Department of Ophthalmology, University Medicine Greifswald, Greifswald, Germany.
Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
JAMA Netw Open. 2023 Jan 3;6(1):e2251512. doi: 10.1001/jamanetworkopen.2022.51512.
One of the biggest challenges when using anti-vascular endothelial growth factor (VEGF) agents to treat retinopathy of prematurity (ROP) is the need to perform long-term follow-up examinations to identify eyes at risk of ROP reactivation requiring retreatment.
To evaluate whether an artificial intelligence (AI)-based vascular severity score (VSS) can be used to analyze ROP regression and reactivation after anti-VEGF treatment and potentially identify eyes at risk of ROP reactivation requiring retreatment.
DESIGN, SETTING, AND PARTICIPANTS: This prognostic study was a secondary analysis of posterior pole fundus images collected during the multicenter, double-blind, investigator-initiated Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity (CARE-ROP) randomized clinical trial, which compared 2 different doses of ranibizumab (0.12 mg vs 0.20 mg) for the treatment of ROP. The CARE-ROP trial screened and enrolled infants between September 5, 2014, and July 14, 2016. A total of 1046 wide-angle fundus images obtained from 19 infants at predefined study time points were analyzed. The analyses of VSS were performed between January 20, 2021, and November 18, 2022.
An AI-based algorithm assigned a VSS between 1 (normal) and 9 (most severe) to fundus images.
Analysis of VSS in infants with ROP over time and VSS comparisons between the 2 treatment groups (0.12 mg vs 0.20 mg of ranibizumab) and between infants who did and did not receive retreatment for ROP reactivation.
Among 19 infants with ROP in the CARE-ROP randomized clinical trial, the median (range) postmenstrual age at first treatment was 36.4 (34.7-39.7) weeks; 10 infants (52.6%) were male, and 18 (94.7%) were White. The mean (SD) VSS was 6.7 (1.9) at baseline and significantly decreased to 2.7 (1.9) at week 1 (P < .001) and 2.9 (1.3) at week 4 (P < .001). The mean (SD) VSS of infants with ROP reactivation requiring retreatment was 6.5 (1.9) at the time of retreatment, which was significantly higher than the VSS at week 4 (P < .001). No significant difference was found in VSS between the 2 treatment groups, but the change in VSS between baseline and week 1 was higher for infants who later required retreatment (mean [SD], 7.8 [1.3] at baseline vs 1.7 [0.7] at week 1) vs infants who did not (mean [SD], 6.4 [1.9] at baseline vs 3.0 [2.0] at week 1). In eyes requiring retreatment, higher baseline VSS was correlated with earlier time of retreatment (Pearson r = -0.9997; P < .001).
In this study, VSS decreased after ranibizumab treatment, consistent with clinical disease regression. In cases of ROP reactivation requiring retreatment, VSS increased again to values comparable with baseline values. In addition, a greater change in VSS during the first week after initial treatment was found to be associated with a higher risk of later ROP reactivation, and high baseline VSS was correlated with earlier retreatment. These findings may have implications for monitoring ROP regression and reactivation after anti-VEGF treatment.
重要性：在使用抗血管内皮生长因子（VEGF）药物治疗早产儿视网膜病变（ROP）时，最大的挑战之一是需要进行长期随访检查，以确定需要重新治疗以防止 ROP 复发的风险眼。
目的：评估基于人工智能（AI）的血管严重程度评分（VSS）是否可用于分析抗 VEGF 治疗后 ROP 的消退和再激活，并有可能识别需要重新治疗以防止 ROP 再激活的风险眼。
设计、设置和参与者：这是一项预后研究，是多中心、双盲、研究者发起的比较抗 VEGF 药物治疗 ROP 的替代剂量的安全性和疗效（CARE-ROP）随机临床试验的二次分析，该试验比较了两种不同剂量的雷珠单抗（0.12mg 与 0.20mg）治疗 ROP。CARE-ROP 试验筛选并招募了 2014 年 9 月 5 日至 2016 年 7 月 14 日之间的婴儿。在预定的研究时间点从 19 名婴儿中分析了总共 1046 张广角眼底图像。VSS 的分析于 2021 年 1 月 20 日至 2022 年 11 月 18 日进行。
干预措施：基于 AI 的算法将眼底图像的 VSS 分配为 1（正常）至 9（最严重）。
主要结果和措施：分析 ROP 婴儿随时间的 VSS 变化，比较两种治疗组（0.12mg 与 0.20mg 雷珠单抗）之间以及接受和未接受 ROP 再激活治疗的婴儿之间的 VSS 差异。
结果：在 CARE-ROP 随机临床试验中，19 名患有 ROP 的婴儿中，首次治疗时的平均（范围）胎龄为 36.4（34.7-39.7）周；10 名婴儿（52.6%）为男性，18 名（94.7%）为白人。基线时的平均（SD）VSS 为 6.7（1.9），显著降低至第 1 周的 2.7（1.9）（P<.001）和第 4 周的 2.9（1.3）（P<.001）。需要重新治疗以防止 ROP 再激活的 ROP 婴儿的平均（SD）VSS 为 6.5（1.9），与第 4 周的 VSS 相比明显升高（P<.001）。两组之间的 VSS 没有显著差异，但需要重新治疗的婴儿的 VSS 变化在基线至第 1 周之间更高（平均[SD]，基线时为 7.8[1.3]，第 1 周时为 1.7[0.7]），而不需要重新治疗的婴儿的 VSS 变化较低（平均[SD]，基线时为 6.4[1.9]，第 1 周时为 3.0[2.0]）。在需要重新治疗的眼睛中，较高的基线 VSS 与更早的重新治疗时间相关（Pearson r=-0.9997；P<.001）。
结论和相关性：在这项研究中，雷珠单抗治疗后 VSS 降低，与临床疾病消退一致。在需要重新治疗以防止 ROP 再激活的病例中，VSS 再次升高至与基线值相当的值。此外，首次治疗后第一周 VSS 的变化较大与以后发生 ROP 再激活的风险较高相关，较高的基线 VSS 与较早的重新治疗相关。这些发现可能对监测抗 VEGF 治疗后 ROP 的消退和再激活具有重要意义。
