In this evaluation of retinal images from multiethnic cohorts of patients with diabetes, the DLS had high sensitivity and specificity for identifying diabetic retinopathy and related eye diseases. Further research is necessary to evaluate the applicability of the DLS in health care settings and the utility of the DLS to improve vision outcomes.

A common detection and classification system is needed for epidemiologic studies of age-related maculopathy (ARM). Such a grading scheme for ARM is described in this paper. ARM is defined as a degenerative disorder in persons > or = 50 years of age characterized on grading of color fundus transparencies by the presence of the following abnormalities in the macular area: soft drusen > or = 63 microns, hyperpigmentation and/or hypopigmentation of the retinal pigment epithelium (RPE), RPE and associated neurosensory detachment, (peri)retinal hemorrhages, geographic atrophy of the RPE, or (peri)retinal fibrous scarring in the absence of other retinal (vascular) disorders. Visual acuity is not used to define the presence of ARM. Early ARM is defined as the presence of drusen and RPE pigmentary abnormalities described above; late ARM is similar to age-related macular degeneration (AMD) and includes dry AMD (geographic atrophy of the RPE in the absence of neovascular AMD) or neovascular AMD (RPE detachment, hemorrhages, and/or scars as described above). Methods to take and grade fundus transparencies are described.

Objective Evaluate intravitreal 0.5 mg ranibizumab or 4 mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME). Design Multicenter, randomized clinical trial. Participants A total of 854 study eyes of 691 participants with visual acuity (approximate Snellen equivalent) of 20/32 to 20/320 and DME involving the fovea. Methods Eyes were randomized to sham injection + prompt laser (n=293), 0.5 mg ranibizumab + prompt laser (n=187), 0.5 mg ranibizumab + deferred (≥24 weeks) laser (n=188), or 4 mg triamcinolone + prompt laser (n=186). Retreatment followed an algorithm facilitated by a web-based, real-time data-entry system. Main Outcome Measures Best-corrected visual acuity and safety at 1 year. Results The 1-year mean change (±standard deviation) in the visual acuity letter score from baseline was significantly greater in the ranibizumab + prompt laser group (+9±11, P<0.001) and ranibizumab + deferred laser group (+9±12, P<0.001) but not in the triamcinolone + prompt laser group (+4±13, P=0.31) compared with the sham + prompt laser group (+3±13). Reduction in mean central subfield thickness in the triamcinolone + prompt laser group was similar to both ranibizumab groups and greater than in the sham + prompt laser group. In the subset of pseudophakic eyes at baseline (n=273), visual acuity improvement in the triamcinolone + prompt laser group appeared comparable to that in the ranibizumab groups. No systemic events attributable to study treatment were apparent. Three eyes (0.8%) had injection-related endophthalmitis in the ranibizumab groups, whereas elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone + prompt laser group. Two-year visual acuity outcomes were similar to 1-year outcomes. Conclusions Intravitreal ranibizumab with prompt or deferred laser is more effective through at least 1 year compared with prompt laser alone for the treatment of DME involving the central macula. Ranibizumab as applied in this study, although uncommonly associated with endophthalmitis, should be considered for patients with DME and characteristics similar to those in this clinical trial. In pseudophakic eyes, intravitreal triamcinolone + prompt laser seems more effective than laser alone but frequently increases the risk of intraocular pressure elevation.

BACKGROUND The relative efficacy and safety of intravitreous aflibercept, bevacizumab, and ranibizumab in the treatment of diabetic macular edema are unknown. METHODS At 89 clinical sites, we randomly assigned 660 adults (mean age, 61±10 years) with diabetic macular edema involving the macular center to receive intravitreous aflibercept at a dose of 2.0 mg (224 participants), bevacizumab at a dose of 1.25 mg (218 participants), or ranibizumab at a dose of 0.3 mg (218 participants). The study drugs were administered as often as every 4 weeks, according to a protocol-specified algorithm. The primary outcome was the mean change in visual acuity at 1 year. RESULTS From baseline to 1 year, the mean visual-acuity letter score (range, 0 to 100, with higher scores indicating better visual acuity; a score of 85 is approximately 20/20) improved by 13.3 with aflibercept, by 9.7 with bevacizumab, and by 11.2 with ranibizumab. Although the improvement was greater with aflibercept than with the other two drugs (P<0.001 for aflibercept vs. bevacizumab and P = 0.03 for aflibercept vs. ranibizumab), it was not clinically meaningful, because the difference was driven by the eyes with worse visual acuity at baseline (P<0.001 for interaction). When the initial visual-acuity letter score was 78 to 69 (equivalent to approximately 20/32 to 20/40) (51% of participants), the mean improvement was 8.0 with aflibercept, 7.5 with bevacizumab, and 8.3 with ranibizumab (P>0.50 for each pairwise comparison). When the initial letter score was less than 69 (approximately 20/50 or worse), the mean improvement was 18.9 with aflibercept, 11.8 with bevacizumab, and 14.2 with ranibizumab (P<0.001 for aflibercept vs. bevacizumab, P = 0.003 for aflibercept vs. ranibizumab, and P = 0.21 for ranibizumab vs. bevacizumab). There were no significant differences among the study groups in the rates of serious adverse events (P = 0.40), hospitalization (P = 0.51), death (P = 0.72), or major cardiovascular events (P = 0.56). CONCLUSIONS Intravitreous aflibercept, bevacizumab, or ranibizumab improved vision in eyes with center-involved diabetic macular edema, but the relative effect depended on baseline visual acuity. When the initial visual-acuity loss was mild, there were no apparent differences, on average, among study groups. At worse levels of initial visual acuity, aflibercept was more effective at improving vision. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01627249.)

Purpose Provide 2-year efficacy, safety and treatment results comparing three anti-vascular endothelial growth factor (anti-VEGF) agents for center-involved diabetic macular edema (DME) utilizing a standardized follow-up and retreatment regimen. Design Randomized clinical trial. Participants 660 participants with DME causing visual acuity (VA) impairment. Methods Randomization to 2.0-mg aflibercept, 1.25-mg repackaged (compounded) bevacizumab, or 0.3-mg ranibizumab intravitreous injections performed as frequently as monthly utilizing a protocol-specific follow-up and retreatment regimen. Focal/grid laser was added if DME persisted and was not improving at 6 months or later. Visits occurred every 4 weeks during year 1, and were extended up to every 4 months thereafter when VA and macular thickness were stable and injections were deferred. Main Outcome Measures Change in VA (efficacy), ocular/systemic adverse events (safety), retreatment frequency. Results Median numbers of injections in year 2 were 5, 6, 6 and over 2 years were 15, 16, 15 in the aflibercept, bevacizumab, and ranibizumab groups, respectively (global P=0.08). Focal/grid laser was administered in 41%, 64%, and 52%, respectively (aflibercept-bevacizumab: P<0.001, aflibercept-ranibizumab: P=0.04, bevacizumab-ranibizumab: P=0.01). From baseline to 2 years, mean VA letter score improved by 12.8 with aflibercept, 10.0 with bevacizumab, and 12.3 with ranibizumab. Treatment group differences varied by baseline VA (interaction P=0.02). With worse baseline VA (20/50-20/320), mean improvement was 18.3, 13.3, and 16.1 letters, respectively (aflibercept-bevacizumab: P=0.02, aflibercept-ranibizumab: P=0.18, ranibizumab-bevacizumab: P=0.18). With baseline VA 20/32-20/40, mean improvement was 7.8, 6.8, and 8.6 letters, respectively (P>0.10 for pairwise comparisons). Anti-Platelet Trialists’ Collaboration (APTC) events occurred in 5% with aflibercept, 8% with bevacizumab, and 12% with ranibizumab (global P=0.047: aflibercept-bevacizumab: P=0.34, aflibercept-ranibizumab: P=0.047, ranibizumab-bevacizumab: P=0.20; global P=0.09 adjusted for potential confounders). Conclusion All 3 anti-VEGF groups had visual acuity improvement at 2 years with a decreased number of injections in year 2. VA outcomes were similar among treatment groups for eyes with baseline VA 20/32-20/40. Among eyes with worse baseline VA, aflibercept, on average, had superior 2-year VA outcomes compared with bevacizumab, but superiority of aflibercept over ranibizumab, noted at 1 year, was no longer identified. Higher APTC event rates with ranibizumab over 2 years warrants continued evaluation in future trials.

Objective To report expanded 2-year follow up of a previously reported randomized trial evaluating intravitreal 0.5-mg ranibizumab or 4-mg triamcinolone combined with focal/grid laser compared with focal/grid laser alone for treatment of diabetic macular edema (DME). Design Multicenter, randomized clinical trial. Participants Eight hundred and fifty four study eyes of 691 participants with visual acuity of 20/32 to 20/320 (approximate Snellen equivalent) and DME involving the fovea. Methods Continuation of procedures previously reported for the randomized trial. Main Outcome Measures Best-corrected visual acuity and safety at the 2-year visit. Results At the 2-year visit, compared with the sham plus prompt laser group, the mean change in the visual acuity letter score from baseline was 3.7 letters greater in the ranibizumab plus prompt laser group (95% confidence interval adjusted for multiple comparisons [aCI]: -0.4 to +7.7) l, 5.8 letters greater in the ranibizumab plus deferred laser group (95% aCI: +1.9 to +9.8) and 1.5 letters worse in the triamcinolone plus prompt laser group (95% aCI : -5.5 to +2.4). After the 1- through the 2-year visit in the ranibizumab with prompt or deferred laser groups, the median numbers of injections were 2 and 3 (potential maximum of 13), respectively. At the 2-year visit, the percentages of eyes with central subfield thickness ≥250 μm were 59% in the sham + prompt laser group, 43% in the ranibizumab + prompt laser group, 42% in the ranibizumab + deferred laser group, and 52% in the triamcinolone + prompt laser group. No systemic events attributable to study treatment were apparent. Three eyes in 3 (0.8%) of 375 participants had injection-related endophthalmitis in the ranibizumab groups while elevated intraocular pressure and cataract surgery were more frequent in the triamcinolone+prompt laser group. Conclusions The expanded 2-year results reported herein are similar to results published previously and reinforce the conclusions originally reported, that ranibizumab should be considered for patients with DME and characteristics similar to the cohort in this clinical trial, including vision impairment with DME involving the center of the macula.

IMPORTANCE Panretinal photocoagulation (PRP) is standard treatment for reducing severe visual loss from proliferative diabetic retinopathy (PDR). However, PRP can damage the retina, resulting in peripheral vision loss or worsening diabetic macular edema (DME). OBJECTIVE Compare ranibizumab versus PRP for PDR. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial (55 U.S. sites) assessing non-inferiority of ranibizumab compared with PRP for vision outcomes; 305 adults with PDR enrolled February-December 2012 (mean age 52, 44% female, 52% white). Both eyes enrolled for 89 participants totaling 394 study eyes. The final 2-year visit was completed January 2015. INTERVENTIONS Ranibizumab group (N=191 eyes): intravitreous 0.5-mg ranibizumab and, PRP if treatment failed; ranibizumab as needed for DME. PRP group (N=203 eyes): PRP; ranibizumab as needed for DME. MAIN OUTCOMES AND MEASURES Primary: mean visual acuity change at 2 years (5-letter non-inferiority margin; intention-to-treat analysis). Secondary: visual acuity area under the curve, peripheral visual field loss, DME development, neovascularization, vitrectomy, and safety. RESULTS Mean visual acuity letter improvement at 2 years was +2.8 in the ranibizumab group versus +0.2 in the PRP group (difference +2.2, 95% confidence interval [CI]: −0.5 to +5.0, non-inferiority P<0.001). Mean treatment group difference in visual acuity area under the curve over 2 years was +4.2 (95% CI: +3.0 to +5.4, P<0.001). Visual field sensitivity loss was worse (mean dB difference 372; 95% CI: 213 to 531, P<0.001), vitrectomy more frequent (15% versus 4%, difference 9%, 95% CI: 4% to 15%, P<0.001), and DME development more frequent (28% versus 9%, difference 19%, 95% CI: 10% to 28%, P<0.001) in the PRP versus ranibizumab group, respectively. Eyes with neither active nor regressed neovascularization at 2 years was similar (35% [ranibizumab group] versus 30% [PRP group], difference 3%, 95% CI: −7% to 12%, P=0.58). One eye (ranibizumab group) developed endophthalmitis. No significant differences between groups in rates of major cardiovascular events were identified. CONCLUSION Among eyes with PDR, treatment with ranibizumab resulted in visual acuity that was non-inferior to (not worse than) PRP treatment at two years. Although longer term follow-up is needed, ranibizumab may be a reasonable treatment alternative, at least through 2 years, for patients with PDR.

Age-related macular degeneration (AMD) is the leading cause of irreversible severe visual loss in the United States in people over 50 years of age. The nonexudative stage includes hard drusen (associated with localized dysfunction of the retinal pigment epithelium [RPE]), soft drusen (associated with diffuse dysfunction of the RPE), and geographic (areolar) atrophy. These fundus changes may predispose the eye to develop the neovascular/exudative stages of AMD. Most patients who develop severe visual loss from AMD have this exudative stage. Treatment for AMD has been shown to be effective for only a small proportion of patients who have a well-defined choroidal neovascular membrane (CNVM) more than 200 microns from the foveal center. Even in successfully treated cases, severe visual loss is postponed only for about 18 months because of the high rate of recurrent CNVMs that extend into the fovea. Thus, despite recent breakthroughs in laser treatment for AMD, most patients who develop the exudative form of AMD will develop central visual impairment. At the present time, the only available treatments for the majority of patients who develop the exudative form of AMD are low vision aids. Investigators are currently evaluating whether treatment is effective for membranes within 200 microns of the foveal center. Future studies need to be directed toward further understanding of the pathogenesis, treatment and prevention of the blinding complications of AMD.