinical course. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:e8-e10.].

  17. Choroid plexus cyst development and growth following ventricular shunting.

    PubMed

    Binning, Mandy J; Couldwell, William T

    2008-01-01

    Choroid plexus cysts are typically incidental, asymptomatic cysts. They have been reported to hemorrhage and grow, causing symptoms of obstruction. However, growth and multiplication has not been reported following ventriculoperitoneal shunt procedures. A 66-year-old woman initially underwent a suboccipital retrosigmoid craniotomy for resection of a large petroclival meningioma. Preoperatively, the patient had hydrocephalus. After surgery the patient required a ventriculoperitoneal shunt. Two years after the initial shunting procedure, imaging demonstrated significant growth of new bilateral choroid plexus cysts as compared with pre-shunt imaging. Post-shunt imaging also demonstrated evidence of diffuse dural enhancement characteristic of intracranial hypotension. Despite radiographic growth and multiplication of the cysts, the patient was clinically asymptomatic and had a good neurological outcome.

  18. Cerebellopontine angle arachnoid cyst containing ectopic choroid plexus--case report.

    PubMed

    Singleton, William G B; Lawrence, Tim; Green, Alex L; Jeans, Alex; Kerr, Richard S C

    2010-05-01

    We present a rare and interesting case of a cerebellopontine angle cyst containing ectopic choroid plexus tissue in a 26 year-old female. Surgical resection was performed, and histological examination confirmed the presence of choroid plexus in the cyst wall. This is the first reported case of ectopic choroid plexus at the cerebellopontine angle in an adult. We present the case and review the literature.

  19. Presumed ocular bartonellosis

    PubMed Central

    Kerkhoff, F; Ossewaarde, J; de Loos, W S; Rothova, A

    1999-01-01

    BACKGROUND—The spectrum of diseases caused by Bartonella henselae continues to expand and ocular involvement during this infection is being diagnosed with increasing frequency.
METHODS—The clinical features and visual prognosis for 13 patients with intraocular inflammatory disease and laboratory evidence of bartonellosis were investigated. There were nine patients with neuroretinitis and four with panuveitis with positive antibody titres against B henselae determined by an enzyme immunoassay (IgG exceding 1:900 and/or IgM exceeding 1:250).
RESULTS—Positive IgG levels were found for eight patients and positive IgM levels for five. Despite animal exposure of 10 patients, only two (IgG positive) cases had systemic symptoms consistent with the diagnosis of cat scratch disease. Pathological fluorescein leakage of the optic disc was observed in all affected eyes. At 6 months' follow up, 3/18 (17%) affected eyes had a visual acuity of less than 20/100, owing to optic disc atrophy and cystoid macular oedema. 12 patients (17 eyes) were treated with antibiotics; visual acuity improved two or more Snellen lines for 9/17 (53%) eyes.
CONCLUSIONS—The possibility of B henselae infection should be considered in patients with neuroretinitis and panuveitis (especially in cases with associated optic nerve involvement) even in the absence of systemic symptoms typical for cat scratch disease.

 Keywords: bartonellosis; Bartonella henselae; intraocular inflammatory disease; cat scratch disease PMID:10365031

  20. Purinergic receptors in ocular inflammation.

    PubMed

    Guzman-Aranguez, Ana; Gasull, Xavier; Diebold, Yolanda; Pintor, Jesús

    2014-01-01

    Inflammation is a complex process that implies the interaction between cells and molecular mediators, which, when not properly "tuned," can lead to disease. When inflammation affects the eye, it can produce severe disorders affecting the superficial and internal parts of the visual organ. The nucleoside adenosine and nucleotides including adenine mononucleotides like ADP and ATP and dinucleotides such as P(1),P(4)-diadenosine tetraphosphate (Ap4A), and P(1),P(5)-diadenosine pentaphosphate (Ap5A) are present in different ocular locations and therefore they may contribute/modulate inflammatory processes. Adenosine receptors, in particular A2A adenosine receptors, present anti-inflammatory action in acute and chronic retinal inflammation. Regarding the A3 receptor, selective agonists like N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine (CF101) have been used for the treatment of inflammatory ophthalmic diseases such as dry eye and uveoretinitis. Sideways, diverse stimuli (sensory stimulation, large intraocular pressure increases) can produce a release of ATP from ocular sensory innervation or after injury to ocular tissues. Then, ATP will activate purinergic P2 receptors present in sensory nerve endings, the iris, the ciliary body, or other tissues surrounding the anterior chamber of the eye to produce uveitis/endophthalmitis. In summary, adenosine and nucleotides can activate receptors in ocular structures susceptible to suffer from inflammatory processes. This involvement suggests the possible use of purinergic agonists and antagonists as therapeutic targets for ocular inflammation.

  1. Ocular Outcomes Comparison Between 14- and 70-day Head-down Tilt Bed Rest

    NASA Technical Reports Server (NTRS)

    Cromwell, R.L.; Taibbi, G.; Zanello, S.B.; Yarbough, P.O.; Ploutz-Snyder, R.J.; Vizzen, G.

    2015-01-01

    INTRODUCTION: Ophthalmological changes, including optic disc edema with optic nerve sheath distension, posterior globe flattening with hyperopic shift, choroidal folds and cotton wool spots have been detected in some astronauts involved in long-duration spaceflights. (sup 1) It is hypothesized that elevated intracranial pressure resulting from microgravity-induced cephalad fluid shifts may be responsible for most of these findings. Head-down tilt bed rest (HTDBR) is a ground-based microgravity analog which also produces cephalad fluid shifts. It is conceivable that prolonged HDTBR exposure may induce ocular changes similar to those experienced in microgravity. Therefore, the purpose of the present study was to compare structural and functional ocular outcomes between 14- and 70-day HDTBR in healthy human subjects. It is hypothesized that 70-d HDTBR induced ocular changes of greater magnitude as compared to 14-d HDTBR. METHODS: Two HDTBR studies were conducted at the NASA Flight Analogs Research Unit, located at The University of Texas Medical Branch at Galveston, TX. Identical NASA standard screening procedures and BR conditions (e.g., strict sleep-wake cycle, standardized diet, continuous video monitoring) were implemented in both studies. Participants spent 14 and/or 70 consecutive days in a 6deg HDT position and did not engage in exercise. Subjects received weekly ocular examinations before, during, and after HDTBR. Ocular testing included: distance and near best-corrected visual acuity (BCVA), cycloplegic refraction, intraocular pressure (IOP) measurement, color vision, red dot test, modified Amsler grid test, confrontational visual field, color fundus photography and Spectral-domain OCT scans of the macula and the optic disc. Pre/post HDTBR differences between the two studies will be evaluated for BCVA, spherical equivalent, IOP, retinal nerve fiber layer (RNFL) thickness and macular OCT parameters. RESULTS: 16 (12 males and 4 females) and 6 (5 males and 1

  2. Effects of heat stress on ocular blood flow during exhaustive exercise.

    PubMed

    Ikemura, Tsukasa; Hayashi, Naoyuki

    2014-01-01

    The hypothesis that heat stress reduces the ocular blood flow response to exhaustive exercise was tested by measuring ocular blood flow, blood pressure, and end- tidal carbon dioxide partial pressure (PETCO2) in 12 healthy males while they performed cycle ergometer exercise at 75% of the maximal heart rate at ambient temperatures of 20°C (control condition) and 35°C (heat condition), until exhaustion. The blood flows in the retinal and choroidal vasculature (RCV), the superior temporal retinal arteriole (STRA) and the superior nasal retinal arteriole (SNRA) were recorded at rest and at 6 and 16 min after the start of exercise period and at exhaustion [after 16 ± 2 min (mean ± SE) and 24 ± 3 min of exercise in the heat and control condition, respectively]. The mean arterial pressure at exhaustion was significantly lower in the heat condition than in the control condition at both 16 min and exhaustion. The degree of PETCO2 reduction did not differ significantly between the two thermal conditions at either 16 min or exhaustion. The blood flow velocity in the RCV significantly increased from the resting baseline value at 6 min in both thermal conditions (32 ± 6% and 25 ± 5% at 20°C and 35°C, respectively). However, at 16 min the increase in RCV blood flow velocity had returned to the resting baseline level only in the heat condition. At exhaustion, the blood flows in the STRA and SNRA had decreased significantly from the resting baseline value in the heat condition (STRA: -19 ± 5% and SNRA: -30 ± 6%), and SNRA blood flow was lower than that in the control condition (-14 ± 6% vs -30 ± 6% at 20°C and 35°C, respectively), despite the finding that both thermal conditions induced the same reductions in PETCO2 and vascular conductance. These findings suggested that the heat condition decreases or suppresses ocular blood flow via attenuation of pressor response during exhaustive exercise. Key PointsThe ocular (retinal and choroidal) blood flow response to

  3. Effects of Heat Stress on Ocular Blood Flow During Exhaustive Exercise

    PubMed Central

    Ikemura, Tsukasa; Hayashi, Naoyuki

    2014-01-01

    The hypothesis that heat stress reduces the ocular blood flow response to exhaustive exercise was tested by measuring ocular blood flow, blood pressure, and end- tidal carbon dioxide partial pressure (PETCO2) in 12 healthy males while they performed cycle ergometer exercise at 75% of the maximal heart rate at ambient temperatures of 20°C (control condition) and 35°C (heat condition), until exhaustion. The blood flows in the retinal and choroidal vasculature (RCV), the superior temporal retinal arteriole (STRA) and the superior nasal retinal arteriole (SNRA) were recorded at rest and at 6 and 16 min after the start of exercise period and at exhaustion [after 16 ± 2 min (mean ± SE) and 24 ± 3 min of exercise in the heat and control condition, respectively]. The mean arterial pressure at exhaustion was significantly lower in the heat condition than in the control condition at both 16 min and exhaustion. The degree of PETCO2 reduction did not differ significantly between the two thermal conditions at either 16 min or exhaustion. The blood flow velocity in the RCV significantly increased from the resting baseline value at 6 min in both thermal conditions (32 ± 6% and 25 ± 5% at 20°C and 35°C, respectively). However, at 16 min the increase in RCV blood flow velocity had returned to the resting baseline level only in the heat condition. At exhaustion, the blood flows in the STRA and SNRA had decreased significantly from the resting baseline value in the heat condition (STRA: -19 ± 5% and SNRA: -30 ± 6%), and SNRA blood flow was lower than that in the control condition (-14 ± 6% vs -30 ± 6% at 20°C and 35°C, respectively), despite the finding that both thermal conditions induced the same reductions in PETCO2 and vascular conductance. These findings suggested that the heat condition decreases or suppresses ocular blood flow via attenuation of pressor response during exhaustive exercise. Key Points The ocular (retinal and choroidal) blood flow response to

  4. Neovascular age-related macular degeneration without drusen in the fellow eye: clinical spectrum and therapeutic outcome

    PubMed Central

    Chung, Wing H; van Dijk, Elon H C; Mohabati, Danial; Dijkman, Greet; Yzer, Suzanne; de Jong, Eiko K; Fauser, Sascha; Schlingemann, Reinier O; Hoyng, Carel B; Boon, Camiel J F

    2017-01-01

    Purpose To investigate the clinical characteristics and therapeutic outcome of patients with neovascular age-related macular degeneration (nAMD) in 1 eye, without drusen in the fellow eye. Patients and methods Medical records of 381 patients were analyzed to identify the cases. The main outcomes included Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) and change in central retinal thickness (CRT). These parameters were reviewed at baseline, first follow-up visit, and after 6, 12, and 24 months. Results Out of 381 patients, 29 cases (8%) were included (of whom 3 had polypoidal choroidal vasculopathy [PCV]) who were treated with anti-vascular endothelial growth factor (anti-VEGF) therapy which was supplemented by photodynamic therapy (PDT) in the PCV patients. Overall, no statistically significant change in mean BCVA was observed during follow-up. BCVA improved or remained stable (defined as a gain in BCVA, a stable BCVA, or a loss of <5 ETDRS letters) in 22 patients (76%), and 7 patients (23%) had lost ≥5 ETDRS letters at final follow-up. A gain of ≥15 ETDRS letters at final follow-up was seen in 5 patients (17%). Mean CRT had decreased significantly with 99 µm (P<0.001) at 24 months after the initial visit. Conclusion There is a clinical spectrum of nAMD that is not associated with drusen in the fellow eye. Patients with nAMD without drusen in the fellow eye respond to anti-VEGF treatment and, in cases of PCV, to supplemental PDT. The pathophysiology of this spectrum of nAMD may be different from drusen-associated age-related macular degeneration. PMID:28053502

  5. 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