Importance As a disabling and frequent disease, geographic atrophy secondary to age-related macular degeneration (AMD) constitutes an important study subject. Emerging clinical trials require suitable end points. The characterization and validation of reading performance as a functional outcome parameter is warranted.

Objective To prospectively evaluate reading performance in geographic atrophy and to assess its association with established visual function assessments and structural biomarkers.

Design, Setting, and Participants The noninterventional, prospective natural history Directional Spread in Geographic Atrophy study included patients with geographic atrophy secondary to AMD who were recruited at the University Hospital in Bonn, Germany. Participants were enrolled from June 2013 to June 2016. Analysis began December 2019 and ended January 2021.

Main Outcomes and Measures Reading acuity and reading speed were assessed using Radner charts. Longitudinal fundus autofluorescence and infrared reflectance images were semiautomatically annotated for geographic atrophy, followed by extraction of shape-descriptive variables. Linear mixed-effects models were applied to investigate the association of those variables with reading performance.

Results A total of 150 eyes of 85 participants were included in this study (median [IQR] age, 77.9 [72.4-82.1] years; 51 women [60%]; 34 men [40%]). Reading performance was impaired with a median (IQR) monocular reading acuity of 0.9 (0.4-1.3) logarithm of the reading acuity determination and a reading speed of 52.8 (0-123) words per minute. In the multivariable cross-sectional analysis, best-corrected visual acuity, area of geographic atrophy in the central Early Treatment Diabetic Retinopathy Study (ETDRS) subfield, classification of noncenter vs center-involving geographic atrophy, and area of geographic atrophy in the inner-right ETDRS subfield showed strongest associations with reading acuity (cross-validated R²for reading acuity = 0.69). Regarding reading speed, the most relevant variables were best-corrected visual acuity, low-luminance visual acuity, area of geographic atrophy in the central ETDRS subfield, in the inner-right ETDRS subfield, and in the inner-upper ETDRS subfield (R² for reading speed = 0.67). In the longitudinal analysis, a similar prediction accuracy for reading performance was determined (R² for reading acuity = 0.73; R² for reading speed = 0.70). Prediction accuracy did not improve when follow-up time was added as an independent variable. Binocular reading performance did not differ from reading performance in the better-seeing eye.

Conclusions and Relevance The association of reading acuity and speed with visual functional and structural biomarkers supports the validity of reading performance as a meaningful end point in clinical trials. These findings suggest that measures in clinical and low-vision care for patients with geographic atrophy should focus primarily on the better-seeing eye.

重要性 作为一种致残和常见的疾病，继发于年龄相关性黄斑变性 (AMD) 的地理萎缩是一个重要的研究课题。新兴的临床试验需要合适的终点。有必要将阅读性能作为功能性结果参数进行表征和验证。

目的 前瞻性评估地理萎缩的阅读表现，并评估其与已建立的视觉功能评估和结构生物标志物的关联。

设计、设置和参与者 非介入性、前瞻性自然史定向传播地理萎缩研究包括在德国波恩大学医院招募的继发于 AMD 的地理萎缩患者。参与者于 2013 年 6 月至 2016 年 6 月注册。分析于 2019 年 12 月开始，至 2021 年 1 月结束。

主要结果和措施 阅读敏锐度和阅读速度使用拉德纳图表进行评估。纵向眼底自发荧光和红外反射图像半自动注释地理萎缩，然后提取形状描述变量。应用线性混合效应模型来研究这些变量与阅读能力的关联。

结果 本研究共纳入 85 名参与者的 150 只眼（中位 [IQR] 年龄，77.9 [72.4-82.1] 岁；51 名女性 [60%]；34 名男性 [40%]）。阅读能力的中位数 (IQR) 单眼阅读敏锐度为 0.9 (0.4-1.3) 的阅读敏锐度测定对数，阅读速度为每分钟 52.8 (0-123) 个单词。在多变量横断面分析中，最佳矫正视力、中央早期治疗糖尿病视网膜病变研究 (ETDRS) 子字段中的地理萎缩区域、非中心与涉及中心的地理萎缩分类以及内部地理萎缩区域右侧 ETDRS 子区域显示出与阅读敏锐度的最强关联（交叉验证R ²阅读敏锐度 = 0.69）。关于阅读速度，最相关的变量是最佳矫正视力、低亮度视力、中央 ETDRS 子域、内右 ETDRS 子域和内上 ETDRS 子域中的地理萎缩区域（R ²阅读速度 = 0.67）。在纵向分析中，确定了类似的阅读性能预测准确度（阅读敏锐度的R ² = 0.73；阅读速度的R ² = 0.70）。将随访时间作为自变量添加后，预测准确性并未提高。双目阅读性能与视力较好的眼睛的阅读性能没有差异。

结论和相关性 阅读敏锐度和速度与视觉功能和结构生物标志物的关联支持阅读能力作为临床试验中有意义的终点的有效性。这些发现表明，对地理萎缩患者的临床和低视力护理措施应主要关注视力更好的眼睛。