Neuro-Ophthalmology Clinic, Department of Ophthalmology and Optometry, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
Graefes Arch Clin Exp Ophthalmol. 2019 Dec;257(12):2751-2757. doi: 10.1007/s00417-019-04444-6. Epub 2019 Sep 3.
Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by a subacute and progressive impairment and subsequent degeneration of retinal ganglion cells (RGCs). In most cases, it results in optic nerve atrophy and permanently reduced visual acuity (VA). Idebenone has recently been approved in Europe for treating LHON. However, published clinical data has only focused on efficacy in patients within the first years after disease onset. The present study is the first to evaluate possible effects of idebenone treatment in patients with LHON when initiated after more than 5 years from disease onset.
Oral treatment with idebenone 300 mg tid was started in seven patients 5 to 51 years after LHON onset. All patients had genetically confirmed primary LHON mutations (m11778G>A, m14484T>C, and m13051G>A). Visual function of all fourteen eyes was tested every 3 months using logarithmic reading charts and automated static threshold perimetry. The obtained clinical data were analyzed retrospectively using a multivariate analysis for VA and the Wilcoxon signed-rank test for visual field data.
Before treatment, VA was 0.78 ± 0.38 logMAR (range 0.24 to 1.50 logMAR). During the first year of therapy, VA improved significantly by an average of - 0.20 ± 0.10 logMAR or 10 ± 5 ETDRS letters (P = 0.002; VA range 0.06 to 1.30 logMAR). Seven of fourteen eyes showed an improvement of 2 or more lines. Visual field mean deviation increased from - 8.02 ± 6.11 to - 6.48 ± 5.26 dB after 12 months, but this change was not statistically significant (P = 0.056).
The increase in VA of patients who have had LHON for more than 5 years observed soon after start of treatment may not constitute a coincidental spontaneous recovery. We hypothesize that the treatment response in chronic LHON was the result of a reactivated signal transduction in surviving dysfunctional RGCs. The results of this study indicate a beneficial effect of idebenone on improvement of visual function in LHON patients with established optic atrophy.
Leber 遗传性视神经病变（LHON）是一种线粒体疾病，其特征为急性和进行性视网膜神经节细胞（RGC）损伤和随后的变性。在大多数情况下，它导致视神经萎缩和永久性视力下降（VA）。依地苯醌最近在欧洲被批准用于治疗 LHON。然而，已发表的临床数据仅集中在疾病发病后最初几年内患者的疗效上。本研究首次评估了 LHON 发病 5 年以上开始依地苯醌治疗时对患者的可能影响。
7 例患者 LHON 发病 5 至 51 年后开始口服依地苯醌 300mg tid。所有患者均经基因证实存在原发性 LHON 突变（m11778G>A、m14484T>C 和 m13051G>A）。使用对数阅读图表和自动静态阈值视野计每 3 个月测试所有 14 只眼的视觉功能。使用 VA 的多元分析和视野数据的 Wilcoxon 符号秩检验对获得的临床数据进行回顾性分析。
治疗前，VA 为 0.78 ± 0.38 logMAR（范围 0.24 至 1.50 logMAR）。治疗第一年，VA 平均改善- 0.20 ± 0.10 logMAR 或 10 ± 5 ETDRS 字母（P = 0.002；VA 范围 0.06 至 1.30 logMAR）。14 只眼中有 7 只眼视力提高了 2 行或以上。12 个月后，视野平均偏差从- 8.02 ± 6.11 增加到- 6.48 ± 5.26 dB，但差异无统计学意义（P = 0.056）。
发病 5 年以上的 LHON 患者治疗后不久观察到的 VA 增加可能不是偶然的自发恢复。我们假设慢性 LHON 中的治疗反应是存活的功能障碍 RGC 中重新激活的信号转导的结果。本研究结果表明依地苯醌对已建立视神经萎缩的 LHON 患者视觉功能改善有有益作用。
