Visual improvement with the use of idebenone in the treatment of Wolfram syndrome.

R ecently in the Journal of Neuro-Ophthalmology, we discussed the potential efficacy of idebenone, a coenzyme Q derivative that acts as a carrier in the mitochondrial electron transport chain, in treating patients with Leber hereditary optic neuropathy (LHON) (1). Within the past 2 decades, Wolfram syndrome (WS) has been mapped to chromosome 4p16.1 (2) and is thought to harbor a mitochondrial genome deletion (3,4) or complex III deficiency (5). The only current treatment for this devastating disease is limited to blood sugar control with lower doses of insulin compared with patients with diabetes mellitus (DM). We had the opportunity to treat a patient with WS with idebenone, hoping for improvement in visual function. A 21-year-old Romanian man was initially evaluated 5 years previously with progressive bilateral visual and hearing loss and a neurogenic bladder. Surgical history was significant for bilateral cataract extractions with intraocular lens implants at 11 years of age. Medications included insulin and effexor. Family history was significant for DM in both parents, without a history of hearing or visual loss. Genetic testing confirmed the diagnosis of WS with the mutation of the WFS1 Wolframin gene. The patient was overweight but appeared younger than his stated age. Visual acuity was light perception to bare hand motion bilaterally. Pupils were sluggishly reactive without a relative afferent pupillary defect. Intraocular pressures were normal and funduscopy revealed bilateral optic disc pallor (Fig. 1). Spectral domain optical coherence tomography (OCT) showed marked thinning of the retinal nerve fiber layer in each eye (Fig. 2). The patient had bilateral sensorineural hearing loss of higher frequency sounds with preservation of hearing lower frequencies. He was prescribed idebenone that was gradually increased from 150 mg daily to 150 mg twice a day at 2 months, and then to 150 mg 3 times a day at 4 months. At 3 months, the patient’s vision improved to hand motions at 1 foot bilaterally. At 6 months, visual acuity was hand motions at 2 feet, right eye, and hand motions at 4 feet, left eye. Ophthalmoscopic and OCT findings remained unchanged. Our patient had difficulty with standard kinetic visual field testing given his poor vision (Fig. 3). To enhance light intensity of the stimulus, we used green and red laser stimuli rather than white. We were able to quantitate the visual field using a kinetic technique with these colored stimuli (Fig. 2). The patient could see the brighter more intense green stimulus, with some false positives with the red stimulus, whereas he previously was unable to detect any such stimulus on visual field testing. Recent publications describe the use of idebenone, a coenzyme Q10 derivative, in the treatment of LHON (1,7,8). Given that WS has features of mitochondrial dysfunction, we decided to initiate idebenone treatment. In our patient, idebenone resulted in progressive but subjective visual recovery at 6 months. Similarly, in reports of response to idebenone in LHON, the effects usually do not begin until after 6 months (1,7). This long-term