Macular Degeneration: Bhisitkul RB

Fung AE, Bhisitkul RB. · No affiliation provided · Br J Ophthalmol. · Pubmed #19029158 No free full text.

This publication has no abstract.

Bhisitkul RB. · Department of Ophthalmology, Beckman Vision Center, University of California San Francisco, 10 Koret Way, K301, San Francisco, CA 94143, USA. · Br J Ophthalmol. · Pubmed #17114590 No free full text.

Abstract: Decades of research on vascular endothelial growth factor (VEGF) have reached fruition with the recent development of intravitreal anti-VEGF treatments for exudative age-related macular degeneration. VEGF is a critical regulator of angiogenesis and vascular permeability with diverse roles, both pathological and physiological, during development and adulthood. The aim of this article is to review aspects of VEGF biology that may be relevant to the clinical use of anti-VEGF agents in ophthalmology: molecular characteristics and isoforms of VEGF; its roles in vasculogenesis, vascular maintenance and angiogenesis; systemic effects of VEGF inhibition; and properties of current anti-VEGF agents.

Bhisitkul RB, Rutar T. · UCSF Beckman Vision Center, San Francisco, CA 94143, USA. · Int Ophthalmol Clin. · Pubmed #17060798 No free full text.

This publication has no abstract.

Bhisitkul RB, Winn BJ, Lee OT, Wong J, Pereira Dde S, Porco TC, He X, Hahn P, Dunaief JL. · Department of Ophthalmology, Epidemiology and Biostatistics Division, University of California at San Francisco, School of Medicine, San Francisco, California, USA. · Invest Ophthalmol Vis Sci. · Pubmed #18421081 No free full text.

Abstract: PURPOSE: To study photoreceptor apoptosis and iron migration as mechanisms of retinotoxicity in a rabbit model of subretinal hemorrhage (SRH) and to assess intravitreal triamcinolone acetonide (IVTA) for anti-apoptotic and neuroprotective effects. METHODS: In adult rabbits, eyes were studied histologically after subretinal injection of autologous blood. For comparisons of control eyes with eyes injected with 2 mg IVTA, morphometric analysis was performed with light microscopy, whereas apoptosis was quantified with terminal dUTP nick end labeling (TUNEL) and fluorescence microscopy. Localization of retinal iron was assessed with Perls' stain. RESULTS: Photoreceptor degeneration was initiated 48 hours after exposure to subretinal blood and progressed over 7 days. Increased TUNEL positivity demonstrating apoptotic cell death was associated with SRH and photoreceptor loss. VIP-Perls staining demonstrated iron in the photoreceptor layer and retinal pigment epithelium that correlated with photoreceptor degeneration. Treatment with IVTA enhanced photoreceptor cell survival by 11% at 48 hours and by 45% at 72 hours (P = 0.01) and reduced photoreceptor apoptosis ratios by 25% at 48 hours (P = 0.006). CONCLUSIONS: Photoreceptor toxicity caused by SRH occurs at least in part by apoptosis and is associated with iron migration to the photoreceptor layer. Treatment with IVTA reduced photoreceptor loss and apoptosis, indicating a neuroprotective action. Therapies to target SRH may augment anti-VEGF treatments in exudative age-related macular degeneration and other diseases of choroidal neovascularization.

Boyer DS, Antoszyk AN, Awh CC, Bhisitkul RB, Shapiro H, Acharya NR, Anonymous00222. · Retina-Vitreous Associates, Beverly Hills, California, USA. · Ophthalmology. · Pubmed #17270674 No free full text.

Abstract: OBJECTIVE: An examination of clinically relevant subgroups of patients in the MARINA study of ranibizumab in treatment of minimally classic or occult with no classic choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) was done. Objectives were to determine the effectiveness of ranibizumab across subgroups, compare the effectiveness of ranibizumab with that of sham injection within subgroups, and evaluate the relationship between selected baseline characteristics and visual acuity (VA) outcomes. DESIGN: Retrospective subgroup analyses of 24-month data from the MARINA study. PARTICIPANTS AND CONTROLS: Seven hundred sixteen patients were randomly assigned to 0.3 mg ranibizumab (n = 238), 0.5 mg ranibizumab (n = 240), or sham treatment (n = 238). METHODS: Efficacy outcomes were compared across subgroups based on patients' gender, age, baseline VA score, baseline CNV lesion size, CNV lesion type, and duration of neovascular AMD using univariate analyses. Multivariate analyses were performed on the change from baseline to 24 months in VA score to assess further the correlation between baseline characteristics and VA outcome. MAIN OUTCOME MEASURES: Proportion of patients losing <15 letters from baseline, proportion gaining > or =15 letters from baseline, and mean VA score change from baseline. RESULTS: For each of the 3 VA end points, all subgroups of ranibizumab-treated patients did better on average than the sham-treated patients. Increasing age, larger CNV lesion size at baseline, and a higher baseline VA score were all associated with greater loss of letters in the sham group or less gain of letters in the ranibizumab groups. However, the net benefit of ranibizumab versus sham treatment was greater in patients who scored higher than in those who scored lower in baseline VA. CONCLUSIONS: This subgroup analysis of 24-month data from the MARINA study indicates that ranibizumab treatment was associated with an average increase from baseline VA in all subgroups evaluated, and that ranibizumab treatment was superior to sham treatment across all subgroups. The most important predictors of VA outcomes were, in decreasing order of importance, baseline VA score, CNV lesion size, and age.

Paskowitz DM, Nune G, Yasumura D, Yang H, Bhisitkul RB, Sharma S, Matthes MT, Zarbin MA, Lavail MM, Duncan JL. · Department of Ophthalmology, University of California, San Francisco, 94143-0730, USA. · Invest Ophthalmol Vis Sci. · Pubmed #15505074 links to  free full text

Abstract: PURPOSE: Verteporfin photodynamic therapy (PDT) is the most effective treatment for age-related macular degeneration, using laser activation of a photosensitizing dye to achieve closure of choroidal neovascularization. Although PDT preferentially affects pathologic vessels, it can also cause collateral damage to the overlying retina. In the current study, it was found that the neuroprotective agent brain-derived neurotrophic factor (BDNF) reduces this retinal damage. METHODS: Normal adult rats received intravitreal BDNF in one eye and PBS or no injection in the other eye 2 days before PDT. RESULTS: Control eyes exhibited choroidal hypofluorescence, moderate to severe photoreceptor loss, and depression of local retinal function measured using multifocal ERG in the laser-treated area. BDNF-injected eyes had more surviving photoreceptors and improved multifocal ERG responses 1 week after PDT. BDNF did not diminish the effect of PDT on the choroidal circulation as assessed by fluorescein angiography, and there was no evidence of retinal toxicity due to BDNF treatment. CONCLUSIONS: These results suggest that adjunctive neuroprotective therapy may reduce collateral damage to photoreceptors and improve visual outcome after PDT.