Residual edema evaluation with ranibizumab 0.5 mg and 2.0 mg formulations for diabetic macular edema (REEF study)

Abstract

Purpose: To compare the efficacy of ranibizumab 0.5-mg and 2.0-mg intravitreal injections for persistent diabetic macular edema (DME) previously treated with bevacizumab.

Methods: In all, 43 patients with residual center-involved DME following intravitreal bevacizumab were included in this 12-month prospective, nonrandomized, multicenter study. Enrolled patients received three monthly ranibizumab 0.5-mg injections. At month 3, patients with residual macular edema switched to three monthly injections of ranibizumab 2.0-mg. Assessments included monthly visual acuity and spectral-domain optical coherence tomography.

Results: Mean visual acuity improved by +6.4 letters at month 3 and +8.8 letters at month 6. Mean central subfield thickness (CST) decreased by -113 μm at month 3 and -165 μm at month 6. Before enrollment, 29/43 (67.4%) patients showed <10% CST reduction following monthly bevacizumab treatment. After three monthly ranibizumab 0.5-mg injections, 22/29 (75.9%) patients showed >10% reduction in CST, whereas 6 showed <10% reduction. Of these six, three (50%) showed >10% reduction in CST after switching to three monthly ranibizumab 2.0-mg doses. No serious adverse events were observed to month 6.

Conclusion: Ranibizumab 0.5-mg or 2.0-mg may improve visual and anatomic outcomes in patients with DME who demonstrated minimal or no response to bevacizumab therapy. Moreover, increased dosage of ranibizumab (2.0-mg) may provide additional benefit over ranibizumab 0.5-mg in some patients. However, 2.0-mg ranibizumab is not currently commercially licensed or available.

Trial registration: ClinicalTrials.gov NCT01292798.

Conflict of interest statement

Dr Dhoot is a consultant for Regeneron. Dr Pieramici is a consultant for Genentech, Inc., Alimera, Allergan, Santen, and ThromboGenics. Dr Castellarin is a consultant for Genentech, Inc. and has a personal financial interest with Alcon. Dr Couvillion has received research funding from Genentech, Inc. Dr Steinle is a speaker for Regeneron. Dr Bennett has received research funding from Genentech, Inc. M. Rabena has received honoraria from Genentech, Inc. Dr Avery is a consultant for Alcon, Allergan, Genentech, Inc., Notal Vision, Novartis, Ophthotech, QLT, Regeneron, and Replenish; has received financial support from Allergan and Genentech, Inc.; has received research funding from Allergan, Genentech, Inc., Novartis, and Regeneron; has a personal financial interest with Alexion, I-Tech JV Development, Novartis, Regeneron, and Replenish; and holds a patent with Replenish. Drs Nasir and See declare no potential conflicts of interest.

Figures

Figure 1

REEF study design. BL, baseline; PRN, pro re nata (as-needed).

Figure 2

(a) Mean change in visual acuity through 6 months compared with baseline. (b) Mean CST from baseline to month 6. Baseline through month 6: n=42; 4 patients did not receive ranibizumab 2.0-mg during months 3 to 5. Vertical bars±standard deviation of the mean. BL, baseline; ETDRS, Early Treatment Diabetic Retinopathy Study.

Figure 3

Complete, partial, and minimal or nonresponse following three ranibizumab 0.5-mg injections and three ranibizumab 2.0-mg injections. *One death, patient not included in analysis.

Figure 4

Percent change in CST through 6 months in six nonresponders following three ranibizumab 0.5-mg injections. The six patients showed minimal reduction in CST following three consecutive ranibizumab 0.5-mg injections; three of six patients showed reduction in CST following ranibizumab 2.0-mg treatment. BL, baseline.