Retinopathy of prematurity affects about 14,000 to 16,000 premature infants weighing less than 1,250 grams born each year in the United States.
Despite advances in treatment and neonatal care, about 600 infants become blind in the United States from ROP each year. Evidence from the Early Treatment for Retinopathy of Prematurity (ETROP) Cooperative Group indicates that early treatment reduces the risk of poor vision from structural damage caused by ROP in infants with type 1 prethreshold ROP.1 Therefore, peripheral ablation of the avascular retina should now be performed when an eye develops type 1 prethreshold ROP and should not be delayed until threshold ROP develops.
Management includes screening with a dilated fundus examination, treatment of acute severe ROP with ablation of the peripheral avascular retina, surgery for tractional retinal detachment resulting from progressive stage 4 or stage 5 ROP and visual rehabilitation.
The severity of acute ROP is determined by zone, presence or absence of plus disease, stage and the clock-hour extent of the worst stage.2
- Zone I. This represents the least amount of retinal vascular development and includes retinal vascularization limited to a circular area centered around the optic nerve. The radius is equivalent to two times the distance from the optic nerve to the fovea. Zone I ROP is a strong predictor for severe ROP and can be estimated visually with indirect ophthalmoscopy, with zone I encompassing about the size of the image seen with a 28-D lens when the optic nerve is centered within the image. This evaluation is essential when examining and screening infants.
- Zone II. Vascularization limited to the circular area outside zone I with the optic nerve as the center. Its radius is equivalent to the distance from the optic nerve to the nasal horizontal ora serrata.
- Zone III. Vascularization within the remaining temporal, crescent-shaped area. Once vascularization extends to the nasal ora serrata and into zone III, there is little risk of a poor visual outcome from ROP.
2. Plus disease. Defined as two quadrants of dilated and tortuous vessels in the ETROP and STOP-ROP (Supplemental Therapeutic Oxygen for Prethreshold ROP) studies and is a strong predictor of severe ROP.
- Stage 1. A demarcation line between vascularized and avascular retina.
- Stage 2. A ridge with volume in the region of the demarcation line.
- Stage 3. Neovascularization growing into the vitreous at the ridge. Stage 3 is a strong predictor of severe ROP and a poor outcome.
- Stage 4. A partial retinal detachment. Treatment of progressive stage 4 ROP can preserve and improve visual outcomes by preventing stage 5 ROP.3
Stage 4 is further classified by whether the macula is involved (4A without macular involvement and 4B with macular involvement) and by whether it is predominantly exudative or tractional. Exudative ROP that occurs after treatment with laser or cryotherapy may resolve spontaneously.
- Stage 5. Total retinal detachment.
4. Prethreshold and threshold disease.
- Prethreshold ROP, Type 1. Zone I, any stage with plus disease; zone I, stage 3 without plus disease; zone II, stage 2 or 3 with plus disease.
- Prethreshold ROP, Type 2. Zone I, stage 1 or 2 without plus disease; zone II, stage 3 without plus disease.
- Threshold ROP. Zone I or II, stage 3 (five contiguous or eight total clock hours with plus disease).
The goal of screening is to detect and treat eyes with type 1 prethreshold ROP when the risk of an untoward outcome is 15 percent.1 For type 2 prethreshold ROP, frequent serial examinations are performed until resolution or progression of disease is observed.
According to the Joint Statements issued by the Academy, the Academy of Pediatrics and the Association for Pediatric Ophthalmology and Strabismus, screening is recommended for 1) all infants who weigh 1,500 g at birth or who are 28 weeks gestational age and 2) those infants who weighed > 1,500 g at birth but who experienced an unstable postnatal course.
The first examination should be performed 1) before the infant is discharged from the hospital, 2) is 4 to 6 weeks old or 3) is between 31 and 33 weeks postgestational age. Screening may be performed with indirect ophthalmoscopy, retinal imaging or both. It should be performed without causing undue infant distress with apnea and bradycardia, because fluctuations in inspired oxygen are recognized as a possible cause of ROP.5
During examination, the infant’s pupils are dilated widely, a topical anesthetic is given and a lid speculum is placed to hold the eyelids open. The posterior pole and vessels should be examined. In addition, care should be taken to avoid placing pressure on the globe, which will falsely constrict arterioles and veins and mask plus disease.
The retinal vessels are followed from their origin to their peripheral extents to determine the zone of disease. This helps one avoid either mistaking the underlying choroidal vascular pattern for retinal vessels, which can occur in a lightly pigmented fundus, or missing the peripheral extent of retinal vessels, which can be difficult to discriminate in a deeply pigmented fundus.
Risk factors for poor visual outcome include zone I involvement, stage 3 ridge appearance (particularly greater than six clock-hours) and plus disease as well as dilated iris vessels. Additional predictors of poor outcomes are low birth weight, out of nursery birth, multiple birth, young gestational age, Caucasian race, lower postgestational age at ROP diagnosis, ROP in zone I at first examination, rapid progression to prethreshold ROP and plus disease observed at first diagnosis of prethreshold disease.
Reported risk factors for progressive stage 4 ROP include two or more quadrants of plus disease, absence of clear vitreous and six or more clock-hours of ridge elevation.4
Laser and Surgery
Laser treatment. ETROP recommends peripheral ablation of the avascular retina for type 1 prethreshold ROP. Treatment can be performed under local or general anesthesia.
Moderate-intensity burns 0.5 to 1 spot size apart are placed within the avascular zone extending out to the ora serrata. Then, the retina is reexamined 360 degrees for skip areas. The use of a wide-angle viewing system is particularly helpful to find skip areas. Cryotherapy spots should be mild in intensity and confluent and should be administered only when laser energy cannot be delivered adequately.
Additional laser treatment. Once a patient is treated, the retina should be monitored closely for regression of plus disease, neovascularization and ridge elevation. With persistent neovascularization, careful examination for skip areas is made and further laser treatment is performed. Several signs—ridge elevation (particularly six clock-hours or more), persistent plus disease or vitreous haze—are particularly worrisome for development of progressive tractional stage 4 ROP.4 Eyes with these signs should be evaluated for possible lens-sparing vitrectomy.
Lens-sparing vitrectomy. This is performed to reattach the retina, to prevent progression to stage 5 ROP and to clear the visual axis.3
The timing of surgery is important: Once it is clear that stage 4 ROP is progressive,3,4 surgery should be performed. Ideally, this takes place before there is vascular engorgement and tortuosity of the retinal vessels or fibrovascular proliferation extending anteriorly to the lens, as these conditions will make it surgically more difficult to save the lens.
Visual rehabilitation is essential to maximize visual development and quality of life. Myopia, strabismus and amblyopia occur more often in children with severe ROP. Patching and contact lenses often are required. Late-onset retinal detachment and cataracts also require aggressive management. Individuals with ROP must be followed for eye disease throughout their lives.
1 Arch Ophthalmol 2003;121(12):1684–1694.
2 Cryotherapy for Retinopathy of Prematurity Cooperative Group. Arch Ophthalmol 2001;119:1110–1118.
3 Capone, A. and M. T. Trese. Ophthalmology 2001;108:2068–2070.
4 Hartnett, M. E. and J. R. McColm. Retina 2004;24:237–241.
5 Cunningham, S. et al. Lancet 1995;346: 1464–1465.
Dr. Hartnett, a retinal specialist, is associate professor of ophthalmology at the University of North Carolina, Chapel Hill.