Do we need India-specific retinopathy of prematurity screening guidelines?

Retinopathy of prematurity (ROP) is a major cause of preventable blindness in children.[1] It is estimated that of about 15 million children born preterm worldwide, about 53,000 develop sight-threatening ROP requiring treatment, and 20,000 suffer blindness or severe visual impairment.[2] More than 60% of preterm births occur in Africa and South Asia.[3] India accounts for the most preterm births in the world (3.5 million).[3] United Nations Children's Fund estimates that 21 million newborns (15% of all births) have low birth weight (LBW).[4] India has the third highest incidence of LBW, with about 1.7 million weighing <2500 g and about 0.4 million <1500 g.[4] Crucially, premature birth and LBW predispose a newborn to develop ROP, for which India is evidently the hotbed.

The occurrence of severe ROP is related to the level of neonatal and ophthalmologic care and the socioeconomic status of a country. Of 15 million infants born prematurely each year, 1.2 million are born in high-income countries with access to optimal neonatal intensive care, another 8.2 million are born in middle- or low-income countries with access to hospital births but with variable and limited infrastructure and expertise, and 5.6 million are born in low-income countries with home care.[56] In high-income countries, where the level of neonatal care is optimal, ROP-associated blindness is relatively uncommon.[6789] However, in middle- and low-income countries with regional variations in technology and capacity, ROP blindness may be substantially high, contributing to about 40% of childhood blindness.[69]

Unfortunately, there is no hard data on the incidence of ROP in India. Of 3.5 million premature births in India, approximately one in six (about 600,000) children are born at <32 weeks gestational age (GA).[1011] Estimating that about 40% of these receive neonatal care and 80% of them survive, about 200,000 children are at risk of developing ROP in India every year. If about 10% of them develop treatable ROP, the number of newborns needing ROP management is at least 20,000 every year.[11] In addition, children with GA 32–36 weeks who receive suboptimal postnatal care and have comorbidities may also be at the risk of developing ROP.

The dynamic and time-bound development of ROP and effectiveness of treatment at an appropriate stage make it amenable for systematic screening. Screening guidelines, however, vary from region to region. The 2019 American Academy of Pediatrics (AAP) guidelines recommend screening of all infants with a BW ≤1500 g or a GA ≤30 weeks and selected infants with a BW between 1500 and 2000 g or GA >30 weeks who are believed to be at risk for ROP (infants with hypotension requiring inotropic support, infants who received oxygen supplementation for more than a few days, or infants who received oxygen without saturation monitoring).[12] United Kingdom guidelines developed by the Royal College of Ophthalmologists (RCO) and Royal College of Pediatrics and Child Health stipulate that babies <32 weeks GA or <1501 g birthweight should be screened for ROP.[13]

It is known that ROP can develop in bigger and more mature babies in India, which may be attributed to the variable and often suboptimal quality of neonatal care.[141516] Studies from India have shown that children with BW of 2000 g can develop ROP.[141516] A prospective study from South India confirmed that severe ROP does occur in babies who lie outside the conventional American or British screening criteria.[15] About 6.7% and 13.3% of severe ROP would have been missed using the RCO or AAP screening criteria, respectively.[15] The authors suggested that broader screening criteria of GA of <34 weeks and birth weight (BW) of <1750 g would be an ideal starting point for the region.[15] Another study from South India noted that 17.7% and 22.6% of children with threshold ROP or worse would have been missed if they were to use the AAP or RCO screening criteria, respectively.[16] A study from India found the mean BW in the group with severe ROP was 1554 g (range 850–2290) and the mean GA was 31.75 weeks (range 28–34).[17] A report from China showed that 30.4% and 16.2% of infants with ROP Stages 3, 4, and 5 outlied the AAP and RCO screening criteria, respectively.[18]

There have been attempts in the past to customize ROP screening criteria to India.[19] Jalali et al. initially suggested screening of all children with BW <1500 g or GA <34–35 weeks and children exposed to oxygen for >30 days and BW <2000 g or GA <37 weeks with high-risk factors.[20] They later proposed a modified screening criteria of BW <1750 g and GA of <34 weeks.[15] Screening guidelines published by the National Neonatology Forum recommends first screening between 2 and 3 weeks for infants born before 28 weeks GA or with a BW <1200 g and not later than 4 weeks after birth for infants born between GA of 28 and 34 weeks or BW ≤2000 g.[21] The latest ROP guidelines (published by a collaborative of neonatal care and ROP experts in India, London School of Hygiene and Tropical Medicine, led by the Indian Institute of Public Health – Public health Foundation of India and supported by the Queen Elizabeth Diamond Jubilee Trust) are an attempt to standardize the screening and management of ROP in India and integrate it with the existing public health delivery system.[11] It proposes screening of all children born ≤34 weeks and those >34 weeks with risk factors if the GA is known, or all infants ≤2000 g BW if GA is unknown [Fig. 1]. It includes an elaborate set of follow-up screening [Fig. 2], treatment [Fig. 3], and long-term follow-up (based on cortical and ocular morbidity) [Figs. 4 and 5] guidelines. In a significant move, it also proposes the use of wide-field fundus imaging and screening by nonophthalmologists.

Figure 1

Retinopathy of prematurity screening guidelines. (Reproduced with permission from “Project operational guidelines. Prevention of Blindness from Retinopathy of Prematurity in Neonatal Care Units, https://phfi.org/wp-content/uploads/2019/05/2018-ROP-operational-guidelines.pdf”)

Figure 2

Algorithm for the follow-up and management of retinopathy of prematurity. (Reproduced with permission from “Project operational guidelines. Prevention of Blindness from Retinopathy of Prematurity in Neonatal Care Units, https://phfi.org/wp-content/uploads/2019/05/2018-ROP-operational-guidelines.pdf”)

Figure 3

Retinopathy of prematurity treatment guidelines. (Reproduced with permission from “Project operational guidelines. Prevention of Blindness from Retinopathy of Prematurity in Neonatal Care Units, https://phfi.org/wp-content/uploads/2019/05/2018-ROP-operational-guidelines.pdf”)

Figure 4

Ophthalmic evaluation guidelines for preterm infants. (Reproduced with permission from “Project operational guidelines. Prevention of Blindness from Retinopathy of Prematurity in Neonatal Care Units, https://phfi.org/wp-content/uploads/2019/05/2018-ROP-operational-guidelines.pdf”)

Figure 5

Ocular and cortical morbidity in preterm infants – follow-up evaluation guidelines. (Reproduced with permission from “Project operational guidelines. Prevention of Blindness from Retinopathy of Prematurity in Neonatal Care Units, https://phfi.org/wp-content/uploads/2019/05/2018-ROP-operational-guidelines.pdf”)

In the absence of large epidemiological studies and mapping of nation-wide ROP data, we may have to agree that the current ROP screening and management guidelines are only a good starting point. Wider screening criteria, no doubt, will increase the rate of pick-up of ROP. It is estimated that approximately 19 hours of ophthalmologists’ time is required to detect one threshold ROP.[22] Although screening workload per child relatively decreases with increasing GA and BW, the overall stress on the healthcare system due to the increased number of children under screening needs an astute evaluation. Screening by nonophthalmologists and tele-screening by wide-field fundus imaging are paradigm changes in concept but need to be validated for agreement with the gold standard (screening by a trained retina specialist) in varied real-life situations before these measures can be widely implemented.

This issue of the Indian Journal of Ophthalmology is a tribute to concerted efforts by several dedicated individuals, institutions, and organizations to the cause of ROP and pediatric retinal diseases. Prof. Mangat Ram Dogra, who retires this month as the Head of the Department, Advanced Eye Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India, needs a special mention for having inspired generations of Indian ophthalmologists to take up the crying cause of ROP and pursue it as their passion.