Genotype–phenotype heterogeneity of ganglion cell and inner plexiform layer deficit in autosomal‐dominant optic atrophy. (19th September 2015)

• Record Type: Journal Article
• Authors: Rönnbäck, Cecilia; Nissen, Claus; Almind, Gitte J.; Grønskov, Karen; Milea, Dan; Larsen, Michael
• Is Part Of: Acta ophthalmologica. Volume 93:Number 8(2015)
• Page Start: 762
• Page End: 766
• Publication Date: 2015-09-19
• Subjects: autosomal‐dominant optic atrophy -- dominant optic atrophy -- ganglion cell layer thickness -- retinal nerve fibre layer thickness; Ophthalmology -- Periodicals; 617.7005
• DOI: 10.1111/aos.12835
• Languages: English
• ISSNs: 1755-375X

Abstract

Abstract: 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.