Imran Karim Janmohamed1
1Foundation Year 2 Doctor, Princess Royal University Hospital, Orpington
Introduction
Retinopathy of prematurity (ROP) is an ophthalmic disorder that arises in premature infants, particularly those born before 32 weeks gestation, or who weigh less than 1,500 grams at birth. In many children, it is mild and presents no problems, but can also be severe and lead to blindness. In the 1940s, it was the leading cause of blindness in children in the US and (1), unfortunately, it still remains a leading cause of blindness in children worldwide (2).
Epidemiology
ROP is found in nearly 60% of babies who weigh less than 1,500 grams at birth (3). In 2010, around 184,700 out of 14.9 million preterm babies developed ROP of any stage. 20,000 of these babies became blind (visual acuity [VA] 20/400) or severely visually impaired (VA <20/200 to > 20/400) (4). Although advancements in treatments and understanding have been made, ROP persists due to the improved survival of infants with extremely low birthweights and gestational ages (5). In underdeveloped countries, however, ROP can occur in children at higher birthweights and gestational ages (6).
Risk Factors
A wide variety of risk factors are implicated in the development of ROP; however, low birth weight, low gestational age and early supplemental oxygen are consistently associated (6). In fact, the first ‘epidemic’ of ROP that occurred in the 1940s-50s was caused by the use of supplemental oxygen in closed incubators; although this helped improve infant survival, it also contributed to blindness (2). Other risk factors include poor postnatal weight gain, complications from preterm delivery, and blood transfusions (7).
Pathophysiology
ROP is caused by an arrest in the normal retinal vascular development and oxygen-induced vascular injury, characterised by proliferative vitreoretinopathy.
Compared to other organs, the eye develops late in pregnancy, particularly the retinal vasculature in the baby’s development. Premature birth, the relative hyperoxia, and other factors in the extrauterine environment disrupts normal vasculogenesis and initially results in non-vascularisation of the anterior retina. The consequent hypoxia then results in a second phase characterised by a pathological compensatory mechanism leading to aberrant vascularisation of the retina, mediated by vascular endothelial growth factor (VEGF), which can ultimately lead to retinal detachment (8,9).
Screening
Many preterm infants will develop ROP to some extent, and the majority of cases spontaneously resolve without the need for treatment. However, to identify the smaller proportion of infants who may go on to develop potentially severe ROP, appropriate screening strategies are vital to prevent the progression and risk of blindness.
The Royal College of Paediatrics and Child Health (RCPCH) have jointly created an evidence-based guideline with the Royal College of Ophthalmologists (RCOphth) and British Association of Perinatal Medicine, which was originally written in 2008 and updated in March 2022. The screening guidelines have been developed by the RCPCH10 and the treatment guidelines by the RCOphth (11). The screening guidelines were developed specifically for use within the UK and recommend screening all infants less than 31 weeks’ gestation or with a birthweight less than 1501 grams (note: this is an update from the original guidelines, which recommended screening less than 32 weeks’ gestation) (10).
ROP screening is aimed at the second half of the pathophysiological process, characterised by vaso-proliferation, and the disease process is classified using international criteria of zone (ranging from zone I to zone III), stage (1, 2, 3, 4a, 4b or 5), and presence of plus disease (which refers to the dilation and tortuosity of the retinal vessels within zone I) (12). The classification of ROP, indications for treatment and guidelines for follow-up are extensive and will not be discussed in this article.
Management
The adequate treatment of ROP is still an active area of research and several recent studies have guided major changes. The first study that showed improved outcomes from an intervention was the CRYO-ROP study in 1988, which investigated cryotherapy at ‘threshold’ ROP compared to no treatment (13).
Since then, advancements have been made. The aim of treatment is to reduce intraocular VEGF and therapies include laser ablation of VEGF-producing avascular retina or anti-VEGF antibody (for example Ranibizumab) (11). A 2014 national surveillance study reported that 4% of screened infants required treatment; 90.5% received laser, 8% received anti-VEGF therapy and one received cryotherapy with laser (14).
The primary choice of ROP treatment varies between centres and is guided by several factors including retreatment rate, what the infant is able to tolerate, and the risk of systemic morbidity, which has previously been suggested with anti-VEGF agents, although studies have reported conflicting results (15,16). The RCOphth Guideline Development Group view that laser may remain the preferred treatment modality (11).
Conclusion
ROP is a leading cause of blindness and visual impairment in infants. Only a minority of patients require treatment; however, it is important to identify these infants as the disease is largely preventable, thus necessitating an appropriate screening programme. The benefits and risks of laser vs. anti-VEGF treatments differ, although centres often display a preference for laser. Alternative treatments, along with potential systemic effects, must be discussed and agreed with parents.
References
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