Retinopathy of prematurity:Altered developmentA disorder with a uniquely American heritage

Early HistorySilverman, WA. Retrolental Fibroplasia: A Modern Parable. Monographs in Neonatology. 1980Dr. Stewart Clifford, Boston pediatrician discovers first case -1941Dr. Harry Messenger, Boston ophthalmologist coined the term RLF

RLF National Cooperative StudyRelative Risk = 3.6 ( 95% CI 1.7 7.75)

GroupScarring RLFNo Scarring RLFTotalRoutine83947Curtailed20405425Total28444472

Normal oxygen valuesAvery et al. Neonatology: Pathophysiology and Management of the Newborn, 4th ed. Pg 130, table 11-2.

Uterine vein (mom)Umbilical arteryUmbilical veinP02401527Hb sat (%)763068Oxygen content12.26.414.5Hb g/dl121616

Retinal vascular development (ontogeny)The choroidal vessels can supply the thin retina via diffusionThe retinal nerve cells (photoreceptors) develop from the optic nerve to the peripheryAdditional blood supply develops as the retinal nerve cell layer becomes thicker

Ontogeny of the retinal vascular bedInner vascular plexusWithin the nerve fiber layerCapillaries appear around the 16th week of gestation and reach the ora serrata at about 32 36 weeks gestation nasally and temporally just before termVasculogenesis

The goal supply blood to the maturing retinahttp://www.tsbvi.edu/Outreach/seehear/winter98/ICROP.gif

Ontogeny of the retinal vascular bedOuter vascular plexusesDevelops later in gestation and continues to develop postnatallyCapillaries arise as cellular buds from the innermost vesselsAngiogenesis

When ROP develops How bad is it ? Stage One A line of demarcation between the vascular and avascular retinaStage Two The line comes a ridgeStage Three The ridge is associated with neonvascularization entering the vitreous

When ROP develops How bad is it ?Stage Four Subtotal detachment of the retinaIV A is extrafoveal detachmentIV B the detachment includes the foveaStage Five Total Detachment The old retrolental fibroplasia

An International Classification of Retinopathy of Prematurity. Arch Ophthalmol. 1987;105: 906-912.

When ROP develops How bad is it ?Plus Disease very tortuous vessels implying high blood flow; badRush Disease Plus disease in zone 1

Stage Onehttp://ropard.org/ The Association for Retinopathy of Prematurity and Related Diseases

Stage Two

Stage Three

Stage Four

Stage Five

When ROP develops where is it?

ROP A disease that can regress

BW < 1250 gm1981 -1985n = 1851985 1988n = 226Mild ROP86 (46%)118 (52%)Moderate ROP24 (13%)35 (15%)Severe ROP10 (5%)12(5%)

ROP A disease that can regressPediatrics. 2005;116:15 23.

Birth weightStage oneStage twoStage three< 750 gm18%34%48%750 999 30%38%31%1000 - 125051%31%18%

Incidence inversely proportional to gestational age at birth

Incidence inversely proportional to gestational age at birth

ETROPCRYO-ROP< 27 wks89%83%> 27- 31 wks52%55%> 32 wks14%30%

Prevention of severe diseasePrimary decrease the number of infants born at the gestations with highest riskSecondary An agent that will prevent the retinal blood vessel drop out after birth in very premature infantsLimit the vasoproliferative phaseSafe oxygen administration

Prevention of severe diseaseCryotherapy and laser therapy limit the vasoproliferative phase by destroying the avascular retina once THRESHOLD has been reachedIntravitreal bevacizumab (Avastin) injection

Prevention of severe diseaseCyrotherapy outcome at 5 yearsArch Opthalmol. 1996;224:417-424

Treated EyeControl EyeNormal103 (49%)68 (33%)Total retinal detachment46 (22%)80 (39%)Blind70 (31%)106 (48 %)

Earlier treatment of disease in Zone OneArch Opthalmol. 2003; 121:1684-96

Early TreatmentConventional TreatmentNormal213 (64%)200 (62%)Blind or Low vision33 (10%)47 (15%)

Limit excessive oxygen exposureConclusion: Inappropriate oxygen use is a neonatal health hazard associated with aging, DNA damage and cancer, retinopathy of prematurity, injury to the developing brain, infection and others. Neonatal exposure to pure O2, even if brief, or to pulse oximetry >95% when breathing supplemental O2 must be avoided as much as possible Sola, A, et al. Acta Paediatrica. 96(6):801-812, June 2007.

Limit oxygen exposureChow et al. Pediatrics. 2003;111:339-45

ScreenAll infants with birth weights less than 1500 grams or gestational age less than 32 weeksBegin at 4 to 6 weeksContinue until mature (vascularized to the periphery)

Other ophthalmologic sequelae Cats B. and Tan K. J Ped Opthamal & Strabismus. 1989:271-75

Regressed ROPNo ROPStrabismus31%19%Myopia > 3 D16%2%Decreased vision31%5%

Myopia related to ROPQuinn GE et al.Opthalmology 1998; 105:1292-1299

Myopia related to ROPQuinn GE et al.Opthalmology 1998; 105:1292-1299

Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*Retinopathy of prematurity*