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Retinal Vein

About: Retinal Vein is a research topic. Over the lifetime, 1756 publications have been published within this topic receiving 33827 citations.


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TL;DR: VEGF's causal role in retinal angiogenesis is demonstrated and the potential of VEGF inhibition as a specific therapy for ischemic retinal disease is proved.
Abstract: 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) 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-microns 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%, respectively. No retinal toxicity was observed by light microscopy. These data demonstrate VEGF's causal role in retinal angiogenesis and prove the potential of VEGF inhibition as a specific therapy for ischemic retinal disease.

1,338 citations

Journal ArticleDOI
TL;DR: Intravitreal triamcinolone is superior to observation for treating vision loss associated with macular edema secondary to CRVO in patients who have characteristics similar to those in the SCORE-CRVO trial.
Abstract: Retinal vein occlusion disease is estimated to be the second most common cause of retinal vascular disease in the United States.1 The prevalence of retinal vein occlusion in the Blue Mountains Eye Study was 1.6%, with 69.5%(41of59)oftheseocclusionsclassified as branch retinal vein occlusion (BRVO).2 Retinal vein occlusion was bilateral in 5.1% of cases.2 The 15-year cumulative incidence of BRVO was 1.8% in the Beaver Dam Eye Study.3 In the Beaver Damcohort,centraland branch retinal vein occlusion accounted for 12% of eyes that developed severe vision loss during a 15-year period.4 Macular edema is a frequent cause of visual acuity loss from BRVO.1,5,6 The natural history of macular edema secondary to BRVO was delineated in the Branch Vein Occlusion Study (BVOS).1 One arm of the BVOS demonstrated a benefit with grid photocoagulation.1 Of 43 treated eyes available for follow-up at the 3-year visit, 28 (65%) had gained 2 or more lines of visual acuity from baseline and maintained this gain for at least 8 months compared with the same gain in 13 of 35 untreated eyes (37%). The BVOS also identified a subset of patients who derived limited benefit from grid photocoagulation. In the BVOS, 40% of treated eyes (n=43) had worse than 20/40 visual acuity at 3 years, and 12% of treated eyes had 20/200 or worse visual acuity at 3 years.1 During the last decade, a number of additional treatments for macular edema secondary to BRVO have been investigated. Such treatments include laser chorioretinal anastomosis, vitrectomy, arteriovenous sheathotomy, and intravitreal injection of antibodies targeted at vascular endothelial growth factor (VEGF).7-12 Numerous reports have suggested that intravitreal injection(s) of triamcinolone acetonide (hereafter referred to as intravit-real triamcinolone) is a potentially efficacious therapy for retinal thickening and vision loss in patients with macular edema secondary to BRVO but that some patients may develop steroid-related complications, such as elevated intraocular pressure (IOP) and cataract.13-26 Most of the information concerning intravitreal triamcinolone for macular edema secondary to BRVO is derived from case series that lacked long-term follow-up and adequate numbers of study participants; a randomized and controlled study has not been performed.13-26 Despite the shortcomings of these case series, intravitreal triamcinolone is currently in use as a treatment for BRVO. The rationale for the use of corticosteroids to treat macular edema secondary to BRVO follows from the observation that the increase in retinal capillary permeability that results in macular edema may be caused by a breakdown of the blood-retina barrier mediated in part by VEGF, a 45-kDa glycoprotein.27-29 Therefore, attenuation of the effects of VEGF may reduce macular edema associated with BRVO.30,31 Corticosteroids have been demonstrated to inhibit the expression of VEGF and therefore may be an effective therapy for macular edema.32,33 Inflammation may also play a role in the pathology of BRVO, and the anti-inflammatory properties of corticosteroids may contribute to the attenuation of the disease process.34 Intravitreal triamcinolone is used by ophthalmologists in the clinical setting as a readily available pharmacologic agent (Kenalog 40; Bristol-Myers Squibb, Princeton, New Jersey, or Triesence; Alcon Inc, Fort Worth, Texas), though use for the treatment of macular edema is off label. Other formulations such as compounded preservative-free triamcinolone acetonide are also used in the clinical setting. The Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) Study, sponsored by the National Eye Institute, is a clinical trial designed to compare 1-mg and 4-mg doses of intravitreal triamcinolone with standard care for vision loss associated with macular edema secondary to per-fused central retinal vein occlusion (CRVO) and BRVO.35,36 This article describes findings from the SCORE-BRVO trial. A companion article that compares intravitreal triamcinolone with observation for vision loss associated with macular edema secondary to CRVO is published concurrently (the SCORE-CRVOtrial).37 The 2 primary study objectives of the SCORE-BRVO trial are (1) to determine whether intravit-real triamcinolone at 1-mg and 4-mg doses produces greater visual benefit, with an acceptable safety profile,than grid photocoagulation, when appropriate, for the treatment of vision loss associated with macular edema secondary to BRVO; and (2) to compare the efficacy and safety of the 1-mg and 4-mg triamcinolone doses.

642 citations

Journal Article
TL;DR: The data suggest a strong association between retinal branch vein occlusion and retinal arteriolar changes, and data from larger populations are needed to further assess associations between risk factors and the incidence of retinal vein Occlusion.
Abstract: PURPOSE: To describe the prevalence and the 5-year incidence of retinal central and branch vein occlusion and associated risk factors. METHODS: The Beaver Dam Eye Study (n = 4,926) is a population-based study in which retinal vein occlusions were detected at baseline (1988-1990) and at a 5-year follow-up examination (1993-1995) by grading of 30 degrees color fundus photographs. RESULTS: The prevalence and 5-year incidence of retinal branch vein occlusion were each 0.6%. The prevalence of retinal central vein occlusion was 0.1%, and the 5-year incidence was 0.2%. While adjusting for age, the prevalence of branch vein occlusion was associated with hypertension (odds ratio [OR] 5.42, 95% confidence interval [CI] 2.18, 13.47), diabetes mellitus (OR 2.43, 95% CI 1.04, 5.70), pulse pressure (OR 1.24 for 10 mm Hg, 95% CI 1.03, 1.48), ocular perfusion pressure (OR 2.09 for 10 mm Hg, 95% CI 1.45, 3.01), arteriovenous nicking (OR 16.75, 95% CI 7.33, 38.24), and focal arteriolar narrowing (OR 22.86, 95% CI 8.43, 62.03). The age-adjusted incidence of retinal branch vein occlusion was associated with current smoking (OR 4.43 95%, CI 1.53, 12.84) compared with nonsmokers and to focal arteriolar narrowing (OR 5.24, 95% CI 1.97, 13.94) at baseline. While controlling for age, the incidence of branch vein occlusion was not associated with serum lipid levels, body mass index, white blood cell count, alcohol consumption, aspirin use, glaucoma, intraocular pressure, or ocular hypertension. CONCLUSIONS: Retinal vein occlusion is infrequent in the population. These data suggest a strong association between retinal branch vein occlusion and retinal arteriolar changes. Data from larger populations are needed to further assess associations between risk factors and the incidence of retinal vein occlusions.

581 citations

Journal Article
TL;DR: In situ hybridization techniques were used to examine the thesis that VEGF functions as the link between retinal ischemia and a pathologic, intraocular, angiogenic response to promote retinal and iris neovascularization in a number of neov vascular eye diseases.

451 citations

Journal Article
TL;DR: The clinical and histopathologic features of 29 eyes from 29 patients with central retinal vein occlusion (CRVO) are reported in this article, and the temporal aspects of the cases, and it notes the different morphologic features, which represent the various stages in the natural evolution of a thrombus.
Abstract: The clinical and histopathologic features of 29 eyes from 29 patients with central retinal vein occlusion (CRVO) are reported. A fresh or a recanalized thrombus was observed in each eye. This study considers the temporal aspects of the cases, and it notes the different morphologic features of the occlusion. These observations explain most of the variability of the changes observed in previous reports. We believe that these different features represent the various stages in the natural evolution of such a thrombus. The interval between CRVO and histopathologic study in our series ranged from six hours to more than 10 years. Local and systemic factors were reviewed and were found to be important in the pathogenesis of thrombus formation. Local diseases with a predisposing effect on CRVO included: glaucoma, papilledema, subdural hemorrhage, optic nerve hemorrhage, and drusen of the optic nerve head. Associated systemic diseases included: hypertension, cardiovascular and cerebrovascular disease, diabetes mellitus, and leukemia with thrombocytopenia. A fresh thrombus in the CRVO was observed in three (10.3%), and a recanalized thrombus in 26 eyes (89.7%). Endothelial-cell proliferation was a conspicuous feature in 14 (48.3%) of the eyes. Chronic inflammation in the area of the thrombus, and/or vein wall or perivenular area was observed in 14 (48.3%) of the eyes. Arterial occlusive disease was observed in seven eyes (24.6%). Cystoid macular edema was found in 26 (89.7%) of the eyes.

440 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202385
2022216
202182
202064
201979
201882