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Retinopathy of Prematurity

Retinopathy of prematurity (ROP) is a disease of the retinal blood vessels and one of the more common sequelae among infants of extremely low birthweight. In recent years, its importance has grown for pediatricians because 1) more infants who have had ROP are in our practices, 2) proven treatment must be performed at a critical time, and 3) late complications (that sometimes can be controlled) may occur as these children grow into adults. We must understand the source of ROP so that we can discuss it with



In the prospective study of cryotherapy for severe ROP (CRYO-ROP study) that systematically examined 4099 infants who weighed less than 1250 g at birth from 70 different hospitals throughout the United States from 1986 to 1988, more than 90% of the infants of less than 750 g birthweight developed some degree of ROP. Fortunately, ROP often regresses (heals) spontaneously, leaving 40% of infants who develop moderately


In the 1940s and early 1950s, ROP was called retrolental fibroplasia and presented as a new epidemic of blindness. It later was learned that this problem began with the introduction of oxygen and less leaky incubators into the premature infant nursery. Unfortunately, it took nearly a decade to realize that the relatively healthy

With oxygen restricted to the minimal levels needed to maintain normal oxygenation, ROP disappeared until the 1970s, when it reappeared in conjunction with the increasing survival of extremely low-birthweight infants (<1000 g). At first it was believed that excessive oxygen once again was the culprit; however, even the most meticulous oxygen monitoring possible failed to prevent ROP in most controlled trials. On


Using a population-based survey of children receiving services for the visually impaired, Gibson has demonstrated that the increased number of children who have had ROP vision loss in recent years is due to an increase in the number of extremely



The vessels that supply the inner retina normally start to grow from the optic disk into the retina at approximately 16 weeks of gestation, becoming complete (reaching the ora serrata) by 40 to 44 weeks. During the time that they are growing, they are particularly vulnerable to injury and may be obliterated by any number of stresses. This is the first event in the development of ROP and is invisible to the examiner. The first visible manifestation of ROP is the neovascular repair response following that


The causes of the initial retinal vascular injury remain elusive, but clearly are multiple. Animal model studies and the experience in human infants of the 1940s have shown that prolonged high blood oxygen levels are one way in which the delicate, incomplete retinal vessels can be obliterated. However, it also is clear that most infants who develop ROP have not experienced any significant periods of hyperoxia. Autopsy tissues have demonstrated that the disease can be initiated by events occurring in utero and that even preterm infants who have cyanotic congenital heart disease sometimes

Clinical Aspects


One of the major advances in this disease has been the development, by


One major effect of active ROP is to delay the progress of vascularization of the retina so that even infants whose ROP is regressing may not


At any stage up to retinal detachments, ROP may stop progressing, regress, and heal. The rate of revascularization is variable, but usually steady. However,


When ROP progresses to stage 3, plus disease represents a quantum increase in severity and the impending risk of retinal detachment. It is at this point that cryotherapy, or more recently laser therapy, is used to ablate the remaining avascular retina in an effort to cause the proliferating vessels to regress. The hypothesis is that the avascular retina is producing angiogenic factor(s) that are causing


Regressed Without Cicatrix

During the first months following regression, the infant who has had ROP should be examined by an ophthalmologist experienced with ROP to determine if there is a significant refractive error requiring glasses and to ensure that there are no

Regressed With Cicatrix

For the child whose ROP has regressed and has left no scar, examinations can be discontinued when the concern over refraction is past. However, when there is a residual cicatrix, at least annual examinations will be required, possibly for

Retinal Detachments

Infants whose retinas have detached in one or both eyes require continued ophthalmic care; some develop acute glaucoma as a complication of the lens being pushed forward into the anterior chamber by the detached retinal tissue behind it. Sudden



The neonatologist must organize ophthalmologic examinations so that each infant is seen before the onset of severe ROP. The Fetus and Newborn Committee of the American Academy of Pediatrics has recommended a useful examination plan (Table 1) that


Ophthalmologists carry the responsibility of performing indirect ophthalmoscopy gently, determining the timing of repeat examinations, and treating the acute disease. The data in Figure 7 show the outcomes at 3.5 years follow-up. Clearly, cryotherapy reduced the chance of an unfavorable outcome, but it is no panacea. Recently, the use of a laser has been shown to be as effective as cryoablation in ROP, and it is easier to perform in some cases, particularly when ROP is very posterior, close to or in zone 1. If ROP continues to progress despite treatment, a variety of heroic efforts have been made to keep the macula (the visual center of the eye) from detaching. Scleral


The role of the pediatrician is to understand why follow-up is important and to know that the peak age of need for cryotherapy is about the time of discharge home from the intermediate care nursery. In the post-surfactant era, discharge home frequently occurs slightly before the infant's due date, and this is approximately the median time that ROP will have progressed to the stage requiring cryotherapy. In the excitement of discharge planning and the chaos of being at home for the first time, infants may not receive the examinations and treatment they need to optimize the chance


Neonatologists, primary care physicians, and ophthalmologists want to give parents accurate information on each infant's ROP prognosis. Data from the infants in the CRYO-ROP natural history study can be used for prognosis of an individual infant after the first examination is complete. In summary, immature vessels in any zone are better than having ROP in that zone, but is no guarantee that ROP will not occur. Zone 1 ROP is