TY - JOUR
T1 - Assessment of Retinopathy of Prematurity Regression and Reactivation Using an Artificial Intelligence-Based Vascular Severity Score
AU - Eilts, Sonja K.
AU - Pfeil, Johanna M.
AU - Poschkamp, Broder
AU - Krohne, Tim U.
AU - Eter, Nicole
AU - Barth, Teresa
AU - Guthoff, Rainer
AU - Lagrèze, Wolf
AU - Grundel, Milena
AU - Bründer, Marie Christine
AU - Busch, Martin
AU - Kalpathy-Cramer, Jayashree
AU - Chiang, Michael F.
AU - Chan, R. V.Paul
AU - Coyner, Aaron S.
AU - Ostmo, Susan
AU - Campbell, J. Peter
AU - Stahl, Andreas
N1 - Publisher Copyright:
© 2023 American Medical Association. All rights reserved.
PY - 2023/1/19
Y1 - 2023/1/19
N2 - Importance: 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. Objective: 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. Interventions: An AI-based algorithm assigned a VSS between 1 (normal) and 9 (most severe) to fundus images. Main Outcomes and Measures: 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. Results: 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). Conclusions and Relevance: 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..
AB - Importance: 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. Objective: 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. Interventions: An AI-based algorithm assigned a VSS between 1 (normal) and 9 (most severe) to fundus images. Main Outcomes and Measures: 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. Results: 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). Conclusions and Relevance: 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..
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U2 - 10.1001/jamanetworkopen.2022.51512
DO - 10.1001/jamanetworkopen.2022.51512
M3 - Article
C2 - 36656578
AN - SCOPUS:85147044467
SN - 2574-3805
VL - 6
SP - E2251512
JO - JAMA Network Open
JF - JAMA Network Open
IS - 1
ER -