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

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.

• Authors: Allen Chiang, Sunir J Garg, Michael A Klufas, Allen C Ho, Lauren Hill, Min Tsuboi, Ivaylo Stoilov
• Journal: Ophthalmology. Retina (Ophthalmol Retina) Vol. 5 Issue 3 Pg. 251-260 (03 2021) ISSN: 2468-6530 [Electronic] United States
• PMID: 32735903 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Vascular Endothelial Growth Factor A
• Ranibizumab

Topics

• Angiogenesis Inhibitors (administration & dosage)
• Diabetic Retinopathy (diagnosis, drug therapy, physiopathology)
• Disease Progression
• Humans
• Intravitreal Injections
• Ranibizumab (administration & dosage)
• Retina (diagnostic imaging)
• Retrospective Studies
• Severity of Illness Index
• Treatment Outcome
• Vascular Endothelial Growth Factor A (antagonists & inhibitors)
• Visual Acuity