Retinopathy of Prematurity

1. Retinopathy of Prematurity Gary Lane, MD Vitreoretinal Service Wilford Hall Medical Center

2. Goals Learn about anatomy and development of the retina “What do all those stages and zones mean?” Understand the devastating visual consequences of ROP Understand your important role in the ROP team Show lots of pictures to keep you awake

3. Definition of ROP Abnormal retinal development in premature babies Some of these infants will have an interruption of normal retinal growth followed by abnormal proliferation of blood vessels and fibrous tissue

4. Who gets ROP? 66% of infants ? 1,250g develop some ROP 82% of infants ? 1,000g develop some ROP 9% become eligible for treatment

6. Retinal Anatomy 101

7. Normal vascular development

8. VEGF and IGF-1 Schematic representation of IGF-IyVEGF control of blood vessel development in ROP. In utero, VEGF is found at the growing front of vessels. IGF-I is sufficient to allow vessel growth. (B) With premature birth, IGF-I is not maintained at in utero levels and vascular growth ceases, despite the presence of VEGF at the growing front of vessels. Both endothelial cell survival (Akt) and proliferation (mitogen-activated protein kinase) pathways are compromised. With low IGF-I and cessation of vessel growth, a demarcation line forms at the vascular front. High oxygen exposure (as occurs in animal models and in some premature infants) may also suppress VEGF, further contributing to inhibition of vessel growth. (C) As the premature infant matures, the developing but nonvascularized retina becomes hypoxic. VEGF increases in retina and vitreous. With maturation, the IGF-I level slowly increases. (D) When the IGF-I level reaches a threshold at ~34 weeks gestation, with high VEGF levels in the vitreous, endothelial cell survival and proliferation driven by VEGF may proceed. Neovascularization ensues at the demarcation line, growing into the vitreous. If VEGF vitreal levels fall, normal retinal vessel growth can proceed. With normal vascular growth and blood flow, oxygen suppresses VEGF expression, so it will no longer be overproduced. If hypoxia (and elevated levels of VEGF) persists, further neovascularization and fibrosis leading to retinal detachment can occur. Hellstrom et al. PNAS Schematic representation of IGF-IyVEGF control of blood vessel development in ROP. In utero, VEGF is found at the growing front of vessels. IGF-I is sufficient to allow vessel growth. (B) With premature birth, IGF-I is not maintained at in utero levels and vascular growth ceases, despite the presence of VEGF at the growing front of vessels. Both endothelial cell survival (Akt) and proliferation (mitogen-activated protein kinase) pathways are compromised. With low IGF-I and cessation of vessel growth, a demarcation line forms at the vascular front. High oxygen exposure (as occurs in animal models and in some premature infants) may also suppress VEGF, further contributing to inhibition of vessel growth. (C) As the premature infant matures, the developing but nonvascularized retina becomes hypoxic. VEGF increases in retina and vitreous. With maturation, the IGF-I level slowly increases. (D) When the IGF-I level reaches a threshold at ~34 weeks gestation, with high VEGF levels in the vitreous, endothelial cell survival and proliferation driven by VEGF may proceed. Neovascularization ensues at the demarcation line, growing into the vitreous. If VEGF vitreal levels fall, normal retinal vessel growth can proceed. With normal vascular growth and blood flow, oxygen suppresses VEGF expression, so it will no longer be overproduced. If hypoxia (and elevated levels of VEGF) persists, further neovascularization and fibrosis leading to retinal detachment can occur. Hellstrom et al. PNAS

11. ROP is caused by prematurity Oxygen is just one of several important factors

13. Retinopathy of Prematurity ICROP – Staging Level of abnormal vascular response observed

17. Stage 3 ROP

21. Plus disease

24. QUIZ

26. Stage 4 (A-extramacular and B-macular)

27. Retinopathy of Prematurity ICROP – Staging Stage 4 Subtotal retinal detachment 4a - extrafoveal

28. Retinopathy of Prematurity ICROP – Staging Stage 4 Subtotal retinal detachment 4b – RD involving fovea

30. Retinopathy of Prematurity ICROP – Staging Stage 5 Open funnel Closed funnel

33. Stage 5 Total retinal detachment “Retrolental fibroplasia”

34. Stage 5 ROP 25-50% anatomic success ¼ of these able to reach out and grab an object Late onset (into adulthood) angle closure Late onset RRD 15%, most requiring multiple surgeries

35. AP-ROP Aggressive Posterior ROP A.K.A. Rush Disease

38. Screening At least 2 dilated exams for: All infants weighing less than 1500 grams at birth or born prior to 32* weeks gestation 1st exam by age 31 weeks or 4 weeks after birth, whichever is later Follow-up exams vary from every few days to every few weeks depending location (Zone) of ROP Exams continue if treatment is needed and are discontinued if regression occurs Selected infants between 1500-2000 grams with unstable clinical course

39. Threshold ROP: treatment

40. Early Treatment of Retinopathy of Prematurity 317 infants with bilateral high risk ROP 1 eye randomized to early treatment RM-ROP2 is a risk analysis program based on natural history data from CRYO-ROP Fellow eye treated at threshold per CRYO-ROP

41. The “New Threshold” Any Zone I ROP with Plus Zone I ROP Stage 3 with or without Plus Zone II Stage 2 or 3 with Plus Pearl: Infants usually reach threshold at about their due date or 38 weeks gestational age

42. Retinopathy of Prematurity Treatment Cryotherapy

43. Retinopathy of Prematurity Treatment Laser photocoagulation

46. Laser vs. Cryo Depends on clear view Minimal conj injection ~1000 spots Cataract (ischemia) Less destructive with comparable results Useful in limited view Massive chemosis 50-60 spots Vitreous hemorrhage Extensive peripheral damage

47. Lens sparing vitrectomy

48. Stage 5 ROP Remove lens +/-Remove iris +/- open sky approach DO NOT create a break Include a scleral buckle Tamponade with healon

51. ROP and Oxygen PaO2 in utero is about 30mmHg SpO2 of 70% Repeated episodes of hypo and hyperoxia are thought to be important in the pathogenesis of ROP Can manipulating PaO2 levels change the course of the disease? From Iowa Neonatology Handbook

52. ROP and SpO2 Chow, et al. Pediatrics 2003 Implemented SpO2 guidelines Careful titration to avoid hypoxia and hyperoxia Target range of 85-93% for high risk babies

54. ROP and Oxygen Brain is similar to the retina Periventricular leukomalacia is strongly correlated with sustained hyperoxia Calls for large multi-center randomized controlled trials Several trials in various countries will be pooled BOOST 2 85-89% vs. 91-95%

55. ROP and Oxygen Provocative Results Anecdotal evidence Confounding variables Needs a randomized, control trial Caveat: Retinal surgeons don’t manage babies – you do Consider risk of pulmonary disease

56. ROP: Creating a Safety Net Adapted from: Retinopathy of Prematurity: Creating a Safety Net Anne M. Menke, R.N., Ph.D. OMIC Risk Manager

57. Case Study A premature infant was born at 29 weeks gestation and weighed 1200grams Baby was examined and noted to have Stage 1 ROP, Zone 2, follow-up 4 weeks

58. Case Study Baby was transferred to another NICU No further eye exams were performed 3 months later, pediatrician received the discharge summary from the first hospital and saw ROP mentioned Child referred to ophthalmologist who diagnosed bilateral Stage V detachments

59. Safety Net Elements Clarification of physician roles Risk analysis of current process of care Hospital ROP Tracking System Coordination of transfer of care Ongoing education of ROP team: physicians, nurses and parents

60. Physician-Patient Relationship Screening infants in the NICU creates many difficulties Once a physician assumes responsibility for a patient, he or she creates a physician-patient relationship from which certain legal duties arise

61. Physician-Patient Relationship Failure to provide follow-up can result in a claim of patient abandonment and harm from failure to follow-up. Breakdowns in the follow-up process are the single most common cause of delays in the diagnosis and treatment of ROP.

62. Inpatient Physician Roles NICU Attending – primary care provider responsible for coordinating all care until the baby is discharged from the hospital or transferred to another facility Ophthalmologist – consultant After examining the baby and determining a follow-up interval, care is finished unless another request is made

63. Outpatient Physician Roles In outpatient care, the ophthalmologist assumes primary responsibility for ROP follow-up until completion Must follow-up on missed appointments and non-compliance

64. Risk Analysis of Current Process of Care Does every step have a person with assigned responsibility? What are the key vulnerabilities? Most ROP lawsuits occur when baby is lost to follow-up What have been the past failures?

65. Hospital Tracking System Single person designated as ROP coordinator, with backup when on vacation ROPC tracks baby until Ophthalmologist determines that ROP exams are no longer necessary Baby is discharged or transferred AND an ophthalmologist accepts care AND an appointment is scheduled

66. Key Vulnerability: Transfers and Discharges Hospital must: Write a discharge order that documents future ROP care ROP follow-up appointment is scheduled Medical record and parent’s contact information have been forwarded

67. Education as a Safety Net Parents NICU attendings Nurses Residents

68. Educating Parents & Caregivers Parents should be aware of the risk of blindness from untreated ROP, and this should be documented in the chart Parents should read and sign “Caregivers: Read this about premature baby’s eyes”

69. Education of NICU team NICU attendings, residents and nurses need periodic education about ROP Attitudes of nurses about ROP exams, positive or negative, are quickly communicated to the parents

70. ROP, Nursing and Parents ROP tends to get bad right around the due date Usually after the baby has made through all the other tough times and is ready to go home Sepsis, RDS, etc. Abstract disease – difficult to understand

71. Message to Parents ROP is caused by prematurity It’s not the fault of doctors, nurses or ventilators Everyone is stressed out by ROP exams “That’s gross” ROP exams prevent blindness Same anesthetic and lid speculum as for cataract surgery or LASIK Parents need to follow up after discharge

72. ROP Follow-up No baby should go home without a car seat And No ROP baby should go home without a confirmed follow-up appointment in Ophthalmology

73. Review Zones refer to location Zone 1 is most immature, worst prognosis Stage refers to extent of disease Stage 3 requires close observation or treatment Stage 4 or 5 involve retinal detachments Plus refers to presence of vascular shunting Treatment is laser of peripheral retina

74. Review ROP tends to get bad right around due date Most common cause of bad outcomes and lawsuits in ROP is missed follow-up appointments after hospital discharge or transfer Good care of ROP babies requires education and a team approach between doctors, nurses and parents

76. No baby deserves to go blind from ROP

77. Questions

78. Www.ROPARD.com