A. Epidemiology

1. Higher with decreasing Birth Weight and lower gestation age
2. Affects 7% of infants < 1250g

B. Risk Factors

1. Hyperoxia
2. Hypoxia
3. Hypercarbia
4. Hyopocarbia
5. Metabolic acidosis
6. Metabolic alkalosis
7. Apnea requiring ventilator support
8. Blood transfusions
9. Sepsis
10. Intraventricular hemorrhage
11. Vitamin E deficiency

C. Pathogenesis

1. Retinas fully developed by 42-43 weeks post-conception
2. Spindle cell migration occurs from 16-29 weeks gestation
3. Retinal arteries later develop along the same path
4. Exact mechanism unknown
5. Hypoxia causes
   1. Developmental arrest of spindle cells
   2. Retinal arterial vasoconstriction and reduced blood flow to developing retina
6. Hyperoxia causes free radical release and damage to the skeletal structure
7. Myofibroblasts
   1. Invade the vitreous and exert traction on the retina
   2. This predisposes to detachment

D. Symptoms

1. No early clinical signs
2. Later may see leukoria (fibrous membrane behind the lens)
3. Mean onset of symptoms at 34.3 weeks post-conception

E. Ophthalmologic Screening

1. All infants <30 weeks and < 1300g
2. Infants < 34 weeks or < 1800g body weight with prolonged oxygen requirement
3. Initial screening at 4-6 weeks of age or at 32 weeks post-conception
4. Repeat screening every 1-2 weeks until vascularization complete

F. Classification

1. Zones
   1. Zone I: circle from optic disc to twice the distance to macula
   2. Zone 2: circle from disc to ora serrata
   3. Zone 3: remainder of retina outside ora serrata
2. Extent of Disease - Clock hours for areas of retinal changes
3. Stages
   1. Stage 1: demarcation between vascular and avascular zones
   2. Stage 2: ridge-like elevation just above the plane of the retina
   3. Stage 3: neovascularization has invaded the vitreous (scars may pull traction)
   4. Stage 4: subtotal retinal detachment (extrafoveal or foveal)
   5. Stage 5: retrolental fibroplasia with total retina detachment
   6. Plus Disease: marked vascular change, enlarged posterior veins and tortuous arterioles

G. Therapy

1. Oxygen therapy to keep PO2 between 50-70 mmHg and O2 saturations 90-95%
2. Vitamin E supplementation if deficient (<3.5 mg/dL)
3. Cryotherapy for advanced retinopathy
4. Photocoagulation to destroy new vessels (questionable long term benefit)
5. Retinal reattachment to provide limited functional vision for stage 5
6. Reduction of light exposure did not prevent ROP [2]

H. Visual Prognosis

1. Outcome based on stage after neovascularization complete
2. Stage 1-2
   1. Typically regresses
   2. Higher associated incidence of refractive errors, amblyopia, and stabismus
3. Stage 3
   1. Higher incidence of refractive errors and strabismus
   2. Late retinal detachments and vitreous hemorrhages are rare
4. Stage 4 associated with functional visual impairment particularly if macula is involved
5. Stage 5 has poor visual outcome

References

1. Trachtenbarg DE and Golemon TB. 1998. Am Fam Phys. 57(10):2383
2. Reynolds JD, Hardy RJ, Kennedy KA, et al. 1998. NEJM. 338(22):1572