Longitudinal Analysis of Mesopic Microperimetry in a Phase II Trial Evaluating Minocycline for Geographic Atrophy

IF 3.2 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-04-01 DOI:10.1016/j.xops.2025.100783

Thilaka Arunachalam BS , Maria Abraham ScM , Christine Orndahl PhD , Supriya Menezes MS , Souvick Mukherjee PhD , Cameron Duic BS , Minali Prasad BA , Fares Siddig BS , Sunil Bellur MD , Alisa T. Thavikulwat MD , Clare Bailey MD , SriniVas R. Sadda MD , Wai T. Wong MD, PhD , Emily Y. Chew MD , Brett G. Jeffrey PhD , Tiarnán D.L. Keenan BM BCh, PhD

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Abstract

Purpose

To analyze mesopic microperimetry data from a recent phase II trial of minocycline for geographic atrophy (GA) for possible efficacy on the change in visual function and, in the absence of efficacy, to perform longitudinal analyses as a natural history study.

Design

Phase II, prospective, single-arm, nonrandomized trial. After a 9-month run-in phase, participants began oral minocycline 100 mg twice daily for 3 years.

Participants

Individuals with GA in ≥1 eye.

Methods

Participants underwent mesopic microperimetry at baseline, month 3, and every 6 months thereafter, using a custom T-shaped test pattern. Rates of change in microperimetry parameters were compared between the 24-month treatment phase and 9-month run-in phase by linear spline regression.

Main Outcome Measures

The mean macular and responding sensitivity; the mean perilesional and extralesional sensitivity; number of absolute and relative scotomatous loci.

Results

Thirty study eyes from 30 participants (mean age 74.1 years) underwent microperimetry (mean follow-up 27.4 months). For 5 of the 6 microperimetry parameters, no significant difference in the rate of change between the treatment and run-in phases was observed. The difference between the 2 phases was −0.74 decibels (dB)/year (standard error [SE] 0.85; P = 0.39) for mean macular sensitivity, −0.30 dB/year (SE 0.85; P = 0.72) for mean responding sensitivity, 1.23 dB/year (SE 1.01; P = 0.22) for mean perilesional sensitivity, and −0.02 (SE 0.01; P = 0.31) for transformed mean extralesional sensitivity. The difference in incidence rate ratios between the 2 phases was 1.17 (SE 0.11; P = 0.14) for absolute scotomatous loci and 0.73 (SE 0.11; P = 0.004) for relative scotomatous loci.

Conclusions

The results do not appear consistent with a clinically meaningful effect of minocycline on the rate of visual function decline from GA progression. This is consistent with previous analyses of the corresponding structural data. The findings demonstrate the advantages and disadvantages of different microperimetry parameters. The optimal testing patterns and parameters represent a trade-off between greater sensitivity vs. greater risk of floor/ceiling effects, with regional averages providing a useful compromise. The results may provide insights to guide the development of microperimetry end points for clinical trials.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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在评估二甲胺环素治疗地理萎缩的II期试验中，中观显微镜的纵向分析

目的分析最近二甲胺四环素治疗地理萎缩（GA）的II期试验的介观显微镜数据，以了解其对视觉功能改变的可能疗效，并在没有疗效的情况下，作为自然历史研究进行纵向分析。II期，前瞻性，单臂，非随机试验。在9个月的磨合期后，参与者开始口服米诺环素100毫克，每天两次，持续3年。参与者：≥1只眼GA患者。方法参与者在基线、第3个月和之后每6个月接受一次介观显微镜检查，采用定制的t形测试模式。采用线性样条回归比较24个月治疗期和9个月磨合期显微测量参数的变化率。主要观察指标：平均黄斑和反应敏感性；平均病灶周围和病灶外敏感性；绝对和相对变异位点的数目。结果30名参与者（平均年龄74.1岁）的30只研究眼进行了显微视野检查（平均随访27.4个月）。对于6个显微测量参数中的5个，在治疗期和磨合期之间的变化率没有观察到显著差异。两个阶段的差异为- 0.74分贝(dB)/年(标准误差[SE] 0.85；P = 0.39)，平均黄斑敏感性为- 0.30 dB/年(SE 0.85；P = 0.72)，平均响应灵敏度为1.23 dB/年(SE 1.01；P = 0.22)，平均病灶周围敏感性为- 0.02 (SE 0.01；P = 0.31)。两期发病率比差异为1.17 (SE 0.11；绝对变异位点P = 0.14)和0.73 (SE 0.11；P = 0.004)。结论该结果与米诺环素对GA进展的视觉功能下降率的临床意义不一致。这与先前对相应结构数据的分析一致。研究结果显示了不同显微测量参数的优缺点。最佳测试模式和参数代表了更高的灵敏度与更高的下限/上限效应风险之间的权衡，区域平均值提供了一个有用的折衷。该结果可能为指导临床试验显微测量终点的发展提供见解。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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