Lynch Anne M, Grove Nathan C, Wagner Brandie D, Palestine Alan G, Holers V Michael, Frazer-Abel Ashley A, Gnanaraj Ramya, Lisker-Cervantes Andres, Patnaik Jennifer L, de Carlo Forest Talisa E, Auer Emily A, McReynolds Arden J, Mathias Marc T, Manoharan Niranjan, Rodriquez De Cordoba Santiago, Mandava Naresh
Department of Ophthalmology, University of Colorado School of Medicine, Aurora.
Department of Biostatistics and Informatics, University of Colorado School of Public Health, Aurora.
JAMA Ophthalmol. 2025 Jun 12. doi: 10.1001/jamaophthalmol.2025.1608.
Understanding the relationship between longitudinally measured systemic complement factors and intermediate AMD (iAMD) progression may enable the introduction of systemic therapeutics earlier in the disease course, before vision loss occurs.
To determine the contribution of longitudinal measures of systemic complement factors and ratios to time to progression to advanced AMD (geographic atrophy [GA] or neovascular AMD [NVAMD]).
DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted at Sue Anschutz Rodgers Eye Center, Aurora, Colorado, from 2014 to 2022. Participants were patients with iAMD and at least 1 month of follow-up. Data analysis was performed from September to December 2024.
Complement factors.
Time to progression to advanced AMD, either GA or NVAMD. Joint models were used to estimate the relationship between the exposures and the outcomes. The hazard ratio (HR) was a measure of association.
Among 325 participants, the mean (SD) age was 76 (7.0) years; 212 participants (65%) were female and 113 (35%) male. During the 8-year follow-up period (mean, 3.9 years), 110 participants (34%) progressed to any advanced AMD. Sixty-four participants (20%) progressed to GA and 46 (14%) to NVAMD. Higher systemic levels of C4 (HR, 6.8; 95% credible interval [CrI], 1.7-26.2; P = .03), C4b (HR, 60.4; 95% CrI, 6.5-544; P < .001), C3a/C3 (HR, 49.4; 95% CrI, 5.2-675; P < .001), C5a/C5 (HR, 29.3; 95% CrI, 4.8-258; P < .001), sC5b-9/C5 (HR, 297; 95% CrI, 10-14 877; P = .003), and factor I (HR, 525.9; 95% CrI, 5.5-107 589; P = .02) were associated with shorter time to progression to any AMD. Levels of C3a/C3 (HR, 9.5; 95% CrI, 1.9-55.9; P = .01) and C5a/C5 (HR, 28.6; 95% CrI, 5.7-157.9; P < .001) were associated with the hazard of GA.
Continued dysregulation of complement pathways appears to increase the hazard of iAMD progression. This supports the possibility of identifying a high-risk group of patients with iAMD for personalized ophthalmic care and targeted treatments to attenuate the risk of iAMD progression.
了解纵向测量的全身补体因子与中度年龄相关性黄斑变性（iAMD）进展之间的关系，可能有助于在视力丧失发生之前，在疾病进程的更早阶段引入全身治疗方法。
确定全身补体因子及其比率的纵向测量对进展为晚期年龄相关性黄斑变性（地理性萎缩[GA]或新生血管性年龄相关性黄斑变性[NVAMD]）时间的影响。
设计、地点和参与者：这项队列研究于2014年至2022年在科罗拉多州奥罗拉市的苏·安舒茨·罗杰斯眼科中心进行。参与者为患有iAMD且至少有1个月随访期的患者。数据分析于2024年9月至12月进行。
补体因子。
进展为晚期年龄相关性黄斑变性（GA或NVAMD）的时间。采用联合模型估计暴露因素与结局之间的关系。风险比（HR）是一种关联度量。
在325名参与者中，平均（标准差）年龄为76（7.0）岁；212名参与者（65%）为女性，113名（35%）为男性。在8年的随访期（平均3.9年）内，110名参与者（34%）进展为任何晚期年龄相关性黄斑变性。64名参与者（20%）进展为GA，46名（14%）进展为NVAMD。全身C4水平较高（HR，6.8；95%可信区间[CrI]，1.7 - 26.2；P = 0.03）、C4b水平较高（HR，60.4；95% CrI，6.5 - 544；P < 0.001）、C3a/C3水平较高（HR，49.4；95% CrI，5.2 - 675；P < 0.001）、C5a/C5水平较高（HR，29.3；95% CrI，4.8 - 258；P < 0.001）、sC5b - 9/C5水平较高（HR，297；95% CrI，10 - 14877；P = 0.003）以及因子I水平较高（HR，525.9；95% CrI，5.5 - 107589；P = 0.02）与进展为任何年龄相关性黄斑变性的时间较短相关。C3a/C3水平（HR，9.5；95% CrI，1.9 - 55.9；P = 0.01）和C5a/C5水平（HR，28.6；95% CrI，5.7 - 157.9；P < 0.001）与GA的风险相关。
补体途径的持续失调似乎会增加iAMD进展的风险。这支持了识别iAMD高危患者群体以进行个性化眼科护理和靶向治疗以降低iAMD进展风险的可能性。
