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Detroit, MI, United States

Almony A.,University of Missouri | Nudleman E.,University of Washington | Shah G.K.,University of Washington | Shah G.K.,Barnes Retina Institute | And 5 more authors.
Retina | Year: 2012

BACKGROUND: The internal limiting membrane represents the structural interface between the retina and the vitreous and has been postulated to serve several essential functions. Recently, internal limiting membrane peeling has been used in the treatment of a variety of retinal disorders. We review the history, techniques, rationale, and outcomes of internal limiting membrane peeling. METHODS: A review of the literature. RESULTS: Internal limiting membrane peeling has been used to successfully treat a variety of retinal disorders including macular hole, epiretinal membrane, diabetic macular edema, retinal vein occlusion, and others. CONCLUSION: Internal limiting membrane peeling may serve as an important component in the armamentarium of retinal surgery. Copyright © by Ophthalmic Communications Society, Inc.

Kowluru R.A.,Kresge Eye Institute
Investigative Ophthalmology and Visual Science | Year: 2010

PURPOSE. Diabetes activates a small molecular weight G-protein, H-Ras, in the retina and its capillary cells, and H-Ras activation is implicated in the apoptosis of retinal capillary cells. Matrix metalloproteinase (MMP)-9 is regulated by H-Ras, and in diabetes its activation is associated with increased vascular permeability. The goal of this study was to investigate the role of sustained activation of MMP-9 in the pathogenesis of diabetic retinopathy and to illustrate the mechanism through which it is upregulated in diabetes. METHODS. Retinal MMP-9 activation and its tissue inhibitor, TIMP-1, were quantified in streptozotocin-induced diabetic rats. Inhibition of H-Ras by simvastatin on diabetes-induced activation of H-Ras was evaluated. The mechanism by which diabetes regulates retinal MMP-9 was confirmed by determining the effect of genetic or pharmacologic regulation of H-Ras on its activation in retinal endothelial cells. RESULTS. In rats, MMP-9 was activated and expression of TIMP-1 was decreased in the retina and its microvasculature at both 2 months and 12 months of diabetes. In retinal endothelial cells, high glucose activated MMP-9, and inhibition of its activation (by pharmacologic inhibitor or siRNA) ameliorated accelerated apoptosis. Inhibition of H-Ras, both in diabetic rats (simvastatin) and in isolated endothelial cells (H-Ras siRNA), abrogated the activation of MMP-9 and prevented the reduction of TIMP-1. CONCLUSIONS. Hyperglycemia-induced activation of MMP-9 accelerates apoptosis of retinal capillary cells, a phenomenon that predicts the development of diabetic retinopathy, and the activation of MMP-9 is downstream of H-Ras. Characterizing the role of MMP-9 in the development of diabetic retinopathy will help explore novel molecular targets for future pharmacological interventions. © Association for Research in Vision and Ophthalmology.

PURPOSE:: To quantify photoreceptor volume changes after successful surgical repair of macula-off retinal detachment and to correlate these volumetric changes to postoperative best-corrected visual acuity (BCVA). METHODS:: Retrospective study of 15 eyes of 15 patients with macula-off retinal detachment who underwent successful surgical repair. A minimum of 4 optical coherence tomography scans that straddled the foveal center was used to quantify the central photoreceptor volume (central 1 mm). RESULTS:: Mean photoreceptor volume at the first postoperative visit was 0.451 mm, increasing to 0.523 mm at the final postoperative visit (P = 0.004). Mean BCVA improved from 1.13 ± 0.59 logarithm of the minimum angle of resolution units (∼20/270) preoperatively to 0.52 ± 0.42 logarithm of the minimum angle of resolution units (∼20/66) at the final postoperative visit (P = 0.001). Mean photoreceptor volume at either the initial or final visit demonstrated significant correlations with final postoperative BCVA (r = −0.670, P = 0.017 and r = −0.753, P = 0.005, respectively). Shorter time interval from diagnosis to surgery was significantly associated with greater mean final postoperative photoreceptor volume (r = −0.588, P = 0.021) and better mean final postoperative BCVA (r = 0.709, P = 0.003). CONCLUSION:: We observed a significant increase in photoreceptor volume after successful retinal detachment repair; photoreceptor volume was positively associated with BCVA and time to surgery. Our series emphasizes the importance of prompt surgical repair and shows that photoreceptor recovery and volumetric improvement correlate significantly with BCVA. © 2016 by Ophthalmic Communications Society, Inc.

Servat J.J.,Yale University | Mears K.A.,Kresge Eye Institute | Black E.H.,Kresge Eye Institute | Huang J.J.,Yale University
Expert Opinion on Biological Therapy | Year: 2012

Introduction: The conventional treatment of uveitis includes corticosteroids and immunosuppressive agents, which are highly efficacious, but can be associated with serious systemic side effects. Over the last two decades, advances in the understanding of the pathogenesis of inflammatory diseases, as well as improved biotechnology, have enabled selective targeting of the chemical mediators of diseases. Recently, a new class of drugs called biologics, that target the various mediators of the inflammation cascade, may potentially provide more effective and less toxic treatment. Areas covered: This article is a review and summary of the peer-reviewed evidence for biologic agents in the treatment of various forms of ocular inflammation and it focuses on the potential use of other biologic agents that have been tested in experimental autoimmune uveitis. Pubmed was used as our main tool for our literature search. Some additional references were taken from books written on the subject. Expert opinion: There are a wide variety of new and emerging biological agents currently being used in the treatment of uveitis which has expanded the therapeutic horizons far beyond previous limitations. © 2012 Informa UK, Ltd.

Sosne G.,Wayne State University | Dunn S.P.,Michigan Cornea Consultants | Kim C.,Kresge Eye Institute
Cornea | Year: 2015

Purpose: Standard therapies for severe dry eye are limited and fail to resolve the problem. The purpose of this study was to evaluate the safety and efficacy of Thymosin b4 eye drops (RGN-259) as a novel therapy forsevere dry eye disease (including that associated with graft vs. host disease). Methods: A small, multicenter,randomized, double-masked, placebo-controlled 56-day phase 2 clinical trial including a 28-day follow-up at 2US sites. Nine patients with severe dry eye were treated with either RGN-259 (0.1%) or vehicle control 6 times daily over a period of 28 days. Dry eye sign and symptom assessments, such as ocular discomfort (using the OSDI questionnaire) and corneal fluorescein staining (using the NEI workshop grading system), were evaluated at various time points. Results: Statistically significant differences in both symptom and sign assessments, wereseen at various time points throughout the study. Of particular note at day 56, the RGN-259-treated group (12 eyes) had 35.1% reduction of ocular discomfort compared with vehicle control (6 eyes) (P = 0.0141), and 59.1% reduction of total corneal fluorescein staining compared with vehicle control (P = 0.0108). Other improvements seen in the RGN-259-treated patients included tear film breakup time and increased tear volume production. Conclusions: In this small trial, RGN-259 eye drops were safe and well tolerated and met key efficacy objectives with statistically significant symptom and sign improvements, compared with vehicle control, at various time intervals, including 28-days posttreatment. © 2015 Wolters Kluwer Health, Inc. All rights reserved.

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