Retinopathy of prematurity (ORPHA:90050)
A rare retinal vasoproliferative disease affecting preterm infants characterized initially by a delay in physiologic retinal vascular development and compromised physiologic vascularity, and subsequently by aberrant angiogenesis in the form of intravitreal neovascularization.
Epidemiology
The incidence of Retinopathy of prematurity (ROP) is increasing as higher numbers of premature neonates survive into infancy, particularly in developing countries. Some estimates among preterm birth infants are over 30%. In some countries, ROP accounts for up to 10% of childhood blindness. Higher prevalence has been reported in South East Asia, Latin America, and subSaharan Africa. Incidence rates are similar in Caucasian and Black populations, but progression to severe forms may be more frequent in Caucasians.
Clinical description
The degree of prematurity generally correlates with the severity of the clinical manifestations, with the smallest neonates having the highest risks. In affected infants, normal retinal development is incomplete at the time of preterm birth. Subsequently, aberrant angiogenesis in the form of intravitreal neovascularization occurs leading to later cicatricial fibrosis causing partial or complete retinal detachment and possible loss of vision. Patients may also develop ametropia, anisometropia, amblyopia or strabismus. Glaucoma has also been reported in affected individuals.
Etiology
The pathophysiological mechanisms underlying ROP remain poorly understood. Associations with severe ROP include high oxygen at birth and oxygenation fluctuations during the neonatal course, low birth weight and young gestational age, and poor postnatal growth. In candidate gene studies, gene mutations associated with severe ROP have been reported, including NDP (Xp11.4-p11.3), FZD4 (11q14-q21), and LRP5 (11q13.4).
Diagnostic methods
Neonates born before 30 weeks of gestation or with a birth weight below 1,500 g should be screened for ROP, but specific guidelines may vary based on regional statistics and characteristics of affected preterm infants world-wide. Diagnosis is based on characterization of ROP severity in preterm infants usually determined by dilated fundus examination with scleral depression but increasingly more with review of photographic images. ROP is categorized into 3 zones and severity in 5 stages (stages 1 to 5, from mild disease to total retinal detachment).
Differential diagnosis
The main differential diagnostic considerations for early ROP are conditions associated with peripheral avascular retina and intravitreal neovascularization, including familial exudative vitreoretinopathy (FEVR) or incontinentia pigmenti (see these terms). For stage 5 ROP, other conditions causing leukocoria are included (e.g. retinoblastoma, persistent fetal vasculature, toxocariasis, etc.).
Management and treatment
Close work with neonatologists is recommended. All attempts are made to avoid high oxygen at birth (100% oxygen). Optimal monitoring and regulation of oxygen saturation is recommended and is chosen based on gestational age and overall health of the infant. However, the optimum saturation level is not known. Following screening of at-risk infants, monitoring is recommended based on retinal findings. Treatment options include transpupillary or sometimes transscleral laser photocoagulation of the peripheral avascular retina. For the most severe forms of ROP like zone I severe ROP and aggressive posterior ROP, intravitreal treatment with agents that interfere with the bioactivity of vascular endothelial growth factor (VEGF) are being studied and considered. Visual rehabilitation is critical because of the association with myopia and refractive errors. Anisometropia should be corrected and associated amblyopia or strabismus treated. Protective eyewear and low-vision aids may be required.
Prognosis
Gestational age and birth weight are the main prognostic factors in ROP. Also associated is poor postnatal weight gain. ROP often resolves but if it develops severe characteristics, it can lead to blindness.

                            Last update: 
                            July 2019


                            - Expert reviewer(s): 
                            Pr Mary Elizabeth HARTNETT