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Purpose: Growing interest in microperimetry (MP) or fundus-controlled perimetry (FCP) as targeted psychometric testing method in geographic atrophy (GA) is warranted due to the disease subclinical/extra-foveal appearance or preexisting foveal loss with visual acuity becoming unreliable. We provide comprehensive pointwise test-retest repeatability reference values on the most widely used MP devices and combine them with targeted testing in areas of retinal pigment epithelium (RPE) as well as photoreceptor (PR) integrity loss, guiding the interpretation of sensitivity loss during the long-term follow-up of GA patients., Design: Prospective reliability study METHODS: Patients with GA underwent consecutive testing on CenterVue (iCare) MAIA and NIDEK MP3 devices. Obtained PWS measurements were spatially co-registered to an optical coherence tomography (OCT) volume scan acquired during the same visit. Areas with RPE and PR integrity loss, drusen and PR thickness as well as the volume of hyperreflective foci (HRF) where identified and quantified using a set of validated deep learning-based algorithms. Test-retest repeatability was assessed according to areas defined by biomarker-specific morphologic changes using Bland-Altmann coefficients of repeatability (CoR). Furthermore, the inter-device correlation, the repeatability of scotoma point detection as well as any potential effects on fixation stability were assessed., Results: 900 stimuli per device from twenty subjects were included. Identical overall PWS test-retest variance could be detected for MAIA (±6.57) and MP3 (±6.59). PR integrity loss was associated with a higher test-retest variance on both devices (MAIA: p=0.002; MP3: p<0.001). Higher CoR for stimuli in areas presenting RPE loss (±10.99 vs ±5.34) or HRF (±9.21 vs ±6.25) could only be detected on MP3 examinations (p<0.001 and p=0.01, respectively). An excellent intra-device correlation (MAIA: 0.94[0.93-0.95] MP3: 0.94[0.94-0.95]) and a good mean inter-device correlation (0.84[0.53-0.92]) could be demonstrated. The chosen device, run order or absence of foveal sparing had no significant effect on fixation stability., Conclusion: Areas presenting automatically quantified PR integrity loss with and without underlying RPE loss are associated with higher test-retest variance for both MAIA and MP3. These findings are crucial for an accurate interpretation of GA progression during long-term follow-up and the planning of future trials with microperimetry testing as functional study endpoint., Competing Interests: Conflicts of interest none, (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Investigating the sequence of morphological changes preceding outer plexiform layer (OPL) subsidence, a marker preceding geographic atrophy, in intermediate AMD (iAMD) using high-precision artificial intelligence (AI) quantifications on optical coherence tomography imaging., Methods: In this longitudinal observational study, individuals with bilateral iAMD participating in a multicenter clinical trial were screened for OPL subsidence and RPE and outer retinal atrophy. OPL subsidence was segmented on an A-scan basis in optical coherence tomography volumes, obtained 6-monthly with 36 months follow-up. AI-based quantification of photoreceptor (PR) and outer nuclear layer (ONL) thickness, drusen height and choroidal hypertransmission (HT) was performed. Changes were compared between topographic areas of OPL subsidence (AS), drusen (AD), and reference (AR)., Results: Of 280 eyes of 140 individuals, OPL subsidence occurred in 53 eyes from 43 individuals. Thirty-six eyes developed RPE and outer retinal atrophy subsequently. In the cohort of 53 eyes showing OPL subsidence, PR and ONL thicknesses were significantly decreased in AS compared with AD and AR 12 and 18 months before OPL subsidence occurred, respectively (PR: 20 µm vs. 23 µm and 27 µm [P < 0.009]; ONL, 84 µm vs. 94 µm and 98 µm [P < 0.008]). Accelerated thinning of PR (0.6 µm/month; P < 0.001) and ONL (0.8 µm/month; P < 0.001) was observed in AS compared with AD and AR. Concomitant drusen regression and hypertransmission increase at the occurrence of OPL subsidence underline the atrophic progress in areas affected by OPL subsidence., Conclusions: PR and ONL thinning are early subclinical features associated with subsequent OPL subsidence, an indicator of progression toward geographic atrophy. AI algorithms are able to predict and quantify morphological precursors of iAMD conversion and allow personalized risk stratification.