Ultra-Response to Ranibizumab: Improvement by 4 or More Steps in Diabetic Retinopathy Severity in Diabetic Retinopathy Clinical Research Network Protocol S.

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.