Doheny Eye Institute, Los Angeles, CA, USA; Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Doheny Eye Institute, Los Angeles, CA, USA; Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Mitochondrion. 2022 Jan;62:181-186. doi: 10.1016/j.mito.2021.12.003. Epub 2021 Dec 13.
In this retrospective, interventional, longitudinal small case series, we looked at the visual effects of pharmacologic intervention with 4-aminopyridine (4-AP) in chronic Leber's Hereditary Optic Neuropathy (LHON) patients who are non-responders to idebenone. We illustrate, as examples, the visual progression of three LHON patients with 4-AP as add-on therapy to idebenone. Each patient had a different primary LHON mutation and was treated with idebenone within one year of onset. No response to idebenone at 300 mg orally three times a day ranged from less than one year to 2.5 years, and the addition of 4-AP at 10 mg orally two times a day ranged from 24 to 29 months. Outcome measures included best-corrected distance visual acuity, color vision, automated perimetry, the average retinal nerve fiber layer (RNFL) thickness, and the full-field photopic negative response (PhNR) amplitude. The 19-year-old man with the LHON mutation 11778A > G had no response to the addition of 4-AP to idebenone. The 27-year-old man with the LHON mutation 3460A > G experienced a significant response to 4-AP. Finally, the 40-year-old man with the LHON mutation 14484 T > C had a milder response. Although this case series was too small to demonstrate the efficacy of idebenone with add-on 4AP, it allowed us to consider a new hypothesis that neuronal activity generated from 4-AP can add more potential for visual recovery in LHON patients.
在这项回顾性、介入性、纵向小病例系列研究中，我们观察了对非应答于依地苯醌的慢性莱伯遗传性视神经病变（LHON）患者进行 4-氨基吡啶（4-AP）药物干预的视觉效果。我们举例说明了三位 LHON 患者在依地苯醌中添加 4-AP 的视觉进展。每位患者均有不同的原发性 LHON 突变，并在发病一年内开始接受依地苯醌治疗。依地苯醌 300mg 口服，每日三次，无反应的时间从不到一年到 2.5 年不等，而依地苯醌 10mg 口服，每日两次，添加 4-AP 的时间从 24 到 29 个月不等。评估指标包括最佳矫正视力、色觉、自动视野计、平均视网膜神经纤维层（RNFL）厚度和全视野光峰负反应（PhNR）振幅。携带 LHON 突变 11778A>G 的 19 岁男性对依地苯醌中添加 4-AP 无反应。携带 LHON 突变 3460A>G 的 27 岁男性对 4-AP 有明显反应。最后，携带 LHON 突变 14484T>C 的 40 岁男性反应较为温和。尽管该病例系列太小，无法证明依地苯醌加用 4AP 的疗效，但它使我们考虑了一个新的假设，即 4-AP 产生的神经元活性可以为 LHON 患者的视觉恢复增加更多潜力。
