年龄相关性黄斑变性中观视网膜敏感性与地理萎缩距离的变化

IF 4.6 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-07-08 DOI:10.1016/j.xops.2025.100879

Souvick Mukherjee PhD , Emily Vance MPH , Leon von der Emde MD , Thilaka Arunachalam BS , Tharindu De Silva PhD , Alisa T. Thavikulwat MD , Christine Orndahl PhD , Caroline Nyaiburi MS , Maria Abraham ScM , Keri Hammel MS , SriniVas R. Sadda MD , Emily Y. Chew MD , Maximilian Pfau MD, PhD , Wai T. Wong MD, PhD , Brett G. Jeffrey PhD , Tiarnán D.L. Keenan BM BCh, PhD

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引用次数: 0

摘要

目的分析老年性黄斑变性（AMD）患者离地理萎缩（GA）病灶边界的距离与视网膜介观敏感性的关系。设计：对近期一项口服米诺环素治疗GA进展的前瞻性、单臂、非随机的II期临床试验的纵向显微测量数据进行探索性分析。参与者：≥1只眼黄斑变性患者。方法在基线、第3个月及以后每6个月，采用自定义的以中央凹为中心的t形测试模式，用眼底引导显微视力仪纵向评估眼底视网膜敏感性。将单个检测位点叠加在对齐的眼底自体荧光图像上，并计算离最近的GA病变边界的距离（GA距离）。使用重复测量回归分析研究眼GA距离与视网膜敏感性之间的关系。主要观察指标：中视视网膜敏感性。结果研究人群包括26只研究眼，来自26名参与者（平均年龄74.2岁）。视网膜外视检测位点的灵敏度在0°和2.05°之间呈二次函数急剧增加(即在2.05°处结；95%置信区间[CI] 1.26°-2.84°)。超过2.05°后，它呈线性增长，增幅较小。在考虑嵌套的非线性分析中，观察到遗传算法距离对视网膜灵敏度的显著影响。当遗传距离为2.05°时，灵敏度以约1.99分贝/°的二次增长(95% CI: 1.15, 2.83 dB/°；P & lt;0.001)或更高。当遗传距离≥2.05°时，灵敏度增加到0.56 dB/°(95% CI: 0.42, 0.70 dB/°；P & lt;0.001)。时间对灵敏度也有显著影响(估计：−0.07 dB/month；95% CI:−0.08,−0.06 dB/month；P & lt;0.001)。结论：在GA边界周围存在2°（~ 580 μm）的病变周围区域，该区域视网膜敏感度随GA距离的变化而急剧变化。在介入研究中，该区域为进一步评估视网膜功能保存或恢复的潜在功效提供了一个重要的焦点。随着GA的发展，视网膜敏感性的下降在GA扩展之前扩展，作为一个推进波。总的来说，视觉功能下降的程度和程度对临床试验的设计、临床实践中的决策以及对AMD病理生理学的认识具有重要意义。财务披露专有或商业披露可在本文末尾的脚注和披露中找到。

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Variation in Mesopic Retinal Sensitivity Relative to Distance from Geographic Atrophy in Age-Related Macular Degeneration

Purpose

To analyze the relationship between distance from geographic atrophy (GA) lesion borders and mesopic retinal sensitivity in age-related macular degeneration (AMD).

Design

Exploratory analyses of the longitudinal microperimetry dataset from a recent phase II, prospective, single-arm, nonrandomized trial of oral minocycline for GA progression.

Participants

Individuals with GA from AMD in ≥1 eye.

Methods

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.

Main Outcome Measures

Mesopic retinal sensitivity.

Results

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/°; P < 0.001) or higher. For GA distances ≥2.05°, sensitivity increased at 0.56 dB/° (95% CI: 0.42, 0.70 dB/°; P < 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; P < 0.001).

Conclusions

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.