Retinopathy of Prematurity
- Author: Mounir Bashour, MD, CM, FRCS(C), PhD, FACS; Chief Editor: Hampton Roy Sr, MD more...
Background
Retinopathy of prematurity (ROP) is a disease that affects immature vasculature in the eyes of premature babies. It can be mild with no visual defects, or it may become aggressive with new blood vessel formation (neovascularization) and progress to retinal detachment and blindness. As smaller and younger babies are surviving, the incidence of ROP has increased.
During the 1940s and 1950s, ROP, also known as retrolental fibroplasia, was the leading cause of blindness in children in the United States. In 1942, Terry first reported the disease that was published in a report on the histologic findings of end-stage cicatricial disease.[1] In 1951, Campbell first suggested that ROP was related to the introduction of oxygen therapy into the newborn nursery, and this was confirmed by Patz.[2] Today, after oxygen therapy has been studied and found not to be the single causative agent, the factors that play a role in the pathogenesis of ROP are still unknown.
Pathophysiology
The retinal vasculature begins in the 16th week of gestation. Retinal vessels grow out of the optic disc as a wave of mesenchymal spindle cells. As these mesenchymal spindle cells lead the shunt, endothelial proliferation and capillary formation follow. These new capillaries will form the mature retinal vessels. The choroidal vessels (that are vascularized by the 6th week of gestation) supply the rest of the avascularized retina. The nasal portion of the retina is completely vascularized to the ora serrata by the 32nd week of gestation. The larger temporal area usually is completed at 40-42 weeks (term).
Two theories exist on the pathogenesis of ROP. The mesenchymal spindle cells, exposed to hyperoxic extrauterine conditions, develop gap junctions. These gap junctions interfere with the normal vascular formation, triggering a neovascular response, as reported by Kretzer and Hittner.[3] Ashton theorizes that 2 phases exist.[4] The first phase, a hyperoxic phase, causes retinal vasoconstriction and irreversible capillary endothelial cell destruction. As the area becomes ischemic, angiogenic factors, such as vascular endothelial growth factor (VEGF), is made by the mesenchymal spindle cells and ischemic retina to provide new vascular channels. These new vascular channels are not mature and do not respond to proper regulation.
The most conspicuous question in the pathophysiology of ROP is why it progresses in some premature infants despite rigorous and timely intervention, while, in other infants with similar clinical characteristics, it regresses. Csak et al believe that perhaps the genetic differences between infants could be an explanation.[5] Although many causative factors, like low birth weight, low gestational age, and supplemental oxygen therapy, are associated with ROP, several indirect lines of evidence suggest the role of a genetic component in the pathogenesis of ROP. The incidence of ROP is more frequent in white infants than in black infants and in male infants than in female infants. Genetic polymorphism may alter the function of the genes that normally control retinal vascularization, such as VEGF, which may also be involved in the pathogenesis of ROP.
In the future, evaluation of candidate genetic polymorphism influencing the outcome of ROP may provide new information about the pathogenesis of the disease. Screening of genetic polymorphisms may also help to identify and treat those infants who are at high risk in a more timely manner.
Epidemiology
Frequency
United States
The incidence of ROP in premature infants is inversely proportional to their birth weight. Fielder studied infants weighing less than 1700 g and noted development of ROP in 51%.[6]
In general, more than 50% of premature infants weighing less than 1250 g at birth show evidence of ROP, and about 10% of the infants develop stage 3 ROP.
International
In 1995, ROP accounted for 10.6% of cases of blindness in children in schools for the blind in South Africa.[7]
Mortality/Morbidity
On average, annually, 500-700 children become blind because of ROP in the United States. In terms of life years of blindness, this translates to 30,000 life years of vision.
Annually, 2100 infants will be affected with cicatricial sequelae, including myopia, strabismus, blindness, and late-onset retinal detachment.
The rule of thumb is that approximately 20% of all premature babies will develop some form of strabismus or refractive error by the time they are age 3 years. This is why babies who are younger than 32 weeks or less than 1500 g receive follow-up care every 6 months, whether or not ROP is present.
Race
Palmer and colleagues showed that African Caribbean infants are less likely to develop ROP than their Caucasian counterparts.[8]
Sex
The incidence is slightly greater in male infants than in female infants.
Age
ROP is a disease of premature infants. All babies less than 1500 g birth weight or younger than 32 weeks' gestational age at birth are at risk of developing ROP.
As younger and smaller infants are surviving, the screening protocols are changing to include earlier gestational age. In any neonatal intensive care unit (NICU), the timing of the first evaluation must be based on the gestational age at birth.
- If the baby is born at 23-24 weeks' gestational age, the first eye examination should be performed at 27-28 weeks gestational age.
- If the baby is born at or beyond 25-28 weeks' gestational age, the first examination should occur at the fourth to fifth week of life.
- Beyond 29 weeks, the first eye examination should probably occur before the child is discharged.
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