Topographic and quantitative correlation of structure and function using deep learning in subclinical biomarkers of intermediate age-related macular degeneration

To examine the morphological impact of deep learning (DL)-quantified biomarkers on point-wise sensitivity (PWS) using microperimetry (MP) and optical coherence tomography (OCT) in intermediate AMD (iAMD). Patients with iAMD were examined by OCT (Spectralis). DL-based algorithms quantified ellipsoid zone (EZ)-thickness, hyperreflective foci (HRF) and drusen volume. Outer nuclear layer (ONL)-thickness and subretinal drusenoid deposits (SDD) were quantified by human experts. All patients completed four MP examinations using an identical custom 45 stimuli grid on MP-3 (NIDEK) and MAIA (CenterVue). MP stimuli were co-registered with corresponding OCT using image registration algorithms. Multivariable mixed-effect models were calculated. 3.600 PWS from 20 eyes of 20 patients were analyzed. Decreased EZ thickness, decreased ONL thickness, increased HRF and increased drusen volume had a significant negative effect on PWS (all p < 0.001) with significant interaction with eccentricity (p < 0.001). Mean PWS was 26.25 ± 3.43 dB on MP3 and 22.63 ± 3.69 dB on MAIA. Univariate analyses revealed a negative association of PWS and SDD (p < 0.001). Subclinical changes in EZ integrity, HRF and drusen volume are quantifiable structural biomarkers associated with reduced retinal function. Topographic co-registration between structure on OCT volumes and sensitivity in MP broadens the understanding of pathognomonic biomarkers with potential for evaluation of quantifiable functional endpoints.