Retinopathy of Prematurity (ROP)

1. Retinopathy of Prematurity (ROP) (With acknowledgements to the Online Journal of Ophthalmology: www.onjoph.com)

2. Contents • Introduction • Epidemiology • Incidence • Pathogenesis and clinical features • Classification of ROP • Terminology • Examination and screening • Management • Conclusion

3. Introduction • ROP  potentially blinding • ICROP and CRYO-ROP – guidelines to screen, discuss and treat ROP. • ↑frequency of ROP • 2 facets Acute phase – normal vasculature goes awry  abnormal vessel proliferation. Chronic phase – late proliferation, retinal detachment and visual loss due to cataracts; squints; amblyopia etc. ** 90% acute ROP regress spontaneously.

4. Epidemiology • Cryo-ROP: Incidence and severity correlates with LBW and early post-conceptual gestational age. • ↑Incidence of more severe posterior ROP in smaller and younger infants. • Caucasians and Hispanics have ↑aggressive ROP compared to African Americans. • Mayet and Cockinos (CHBara) – There is a similar incidence of ROP in Africans compared to other races but with less severity (3%).

5. Incidence • Related to gestational age (GA) and birth weight (bw). • ROP rare in bw > 2000 grams. • 70% ROP in bw < 1250g and 7% develop threshold ROP. • Threshold ROP very rare in bw > 1250g. (Mayet & Cockinos) • 95% ROP begins at 32-34 weeks GA. • Threshold disease at 36 weeks. • Regression with spontaneous healing at 45-48 weeks GA. • Long term ophthalmic follow up of formerly premature neonates who suffered severe ROP.

6. Pathogenesis and clinical features • Incomplete retinal vascularisation. • Vessels migrate from disc to ora at 16 weeks. • Mature vessels extend to nasal ora at 36 weeks. • Vessels extend to temporal ora at 39-41 weeks. • STOP-ROP : supplemental treatment of oxygen in progression of ROP did not yield statistically significant difference in the progression to threshold ROP. • LIGHT-ROP : Light reduction in ROP showed no role in the incidence or severity of ROP.

7. Pathogenesis Cont.

8. Classification of ROP • International Classification of Retinopathy of Prematurity (ICROP) • Describe ROP according to - Zone, Extent and Stage.

9. Classification of ROP cont. • Staging: 5 stages - describe abnormal vascular response. Most severe stage is used to determine the stage of the eye as whole. • Stage 1: Demarcation line • Stage 2: Ridge

10. Classification of ROP cont. • Stage 3: Extaretinal Fibrovascular Proliferation • Stage 4: Partial Retinal Detachment 4a - Extrafoveal 4b – Foveal • Stage 5: Total Retinal Detachment

11. Classification of ROP cont. • Plus disease – signs indicating severity. Venous dilatation or arteriolar tortuosity in at least two quadrants; vitreous haze; poor pupil dilatation; vascular engorgement of the iris.

12. Terminology • Threshold disease : Stage 3 in zone 1 or 2 in at least 5 contiguous or 8 non-contiguous clock hours with plus disease. Point at which infant is treated. • Pre-threshold disease : ETROP. High and low risk prethreshold disease. High risk prethreshold : Zone1, any stage ROP with plus disease. Zone 1, stage 3 with or without plus disease. Zone 2, stage 2/3 with plus disease. • Rush disease : Rapid progressive severe form of ROP. Posterior location. Dilated, tortuous vessels with shunt vessels throughout retina.

13. Examination and screening • Dilate with cyclomydril. • Screening guidelines vary depending on resources, financial implications and medicolegal liability. • Universal criteria for screening : 1. Infants with bw < 1500g or GA < 31 weeks. 2. First examination 4/52 after birth. 3. Examine 1 or 2 weekly depending on stage of disease at initial visit. 4. Treat threshold disease. 5. Examine until 45 weeks GA without threshold disease or till vascularisation reaches zone 3.

14. Management • ETROP & Cryo-ROP Treat threshold disease as it decreases unfavourable outcome from 15 to 9%. Ablation is beneficial for prethreshold ROP. • Photograph screening for ROP Telemedicine with on-site treatment. • Evidence based screening criteria Screen at 31 weeks GA or 4 weeks chronologic age if born before 27 weeks. Continue screening till 45 weeks GA or vascularisation in zone 3. Screening of 1250g-1800g infants is cost effective. ETROP : Recognize prethreshold disease and follow up 2 weekly. Follow up weekly if zone 2, stage 2 ROP or if vascularisation ends in zone 1.

15. Management Cont. • Treatment of ROP Portable indirect laser units. Laser superior to cryotherapy. • Rush disease Poor prognosis if found in zone 1. 64% anterior zone 1 required surgery after laser. 100% posterior zone 1 required surgery after laser treatment. • ROP related retinal detachment * misconceptions 1. Stage 4A = benign and can wait till stage 4B before treating. 2. Poor prognosis with total detachment. Surgery reserved for stages 4A, 4B and 5. Intravitreal triamcinolone in Stage 5  reattachment success rate. Vision restoration technology – future.

16. Conclusion • Ultimate prevention = prevent premature births. • The role of VEGF and IGF-1 may lead to pharmacologic interventions in preventing progression. • Evidence based data reshape our understanding of who to screen and determines the critical timing of treatment. • Digital fundus imaging may revolutionalise screening. • ROP is a lifelong disease with sequelae manifesting into the 2nd decade. • Surgical intervention preserves vision in ROP-related retinal detachment esp. before macular detachment.