Assessment of Retinopathy of Prematurity Regression and Reactivation Using an Artificial Intelligence–Based Vascular Severity Score
Authors: Eilts Sonja K. , Pfeil Johanna M. , Poschkamp Broder , Krohne Tim U. , Eter Nicole , Barth Teresa , Guthoff Rainer , Lagrèze Wolf , Grundel Milena , Bründer Marie-Christine , Busch Martin , Kalpathy-Cramer Jayashree , Chiang Michael F. , Chan R. V. Paul , Coyner Aaron S. , Ostmo Susan , Campbell J. Peter , Stahl Andreas ,   Comparing Alternative Ranibizumab Dosages for Safety and Efficacy in Retinopathy of Prematurity (CARE-ROP) Study Group, Grundel Milena , Pfeil Johanna M , Stahl Andreas , Bründer Marie-Christine , Bühler Anima , Daniel Moritz , Felzmann Susanne , Gross Nicolai , Horn Stefanie , Lagrèze Wolf A , Molnár Fanni , Müller Claudia , Reichl Sabine , Reiff Charlotte , Richter Olga , Stech Milena , Hentschel Roland , Stavropolou Dimitria , Tautz Juliane , Bartsch Kerstin , Braunstein Jennifer , Brinken Ralf , Brinkmann Christian Karl , Czauderna Joanna , Dralle Wiebke , Gliem Martin , Goebel Arno , Heymer Philipp , Hofmann Martina , Holz Frank G , Krohne Tim U , Kupitz David , Müller Philipp , Petrak Michael , Schmitz Eva Janine , Schmitz-Valckenberg Steffen , Schröder Moritz , Steinberg Julia , Supé Julia , Kant Evelyn , Kunze Diana , Müller Andreas , Adorf Adeline , Alex Anne , Alten Florian , Clemens Christoph R , Eter Nicole , Falkenau Silvia , Friedhoff Caroline , Loos Desiree Sandra , Mihailovic Natasa , Termühlen Julia , Uhlig Constantin , Hörnig-Franz Isabell , Rieger-Fackeldey Esther , Tekaat Maria , Werner Claudius , Altmann Mathias , Barth Teresa , Blecha Christiane , Brandl-Rühle Sabine , Helbig Horst , Hufendiek Karsten , Jägle Herbert , Konrad Julia , Kopetzky Eva , Lehmann Fabian , Oberacher-Velten Isabel , Keller-Wackerbauer Annette , Kittel Jochen , Segerer Hugo , Ackermann Phillip , Benga Jemina , Guthoff Rainer , Guthoff Tanja , Kleinert Elena , Mayatepek Ertan , Schrader Stefan , Völker Magdalena , Höhn Thomas , Lohmeier Klaus , Sabir Hemmen , Brevis Francisco , Mönig Tina , Schwarz Simone , Ehmer Angela , Meltendorf Synke , Schuart Claudia , Avenarius Stefan , Böttger Ralf , Apel Christoph , Bergmann Anne , Herrmann Karsten , Ockert-Schön Franziska , Wegener Sabine , Ehrt Oliver , Nentwich Martin , Pressler Angelika , Rudolph Günther , Genzel-Boroviczeny Orsolya , Schmidt Susanne , Münch Hans-Georg , Thilmany Claude , Aisenbrey Sabine , Bruckmann Anna , Dimopoulos Spyridon , Hagemann Ulrike , Inhoffen Werner , Partsch Michael , Schrader Merle , Süsskind Daniela , Völker Michael , Bialkowski Anja , Müller-Hansen Ingo , Gerberth Andrea , Hasselbach Heike Christine , Lindemann Solveig , Purtskhvanidze Konstantine , Raffel Yvonne , Roider Johann , Schröder Greta , Szymanek Beke , Tode Jan , Bendiks Meike , Modlich Simon , Jandeck Isabel , Gerding Heinrich , Smith Lois E H 
Published: January 2023

ImportanceOne 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.ObjectiveTo 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 ParticipantsThis 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.InterventionsAn AI-based algorithm assigned a VSS between 1 (normal) and 9 (most severe) to fundus images.Main Outcomes and MeasuresAnalysis 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.ResultsAmong 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 &amp;lt; .001) and 2.9 (1.3) at week 4 (P &amp;lt; .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 &amp;lt; .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 &amp;lt; .001).Conclusions and RelevanceIn 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.