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Retinopathy of Prematurity

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Emerging Topics and Controversies in Neonatology

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Abstract

Retinopathy of prematurity (ROP) is a potentially treatable sight threatening disorder that results from the abnormal development of intra-retinal vasculature in preterm infants. ROP occurs worldwide and in the United States, is the third most common cause of blindness in children. Rates of visual impairment arising from ROP vary, with between 2% and 12% occurrence in highly industrialised nations in Northern Europe, and 0 to 38% in middle to low income countries such as Latin America and South East Asia.

Babies born at less than 32 weeks of gestation and those with extremely low birth weight of less than 1000 g are particularly vulnerable to ROP that requires treatment. In less developed or middle-income countries, ROP also occurs in heavier and older infants and it is recognised that the financial resources available for ROP screening and neonatal care will impact the reported prevalence of ROP. Although this has remained stable in the United States, the increasing problem of ROP worldwide has driven the need to target screening and assessment as well explore new treatments.

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References

  1. 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.

    Article  PubMed  Google Scholar 

  2. Kong L, Fry M, Al-Samarraie M, Gilbert C, Steinkuller PG. An update on progress and the changing epidemiology of causes of childhood blindness worldwide. J AAPOS. 2012;16:501–7.

    Article  PubMed  Google Scholar 

  3. Gilbert C, Rahi J, Eckstein M, O’Sullivan J, Foster A. Retinopathy of prematurity in middle-income countries. Lancet. 1997;350:12–4.

    Article  CAS  PubMed  Google Scholar 

  4. International Committee for the Classification of Retinopathy of Prematurity. The international classification of retinopathy of prematurity revisited. Arch Ophthalmol. 2005;123:991–9.

    Article  Google Scholar 

  5. Gilbert C. Characteristics of infants with severe retinopathy of prematurity in countries with low, moderate, and high levels of development: implications for screening programs. Pediatrics. 2005;115:e518–25.

    Article  PubMed  Google Scholar 

  6. Gergely K, Gerince A. Retinopathy of prematurity—epidemics, incidence, prevalence, blindness. Bratisl Lek List. 2010;111:514–7.

    CAS  Google Scholar 

  7. Quinn GE, Barr C, Bremer D, et al. Changes in course of retinopathy of prematurity from 1986 to 2013 comparison of three studies in the United States. Ophthalmology. 2016;123:1595–600.

    Article  PubMed  Google Scholar 

  8. Blencowe H, Lawn JE, Vazquez T, Fielder A, Gilbert C. Preterm-associated visual impairment and estimates of retinopathy of prematurity at regional and global levels for 2010. Pediatr Res. 2013;74(Suppl 1):35–49.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Claxton S, Fruttiger M. Role of arteries in oxygen induced vaso-obliteration. Exp Eye Res. 2003;77:305–11.

    Article  CAS  PubMed  Google Scholar 

  10. Hartnett ME, Penn JS. Mechanisms and management of retinopathy of prematurity. N Engl J Med. 2012;367:2515–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Good WV. Final results of the early treatment for retinopathy of prematurity (ETROP) randomized trial. Trans Am Ophthalmol Soc. 2004;102:233–48; discussion 248–50

    PubMed  PubMed Central  Google Scholar 

  12. Wallace DK, Quinn GE, Freedman SF, Chiang MF. Agreement among pediatric ophthalmologists in diagnosing plus and pre-plus disease in retinopathy of prematurity. J AAPOS. 2008;12:352–6.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Stoll BJ, Hansen NI, Bell EF, et al. Neonatal outcomes of extremely preterm infants from the NICHD neonatal research network. Pediatrics. 2010;126:443–56.

    Article  PubMed  Google Scholar 

  14. Good WV, Hardy RJ, Dobson V, Palmer EA, Phelps DL, Quintos M, Tung B, Early Treatment for Retinopathy of Prematurity Cooperative Group. The incidence and course of retinopathy of prematurity: findings from the early treatment for retinopathy of prematurity study. Pediatrics. 2005;116:15–23.

    Article  PubMed  Google Scholar 

  15. Adams GGW, Bunce C, Xing W, Butler L, Long V, Reddy A, Dahlmann-Noor AH. Treatment trends for retinopathy of prematurity in the UK: active surveillance study of infants at risk. BMJ Open. 2017;7:1–7.

    Google Scholar 

  16. Ng EYJ, Lanigan B, O’Keefe M. Fundus fluorescein angiography in the screening for and management of retinopathy of prematurity. J Pediatr Ophthalmol Strabismus. 2015;43:85–90.

    Article  Google Scholar 

  17. Zepeda-Romero LC, Oregon-Miranda AA, Lizarraga-Barrón DS, Gutiérrez-Camarena O, Meza-Anguiano A, Gutiérrez-Padilla JA. Early retinopathy of prematurity findings identified with fluorescein angiography. Graefes Arch Clin Exp Ophthalmol. 2013;251:2093–7.

    Article  CAS  PubMed  Google Scholar 

  18. Azad R, Chandra P, Khan M, Darswal A. Role of intravenous fluorescein angiography in early detection and regression of retinopathy of prematurity. J Pediatr Ophthalmol Strabismus. 2008;45:36–9.

    Article  PubMed  Google Scholar 

  19. Lepore D, Molle F, Pagliara MM, Baldascino A, Angora C, Sammartino M, Quinn GE. Atlas of fluorescein angiographic findings in eyes undergoing laser for retinopathy of prematurity. Ophthalmology. 2011;118:168–75.

    Article  PubMed  Google Scholar 

  20. Theodoropoulou S, Ainsworth S, Blaikie A. Ultra-wide field imaging of retinopathy of prematurity (ROP) using Optomap-200TX. BMJ Case Rep. 2013;2:1–2.

    Google Scholar 

  21. Patel CK, Fung THM, Muqit MMK, Mordant DJ, Brett J, Smith L, Adams E. Non-contact ultra-widefield imaging of retinopathy of prematurity using the Optos dual wavelength scanning laser ophthalmoscope. Eye. 2013;27:589–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Huang D, Swanson EA, Lin CP, et al. Optical coherence tomography. Science. 1991;254:1178–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Patel CK. Optical coherence tomography in the management of acute retinopathy of prematurity. Am J Ophthalmol. 2006;141:582–4.

    Article  PubMed  Google Scholar 

  24. Vinekar A, Sivakumar M, Shetty R, Mahendradas P, Krishnan N, Mallipatna A, Shetty KB. A novel technique using spectral-domain optical coherence tomography (Spectralis, SD-OCT+HRA) to image supine non-anaesthetized infants: utility demonstrated in aggressive posterior retinopathy of prematurity. Eye (Lond). 2010;24:379–82.

    Article  CAS  Google Scholar 

  25. Maldonado RS, J a I, Sarin N, Wallace DK, Freedman S, Cotten CM, Toth CA. Optimizing hand-held spectral domain optical coherence tomography imaging for neonates, infants, and children. Invest Ophthalmol Vis Sci. 2010;51:2678–85.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Mallipatna A, Vinekar A, Jayadev C, Dabir S, Sivakumar M, Krishnan N, Mehta P, Berendschot T, Yadav N. The use of handheld spectral domain optical coherence tomography in pediatric ophthalmology practice: our experience of 975 infants and children. Indian J Ophthalmol. 2015;63:586–93.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Chavala SH, Farsiu S, Maldonado R, Wallace DK, Freedman SF, Toth CA. Insights into advanced retinopathy of prematurity using handheld spectral domain optical coherence tomography imaging. Ophthalmology. 2009;116:2448–56.

    Article  PubMed  Google Scholar 

  28. Muni RH, Kohly RP, Charonis AC, Lee TC. Retinoschisis detected with handheld spectral-domain optical coherence tomography in neonates with advanced retinopathy of prematurity. Arch Ophthalmol. 2010;128:57–62.

    Article  PubMed  Google Scholar 

  29. Vinekar A, Avadhani K, Sivakumar M, Mahendradas P, Kurian M, Braganza S, Shetty R, Shetty BK. Understanding clinically undetected macular changes in early retinopathy of prematurity on spectral domain optical coherence tomography. Invest Ophthalmol Vis Sci. 2011;52:5183–8.

    Article  PubMed  Google Scholar 

  30. Maldonado RS, O’Connell R, Ascher SB, Sarin N, Freedman SF, Wallace DK, Chiu SJ, Farsiu S, Cotten M, Toth CA. Spectral-domain optical coherence tomographic assessment of severity of cystoid macular edema in retinopathy of prematurity. Arch Ophthalmol (Chicago, Ill 1960). 2012;130:569–78.

    Google Scholar 

  31. Maldonado RS, Yuan E, Tran-Viet D, Rothman AL, Tong AY, Wallace DK, Freedman SF, Toth CA. Three-dimensional assessment of vascular and perivascular characteristics in subjects with retinopathy of prematurity. Ophthalmology. 2014;121:1289–96.

    Article  PubMed  Google Scholar 

  32. Anwar SA, Nath M, Patel A, Lee H, Brown S, Gottlob T, Proudlock F. Potential utility of foveal morphology in preterm infants measured using hand-held optical coherence tomography in retinopathy of prematurity screening. Retina. 2019. https://doi.org/10.1097/IAE.0000000000002622. [Epub ahead of print].

  33. Vajzovic L, Hendrickson AE, O’connell RV, Clark L, Tran-Viet D, Possin D, Chiu SJ, Farsiu S, Toth CA. Maturation of the human fovea: correlation of spectral-domain optical coherence tomography findings with histology. Am J Ophthalmol. 2012;154:779–789.e2.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Vajzovic L, Rothman AL, Tran-viet D, Cabrera MT, Freedman SF, Toth CA. Delay in retinal photoreceptor development in very preterm compared to term infants. Invest Ophthalmol Vis Sci. 2015;56(2):908–13.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Palmer EA, Flynn JT, Hardy RJ, Phelps DL, Phillips CL, Schaffer DB, Tung B. Incidence and early course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group. Ophthalmology. 1991;98:1628–40.

    Article  CAS  PubMed  Google Scholar 

  36. Royal College of Paediatrics and Child Health RC of OBA of PM, BLISS. Guideline for the screening and treatment of retinopathy of prematurity UK retinopathy of prematurity guideline. 2008.

    Google Scholar 

  37. Jefferies AL, Canadian Paediatric Society, Fetus and Newborn Committee. Retinopathy of prematurity: an update on screening and management. Paediatr Child Health. 2016;21(2):101–8.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Fierson WM, American Academy of Pediatrics Section on Ophthalmology; American Academy of Ophthalmology; American Association for Pediatric Ophthalmology and Strabismus; American Association of Certified Orthoptists. Screening examination of premature infants for retinopathy of prematurity. Pediatrics. 2013;131:189–95.

    Article  PubMed  Google Scholar 

  39. Blencowe H, Lee ACC, Cousens S, et al. Preterm birth-associated neurodevelopmental impairment estimates at regional and global levels for 2010. Pediatr Res. 2013;74(Suppl 1):17–34.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Allegaert K, Vanhole C, Casteels I, Naulaers G, Debeer A, Cossey V, Devlieger H. Perinatal growth characteristics and associated risk of developing threshold retinopathy of prematurity. J Am Assoc Pediatr Ophthalmol Strabismus. 2003;7:34–7.

    Article  Google Scholar 

  41. Wallace DK, Kylstra JA, Phillips SJ, Hall JG. Poor postnatal weight gain: a risk factor for severe retinopathy of prematurity. J AAPOS. 2000;4:343–7.

    Article  CAS  PubMed  Google Scholar 

  42. Löfqvist C, Andersson E, Sigurdsson J, Engström E, Hård A, Niklasson A, Smith L, Hellström A. Longitudinal postnatal weight and insulin-like growth factor I measurements in the prediction of retinopathy of prematurity. Arch Ophthalmol. 2006;124:1711–8.

    Article  PubMed  Google Scholar 

  43. Hellström A, Hard A-L, Engstrom E, Niklasson A, Andersson E, Smith L, Löfqvist C. Early weight gain predicts retinopathy in preterm infants: new, simple, efficient approach to screening. Pediatrics. 2009;123:e638–45.

    Article  PubMed  Google Scholar 

  44. Lundgren P, Stoltz Sjöström E, Domellöf M, Källen K, Holmström G, Hård AL, Smith LE, Löfqvist C, Hellström A. WINROP identifies severe retinopathy of prematurity at an early stage in a nation-based cohort of extremely preterm infants. PLoS One. 2013;8:1–6.

    Article  CAS  Google Scholar 

  45. Binenbaum G, Ying GS, Quinn GE, Dreiseitl S, Karp K, Roberts RS, Kirpalani H. A clinical prediction model to stratify retinopathy of prematurity risk using postnatal weight gain. Pediatrics. 2011;127:e607–14.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Binenbaum G, Ying G-S, Quinn GE, Huang J, Dreiseitl S, Antigua J, Foroughi N, Abbasi S. The CHOP postnatal weight gain, birth weight, and gestational age retinopathy of prematurity risk model. Arch Ophthalmol (Chicago, Ill 1960). 2012;130:1560–5.

    Article  Google Scholar 

  47. Binenbaum G, Ying GS, Tomlinson LA. Validation of the Children’s Hospital of Philadelphia retinopathy of prematurity (CHOP ROP) model. JAMA Ophthalmol. 2017;135:871–7.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Cao JH, Wagner BD, McCourt EA, et al. The Colorado-retinopathy of prematurity model (CO-ROP): postnatal weight gain screening algorithm. J AAPOS. 2016;20:19–24.

    Article  PubMed  Google Scholar 

  49. Eckert GU, Fortes Filho JB, Maia M, Procianoy RS. A predictive score for retinopathy of prematurity in very low birth weight preterm infants. Eye. 2012;26:400–6.

    Article  CAS  PubMed  Google Scholar 

  50. Hellstrom A, Engstrom E, Hard A, et al. Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth. Pediatrics. 2003;112:1016–20.

    Article  PubMed  Google Scholar 

  51. University of Gothenberg. https://www.winrop.com.

  52. Wu C, Löfqvist C, Smith LEH, VanderVeen DK, Hellström A, WINROP Consortium. Importance of early postnatal weight gain for normal retinal angiogenesis in very preterm infants. Arch Ophthalmol. 2012;130:992–9.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev. 2004;25:581–611.

    Article  CAS  PubMed  Google Scholar 

  54. Carmeliet P, Ferreira V, Breier G, et al. Abnormal blood vessel development and lethality in embryos lacking a single VEGF allele. Nature. 1996;380:435–9.

    Article  CAS  PubMed  Google Scholar 

  55. Ferrara N. VEGF and intraocular neovascularization: from discovery to therapy. Transl Vis Sci Technol. 2016;5:10.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Malecaze F. Detection of vascular endothelial growth factor messenger RNA and vascular endothelial growth factor-like activity in proliferative diabetic retinopathy. Arch Ophthalmol. 1994;112:1476.

    Article  CAS  PubMed  Google Scholar 

  57. Kvanta A. Ocular angiogenesis: the role of growth factors. Acta Ophthalmol Scand. 2006;84:282–8.

    Article  CAS  PubMed  Google Scholar 

  58. Aiello LP, Avery RL, Arrigg PG, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994;331:1480–7.

    Article  CAS  PubMed  Google Scholar 

  59. Chung EJ, Kim JH, Ahn HS, Koh HJ. Combination of laser photocoagulation and intravitreal bevacizumab (Avastin®) for aggressive zone I retinopathy of prematurity. Graefes Arch Clin Exp Ophthalmol. 2007;245:1727–30.

    Article  CAS  PubMed  Google Scholar 

  60. Travassos A, Teixeira S, Ferriera P, Regadas I, Travassos A, Esperancinha F, Prieto I, van Velze R, Valido A, Machado MC. Intravitreal bevacizumab in aggressive posterior retinopathy of prematurity. Ophthalmic Surg Lasers Imaging Retina. 2007;38:233–7.

    Article  Google Scholar 

  61. Quiroz-Mercado H, Martinez-Castellanos MA, Hernandez-Rojas ML, Salazar-Teran N, Chan RVP. Antiangiogenic therapy with intravitreal bevacizumab for retinopathy of prematurity. Retina. 2008;28:S19–25.

    Article  PubMed  Google Scholar 

  62. Mintz-Hittner HA, Kuffel RR. Intravitreal injection of Bevacizumab (Avastin) for treatment of stage 3 retinopathy of prematurity in zone 1 or posterior zone II. Retina. 2008;28:831–8.

    Article  PubMed  Google Scholar 

  63. Wallace DK, Dean TW, Hartnett ME, et al. A dosing study of Bevacizumab for retinopathy of prematurity: late recurrences and additional treatments. Ophthalmology. 2018;125(12):1961–6.

    Article  PubMed  Google Scholar 

  64. Hillier RJ, Connor AJ, Shafiq AE. Ultra-low-dose intravitreal bevacizumab for the treatment of retinopathy of prematurity: a case series. Br J Ophthalmol. 2018;102(2):260–4.

    Article  PubMed  Google Scholar 

  65. Avery RL. Bevacizumab (Avastin) for retinopathy of prematurity: wrong dose, wrong drug, or both? J AAPOS. 2012;16:2–4.

    Article  PubMed  Google Scholar 

  66. Morin J, Luu TM, Superstein R, Ospina LH, Lefebvre F, Simard M-N, Shah V, Shah PS, Kelly EN. Neurodevelopmental outcomes following Bevacizumab injections for retinopathy of prematurity. Pediatrics. 2016;137:e20153218.

    Article  PubMed  Google Scholar 

  67. Hu J, Blair MP, Shapiro MJ, Lichtenstein SJ, Galasso JM, Kapur R. Reactivation of retinopathy of prematurity after bevacizumab injection. Arch Ophthalmol. 2012;130:1000–6.

    Article  CAS  PubMed  Google Scholar 

  68. Zepeda-Romero LC, Liera-Garcia JA, Gutiérrez-Padilla JA, Valtierra-Santiago CI, Cardenas-Lamas LJ. Paradoxical vascular-fibrotic reaction after intravitreal bevacizumab for retinopathy of prematurity. Eye. 2010;24:931–3.

    Article  CAS  PubMed  Google Scholar 

  69. Tahija SG, Hersetyati R, Lam GC, Kusaka S, McMenamin PG. Fluorescein angiographic observations of peripheral retinal vessel growth in infants after intravitreal injection of bevacizumab as sole therapy for zone I and posterior zone II retinopathy of prematurity. Br J Ophthalmol. 2014;98:507–12.

    Article  PubMed  Google Scholar 

  70. Jang SY, Choi KS, Lee SJ. Delayed-onset retinal detachment after an intravitreal injection of ranibizumab for zone 1 plus retinopathy of prematurity. J AAPOS. 2010;14:457–9.

    Article  PubMed  Google Scholar 

  71. Mintz-Hittner H, Geloneck MM, Chuang AZ. Clinical Management of recurrent retinopathy of prematurity after intravitreal Bevacizumab monotherapy. Ophthalmology. 2016;123:1845–55.

    Article  PubMed  Google Scholar 

  72. Yang X-M, Zhao Y-X, Wang Z-H, Liu L. Effect of anti-VEGF treatment on retinopathy of prematurity in zone II stage 3. Int J Ophthalmol. 2018;11:641–4.

    PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. University Hospitals of Leicester NHS Trust, Leicester, UK

    Samira Anwar

  2. Department of Neuroscience, Psychology and Behaviour, University of Leicester, Leicester, UK

    Samira Anwar

  3. Ulverscroft Eye Unit, University of Leicester, Leicester, UK

    Aarti Patel

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  1. Samira Anwar
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  2. Aarti Patel
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Correspondence to Samira Anwar .

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Editors and Affiliations

  1. Department of Health Sciences, George Davies Centre for Medicine, University of Leicester, Leicester, UK

    Elaine M. Boyle

  2. Department of Health Sciences, George Davies Centre for Medicine, University of Leicester, Leicester, UK

    Jonathan Cusack

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Anwar, S., Patel, A. (2020). Retinopathy of Prematurity. In: Boyle, E., Cusack, J. (eds) Emerging Topics and Controversies in Neonatology. Springer, Cham. https://doi.org/10.1007/978-3-030-28829-7_18

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