The Tony and Leona Campane Center for Excellence in Image-Guided Surgery and Advanced Imaging Research, Cleveland Clinic, Cleveland, Ohio; Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio.
Department of Ophthalmology, Duke University, Durham, North Carolina.
Ophthalmol Retina. 2022 Nov;6(11):1019-1027. doi: 10.1016/j.oret.2022.05.002. Epub 2022 May 13.
The purpose of the study was to perform a post hoc analysis to explore the effect of baseline anatomic characteristics identified on OCT on best-corrected visual acuity (BCVA) responses to risuteganib from the completed phase II study in subjects with dry age-related macular degeneration (AMD).
Post hoc analysis of a randomized, double-masked, placebo-controlled, phase II study.
Eyes with intermediate dry AMD with BCVA between 20/40 and 20/200. Patients with concurrent vision-influencing or macula-obscuring ocular pathologies were excluded.
Patients were randomized to receive a 1-mg intravitreal risuteganib injection or a sham injection at baseline. A second 1-mg intravitreal injection of risuteganib was given at week 16 to those in the treatment arm. Two independent, masked reading centers evaluated the baseline anatomic characteristics on OCT to explore features associated with positive responses to risuteganib.
Treatment response was defined as a gain of ≥ 8 letters in BCVA from baseline to week 28 in the treatment arm, compared with baseline to week 12 in the sham group. Anatomic parameters, measured by retinal segmentation platforms, including measures of retinal thickness were compared between the responders and nonresponders to risuteganib.
Thirty-nine patients completed the study and underwent analysis. In the treatment arm, 48% of eyes demonstrated treatment responses, compared with 7% in the sham group. In the quantitative anatomic assessment, enhanced ellipsoid integrity, greater outer retinal thickness, and decreased geographic atrophy were associated with increased BCVA gains to risuteganib.
This post hoc analysis demonstrated that baseline OCT features may help determine the likelihood of a functional response to risuteganib. The characterization of higher-order OCT features may provide important information regarding biomarkers for treatment response and could facilitate optimized clinical trial enrollment and enrichment.
本研究旨在进行一项事后分析，以探讨在干性年龄相关性黄斑变性（AMD）患者中完成的 II 期研究中，基线 OCT 上确定的解剖特征对 risuteganib 最佳矫正视力（BCVA）反应的影响。
一项随机、双盲、安慰剂对照的 II 期研究的事后分析。
BCVA 在 20/40 至 20/200 之间的中间干性 AMD 眼。排除伴有影响视力或黄斑遮蔽的眼疾的患者。
患者在基线时随机接受 1mg 玻璃体内 risuteganib 注射或假注射。治疗组患者在第 16 周时接受第二次 1mg 玻璃体内 risuteganib 注射。两个独立的、盲法阅读中心评估 OCT 上的基线解剖特征，以探索与 risuteganib 阳性反应相关的特征。
治疗反应定义为治疗组从基线到第 28 周的 BCVA 增益≥8 个字母，与假手术组从基线到第 12 周相比。通过视网膜分割平台测量的解剖参数，包括视网膜厚度测量值，在 risuteganib 的应答者和无应答者之间进行比较。
39 例患者完成研究并接受分析。在治疗组中，48%的眼显示治疗反应，而假手术组为 7%。在定量解剖评估中，增强的椭圆体完整性、更大的外视网膜厚度和减少的地图样萎缩与 risuteganib 带来的 BCVA 增益增加相关。
这项事后分析表明，基线 OCT 特征可能有助于确定对 risuteganib 产生功能反应的可能性。高阶 OCT 特征的特征描述可能提供有关治疗反应生物标志物的重要信息，并有助于优化临床试验入组和富集。
