Chew Emily Y, Cukras Catherine, Duncan Jacque L, Dysli Chantal, He Ye, Henry Erin, Holz Frank, Moult Eric, Owsley Cynthia, Roorda Austin, Sarraf David, Schwartz Roy, Spaide Richard, Taylor Lori, Teussink Michel, Zhang Yuhua, Staurenghi Giovanni
Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
F. Hoffman-La Roche Ltd, Basel, Switzerland.
Exp Eye Res. 2025 Jun;255:110349. doi: 10.1016/j.exer.2025.110349. Epub 2025 Mar 22.
Age-related macular degeneration (AMD), a neurodegenerative disease, is the leading cause of visual impairment in industrialized countries. Challenges in defining structural/functional relationships at various stages of disease especially with non-neovascular AMD, have slowed therapeutic development. Development of such sensitive and specific markers associated with AMD progression could provide the basis necessary for future regulatory outcome variables that will be useful in assessing new, innovative AMD therapies. Advanced imaging technologies such as high-resolution optical coherence tomography, fundus autofluorescence and near infrared imaging; and functional tests including rod-mediated dark adaptation, microperimetry, fluorescence lifetime imaging ophthalmoscopy and others will be important in the evaluation of these structure/function correlations. Development of more advanced methods to study structure such as high-resolution OCT and en face OCT offer further opportunities to better correlate structure and function in clinical trials, and to better define useful biomarkers of visual outcome endpoints. Dark adaptation, although correlated with AMD stage, is difficult to incorporate as endpoint in clinical trials because dark adaptation changes slowly and the technique is time consuming. Microperimetry has become a useful outcome variable in many clinical trials and new methodology may improve its utility in structure-function correlation. These and other newer techniques will require further prospective studies to determine their clinical utility in early AMD detection, prediction of disease progression from intermediate to late stages, and the ability to monitor the advancement of non-neovascular AMD.
年龄相关性黄斑变性（AMD）是一种神经退行性疾病，是工业化国家视力损害的主要原因。在疾病各个阶段定义结构/功能关系面临挑战，尤其是对于非新生血管性AMD，这减缓了治疗进展。开发与AMD进展相关的敏感且特异的标志物可为未来监管结果变量提供必要基础，这些变量将有助于评估新型、创新的AMD疗法。高分辨率光学相干断层扫描、眼底自发荧光和近红外成像等先进成像技术，以及包括视杆介导的暗适应、微视野计、荧光寿命成像眼底镜检查等在内的功能测试，在评估这些结构/功能相关性方面将具有重要意义。开发更先进的研究结构的方法，如高分辨率OCT和正面OCT，为在临床试验中更好地关联结构和功能，以及更好地定义视觉结果终点的有用生物标志物提供了更多机会。暗适应虽然与AMD阶段相关，但由于暗适应变化缓慢且该技术耗时，很难在临床试验中作为终点指标纳入。微视野计已成为许多临床试验中有用的结果变量，新方法可能会提高其在结构-功能相关性方面的效用。这些以及其他更新的技术将需要进一步的前瞻性研究，以确定它们在早期AMD检测、疾病从中期到晚期进展的预测以及监测非新生血管性AMD进展方面的临床效用。
