Retinopathy of prematurity: epidemiology
Retinopathy of prematurity (ROP: or retrolental fibroplasia as it was called previously) was an unknown condition before the 1940s. It was first described in children who had been born prematurely in the United States of America, and, during the 1950s, ROP was an important cause of blindness in children in industrialised countries, being the single commonest cause in some countries (the ‘first epidemic’). Retinopathy of prematurity occurred because preterm and low birth weight babies were given unmonitored supplemental oxygen (see Graph). This meant that premature babies started to survive, but the high blood oxygen levels damaged the immature retinal capillaries, causing abnormalities in the process of peripheral retinal vascularisation. Towards the end of the 1950s supplemental oxygen was realised to be a risk factor, and its use was restricted. This was followed by a reduction in the incidence of blindness from ROP, but a higher infant mortality rate and, very unfortunately, a higher incidence of children with cerebral palsy as a result of hypoxia and brain damage. Oxygen was used again in the 1960s, with monitoring of blood oxygen levels, but blindness from ROP began to re-emerge. The introduction of increasingly advanced technology, with accurate methods of monitoring blood oxygen levels and other parameters in the 1970s, was probably the major factor responsible for the low incidence of blindness due to ROP observed during this period. In situations where accurate monitoring of blood oxygen levels is not possible clinicians have to make difficult decisions between withholding oxygen on the one hand, which increases the risk of ischaemic cortical brain damage, and giving unmonitored supplemental oxygen on the other hand, which can cause blindness from ROP.
Table 1. Proportion of severe visual impairment and blindness in children in schools for the blind in different regions of the world
|Region||Number of countries||Number of children examined||SVI/blind due to ROP (%)|
|Africa||9||1,234||0 – 10.6|
|Asia||5||1,930||0 – 16.9|
|E Europe||3||275||0 – 25.9|
|L America||6||682||4.1 – 38.6|
|Europe||5||Various sources||6 – 17|
SVI = Severe Visual Impairment
The risk of ROP is inversely related to gestational age and birth weight; in other words, the more premature or low birth weight the baby the greater the risk of developing ROP. More very low birth weight (VLBW, less than 1,500 grams at birth) and extremely low birth weight (ELBW, less than 1,000 grams at birth) babies are surviving as neonatal services continue to improve. The population of babies at risk is therefore increasing, and there is some evidence that blindness from ROP is increasing again in some industrialised countries (the ‘second epidemic’) (see Graph). In industrialised countries blindness from ROP is now largely restricted to infants in the ELBW group.
Risk factors for retinopathy of prematurity
Many case control studies have been undertaken to determine risk factors for ROP, and all identify preterm birth and low birth weight as the major risk factors. A recent study has shown that variable (fluctuating) oxygen levels are an important risk factor for the development of ROP. Sequential oxygen levels in babies who subsequently did and did not develop acute ROP were compared, and the results suggested that the infant retina is particularly susceptible to fluctuations in oxygen levels in the first few weeks after birth. Other factors associated with the development of ROP (but not necessarily causally associated) include hypoxia, acidosis, intra-ventricular haemorrhage, exposure to light, vitamin E deficiency and septicaemia. Progression to advanced, blinding disease seems to be determined by the immaturity of the retina and the degree of early damage to the tissues.
Incidence of ROP in low birth weight babies
Studies undertaken in neonatal intensive care units in industrialised countries have shown that up to 60% of LBW babies develop ROP, which rises to 72% in ELBW babies. The proportion of VLBW babies which develop Stage III ‘plus disease’ and subsequent blindness can be as high as 11 % and 8% respectively. There is wide variation in the reported prevalence of the different stages of ROP, which is probably due to selection bias due to different referral patterns, varying standards of neonatal intensive care and selection criteria for neonatal intensive care.
At the moment there are very few reports from non-European countries on the proportion of preterm babies who develop ROP, but ROP has recently been described in infants in a neonatology unit in India.
Prevention of ROP
Systemic steroids given immediately before preterm birth have been shown to reduce the incidence of respiratory distress syndrome (RDS) which may in turn prevent the development and severity of ROP. Many randomised clinical trials have been undertaken to determine whether vitamin E supplementation prevents the development of ROP, and overall a significant positive benefit has not been demonstrated. Examination of babies enrolled in clinical trials of surfactant have suggested that prophylactic surfactant replacement therapy may be of benefit in preventing ROP. (Surfactant is a complex mixture of phospholipids and proteins produced by the lungs. It is deficient in premature babies with the respiratory distress syndrome).
Retinopathy of prematurity as a cause of blindness in children
Data from European countries show that 6-17% of blindness in children is due to ROP. Data obtained from examining children in schools for the blind in different regions of the world suggest that ROP may be becoming an important cause of blindness in Latin American countries,1 and in other middle income countries (Table 1). Data from Thailand and the Philippines2 has shown that there were no children blind from ROP in schools for the blind with rural populations, whereas 15% of children in schools with urban populations were blind from ROP. A recent blind school study undertaken in South Africa has shown that 10.6% of children were blind from ROP.3 This is the only country in Africa where blindness from ROP has been reported.
Retinopathy of prematurity was a major cause of blindness in children in industrialised countries 40-50 years ago, and there is evidence that it may be becoming an important cause in some middle income countries as neonatal intensive care services are introduced. Many of the risk factors are known, and there is a need to increase awareness among neonatologists and ophthalmologists of the problem of ROP so that appropriate preventive measures can be taken.
1 Gilbert CE, Canovas R, Kocksch R, Foster A. Causes of blindness and severe visual impairment in children in Chile. Dev Med Child Neurol: 1994: 36: 334-43.
2 Gilbert C, Foster A. Causes of blindness in children attending four schools for the blind in Thailand and the Philippines – a comparison between urban and rural blind school populations. Int Ophthalmol: 1993; 17: 229-34.
3 O’Sullivan J, Gilbert C, Foster A. The causes of childhood blindness in South Africa. S Afr Med J: In press.