Melanopsin-Mediated Post-Illumination Pupil Response in Early Age-Related Macular Degeneration

To determine whether melanopsin-expressing intrinsically photosensitive retinal ganglion cell (ipRGC) inputs to the pupil light reflex (PLR) are affected in early age-related macular degeneration (AMD).

The PLR was measured in 40 participants (20 early AMD and 20 age-matched controls) using a custom-built Maxwellian view pupillometer. Sinusoidal stimuli (0.5 Hz, 11.9 seconds duration, 35.6° diameter) were presented to the study eye and the consensual pupil response was measured to lights with high melanopsin excitation (464 nm [blue]) and with low melanopsin excitation (638 nm [red]) that biased activation to the outer retina. Two melanopsin PLR metrics were quantified: the phase amplitude percentage (PAP) during the sinusoidal stimulus presentation and the post-illumination pupil response (PIPR). The PLR during stimulus presentation was analyzed using latency to constriction, the transient pupil response and maximum pupil constriction metrics. Diagnostic accuracy was evaluated using receiver operating characteristic (ROC) curves.

The blue PIPR was significantly less sustained in the early AMD group (P < 0.001). The red PIPR was not significantly different between groups (P > 0.05). The PAP and blue stimulus constriction amplitude were significantly lower in the early AMD group (P < 0.05). There was no significant difference between groups in the latency or transient amplitude for both stimuli (P > 0.05). ROC analysis showed excellent diagnostic accuracy for the blue PIPR metrics (area under the curve > 0.9).

This is the initial report that the melanopsin-controlled PIPR is dysfunctional in early AMD. The noninvasive, objective measurement of the ipRGC controlled PIPR has excellent diagnostic accuracy for early AMD.