In this study we compared the ROP examination and treatment outcomes between the semi-urban and urban population cohorts of babies who received neonatal care in two neonatal units in two different states of North India. The results of our study suggested that the overall proportion of ROP was 15.1% and a higher proportion of ROP was found in babies with BW ≤ 1500 g, GA ≤ 28 weeks, screening done before 30 days of life and in the semi-urban setting. The proportion of ROP was almost 3-fold higher in the semi-urban setting (31.9%) compared to the urban setting (11.7%). Also, the drop-out rate for ROP examination was higher in the semi-urban setting. 29% of the babies in the semi-urban setting did not complete their all required examination visits.
In this study, in both settings a higher proportion of those examined were boys (67%), and girls were less likely to complete all the examinations required. One of the more probable reasons could be that the parents consider boys to be more valuable and hence, they bring them for examination and treatment.
There was a considerable delay in undergoing first screening in the semi-urban cohort of babies. Jalali et al  had discussed the role of early screening strategy for preterm babies. Their study suggested early screening before one month of age in neonatal centres can detect early disease and prompt treatment can lead to favourable outcomes. In our study, the mean time interval for the first ROP examination in the urban group was considerably lower than the 30 days recommended, and the large standard deviation suggested that some may have been examined far too early. In the urban setting, 66% of the babies were examined before 25 days of life and 28% were examined after 30 days of life. While, in the semi-urban setting, more proportion of babies (68%) were examined after 30 days of life. Thus, systematic screening in the neonatal unit is more likely to lead to the first examination being undertaken at the correct time i.e., between 25 and 30 days after birth. Also, the results from this study suggested that one of the important reasons for the delay in ROP examination could be that babies were only referred to the retina clinic after they had been stabilised, except in a few instances where visits were made to the NICU to examine babies in the unit. This approach of ROP examination is far from ideal as sick babies are those most at risk of ROP. The impact of late examination is shown in Table 2 where 5 of the 30 (16.7%) babies in the semi urban group with any ROP had stage 4 or 5, compared with 1 of the 54 (1.8%) in the urban group who were examined earlier. The median time interval for first examination babies with stage 4 or stage 5 ROP in the urban and semi-urban cohort was 77 and 156 days respectively. The low uptake for ROP examination and the lateness of examination highlight how this approach for ROP evaluation is far away from ideal. In our study, we found the mean GA to be similar in both groups while in semi-urban setup more heavier babies were screened for ROP (1348.6 ± 395.21 gm in urban; 1703.77 ± 401.76 gm in semi-urban setting). Our study revealed higher proportion of stage 5 ROP with total inoperable retinal detachment in 4 eyes in the semi-urban cohort and none in the urban population; thereby further stressing on the need for timely screening for ROP to detect the disease early.
Only 91 babies of the eligible 240 babies underwent ROP examination in the semi-urban cohort accounting to a drop-out rate of about 62% while the drop-out rate in the urban cohort was only 2.9%. In India, currently, most of the ROP examinations are done by retina specialists. Paediatric ophthalmology is still not a well-established separate subspecialty in India. [18, 19] Most of the vitreo-retinal surgeons and paediatric ophthalmologists practise in bigger cities. As a result, there is a paucity of ROP care givers in semi-urban and rural areas. Also, the profile of babies who develop ROP in developing countries like ours are older and heavier babies. [8, 9] This further increases the burden of babies who need to be included for screening in our population. Hence, preterm babies born in the semi-urban/rural areas are not being subjected for ROP examination as per the screening guidelines. Studies have shown paediatricians and ophthalmologists practising in the interiors of the country to have poor knowledge regarding ROP and its screening strategies. [20, 21] Creating awareness amongst the medical staff like ophthalmologists, paediatricians, gynaecologists and nurses in the NICU and providing training and basic infrastructure like indirect ophthalmoscopy for screening preterm babies can increase the overall screening rate. Also stressing the need for screening at the time discharge to parents/guardians can help in increasing the ROP screening rate in rural/semi-urban areas.
Lack of availability of treatment facilities like laser in these areas could be responsible for the high drop-out rate as well. Providing treatment to such high-risk babies at the screening site would be beneficial in preventing childhood blindness due to ROP. Currently in India, there are massive efforts made to integrate screening for ROP into government neonatal units and Special New-born Care Units at district level. Screening was integrated into sick new-born care units at the district level and treatment facilities were provided and improved at the closest publicly funded medical schools. In the first two years, there were substantial improvements in awareness, screening, treatment and partnership between stakeholders, and changes in public health policy.  Other strategies which are being currently used include training members of the neonatal team to capture retinal images using wide-field imaging which are then read by ROP experts. A KIDROP like screening model can provide ROP screening in low-resource settings, remote centres, and regions with few ROP specialists. [10, 23]In our study, we did screen preterm babies from 2 population groups who were socially and economically unequal.
The quality of neonatal care provided in the urban and semi-urban NICUs is highly variable. The urban NICU at Delhi is a level IIIA NICU providing a high level of neonatal care to very low birth-weight premature babies. They have a wide variety of trained staff available on-site including neonatologists, neonatal nurses and respiratory therapists who are available 24-hours a day. In comparison, the semi-urban NICU at Alwar is a level II NICU providing care to infants who are moderately ill with problems that are expected to resolve rapidly. [24, 25] Care in this setting is usually limited to new-born infants who are > 32 weeks' GA and weigh > 1500 g at birth or who are recovering from serious illness treated in a level III NICU. The NICU in Alwar takes care of extremely sick babies and this could contribute to the higher proportion of severe ROP cases seen in this semi-urban cohort. A recently published meta-analysis showed that lower Spo2 target range was associated with a lower risk of retinopathy of prematurity treatment and a higher risk of mortality and necrotizing enterocolitis.  Chow et al had observed a significant decrease in the prevalence of ROP with training of the NICU staff and better implementation and enforcement of clinical practices related to oxygen (O2) management and monitoring. In their study, the prevalence of ROP decreased consistently in a 5-year period from 12.5% in 1997 to 2.5% in 2001. The need for ROP laser treatment decreased from 4.5% in 1997 to 0% over the last 3 years.  Even in our study we found a significantly lower prevalence of ROP in the urban setting due to the high level of neonatal care provided, increased awareness for early screening of preterm babies and better understanding of the disease amongst the paediatricians.
Our study highlights important key issues related to method of ROP evaluation and treatment in the urban and semi-urban population settings. This study stresses the need for more medical personnel, especially those belonging to the semi-urban/rural setups to be trained for ROP screening by premier tertiary eye care institutions. Our study also emphasizes on the need for newer ROP screening strategies like tele-ophthalmology to be implemented in the semi-urban/rural areas. This, in turn will reduce the visual impairment and blindness from ROP in our country.