Atypical Late-Onset Leber Hereditary Optic Neuropathy (LHON) Associated With T14484C Mutation.

Abstract

A 75-year-old man presented with a 6-week history of left eye acute vision loss first noticed while driving his boat. The patient denied any headache, pain with eye movement, or eye trauma. He had bilateral uneventful cataract extraction 7 years before presentation and underwent a yttrium aluminum garnet (YAG) laser capsulotomy of the left eye at the onset of the blurry vision with no improvement. He has a history of diabetes mellitus, atrial fibrillation, and prostate cancer. Medication included metformin, apixaban, tadalafil, and multivitamins. The patient is a former smoker who quit smoking at the age of 35 years and is a mild social alcohol drinker. The best-corrected visual acuity (BCVA) was 20/50 in the right eye and 20/400 in the left eye. Ishihara color plates showed 10/10 in the right eye and 0/10 in the left eye with a left relative afferent pupillary defect (RAPD). Slitlamp examination revealed moderate opacification of the right posterior capsule and normal-looking optic discs. The visual field (VF) showed a cecocentral scotoma in the left eye. Brain and orbital MRI with contrast showed no optic nerve enhancement or atrophy of the left eye. Blood workup was negative for anti-myelin oligodendrocyte glycoprotein (MOG), anti-aquaporin-4 antibody (AQP4-Ab), rapid plasma reagin (RPR), fluorescent treponemal antibody test absorption test (FTA-ABS), angiotensin-converting enzyme (ACE), lysozyme, and nutritional and toxic blood panel. Despite the negative workup, the patient was started on 1-g intravenous methylprednisolone (IVMP) daily for 5 days, with some improvement in right eye color vision and brightness, without any changes in the left eye. Three weeks later, the BCVA was 20/100 in the right eye and 20/400 in the left eye. Ishihara color plates were 3/10 in the right eye and 0/10 in the left eye with trace left RAPD. Fundus examination showed bilateral optic disc pallor. Visual fields showed cecocentral scotoma, the left eye worse than the right eye. YAG capsulotomy right eye was performed without any improvement in vision. At that point, it was a case of unexplained sequential vision loss of 9-week duration. Full-field electroretinography (ffERG) and serum paraneoplastic antibody panel were unremarkable. Leber hereditary optic neuropathy (LHON) testing panel (Athena Diagnostics) came back positive for T14484C ND6 mitochondrial mutation. The patient was started on off-label use idebenone 300 mg 3 times daily.1 Six months later, his BCVA was 20/300 in the right eye and 20/350 in the left eye with bilateral cecocentral scotomas. Optical coherence tomography (OCT) of the optic nerve head revealed temporal thinning of the retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL) analysis showed diffuse thinning of the ganglion cell complex. After 5 years of annual follow-up, the patient reported stable vision. The BCVA remained at 20/300 in the right eye and 20/350 in the left eye. Repeated visual field testing (Fig. 1) showed central scotoma in the right eye and cecocentral scotoma in the left eye; RNFL (Fig. 2A) and GCL thicknesses (Fig. 2B) were unchanged. Fundus examination showed temporal pallor of the optic disc in both eyes (Fig. 2C).FIG. 1.: Automated visual field testing (AVF) showing central scotoma in the right eye and centrocecal scotomas in the left eye at the last follow-up visit.FIG. 2.: A. RNFL thickness shows mostly temporal loss. B. Diffuse GCL thinning. C. Fundus photographs showing temporal pallor of both optic nerves. GCL, ganglion cell layer; RNFL, retinal nerve fiber layer.To the best of our knowledge, our case is one of the most delayed onsets of patients with T14484C LHON and underscores that LHON should be considered in the differential diagnosis of subacute blindness, even in older patients. The 3 most common mutations responsible for 90% of LHON are G11778A, T14484C, and G3460A. LHON usually affects male patients more than female patients and presents in the second to fourth decade of life but can present at any age.2 The oldest reported ages of onset of visual loss were a 76-year-old man with 11778 mutation,3 a 75-year-old man with 3460 mutation,3 and a 57-year-old man with 14484 mutation associated with longitudinal extensive myelitis.4 The inciting factors for visual loss in patients with one of the typical mutations for LHON are not fully known. Apart from alcohol and smoking, for which a correlation was demonstrated,2,5 many other nonspecific triggers have been described in some case reports. Except for the very late age of onset, our case has typical sequential subacute vision loss of LHON with typical clinical findings in the clinical examination and ancillary testing. In addition, there were no triggering factors other than the very remote smoking history and social alcohol consumption which could cause a cumulative effect on the optic nerves.