New opportunities in management of patients with retinopathy prematurity (literature review and analysis of own data)

Insufficient effectiveness of laser coagulation of the avascular retinal areas in retinopathy of prematurity (ROP) plus-disease in zone I and aggressive posterior retinopathy of prematurity (APROP) requires new treatment approaches, based on the regulation of retinal angiogenesis and anti-VEGF drugs use. The BEAT-RAP study, which was the first major randomized study of anti-VEGF therapy in ROP, revealed a higher effectiveness of bevacizumab compared to retinal laser coagulation in stage 3 plus-disease of zone I. A prospective randomized trial, RAINBOW, demonstrated the effectiveness of ranibizumab in plus-disease stages 1, 2 and 3 in zone I and stage 3 in zone II and in APROP, so that the drug may be recommended for use in children with ROP. The demonstrated high effect of anti-VEGF therapy in ROP is consistent with our own data. Anti-VEGF therapy opens up new possibilities in the treatment of a particular class of ROP forms. The advantages of anti-VEGF therapy include higher clinical effectiveness of treatment of ROP type I with localization in the posterior pole (I and posterior II zone), absence of "blockage" of the peripheral retina, lower frequency of myopia development and degree, relative fastness of the procedure, the acceptability for patients whose fundus is difficult to visualize, and somatically burdened patients who are contraindicated for prolonged anesthesia used for retinal laser coagulation. When using anti-VEGF drugs in the post-threshold stages of the disease, one should take account of an increased risk of proliferation progression and retinal detachment development. Premature infants with retinopathy regression after anti-VEGF therapy require a longer duration of regular and frequent follow-up (up to 70 weeks of postmenstrual age) due to the risk of relapse and extraretinal proliferation in future.

retinopathy of prematurity, inhibitors of vascular endothelial growth factor, recurrence of retinopathy, aggressive posterior retinopathy of prematurity, plus disease

1. Solebo A.L., Teoh L., Rahi J. Epidemiology of blindness in children. Arch. Dis. Child. 2017; 102: 853–7. doi:10.1136/archdischild-2016-310532

2. Stahl A., Lepore D., Fielder A., et al. Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled trial. The Lancet. 2019; 394 (10208): 1551–9. http://dx.doi.org/10.1016/S0140-6736(19)31344-3

3. The early treatment for retinopathy of prematurity cooperative group. Final visual acuity results in the early treatment for retinopathy of prematurity study. Arch Ophthalmol. 2010 June; 128(6): 663–71. doi:10.1001/archophthalmol.2010.72

4. Yoon J.M., Shin D.H., Kim S.J., et al. Outcomes after laser versus combined laser and bevacizumab treatment for type 1 retinopathy of prematurity in zone 1. Retina. 2017; 37 (1): 88–96. doi:10.1097/IAE.0000000000001125

5. Sankar M.J., Sankar J., Chandra P. Anti-vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity. Cochrane Database Syst. Rev. 2018; 1: CD009734. doi:10.1002/14651858.CD009734.pub3

6. Kennedy K.A., Mintz-Hittner H.A. Medical and developmental outcomes of bevacizumab versus laser for retinopathy of prematurity. J. AAPOS. 2018; 22: 61–5. doi:10.1016/j.jaapos.2017.10.006

7. Lien R., Yu M.H., Hsu K.H., et al. Neurodevelopmental outcomes in infants with retinopathy of prematurity and bevacizumab treatment. PLoS One 2016; 11: e01480. doi:10.1371/journal.pone.0148019

8. Morin J., Luu T.M., Superstein R., et al. Neurodevelopmental outcomes following bevacizumab injections for retinopathy of prematurity. Pediatrics. 2016; 137: e20153218. doi:10.1542/peds.2015-3218

9. Storey P.P., Tauqeer Z., Yonekawa Y., et al. The impact of prefilled syringes on endophthalmitis following intravitreal injection of ranibizumab. Am. J. Ophthalmol. 2019; 199: 200–8. doi:10.1016/j.ajo.2018.11.023

10. Lyu J., Zhang Q., Chen C.L., et al. Recurrence of retinopathy of prematurity after intravitreal ranibizumab monotherapy: timing and risk factors. Invest. Ophthalmol. Vis. Sci. 2017; 58: 1719–25. doi:10.1167/iovs.16-20680

11. Lepore D., Quinn G.E., Molle F., et al. Follow-up to age 4 years of treatment of type 1 retinopathy of prematurity intravitreal bevacizumab injection versus laser: fluorescein angiographic findings. Ophthalmol. 2018; 125: 218–26. doi:10.1016/j.ophtha.2017.08.005

12. Mintz-Hittner H.A., Kennedy K.A., Chuang A.Z. Group B-RC. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N. Engl. J. Med. 2011 Feb 17; 364 (7): 603–15. doi: 10.1056/NEJMoa1007374

13. Early Treatment for Retinopathy of Prematurity Cooperative G. Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial. Arch. Ophthalmol. 2003 Dec; 121 (12): 1684–94. doi: 10.1001/archopht.121.12.1684

14. Autrata R., Krejcirova I., Senkova K., et al. Intravitreal pegaptanib combined with diode laser therapy for stage 3+ retinopathy of prematurity in zone I and posterior zone II. Eur. Jour. Ophthal. 2012; 22 (5): 687–94. doi:10.5301/ejo.5000166

15. Lucentis® : Medical Guidelines. LSR-004567/8, 15.06.2020. https://grls.rosminzdrav.ru/GRLS.aspx (In Russian).

16. Gonzales J.M.G., Snider L., Blair M., et al. Prophylactic peripheral laser and fluorescein angiography after bevacizumab for retinopathy of prematurity. Retina. 2018; 38 (4): 764–72. doi:10.1097/IAE.0000000000001581

17. Wallace D.K., Dean T.W., Hartnett M.E., et al. A dosing study of bevacizumab for retinopathy of prematurity. Ophthalmology. 2018 Dec; 125 (12): 1961–6. doi: 10.1016/j.ophtha.2018.05.001

18. Chan J.J., Lam C.P., Kwok M.K., et al. Risk of recurrence of retinopathy of prematurity after initial intravitreal ranibizumab therapy. Sci Rep. 2016; 6: 27082. doi: 10.1038/srep27082

19. Moshfeghi D.M. Systemic solutions in retinopathy of prematurity. Am. J. Ophthalmol. 2018 Sep; 193:xiv-xviii. doi: 10.1016/j.ajo.2018.05.013

20. Katargina L.A., Demchenko E.N. Medicament therapy of active retinopathy of prematurity (anti-VEGF therapy of retinopathy of prematurity). V kn.: V.V. Neroev, L.A. Katargina. Retinopathy of prematurity. Moscow: Izdatel'stvo IKAR. 2020 (in Russian).

21. Stahl A., Krohne T.U., Eter N., et al. Comparing alternative Ranibizumab dosages for safety and efficacy in retinopathy of prematurity: A randomized clinical trial. JAMA Pediatrics. 2018; 172 (3): 278–86. http://dx.doi.org/10.1001/jamapediatrics.2017.4838

22. Zhang G., Yang M., Zeng J., et al. Comparison of intravitreal injection of ranibizumab versus laser therapy for zone ii treatment-requiring retinopathy of prematurity. Retina. 2017; 37 (4): 710–7. http://dx.doi.org/10.1097/iae.0000000000001241

23. Feng J., Qian J., Jiang Y., et al. Efficacy of primary intravitreal ranibizumab for retinopathy of prematurity in China. Ophthalmology. 2017 March; 124 (3): 408–9. doi:10.1016/j.ophtha.2016.10.032

24. US National Institutes of Health. ClinicalTrials.gov. NCT02640664. Rainbow Extension Study (Rainbow Ext). Available at: https://clinicaltrials.gov/ct2/show/NCT02640664

25. Yonekawa Y., Wu W.-C., Nitulescu C.E., et al. Progressive retinal detachment in infants with retinopathy of prematurity treated with intravitreal bevacizumab or ranibizumab. Retina. 2018; 38: 1079–83. doi:10.1097/IAE.0000000000001685