Response Reliability during Automated Visual Photosensitivity Assessment in Achromatopsia

Abstract

Purpose : The Ocular Photosensitivity Analyzer (OPA, Fig. 1, Aguilar et al. BOE 2018,9(11):5583-5596) is an automated instrument designed to quantify visual photosensitivity thresholds (VPT) to light stimuli while incorporating catch trials throughout the test as an index of response reliability. A catch trial is defined as a repetition of a randomly-selected previously presented light stimulus. The response to a light stimulus is compared to the response of a subsequent catch trial stimulus for agreement. This study examined the differences in catch trial agreement between healthy subjects and subjects with achromatopsia (rod monochromatism), a retinal genetic disorder characterized by severe light sensitivity.

Methods : From 2014-2018, 278 OPA tests have been conducted on 16 subjects with genetic proven CNGB3 or CNGA3 achromatopsia (age 7 to 57 years) and 35 healthy subjects (age 8 to 61 years). Monocular and binocular (OD, OS, & OU) VPT measurements were obtained at two time points. Exam room lighting was adjusted to 4 lux, while subjects rested for 10 minutes. Synthesized speech audio test instructions were provided and subjects were instructed to indicate when a light stimulus was uncomfortable by pressing a push-button. The VPT was calculated from the mean of 10 response reversals (Fig. 2). Every third light stimulus is a catch trial presented to the subject at the same intensity as a previously presented stimulus.

Results : The VPT of the achromatopsia subjects was significantly lower than in the healthy subjects (0.74 ± 0.55 log Lux vs. 2.18 ± 0.83 log Lux, respectively; p<.001). Notably, poorer response agreement was observed in the achromatopsia subjects than in the healthy subjects (p<.001). Catch trial agreement for the healthy subjects was 81.0 ± 0.2% compared with 70.1 ± 0.2% for the achromatopsia subjects. VPT was significantly associated with catch trial agreement (r=0.241, p<.001).

Conclusions : Achromatopsia subjects demonstrated diminished light sensitivity response reliability compared with healthy subjects. With repeated test trials as used in psychophysical thresholding methodology, greater variability of light sensitivity response agreement may be expected in subjects with impaired visual photosensitivity depending on disease severity. Our findings have implications in the use of the OPA as an outcome measure in achromatopsia clinical trials.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.