Abstract

Purpose: Autosomal Dominant Optic Atrophy (ADOA) is a genetically heterogenous disease, however a large proportion is accounted for by mutations in OPA1. The aim of this longitudinal study was to investigate disease progression in Australian ADOA patients with confirmed OPA1 mutations.

Methods: Probands with characteristic clinical findings of ADOA were screened for OPA1 mutations, and relatives of identified mutation carriers were invited to participate. Disease progression was determined by sequential examination or using historical records over a mean of 9.6 years (range 1-42 years).

Results: 158 OPA1 mutation carriers were identified in 11 ADOA pedigrees. 69 mutation carriers were available for longitudinal follow up. Using the right eye as the default, best-corrected visual acuity (BCVAR) remained unchanged (defined as visual acuity at or within one line of original measurement) in 43 patients (62%). BCVAR worsened by 2 lines in 13 patients (19%). BCVAR deteriorated in by more than 2 lines in 6 patients (9%). 10% of patients had an improvement in visual acuity. Mean time to follow up was 9.6 years and interestingly mean visual acuity was 6/18 for both the initial and subsequent measurements. There was no statistical significance in the rate of BCVAR loss across different OPA1 mutations (P = 0.55).

Conclusion: OPA1-related ADOA generally progresses slowly and functional visual acuity is usually maintained. Longitudinal disease studies are important for allowing appropriate counselling of patients and this study allows for the better understanding of the natural history of ADOA.