Overview. Retinal vascularisation during development. Classification of ROP. Visual loss from retinopathy of prematurity: first global estimates

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1 Visual loss from retinopathy of prematurity: first global estimates Overview ROP - the condition, risk factors and control ROP as a cause of visual loss Earlier estimates New global estimates MARCH seminar, February 4 th 2014 Clare Gilbert Retinal vascularisation during development 16 weeks GA 26 weeks GA Peripheral retinal hypoxia drives the new blood vessel growth 36 weeks GA 40 weeks GA Classification of ROP Classification of ROP - by zone (site) Site (zones and clock hours) Severity (Stages) Signs of BRB breakdown ( plus disease ) Scarring Zone 3 Zone 2 Zone 1 1

2 Classification of ROP - by zone (site) Classification of ROP - by stage (severity) Zone 3 Zone 2 Zone 1 Stage I II III Iva,b Va,b Features Demarcation line Ridge Fibrovascular ridge Subtotal retinal detachment Total retinal detachment Stage 1 demarcation line Stage II ROP Stage III ROP Stage 4 subtotal retinal detachment Courtesy Ells Courtesy Azad 2

3 Stage V - inoperable retinal detachment End stage eye blind from ROP Cicatricial ROP with dragging of the retinal vasculature Natural history of ROP Starts 4-7 weeks after birth Progresses / regresses over following few weeks Treatment indications: earlier: constellation of signs indicating 50% risk of progression to retinal detachment (CRYO-ROP trial*) current: constellation of signs indicating 15% risk of progression to retinal detachment (ET-ROP trial*) Courtesy Ells *provided data on visual outcomes after treatment, or no treatment (CRYO-ROP) Confluent laser to peripheral avascular retina Disease regresses with treatment Before treatment 4 weeks after treatment Courtesy Ells 3

4 Characteristics of babies with severe ROP in UK, USA and Canada Characteristics of babies with severe ROP in low/middle income countries UK screening criteria Birth weight (gm ms) Argentina (C ) Argentina (G) Argentina (L) Argentina (M) Argentina (P) Argentina (T) Brazil Chile Colombia Cuba Ecuador India (D) India (H) India (M) Lithuania (K) Lithuania (V) Peru SS Peru Public Vietnam Full term Gestational age (weeks) Gilbert et al. Paediatrics Gilbert et al. Paediatrics Risk factors for ROP Prematurity, prematurity, prematurity! But also: no antenatal steroids inadequately controlled oxygen sepsis etc poor early weight gain Inadequate health systems: inadequate equipment poor staff numbers; training; motivation weak management information systems poor leadership inadequate governance Prevention of blindness from ROP Primary prevention: prevent preterm birth antenatal steroids gentle newborn care/no 100% oxygen in first golden hour good health systems with excellent neonatal care Prevention of blindness from ROP ROP the condition Secondary prevention: examination of infants at risk by ophthalmologists in unit treat those with advanced disease by laser BUT not all countries have high coverage with ROP programs Tertiary prevention: sight cannot be restored once lost Well classified disease and natural history known Risk factors largely known Non-invasive examination Non-invasive examination Effective treatment Early treatment gives better results Ideal for a screening and treatment programme 4

5 Visual loss from ROP ROP as a cause of blindness Causes of visual loss individual level: Retinal detachment (inoperable) Scarring and distortion of the retina Rates of visual loss population level: Rates of preterm birth Survival of preterm infants - access to neonatal care Level of neonatal care exposure to risk factors Coverage with ROP programs Quality of treatment Proportion of blindness due to ROP, by World Bank region Estimates of numbers blind (<6/60) from ROP, by World Bank region (2000) Total >50,000 Gilbert, The Lancet The third epidemic of blindness due to ROP. Estimates of numbers blind (<6/60) from ROP, by World Bank region (2000) Proportion of blindness due to ROP, by infant mortality rates (2000) Total >50, ,000 worldwide 5

6 ROP blindness likely risk using IMR as a proxy (2000) Methods used to estimate the incidence of blindness and visual impairment from ROP Potential outcomes Potential outcomes Countries grouped by neonatal mortality rate Parameters required and methods for estimation ( ) Level 1: NMR <5/1000 Level 2: NMR 5 to <15/1000 Level el 3: NMR 15/1000 Used as a proxy for access to neonatal care and survival if data limited 6

7 Parameters required and methods for estimation (2000 to 2010) Parameters required and methods for estimation (2000 to 2010) Review of available data, meta-analyses, other data and assumptions to estimate: In 3 country groupings using NMR: Step 1: Number of preterm births Step 2: Survival rate amongst infants receiving neonatal care Step 3: Incidence of any ROP; risk of progression to stage requiring treatment; proportion treated For all countries: Risk of visual loss amongst those treated and not treated Results Step 1: preterm births (<36 weeks) 14,900,000 Step 2: surviving neonatal care 848,300 Step 3: any ROP in survivors 184,700 ROP needing treatment 53,800 number treated 22,700 Blind (treated and untreated) 20,000 Visual impairment 12,300 TOTAL blind/vi 32,300/year Regional incidence Annual incidence, by region Blind (20,000) Vision impaired (12,300) High Income Latin America and Caribbean North Africa and Middle East Sub-Saharan Africa Eastern Europe/ Central Asia East and S.East Asia and Pacific South Asia 7

8 Annual incidence of blindness/vi, relative to high income countries Annual incidence of blindness relative to high income countries Increasing survival; sub-optical neonatal care; low coverage with ROP programs High mortality amongst preterm infants 0 High Income Eastern Latin America East and Europe/ Central and Caribbean S.East Asia Asia and Pacific North Africa and Middle East South Asia Sub-Saharan Africa 0 High Income Eastern Latin America East and Europe/ Central and Caribbean S.East Asia Asia and Pacific North Africa and Middle East South Asia Sub-Saharan Africa Summary Annual incidence of visual loss higher than anticipated Reflects increasing provision of neonatal care with increased survival, particularly in Asia More needs to be done to improve neonatal care and access to screening and treatment for severe ROP More data are needed to refine assumptions and provide more precise estimates at each step datasets used in this analysis... 8