年龄相关性黄斑变性继发地图状萎缩的自然病程：前瞻性 Proxima A 和 B 临床试验结果。

Natural History of Geographic Atrophy Secondary to Age-Related Macular Degeneration: Results from the Prospective Proxima A and B Clinical Trials.

机构信息

Pepose Vision Institute, Chesterfield, Missouri; Washington University School of Medicine, St. Louis, Missouri.

Retina Consultants of Houston, Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas.

出版信息

Ophthalmology. 2020 Jun;127(6):769-783. doi: 10.1016/j.ophtha.2019.12.009. Epub 2019 Dec 14.

DOI:10.1016/j.ophtha.2019.12.009

PMID:32081489

Abstract

PURPOSE

To better characterize visual function decline and geographic atrophy (GA) progression secondary to age-related macular degeneration (AMD).

DESIGN

Proxima A (NCT02479386)/Proxima B (NCT02399072) were global, prospective, noninterventional, observational clinical trials.

PARTICIPANTS

Eligible patients were aged ≥50 years. Patients in Proxima A had bilateral GA without choroidal neovascularization (CNV) in either eye (N = 295). Patients in Proxima B had GA without CNV in the study eye and CNV±GA in the fellow eye (fellow eye CNV cohort, n = 168) or GA without CNV in the study eye, no CNV/GA in the fellow eye (fellow eye intermediate AMD cohort, n = 32).

METHODS

Changes in visual function and imaging/anatomic parameters were evaluated over time using a mixed model for repeated measurement accounting for key baseline characteristics.

MAIN OUTCOME MEASURES

Prespecified end points included change in GA area from baseline, best-corrected visual acuity (BCVA) score assessed by Early Treatment Diabetic Retinopathy Study (ETDRS), and visual acuity under low-luminance (LLVA).

RESULTS

At 24 months, adjusted mean (standard error) change in GA lesion area from baseline was 3.87 (0.15) mm in participants with bilateral GA (Proxima A), 3.55 (0.16) mm in the fellow eye CNV cohort (Proxima B), and 2.96 (0.25) mm in the fellow eye intermediate AMD cohort (Proxima B). Progression of GA was greater in patients with baseline nonsubfoveal (vs. subfoveal) GA lesions and tended to increase as baseline low-luminance deficit increased (all patients). Conversion to GA or CNV in the fellow eye occurred in 30% and 6.7% of participants, respectively, in the Proxima B intermediate AMD cohort at month 12. Adjusted mean (standard error) changes in BCVA and LLVA (ETDRS letters) in the study eye from baseline to 24 months were -13.88 (1.40) and -7.64 (1.20) in Proxima A, -9.49 (1.29) and -7.57 (1.26) in Proxima B fellow eye CNV cohort, and -11.48 (3.39) and -8.37 (3.02) in Proxima B fellow eye intermediate AMD cohort, respectively.

CONCLUSIONS

The prospective Proxima A and B studies highlight the severe functional impact of GA and the rapid rate of GA lesion progression over a 2-year period, including in patients with unilateral GA at baseline.

摘要

目的

更好地描述与年龄相关性黄斑变性（AMD）相关的视觉功能下降和地图状萎缩（GA）进展。

设计

Proxima A（NCT02479386）/Proxima B（NCT02399072）是两项全球性、前瞻性、非干预性、观察性临床试验。

参与者

符合条件的患者年龄≥50 岁。Proxima A 中的患者双眼均患有 GA，且无脉络膜新生血管（CNV）（N=295）。Proxima B 中的患者研究眼患有 GA 且无 CNV，对侧眼（对侧眼 CNV 队列，n=168）或研究眼患有 GA 且无 CNV，对侧眼无 CNV/GA（对侧眼中间 AMD 队列，n=32）。

方法

使用混合模型重复测量法评估随时间变化的视觉功能和成像/解剖学参数，并考虑关键基线特征。

主要观察指标

预先设定的终点包括从基线开始的 GA 面积变化、最佳矫正视力（BCVA）评分（由早期糖尿病视网膜病变研究评估）和低亮度下的视力（LLVA）。

结果

24 个月时，双侧 GA 患者（Proxima A）从基线开始的 GA 病变面积的平均（标准误差）变化为 3.87（0.15）mm，对侧眼 CNV 队列（Proxima B）为 3.55（0.16）mm，对侧眼中间 AMD 队列（Proxima B）为 2.96（0.25）mm。基线下非中心凹（vs. 中心凹）GA 病变患者的 GA 进展更大，且随着基线低亮度缺陷的增加而趋于增加（所有患者）。在 Proxima B 中间 AMD 队列中，12 个月时，分别有 30%和 6.7%的患者在对侧眼出现 GA 或 CNV。从基线到 24 个月，研究眼的 BCVA 和 LLVA（ETDRS 字母）的平均（标准误差）变化分别为-13.88（1.40）和-7.64（1.20）在 Proxima A，-9.49（1.29）和-7.57（1.26）在 Proxima B 对侧眼 CNV 队列，和-11.48（3.39）和-8.37（3.02）在 Proxima B 对侧眼中间 AMD 队列。