Retinopathy of prematurity is a bilateral disorder of abnormal retinal vascularization in preterm infants
The inner retinal blood vessels start growing about midpregnancy, but the retina is not fully vascularized until term. Retinopathy of prematurity (ROP) results if these vessels continue their growth in an abnormal pattern, forming a ridge of tissue between the vascularized central retina and the nonvascularized peripheral retina. In severe retinopathy of prematurity, these new vessels invade the vitreous. Sometimes the entire vasculature of the eye becomes engorged (plus disease).
Susceptibility to retinopathy of prematurity correlates with the proportion of retina that remains avascular at birth. One large, multicenter study of 6998 infants found retinopathy of prematurity in 68% of neonates weighing < 1251 g at birth (1). The percentage is higher when many comorbidities exist (eg, infection, intraventricular hemorrhage, bronchopulmonary dysplasia).
Although the etiology of retinopathy of prematurity is multifactorial, excessive (especially prolonged) oxygen therapy is known to increase the risk. However, supplemental oxygen is often needed to adequately oxygenate the infant even though a safe level and duration of oxygen therapy have not been determined.
General reference
1. Good WV, Hardy RJ, Dobson V, et al: The incidence and course of retinopathy of prematurity: Findings from the early treatment for retinopathy of prematurity study. Pediatrics 116(1):15–23, 2005. doi: 10.1542/peds.2004-1413
Diagnosis of Retinopathy of Prematurity
Ophthalmoscopy
Diagnosis of retinopathy of prematurity is made by ophthalmoscopic examination, done by an ophthalmologist, which shows a line of demarcation and a ridge in mild cases and proliferation of retinal vessels in more severe cases.
Screening ophthalmoscopy is done in all infants weighing < 1500 g or < 30 weeks gestation at birth. Because disease onset is usually at 32 to 34 weeks gestational age, screening begins at about 31 weeks gestational age. Ophthalmologic examinations continue every 1 to 3 weeks (depending on the severity of the eye disease) until infants have growth of vessels into the periphery (equivalent to term).
Because significant retinopathy of prematurity is rare in appropriately managed infants weighing > 1500 g at birth, alternative diagnoses should be considered in these infants (eg, familial exudative retinopathy, Norrie disease).
Treatment of Retinopathy of Prematurity
Laser photocoagulation
Bevacizumab
In severe retinopathy of prematurity, laser photocoagulation to ablate the peripheral avascular retina reduces the incidence of retinal fold and detachment. Retinal vascularization must be monitored at 1- to 2-week intervals until the vessels have matured sufficiently. If retinal detachments occur in infancy, scleral buckling surgery or vitrectomy with lensectomy may be considered, but these procedures are late rescue efforts with low benefit.
Patients with residual scarring should be followed at least annually for life. Treatment of amblyopia and refractive errors in the first year optimizes vision. Infants with total retinal detachments should be monitored for secondary glaucoma and poor eye growth and referred to intervention programs for the visually impaired.
bevacizumab has a lower rate of recurrence and fewer structural abnormalities in select cases (1, 2). When retinopathy did recur, it recurred months later; long-term ophthalmology follow-up is required. Concerns regarding systemic absorption and possible infection coupled with the need for optimal dose and timing of follow-up are reasons why this agent has remained a second-line therapy that can be used to treat severe disease or in conjunction with laser therapy.
Treatment references
1. Mintz-Hittner HA, Kennedy KA, Chuang AZ: Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity. N Engl J Med 364(7):603–615, 2011. doi: 10.1056/NEJMoa1007374
2. Wallace DK, Kraker RT, Freedman SF, et al: Short-term Outcomes After Very Low-Dose Intravitreous Bevacizumab for Retinopathy of Prematurity. JAMA Ophthalmol 138(6):698-701, 2020. doi: 10.1001/jamaophthalmol.2020.0334
Prognosis for Retinopathy of Prematurity
Abnormal blood vessel growth often subsides spontaneously but, in a small percentage of survivors weighing < 1000 g at birth, it progresses to produce retinal detachments and vision loss within 2 to 12 months postpartum.
Children with healed retinopathy of prematurity have a higher incidence of myopia, strabismus, and amblyopia. A few children with moderate, healed retinopathy of prematurity are left with cicatricial scars (eg, dragged retina or retinal folds) and are at risk of retinal detachments later in life; rarely, glaucoma and cataracts can also occur.
Prevention of Retinopathy of Prematurity
After a preterm birth, oxygen should be supplemented only as needed to avoid swings in oxygen because both hyperoxia and hypoxia increase risk of retinopathy of prematurity.
Vitamin E and restricted light are not effective.
Key Points
Retinopathy of prematurity (ROP) typically develops in infants weighing < 1500 g or < 30 weeks gestation at birth, particularly those who had serious medical complications or who received excessive and/or prolonged oxygen therapy.
Risk increases with increasing prematurity.
Most cases subside spontaneously, but a small number develop retinal detachment and vision loss 2 to 12 months postpartum.
Screen at-risk infants by ophthalmoscopic examination (done by an ophthalmologist) beginning at 31 weeks gestation.
Treat severe ROP using laser photocoagulation or an anti-VEGF agent injected intravitreally.
Minimize use of supplemental oxygen after preterm birth.
