gms | German Medical Science

Background: Age-related macular degeneration (AMD) is a chronic, multifactorial and degenerative retinal disease and still is a main cause for an irreversible vision loss in industrialized countries. Longitudinal structure-function correlations are needed to identify structural and functional biomarkers as early outcome measures for disease progression.

Purpose: To correlate presence of age-related macular degeneration (AMD) associated structural biomarkers and changes of retinal morphology to spatially resolved retinal sensitivity assessments by mesopic and scotopic fundus-controlled perimetry (FCP) in patients with intermediate iAMD longitudinally over a follow-up period of 6 years.

Methods: Fifty-nine eyes of 59 patients (mean ± standard deviation (SD): 71.3±8.7 years) with large drusen (>125µm) secondary to iAMD and 27 eyes of 27 age-matched healthy controls were included. Annual follow-up visits were performed over 6 years. Participants underwent multimodal retinal imaging, including spectral domain optical coherence tomography (SD-OCT, volume: 30°x25°, 61 B-scans), as well as mesopic and scotopic FCP (56-stimulus grid: MP-1S, Nidek). At each FCP stimuli position and visit, presence of structural biomarkers was computer-assisted manually graded (including sub-retinal pigment epithelium (sub-RPE) drusen, subretinal drusenoid deposits (SDDs), hyperreflective foci (HRF), incomplete/complete retinal pigment epithelium and outer retinal atrophy (i/cRORA)), and spatially-resolved retinal layer thicknesses extracted using an ImageJ plugin. Mixed-effect models were applied analyzing the association of structural biomarkers and retinal layer thickness changes with mesopic/scotopic sensitivity losses.

Results: Over a 6-year observation period there was a mean change of -0.90 dB±2.13 dB/year for mesopic and -0.79 dB±3.01 dB/year for scotopic testing. Decline was more pronounced for scotopic than mesopic sensitivity in presence of SDDs and sub-RPE drusen (scotopic: estimate: -0.97 dB; p=0.0005, mesopic: -0.53 dB; p=0.016) compared to study eyes with sub-RPE drusen only (scotopic: +0.05 dB; p=0.50 and mesopic: -0.13 dB; p=0.03). Presence of HRF had a stronger correlation to mesopic (-0.37 dB; p<0.001) than scotopic testing (-0.15 dB; p=0.106). A similar correlation was found at FCP positions with atrophy development (mesopic: -0.30 dB; p<0.005 (iRORA) and -0.18 dB; p=0.225 (cRORA) vs. scotopic: -0.16 dB; p=0.136 and -0.26 dB; p=0.149). With decreasing outer photoreceptor layer thicknesses (OS), there was a significant loss of scotopic and mesopic sensitivity testing (-0.02dB; p=0.022 (mesopic) and -0.02dB; p=0.011 (scotopic)).

Conclusions: Presence of SD-OCT based structural biomarkers and retinal layers thickness changes significantly impact longitudinal spatially resolved mesopic and scotopic retinal function in iAMD.