Abstract
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. Trial Registration: ClinicalTrials.gov Identifier: NCT01489189.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1138-1148 |
| Number of pages | 11 |
| Journal | JAMA ophthalmology |
| Volume | 136 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 2018 |
Funding
completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Gross reports grants from Jaeb Center for Health Research, Acucela, Genentech, Regeneron, and Ohr Pharmaceutical Inc and personal fees from Jaeb Center for Health Research during the conduct of the study. Mr Glassman reports grants from the National Institutes of Health and Genentech during the conduct of the study; nonfinancial support from Genentech and Allergan during the conduct of the study; and grants from Regeneron outside the submitted work. Ms Liu reports cooperative agreements from the National Eye Institute and National Institute of Diabetes and Digestive and Kidney Diseases and nonfinancial support and other from Genentech during the conduct of the study. Dr Sun reports grants from Genentech, Juvenile Diabetes Research Foundation, KalVista Pharmaceuticals, and Boehringer Ingelheim; personal fees from Eleven Biotherapeutics Inc, Vindico Medical Education, Current Diabetes Reports, Merck & Co, Allergan, Kowa Company Ltd, Novartis, Regeneron, and Bayer; nonfinancial support from Optovue, Boston Micromachines Corporation, Genentech, Novartis, Novo Nordisk, and Adaptive Sensory Technologies; and other from KalVista Pharmaceuticals outside the submitted work. Dr Antoszyk reports consultant fees from Roche Genentech, Opthea, and Jaeb Center for Health Research. Dr Baker reports grants for clinical research from Regeneron, Genentech, Alcon Novartis, Allergan, and Ophthotech outside the submitted work. Dr Bressler reports grants from the National Institutes of Health to his institution during the conduct of the study and grants from Bayer, Novartis, Roche Genentech, and Samsung Bioepis Co Ltd outside the submitted work to his institution. Dr Elman reports grants from Jaeb Center for Health Research during the conduct of the study; grants from Roche Genentech and Regeneron outside the submitted work, personal fees from Roche Genentech outside the submitted work; and nonfinancial support from Roche Genentech outside the submitted work. Dr Gardner reports grants from Novo Nordisk and Zebra Biologicals Inc outside the submitted work. Dr Jampol reports a grant from the National Eye Institute during the conduct of the study. Ms Melia reports a grant from National Eye Institute to their institution during the conduct of the study; other from Genentech during the conduct of the study; and other from Regeneron outside the submitted work. Ms Stockdale reports grants from the National Institutes of Health and Genentech and nonfinancial support from Genentech during the conduct of the study. Dr Beck reports grants to his employer from the National Eye Institute and Genentech during the conduct of the study; nonfinancial support from Genentech during the conduct of the study; and a grant and nonfinancial support from Regeneron outside the submitted work. No other disclosures were reported. A complete list of all Diabetic Retinopathy Clinical Research Network investigator financial disclosures can also be found at http://www.drcr.net. through a cooperative agreement from the National Eye Institute, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, and US Department of Health and Human Services (grants EY14231, EY23207, EY18817). Genentech provided ranibizumab for the study and funds to the Diabetic Retinopathy Clinical Research Network to defray the study’s clinical site costs.
ASJC Scopus subject areas
- Ophthalmology
