Effect of Intravitreous Aflibercept vs Vitrectomy With Panretinal Photocoagulation on Visual Acuity in Patients With Vitreous Hemorrhage From Proliferative Diabetic Retinopathy: A Randomized Clinical Trial

Abstract

Importance: Vitreous hemorrhage from proliferative diabetic retinopathy can cause loss of vision. The best management approach is unknown.

Objective: To compare initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation for vitreous hemorrhage from proliferative diabetic retinopathy.

Design, setting, and participants: Randomized clinical trial at 39 DRCR Retina Network sites in the US and Canada including 205 adults with vison loss due to vitreous hemorrhage from proliferative diabetic retinopathy who were enrolled from November 2016 to December 2017. The final follow-up visit was completed in January 2020.

Interventions: Random assignment of eyes (1 per participant) to aflibercept (100 participants) or vitrectomy with panretinal photocoagulation (105 participants). Participants whose eyes were assigned to aflibercept initially received 4 monthly injections. Both groups could receive aflibercept or vitrectomy during follow-up based on protocol criteria.

Main outcomes and measures: The primary outcome was mean visual acuity letter score (range, 0-100; higher scores indicate better vision) over 24 weeks (area under the curve); the study was powered to detect a difference of 8 letters. Secondary outcomes included mean visual acuity at 4 weeks and 2 years.

Results: Among 205 participants (205 eyes) who were randomized (mean [SD] age, 57 [11] years; 115 [56%] men; mean visual acuity letter score, 34.5 [Snellen equivalent, 20/200]), 95% (195 of 205) completed the 24-week visit and 90% (177 of 196, excluding 9 deaths) completed the 2-year visit. The mean visual acuity letter score over 24 weeks was 59.3 (Snellen equivalent, 20/63) (95% CI, 54.9 to 63.7) in the aflibercept group vs 63.0 (Snellen equivalent, 20/63) (95% CI, 58.6 to 67.3) in the vitrectomy group (adjusted difference, -5.0 [95% CI, -10.2 to 0.3], P = .06). Among 23 secondary outcomes, 15 showed no significant difference. The mean visual acuity letter score was 52.6 (Snellen equivalent, 20/100) in the aflibercept group vs 62.3 (Snellen equivalent, 20/63) in the vitrectomy group at 4 weeks (adjusted difference, -11.2 [95% CI, -18.5 to -3.9], P = .003) and 73.7 (Snellen equivalent, 20/40) vs 71.0 (Snellen equivalent, 20/40) at 2 years (adjusted difference, 2.7 [95% CI, -3.1 to 8.4], P = .36). Over 2 years, 33 eyes (33%) assigned to aflibercept received vitrectomy and 34 eyes (32%) assigned to vitrectomy received subsequent aflibercept.

Conclusions and relevance: Among participants whose eyes had vitreous hemorrhage from proliferative diabetic retinopathy, there was no statistically significant difference in the primary outcome of mean visual acuity letter score over 24 weeks following initial treatment with intravitreous aflibercept vs vitrectomy with panretinal photocoagulation. However, the study may have been underpowered, considering the range of the 95% CI, to detect a clinically important benefit in favor of initial vitrectomy with panretinal photocoagulation.

Trial registration: ClinicalTrials.gov Identifier: NCT02858076.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Antoszyk reported receiving grants from Roche Genentech; and serving as a consultant to the Jaeb Center for Health Research, Opthea, Clearside, Roche Genentech, Regeneron, and Novartis. Mr Glassman reported receiving grants and nonfinancial support from Genentech, Regeneron, and Allergan. Dr Beaulieu reported receiving grants and nonfinancial support from Genentech, Regeneron, and Allergan. Dr Jampol reported receiving personal fees from Sanofi. Dr Jhaveri reported receiving personal fees from Genentech, Allergan, and Novartis. Dr Wells reported receiving grants and personal fees from Genentech and Adverum; and participating in clinical research with Emmes, Genentech, Kodiak, Lpath Incorporated, Neurotech, Ophthotech, Opthea, Regeneron, and Thrombogenics. Dr Maguire reported receiving personal fees from Genentech; and receiving payment from the Jaeb Center for Health Research paid to her institution. Ms Stockdale reported receiving grants and nonfinancial support from Genentech, Regeneron, and Allergan. Dr Sun reported receiving grants from the Jaeb Center for Health Research, Roche Genentech, the Juvenile Diabetes Research Foundation, and Kalvista; receiving personal fees from Current Diabetes Reports, JAMA Ophthalmology, and Merck; receiving nonfinancial support from Optovue (equipment loaned for research), Boston Micromachines, Adaptive Sensory Technologies, Roche Genentech (food/beverage), Novartis, and Kalvista (travel support); and receiving grants and nonfinancial support from Novo Nordisk, Boehringer Ingelheim, and Roche. No other disclosures were reported.

Figures

Figure 1.. Randomization and Participant Flow in the Trial

aMissing data were imputed via multiple imputation for the primary analysis of visual acuity over 24 weeks. Participants were not formally screened before obtaining informed consent. The reasons for participant ineligibility were not systematically collected. Visit completion at 2 years was prespecified as completion of any study visit from 92 to 116 weeks.

Figure 2.. Visual Acuity Letter Score Through 2 Years

Within each box and whisker plot, the horizontal bar represents the median and the white square represents the mean. The top of the box is the third quartile (75th percentile) and the bottom of the box is the first quartile (25th percentile). Whiskers extend from the nearest quartile to the most extreme data point within 1.5 times the interquartile range; values beyond these limits are plotted as circles. The number of eyes completing each visit and the cumulative number of eyes that received alternative treatment through the visit (eg, aflibercept in the vitrectomy group or vitrectomy in the aflibercept group) appear below the plot. The best-corrected visual acuity was collected after protocol-defined refraction. Visual acuity was measured using electronic Early Treatment for Diabetic Retinopathy Study visual acuity testing on a scale from 100 letters (Snellen equivalent, 20/10) to 0 letters (Snellen equivalent,