Biweekly Dosing for Refractory Neovascular Age-Related Macular Degeneration

Eric W. Schneider, MD

Increasing the frequency of anti-VEGF dosing in patients with refractory neovascular age-related macular degeneration (nAMD) may lead to significant reductions in nAMD-related intraretinal and subretinal fluid with improvements in visual acuity. 



Eric Schneider, MD, ophthalmologist with Tennessee Retina, presented results of a study at the 2019 American Society of Retina Specialists Annual Meeting that found biweekly anti-VEGF dosing led to reductions in refractory nAMD-related intraretinal and subretinal fluid with improvements in visual acuity among patients after just 5 weeks. 



Investigators noted previous data suggesting a peak effect of anti-VEGF dosing of 2 to 3 weeks post-injection and sought to determine the safety and efficacy of bi-weekly dosing in patients with nAMD-related refractory intraretinal and/or subretinal fluid. In order to evaluate the safety and efficacy of biweekly dosing, investigators conducted a retrospective analysis of 18 patients whose nAMD-related refractory intraretinal or subretinal fluid was determined via optical coherence tomography (OCT). The primary endpoint of the study was OCT central subfield thickness (CST) after the biweekly injection at visit 5.

To be included, patients had to have undergone at least 6 month of monthly anti-VEGF therapy. The mean duration of treatment among the 18 patients was 35.5 months at a mean interval of 30.9 days. Patients included in the analysis received at least 5 consecutive biweekly anti-VEGF doses, which investigators defined as an injection followed by a subsequent injection within 14 (±7) days.

Investigators assessed safety, OCT thickness parameters, and Snellen vision data at all visits beginning with the baseline visit, which was the first biweekly injection, through the first 1-month follow-up visit.

During the study period, patients underwent a mean of 18.1 biweekly injections at a mean interval of 16.5 days. Investigators noted significant improvements in mean CST from baseline to visit 5. 


Additionally, the observed improvement was sustained through the end of biweekly dosing but was lost after returning to standard monthly anti-VEGF dosing. Investigators also found significant improvement in cube volume and average cube thickness at visit 5, but these improvements were sustained upon return to monthly dosing. The complete resolution of fluid was noted in 16.7% of patients at visit 5 and 27.8% of patients at the final biweekly visit.

Of the 18 patients, 16 of them had baseline subretinal fluid. At visit 5, this was resolved in 31.2% of patients and, at the final biweekly visit, it was resolved in 37.5% of patients. Conversely, investigators found that intraretinal fluid, which was found in 5 patients at baseline, was less responsive to biweekly dosing.

Significant improvements in visual acuity from baseline (20/82) to visit 5 (20/47) were noted but not sustained. Investigators reported no cases of endophthalmitis. In their conclusion, investigators noted the need for a prospective study to further understand the value of biweekly dosing in among a similar patient population.

This study, titled “Biweekly Anti-VEGF Dosing for Chronic Refractory Neovascular Age-Related Macular Degeneration Unresponsive to Standard Monthly Dosing,” was presented at ESRS 2019.