Toward a Clinical Protocol for Assessing Rod, Cone and Melanopsin Contributions to the Human Pupil Response

Abstract

Purpose: : Because the pupil’s response to light is controlled by a combination of rod, cone and melanopsin contributions,[1-4] it has been suggested as a possible clinical measure.[3] Here we test a protocol for measuring these contributions.

Methods: : 12 individuals with healthy vision and 3 with severe (1 HM; 2 LP) autosomal recessive retinitis pigmentosa were tested. fdOCT scans revealed missing photoreceptor layers in the macula for the RP patients. The pupil responses were measured with an eye tracker (Arrington Research) and the stimuli controlled with a Ganzfeld system (Espion E², Diagnosys LLC). All individuals were tested with an extended clinical protocol consisting of: 1 sec blue (467+/-17nm) and red (640+/-10nm) stimuli of -3, -2, and 2.6 log cd/m² after 8 min. dark adaptation, and 2.6 log cd/m² on a blue 0.8 log cd/m² background. Isolation of the appropriate responses was assessed via amplitude vs. intensity data from 6 controls, obtained in the dark and on the blue background, over a range of -4 to 2.6 log cd/m² (0.5 log unit steps) of red and blue flashes, photopically matched.

Results: : In the dark, the pupil responses to both red and blue flashes were dominated by the rods up to 0 log cd/m². For blue, but not red, flashes above 0.5 log log cd/m², a sustained response appeared, attributed to melanopsin.[1-3] Based upon the amplitude-intensity data, the responses to all the red and blue flashes on the blue background are cone controlled with a small melanopsin response at the most intense blue flashes. In the dark, the patients with severe RP had little or no rod response (e.g. to flashes below 0 log cd/m²), and a normal or near normal melanopsin response (e.g. to 2.6 log cd/m²). On the blue background, they showed a diminished cone response, but a larger than normal sustained, melanopsin response. The responses to the flashes of the extended clinical protocol showed good reproducibility across days and individuals.

Conclusions: : It is possible to assess the rod, cone and melanopsin contributions to the pupil response with 2 or 3 blue flashes in the dark and one red flash on a blue background. Robust melanopsin responses can be seen in RP patients with little receptor function. The ultimate clinical utility of this approach will depend upon evaluation of intra- and inter-individual variability. 1. Dacey et al (2005); 2. Gamlin et al (2007) 3. Kardon et al (2009); 4. McDougal & Gamlin (2009)

Keywords: photoreceptors • ganglion cells • pupillary reflex