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Parafoveal Dark Adaptation in Early and Intermediate Age-Related Macular Degeneration

Ansari, G.; Oertli, J.; Maechler, L.; Lipsky, T.; Jeffrey, B. G.; Cukras, C. A.; Feltgen, N.; Klaver, C. C. W.; Pfau, K.; Pfau, M.

2025-11-22 ophthalmology
10.1101/2025.11.21.25340690 medRxiv
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PurposeRod-mediated dark adaptation delays are among the earliest functional abnormalities in age-related macular degeneration (AMD), preceding photoreceptor loss. This study evaluated whether parafoveal fundus-tracked dark adaptometry detects earlier rod dysfunction than more eccentric mid-macula testing and assessed the diagnostic performance of dynamic and steady-state parameters across eccentricities. MethodsIn this cross-sectional study, 35 patients with predominantly early / intermediate AMD and 32 age-spanning controls underwent fundus-controlled dark adaptometry (S-MAIA-2; iCare/CenterVue) and multimodal imaging. After standardized bleaching, cyan stimuli were presented 2{degrees}, 4{degrees}, and 6{degrees} temporal to the fovea. Dark-adaptation curves were modeled to derive rod intercept time (RIT), final rod threshold (FT), and cone threshold (CT), each compared with age-adjusted normative data. Diagnostic accuracy was quantified using age-adjusted receiver operating characteristic (ROC) analyses. ResultsAmong 67 analyzed eyes, RIT was abnormal in 89% of AMD eyes at 2{degrees}, 77% at 4{degrees}, and 74% at 6{degrees}, whereas FT and CT were less frequently abnormal (29 to 51% and 17 to 23%, respectively). Median RIT at 2{degrees} reached 60 minutes, indicating incomplete recovery in many eyes. RIT achieved the highest diagnostic accuracy, with age-adjusted AUC values of 0.91 (95% CrI, 0.81-0.98) at 2{degrees}, 0.88 (0.77-0.96) at 4{degrees}, and 0.87 (0.76-0.95) at 6{degrees}. ConclusionsFundus-tracked dark adaptometry enables spatially precise assessment of parafoveal rod recovery. Parafoveal RIT prolongation represents the earliest and most frequent functional abnormality in AMD and demonstrates excellent diagnostic performance, supporting its potential as a sensitive functional biomarker for early disease and therapeutic trials.

Published in Investigative Ophthalmology & Visual Science · not in our set (fewer than 10 published preprints to learn from) · training set

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