Retinopathy of prematurity: the need for prevention

Abstract

More than 450,000 babies are born prematurely in the USA every year. The improved survival of even the most vulnerable low body weight preterm infants has, despite improving health outcomes, led to the resurgence in preterm complications including one of the major causes for blindness in children, retinopathy of prematurity (ROP). The current mainstay in ROP therapy is laser photocoagulation and the injection of vascular endothelial growth factor (VEGF) antibodies in the late stages of the disease after the onset of neovascularization. Both are proven options for ophthalmologists to treat the severe forms of late ROP. However, laser photocoagulation destroys major parts of the retina, and the injection of VEGF antibodies, although rather simple to administer, may cause a systemic suppression of normal vascularization, which has not been studied in sufficient depth. However, the use of neither VEGF antibody nor laser treatment prevents ROP, which should be the long-term goal. It should be possible to prevent ROP by more closely mimicking the intrauterine environment after preterm birth. Such preventive measures include preventing the toxic postbirth influences (eg, oxygen excess) as well as providing the missing intrauterine factors (eg, insulin growth factor 1) and are likely to also reduce other complications of premature birth as well as ROP. This review is meant to summarize the current knowledge on the prevention of ROP with a particular emphasize on the use of insulin growth factor 1 supplementation.

Keywords: IGF-1; ROP; insulin growth factor 1.

Figure 1

The ICROP committee published three parts on the classification of retinopathy of prematurity. Note: The location and extent of the disease is specified using the images of the right and left eyes, zones I–III, and clock hours. Abbreviation: ICROP, International Classification of Retinopathy of Prematurity.

Figure 2

Timecourse of ROP. Notes: (A) Normal vessel growth starts at the beginning of the second trimester and is usually completed shortly before the full-term birth. This process is strongly associated with the adequate serum IGF-1 levels and postnatal growth. Hence, preterm birth will result in an incomplete vascularization of retina at birth. (B) The lack of growth factors, such as IGF-1, and the increased oxygen pressure (PaO₂) after birth result in a persistently avascular and thus hypoxic retina (Phase I), which will subsequently cause VEGF and other oxygen-sensitive vascular GFs to be produced in excess. (C) The result is retinal neovascularization (Phase II). In order to prevent vessel loss, infants at risk could be supplemented with IGF-1 starting at birth. This will make up for the lack of IGF-1 compared to the in-utero levels at a comparable gestational age to promote an adequate vessel growth. (D) If this preventative measure is not successful or if Phase II ROP has already occurred for other reasons, either laser coagulation or intravitreal anti-VEGF drugs could be used to treat these infants. Abbreviations: IGF-1, insulin growth factor 1; PaO₂, partial pressure of oxygen; VEGF, vascular endothelial growth factor; GFs, growth factors; ROP, retinopathy of prematurity.