Visual and psychological morbidity among patients with autosomal dominant optic atrophy.

Abstract

Editor, Autosomal dominant optic atrophy (DOA) is the most common inherited optic nerve disorder seen in neuro-ophthalmological practice (Yu-Wai-Man et al. 2011). The majority of patients with DOA harbour pathogenic mutations within the OPA1 gene, which codes for an inner mitochondrial membrane protein intricately involved in mitochondrial biogenesis, mitochondrial DNA replication and network stability (Amati-Bonneau et al. 2009). The pathological hallmark of this nuclear mitochondrial disorder is progressive retinal ganglion cell loss, leading to optic nerve degeneration and bilateral visual failure from early childhood. About 20% of OPA1 mutation carriers will develop a more severe form of the disease (DOA+) characterized by prominent extraocular neurological features including deafness, ataxia, peripheral neuropathy and myopathy (Yu-Wai-Man et al. 2010). The visual and psychological impact of DOA has not yet been reported. The aim of this study was to quantify the functional impact of DOA on patients’ quality of life and to determine, in particular, whether the additional neurological burden that develops in DOA+ further compounds the visual disability in this group of patients. A total of 38 patients harbouring confirmed pathogenic OPA1 mutations were recruited into this study: 30 patients with isolated optic atrophy and eight patients with DOA+ phenotypes. A telephone interview was conducted by a single investigator (MB), who was blinded to the patients’ mutational status and clinical history, using two well-validated questionnaires: the Visual Function Index (VF-14) (Kirkman et al. 2009) and the Hospital Anxiety and Depression Scale (HADS) (Hinz et al. 2010). Visual acuity data were obtained from the patients’ records. This study had the relevant institutional ethical approval and complied with the Declaration of Helsinki. The mean VF-14 score for the entire patient cohort was 37.3 (Standard deviation = 25.6). Patients with DOA+ had significantly worse visual acuities and VF-14 scores compared with those with pure DOA (Fig. 1A). Borderline or definite symptoms of anxiety and depression were present in 19/38 (50.0%) and 7/38 (18.4%) patients, respectively. Compared with the general adult population, the mean HADS scores were significantly increased for both anxiety (p = 0.0490) and depression scales (p = 0.0287) (data not shown). On subgroup analysis, significantly higher depression scores, but not anxiety scores, were found in patients with DOA+ compared with those with pure DOA (Fig. 1B,C). There was a statistically significant correlation between VF-14 score and (i) LogMAR vision, (ii) anxiety score and (iii) depression score (Fig. 1D–F). Fig 1 OPA1 patient cohort analysis. The data have been represented as box plots with the whiskers representing the minimum and maximum values. The ends of the boxes are the upper and lower quartiles, the vertical lengths of the boxes indicate the interquartile ... Patients with DOA experience significant difficulties in their activities of daily living, the severity being comparable to the degree of functional handicap in Leber hereditary optic neuropathy (LHON) – a classical primary mitochondrial DNA disorder that typically presents with catastrophic bilateral blindness in early adulthood (Kirkman et al. 2009). Unlike LHON, visual failure in DOA has a more insidious course, but it is invariably progressive, and the VF-14 score clearly indicates the considerable visual morbidity associated with this disorder. Furthermore, although half of all OPA1 mutation carriers will eventually fulfil the legal requirement for blind registration (LogMAR < 1.30 in the United Kingdom), impaired activities of daily living were also apparent for those with visual acuities below this threshold, and this patient group should not be denied support from social services. Another observation from our study is the significant psychological impact of DOA, with levels of anxiety and depression approaching those seen in patients undergoing cancer treatment (Hinz et al. 2010). Importantly, the psychological distress seemed magnified in patients manifesting DOA+ phenotypes. From a practical perspective, these patients therefore represent a high-risk group that requires greater clinical input and improved access to rehabilitative services to lessen the impact of the neurological complications on the already considerable visual deficits.