CRB1 相关视网膜营养不良：未来临床试验预期的前瞻性自然病史研究。

CRB1-Associated Retinal Dystrophies: A Prospective Natural History Study in Anticipation of Future Clinical Trials.

机构信息

From the Department of Ophthalmology (X.-T.-A.N., M.T., J.W., N.E.S.-D., H.E.T., C.J.F.B.), Leiden University Medical Center, Leiden, the Netherlands.

Department of Ophthalmology (M.J.v.S., C.J.F.B.), Amsterdam University Medical Center (UMC), Academic Medical Center, Amsterdam, the Netherlands.

出版信息

Am J Ophthalmol. 2022 Feb;234:37-48. doi: 10.1016/j.ajo.2021.07.021. Epub 2021 Jul 25.

DOI:10.1016/j.ajo.2021.07.021

PMID:34320374

Abstract

PURPOSE

To investigate the natural disease course of retinal dystrophies associated with crumbs cell polarity complex component 1 (CRB1) and identify clinical end points for future clinical trials.

DESIGN

Single-center, prospective case series.

METHODS

An investigator-initiated nationwide collaborative study that included 22 patients with CRB1-associated retinal dystrophies. Patients underwent ophthalmic assessment at baseline and 2 years after baseline. Clinical examination included best-corrected visual acuity (BCVA) using Early Treatment Diabetic Retinopathy Study charts, Goldmann kinetic perimetry (V4e isopter seeing retinal areas), microperimetry, full-field electroretinography, full-field stimulus threshold (FST), fundus photography, spectral-domain optical coherence tomography, and fundus autofluorescence imaging.

RESULTS

Based on genetic, clinical, and electrophysiological data, patients were diagnosed with retinitis pigmentosa (19 [86%]), cone-rod dystrophy (2 [9%]), or isolated macular dystrophy (1 [5%]). Analysis of the entire cohort at 2 years showed no significant changes in BCVA (P = .069) or V4e isopter seeing retinal areas (P = .616), although signs of clinical progression were present in individual patients. Macular sensitivity measured on microperimetry revealed a significant reduction at the 2-year follow-up (P < .001). FST responses were measurable in patients with nonrecordable electroretinograms. On average, FST responses remained stable during follow-up.

CONCLUSION

In CRB1-associated retinal dystrophies, visual acuity and visual field measures remain relatively stable over the course of 2 years. Microperimetry showed a significant decrease in retinal sensitivity during follow-up and may be a more sensitive progression marker. Retinal sensitivity on microperimetry may serve as a functional clinical end point in future human treatment trials for CRB1-associated retinal dystrophies.

摘要

目的

研究与crumbs 细胞极性复合物成分 1（CRB1）相关的视网膜营养不良的自然病程，并确定未来临床试验的临床终点。

设计

单中心、前瞻性病例系列。

方法

一项由研究者发起的全国性合作研究，纳入 22 例 CRB1 相关性视网膜营养不良患者。患者在基线和基线后 2 年均接受眼科评估。临床检查包括使用早期糖尿病视网膜病变研究图表的最佳矫正视力（BCVA）、Goldmann 动态视野计（V4e 同视圈观察视网膜区域）、微视野计、全视野视网膜电图、全视野刺激阈值（FST）、眼底照相、谱域光学相干断层扫描和眼底自发荧光成像。

结果

根据遗传、临床和电生理数据，患者被诊断为色素性视网膜炎（19 例[86%]）、锥-杆营养不良（2 例[9%]）或孤立性黄斑营养不良（1 例[5%]）。对整个队列在 2 年时的分析显示，BCVA（P=0.069）或 V4e 同视圈观察视网膜区域（P=0.616）无显著变化，尽管个别患者存在临床进展迹象。微视野测量的黄斑敏感性在 2 年随访时显示出显著降低（P<0.001）。FST 反应在无法记录视网膜电图的患者中是可测量的。平均而言，FST 反应在随访过程中保持稳定。