Adaptive optics retinal imaging in patients with GNAT2 mutations

Purpose To investigate the retinal structure in three subjects, from two pedigrees, with molecularly confirmed GNAT2 gene mutations with heterogeneous phenotype. Methods Spectral Domain OCT (SD‐OCT) scans and custom‐built Adaptive Optics Scanning Laser Ophthalmoscope (AOS0LO) sequences were acquired after full ophthalmological examination, ERG and colour vision testing twice, 1‐2 years apart. The foveal outer nuclear layer (ONL) retinal thickness was measured using Bioptigen SD‐OCT; 120 B‐scans were acquired with a 7mm nominal scan width, aligned, registered and averaged in ImageJ. A 5‐pixel wide longitudinal reflectivity profile provided the distance between the internal and external limiting membrane. Peak cone density and inter‐cone spacing were measured at 0.5 degree from the fovea using confocal AOS0LO images. Voronoi analysis was also performed. Results Hardy‐Rittler‐Rand plates suggested normal colour vision in one of our subjects. Conversely, the colour vision test for the other two subjects (from the other pedigree) suggested colour blindness. All three subjects had non‐detectable cone ERG. The peak para‐foveal density varied from 30 543 to 50 943 cones/mm2 and was significantly lower than previously reported values for unaffected subjects at 168 162 ± 23 529 cones/mm2 (mean ± SD). Voronoi diagrams revealed the heterogeneity of the cone mosaic with only 44% ‐ 53% of photoreceptors having six neighbouring cells. The ONL thickness was variable and due to the small sample size no conclusion could be drawn. Conclusions Microscopic retinal imaging allowed photoreceptor visualisation and quantification. It can play a significant role in a multimodal investigation, including functional and structural measurements for an in depth phenotyping of GNAT2 gene, implicated in achromatopsia and other inherited retinal diseases.