Genotype–phenotype heterogeneity of ganglion cell and inner plexiform layer deficit in autosomal‐dominant optic atrophy

• Published in: Acta ophthalmologica (Oxford, England) Vol. 93; no. 8; pp. 762 - 766
• Main Authors: Rönnbäck, Cecilia, Nissen, Claus, Almind, Gitte J., Grønskov, Karen, Milea, Dan, Larsen, Michael
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-12-2015
• Subjects: Adolescent; Adult; Aged; Aging - physiology; autosomal‐dominant optic atrophy; Axial Length, Eye - pathology; Child; Cross-Sectional Studies; dominant optic atrophy; Female; ganglion cell layer thickness; Genetic Association Studies; GTP Phosphohydrolases - genetics; Humans; Male; Middle Aged; Nerve Fibers - pathology; Ophthalmology; Optic Atrophy, Autosomal Dominant - genetics; Optic Atrophy, Autosomal Dominant - pathology; Polymorphism, Single Nucleotide; Retinal Ganglion Cells - pathology; retinal nerve fibre layer thickness; Tomography, Optical Coherence; Visual Acuity - physiology; autosomal-dominant optic atrophy; dominant optic atrophy; retinal nerve fibre layer thickness; ganglion cell layer thickness
• ISSN: 1755-375X; 1755-3768
• DOI: 10.1111/aos.12835

Purpose
To describe the thickness of the combined ganglion cell and inner plexiform layers (GC‐IPL) and the peripapillary retinal nerve fibre layer (RNFL) in patients with OPA1 c.983A>G or c.2708_2711delTTAG autosomal‐dominant optic atrophy (ADOA).
Methods
The study included 20 individuals with c.983A>G and nine individuals with c.2708_2711delTTAG. Data for comparison were drawn from 49, previously published, individuals with OPA1 c.2826_2836delinsGGATGCTCCA and 51 individuals with no OPA1 mutation. Subjects underwent refraction, best‐corrected visual acuity assessment, axial length measurement and high‐definition optical coherence tomography.
Results
There was overlap in GC‐IPL thickness in subjects younger than 20–30 years between the two new groups of ADOA patients and controls. Numerical decreases in GC‐IPL thickness with age did not reach statistical significance in individuals with c.983A>G (p = 0.18) or in healthy controls (p = 0.22), but it did in individuals with c.2708_2711delTTAG (p = 0.02). Visual acuity decreased with decreasing GC‐IPL thickness (p = 0.0006 in c.983A>G and p = 0.0084 in c.2708_2711delTTAG). Unlike c.2826_2836delinsGGATGCTCCA, individuals with c.983A>G or c.2708_2711delTTAG did not show a pattern of maximum GC‐IPL deficit inferonasal of the fovea.
Conclusion
Genotype–phenotype heterogeneity in OPA1 ADOA is evident when inner retinal atrophy is examined as a function of age. Thus, a pronounced decline with age in GC‐IPL thickness is observed in c.2708_2711delTTAG ADOA, an intermediate decline with age is observed in c.983A>G ADOA, whereas little or no change with age is observed in c.2826_2836delinsGGATGCTCCA ADOA. This genotype–phenotype heterogeneity may explain why some patients have progressive visual loss while others have a relatively stable prognosis.