Cyclosporine A does not prevent second-eye involvement in Leber's hereditary optic neuropathy

Abstract

Backrground: Evaluation of the efficacy of oral cyclosporine A as a prophylactic agent in preventing second-eye involvement in Leber's hereditary optic neuropathy (LHON) in a prospective, open-label, non-randomized, multicenter pilot study. Only LHON patients aged 18 years or more, with confirmed primary mitochondrial DNA mutations and strictly unilateral optic neuropathy occurring within 6 months prior to enrolment, were included in the study. All these patients, receiving treatment with oral cyclosporine (Neoral®, Novartis) at 2.5 mg/kg/day, were examined at three-month intervals for a year. The primary endpoint was the best corrected visual acuity in the unaffected eye; the secondary endpoints were the best corrected visual acuity in the first eye affected, the mean visual field defect on automated perimetry, the thickness of the perifoveal retinal ganglion cell inner plexiform layer, and the thickness of the peripapillary retinal nerve fiber layer in both eyes.

Results: Among the 24 patients referred to our institution with genetically confirmed LHON, between July 2011 and April 2014, only five patients, four males and one female, fulfilled the inclusion criteria. Age at enrolment ranged from 19 to 42 years (mean: 27.2 years; median: 26 years), four patients harbored the m.11778G > A pathogenic variant, and one the m.14484 T > C pathogenic variant. The time-interval between the onset of symptoms and inclusion in the study ranged from 7 to 17 weeks (mean: 11.8 weeks; median: 9 weeks). Despite treatment with oral cyclosporine A, all patients eventually experienced bilateral eye involvement, occurring within 11-65 weeks after the initiation of treatment. Over the study time period, the average best corrected visual acuity worsened in the first eye affected; by the end of the study, both eyes were equally affected.

Conclusions: Oral cyclosporine, at 2.5 mg/kg/day, did not prevent second-eye involvement in patients with strictly unilateral Leber's hereditary optic neuropathy.

Trial registration: ClinicalTrials.gov Identifier: NCT02176733 . Registrated June 25, 2014.

Keywords: Cyclosporine; Leber’s hereditary optic neuropathy; Second-eye involvement.

Fig. 1

Fundoscopy of an 18-year-old patient with Leber’s hereditary optic neuropathy and recent visual loss (20/250) in his right eye, showing peripapillary telangiectatic microangiopathy in both eyes, despite normal visual function in the left eye

Fig. 2

Graph displaying the visual acuities of included patients (full lines indicate the visual acuity in the first involved eye and dotted lines indicate visual acuity in the second involved eye. Blue lines: patient 1; grey lines: patient 2; red lines: patient 3; yellow lines: patient 4; green lines: patient 5

Fig. 3

Visual fields in a patient with an asymptomatic eye at the initial visit. Despite normal visual acuity (20/20), there is a relative central depression on the pattern deviation plot

Fig. 4

Optical coherence tomography, GC-IPL thickness map. a SD-OCT showing the GC-IPL thickness map in the right unaffected eye at baseline examination; in the inferior sector, there is a thinning of the GC-IPL before the acute stage of the disease. b The thinning of the GC-IPL already involves a full quadrant in the affected left eye