Effects of idebenone on color vision in patients with leber hereditary optic neuropathy

Abstract

Background: The authors investigated the correlation of protan and tritan color vision with disease characteristics in Leber hereditary optic neuropathy (LHON). The authors also characterized the therapeutic potential of idebenone in protecting patients from developing dyschromatopsia in LHON.

Methods: Color contrast data of 39 LHON patients participating in a randomized, double-blind placebo-controlled intervention study were evaluated. Patients reported disease onset <5 years before enrolment and were genetically confirmed. Protan and tritan color contrast sensitivity was measured using a computer graphics method in patients receiving idebenone (Catena; 900 mg/d; N = 28) or placebo (N = 11) for 6 months.

Results: Mean age of patients was 28.1 years, 87.2% were men, 76.9% carried the m11778G>A mutation, and mean duration since onset was 2 years. Assessing protan and tritan color vision at baseline revealed a high degree of color confusion even in young patients (<25 years) and with a short history of disease (<1 year). Treatment with idebenone improved tritan color vision compared with placebo (P = 0.008 at week 24); a similar trend was seen for protan. The effect of idebenone was most prominent in patients with discordant visual acuity (interocular difference of logMAR >0.2). In this subgroup, the treatment effect at week 24 was 20.4% (P = 0.005) in favor of idebenone for the tritan color domain and 13.5% (P = 0.067) for the protan domain.

Conclusion: This study confirms that protan and tritan color confusion is an early symptom in LHON. Treatment with idebenone can protect from loss of color vision, particularly in patients who are at imminent risk of further vision loss.

Conflict of interest statement

C. Rummey and T. Meier are regular employees of Santhera Pharmaceuticals (Liestal, Switzerland), the sponsor of the study. T. Klopstock received research support for this and other studies from Santhera Pharmaceuticals. He also has received research support from government entities (Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, European Commission 7th Framework Programme) and from commercial entities (Santhera Pharmaceuticals; Actelion Pharmaceuticals, Ltd; H. Lundbeck A/S). T. Klopstock serves on scientific advisory boards for commercial entities (Santhera Pharmaceuticals; Actelion Pharmaceuticals, Ltd) and for nonprofit entities (Center for Rare Diseases, Bonn, Germany; Hoffnungsbaum e.V., Germany). He has received speaker honoraria and travel costs from commercial entities (Dr. Willmar Schwabe GmbH & Co. KG; Eisai Japan; Santhera Pharmaceuticals; Actelion Pharmaceuticals, Ltd) and performs consultancies for the Gerson Lehrman Group, USA.

Figures

FIG. 1

Distribution of color contrast sensitivities for Leber hereditary optic neuropathy patients at baseline of the Rescue of Hereditary Optic Disease Outpatient Study show markedly elevated color confusion for protan (A) and tritan (B) color domains. C. Correlation of protan and tritan color confusion levels for all eyes (data points are slightly jittered for clarity). Note that many eyes had color confusion of >90% in both color domains resulting in a dense cluster of data points at the upper right hand corner of the graph.

FIG. 2

Relationship between color contrast sensitivities and age (A, B), disease duration (C, D), and visual acuity (E, F) at baseline of the Rescue of Hereditary Optic Disease Outpatient Study. Each dot represents one eye. Data are shown for the protan (A, C, D) and tritan (B, D, F) color domains. Data points in all graphs are slightly jittered for clarity.