Impact of Inner Retinal Layer Thinning on Visual Function in OPA1 Autosomal Dominant Optic Atrophy and Associations With Age and Genetic Variant Class.
Schrittwieser Johannes, Reitner Andreas, Kircher Karl, Bertich Martin, Stapf Christoph, Lilja Stephanie V, Paquay Amina, Reiter Gregor S, Bittner Reginald E, Schmidt Wolfgang M
AI Summary
OPA1 missense variants lead to worse vision and greater inner retinal thinning than haploinsufficiency. Macular GCL thickness and papillomacular bundle sensitivity are key clinical indicators for ADOA progression and severity.
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.
MeSH Terms
Key Concepts6
In patients with OPA1 autosomal dominant optic atrophy (ADOA), 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).
In patients with OPA1 autosomal dominant optic atrophy (ADOA), age impacted mGCL thickness, with a reduction of -0.06 µm/year (P = 0.023).
In available long-term follow-ups of patients with OPA1 autosomal dominant optic atrophy (ADOA), macular ganglion cell layer (mGCL) lost 0.26 ± 0.10 µm/year.
In patients with OPA1 autosomal dominant optic atrophy (ADOA), 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.
In patients with OPA1 autosomal dominant optic atrophy (ADOA), missense variants resulted in lower mGCL (20.12 vs. 21.97 µm, P = 0.044) and pRNFL thickness (52.41 vs. 66.41 µm, P < 0.001) compared to haploinsufficiency variants.
Twenty-three of 57 detected variants in OPA1 are newly reported in a retrospective cohort study of 108 patients with OPA1 autosomal dominant optic atrophy (ADOA).
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