Secondary analyses of the effects of lutein/zeaxanthin on age-related macular degeneration progression: AREDS2 report No. 3.

IMPORTANCE: The Age-Related Eye Disease Study (AREDS) formulation for the treatment of age-related macular degeneration (AMD) contains vitamin C, vitamin E, beta carotene, and zinc with copper. The Age-Related Eye Disease Study 2 (AREDS2) assessed the value of substituting lutein/zeaxanthin in the AREDS formulation because of the demonstrated risk for lung cancer from beta carotene in smokers and former smokers and because lutein and zeaxanthin are important components in the retina. OBJECTIVE: To further examine the effect of lutein/zeaxanthin supplementation on progression to late AMD. DESIGN, SETTING, PARTICIPANTS: The Age-Related Eye Disease Study 2 is a multicenter, double-masked randomized trial of 4203 participants, aged 50 to 85 years, at risk for developing late AMD; 66% of patients had bilateral large drusen and 34% had large drusen and late AMD in 1 eye. INTERVENTIONS: In addition to taking the original or a variation of the AREDS supplement, participants were randomly assigned in a factorial design to 1 of the following 4 groups: placebo; lutein/zeaxanthin, 10 mg/2 mg; omega-3 long-chain polyunsaturated fatty 3 acids, 1.0 g; or the combination. MAIN OUTCOMES AND MEASURE: S Documented development of late AMD by central, masked grading of annual retinal photographs or by treatment history. RESULTS In exploratory analysis of lutein/zeaxanthin vs no lutein/zeaxanthin, the hazard ratio of the development of late AMD was 0.90 (95% CI, 0.82-0.99; P = .04). Exploratory analyses of direct comparison of lutein/zeaxanthin vs beta carotene showed hazard ratios of 0.82 (95% CI, 0.69-0.96; P = .02) for development of late AMD, 0.78 (95% CI, 0.64-0.94; P = .01) for development of neovascular AMD, and 0.94 (95% CI, 0.70-1.26; P = .67) for development of central geographic atrophy. In analyses restricted to eyes with bilateral large drusen at baseline, the direct comparison of lutein/zeaxanthin vs beta carotene showed hazard ratios of 0.76 (95% CI, 0.61-0.96; P = .02) for progression to late AMD, 0.65 (95% CI, 0.49-0.85; P = .002) for neovascular AMD, and 0.98 (95% CI, 0.69-1.39; P = .91) for central geographic atrophy. CONCLUSION AND RELEVANCE: The totality of evidence on beneficial and adverse effects from AREDS2 and other studies suggests that lutein/zeaxanthin could be more appropriate than beta carotene in the AREDS-type supplements. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00345176.

Lutein/zeaxanthin for the treatment of age-related cataract: AREDS2 randomized trial report no. 4.

IMPORTANCE: Age-related cataract is a leading cause of visual impairment in the United States. The prevalence of age-related cataract is increasing, with an estimated 30.1 million Americans likely to be affected by 2020. OBJECTIVE: To determine whether daily oral supplementation with lutein/zeaxanthin affects the risk for cataract surgery. DESIGN, SETTING, AND PATIENTS: The Age-Related Eye Disease Study 2 (AREDS2), a multicenter, double-masked clinical trial, enrolled 4203 participants, aged 50 to 85 years, at risk for progression to advanced age-related macular degeneration. INTERVENTIONS: Participants were randomly assigned to daily placebo; lutein/zeaxanthin, 10mg/2mg; omega-3 long-chain polyunsaturated fatty acids, 1 g; or a combination to evaluate the effects on the primary outcome of progression to advanced age-related macular degeneration. MAIN OUTCOMES AND MEASURES: Cataract surgery was documented at annual study examination with the presence of pseudophakia or aphakia, or reported during telephone calls at 6-month intervals between study visits. Annual best-corrected visual acuity testing was performed. A secondary outcome of AREDS2 was to evaluate the effects of lutein/zeaxanthin on the subsequent need for cataract surgery. RESULTS: A total of 3159 AREDS2 participants were phakic in at least 1 eye and 1389 of 6027 study eyes underwent cataract surgery during the study, with median follow-up of 4.7 years. The 5-year probability of progression to cataract surgery in the no lutein/zeaxanthin group was 24%. For lutein/zeaxanthin vs no lutein/zeaxanthin, the hazard ratios for progression to cataract surgery was 0.96 (95% CI, 0.84-1.10; P = .54). For participants in the lowest quintile of dietary intake of lutein/zeaxanthin, the hazard ratio comparing lutein/zeaxanthin vs no lutein/zeaxanthin for progression to cataract surgery was 0.68 (95% CI, 0.48-0.96; P = .03). The hazard ratio for 3 or more lines of vision loss was 1.03 (95% CI, 0.93-1.13; P = .61 for lutein/zeaxanthin vs no lutein/zeaxanthin). CONCLUSIONS AND RELEVANCE: Daily supplementation with lutein/zeaxanthin had no statistically significant overall effect on rates of cataract surgery or vision loss. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00345176.

Ocular side effects associated with peribulbar injections of triamcinolone acetonide for diabetic macular edema.

PURPOSE: To evaluate long-term effects of anterior and posterior peribulbar injections of triamcinolone acetonide on intraocular pressure (IOP) elevation and cataract development. METHODS: This study reports on IOP and cataract progression through 2 years in 96 eyes with diabetic macular edema randomized to focal/grid photocoagulation, 20 mg triamcinolone acetonide anterior injection, anterior injection followed by laser, 40 mg triamcinolone acetonide posterior injection, or posterior injection followed by laser. RESULTS: Intraocular pressure increased from baseline by ≥ 10 mmHg at ≥ 1 visit through 2 years in 2 eyes (8%) in the laser group, 11 eyes (31%) in the anterior groups, and 6 eyes (17%) in the posterior groups. Among phakic eyes at baseline, 0, 5 (17%), and 1 (3%) in the 3 groups, respectively, underwent cataract surgery before the 2-year visit. CONCLUSION: Based on this small randomized trial, it appears that over 2 years, anterior peribulbar triamcinolone acetonide injections are associated with an increased incidence of IOP elevation and an increased risk of cataract development compared with laser or posterior peribulbar injections. The association of posterior injections with IOP elevation is less certain. Although the study involved eyes with diabetic macular edema, the results should be relevant to other conditions treated with peribulbar corticosteroids.

Preliminary assessment of celecoxib and microdiode pulse laser treatment of diabetic macular edema.

PURPOSE: Inflammation may play an important role in the pathogenesis of diabetic macular edema, a major cause of vision loss in persons with diabetes. The purpose of this study was to evaluate combined antiinflammatory therapy and laser approaches for treating patients with diabetic macular edema. METHODS: In this prospective, factorial, randomized, multicenter trial, we compared cyclo-oxygenase-2 inhibitor (celecoxib) with placebo and diode grid laser with standard Early Treatment Diabetic Retinopathy Study focal laser treatment in 86 participants with diabetic macular edema. The primary outcome is change in visual acuity of > or = 15 letters from baseline, and the secondary outcomes include a 50% reduction in the retinal thickening of diabetic macular edema measured by optical coherence tomography and a 50% reduction in leakage severity on fluorescein angiography. RESULTS: Visual acuity and retinal thickening data from >2 years of follow-up did not show evidence of differences between the medical and laser treatments. However, participants assigned to the celecoxib group were more likely to have a reduction in fluorescein leakage when compared with the placebo group (odds ratio = 3.6; P < 0.01). CONCLUSION: This short-term study did not find large visual function benefits of treatment with celecoxib or diode laser compared with those of standard laser treatment. A suggestive effect of celecoxib in reducing fluorescein leakage was observed.

Intravitreous bevacizumab in the treatment of macular edema from branch retinal vein occlusion and hemisphere retinal vein occlusion (an AOS thesis).

PURPOSE: To compare intravitreous bevacizumab to other current treatments of branch retinal vein occlusion (BRVO) and hemisphere retinal vein occlusion (HRVO) with consideration to visual outcome, cost, convenience, and risk of treatment. METHODS: This is a retrospective chart review from a large referral retina practice. The data comprise 56 patients with BRVO and HRVO treated by intravitreous bevacizumab, with and without intravitreous triamcinolone acetonide. Initial visual acuities at the time of first bevacizumab injection, best acuities through the follow-up time, final acuity at last visit before review, initial macular thickness, and final macular thickness were measured. Changes in vision and thickness were calculated, as were the percentage of eyes improving, stabilizing, and worsening. RESULTS: The data were compared to composite data derived from several current treatments of BRVO. The subgroup of 39 eyes that received only bevacizumab without triamcinolone acetonide had the most improvement in vision. The median change in visual acuity was 1.5 lines (P = .012) over a mean follow-up of 8.8 months. Twenty-three eyes (59%) improved visually, with 20 eyes (51%) improving 2 or more lines. These results are similar to those for eyes that received argon grid laser and chorioretinal anastomosis, but are worse than in eyes that received arteriovenous adventitial sheathotomy, macular decompression surgery, and intravitreous triamcinolone acetonide. CONCLUSIONS: Visual benefit from intravitreous bevacizumab compares well against laser treatments for BRVO and HRVO but not as well opposed to surgical techniques and intravitreous triamcinolone acetonide. Intravitreous bevacizumab injection has a risk, cost, and convenience profile that is favorable.