Tolerating Subretinal Fluid in the Treatment of Neovascular Age-Related Macular Degeneration With Ranibizumab Using a Treat and Extend Regimen

Abstract

Purpose : It is unknown whether subretinal fluid (SRF) presence can be tolerated when treating patients with anti-VEGF therapy without compromising visual outcomes. The FLUID study was a 24 month, phase IV, single masked, multicentre, randomized clinical trial of eyes with neovascular age-related macular degeneration (nAMD) treated with ranibizumab. We tested the hypothesis that tolerating SRF can achieve similar visual acuity outcomes using a treat and extend (T&E) regimen relative to SRF not being tolerated.

Methods : We randomized subjects with active CNV affecting the fovea to receive monthly 0.5 mg ranibizumab until complete resolution of SRF and intraretinal fluid (IRF) (intensive arm i.e. SRF intolerant) or resolution of IRF and >200 µm SRF (relaxed arm i.e. SRF tolerant) before extending intervals. A 5 letter non-inferiority margin was applied to the primary outcome of mean change in BCVA from Baseline to Month 24.

Results : Of the 349 subjects randomised (174 in intensive group, 175 in relaxed group), 279 (79.9%) completed the Month 24 study. Baseline characteristics were well-balanced with the exception of area of lesion (p<0.05) and area of CNV (p<0.01) both of which were larger in the intensive group. The mean (SD) change in BCVA from Baseline to Month 24 was 3.2 (16.51) letters in the intensive group and 2.5 (16.56) letters in the relaxed group demonstrating non-inferiority of the relaxed treatment to the intensive treatment (p=0.787). There was no difference between the intensive and relaxed groups for the proportion of subjects with ≥20/40 VA (55.1% and 58.3%, respectively; p=0.901) nor ≤20/200 VA (8.2% and 8.6%, respectively; p=0.397). The average reduction in central retinal thickness was larger numerically in the intensive group compared to the relaxed group (p=0.054). Numerically, more subjects in the relaxed group never resolved their baseline SRF (15%) nor their baseline IRF (14.8%) compared to the intensive group (9.5%; p=0.249 and 7.5%; p=0.059, respectively). Subjects in the relaxed group received fewer ranibizumab injections over the 24-month study (mean [SD]; 15.8 [5.91]) than those in the intensive group (17 [6.48]; p=0.001).

Conclusions : Patients treated with a ranibizumab T&E protocol that tolerates <200 µm SRF may achieve visual acuity that is comparable to that achieved when treatment aims to completely resolve all SRF.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.