Retinopathy of Retinopathy of PrematurityPrematurity

Meena KumarMeena Kumar10/1/0310/1/03

DefinitionDefinition

Retinopathy of prematurity (ROP) was Retinopathy of prematurity (ROP) was formerly known as retrolental fibroplasia.formerly known as retrolental fibroplasia.It is a developmental vascular proliferative It is a developmental vascular proliferative disorder that occurs in the incompletely disorder that occurs in the incompletely vascularized retina of primarily premature vascularized retina of primarily premature infants.infants.ROP is one of the most common causes ROP is one of the most common causes of blindness in children.of blindness in children.

Incidence of ROPIncidence of ROP

Hussain et al. (Pediatrics 1999; 104:e26): Hussain et al. (Pediatrics 1999; 104:e26): 950 infants born between 1989 and 1997 950 infants born between 1989 and 1997 had serial eye exams if they were less had serial eye exams if they were less than 30 wks GA, less than 1300g BW, or than 30 wks GA, less than 1300g BW, or required Orequired O22 supplementation. supplementation.

Incidence of ROP increased with Incidence of ROP increased with decreasing GA or decreasing BW.decreasing GA or decreasing BW.

Vascular Development of the EyeVascular Development of the Eye

Nasal side Temporal side

PathogenesisPathogenesisNot well understood but thought to involve two stages:Not well understood but thought to involve two stages:

Stage I: an initial injury (such as hypotension, hypoxia, or Stage I: an initial injury (such as hypotension, hypoxia, or hyperoxia) causes vasoconstriction and reduced blood flow to hyperoxia) causes vasoconstriction and reduced blood flow to the retina, disrupting the normal process of vascularization.the retina, disrupting the normal process of vascularization.

Stage II: Vessels then either resume normal growth or new Stage II: Vessels then either resume normal growth or new vessels grow abnormally out from the retina into the vitreous. vessels grow abnormally out from the retina into the vitreous. The abnormal vessels have increased permeability which can The abnormal vessels have increased permeability which can result in edema and hemorrhage. Inflammation result in edema and hemorrhage. Inflammation → fibrous tissue → fibrous tissue → traction on the retina and detachment. Alternatively, the → traction on the retina and detachment. Alternatively, the abnormal vascularization may regress with little residual effect.abnormal vascularization may regress with little residual effect.

Recently, the interaction between insulin-like growth Recently, the interaction between insulin-like growth factor-1 (IGF-1) and VEGF has been studied and factor-1 (IGF-1) and VEGF has been studied and proposed to play a role in the pathogenesis of ROP proposed to play a role in the pathogenesis of ROP (Hellstrom et al. PNAS 2001; 98:5804).(Hellstrom et al. PNAS 2001; 98:5804).

Role of IGF-1 and VEGF in the pathogenesis of ROPRole of IGF-1 and VEGF in the pathogenesis of ROP

Fig. 1.   Effect of IGF-I inhibition on vascular growth. Flat-mounted whole retina shows that, in IGF-I -/- mice (A), there is less progression of vascular development (bright area) compared with IGF-I+/+ littermate controls (B).

Fig. 3.   Mean serum IGF-I at matched gestational ages in infants with and without ROP. The mean IGF-I level for infants with ROP (○) and without ROP (●) is shown vs. gestational age. (Bars = SEM.)

Fig. 5.   Schematic representation of IGF-I/VEGF control of blood vessel development in ROP.

(Hellstrom et al. PNAS 2001; 98:5804)

Known or Suspected Risk FactorsKnown or Suspected Risk Factors

Prematurity (most significant)Prematurity (most significant)LBWLBWAssisted ventilation longer than one weekAssisted ventilation longer than one weekSurfactant therapySurfactant therapyHigh blood transfusion volumeHigh blood transfusion volumeSepsisSepsisIVHIVHBronchopulmonary dysplasiaBronchopulmonary dysplasiaElevated arterial oxygen tension Elevated arterial oxygen tension

International Classification for International Classification for Retinopathy of Prematurity (ICROP)Retinopathy of Prematurity (ICROP)

Four features are evaluated:Four features are evaluated: Zone (1-3)Zone (1-3) Stage (1-5)Stage (1-5) ExtentExtent Presence or absence of plus diseasePresence or absence of plus disease

ZonesZones

International Classification for International Classification for Retinopathy of Prematurity (ICROP)Retinopathy of Prematurity (ICROP)

Four features are evaluated:Four features are evaluated: Zone (1-3)Zone (1-3) Stage (1-5)Stage (1-5) ExtentExtent Presence or absence of plus diseasePresence or absence of plus disease

Stage 1Stage 1

Stage 2Stage 2

Stage 3Stage 3

Stage 4Stage 4

Stage 4A: excludes the maculaStage 4B: includes the macula

Stage 5Stage 5

International Classification for International Classification for Retinopathy of Prematurity (ICROP)Retinopathy of Prematurity (ICROP)

Four features are evaluated:Four features are evaluated: Zone (1-3)Zone (1-3) Stage (1-5)Stage (1-5) ExtentExtent Presence or absence of plus diseasePresence or absence of plus disease

ExtentExtent

Described by dividing the retinal surface Described by dividing the retinal surface into 12 segments (clock hours). The stage into 12 segments (clock hours). The stage of retinopathy can vary among segments.of retinopathy can vary among segments.

International Classification for International Classification for Retinopathy of Prematurity (ICROP)Retinopathy of Prematurity (ICROP)

Four features are evaluated:Four features are evaluated: Zone (1-3)Zone (1-3) Stage (1-5)Stage (1-5) ExtentExtent Presence or absence of plus diseasePresence or absence of plus disease

Plus diseasePlus disease

Presence indicates severe ROP and is often followed by rapid progression to retinal detachment. May be accompanied by vitreous haze, engorgement of the iris vessels, and poor dilation of the pupil.

Rush disease: ROP in zone 1 with plus disease.

SCREENING GUIDELINESSCREENING GUIDELINESRecommendations based on review of data from the Recommendations based on review of data from the

CRYO-ROP and LIGHT-ROP studiesCRYO-ROP and LIGHT-ROP studies

Initial screening should be Initial screening should be performed by 31 wks PMA or 4 performed by 31 wks PMA or 4 wks CA, whichever is later.wks CA, whichever is later.Screening can be discontinued Screening can be discontinued when any of the following three when any of the following three signs are identified:signs are identified:

Lack of development of Lack of development of prethreshold or worse ROP by 45 prethreshold or worse ROP by 45 wks PMA.wks PMA.

Progression of retinal Progression of retinal vascularization into zone 3 vascularization into zone 3 without previous ROP in zone 2.without previous ROP in zone 2.

Full vascularizationFull vascularization

(Reynolds et al. Arch Ophthalmol 2002; 120:1470)

Treatment CriteriaTreatment CriteriaTreat when threshold ROP is reached. Treat when threshold ROP is reached. Threshold ROP:Threshold ROP: 5 contiguous clock hours or 8 total clock hours of stage 3 5 contiguous clock hours or 8 total clock hours of stage 3

and plus disease in zone 1 or 2.and plus disease in zone 1 or 2.Prethreshold ROPPrethreshold ROP – one of the following: – one of the following: ROP at any stage less than threshold in zone 1ROP at any stage less than threshold in zone 1 Stage 2 and plus disease in zone 2Stage 2 and plus disease in zone 2 Stage 3 without plus disease in zone 2Stage 3 without plus disease in zone 2 Stage 3 with plus disease in zone 2 but with fewer clock Stage 3 with plus disease in zone 2 but with fewer clock

hours of stage 3 than required to meet threshold.hours of stage 3 than required to meet threshold.Approx. 1/3 of infants with prethreshold ROP progress to Approx. 1/3 of infants with prethreshold ROP progress to

threshold disease and can do so rapidly. Therefore threshold disease and can do so rapidly. Therefore repeat exams are usually needed every 2-4 days.repeat exams are usually needed every 2-4 days.

Treatment OptionsTreatment Options

CryotherapyCryotherapyLaser photocoagulation – standard Laser photocoagulation – standard treatmenttreatmentSurgical interventionsSurgical interventions Scleral bucklingScleral buckling VitrectomyVitrectomy

CryotherapyCryotherapy

Laser photocoagulationLaser photocoagulation

Scleral BucklingScleral Buckling

VitrectomyVitrectomy

Long Term Complications of ROPLong Term Complications of ROP

Retinal Dragging and Folds

Others:

Glaucoma

Late onset Retinal Detachment

Significant myopia

Anisometropia

AmblyopiaStrabismus

Importance of Follow-UpImportance of Follow-Up

Prematurity (even in the absence of ROP) Prematurity (even in the absence of ROP) puts infants at increased risk of puts infants at increased risk of ophthalmologic complications.ophthalmologic complications.Therefore, all premature infants should Therefore, all premature infants should undergo examination by an undergo examination by an ophthalmologist at 9-12 mos. of age and ophthalmologist at 9-12 mos. of age and be followed more frequently in the first few be followed more frequently in the first few years of life than term infants. years of life than term infants.