EPI-743 May Improve Visual Acuity in LHON: Data from a Brazilian Cohort

Abstract

Purpose: To describe the results of the first 12 months of treatment with EPI-743(alphatocotrienol quinone) in a Brazilian cohort of Leber’s Hereditary Optic Neuropathy (LHON), 11778 haplogroup J mutation.

Methods: Six Brazilian patients with severe visual loss due to LHON were offered the experimental therapeutic EPI-743 as part of an open label trial. Two patients received EPI-743 at time of vision loss and four patients received EPI-743 more than five years after vision loss. Best corrected vision was assessed by Snellen visual acuity (Va). If patients could not detect any target on a standard Humphrey Visual Field (HVF), the mean deviation (MD) was set at a floor value of -35dB. Mean retinal nerve fiber layer (RNFL) thickness was measured using time domain (2007-2009) or spectral domain (2010-2013) Optical Coherence Tomography (OCT).

Results: All six patients showed an initial decline or at best a stabilization in Va in the first 6 months of treatment (mean 1.69 logMAR declined to mean 1.79 logMAR), but then showed an improvement in Va during the following 6 months (mean 1.51 logMAR). The MD of four patients remained at -35 dB, while in two patients who converted >5 years prior to treatment the MD improved to -18.32 ± 6.45 dB by 9 months after the start of treatment. The two patients who were treated at time of conversion showed continued bilateral progression for the first six months, consistent with the natural history of LHON. As expected, all eyes showed a decline in nerve fiber thickness on OCT that then stabilized after treatment.

Conclusions: This is the first report of clinical data for the third generation quinone EPI-743’s use in LHON patients from Brazil. Within 12 months of treatment initiation with EPI-743, all patients demonstrated improvement in visual acuity and two patients who had vision loss over 5 years earlier showed improvement in their visual fields. It is intriguing that improvement in vision occurred years after visual loss and that recovery was delayed by six months from the start of treatment, suggesting that longer duration of therapy may be necessary before a clinical response is observed.

Keywords: 613 neuro-ophthalmology: optic nerve • 642 perimetry • 600 mitochondria