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.

; for the Diabetic Retinopathy Clinical Research Network IMPORTANCE Ranibizumab is a viable treatment option for eyes with proliferative diabetic retinopathy (PDR) through 2 years. However, longer-term results are needed. OBJECTIVE To evaluate efficacy and safety of 0.5-mg intravitreous ranibizumab vs panretinal photocoagulation (PRP) over 5 years for PDR. DESIGN, SETTING, AND PARTICIPANTS Diabetic Retinopathy Clinical Research Network multicenter randomized clinical trial evaluated 394 study eyes with PDR enrolled February through December 2012. Analysis began in January 2018. INTERVENTIONS Eyes were randomly assigned to receive intravitreous ranibizumab (n = 191) or PRP (n = 203). Frequency of ranibizumab was based on a protocol-specified retreatment algorithm. Diabetic macular edema could be managed with ranibizumab in either group. MAIN OUTCOMES AND MEASURES Mean change in visual acuity (intention-to-treat analysis) was the main outcome. Secondary outcomes included peripheral visual field loss, development of vision-impairing diabetic macular edema, and ocular and systemic safety. RESULTS The 5-year visit was completed by 184 of 277 participants (66% excluding deaths). Of 305 enrolled participants, the mean (SD) age was 52 (12) years, 135 (44%) were women, and 160 (52%) were white. For the ranibizumab and PRP groups, the mean (SD) number of injections over 5 years was 19.2 (10.9) and 5.4 (7.9), respectively; the mean (SD) change in visual acuity letter score was 3.1 (14.3) and 3.0 (10.5) letters, respectively (adjusted difference, 0.6; 95% CI, −2.3 to 3.5; P = .68); the mean visual acuity was 20/25 (approximate Snellen equivalent) in both groups at 5 years. The mean (SD) change in cumulative visual field total point score was −330 (645) vs −527 (635) dB in the ranibizumab (n = 41) and PRP (n = 38) groups, respectively (adjusted difference, 208 dB; 95% CI, 9-408). Vision-impairing diabetic macular edema developed in 27 and 53 eyes in the ranibizumab and PRP groups, respectively (cumulative probabilities: 22% vs 38%; hazard ratio, 0.4; 95% CI, 0.3-0.7). No statistically significant differences between groups in major systemic adverse event rates were identified. CONCLUSIONS AND RELEVANCE Although loss to follow-up was relatively high, visual acuity in most study eyes that completed follow-up was very good at 5 years and was similar in both groups. Severe vision loss or serious PDR complications were uncommon with PRP or ranibizumab; however, the ranibizumab group had lower rates of developing vision-impairing diabetic macular edema and less visual field loss. Patient-specific factors, including anticipated visit compliance, cost, and frequency of visits, should be considered when choosing treatment for patients with PDR. These findings support either anti-vascular endothelial growth factor therapy or PRP as viable treatments for patients with PDR.

Large PED size is a predictor for RPE tears, and a small ratio of CNV size to PED size (<50%) is more common in eyes with RPE tears. Vision may be preserved despite RPE tears.

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Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.