Use of Total Retinal Fluid Index to Estimate Fluid Volume in Wet AMD

Total retinal fluid index (TRFI) is a novel optical coherence tomography (OCT) parameter in wet age-related macular degeneration (AMD) that estimates the proportion of fluid volume against total retinal volume in a designated area, represented as a fluid percentage. A study found that TRFI analysis provides a unique estimate of fluid burden following anti-vascular endothelial growth factor therapy in wet AMD. The results of the study were published as part of the American Society of Retina Specialists 2020 Virtual Annual Meeting.

The randomized, double-masked, prospective, phase II, 56-week OSPREY trial compared brolucizumab 6 mg (every eight weeks followed by every 12 weeks) versus aflibercept 2 mg (every eight weeks) in 90 treatment-naïve patients with wet AMD. Macular OCT scans underwent multi-layer segmentation with fluid object extraction using a novel analysis platform.

TRFI was defined as 100 × (intraretinal + subretinal fluid volume) / total retina + fluid compartment volume; total retina + fluid compartment volume was the space between the internal limiting membrane and retinal pigment epithelium. Zone of TRFI assessment included total macular (entire macular cube), central macular (central 2 mm), and central subfield (central 1 mm).

The study observed a rapid decrease in the TRFI in all zones (total macular, central macular, and central subfield) from baseline in both the brolucizumab and aflibercept groups (P<0.005 for all time points).

Total macular TRFI at baseline was 3.8% in the brolucizumab cohort and 3.4% in the aflibercept group. At week 40, total macular TRFI decreased to 0.2% and 0.3%, respectively, with similar values observed at week 56. Central macular TRFI at baseline was 8.7% in the brolucizumab cohort and 7.4% in the aflibercept group. At weeks four, 40, and 56, these values were 0.9%, 0.7%, and 0.7%, respectively, in the brolucizumab group and 2.6%, 0.9%, and 2.0%, respectively, in the aflibercept group.

Central subfield TRFI at baseline was 13.9% and 11.2% in the brolucizumab and aflibercept groups, respectively. The central subfield TRFI following brolucizumab versus aflibercept treatment was 1.6% versus 4.0% (P=0.04), 1.3% versus 1.6% (P=0.74), and 1.0% versus 3.1% (P=0.08) at weeks four, 40, and 56, respectively.

“This novel OCT parameter needs further exploration as a biomarker for response and outcomes. The results in this analysis are consistent with previous OSPREY analyses demonstrating a reduction in fluid burden with brolucizumab every eight weeks, which is maintained with every 12 week dosing,” the researchers concluded.

Srivastava S, Clark J, Uchida A, et al. Longitudinal Total Retinal Fluid Index Assessment in nAMD From the OSPREY Study: A Novel Assessment of Fluid Drying Effect. Presented during the ASRS 2020 Virtual Annual Meeting, July 24-26, 2020.