Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science University, Portland, Oregon.
Casey Eye Institute, Department of Ophthalmology, Oregon Health & Science University, Portland, Oregon.
Ophthalmology. 2016 Jul;123(7):1606-20. doi: 10.1016/j.ophtha.2016.03.003. Epub 2016 Apr 19.
To provide an initial assessment of the safety of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in adults and children with retinal degeneration caused by RPE65 mutations.
Nonrandomized, multicenter clinical trial.
Eight adults and 4 children, 6 to 39 years of age, with Leber congenital amaurosis (LCA) or severe early-childhood-onset retinal degeneration (SECORD).
Patients received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of 2 dose levels, and were followed up for 2 years after treatment.
The primary safety measures were ocular and nonocular adverse events. Exploratory efficacy measures included changes in best-corrected visual acuity (BCVA), static perimetry central 30° visual field hill of vision (V30) and total visual field hill of vision (VTOT), kinetic perimetry visual field area, and responses to a quality-of-life questionnaire.
All patients tolerated subretinal injections and there were no treatment-related serious adverse events. Common adverse events were those associated with the surgical procedure and included subconjunctival hemorrhage in 8 patients and ocular hyperemia in 5 patients. In the treated eye, BCVA increased in 5 patients, V30 increased in 6 patients, VTOT increased in 5 patients, and kinetic visual field area improved in 3 patients. One subject showed a decrease in BCVA and 2 patients showed a decrease in kinetic visual field area.
Treatment with rAAV2-CB-hRPE65 was not associated with serious adverse events, and improvement in 1 or more measures of visual function was observed in 9 of 12 patients. The greatest improvements in visual acuity were observed in younger patients with better baseline visual acuity. Evaluation of more patients and a longer duration of follow-up will be needed to determine the rate of uncommon or rare side effects or safety concerns.
初步评估重组腺相关病毒载体表达 RPE65（rAAV2-CB-hRPE65）在 RPE65 突变引起的视网膜变性的成人和儿童中的安全性。
非随机、多中心临床试验。
8 名成人和 4 名 6 至 39 岁的儿童，患有莱伯先天性黑蒙（LCA）或严重的早发性儿童期视网膜变性（SECORD）。
患者在较差视力的眼睛中接受 rAAV2-CB-hRPE65 的视网膜下注射，剂量水平为 2 个，治疗后随访 2 年。
主要安全性措施是眼部和非眼部不良事件。探索性疗效措施包括最佳矫正视力（BCVA）、静态视野中央 30°视野视野（V30）和总视野视野（VTOT）、运动视野视野、生活质量问卷的反应变化。
所有患者均能耐受视网膜下注射，无治疗相关严重不良事件。常见的不良事件与手术过程有关，包括 8 例患者出现结膜下出血和 5 例患者出现眼部充血。在治疗眼中，5 名患者的 BCVA 增加，6 名患者的 V30 增加，5 名患者的 VTOT 增加，3 名患者的运动视野面积增加。1 名患者的 BCVA 下降，2 名患者的运动视野面积下降。
rAAV2-CB-hRPE65 治疗与严重不良事件无关，12 名患者中有 9 名观察到 1 项或多项视力功能改善。视力提高最大的是基线视力较好的年轻患者。需要评估更多患者并进行更长时间的随访，以确定罕见或罕见的副作用或安全问题的发生率。
