Correlations between visual function and inner retinal structure in OPA1 autosomal dominant optic atrophy

Purpose: To evaluate the influence of autosomal dominant optic atrophy (ADOA) on visual function and inner retinal layer thickness in patients harbouring a pathogenic variant in the OPA1 gene. Methods: We retrospectively investigated clinical data of 59 patients (118 eyes) with ADOA and genetically confirmed OPA1 variants. Visual function was evaluated by best corrected visual acuity (VA), and by mean deviation (MD) of automated static threshold perimetry. Macular ganglion cell layer (mGCL) volume and peripapillary retinal nerve fibre layer (pRNFL) thickness were measured by optical coherence tomography. The analysis was performed for all available data from both eyes in the whole sample. Furthermore, patients were stratified in 2 groups based on variant type (haploinsufficiency: 86 eyes, missense variants: 14 eyes). Results: The mean age at examination was 30.5 ± 16.1 years, VA was 0.55 ± 0.33 logMAR, MD was −4.73 ± 3.59 dB, mGCL volume was 0.60 ± 0.10 mm 3 , and pRNFL thickness was 63.8 ± 10.6 μm. VA correlated significantly with mGCL volume ( p < 0.001) and with pRNFL thickness ( p = 0.021). MD also correlated with pRNFL thickness ( p = 0.017). Patient age was associated with mGCL volume ( p < 0.001) and pRNFL thickness ( p = 0.024), but not with VA or MD. MD was significantly lower in the missense group than in the haploinsufficiency group (−9.31 ± 4.07 dB vs. −4.03 ± 2.85 dB; p < 0.001), whereas VA did not differ between groups. Thickness of the pRNFL was also lower in the patients with missense variants, but only the nasal sector was significantly thinner (48.2 ± 12.8 μm vs. 58.2 ± 19.2 μm; p = 0.035). Conclusions: Visual function and inner retinal structure are closely associated in ADOA patients with OPA1 variants. Increasing age may be accompanied by a continuing degeneration of retinal ganglion cells, but seems to have less effect on further loss of visual function. Patients carrying missense variants show more pronounced optic atrophy and visual field defect.