Baillif Stéphanie, Nahon-Esteve Sacha, Pace-Loscos Tanguy, Pagès Gilles, Dufies Maeva
Department of Ophthalmology, Pasteur 2 University Hospital, Université Côte-d'Azur, Nice, France; Roca Therapeutics, Nice, France.
Department of Ophthalmology, Pasteur 2 University Hospital, Université Côte-d'Azur, Nice, France.
Cytokine. 2025 Jun;190:156921. doi: 10.1016/j.cyto.2025.156921. Epub 2025 Mar 26.
To monitor intraocular mediator dynamics in treatment-naïve neovascular age-related macular degeneration (nAMD) patients treated with anti-VEGF intravitreal injections (IVIs) to identify individual mediator patterns correlating with treatment response.
Interventional, monocentric, prospective, clinical study.
Treatment-naïve nAMD patients.
Aqueous humor samples (100-200 μL) were collected by clear cornea paracentesis at baseline (before the first anti-VEGF IVI) and before the second and third anti-VEGF IVIs. The levels of 13 intraocular mediators were measured (VEGF-A, VEGF-C, PlGF, IL-1β, IL-6, IL-10, IL-18, CXCL1, CXCL5, CXCL7, CXCL8, MIP-1α and TNFα) using multiplex arrays.
The primary endpoint was the changes in intraocular inflammatory mediator levels between baseline and month 3. Secondary endpoints were the changes in best-corrected visual acuity (BCVA) and Central Retinal Thickness (CRT) between baseline and month 4.
Fifteen eyes were included in the study. BCVA remained stable throughout the study (p = 0.07). CRT, foveal thickness, and the presence of intraretinal and subretinal fluid significantly decreased after anti-VEGF IVIs (p < 0.0001, p < 0.0001, p < 0.001 and p < 0.001, respectively). After anti-VEGF IVIs, VEGF-A levels significantly decreased (p < 0.0001). No significant differences in all other mediator levels were observed. Three patients had baseline VEGF-A levels ≤50 pg/mL: they showed higher baseline IL-6 levels (p = 0.05), and elevated IL-6 (p = 0.03), PlGF (p = 0.02), VEGF-C (p = 0.005), IL-8 (p = 0.04), and TNFα (p = 0.013) levels after the first IVI. Good clinical responders had significantly higher baseline VEGF-A levels (p = 0.007). Patients who required a fourth IVI within 8 weeks of the loading dose had higher baseline TNFα levels (p = 0.05); higher MIP-1α levels after the first IVI (p = 0.045); and elevated TNFα (p = 0.026) and IL-8 (p = 0.029) levels after the second IVI.
The aqueous humor levels of the studied mediators remained stable after anti-VEGF IVIs, except for a significant decrease in VEGF-A levels in all patients. Patients with low baseline intraocular VEGF-A levels (i.e., ≤50 pg/mL) showed an intraocular inflammatory profile with elevated IL-6, PlGF, VEGF-C, IL-8 and TNFα levels. Treatment response correlated with high baseline VEGF-A levels. An interval > 8 weeks between the third and fourth anti-VEGF IVIs was associated with a pro-angiogenic/pro-inflammatory environment.
监测初治的新生血管性年龄相关性黄斑变性（nAMD）患者在接受抗VEGF玻璃体内注射（IVI）治疗时眼内介质的动态变化，以确定与治疗反应相关的个体介质模式。
干预性、单中心、前瞻性临床研究。
初治的nAMD患者。
通过透明角膜穿刺在基线（首次抗VEGF IVI之前）以及第二次和第三次抗VEGF IVI之前采集房水样本（100 - 200μL）。使用多重阵列测量13种眼内介质的水平（VEGF - A、VEGF - C、PlGF、IL - 1β、IL - 6、IL - 10、IL - 18、CXCL1、CXCL5、CXCL7、CXCL8、MIP - 1α和TNFα）。
主要终点是基线至第3个月期间眼内炎性介质水平的变化。次要终点是基线至第4个月期间最佳矫正视力（BCVA）和中心视网膜厚度（CRT）的变化。
该研究纳入了15只眼。在整个研究过程中BCVA保持稳定（p = 0.07）。抗VEGF IVI后CRT、黄斑中心凹厚度以及视网膜内和视网膜下液的存在情况均显著降低（分别为p < 0.0001、p < 0.0001、p < 0.001和p < 0.001）。抗VEGF IVI后，VEGF - A水平显著降低（p < 0.0001）。在所有其他介质水平上未观察到显著差异。3例患者的基线VEGF - A水平≤50 pg/mL：他们的基线IL - 6水平较高（p = 0.05），并且在首次IVI后IL - 6（p = 0.03）、PlGF（p = 0.02）、VEGF - C（p = 0.005）、IL - 8（p = 0.04）和TNFα（p = 0.013）水平升高。良好的临床反应者基线VEGF - A水平显著更高（p = 0.007）。在负荷剂量后8周内需要进行第四次IVI的患者基线TNFα水平较高（p = 0.05）；首次IVI后MIP - 1α水平较高（p = 0.045）；第二次IVI后TNFα（p = 0.026）和IL - 8（p = 0.029）水平升高。
除所有患者的VEGF - A水平显著降低外，抗VEGF IVI后所研究介质的房水水平保持稳定。基线眼内VEGF - A水平较低（即≤50 pg/mL）的患者表现出眼内炎性特征，IL - 6、PlGF、VEGF - C、IL - 8和TNFα水平升高。治疗反应与高基线VEGF - A水平相关。第三次和第四次抗VEGF IVI之间的间隔> 8周与促血管生成/促炎环境相关。
