Association Between Change in Visual Acuity and Change in Central Subfield Thickness During Treatment of Diabetic Macular Edema in Participants Randomized to Aflibercept, Bevacizumab, or Ranibizumab: A Post Hoc Analysis of the Protocol T Randomized Clinical Trial
Neil M Bressler, Isoken Odia, Maureen Maguire, Adam R Glassman, Lee M Jampol, Mathew W MacCumber, Chirag Shah, Daniel Rosberger, Jennifer K Sun, DRCR Retina Network, Neil M Bressler, Isoken Odia, Maureen Maguire, Adam R Glassman, Lee M Jampol, Mathew W MacCumber, Chirag Shah, Daniel Rosberger, Jennifer K Sun, DRCR Retina Network
Abstract
Importance: The determination of optical coherence tomography (OCT) central subfield thickness (CST) is an objective measure, and visual acuity (VA) is a subjective measure. Therefore, using OCT CST changes as a surrogate for VA changes in diabetic macular edema seems reasonable. However, studies suggest that change in OCT CST following anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema is correlated with changes in VA but varies substantially among individuals, and so may not be a good surrogate for changes in VA.
Objective: To determine associations between changes in VA and changes in OCT CST across 3 anti-VEGF agents (aflibercept, bevacizumab, or ranibizumab) used in a randomized clinical trial for diabetic macular edema.
Design, setting, and participants: Post hoc analyses were conducted of DRCR Retina Network Protocol T among 652 of 660 participants (98.8%) meeting inclusion criteria for this investigation. The study was conducted between August 22, 2012, and September 23, 2015. The post hoc data collection and analysis were performed from May 29 to July 11, 2018.
Interventions: Six monthly intravitreous anti-VEGF injections (unless success was achieved after 3-5 months) were administered; subsequent injections or focal/grid laser photocoagulation treatments were given as needed per protocol to achieve stability.
Main outcomes and measures: Association between changes in VA letter score with changes in CST at 12, 52, and 104 weeks after randomization to aflibercept, bevacizumab, or ranibizumab.
Results: Of the 652 participants, 304 were women (46.6%); median age was 61 years (interquartile range, 54-67 years). The correlation between CST and VA at the follow-up visits was 0.24 (95% CI, 0.16-0.31) in 616 patients at 12 weeks, 0.31 (95% CI, 0.24-0.38) in 609 patients at 52 weeks, and 0.23 (95% CI, 0.15-0.31) in 566 patients at 104 weeks. The correlation coefficients of change in VA vs change in OCT CST for these time intervals were 0.36 (95% CI, 0.29-0.43) at 12 weeks, 0.36 (95% CI, 0.29-0.43) at 52 weeks, and 0.33 (95% CI, 0.26-0.41) at 104 weeks.
Conclusions and relevance: Changes in CST appear to account for only a small proportion of the total variation in changes in VA. These findings do not support using changes in OCT CST as a surrogate for changes in VA in phase 3 clinical trials evaluating anti-VEGF for diabetic macular edema or as a guide to inform the physician or patient about changes in VA after anti-VEGF treatment.
Trial registration: ClinicalTrials.gov identifier: NCT01627249.
Conflict of interest statement
Conflict of Interest Disclosures: Dr Bressler reported grants from the National Eye Institute (NEI) during the conduct of the study as well as grants from Bayer, Genentech/Roche, Novartis, and Samsung Bioepis outside the submitted work. Dr Odia reported grants from the National Institutes of Health (NIH) and nonfinancial support from Regeneron and Genentech during the conduct of the study. Dr Maguire reported grants from NEI Funding through the Jaeb Center for Health Research during the conduct of the study and personal fees from Genentech/Roche outside the submitted work. Dr Glassman reported grants from NEI during the conduct of the study and grants from Genentech, Regeneron, and Allergan outside the submitted work. Dr Jampol reported grants from the NEI during the conduct of the study. Dr MacCumber reported grants from Allergan, Genentech, Aerpio, and Regeneron during the conduct of the study; personal fees from Genentech, Regeneron, Allergan, Novartis, and the NEI outside the submitted work. Dr Shah reported other support from Regeneron and other support from Genentech/Roche outside the submitted work. Dr Sun reported grants from the Jaeb Center for Health Research during the conduct of the study and nonfinancial support from Optovue, Zeiss, and Heidelberg outside the submitted work. No other disclosures were reported.
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Source: PubMed