Muth Daniel R, Quérat Laurence, Venkataraman Abinaya P, Dominguez-Vicent Alberto, Petrovski Goran, Williams Pete A, Locri Filippo, Zweifel Sandrine A, Kvanta Anders
Division of Eye and Vision, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
St. Erik Eye Hospital, Solna, Sweden.
Transl Vis Sci Technol. 2025 May 1;14(5):5. doi: 10.1167/tvst.14.5.5.
To evaluate the long-term fundus autofluorescence-based growth rate (GR) of treatment-naïve patients with geographic atrophy (GA) in age-related macular degeneration.
We conducted a prospective, single-center, observational study between February 2013 and September 2024 at the Department of Clinical Neuroscience, Karolinska Institutet, and St. Erik Eye Hospital, Stockholm/Solna, Sweden. Clinical examination and fundus autofluorescence were performed in patients with GA owing to dry age-related macular degeneration. The area and the absolute and square root transformed GR were analyzed every 6 months.
We examined 432 eyes and enrolled 204 eyes (111patients). The median follow-up was 21 months (minimum-maximum, 5-123). Of 73 fovea-sparing, 22 eyes converted to foveal-involving over a median of 24 months. The mean growth for the total cohort was 1.597 mm2/y and 0.264 mm/y after square root transformation. Bilateral (1.621 mm2/y; 0.267 mm/y), multifocal (1.961 mm2/y; 0.322 mm/y), and fovea-sparing (1.987 mm2/y; 0.234 mm/y) lesions showed significantly faster growth when analyzed in isolation. In a mixed statistical model that controlled for bilaterality, only fovea status remained a significant influencer on the square root transformed GR (P < 0.001).
In this long-term GA cohort, an influence of lesion characteristics on GRs can be observed. Fovea sparing, multifocality, and bilaterality showed faster growth, depending on the statistical model. Patients presenting with one or more of these lesion characteristics hold a high potential for benefit of future treatments because a growth slow down may be more likely to be achieved. In fovea-sparing cases, functional preservation may be possible.
By analyzing the data of one of the most extensive geographic atrophy patient cohorts in the Nordics, this study establishes a dataset on the long-term treatment-naïve growth dynamics. It provides a reference for upcoming preclinical treatment developments and clinical trial end points.
评估年龄相关性黄斑变性中初治地图样萎缩（GA）患者基于眼底自发荧光的长期生长率（GR）。
2013年2月至2024年9月期间，我们在瑞典斯德哥尔摩/索尔纳的卡罗林斯卡学院临床神经科学系和圣埃里克眼科医院进行了一项前瞻性、单中心观察性研究。对干性年龄相关性黄斑变性导致的GA患者进行临床检查和眼底自发荧光检查。每6个月分析一次病变面积以及绝对和平方根转换后的GR。
我们检查了432只眼，纳入204只眼（111例患者）。中位随访时间为21个月（最短-最长，5-123个月）。在73只未累及黄斑中心凹的眼中，22只眼在中位24个月后转变为累及黄斑中心凹。整个队列的平均生长率在平方根转换后为1.597mm²/年和0.264mm/年。单独分析时，双侧病变（1.621mm²/年；(0.267mm/年)）、多灶性病变（1.961mm²/年；(0.3)22mm/年）和未累及黄斑中心凹的病变（1.987mm²/年；(0.234mm/年)）显示出明显更快的生长速度。在控制双侧性的混合统计模型中，只有黄斑中心凹状态仍然是平方根转换后GR的显著影响因素（P<0.001）。
在这个长期的GA队列中，可以观察到病变特征对GR的影响。根据统计模型，未累及黄斑中心凹、多灶性和双侧性病变显示出更快的生长速度。具有这些病变特征中一种或多种的患者具有很大的潜在获益可能，因为未来更有可能实现生长速度减缓。在未累及黄斑中心凹的病例中，可能实现功能保留。
通过分析北欧地区最广泛的地图样萎缩患者队列之一的数据，本研究建立了一个关于初治患者长期生长动力学的数据集。它为即将开展的临床前治疗开发和临床试验终点提供了参考。
