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I. Intensive care

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  1. Retinopathy of prematurity

    1. Definition

      1. Retinopathy of prematurity (ROP) is an eye disease that affects the blood vessels and neurons of the incompletely developed retina in infants born preterm.

      2. Normal retinal vascular growth and development is suppressed after premature birth as the infant enters an environment that is missing factors provided by the mother and that has higher oxygen levels than in utero.

      3. Abnormal vascular shunting and neovascularization may occur as the retina reacts to subsequent hypoxia.

      4. This pathological process may stop and spontaneously regress without treatment in milder cases or lead to progressive retinal traction and detachment, resulting in vision loss in more severe cases.

    2. Incidence

      1. ROP is a leading cause of potentially preventable childhood blindness in developed countries.

      2. Each year, ROP affects approximately 14,000 to 16,000 premature infants in the United States.

      3. Approximately 1100 to 1500 of these infants will develop ROP severe enough to require treatment and 400 to 600 infants will become legally blind from ROP.

      4. Two large multicenter studies have reported on the natural history of ROP in premature infants weighing <1251 g at birth. Similar rates of ROP were found between the two studies that involved infants born 15 years apart.

        • Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) Study (1986-1987): 4099 infants with a mean birthweight (BW) of 954 g and mean gestational age (GA) of 27.9 weeks; 65.8% developed any ROP; 27.1% developed prethreshold ROP; 6% developed threshold ROP requiring treatment.

        • The Early Treatment for Retinopathy of Prematurity (ETROP) Study (2000-2002): 6998 infants with a mean BW of 907 g and mean GA of 27.4 weeks; 68% developed any ROP; 36.9% developed prethreshold ROP; 8% developed type 1 ROP requiring treatment.

    3. Pathophysiology

      1. Retinal vascularization begins at the optic nerve at 16 weeks' GA and is completed by 40 weeks' GA. Infants born prematurely, thus, have incompletely vascularized retinas.

      2. The degree of immaturity reflects the susceptibility of the retina to loss of factors provided by the mother and the relative hyperoxia of the extrauterine environment.

      3. ROP is a biphasic disease consisting of an initial phase of vessel growth cessation and loss followed by a second phase of vessel proliferation (Figure 23-1).

        • Phase 1 occurs from birth to approximately 30 to 32 weeks' postmenstrual age (PMA). The extrauterine environment is relatively hyperoxic, causing vaso-obliteration of the developing retinal vessels and/or cessation of vessel growth. As the retina matures, metabolic demands increase and the peripheral avascular retina becomes hypoxic, leading to the second neovascular phase of ROP.

        • Phase 2 begins at approximately 32 to 34 weeks' PMA. The hypoxic retina stimulates release of oxygen-regulated angiogenic factors such as vascular endothelial growth factor (VEGF) and erythropoietin, leading to abnormal growth of fibrovascular tissue at the junction of the vascularized and nonvascularized retina.

    4. Risk factors

      1. Birth characteristics that reflect the degree of retinal vascular development and susceptibility to insult.

        • GA and BW correlate with the level of retinal immaturity. Younger GA and lower BW are key risk factors for the development of ROP. In the CRYO-ROP and ETROP studies, the incidence of any ROP increased to 81.6% to 82.5% ...

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