Hiroto Ishikawa1, Yoichiro Masuda2, Hitoshi Ishikawa3, Keigo Shikisima2, Toshiaki Goseki3, Takeshi Kezuka4, Masahiko Terao5, Atsushi Miyazaki6, Kenji Matsumoto6, Hiroki Nishikawa7, Fumi Gomi8, Osamu Mimura8. 1. Department of Ophthalmology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan. ohmyeye@gmail.com. 2. Department of Ophthalmology, The Jikei University School of Medicine, Nishi-Shinbashi, Minato-ku, Tokyo, Japan. 3. Department of Ophthalmology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. 4. Department of Ophthalmology, Tokyo Medical University, Nishi-Shinjuku, Shinjuku-ku, Tokyo, Japan. 5. Research Institute for Time Studies, Yamaguchi University, Yamaguchi, Japan. 6. Brain Science Institute, Tamagawa University, Machida, Japan. 7. Center for Clinical Research and Education, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. 8. Department of Ophthalmology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
Abstract
PURPOSE: Leber's hereditary optic neuropathy (LHON) is a mitochondrial neuropathy that causes acute vision loss. Idebenone, a short-chain ubiquinone analog that preserves mitochondrial function is thought to suppress disease progression in early-onset LHON patients. We investigated the effects of idebenone in Japanese LHON patients. STUDY DESIGN: Prospective, interventional, non-comparative study in patients with definite LHON diagnosis, under trial registration number UMIN000017939. METHODS: Fifty-seven patients received 900 mg/day idebenone for 24 weeks. We measured baseline best-corrected visual acuity, visual fields, critical fusion frequency and retinal ganglion cell layer complex thickness; we assessed efficacy at 24 and 48 weeks, and safety throughout. RESULTS: Patients were predominantly male (91.2%) and most had an mt.11778G>A mutation (94.7%). All patients tolerated idebenone therapy well. Data from the 51 mt.11778 patients were compared with their baseline data. At 48 weeks, significant improvement in best-corrected visual acuity was observed in 17 patients (33.3%). Furthermore, 25.5% of patients showed improvements in visual fields and 33.3% in critical fusion frequency. However, retinal ganglion cell layer complex thickness was significantly reduced. Among patients who started idebenone >1 year after disease onset, visual improvement was found in 12 (38.7%). Among patients who developed LHON before 19 years of age, visual improvement was found in 11 (42.3%). CONCLUSION:Idebenone's potential and favorable safety profile were confirmed in Japanese LHON patients. However, this study had no placebo group; therefore, we need to undertake a prospective intervention study to further investigate the therapeutic effects of Idebenone in Japanese LHON patients.
RCT Entities:
PURPOSE:Leber's hereditary optic neuropathy (LHON) is a mitochondrial neuropathy that causes acute vision loss. Idebenone, a short-chain ubiquinone analog that preserves mitochondrial function is thought to suppress disease progression in early-onset LHON patients. We investigated the effects of idebenone in Japanese LHON patients. STUDY DESIGN: Prospective, interventional, non-comparative study in patients with definite LHON diagnosis, under trial registration number UMIN000017939. METHODS: Fifty-seven patients received 900 mg/day idebenone for 24 weeks. We measured baseline best-corrected visual acuity, visual fields, critical fusion frequency and retinal ganglion cell layer complex thickness; we assessed efficacy at 24 and 48 weeks, and safety throughout. RESULTS:Patients were predominantly male (91.2%) and most had an mt.11778G>A mutation (94.7%). All patients tolerated idebenone therapy well. Data from the 51 mt.11778 patients were compared with their baseline data. At 48 weeks, significant improvement in best-corrected visual acuity was observed in 17 patients (33.3%). Furthermore, 25.5% of patients showed improvements in visual fields and 33.3% in critical fusion frequency. However, retinal ganglion cell layer complex thickness was significantly reduced. Among patients who started idebenone >1 year after disease onset, visual improvement was found in 12 (38.7%). Among patients who developed LHON before 19 years of age, visual improvement was found in 11 (42.3%). CONCLUSION:Idebenone's potential and favorable safety profile were confirmed in Japanese LHON patients. However, this study had no placebo group; therefore, we need to undertake a prospective intervention study to further investigate the therapeutic effects of Idebenone in Japanese LHON patients.