Macular Degeneration: Wong J

Wong J, Molyneaux L, Constantino M, Twigg SM, Yue DK. · Diabetes Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. · Diabetes Care. · Pubmed #18628565 links to  free full text

Abstract: OBJECTIVE: To test the hypothesis that age of type 2 diabetes onset influences inherent susceptibility to diabetic retinopathy, independent of disease duration and degree of hyperglycemia. RESEARCH DESIGN AND METHODS: Retinopathy data from 624 patients with a type 2 diabetes duration of 20-30 years (group A) were analyzed by stratifying patients according to age of onset of diabetes and glycemic control. Retinopathy status was scored clinically as per a modified Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. To obviate possible bias due to a higher attrition from comorbidities in those with later-onset diabetes and retinopathy, 852 patients with type 2 diabetes of shorter duration (10-12 years, group B) were similarly studied. RESULTS: Prevalence and severity of retinopathy was significantly higher in the younger-onset, group A patients. When further stratified according to mean A1C, retinopathy risk remained increased in younger-onset patients. The greatest impact was seen in those with a mean A1C >9% (odds ratio [OR] for retinopathy 16.6, 7.5, and 2.7 for age of diagnosis <45, 45-55, and >55 years, respectively, P = 0.003). By logistic regression, earlier type 2 diabetes onset is associated with increased retinopathy risk, independent of traditional risk factors (OR of retinopathy 1.9, 1.1, and 1 for age of onset <45, 45-55, and >55 years, respectively). Similar results were found in group B patients. CONCLUSIONS: These data suggest an increased inherent susceptibility to diabetic retinopathy with earlier-onset type 2 diabetes. This further supports the importance of delaying development of diabetes and also implies a need for more stringent metabolic targets for younger individuals.

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.

Hollands H, Wong J, Bruen R, Campbell RJ, Sharma S, Gale J. · Department of Ophthalmology, Queen's University, Hotel Dieu Hospital, Kingston, ON K7L 5S9. · Can J Ophthalmol. · Pubmed #18026202 links to  free full text

Abstract: BACKGROUND: This study examines the changes in short-term intraocular pressure (IOP) in patients receiving intravitreally administered bevacizumab. A prospective series of consecutive patients undergoing injection of intravitreal bevacizumab was investigated. METHODS: All patients received bevacizumab (0.05 cc) injected intravitreally in a standard fashion. IOP was measured at baseline, 2, 5, and 30 minutes after injection by 1 of 2 observers using Goldman applanation tonometry. An intraobserver study was done to assess agreement in IOP measurements. RESULTS: We accrued 104 patients with a mean age of 76 years: 58% were female, and 42% were male. Most patients (85%) were being treated for neovascular age-related macular degeneration. The mean IOP values at baseline, 2, 5, and 30 minutes after injection were 14.0 (95% confidence interval [CI] 13.4-14.7) mm Hg, 36.1 (95% CI 33.5-38.6) mm Hg, 25.7 (95% CI 23.8-27.5) mm Hg, and 15.5 (95% CI 12.4-16.51) mm Hg, respectively. Three patients (2.9%) had an IOP of 25 mm Hg or higher at 30 minutes. IOP normalized within 2 hours without medical therapy in 2 of these patients, and 1 patient required a 1-week course of glaucoma medication. Regression analysis showed a trend towards phakic patients having higher IOP at 30 minutes (odds ratio = 3.2; p = 0.089). INTERPRETATION: Intravitreal injection of bevacizumab is safe with respect to short-term IOP changes, as almost all patients' IOP returned to a safe range (<25 mm Hg) within 30 minutes. Elevated IOP at 30 minutes after injection does occur, rarely, thus clinicians should consider checking IOP after injection as a precaution. Transient extreme IOP elevations occur in a significant percentage of patients, but the consequences of these events are unknown.