Abstract
Purpose :
Intrinsically photosensitive retinal ganglion cells (ipRGCs) have their own photopigment (melanopsin) which absorbs blue light. ipRGCs mediate myriad functions including pupil light reflexes (PLR), photo-entrainment and circadian rhythms, sleep, alertness, cognition, and visual perception. Our purpose was to develop a new, clinically expedient method for quantifying pupil responses derived from ipRGCs.
Methods :
Selective chromatic adaptation, like SWAP perimetry, was used to isolate the ipRGC PLR. A blue flashing light was superimposed on a bright amber, Ganzfeld background to suppress sensitivity of rod, L cone, and M cone photoreceptors. An infrared pupilometer (Diagnosis, LLC) measured pupil area in response to a 200-msec. blue (460 nm) flashing light (5x every 10 sec., 0.5 Hz) superimposed on a constant amber rod, L and M cone saturating background (590 nm, 560 cd/m2). Pupil area (mm2) was measured over a 3-log unit blue luminance range (0.17 – 17 cd/m2). Twenty-seven healthy young adults participated after providing written informed consent in accord with our IRB approved protocol.
Results :
Pupil area showed periodic dilatory peaks separated by pupil constriction troughs within each 10 sec recording period. Pupil area constriction varied directly with blue light intensity over the 3 log unit range. Linear regression showed a robust relation between the degree pf pupil constriction and log blue light intensity (F = 65.28, r2 = .83, P < .0001, range: 1.1 to 2.7 mm2). Since S cones also respond to blue light, control testing with an S cone blocking filter (Rosco GamColor #480) showed no difference in PLR with or without the blocking filter confirming that the PLR was derived from stimulation of ipRGCs. Further support stems from paradoxical pupil dilation from S cone stimulation.
Conclusions :
This novel approach provides a rapid, clinically expedient method to measure the ipRGC PLR. Testing at a single intensity or perhaps the slope of the intensity response function may prove useful for early detection of ocular and neurologic disease and/or potentially serve as a full-field adjunctive outcome measure in studies assessing efficacy of gene therapy in retinal and neurologic disease.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.