Bethany M. Erb MD , Elaine Botros , Thomas F. Saunders OD , Anna-Maria Haas MD , Rick Voland PhD , Rachel Linderman PhD , Amitha Domalpally MD, PhD , Karl G. Csaky MD
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This study evaluates how retinal tissue and photoreceptor integrity within the central 1-mm and 3-mm circles centered on the fovea correlate with visual function.</div></div><div><h3>Design</h3><div>Retrospective, longitudinal analysis of a GA clinical trial cohort.</div></div><div><h3>Subjects</h3><div>Forty-three eyes from 43 participants enrolled in GA clinical trials.</div></div><div><h3>Methods</h3><div>Baseline and 1-year fundus autofluorescence (FAF) and OCT scans were analyzed. The percentages of non-GA areas within the 1-mm and 3-mm circles centered on the fovea were quantified to calculate the Macular Tissue Integrity Index (MTII) using FAF images. The percentages of intact ellipsoid zones within the same circles were used to define the EZ Integrity Index (EZII). Longitudinal changes in MTII and EZII were compared to overall GA area growth and change in visual acuity (VA).</div></div><div><h3>Main Outcome Measures</h3><div>Correlations between MTII, EZII, GA area, and VA (best-corrected VA [BCVA] and low-luminance VA [LLVA]) were assessed.</div></div><div><h3>Results</h3><div>Macular Tissue Integrity Index and EZII within the central 1 mm correlated significantly with BCVA (R<sup>2</sup> = 0.20, P = 0.003 and R<sup>2</sup> = 0.29, P < 0.001, respectively), while EZII in the 3-mm zone correlated with both BCVA and LLVA (R<sup>2</sup> = 0.17, P < 0.01 for both). Changes in MTII or EZII over time were not associated with GA area growth or with baseline integrity indices.</div></div><div><h3>Conclusions</h3><div>Macular Tissue Integrity Index and EZII are novel biomarkers for macular photoreceptor integrity, with distinct correlations to BCVA and LLVA depending on the measurement zone. These findings support the utility of MTII and EZII in assessing macular integrity and highlight the heterogeneity of GA progression, warranting further validation in larger studies.</div></div>","PeriodicalId":74363,"journal":{"name":"Ophthalmology science","volume":"5 6","pages":"Article 100871"},"PeriodicalIF":4.6000,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Investigating Macular Tissue Integrity Index as a Novel Biomarker in Geographic Atrophy\",\"authors\":\"Bethany M. Erb MD , Elaine Botros , Thomas F. Saunders OD , Anna-Maria Haas MD , Rick Voland PhD , Rachel Linderman PhD , Amitha Domalpally MD, PhD , Karl G. Csaky MD\",\"doi\":\"10.1016/j.xops.2025.100871\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Purpose</h3><div>The rate of geographic atrophy (GA) enlargement is commonly used as an outcome in clinical trials. 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The percentages of intact ellipsoid zones within the same circles were used to define the EZ Integrity Index (EZII). Longitudinal changes in MTII and EZII were compared to overall GA area growth and change in visual acuity (VA).</div></div><div><h3>Main Outcome Measures</h3><div>Correlations between MTII, EZII, GA area, and VA (best-corrected VA [BCVA] and low-luminance VA [LLVA]) were assessed.</div></div><div><h3>Results</h3><div>Macular Tissue Integrity Index and EZII within the central 1 mm correlated significantly with BCVA (R<sup>2</sup> = 0.20, P = 0.003 and R<sup>2</sup> = 0.29, P < 0.001, respectively), while EZII in the 3-mm zone correlated with both BCVA and LLVA (R<sup>2</sup> = 0.17, P < 0.01 for both). 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引用次数: 0
摘要
目的：地理萎缩（GA）扩大率是临床试验中常用的指标。然而，这一指标通常缺乏对中央黄斑受累和结构功能关系的特异性。我们提出了一种有针对性的方法来监测中央黄斑内GA的进展，强调在分析视觉功能时，将GA扩展到3mm周围区域的有限益处。本研究评估了以中央凹为中心的1毫米和3毫米圆圈内的视网膜组织和光感受器完整性与视觉功能的相关性。设计对GA临床试验队列进行回顾性、纵向分析。来自43名参与者的43只眼睛参加了GA临床试验。方法分析基线和1年眼底自身荧光（FAF）和OCT扫描结果。利用FAF图像量化以中央凹为中心的1 mm和3 mm圆圈内非ga区域的百分比，计算黄斑组织完整性指数（MTII）。用同一圆内完整椭球区的百分比来定义EZ完整性指数（EZII）。MTII和EZII的纵向变化与总体GA面积的增长和视力（VA）的变化进行比较。评估MTII、EZII、GA面积和VA（最佳校正VA [BCVA]和低亮度VA [LLVA]）之间的相关性。结果中心1 mm内的斑组织完整性指数和EZII与BCVA有显著相关性（R2 = 0.20, P = 0.003和R2 = 0.29, P < 0.001）， 3 mm内的EZII与BCVA和LLVA均有显著相关性（R2 = 0.17, P < 0.01）。MTII或EZII随时间的变化与GA面积增长或基线完整性指数无关。结论黄斑组织完整性指数和EZII是黄斑光感受器完整性的新型生物标志物，随测量区域的不同，与BCVA和LLVA具有明显的相关性。这些发现支持MTII和EZII在评估黄斑完整性方面的效用，并强调了GA进展的异质性，需要在更大规模的研究中进一步验证。
Investigating Macular Tissue Integrity Index as a Novel Biomarker in Geographic Atrophy
Purpose
The rate of geographic atrophy (GA) enlargement is commonly used as an outcome in clinical trials. However, this metric typically lacks specificity for central macular involvement and structure–function relationships. We propose a targeted approach in monitoring GA progression within the central macula, highlighting the limited benefit of including GA expansion beyond the 3-mm perifoveal zone when analyzing visual function. This study evaluates how retinal tissue and photoreceptor integrity within the central 1-mm and 3-mm circles centered on the fovea correlate with visual function.
Design
Retrospective, longitudinal analysis of a GA clinical trial cohort.
Subjects
Forty-three eyes from 43 participants enrolled in GA clinical trials.
Methods
Baseline and 1-year fundus autofluorescence (FAF) and OCT scans were analyzed. The percentages of non-GA areas within the 1-mm and 3-mm circles centered on the fovea were quantified to calculate the Macular Tissue Integrity Index (MTII) using FAF images. The percentages of intact ellipsoid zones within the same circles were used to define the EZ Integrity Index (EZII). Longitudinal changes in MTII and EZII were compared to overall GA area growth and change in visual acuity (VA).
Main Outcome Measures
Correlations between MTII, EZII, GA area, and VA (best-corrected VA [BCVA] and low-luminance VA [LLVA]) were assessed.
Results
Macular Tissue Integrity Index and EZII within the central 1 mm correlated significantly with BCVA (R2 = 0.20, P = 0.003 and R2 = 0.29, P < 0.001, respectively), while EZII in the 3-mm zone correlated with both BCVA and LLVA (R2 = 0.17, P < 0.01 for both). Changes in MTII or EZII over time were not associated with GA area growth or with baseline integrity indices.
Conclusions
Macular Tissue Integrity Index and EZII are novel biomarkers for macular photoreceptor integrity, with distinct correlations to BCVA and LLVA depending on the measurement zone. These findings support the utility of MTII and EZII in assessing macular integrity and highlight the heterogeneity of GA progression, warranting further validation in larger studies.
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