Allen Chiang1, Sunir J Garg2, Michael A Klufas2, Allen C Ho2, Lauren Hill3, Min Tsuboi3, Ivaylo Stoilov3. 1. Mid Atlantic Retina, The Retina Service of Wills Eye Hospital, Philadelphia, Pennsylvania. Electronic address: achiang@midatlanticretina.com. 2. Mid Atlantic Retina, The Retina Service of Wills Eye Hospital, Philadelphia, Pennsylvania. 3. Genentech, Inc., South San Francisco, California.
Abstract
PURPOSE: To quantify and evaluate patients with diabetic retinopathy (DR) who had at least a 4-step improvement on the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) in response to treatment with ranibizumab in the Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol S study, and factors predictive of such improvements. DESIGN: Post hoc retrospective analysis of 2-year outcomes in the phase 3 Protocol S study. PARTICIPANTS: Patients randomized to treatment with ranibizumab 0.5 mg with sufficient baseline DRSS severity (≥47) to allow for an at least 4-step improvement (n = 181). METHODS: Study eyes received a ranibizumab 0.5 mg injection at baseline and every 4 weeks for 12 weeks, with subsequent as-needed injections. Fundus photographs graded at baseline and years 1 and 2 using DRSS were used for this analysis. The data source is DRCR.net, but analyses, content, and conclusions of this report are solely the responsibility of the authors. MAIN OUTCOME MEASURES: Proportion of eyes achieving at least a 4-step DRSS improvement (DR ultra-response) at years 1 and 2; treatment course for eyes achieving ultra-response; mean change in best-corrected visual acuity (BCVA) in eyes with and without ultra-response; factors associated with ultra-response (identified by univariate and multivariable analyses). RESULTS: Approximately 30% of ranibizumab-treated eyes achieved DR ultra-response at year 1 (43/148; 29.1%) and year 2 (38/136; 27.9%); 74% of eyes with ultra-response at year 1 maintained their response at year 2. At year 2, patients with DR ultra-response had gained more than 5 additional ETDRS letters compared with those without DR ultra-response. Multivariable analyses identified presence of vitreous hemorrhage at baseline, increasing age, absence of epiretinal membrane, and glycated hemoglobin below 9 as predictive of DR ultra-response. Mean number of injections received was similar for eyes with versus without DR ultra-response to ranibizumab (mean, 7.4 vs. 7.6 in year 1; mean, 4.2 vs. 3.9 in year 2). CONCLUSIONS: Approximately 30% of eyes with a DRSS score of at least 47 receiving ranibizumab 0.5 mg per study protocol experienced at least a 4-step DR severity improvement on the DRSS, accompanied by meaningful improvements in BCVA.
RCT Entities:
PURPOSE: To quantify and evaluate patients with diabetic retinopathy (DR) who had at least a 4-step improvement on the Early Treatment Diabetic Retinopathy Study (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) in response to treatment with ranibizumab in the Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol S study, and factors predictive of such improvements. DESIGN: Post hoc retrospective analysis of 2-year outcomes in the phase 3 Protocol S study. PARTICIPANTS: Patients randomized to treatment with ranibizumab 0.5 mg with sufficient baseline DRSS severity (≥47) to allow for an at least 4-step improvement (n = 181). METHODS: Study eyes received a ranibizumab 0.5 mg injection at baseline and every 4 weeks for 12 weeks, with subsequent as-needed injections. Fundus photographs graded at baseline and years 1 and 2 using DRSS were used for this analysis. The data source is DRCR.net, but analyses, content, and conclusions of this report are solely the responsibility of the authors. MAIN OUTCOME MEASURES: Proportion of eyes achieving at least a 4-step DRSS improvement (DR ultra-response) at years 1 and 2; treatment course for eyes achieving ultra-response; mean change in best-corrected visual acuity (BCVA) in eyes with and without ultra-response; factors associated with ultra-response (identified by univariate and multivariable analyses). RESULTS: Approximately 30% of ranibizumab-treated eyes achieved DR ultra-response at year 1 (43/148; 29.1%) and year 2 (38/136; 27.9%); 74% of eyes with ultra-response at year 1 maintained their response at year 2. At year 2, patients with DR ultra-response had gained more than 5 additional ETDRS letters compared with those without DR ultra-response. Multivariable analyses identified presence of vitreous hemorrhage at baseline, increasing age, absence of epiretinal membrane, and glycated hemoglobin below 9 as predictive of DR ultra-response. Mean number of injections received was similar for eyes with versus without DR ultra-response to ranibizumab (mean, 7.4 vs. 7.6 in year 1; mean, 4.2 vs. 3.9 in year 2). CONCLUSIONS: Approximately 30% of eyes with a DRSS score of at least 47 receiving ranibizumab 0.5 mg per study protocol experienced at least a 4-step DR severity improvement on the DRSS, accompanied by meaningful improvements in BCVA.