Gnanaraj Ramya, Lisker-Cervantes Andres, Patnaik Jennifer, Rajeswaren Vivian, Mehta Nihaal, Gange William, Lynch Anne M, Palestine Alan, Mathias Marc, Manoharan Niranjan, Mandava Naresh, Forest Talisa E de Carlo
Department of Ophthalmology, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, USA.
Department of Ophthalmology, University of Colorado Anschutz Medical Campus School of Medicine, Aurora, Colorado, USA
BMJ Open Ophthalmol. 2025 Apr 5;10(1):e002112. doi: 10.1136/bmjophth-2024-002112.
To evaluate multimodal imaging (MMI) biomarkers for predicting progression from intermediate to advanced age-related macular degeneration (AMD).
This prospective longitudinal cohort study included patients with intermediate AMD (iAMD) enrolled in the University of Colorado AMD registry between July 2014 and August 2023, with follow-up through February 2024. At enrolment, patients' medical histories and MMI were collected. Baseline and follow-up imaging were reviewed for progression to geographic atrophy (GA) and neovascular AMD (nAMD). Univariate and multivariable Cox proportional hazard modelling with competing risks to determine HRs for progression.
A total of 367 patients (733 eyes) with iAMD were included in the study, with a median follow-up of 27.8 months. During this period, 100 eyes progressed to GA, 58 to nAMD. Adjusted for age, BMI and hypertension, progression to nAMD was significantly associated with soft drusen (HR 5.31, 95% CI 1.95 to 14.4, p=0.001), pigmentary changes (HR 2.74, 95% CI 1.52 to 4.92, p=0.0008) on colour fundus photography (CFP) and subretinal hyper-reflective material (SHRM) (HR 3.36, 95% CI 1.88 to 6.02, p<0.0001) and intraretinal hyper-reflective foci (IHRF) (HR 3.12, 95% CI 1.74 to 5.57, p=0.0001) on optical coherence tomography (OCT). Adjusted for age, progression to GA was predicted by soft drusen (HR 1.90, 95% CI 1.11 to 3.27, p=0.020), drusenoid pigment epithelial detachment (PED) (HR 5.51, 95% CI 2.49 to 12.2, p<0.0001), avascular non-drusenoid PED (HR 6.59, 95% CI 1.54 to 28.1, p=0.011), pigmentary changes (HR 4.44, 95% CI 2.84 to 6.96, p<0.0001) on CFP and nnSRF (HR 6.41, 95% CI 1.39 to 29.6, p=0.017), SHRM (HR 2.55, 95% CI 1.45 to 4.49, p=0.001), drusenoid PED (HR 2.25, 95% CI 1.43 to 3.55, p=0.0005), avascular non-drusenoid PED (HR 4.67, 95% CI 2.45 to 8.92, p<0.0001), IHRF (HR 6.27, 95% CI 3.89 to 10.1, p<0.0001) and incomplete retinal pigment epithelium and outer retinal atrophy (HR 9.42, 95% CI 5.82 to 15.2, p<0.0001) on OCT (table 3).
Key imaging biomarkers associated with the progression were identified, which may offer prognostic information for providers. However, the study is limited by its predominantly Caucasian population and single-centre design, which may affect the generalisability of certain biomarkers.
评估多模态成像（MMI）生物标志物预测中度年龄相关性黄斑变性（AMD）进展为晚期AMD的情况。
这项前瞻性纵向队列研究纳入了2014年7月至2023年8月在科罗拉多大学AMD登记处登记的中度AMD（iAMD）患者，并随访至2024年2月。入组时，收集患者的病史和MMI。对基线和随访影像进行评估，以确定是否进展为地图样萎缩（GA）和新生血管性AMD（nAMD）。采用单变量和多变量Cox比例风险模型及竞争风险分析来确定进展的风险比（HR）。
本研究共纳入367例（733只眼）iAMD患者，中位随访时间为27.8个月。在此期间，100只眼进展为GA，58只眼进展为nAMD。在调整年龄、体重指数和高血压因素后，进展为nAMD与彩色眼底照相（CFP）上的软性玻璃膜疣（HR 5.31，95%CI 1.95至14.4，p = 0.001）、色素改变（HR 2.74，95%CI 1.52至4.92，p = 0.0008）、视网膜下高反射物质（SHRM）（HR 3.36，95%CI 1.88至6.02，p < 0.0001）以及光学相干断层扫描（OCT）上的视网膜内高反射灶（IHRF）（HR 3.12，95%CI 1.74至5.57，p = 0.0001）显著相关。在调整年龄后，进展为GA可由CFP上的软性玻璃膜疣（HR 1.90，95%CI 1.11至3.27，p = 0.020）、玻璃膜疣样色素上皮脱离（PED）（HR 5.51，95%CI 2.49至12.2，p < 0.0001）、无血管非玻璃膜疣样PED（HR 6.59，95%CI 1.54至28.1，p = 0.011）、色素改变（HR 4.44，95%CI 2.84至6.96，p < 0.0001）以及OCT上的神经视网膜下液（nnSRF）（HR 6.41，95%CI 1.39至29.6，p = 0.017）、SHRM（HR 2.55，95%CI 1.45至4.49，p = 0.001）、玻璃膜疣样PED（HR 2.25，95%CI 1.43至3.55，p = 0.0005）、无血管非玻璃膜疣样PED（HR 4.67，95%CI 2.45至8.92，p < 0.0001）、IHRF（HR 6.27，95%CI 3.89至10.1，p < 0.0001）以及视网膜色素上皮和外层视网膜不完全萎缩（HR 9.42，95%CI 5.82至15.2，p < 0.0001）预测（表3）。
确定了与进展相关的关键影像生物标志物，可为医疗人员提供预后信息。然而，本研究受主要为白种人群体和单中心设计的限制，这可能影响某些生物标志物的普遍性。
