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Editor,—Leber's hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease that results in bilateral visual loss. It primarily affects young men. The typical optic nerve head appearance is one of circumpapillary telangiectatic microangiopathy, swelling of the nerve fibre layer around the optic disc, and the absence of capillary leakage on fluorescein angiography.1
The mitochondrial inheritance of the disease was confirmed in 1988 by Wallace et al who identified a mitochondrial DNA replacement mutation at nucleotide position 11778.2Further mutations have been identified at positions 3460, 14484, and 15257.3 4 The 11778 mutation is responsible for 31–89% of LHON pedigrees in Europe, North America, and Australia, while the 3460 and 14484 mutations each account for approximately 10–15% of cases.5 The discovery of the molecular basis of LHON has provided insights into the heterogeneous clinical spectrum of disease that may result. Although the causal mutations are established, the pathophysiology of the optic nerve damage is not known. The relation between metabolic dysfunction, such as diabetes mellitus, and the development of Leber's hereditary optic neuropathy has been described only rarely.
Du Bois and Feldon described a case of a 9 year old girl with juvenile onset diabetes mellitus and LHON whose vision recovered once the diabetes was well controlled.6 In their series of 49 Leber's pedigrees, Newman et al described the case of another 9 year old girl with visual loss due to LHON in the setting of 6 months of unrecognised diabetes mellitus.7These authors suggest that diabetes mellitus may have placed overdue stress on mitochondrial function.
The following case report suggests a relation between the development of non-insulin dependent diabetes mellitus in an adult patient and the expression of Leber's hereditary optic neuropathy.
In February 1998, a previously healthy 50 year old man presented with a 5 week history of progressive deterioration of vision in both eyes. He had recently been diagnosed with non-insulin dependent diabetes mellitus. No family history of visual disturbance was elicited. At the time of presentation, his best corrected visual acuities were 3/60 right and 1/60 left. Anterior segment examination was normal and fundal examination revealed subtle swelling of the optic discs. Pupil reactions were normal and there was no nystagmus. He was unable to identify any of the Ishihara pseudoisochromatic plates. Visual field analysis revealed bilateral small central scotomas.
A provisional diagnosis of diabetic optic neuropathy was made. The patient's vision continued to deteriorate and by May 1998, the visual acuities were counting fingers (CF) right and left and he was unable to identify the food on his plate. Anterior segment examination was again normal and fundal examination revealed slight superior disc swelling in both eyes associated with surface capillary dilatation. The visual fields now showed superior defects on both sides in addition to the central scotomata. Magnetic resonance imaging of the brain did not reveal any abnormalities and lumbar puncture was also normal. ERG showed normal photoreceptor function and the VEP results were consistent with his reduced visual acuity. DNA analysis was carried out and the patient was found to be a carrier of the Leber's hereditary optic neuropathy 11778 mutation.
Leber's hereditary optic neuropathy is known to segregate in a non-mendelian, maternal pattern. It is also evident that other determinants, whether genetic or epigenetic, play a part in disease expression. All the mDNA mutations associated with LHON alter polypeptides of the mitochondrial oxidative phophorylation chain which may lead to inhibition of cellular energy production.8Epigenetic factors that may play a part in the expression of LHON include tobacco use,8 alcohol abuse,3metabolic disease (especially diabetes mellitus),8 and trauma.4 Other systemic illnesses including hypertriglyceridaemia and Crohn's disease have also been associated with the disease.3 4 It has been hypothesised that these conditions serve to reduce the energy for the cellular requirements of the optic nerve leading to inhibition of the functions which repair and maintain the cell, such as DNA and RNA synthesis and protein turnover. Diabetic optic neuropathy is a recognised, though rare, condition, which must be distinguished from Leber's hereditary optic neuropathy. Diabetic optic neuropathy has been described as a distinct circumscribed syndrome. Patients typically experience mild to moderate visual loss.9 The nature of the disc swelling ranges from minimal oedema without haemorrhages to florid swelling with capillary telangiectasia, haemorrhages, and exudates.9 10 The neuropathy may be unilateral or bilateral. Fluorescein angiography shows capillary dilatation and extravasation of dye in the region of the disc.10 11 Visual field tests may be normal, show enlarged blind spots, or central scotomas.10 11 The disc oedema clears with time and vision typically returns to normal or near normal within 6–12 months9 11 leaving residual nerve fibre bundle field defects and/or optic atrophy. In cases of suspected diabetic optic neuropathy, with progressive visual loss and circumpapillary capillary dilatation which does not leak on fluorescein angiography, a diagnosis of LHON warrants consideration. This case highlights the possibility that patients labelled in the past as having diabetic optic neuropathy may have had an additional unrecognised Leber's genetic predisposition.