The impact of the total macular hyperpigmentation on the onset of persistent choroidal hypertransmission defects in intermediate AMD

Abstract

Purpose : The natural history of total macular hyperpigmentation (hyperPig) in eyes with intermediate AMD (iAMD) was studied using swept-source optical coherence tomography (SS-OCT) to determine its association with the onset of persistent choroidal hypertransmission defects (hyperTDs).

Methods : Retrospective review of eyes with iAMD from subjects enrolled in a prospective SS-OCT study who were imaged using 6x6mm SS-OCT angiography (SS-OCTA) scans at baseline and at follow-up visits. En face sub-retinal pigment epithelium (RPE) slabs (64-400 µm beneath Bruch's membrane) were used to identify persistent choroidal hyperTDs. The same subRPE slab was used to identify choroidal hypotransmission defects attributable to hyperPig based on corresponding B-scans and defined as either RPE thickening or intraretinal hyperreflective foci. A semiautomated algorithm was used by two independent graders to validate and refine the outlines of hyperPig foci. The hyperPig area and the drusen volume within a 5mm fovea-centered circle were measured at each visit.

Results : Median follow-up for the 171 eyes from 121 patients in this study was 59.1 months (95% CI: 52.0 to 67.8 months), and 82 eyes developed at least one persistent hyperTD during follow-up. The average baseline hyperPig area measurements differed significantly between eyes that developed hyperTDs (0.085±0.128 mm²) compared with those that did not (0.022±0.053 mm²), P<.001. The hyperPig area increased over time, reaching 0.153±0.183 mm² one year before the appearance of the first hyperTD compared with 0.075 ± 0.127 mm² one year before the last available follow-up visit for the non-hyperTD group (P=.002). A hyperPig area of 0.07 mm² was found to be a significant predictor of hyperTD onset within one year (P<.001). While drusen volume was also a predictor of hyperTD onset, multivariable Cox regression analysis showed that the hyperPig area remained the only significant predictor for hyperTD onset (P<.001).

Conclusions : Total macular hyperPig, which includes both hyperPig along the RPE and within the retina, is an important predictor of disease progression from iAMD to the onset of persistent hyperTDs and a key OCT biomarker for patient selection in future clinical trials.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.