Keywords
anti-VEGF
neonatal intensive care
How to Cite
Abstract
Background: Retinopathy of prematurity (ROP) is a significant cause of preventable childhood blindness. Twin births offer a unique opportunity to evaluate how individual neonatal factors contribute to ROP development, as co-twins typically share similar prenatal and perinatal environments.
Objective: To evaluate how individual neonatal risk factors contribute to ROP severity, differences, and treatment outcomes among preterm twin pairs managed under identical neonatal intensive care conditions.
Materials and Methods: This prospective observational study included 24 twin pairs and two singletons born at 27–34 weeks’ gestation (birth weight 850–2650 g) and was screened in accordance with ICROP3 guidelines. Clinical variables, such as gestational age, birth weight, respiratory support, and metabolic stability, were compared within twin pairs. Discordance was defined as any inter-twin difference in ROP stage, severity, or treatment requirement. Treatment options included intravitreal injection, laser photocoagulation, and vitrectomy.
Results: Seven twin pairs (2.9 %) demonstrated discordant ROP. In each pair, one twin developed any stage of ROP, including aggressive (treatment-requiring) ROP, while the co-twin exhibited mild or no ROP. Discordant pairs were delivered at 28–31 weeks, with mean birth weights of 1496 ± 523g (affected) and 1322 ± 333g (unaffected). One twin pair had the same ROP stage, but regression occurred at different times. Despite similar durations of oxygen therapy, affected infants experienced more episodes of early respiratory instability and metabolic fluctuations. All affected infants required intravitreal anti-VEGF therapy; one needed supplemental laser for recurrence. Two progressed to stage 4 ROP requiring vitrectomy, with one developing secondary glaucoma.
Conclusion: The observed discordance underscores the need for further research with larger sample sizes, inviting the scientific community to contribute to the understanding of ROP variability in twins.
References
Kaur K, Mikes BA. Retinopathy of Prematurity. [Updated 2025 Jun 2]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK562319/
Bingöl Kızıltunç, P., İdil, A., Atilla, H., Topalkara, A., & Alay, C. (2017). Results of Screening in Schools for Visually Impaired Children. Turkish journal of ophthalmology, 47(4), 216–220. https://doi.org/10.4274/tjo.82246
Gilbert C. Retinopathy of prematurity: A global perspective of the epidemics, population of babies at risk and implications for control. Early Hum Dev. 2008; 84:77–82. doi: 10.1016/j.earlhumdev.2007.11.009.
Tseng H-C, Sung F-C, Mou C-H, et al. Population-based retrospective cohort study on risk of retinopathy of prematurity in twins. PLoS ONE. 2020;15(3):e0230346. doi: 10.1371/journal.pone.0230346.
Rudanko, S. L., Fellman, V., & Laatikainen, L. (2003).Visual impairment in children born prematurely from 1972 through 1989. Ophthalmology. 2003;110(8):1639–45. doi: 10.1016/S0161-6420(03)00498-6. doi: 10.1016/S0161-6420(03)00498-6 pmid: 12917186.
Kim, S. J., Port, A. D., Swan, R., Campbell, J. P., Chan, R. V. P., & Chiang, M. F. (2018). Retinopathy of prematurity: a review of risk factors and their clinical significance. Survey of ophthalmology, 63(5), 618–637. https://doi.org/10.1016/j.survophthal.2018.04.002
Hong, E. H., Shin, Y. U., & Cho, H. (2022). Retinopathy of prematurity: a review of epidemiology and current treatment strategies. Clinical and experimental pediatrics, 65(3), 115–126. https://doi.org/10.3345/cep.2021.00773
Blazon, M. N., Rezar-Dreindl, S., Wassermann, L., Neumayer, T., Berger, A., & Stifter, E. (2024). Retinopathy of Prematurity: Incidence, Risk Factors, and Treatment Outcomes in a Tertiary Care Center. Journal of Clinical Medicine, 13(22), 6926. https://doi.org/10.3390/jcm13226926
Blumenfeld LC, Siatkowski RM, Johnson RA, et al. Retinopathy of prematurity in multiple-gestation pregnancies. Am J Ophthalmol. 1998; 125:197–203. doi: 10.1016/s0002-9394(99)80092-0.
Dos Santos Motta, M. M., Fortes Filho, J. B., Coblentz, J., & Fiorot, C. A. (2011). Multiple pregnancies and its relationship with the development of retinopathy of prematurity (ROP). Clinical ophthalmology (Auckland, N.Z.), 5, 1783–1787. https://doi.org/10.2147/OPTH.S25431.
Riazi-Esfahani M, Alizadeh Y, Karkhaneh R, et al. Retinopathy of prematurity: single versus multiple-birth pregnancies. J Ophthalmic Vis Res. 2008; 3:47–51.
Silahli, M., Tekin, M., Kal, A., Ulusoy, M. O., & Gokmen, Z. (2022). Discordant ROP (Retinopathy of prematurity) development in twins less than 32 weeks of gestational age. Acta bio-medica: Atenei Parmensis, 92(6), e2021373. https://doi.org/ 10.23750/ abm. v92i6.11729.
Sheales MP, Sheth S, Edwards AG, Carden SM. Discordant retinopathy of prematurity in twin anemia-polycythemia sequence. J AAPOS. 2017 Apr;21(2):173–174. doi: 10.1016/j.jaapos.2016.11.026. doi: 10.1016/j.jaapos. 2016.11.026. Epub 2017 Feb 24. PMID: 28238729.
International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol. 2005;123(7):991–999. doi: 10.1001/archopht. 123.7.991.
Azad R, Chandra P, Patwardhan SD, Gupta A. Profile of asymmetrical retinopathy of prematurity in twins. Indian J Ophthalmol. 2010;58(3):209–211. doi: 10.4103/0301-4738.62645. doi: 10.4103/0301-4738.62645.
Kim, H. E., Song, I. G., Chung, S. H., Choi, Y. S., & Bae, C. W. (2019). Trends in Birth Weight and the Incidence of Low Birth Weight and Advanced Maternal Age in Korea between 1993 and 2016. Journal of Korean Medical Science, 34(4), e34. https://doi.org/10.3346/jkms.2019.34.e34
Binenbaum G. Algorithms for the prediction of retinopathy of prematurity based on postnatal weight gain. Clin Perinatol. 2013;40(2):261–70. doi: 10.1016/j.clp.2013.02.004. PMID: 23719309; PMCID: PMC3692738.
Hellström A, Engström E, Hård AL, et al. Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth. Pediatrics. 2003 Nov;112(5):1016–20. doi: 10.1542/peds.112.5.1016. PMID: 14595040. [PubMed: 14595040]
Sanghi G, Dogra MR, Dutta S, et al. Intersibling variability of retinopathy of prematurity in twins and its risk factors. Int Ophthalmol. 2012 Apr;32(2):113–7. doi: 10.1007/s10792-012-9533-5. Doi: 10.1007/s10792-012-9533-5. Epub 2012 Feb 24. PMID: 22361892.
Sanghi, G., Dogra, M.R., Dutta, S. et al. Intersibling variability of retinopathy of prematurity in twins and its risk factors. Int Ophthalmol 32, 113–117 (2012). https://doi.org/10.1007/s10792-012-9533-5