Temporal, spatial and chromatic sensitivity losses associated with OPA1 mutations

Abstract

Purpose : Autosomal dominant optic atrophy (DOA) caused by OPA1 gene mutations leads to retinal ganglion cell (RGC) loss, but the pattern and chronology of loss remain poorly understood. Our aim was to characterise psychophysically the visual losses caused by DOA, and to infer any selective or progressive losses in the distinct visual pathways subserved by different RGC types.

Methods : The participants were 11 patients with pathogenic OPA1 mutations and 15 age-matched healthy individuals. Achromatic spatial contrast sensitivity was measured as a function of spatial frequency. Long (L-) and short-wavelength (S-) sensitive cone temporal acuities were measured as a function of target illuminance, and L-cone temporal contrast sensitivity as a function of temporal frequency. Chromatic contrast sensitivity was measured using the Cambridge Colour Test. Spearman’s rank correlation and ANCOVA tests were used for the statistical analyses. OPA1 patients underwent an ophthalmologic investigation.

Results : Spatial contrast sensitivity was impaired in all OPA1 patients (1.58±0.04, normal 2.23±0.03 [mean log₁₀ unit ± SEM]) with the loss increasing with spatial frequency. Chromatic thresholds along the Protan and the Deutan axes were 8 and 9 times higher than normal with age-related regression (Spearman r=0.673, p=0.023). L-cone temporal acuity was impaired peaking at 29.9±0.9 Hz (normal 40.2±0.9 Hz [mean ± SEM]) and contrast sensitivity suppressed by 0.5 log₁₀ unit. Chromatic thresholds along the Tritan axis were 14 times higher than normal with age-related regression (Spearman r=0.725, p=0.012). The S-cone temporal acuity showed even steeper age-related decline (Spearman r=0.916, p<0.001) that was significantly different from normal (ANCOVA, p=0.002).

Conclusions : Midget RGC loss can be linked to the loss of high spatial frequency sensitivity in DOA, and (given midget RGCs also subserve red-green colour vision) to the increased Protan and Deutan thresholds. The loss of high temporal frequency sensitivity by contrast can be linked to parasol RGC loss. The most striking visual losses, however, were for the S-cone mediated chromatic and temporal sensitivities, which can be linked to small bistratified RGC loss, and showed a significant age-related decline. Thus, S-cone tests may serve as potential markers for disease progression.

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