Leber Hereditary Optic Neuropathy Gene Therapy: Longitudinal Relationships Among Visual Function and Anatomical Measures.
Leber Hereditary Optic Neuropathy Gene Therapy: Longitudinal Relationships Among Visual Function and Anatomical Measures.
复制标题
莱伯遗传性视神经病变基因治疗：视觉功能和解剖测量之间的纵向关系。
DOI：
10.1016/j.ajo.2023.09.005
复制
发表时间：
2024
影响因子：
4.2
通讯作者：
Guy,John
中科院分区：
文献类型：
--
作者：
Lam,ByronL;Feuer,WilliamJ;Porciatti,Vittorio;Davis,JanetL;Zheng,DDiane;Vanner,ElizabethA;Savatovsky,EleonoreJ;Alba,DiegoE;Guy,John
目的：评估G11778 A Leber遗传性视神经病变（LHON）基因治疗的视觉功能和解剖学测量之间的纵向关系。慢性双侧视力丧失>12个月的患者（组1，n = 11），急性双侧视力丧失<12个月（组2，n = 9），或单侧视力丧失（组3，n = 8）给予单侧玻璃体内AAV 2（Y 444，500，730 F）-P1 ND 4v 2注射，低、中、高和更高剂量用于组1和2的较差眼睛和组3的较好眼睛。结果指标为最佳矫正视力（BCVA）、视野平均偏差（VF MD）、稳态模式视网膜电图（SS-PERG）、光学相干断层扫描（OCT）视网膜神经纤维层（RNFL）厚度和神经节细胞+内丛状层（GCIPL）厚度以及国家眼科研究所视功能问卷（NEI-VFQ-25）评分。平均随访时间为33.6个月（范围= 18-36个月）。所有组的双眼（包括第3组的无症状眼）的基线SS-PERG振幅均大幅降低，并且无论疾病分期和治疗如何，均未显示明显变化。所有患眼均发生显著和进行性GCIPL和RNFL变薄;治疗眼和对侧患眼的BCVA和VF MD波动，有些患眼有适度改善，可能与自然病史或基因治疗有关。第3组受试者的平均NEI-VFQ-25评分下降（P= 0.023）。结论单侧视力丧失的LHON患者的无症状眼可能超出了降低GCIPL和SS-PERG的有效神经保护窗口。将患者随机分配至未治疗的对照组将有助于通过解释可变的自然史来评估治疗效果。注：本文的出版由美国眼科学会赞助。
PURPOSETo assess longitudinal relationships among visual function and anatomical measures of gene therapy in G11778A Leber hereditary optic neuropathy (LHON).DESIGNPhase 1 clinical trial.METHODSThis was a single-institution study of patients with G11778A LHON. Patients with chronic bilateral visual loss >12 months (group 1, n = 11), acute bilateral visual loss <12 months (group 2, n = 9), or unilateral visual loss (group 3, n = 8) were administered unilateral intravitreal AAV2(Y444,500,730F)-P1ND4v2 injection with low, medium, high, and higher doses to worse eye for groups 1 and 2 and better eye for group 3. Oucome measures were best-corrected visual acuity (BCVA), visual field mean deviation (VF MD), steady-state pattern electroretinogram (SS-PERG), optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) thickness and ganglion cell+inner plexiform layer (GCIPL) thickness, and National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) scores. Mean follow-up was 33.6 months (range = 18-36 months).RESULTSBaseline SS-PERG amplitude was much reduced in both eyes of all groups including asymptomatic eyes of group 3, and showed no appreciable changes irrespective of disease stage and treatment. Significant and progressive GCIPL and RNFL thinning occurred in all eyes; BCVA and VF MD fluctuated in treated and fellow eyes, with some eyes having modest improvement that may be related to natural history or to gene therapy. Mean NEI-VFQ-25 scores declined in group 3 subjects (P= .023),CONCLUSIONAsymptomatic eyes in LHON patients with unilateral visual loss may be beyond the window of effective neuroprotection given reduced GCIPL and SS-PERG. Randomization of patients to an untreated control group would help to assess treatment effect by accounting for variable natural history. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.