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      Construction of a nomogram model to predict the risk of retinopathy of prematurity reactivate after intravitreal anti-vascular endothelial growth factor therapy: a retrospective study

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          Abstract

          Objective

          To explore the risk factors for the reactivate of retinopathy of prematurity (ROP) after intravitreal injection of anti-vascular endothelial growth factor (VEGF) and to construct a nomogram model to predict the risk of ROP reactivate.

          Methods

          A retrospective analysis was conducted on 185 ROP children who underwent anti-VEGF treatment at the First Affiliated Hospital of Zhengzhou University from January 2017 to October 2023. They were randomly divided into a training set (129 cases) and a validation set (56 cases) at a ratio of 7:3. The training set was further divided into a reactivate group ( n = 18) and a non-reactivate group ( n = 111) based on whether ROP recurred after treatment. Multivariable logistic regression analysis was used to screen for risk factors for ROP reactivate. A nomogram model was constructed using R software and validated using the validation set. The discrimination, calibration, and clinical net benefit of the model were evaluated using the receiver operating characteristic curve (ROC curve), calibration curve, and decision curve analysis, respectively.

          Results

          Multivariable logistic regression analysis showed that the number of red blood cell transfusions, use of pulmonary surfactant (PS) 2 times or more, and preoperative fundus hemorrhage were independent risk factors for ROP reactivate ( P < 0.05). The area under the ROC curve (AUC) of the training set was 0.810 (95% CI: 0.706–0.914), and that of the validation set was 0.756 (95% CI: 0.639–0.873). The Hosmer-Leme show goodness-of-fit test indicated a good fit of the model ( P = 0.31). Calibration curve analysis and decision curve analysis suggested high predictive efficacy and clinical application value of the model.

          Conclusions

          The number of red blood cell transfusions, use of PS 2 times or more, and preoperative fundus hemorrhage are independent risk factors for ROP reactivate. The nomogram model constructed based on these factors has high predictive efficacy and clinical application value.

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          Most cited references37

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          Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity.

          Retinopathy of prematurity is a leading cause of childhood blindness worldwide. Peripheral retinal ablation with conventional (confluent) laser therapy is destructive, causes complications, and does not prevent all vision loss, especially in cases of retinopathy of prematurity affecting zone I of the eye. Case series in which patients were treated with vascular endothelial growth factor inhibitors suggest that these agents may be useful in treating retinopathy of prematurity. We conducted a prospective, controlled, randomized, stratified, multicenter trial to assess intravitreal bevacizumab monotherapy for zone I or zone II posterior stage 3+ (i.e., stage 3 with plus disease) retinopathy of prematurity. Infants were randomly assigned to receive intravitreal bevacizumab (0.625 mg in 0.025 ml of solution) or conventional laser therapy, bilaterally. The primary ocular outcome was recurrence of retinopathy of prematurity in one or both eyes requiring retreatment before 54 weeks' postmenstrual age. We enrolled 150 infants (total sample of 300 eyes); 143 infants survived to 54 weeks' postmenstrual age, and the 7 infants who died were not included in the primary-outcome analyses. Retinopathy of prematurity recurred in 4 infants in the bevacizumab group (6 of 140 eyes [4%]) and 19 infants in the laser-therapy group (32 of 146 eyes [22%], P=0.002). A significant treatment effect was found for zone I retinopathy of prematurity (P=0.003) but not for zone II disease (P=0.27). Intravitreal bevacizumab monotherapy, as compared with conventional laser therapy, in infants with stage 3+ retinopathy of prematurity showed a significant benefit for zone I but not zone II disease. Development of peripheral retinal vessels continued after treatment with intravitreal bevacizumab, but conventional laser therapy led to permanent destruction of the peripheral retina. This trial was too small to assess safety. (Funded by Research to Prevent Blindness and others; ClinicalTrials.gov number, NCT00622726.).
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            International Classification of Retinopathy of Prematurity, Third Edition

            The International Classification of Retinopathy of Prematurity is a consensus statement that creates a standard nomenclature for classification of retinopathy of prematurity (ROP). It was initially published in 1984, expanded in 1987, and revisited in 2005. This article presents a third revision, the International Classification of Retinopathy of Prematurity, Third Edition (ICROP3), which is now required because of challenges such as: (1) concerns about subjectivity in critical elements of disease classification; (2) innovations in ophthalmic imaging; (3) novel pharmacologic therapies (e.g., anti-vascular endothelial growth factor agents) with unique regression and reactivation features after treatment compared with ablative therapies; and (4) recognition that patterns of ROP in some regions of the world do not fit neatly into the current classification system.
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              Retinopathy of prematurity: a review of risk factors and their clinical significance

              Retinopathy of prematurity (ROP) is a retinal vasoproliferative disease that affects premature infants. Despite improvements in neonatal care and management guidelines, ROP remains a leading cause of childhood blindness worldwide. Current screening guidelines are primarily based on two risk factors: birth weight and gestational age; however, many investigators have suggested other risk factors, including maternal factors, prenatal and perinatal factors, demographics, medical interventions, comorbidities of prematurity, nutrition, and genetic factors. We review the existing literature addressing various possible ROP risk factors. Although there have been contradictory reports, and the risk may vary between different populations, understanding ROP risk factors is essential to develop predictive models, to gain insights into pathophysiology of retinal vascular diseases and diseases of prematurity, and to determine future directions in management of and research in ROP.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2741005/overviewRole: Role: Role: Role: Role: Role: Role:
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                Journal
                Front Pediatr
                Front Pediatr
                Front. Pediatr.
                Frontiers in Pediatrics
                Frontiers Media S.A.
                2296-2360
                07 January 2025
                2024
                : 12
                : 1440437
                Affiliations
                Department of Neonatology, The First Affiliated Hospital of Zheng Zhou University , Zhengzhou, China
                Author notes

                Edited by: Alistair R. Fielder, City University of London, United Kingdom

                Reviewed by: Deliang Liu, Shenzhen Traditional Chinese Medicine Hospital, China

                Brian Fleck, University of Edinburgh, United Kingdom

                [* ] Correspondence: Xiuyong Cheng fccchengxy@ 123456zzu.edu.cn
                Article
                10.3389/fped.2024.1440437
                11747279
                39840320
                f64834e0-af23-49ce-866e-38c89c4131bd
                © 2025 Shen, Hao, Yang and Cheng.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 May 2024
                : 24 December 2024
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 37, Pages: 9, Words: 0
                Funding
                The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.
                Categories
                Pediatrics
                Original Research
                Custom metadata
                Neonatology

                anti-vascular endothelial growth factor,retinopathy of prematurity,reactivate,nomogram,preterm

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