31.: The neuro-ophthalmology of mitochondrial disease with a particular focus on the morphology of the optic nerve head

Abstract

Mitochondrial diseases are a clinically heterogenous group of disorders that are the result of dysfunction of the mitochondrial respiratory chain. Neuro-ophthalmological signs are a frequent clinical finding in mitochondrial disease. We aimed to establish the presence of neuro-ophthalmological signs in a cohort of 117 patients with mitochondrial disease. We also aimed to look at the optic nerve head in detail to confirm the finding of an increased cup to disc ratio in these patients, as this had been noted anecdotally but not objectively demonstrated. A total of 117 patients from the neurogenetics clinic at Royal North Shore Hospital were included in the initial neuro-ophthalmology database. Patient notes were analysed retrospectively and the presence of ptosis, external ophthalmoplegia, optic nerve abnormalities, retinal abnormalities, visual acuity and intraocular pressure were noted. Patients were included if they had clinically definite or probable mitochondrial disease using the modified Walker criteria. Ophthalmic findings were then correlated with the clinical phenotype and the genotype. We then performed optical coherence tomography (OCT) on 54 of the patients and quantitatively measured the cup to disc ratio and cup volume. These values were compared to normal data. Our results confirmed that neuro-ophthalmological abnormalities are commonly found in patients with mitochondrial disease. Eighty-one percent of patients had at least one neuro-ophthalmological abnormality. Retinal pigmentary abnormalities were found frequently, affecting 50.9% of patients; ptosis was also common, affecting 49.6%. External ophthalmoplegia and optic disc abnormalities (including an increased cup to disc ratio) were also seen in nearly half of patients. Visual loss was relatively uncommon, and notably only one patient had severe visual loss worse than 6/60. The OCT data confirmed increased cup to disc ratio and cup volume in patients with mitochondrial disease when compared with normal controls. Neuro-ophthalmological examination is abnormal in the majority of patients with suspected or confirmed mitochondrial disease. Both retinal and optic nerve abnormalities may be asymptomatic and need to be specifically sought. Our patient group showed a high incidence of optic nerve head cupping, and we propose that this be considered as a potential marker for mitochondrial disease. Our results also show a low incidence of significant visual loss, except in those patients where it is the defining characteristic of the mutation. Patients with other mitochondrial syndromes can be reassured that significant visual loss as a result of their disease is uncommon.