Onset and progression of persistent choroidal hypertransmission defects in intermediate AMD: A novel clinical trial endpoint

Abstract

Purpose : The appearance and growth of persistent choroidal hypertransmission defects (hyperTDs) detected on en face swept-source OCT (SS-OCT) images from eyes with intermediate AMD (iAMD) were studied to determine if they could serve as novel clinical trial endpoints.

Methods : Subjects with iAMD underwent 6x6mm SS-OCT angiography (SS-OCTA) imaging at baseline and during their follow-up visits. The drusen volume measurements within a 5mm fovea-centered circle were obtained using a validated SS-OCT algorithm. En face images were generated using a slab with segmentation boundaries positioned 64 to 400 µm beneath Bruch’s membrane. Two graders independently evaluated all en face structural images for the presence of persistent hyperTDs, which are defined as bright areas having a greatest linear dimension of ≥ 250 µm. At each visit, the number and area of all hyperTDs as well as drusen volume were obtained from all SS-OCTA scans. Eyes were censored from further follow-up once exudative AMD developed.

Results : A total of 171 eyes from 121 patients with iAMD were included with a mean follow up of 43 months. Of the 171 eyes, 68 eyes developed at least one hyperTD. The drusen volume at one year preceding the formation of the first hyperTD was approximately 0.18 mm³. Within a year after developing a hyperTD, 25% of eyes developed new hyperTDs for an average of 0.44 additional hyperTDs. Over two years, as hyperTDs appeared, enlarged, and merged, the average area growth rate of these hyperTDs was 0.220 mm/yr using the square-root transformation strategy. Based on the natural history study results, we propose a 2-year randomized, prospective clinical trial to test therapies that may slow disease progression in eyes with iAMD. We will enroll at least 100 subjects with a drusen volume ≥ 0.20 mm³ into each arm of the study so that at least 71 eyes in the control group develop hyperTDs after 1-year of follow-up. After 2-years of follow-up, the study will then have a 90% power, with an alpha of 0.05, to detect a 50% decrease in the overall enlargement rate of these hyperTDs.

Conclusions : The appearance and growth of persistent choroidal hyperTDs in eyes with iAMD can be easily detected and measured using en face OCT imaging and can serve as novel clinical trial endpoints for the study of therapies that may slow disease progression from iAMD to late AMD.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.