Ranibizumab Shows Improved Outcomes for Patients with Concurrent DME, Macular Nonperfusion

Rahul Reddy, MD, MHS

According to the results of a recent post hoc analysis for the RIDE and RISE studies, participants who had diabetic macular edema (DME) and concurrent baseline macular nonperfusion (MNP) experienced improved outcomes when treated with ranibizumab.

Despite these patients having worse vision and more central subfield thickness (CST) than participants without baseline MNP upon entering the trials, they still benefited from the treatment, including increased visual acuity along with improvements in anatomy.

“When we initiated this study, we intended to investigate ranibizumab and its effect not only on [DME] but more specifically on those patients with central ischemia and [DME],” lead author Rahul Reddy, MD, MHS, the director of Clinical Trials and the fellowship director at the Associated Retinal Consultants of Phoenix, told MD Mag. “Conventional teaching was that, in this subgroup, the clinical results may not be as good as those without ischemia, and perhaps an aggressive course of treatment may not be warranted.”

Reddy, also an assistant clinical professor at University of Arizona School of Medicine, and his team analyzed the 2 studies in an attempt to determine if patients with concurrent DME and MNP who were treated with ranibizumab experienced favorable outcomes in best corrected visual acuity (BVCA), anatomy, and diabetic retinopathy compared with patients who entered the studies without concurrent MNP at baseline.

Patients were tracked over a period of 2 years to follow their results post the RIDE and RISE trials—both phase 3, randomized, parallel, double-masked, and multicenter. These patients had the and fluorescein angiogram at baseline. The analysis looked at visual acuity, MNP area, and CST at 1 year and then again at 2 years. They also examined the incidence of ≥2-step diabetic retinopathy improvement in the eyes at 3, 6, 12, 18, and 24 months.

“Our analysis returned a very interesting result: It actually demonstrated that those eyes with ischemia gained more vision than those eyes without ischemia, which goes against conventional thinking and may change practice patterns,” Reddy explained. “This highlights 2 important points: First, we may not fully understand what macular ischemia is. This will likely be delineated in the near future with our new OCT technology. Second, we may want to be aggressive with treatment in that patient population as they may have significant vision to gain.”

Patients’ MNP was measured by laying the Early Treatment for Diabetic Retinopathy Study (ETDRS) grid over the macular fluorescein angiograms. The authors determined the estimated percentage of capillary loss in the inner, outer, and central subfields to determine the MNP and then using an algorithm to convert it into disc areas.

According to their results, 28.2% of patients in the ranibizumab 0.3-mg group (n = 213) had baseline MNP, along with 25.8% in the ranibizumab 0.5-mg arm (n = 225), and 26.3% in the sham arm (n = 225). The patients with baseline MNP tended to be younger, and also began with shorter duration of diabetes, higher CST, worse severity of DR, and worse vision compared with patients without MNP (P <0.01).

Patients in the ranibizumab 0.3-mg group had lower BCVA at baseline (53.4 vs. 57.2 EDTRS letters; P = .05). Although, they experienced a comparable gain in BCVA after 24 months (+15.6 vs. +13.4 EDTRS letters; P = .20).

At the end of 24 months, the eyes with MNP at baseline had reduced CST, even though they’d had higher CST at baseline. In all groups, eyes with MNP experienced a higher improvement in ≥2-step diabetic retinopathy compared with eyes without MNP in all study groups.

Reddy concluded that “the study was retrospective in nature; however, it gives credence to the need for further studies designed to answer this question.”

The complete analysis, “Efficacy of Ranibizumab in Eyes with Diabetic Macular Edema and Macular Nonperfusion in RIDE and RISE,” was published in Ophthalmology.