Mukherjee Souvick, Vance Emily, von der Emde Leon, Arunachalam Thilaka, De Silva Tharindu, Thavikulwat Alisa T, Orndahl Christine, Nyaiburi Caroline, Abraham Maria, Hammel Keri, Sadda SriniVas R, Chew Emily Y, Pfau Maximilian, Wong Wai T, Jeffrey Brett G, Keenan Tiarnán D L
National Eye Institute, National Institutes of Health, Bethesda, Maryland.
The Emmes Company, LLC, Rockville, Maryland.
Ophthalmol Sci. 2025 Jul 8;5(6):100879. doi: 10.1016/j.xops.2025.100879. eCollection 2025 Nov-Dec.
To analyze the relationship between distance from geographic atrophy (GA) lesion borders and mesopic retinal sensitivity in age-related macular degeneration (AMD).
Exploratory analyses of the longitudinal microperimetry dataset from a recent phase II, prospective, single-arm, nonrandomized trial of oral minocycline for GA progression.
Individuals with GA from AMD in ≥1 eye.
Mesopic retinal sensitivity was assessed longitudinally with a fundus-guided microperimetry device at baseline, month 3, and every 6 months thereafter, using a custom T-shaped test pattern centered on the fovea. Individual test loci were superimposed on an aligned fundus autofluorescence image and distance from the closest GA lesion border (GA distance) was computed. The relationship between GA distance and retinal sensitivity was analyzed in study eyes using repeated-measures regression.
Mesopic retinal sensitivity.
The study population comprised 26 study eyes from 26 participants (mean age 74.2 years). Retinal sensitivity of extralesional testing loci increased steeply, as a quadratic function, between 0° and 2.05° (i.e., knot at 2.05°; 95% confidence interval [CI] 1.26°-2.84°) of GA distance. Beyond 2.05°, it increased linearly and less steeply. In nonlinear analyses accounting for nesting, a significant effect of GA distance on retinal sensitivity was observed. For GA distances <2.05°, sensitivity increased quadratically by approximately 1.99 decibels (dB)/° (95% CI: 1.15, 2.83 dB/°; < 0.001) or higher. For GA distances ≥2.05°, sensitivity increased at 0.56 dB/° (95% CI: 0.42, 0.70 dB/°; < 0.001). There was also a significant effect of time on sensitivity (estimate: -0.07 dB/month; 95% CI: -0.08, -0.06 dB/month; < 0.001).
The results demonstrate a perilesional zone 2° (∼580 μm) around the GA border in which retinal sensitivity changes steeply according to GA distance. This zone presents an important focus for closer evaluation in interventional studies examining potential efficacy for the preservation or recovery of retinal function. With GA progression, decreased retinal sensitivity expands ahead of GA expansion itself, as an advancing wave. Overall, the degree and extent of decreased visual function beyond GA borders have important implications for the design of clinical trials, decision-making in clinical practice, and insights into AMD pathophysiology.
Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
分析年龄相关性黄斑变性（AMD）中距地图样萎缩（GA）病变边界的距离与中视视网膜敏感度之间的关系。
对近期一项口服米诺环素治疗GA进展的II期前瞻性单臂非随机试验的纵向微视野数据集进行探索性分析。
一只或多只眼睛患有AMD相关性GA的个体。
使用以中央凹为中心的定制T形测试图案，在基线、第3个月以及此后每6个月，通过眼底引导的微视野设备纵向评估中视视网膜敏感度。将各个测试位点叠加在对齐的眼底自发荧光图像上，并计算距最近GA病变边界的距离（GA距离）。使用重复测量回归分析研究眼中GA距离与视网膜敏感度之间的关系。
中视视网膜敏感度。
研究人群包括来自26名参与者的26只研究眼（平均年龄74.2岁）。GA距离在0°至2.05°（即节点在2.05°；95%置信区间[CI] 1.26° - 2.84°）之间时，病变外测试位点的视网膜敏感度呈二次函数急剧增加。超过2.05°后，其呈线性增加且增加幅度较小。在考虑嵌套的非线性分析中，观察到GA距离对视网膜敏感度有显著影响。对于GA距离<2.05°，敏感度以约1.99分贝（dB）/°的二次函数增加（95% CI：1.15，2.83 dB/°；P < 0.001）或更高。对于GA距离≥2.05°，敏感度以0.56 dB/°增加（95% CI：0.42，0.70 dB/°；P < 0.001）。时间对敏感度也有显著影响（估计值：-0.07 dB/月；95% CI：-0.08，-0.06 dB/月；P < 0.001）。
结果表明GA边界周围存在一个2°（约580μm）的病变周围区域，其中视网膜敏感度根据GA距离急剧变化。该区域是介入研究中更密切评估视网膜功能保存或恢复潜在疗效的重要重点。随着GA进展，视网膜敏感度降低在GA扩展之前呈前进波状扩展。总体而言，GA边界以外视觉功能降低的程度和范围对临床试验设计、临床实践决策以及对AMD病理生理学的认识具有重要意义。
在本文末尾的脚注和披露中可能会发现专有或商业披露信息。
