Retinopathy of Prematurity (ROP) is a vasoproliferative disorder of the developing retina and remains one of the leading preventable causes of childhood blindness worldwide. The disease predominantly affects preterm infants with low birth weight due to incomplete retinal vascularization at birth.(1) Advances in neonatal intensive care have significantly improved the survival of premature infants; however, this has been accompanied by an increased incidence of ROP, particularly in low- and middle-income countries where neonatal services have expanded rapidly but standardized screening programs remain inconsistent. The pathogenesis of ROP is multifactorial and is primarily driven by disruption of normal retinal vascular development following premature birth. Exposure to fluctuating oxygen concentrations suppresses physiological retinal vascularization during the early postnatal period, followed by hypoxia-induced pathological neovascularization mediated by vascular endothelial growth factor (VEGF). If left untreated, progressive retinal neovascularization may result in retinal detachment and irreversible visual impairment. Gestational age and birth weight are well-established non-modifiable risk factors for ROP.(2) Several neonatal factors, including prolonged oxygen supplementation, continuous positive airway pressure (CPAP), mechanical ventilation, respiratory distress syndrome (RDS), sepsis, blood transfusions, and other intensive care interventions, have also been implicated in disease development.(3) Nevertheless, the relative contribution of these factors varies across different populations depending on neonatal care practices, oxygen monitoring protocols, and regional healthcare infrastructure. India is currently experiencing the “third epidemic” of ROP, characterized by increasing survival of preterm infants and a growing burden of preventable childhood blindness.(4) Previous Indian studies have reported considerable variation in the incidence of ROP across tertiary care centres, highlighting the importance of institution-specific data to optimize screening strategies and identify locally relevant risk factors. Early identification through systematic screening and timely intervention remain the most effective approaches for preventing severe visual disability. Evaluating the incidence and determinants of ROP in individual neonatal intensive care units provides valuable evidence for improving neonatal management and strengthening screening programs. Therefore, the present study was undertaken to determine the incidence of Retinopathy of Prematurity and evaluate neonatal risk factors associated with its development among preterm infants admitted to the Neonatal Intensive Care Unit of a tertiary care hospital.

Study Design and Setting A cross-sectional observational study was conducted in Neonatal Intensive Care Units (NICU) of GMERS Medical College and Hospital,Valsad, Gujarat, India. The study was carried out over 18-month period from March 2023 to September 2024 after obtaining approval from the Institutional Human Ethics Committee. Study Population All eligible preterm neonates admitted to NICU during study period. Inclusion Criteria • Gestational age ≤32 weeks. • Birth weight ≤1500 gms Exclusion Criteria • died before first ophthalmologic examination. • failed to attend initial ROP screening examination. Sample Size The sample size was calculated using estimated prevalence of ROP reported in previous Indian studies. Although the minimum calculated sample size was 138 neonates, a total of 290 eligible neonates were enrolled to improve statistical precision and facilitate subgroup analyses. Study Procedure Written informed consent was obtained from parents or legal guardians before enrolment. Baseline demographic and clinical information was recorded using a structured data collection form. ROP screening was performed by an experienced vitreoretinal surgeon using indirect ophthalmoscopy. Initial screening was performed according to institutional protocol and retinal findings were classified using the International Classification of Retinopathy of Prematurity (ICROP). Outcome Measures Primary outcome: Incidence of ROP among enrolled neonates. Secondary outcomes: • Distribution of ROP according to gestational age and birth weight. • Clinical staging of ROP. • Association between neonatal risk factors and development of ROP. Statistical Analysis Data were entered into Microsoft Excel and analyzed using appropriate statistical methods. Categorical variables were expressed as frequencies and percentages. Associations between categorical variables were evaluated using the Chi-square test. A p-value of <0.05 was considered statistically significant.

Baseline Characteristics A total of 290 preterm with eligibility criteria were enrolled during the 18-month study period. ROP was diagnosed in 17 neonates, resulting in an overall incidence of 5.9%. There was no significant difference in incidence of ROP between male and female neonates (5.96% vs. 5.76%; p = 0.941). Table 1: Birth Weight wise distribution of Study Subjects Gestational Age ROP +ve ROP -ve p Value No. Percentage No. Percentage ≤28 Weeks 4 8.16% 45 91.84% 0.202 28 to ≤30 Weeks 9 12.00% 66 88.00% 31 to ≤32 Weeks 4 4.44% 86 95.56% Similarly, lower birth weight was associated with a greater frequency of ROP. Neonates weighing ≤1.0 kg had the highest incidence (10.96%), compared with 5.36% among infants weighing 1.0–1.25 kg and 3.19% among those weighing >1.25–1.50 kg (p = 0.105). Table 2: ROP Stage wise distribution of Study Subjects Stage of ROP No. Percentage Stage 1 5 29.41% Stage 2 3 17.65% Stage 3 1 5.88% Pre-plus Disease 7 41.18% Plus Disease 1 5.88% Table 3: Risk Factor wise distribution of Study Subjects Risk Factor ROP +ve ROP -ve p Value No. Percentage No. Percentage O2 by NP 17 18.09% 77 81.91% <0.0001 0 0.00% 196 100.00% CPAP 9 21.43% 33 78.57% <0.0001 8 3.23% 240 96.77% Mechanical ventilation 5 14.29% 30 85.71% 0.024 12 4.71% 243 95.29% RDS 7 14.89% 40 85.11% 0.004 10 4.12% 233 95.88% Surfactant 5 10.87% 41 89.13% 0.115 12 4.92% 232 95.08% Blood Transfusion 2 11.11% 16 88.89% 0.328 15 5.51% 257 94.49% Phototherapy 6 4.88% 117 95.12% 0.54 11 6.59% 156 93.41% Resuscitation at birth 3 6.52% 43 93.48% 0.836 14 5.74% 230 94.26% Table 4 : Different Treatment Modalities of ROP Mode of Treatment No. Percentage Anti VEGF{ Vascular endothelial growth factor} 8 47.06% Laser Therapy 1 5.88%

This study demonstrated an overall incidence of Retinopathy of Prematurity of 5.9% among preterm neonates admitted to a tertiary care NICU. The observed incidence was lower than that reported by many Indian studies like Balamurli M et al(5), Chaudhary M et al(6), Sivananand et al(7) where rates ranging from approximately 15% to 40% been described. The comparatively lower incidence observed in the present study may reflect improvements in neonatal intensive care, meticulous oxygen administration, early ophthalmological screening, and adherence to evidence-based neonatal management protocols. Although gestational age and birth weight did not achieve statistical significance, both demonstrated clinically meaningful inverse relationships with ROP occurrence. Infants born at lower gestational ages and with extremely low birth weights exhibited a greater frequency of disease, consistent with the established biological mechanism of incomplete retinal vascular maturation in premature infants. (8) Neonates born at <30 weeks gestation had higher ROP incidence, aligning with data from Parekh et al.(9) 88.6% of ROP cases occurred in ≤32 weeks GA (mean 30.1 weeks) and Freitas et al(10). also reported a mean GA of 30.7 weeks with lower GA linked to significantly increased odds (OR = 0.81; p < 0.001) Regarding risk factors, Akher Ali et al.(11) showed significant associations with oxygen (p=0.000), apnea (p<0.001), CPAP (p=0.000), and sepsis (p=0.009). Debolina et al.(12) emphasized early neonatal surgeries, sepsis, anemia, and mechanical ventilation as strong contributors.Patel et al.(13) also included phototherapy in their multivariate analysis and found significance, suggesting oxidative stress from high ambient light exposure might play a subtle role.Blood transfusions showed a strong correlation, as 64.7% of affected neonates had multiple transfusions. This is in agreement with Hakeem et al.(14) and Debolina et al.(12), who suggest that transfusions can disrupt oxygen-carrying capacity, elevate free iron, and modulate VEGF levels—all facilitating abnormal angiogenesis.Table 4 addressed treatment modalities, revealing a transition toward anti-VEGF (Bevacizumab) therapy as the primary intervention for severe ROP. This is supported by the landmark BEAT-ROP trial (Mintz-Hittner et al.(15), which demonstrated superior outcomes in Zone I ROP with anti-VEGF agents over laser. Unlike laser therapy, which causes irreversible retinal damage, bevacizumab allows continued peripheral retinal vascularization, preserving visual field integrity. Overall, the findings emphasize that optimizing respiratory management, maintaining strict oxygen saturation targets, and ensuring regular ophthalmic screening remain the cornerstone strategies for reducing the burden of ROP in tertiary neonatal care settings.

Retinopathy of Prematurity remains an important complication among preterm neonates despite advances in neonatal intensive care. Prematurity and extremely low birth weight were associated with an increased occurrence of ROP. Significant neonatal risk factors included oxygen supplementation through nasal prongs, Continuous Positive Airway Pressure, mechanical ventilation, and respiratory distress syndrome. These findings reinforce the importance of judicious oxygen administration, careful respiratory support, and adherence to standardized screening protocols. Early identification through regular retinal screening enables timely intervention and may substantially reduce progression to vision-threatening disease. Continued strengthening of neonatal care practices and multidisciplinary collaboration between neonatologists and ophthalmologists is essential to improve visual outcomes among high-risk preterm infants. Limitations First, it was conducted at a single tertiary care centre, which may limit the generalizability of the results to other healthcare settings with different neonatal care practices. Second, the cross-sectional observational design identifies associations but cannot establish causal relationships between individual risk factors and the development of ROP. Third, only 17 infants developed ROP, reducing the statistical power to detect significant associations for less common risk factors such as blood transfusion and surfactant therapy. Fourth, multivariable logistic regression analysis was not performed; therefore, independent predictors of ROP could not be identified after adjustment for potential confounding variables. Fifth, maternal and perinatal variables, including pregnancy-induced hypertension, maternal diabetes, antenatal infections, multiple gestation, mode of delivery, and antenatal corticosteroid exposure, were not comprehensively evaluated. Finally, long-term ophthalmological and neurodevelopmental follow-up was beyond the scope of the present study, preventing assessment of visual outcomes, recurrence after treatment, refractive errors, and neurodevelopmental sequelae. Future multicentre prospective studies involving larger cohorts, standardized oxygen-monitoring protocols, multivariable risk modelling, and long-term follow-up are warranted to validate these findings and develop robust prediction models for early identification of infants at risk of developing severe Retinopathy of Prematurity

1. Kaur, K., & Mikes, B. A. (2025). Retinopathy of prematurity. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK562319/ 2. Prasad M, Ingolfsland EC, Christiansen SP. Modifiable Risk Factors and Preventative Strategies for Severe Retinopathy of Prematurity. Life (Basel). 2023;13(5):1075. doi:10.3390/life13051075 3. Wu Y. Analysis of risk factors for retinopathy of prematurity: a single-center retrospective cohort study. Transl Pediatr. 2025;14(10):2629-2639. PMID: 41216448. 4. Kiranmayee PS, Kalluri V. India to gear up to the challenge of “third epidemic” of retinopathy of prematurity in the world. Indian J Ophthalmol. 2019;67(6):726-731. doi:10.4103/IJO.IJO_700_18. 5. Balamurali M, Balakrishnan N, Devimeenakshi K, Naaraayan SA. Incidence and risk factors of retinopathy of prematurity – a prospective observational study. Perinatal Journal. 2023;31(2):111-117. doi:10.59215/prn.23.0312006. 6. Choudhary M, Sharma J, Dulani N, Solanki M, Dulani H. Incidence and prevalence of retinopathy of prematurity in a tertiary care centre of North India. Maedica (Bucur). 2023;18(2):232-237. doi:10.26574/maedica.2023.18.2.232. 7. Sivanandan S, Chandra P, Deorari AK, Agarwal R. Retinopathy of prematurity: AIIMS, New Delhi experience. Indian Pediatr. 2016;53(Suppl 2):S123-S128. 8. Lundgren P, Kistner A, Andersson EM, Hansen Pupp I, Holmström G, Ley D, et al. Low birth weight is a risk factor for severe retinopathy of prematurity depending on gestational age. PLoS One. 2014;9(10):e109460. doi:10.1371/journal.pone.0109460. 9. Parekh A, Behera M, Kulkarni S, Narwadkar P, Natu S. Retinopathy of prematurity: a study of incidence and risk factors. Int J Contemp Pediatr. 2016 Nov;3(4):1320-1325. 10. Freitas AM, Mörschbächer R, Thorell MR, Rhoden EL. Incidence and risk factors for retinopathy of prematurity: a retrospective cohort study. Int J Retin Vitr. 2018;4:20. 11. Ali MA, Begum R, Rahman F. Retinopathy of prematurity: Incidence and risk factor: A hospital-based study. IOSR J Dent Med Sci. 2019;18(7):5-12 12. Patel SS, Shendurnikar N. Retinopathy of prematurity in India: incidence, risk factors, outcome and the applicability of current screening criteria. Int J Contemp Pediatr. 2019 Nov;6(6):2235-2241. 13. Deb D, Annamalai R, Muthukumar M. Incidence, risk factors, progression, and involution in retinopathy of prematurity at a tertiary care center in South India. Oman J Ophthalmol. 2023;16:452-60. 14. Abdel Hakeem AHA, Mohamed GB, Othman MF. Retinopathy of prematurity: A study of incidence and risk factors in NICU of Al-Minya University Hospital in Egypt. J Clin Neonatol. 2012;1(2):76-81. 15. Mintz-Hittner HA, Kennedy KA, Chuang AZ; BEAT-ROP Cooperative Group. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med. 2011;364(7):603-615.