Functional outcomes across high-risk OCT-based phenotypes in intermediate age-related macular degeneration in the prospective PINNACLE study

Abstract

Purpose : to examine how individual OCT biomarkers predict functional outcomes in eyes with intermediate (i)AMD and to investigate whether stratifying eyes by biomarkers identifies phenotypes of iAMD with impaired visual function.

Methods : from the baseline cohort of the PINNACLE trial, 190 patients (247 eyes) underwent OCT imaging, standardized 24-point microperimetry, BCVA and LLVA testing. OCT volumes were assessed by retinal experts for the presence of morphologic features, including hyperreflective foci (HRF), subretinal drusenoid deposits (SDD), hyporeflective drusen cores, refractile drusen, double-layer sign, vitelliform material and the atrophic markers, outer plexiform layer subsidence, hyporeflective wedge, incomplete retinal pigment epithelium and outer retinal atrophy (iRORA). Deep learning algorithms quantified drusen volume, outer nuclear layer (ONL) and ellipsoid zone (EZ) thickness. Linear mixed-effect models (LMMs) evaluated associations between each biomarker and functional outcomes. Eyes were then stratified into groups based on significant OCT features (see Figure 1), with each eye assigned to a single group. Functional outcomes were compared across the four defined groups using LMMs.

Results : in the multivariable LMM, SDD and atrophic markers were associated with significantly lower mean retinal sensitivity (-0.718 dB [p=0.022] and -0.893 dB [p=0.009], respectively). Higher drusen volume and lower ONL and EZ thickness also corresponded to lower sensitivity (-0.003 dB/nL [p=0.003], -0.053 dB/µm [p=0.027], and -0.183 dB/µm [p=0.017], respectively). BCVA and LLVA decreased with increasing drusen volume (-0.006 ltrs/nL [p=0.017] and -0.014 ltrs/nL [p<0.001]). LLVA also decreased with HRF (-3.717 ltrs [p=0.003]). Significant retinal sensitivity differences were found between the structurally defined groups (A:C [1.145 dB, p=0.003], A:D [1.911 dB, p<0.001], B:D [1.009 dB, p=0.024], C:D [0.766 dB, p=0.038]). Predicted outcomes for BCVA and LLVA were significantly lower for groups with signs of early atrophy.

Conclusions : combining detailed analysis of structural OCT biomarkers with functional measures characterizes different disease stages in iAMD and highlights the existence of distinct phenotypes with significant functional impairment. Stratifying patients by high-risk drusen and atrophy markers may enhance patient selection and risk assessment.

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Identifiers

ORCID for Andrew Lotery: orcid.org/0000-0001-5541-4305

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