Higher-Order Optical Coherence Tomography (OCT) Fluid Burden Assessment: Analysis From the OSPREY Extended Phase

Abstract

Purpose : Current conventional OCT metrics are traditionally limited to global measures of retinal thickness or retinal volume. These metrics do not provide insight regarding specific underlying pathologic features, such as quantifying intraretinal fluid (IRF) and subretinal fluid (SRF). Higher-order OCT assessment enables in-depth evaluation of Spectral Domain-OCT (SD-OCT) imaging biomarkers for therapeutic effect, including volumetric and area measurements of IRF/SRF. This analysis evaluated the fluid burden metrics in the OSPREY phase II trial for neovascular age-related macular degeneration (nAMD) following treatment with brolucizumab or aflibercept during the extended phase.

Methods : The OSPREY trial is a phase II randomized, double-masked, active-controlled study of 56 weeks’ duration comparing brolucizumab to aflibercept in nAMD. In OSPREY, nAMD subjects were randomized 1:1 to brolucizumab 6 mg or aflibercept 2 mg, both at q8w dosing through Week 40 after 3 monthly loading doses. The final cycle was extended in the brolucizumab group for assessment of q12w dosing, with the aflibercept group maintained on q8w dosing. Weeks 32, 36, 40, 44, 48, 52, and 56 were selected as timepoints for higher-order OCT analysis to provide information on differential responses at extended-interval dosing. Macular cube scans were uploaded into a novel analysis software platform, and macular IRF volume, macular central foveal IRF area (single B-scan fluid area), and macular SRF volume were quantified using an advanced-analysis algorithm.

Results : Eyes that perform optimally to q12w dosing with brolucizumab may be identified, as well as eyes at risk for fluid rebound with extended interval dosing. Baseline features that may be predictive of tolerance at various treatment intervals will be evaluated. This analysis will also enable comparative assessment of fluid dynamics during treatment with q12w brolucizumab and q8w aflibercept.

Conclusions : Following anti-VEGF therapy for nAMD, varying degrees of fluid frequently persist. In this study, a novel OCT analysis approach enabled volumetric characterization of IRF/SRF. This allows for a unique assessment of persistent fluid and provides opportunities for identification of imaging biomarkers that may predict optimal response to therapeutics, and determination of best dosing regimens and overall prognosis.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.