Retinopathy of Prematurity (ROP) is a significant ophthalmic disorder affecting preterm infants primarily due to the incomplete development of retinal blood vessels at birth. Initially identified by Terry in 1942 as Retrolental Fibroplasia (RLF), this condition has since been extensively studied and recognized as a leading cause of preventable childhood blindness. The disease is characterized by an abnormal proliferation of retinal blood vessels, often triggered by postnatal exposure to fluctuating oxygen levels.[1,2] Over the past decade, improvements in neonatal intensive care have significantly enhanced the survival of premature and low birth weight infants. However, this increased survival has been accompanied by a parallel rise in ROP cases. Estimates suggest that approximately 20% to 40% of preterm infants develop some form of ROP, with 3% to 7% progressing to severe stages, which can result in permanent blindness if not managed appropriately.[3,4] High-income countries have successfully implemented structured screening programs, reducing ROP-related blindness. In contrast, many middle- and low-income countries, including India, are witnessing an alarming rise in ROP cases due to inconsistent screening, resource limitations, and gaps in neonatal care infrastructure.[5,6] ROP pathogenesis involves a two-phase process: initial hyperoxia suppresses vascular endothelial growth factor (VEGF) and halts normal vascular growth, followed by relative hypoxia that triggers pathological neovascularization. Established risk factors include low gestational age, low birth weight, prolonged oxygen therapy, and systemic complications such as sepsis, respiratory distress syndrome, intraventricular hemorrhage, and apnea. In India, most available data come from urban tertiary hospitals with established screening programs, while rural and semi-urban regions remain underrepresented. Many infants in these settings present with advanced disease that could have been prevented by timely detection. This highlights the need for localized studies to define the incidence, risk factors, and clinical patterns of ROP in resource-limited areas. The present study was undertaken to determine the incidence, distribution, and associated risk factors of ROP among at-risk neonates admitted to the NICU of Shri Lal Bahadur Shastri Government Medical College & Hospital, Mandi, Himachal Pradesh. The findings are intended to strengthen screening and management strategies in similar settings.

STUDY METHOD This prospective observational study was conducted in the Neonatal Intensive Care Unit (NICU) of Shri Lal Bahadur Shastri Government Medical College & Hospital, Mandi, Himachal Pradesh, between January 2023 and December 2023. The study was carried out in collaboration with the Departments of Pediatrics and Ophthalmology to ensure multidisciplinary evaluation and management of at-risk neonates. Inclusion criteria: • Gestational age (GA) <34 weeks, or • Birth weight (BW) <2000 g, or • GA 34–36 weeks with an unstable clinical course, defined by at least one of the following: prolonged oxygen therapy (≥7 days), respiratory distress syndrome (RDS), sepsis, birth asphyxia, surfactant therapy, necrotizing enterocolitis (NEC), mechanical ventilation, apnea, intraventricular hemorrhage (IVH), double-volume exchange transfusion (DVET), or blood transfusion. Exclusion criteria: • Parental refusal of consent, • Neonates who died before first ophthalmological examination, • Infants with congenital ocular anomalies, chromosomal syndromes, or inborn errors of metabolism affecting retinal vasculature. Sample size: Based on an estimated ROP prevalence of 25.8% in India, with 6% absolute precision and 95% confidence level, the minimum required sample size was calculated as 200. Accordingly, 200 neonates were enrolled. Ethical considerations: Institutional Ethics Committee approval was obtained prior to study initiation. Written informed consent was taken from parents/guardians. Confidentiality and voluntary participation were ensured. Ophthalmological examination: All eligible neonates underwent retinal screening at 4 weeks of age by a trained pediatric ophthalmologist. Pupillary dilatation was achieved with tropicamide (0.8%) and phenylephrine (2.5%) drops, instilled thrice at 15-minute intervals. Indirect ophthalmoscopy with a 20D lens was performed using a lid speculum and scleral depressor as needed. ROP was classified according to the International Classification of Retinopathy of Prematurity (ICROP). Follow-up and referral: Infants with ROP were followed at regular intervals until regression or referral. Those requiring treatment (laser photocoagulation or intravitreal anti-VEGF) were referred to higher ophthalmology centres. Statistical Analysis Data were entered and analyzed using SPSS software (version 16.0; IBM Corp., Armonk, NY, USA). Continuous variables were summarized as mean ± standard deviation (SD), while categorical variables were expressed as frequencies and percentages. The incidence of retinopathy of prematurity (ROP) was calculated as a proportion of the total neonates screened. Associations between ROP occurrence and potential risk factors were assessed using the chi-square (χ²) test. A p-value <0.05 was considered statistically significant. Multivariate logistic regression analysis was performed to identify independent predictors of ROP, and adjusted odds ratios (AOR) with 95% confidence intervals (CI) were reported. The primary study outcome was the incidence of ROP among the study population. Secondary outcomes included the distribution of ROP according to stage and zone, and the association of key neonatal risk factors with ROP development.

The present study was conducted to evaluate the incidence, distribution, severity, and risk factors associated with Retinopathy of Prematurity (ROP) in preterm neonates. The primary objective was to determine the overall incidence of ROP among neonates admitted to the neonatal intensive care unit (NICU) and to analyze the impact of various maternal and neonatal factors on its development. Additionally, the study aimed to assess the role of gestational age, birth weight, oxygen therapy, and other clinical conditions in predisposing neonates to ROP while also categorizing the disease based on its location, severity, and progression to advanced stages requiring intervention. To achieve these objectives, a hospital-based observational study was conducted, including 200 preterm neonates who underwent routine ophthalmologic screening for ROP. The overall incidence of Retinopathy of Prematurity (ROP) in the study population, highlighting that out of 200 neonates screened, 55 (27.5%) were diagnosed with ROP, while 145 (72.5%) did not develop the condition. Among the affected neonates, 67.3% had ROP in Zone 1, which is associated with the highest risk of severe visual impairment, while 27.3% had involvement in Zone 2, and 5.5% in Zone 3, indicating milder disease. In terms of severity, the majority of neonates had Stage 1 ROP (65.5%), followed by Stage 2 (30.9%) and Stage 3 (3.6%). These findings highlight that while early-stage ROP is more common, cases involving Zone 1 require close monitoring, as they have a higher potential for rapid progression to blindness if left untreated. Figure-2: Distribution of ROP by Location and Severity Among Affected Neonates Plus Disease, characterized by significant vascular abnormalities, was observed in 14.5% of cases, while 3.6% had Pre-Plus Disease, indicating early vascular changes. Pre-Threshold ROP was present in 12.7% of neonates, necessitating close monitoring for progression. Notably, none of the neonates reached Threshold ROP, suggesting that timely interventions and effective neonatal care may have prevented disease progression. Figure-3: Presence of Plus Disease, Pre-Plus Disease, Pre-Threshold, and Threshold ROP in Study Population The majority of neonates with ROP (78.2%) were delivered via normal vaginal delivery, while 14.5% were delivered by lower segment cesarean section (LSCS), and 7.3% via emergency LSCS (Em LSCS), suggesting that spontaneous preterm deliveries may be associated with increased ROP risk. Gestational age was a significant determinant, with 81.8% of affected neonates born between 28-34 weeks, while only 3.6% of the neonates born beyond 36 weeks developed ROP, highlighting a strong association between prematurity and ROP risk (p = 0.000). Birth weight also played a crucial role, as 54.5% of neonates with ROP weighed between 1000-1500g, reinforcing the well-established correlation between low birth weight and increased susceptibility to ROP. These findings emphasize the need for rigorous screening among preterm neonates with low birth weight, particularly those born vaginally. Figure-5: Impact of Mode of Delivery, Gestational Age, and Birth Weight on ROP Development Among neonates diagnosed with ROP, 69.1% had received nasal CPAP, 12.7% required mechanical ventilation, and 3.6% had high flow nasal cannula (HFNC), suggesting that prolonged oxygen exposure significantly contributes to ROP pathogenesis. The duration of oxygen therapy was another critical factor, with 72.7% of neonates who received oxygen for more than seven days developing ROP, compared to 12.7% among those who received oxygen for seven days or less, showing a strong statistical association (p = 0.000). These findings confirm that prolonged oxygen supplementation is a key modifiable risk factor, highlighting the necessity for cautious oxygen titration in preterm infants to minimize ROP progression while ensuring adequate respiratory support. Figure-6: Influence of Oxygen Therapy and Its Duration on the Incidence of ROP Respiratory distress syndrome (RDS) was significantly associated with ROP, as 76.4% of neonates with RDS developed the condition compared to 23.6% without RDS (p = 0.001). Neonatal sepsis was another major contributor, with 45.5% of affected neonates developing ROP (p = 0.000). Surfactant administration and apnea were also strongly associated with ROP, with 49.1% and 23.6% of affected neonates, respectively, demonstrating the impact of these conditions on disease development. Blood transfusion showed a weaker correlation with ROP, affecting only 1.8% of cases (p = 0.104), while other conditions such as DVET (5.5%) and shock (7.3%) were present in a smaller proportion of neonates but remained statistically relevant (p = 0.029). These findings highlight the need for stringent monitoring of neonates with RDS, sepsis, and prolonged oxygen therapy, as these factors substantially elevate ROP risk and may necessitate early ophthalmologic intervention. Figure-7: Relationship Between Clinical Conditions and the Risk of ROP

Retinopathy of Prematurity (ROP) is a significant preventable cause of childhood blindness, particularly affecting preterm neonates with low birth weight, prolonged oxygen exposure, and systemic complications. While improvements in neonatal intensive care have increased survival rates for preterm infants, they have also contributed to a higher incidence of ROP, especially in resource-limited settings where neonatal care protocols and oxygen therapy management vary significantly. Early detection and timely intervention remain crucial in preventing severe disease progression and long-term visual impairment.[7-11] The present study was conducted to assess the incidence, distribution, severity, and risk factors of ROP in a tertiary care hospital in Himachal Pradesh, India. This study found an overall incidence of retinopathy of prematurity (ROP) of 27.5%, which is comparable to previous Indian studies reporting rates between 25–33%【12–14】, but substantially higher than those reported from developed countries (5–10%)【15】. The variation reflects differences in neonatal care quality, oxygen therapy practices, and systematic screening coverage. The findings underscore that ROP continues to pose a significant burden in India, particularly in semi-urban and rural regions. Most neonates presented with early-stage disease (Stage 1–2), with only 3.6% progressing to Stage 3 and none to advanced Stage 4–5. Plus disease was seen in 14.5% of cases. A striking feature was the predominance of Zone I involvement (67.3%), which is known to carry a higher risk of progression. The absence of threshold ROP in this study suggests that timely screening and neonatal care were effective in preventing severe disease progression. Prematurity and low birth weight emerged as the strongest predictors of ROP. Infants <28 weeks and <1000 g had the highest risk, consistent with global literature【16,17】. Prolonged oxygen therapy (>7 days) significantly increased ROP incidence, confirming oxygen exposure as a key modifiable factor【18,19】. Among clinical conditions, respiratory distress syndrome and neonatal sepsis were strongly associated with ROP, highlighting the role of systemic instability and inflammation in disease pathogenesis. Our results parallel findings from other Indian studies【20,21】, which identified low gestational age, very low birth weight, and prolonged oxygen therapy as the most important risk factors. However, the relatively low proportion of advanced ROP cases in this cohort contrasts with reports from centers with less stringent screening programs【22,23】. This difference emphasizes the value of systematic screening and proactive neonatal care. The study reaffirms that prematurity, low birth weight, prolonged oxygen therapy, RDS, and sepsis are the most important determinants of ROP. As many of these are either preventable or modifiable, neonatal care protocols must focus on judicious oxygen regulation, infection prevention, and early ophthalmologic screening. The absence of threshold ROP cases in this study is encouraging and highlights that effective neonatal management can substantially reduce the risk of blindness. Strengths include the prospective design and robust sample size. Limitations include the single-center setting and relatively short follow-up, which may underestimate late-onset severe ROP. Limitations This study has certain limitations that must be acknowledged. First, it was conducted in a single tertiary care hospital, which may limit the generalizability of the findings to broader populations, particularly in rural or peripheral healthcare settings where neonatal care practices may vary. Second, while the study successfully identified key neonatal risk factors—such as low gestational age, very low birth weight, prolonged oxygen therapy, and sepsis—it did not assess long-term visual outcomes of affected infants. Such follow-up data would have provided more comprehensive insights into the effectiveness of early detection and interventions. Additionally, maternal health factors (e.g., preeclampsia, diabetes, antenatal steroid use) and possible genetic predispositions were not extensively examined, though they may also contribute to ROP development. Another limitation is the reliance on hospital-based screening, which may have excluded high-risk neonates who were discharged early and subsequently lost to follow-up. Finally, although logistic regression strengthened the reliability of risk factor associations, larger multicentric studies with extended follow-up are warranted to validate these results and to evaluate the long-term impact of neonatal care practices on ROP outcomes.

1. Shah PK, Prabhu V, Karandikar SS, Ranjan R, Narendran V, Kalpana N. Retinopathy of prematurity: Past, present and future. World J Clin Pediatr. 2016;5(1):35-46. 2. Jaju S, Patil N, Gajra B, Kumawat G, Hashim R, Subramaniam P, Shah PK. Evolution of classification and treatment of retinopathy of prematurity: a review article. TNOA J Ophthalmic Sci Res. 2023;61(3):281-9. 3. Hakeem AH, Mohamed GB, Othman MF. Retinopathy of prematurity: a study of prevalence and risk factors. Middle East Afr J Ophthalmol. 2012;19(3):289-94. 4. Ward RM, Beachy JC. Neonatal complications following preterm birth. BJOG. 2003;110 Suppl 20:8-16. 5. Sobhy M, Cole E, Jabbehdari S, et al. Operationalization of retinopathy of prematurity screening by the application of the essential public health services framework. Int Ophthalmol Clin. 2023;63(1):39-63. 6. Alfaar AS, Parlak M, Hassanain O, Abdelmaksoud E, Wolf A. The incidence of retinopathy of prematurity in neonates in Germany in 2019: a nationwide epidemiological cohort study. Eur J Pediatr. 2024;183(2):827-34. 7. Nair A, El Ballushi R, Anklesaria BZ, Kamali M, Talat M, Watts T. A review on the incidence and related risk factors of retinopathy of prematurity across various countries. Cureus. 2022;14(11):e32007. 8. Reddy B, Doddamani RM, Koujalagi MB, Guruprasad G, Ashwini RC, Aradya GH, 9. Raghoji C. Retinopathy of prematurity in a tertiary care hospital: incidence and risk factors. Int J Pediatr Res. 2016;3(5):364-70. 10. Chaudhari S, Patwardhan V, Vaidya U, Kadam S, Kamat A. Retinopathy of prematurity in a tertiary care center: incidence, risk factors and outcome. Indian Pediatr. 2009;46:219-24. 11. Swathy T, Swetha C, Archana CH, Sethi A, Chowhan MP. A study of incidence and risk factors of retinopathy of prematurity in a tertiary care modern government maternity hospital. J Cardiovasc Dis Res. 2022;13(7):205-14. 12. Archana J, Vijaya Lakshmi B. Evaluate the incidence, risk factors and severity of retinopathy of prematurity in a tertiary care center. Int J Acad Med Pharm. 2023;5(5):858- 61. 13. Seema D, et al. The prevalence of retinopathy of prematurity in the hilly terrain of Himachal Pradesh. Int J Curr Adv Res. 2020;9(7):22833-5. 14. Elumalai S, Kathavarayan R, Govindasamy V. Incidence and risk factors for retinopathy of prematurity at a medical college hospital in rural Tamil Nadu, India. Int J Contemp Pediatr. 2020;7(11):2119–24. 15. Tekchandani U, Katoch D, Dogra MR. Five-year demographic profile of retinopathy of prematurity at a tertiary care institute in North India. Indian J Ophthalmol. 2021;69:2127- 16. Patel AS, Mehta R. Prevalence of retinopathy of prematurity: a 3-year retrospective study. Int J Res Med Sci. 2021;9:3352-5. 17. Blazon MN, Rezar-Dreindl S, Wassermann L, Neumayer T, Berger A, Stifter E. Retinopathy of prematurity: Incidence, risk factors, and treatment outcomes in a tertiary care center. J Clin Med. 2024;13:6926. 18. Kar SK, Satapathy AK. Prevalence, patterns, and risk factors of retinopathy of prematurity in a tertiary multi-speciality hospital in Western Odisha. J Ophthalmol Clin Res. 2025;9(1):1-6. 19. Abrishami M, Maemori GA, Boskabadi H, Yaeghobi Z, Mafi-Nejad S, Abrishami M. Incidence and risk factors of retinopathy of prematurity in Mashhad, Northeast Iran. Iran Red Crescent Med J. 2013;15(3):229-33. 20. AlGhamdi MA, AlZahrani AJ, AlGarni SM, et al. Retinopathy of prematurity in neonatal intensive care unit at King Fahd University Hospital, Eastern Province: Prevalence, risk factors, and pattern of severity. F1000Research. 2024;13:516. 21. Dwivedi A, Dwivedi D, Lakhtakia S, Chalisgaonkar C, Jain S. Prevalence, risk factors and pattern of severe retinopathy of prematurity in eastern Madhya Pradesh. Indian J Ophthalmol. 2019;67:819-23. 22. Tekchandani U, Katoch D, Dogra MR. Five-year demographic profile of retinopathy of prematurity at a tertiary care institute in North India. Indian J Ophthalmol. 2021;69:2127- 31. 23. 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;6:2235-41. 24. Elumalai S, Kathavarayan R, Govindasamy V. Incidence and risk factors for retinopathy of prematurity at a medical college hospital in rural Tamil Nadu, India. Int J Contemp Pediatr. 2020;7(11):2119–24.