Dynamic Pupillary Responses in Age-Related Macular Degeneration: A Controlled Clinical Study Using High-Frequency...

To investigate whether dynamic pupillary responses differ between patients with age-related macular degeneration (AMD) and healthy controls (HC), and to evaluate their potential as functional biomarkers using high-frequency, VR-based video-oculography.

A controlled clinical study included 17 AMD patients and 17 age-matched HCs; four AMD participants were excluded for low recording quality. Dynamic pupillary responses were recorded with the BulbiCam video-oculography system (400 Hz), which presented independent monocular light stimuli through multiple permutations of bright (300 cd/m²) and dark (5 cd/m²) conditions. Measured variables included pupil diameter, latency, peak velocity, and pupil diameter-time integral (PDTI). Each eye was tested separately, and repeated sessions were analysed for reliability (intraclass correlation coefficient, ICC), repeatability (agreement index, AI), and stability (stability index, SI). Group differences were assessed using analysis of variance (ANOVA) and receiver operating characteristic (ROC) analysis.

AMD eyes showed larger steady-state pupil diameter and higher PDTI than controls (p < 0.05). First peak velocity was reduced in the worst eye only, while latencies were unchanged. PDTI and diameter demonstrated high reliability and stability across repetitions, and ROC analysis confirmed effective group discrimination.

High-frequency VR pupillometry detected reproducible functional alterations in AMD, consistent with impaired macular photoreceptor input but preserved reflex transmission. PDTI and diameter serve as diagnostic (population-level) and monitoring (patient-level) biomarkers, offering a non-invasive and objective method for AMD detection and follow-up in clinical and research settings.