The Pattern of Retinal Ganglion Cell Loss in OPA1-Related Autosomal Dominant Optic Atrophy Inferred From Temporal, Spatial, and Chromatic Sensitivity Losses

• Published in: Investigative ophthalmology & visual science Vol. 58; no. 1; pp. 502 - 516
• Main Authors: Majander, Anna, João, Catarina, Rider, Andrew T, Henning, G Bruce, Votruba, Marcela, Moore, Anthony T, Yu-Wai-Man, Patrick, Stockman, Andrew
• Format: Journal Article
• Language: English
• Published: United States The Association for Research in Vision and Ophthalmology 01.01.2017
• Subjects: Adolescent; Adult; Aged; Color Perception - physiology; Contrast Sensitivity - physiology; Disease Progression; DNA - genetics; DNA Mutational Analysis; Female; Flicker Fusion - physiology; GTP Phosphohydrolases - genetics; GTP Phosphohydrolases - metabolism; Humans; Male; Middle Aged; Mutation; Optic Atrophy, Autosomal Dominant - genetics; Optic Atrophy, Autosomal Dominant - metabolism; Optic Atrophy, Autosomal Dominant - physiopathology; Photic Stimulation; Retinal Cone Photoreceptor Cells - metabolism; Retinal Ganglion Cells - metabolism; Retinal Ganglion Cells - pathology; Visual Acuity; Visual Neuroscience; Visual Pathways - physiopathology; Young Adult
• ISSN: 1552-5783; 0146-0404; 1552-5783
• DOI: 10.1167/iovs.16-20309

Progressive retinal ganglion cell (RGC) loss is the pathological hallmark of autosomal dominant optic atrophy (DOA) caused by pathogenic OPA1 mutations. The aim of this study was to conduct an in-depth psychophysical study of the visual losses in DOA and to infer any selective vulnerability of visual pathways subserved by different RGC subtypes. We recruited 25 patients carrying pathogenic OPA1 mutations and age-matched healthy individuals. Spatial contrast sensitivity functions (SCSFs) and chromatic contrast sensitivity were quantified, the latter using the Cambridge Colour Test. In 11 patients, long (L) and short (S) wavelength-sensitive cone temporal acuities were measured as a function of target illuminance, and L-cone temporal contrast sensitivity (TCSF) as a function of temporal frequency. Spatial contrast sensitivity functions were abnormal, with the loss of sensitivity increasing with spatial frequency. Further, the highest L-cone temporal acuity fell on average by 10 Hz and the TCSFs by 0.66 log10 unit. Chromatic thresholds along the protan, deutan, and tritan axes were 8, 9, and 14 times higher than normal, respectively, with losses increasing with age and S-cone temporal acuity showing the most significant age-related decline. Losses of midget parvocellular, parasol magnocellular, and bistratified koniocellular RGCs could account for the losses of high spatial frequency sensitivity and protan and deutan sensitivities, high temporal frequency sensitivity, and S-cone temporal and tritan sensitivities, respectively. The S-cone-related losses showed a significant deterioration with increasing patient age and could therefore prove useful biomarkers of disease progression in DOA.