Neil M Bressler1,2, Isoken Odia3, Maureen Maguire4, Adam R Glassman3, Lee M Jampol5, Mathew W MacCumber6, Chirag Shah7, Daniel Rosberger8, Jennifer K Sun9,10. 1. Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland. 2. Editor, JAMA Ophthalmology. 3. Jaeb Center for Health Research, Tampa, Florida. 4. Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania. 5. Feinberg School of Medicine, Northwestern University, Chicago, Illinois. 6. Rush University Medical Center, Chicago, Illinois. 7. Ophthalmic Consultants of Boston, Boston, Massachusetts. 8. MaculaCare, New York, New York. 9. Joslin Diabetes Center, Beetham Eye Institute, Harvard Department of Ophthalmology Boston, Massachusetts. 10. CME Editor, JAMA Cardiology.
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.
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.
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