Assessing Rod, Cone and Melanopsin Contributions to the Human Pupil Response in Healthy Controls and in Patients with Disease of the Photoreceptors

Purpose: To better understand the relative contributions of rod, cone, and melanopsin to the human pupillary light reflex (PLR) and to determine the optimal conditions for assessing the health of the rod, cone, and melanopsin pathways with a relatively brief clinical protocol using the PLR. Methods: The PLR was measured with an eye tracker and stimuli controlled with a Ganzfeld system. Exp.1: 2.5-log cd/m² red (640±10nm) and blue (467±17nm) stimuli of various durations were presented after dark-adaptation. Exp. 2 and 3: 1-sec red and blue stimuli were presented at different intensity levels in the dark (Exp.2) or on a 0.78-log cd/m² blue background (Exp.3). Based on the results of Exp. 1-3, a clinical protocol was designed and tested on healthy controls (Exp. 4) and patients (Exp. 5) with retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), and achmatopsia (ACHM). Results: The optimal duration for producing the melanopsin-driven sustained pupil response following termination of an intense blue stimulus was 1 sec. PLR rod- and melanopsin-driven components are best studied with low and high intensity flashes, respectively, presented in the dark (Exp. 2). A blue background suppressed rod and melanopsin responses, making it easy to assess the cone contribution with a red flash (Exp. 3). The proposed clinical protocol successfully provided reliable data from 8 normal subjects (Exp. 4). With the clinical protocol, robust melanopsin responses could be seen in the all patients with little or no contribution from the rods and cones (Exp. 5). Conclusions: It is possible to identify the rod, cone, and melanopsin contributions to the PLR with blue flashes at 2 or 3 intensity levels in dark and one red flash on a blue background.