Invest Ophthalmol Vis Sci. 2026 Apr 1;67(4):13. doi: 10.1167/iovs.67.4.13.
ABSTRACT
PURPOSE: Inner retinal layer thinning in autosomal dominant optic atrophy (ADOA) can affect visual acuity (VA), but impact on perimetric parameters and disease-related changes with increasing age are undefined.
METHODS: One hundred eight patients with ADOA harboring a disease-causing variant in OPA1 were analyzed retrospectively, including best-corrected VA, mean deviation (MD) from 30-2 threshold perimetry, MD in the papillomacular bundle (PMB) subfield, and retinal layer thickness in spectral-domain optical coherence tomography (OCT).
RESULTS: Twenty-three of 57 detected variants in OPA1 are newly reported. In multivariable mixed-effect models, peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell layer (mGCL) thicknesses impacted visual function, with an average deterioration of 0.1 logMAR per 3.2 µm mGCL reduction (P < 0.001), PMB-MD loss of 0.75 dB/µm mGCL (P = 0.002), and MD loss of 0.11 dB/µm pRNFL (P = 0.048). Age impacted mGCL thickness (-0.06 µm/year; P = 0.023). In available long-term follow-ups mGCL lost 0.26 ± 0.10 µm/year. Missense variants caused worse VA (0.83 vs. 0.49 logMAR, P = 0.016), MD (-11.48 vs. -3.04 decibel [dB], P = 0.005), and PMB-MD (-16.25 vs. -4.17 dB, P = 0.001) than haploinsufficiency variants, and lower mGCL (20.12 vs. 21.97 µm, P = 0.044) and pRNFL thickness (52.41 vs. 66.41 µm, P < 0.001).
CONCLUSIONS: VA and central scotoma severity in OPA1-related ADOA are significantly associated with inner retinal layer thickness, which is impacted by patient age. The mGCL thickness and sensitivity in the PMB subfield were the most indicative clinical parameters for disease-related changes, with worse outcomes in heterozygotes with missense variants in OPA1.
PMID:41944540 | DOI:10.1167/iovs.67.4.13