Assessing color vision in congenital achromatopsia

Abstract

Purpose : Congenital achromatopsia (ACHM) is an autosomal recessive disorder characterized by impaired visual acuity, absent color vision, nystagmus and photophobia. Crucial to the success of emerging gene therapy trials for ACHM is the development of accurate outcome measures to monitor treatment efficacy. Although color vision loss may be one of the least troublesome manifestations of ACHM, its measurement has potential as a valuable assessment tool in upcoming clinical trials. Here we sought to evaluate the Color Assessment and Diagnosis (CAD) test in patients with ACHM.

Methods : Thirty-nine subjects with CNGB3 mutations (aged 8-56 years) and 13 normal controls (aged 23-49 years) were recruited. Chromatic discrimination was measured using a modified version of the CAD test: stimuli had lower temporal frequency and greater random luminance modulation to mask the detection of rod-mediated signals, and the target was larger to compensate for reduced visual acuity. Thirteen subjects completed additional testing at a 6-month follow-up visit.

Results : Although ACHM subjects had elevated CAD thresholds (ranging from 27.10 to 40.09 CAD units for red-green (RG) and 11.01 to 15.21 for yellow-blue (YB)), compared to normal controls (1.16 to 2.04 and 0.91 to 1.73) using the modified protocol, twenty-four displayed some residual chromatic discrimination for RG, and four for YB. Those who showed residual RG discrimination also demonstrated good test-retest repeatability [F(1,12) = 0.21, p = 0.65)]. Color matching behavior on the Nagel anomaloscope was variable, but showed no relationship with CAD performance. Follow-up testing revealed no significant change in CAD performance over a 6-month period.

Conclusions : The source of variation in the chromatic discrimination abilities of ACHM subjects remains unknown. It is possible that differences in the retinal distribution, numerosity, and cortical representation of rods could affect the ability to discriminate isochromatic stimuli based on rod-mediated luminance signals. On the other hand, patients with ACHM have been shown to have residual 30-Hz ERG responses, and AOSLO has provided evidence of remnant cone inner segment structure in these patients. Regardless of the mechanisms underlying residual discrimination, it appears that the CAD test is a reliable method to assess chromatic discrimination in patients with ACHM.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.