Predictors of Early Diabetic Retinopathy Regression with Ranibizumab in the RIDE and RISE Clinical Trials

Michael Singer; Mimi Liu; Patricio G Schlottmann; Arshad M Khanani; Miranda Hemphill; Lauren Hill; Lisa Tuomi; Zdenka Haskova

doi:10.2147/OPTH.S247061

Predictors of Early Diabetic Retinopathy Regression with Ranibizumab in the RIDE and RISE Clinical Trials

Clin Ophthalmol. 2020 Jun 17:14:1629-1639. doi: 10.2147/OPTH.S247061. eCollection 2020.

Authors

Michael Singer¹, Mimi Liu², Patricio G Schlottmann³, Arshad M Khanani⁴, Miranda Hemphill⁵, Lauren Hill⁵, Lisa Tuomi⁵, Zdenka Haskova⁵

Affiliations

¹ Medical Center Ophthalmology Associates, San Antonio, TX, USA.
² Colorado Retina Associates, Denver, CO, USA.
³ Organizacion Medica de Investigacion, Buenos Aires, Argentina.
⁴ Sierra Eye Associates, Reno, NV, USA.
⁵ Genentech, Inc., South San Francisco, CA, USA.

Abstract

Purpose: To investigate the predictors of early diabetic retinopathy (DR) improvement in the RIDE/RISE (NCT00473382/NCT00473330) clinical trials.

Patients and methods: In RIDE/RISE, adult patients with vision loss due to diabetic macular edema (DME) were randomized to monthly intravitreal ranibizumab 0.3 or 0.5 mg (n=502 total) or sham (n=257). DR severity was graded (using the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale). In this post hoc analysis of RIDE/RISE, eyes with baseline DR score ≥35 were evaluated for ≥2-step improvements, and eyes with baseline DR score ≥43 were evaluated for ≥3-step improvements. The characteristics associated with ≥2- or ≥3-step DR improvement at months 3 or 6 were assessed using univariate and/or multivariable analyses.

Results: The percentage of eyes with a ≥2- or ≥3-step DR improvement was 20.1% and 3.7% at month 3 and 31.2% and 5.8% at month 6. Odds of ≥2-step DR improvement at months 3 or 6 were significantly greater in eyes with moderately severe to severe nonproliferative DR (NPDR) at baseline versus less severe or more severe DR (both P<0.0001). At month 6, odds of ≥2-step DR improvement were significantly greater in eyes with no DME at month 3 (P=0.008). Most patients with ≥3-step DR improvement at months 3 or 6 had proliferative DR (PDR) at baseline (83.3% and 66.7%).

Conclusion: The strongest predictors of DR response to ranibizumab at month 6 were baseline DR severity and DME quiescence at month 3. Eyes with the most robust early improvements had moderately severe or severe NPDR or PDR at baseline.

Keywords: anti-VEGF; diabetic macular edema; diabetic retinopathy; post hoc; ranibizumab.

Associated data

ClinicalTrials.gov/NCT00473330

Grants and funding

Genentech, Inc., South San Francisco, CA, USA, provided support for the study and participated in the study design; conducting the study; and data collection, management, and interpretation.