In our study we found a high incidence of type 1 ROP and a significant disparity between local and international screening criteria for ROP as well as key associations between screening practices, zones of ROP and treatment modalities utilized. We found that 25% of screened babies had retinopathy of prematurity, which aligns with findings from other studies conducted in Lahore. For instance, a study at Hamid Latif Hospital, (11) Lahore found a 28% ROP incidence, while a study at Ganga Ram Hospital, Lahore by Abdul Rauf et al. observed that 43 out of 160 screened babies developed ROP.(4) In contrast, a 2016 study at Mayo Hospital reported a significantly lower ROP incidence of 15%.(3) This variation can be attributed to advancements in neonatal intensive care, which have led to improved survival rates among preterm infants, as well as the implementation of enhanced screening protocols and diagnostic tools that have facilitated earlier detection of retinopathy of prematurity. (12) Additionally, studies at Shifa Hospital and Aga Khan University reported lower ROP incidences of 3.2% and 11.2%, respectively. (13, 14) These lower rates may be linked to improved neonatal intensive care and better-controlled oxygen therapy for premature infants in those healthcare settings.
Comparative international data suggests that the incidence of retinopathy of prematurity varies significantly between developed and developing regions. Studies from Iran and North India reported ROP incidence rates of 23.5% and 18.18% respectively among preterm infants, while a Chinese study found a 13.99% incidence of ROP requiring treatment.(15–17) In contrast, developed countries like Poland exhibited a lower incidence, with only 6.1% of infants requiring ROP treatment.(18) Similarly, the incidence of type 1 ROP in North America was reported to be 6%, markedly lower than the rate observed in our cohort.(19) These disparities may be attributed to the more advanced neonatal intensive care services and improved screening and treatment modalities available in developed nations, which contribute to better management and prevention of ROP.
Regarding screening practices, we found that 29.2% of infants with Type 1 ROP would have been missed if only international screening criteria was applied, highlighting the importance of local criteria development and refinement. Ours is not the first study assessing ROP screening criteria suitability in Pakistan. A study conducted in our centre in 2017 to 2019 on 51 ROP blind children found that international criteria would have missed 4 (7.8%) of these children. (20) Contrasting our results a study in Karachi from 2010 to 2012 found that no children developing ROP fell outside international screening guidelines. (2) Another study taking place in our centre also found only 4 infants > 32 weeks and 1 infant > 1500g in 2016. (3) Another study in Lahore in 2019 found international criteria would have missed 4(19%) infants based on GA and 2 (9%) infants based on BW. (11) These studies combined with our results indicate a concerning trend of an increased amount of older and heavier babies presenting with ROP.
The importance of robust and extensive ROP screening programmes cannot be ignored in this era as the world goes through the third documented ROP epidemic. Unlike the first 2 waves this third wave mostly targets lower and lower middle-income countries like Pakistan where the rise in premature infant survival through increasing supplemental oxygen provision, coupled with a lack of ROP awareness, education in the general l population, lack of resources and loss to follow-up creates a dangerous breeding ground for this epidemic to go on rising unchecked ( 21). In these conditions, the need for an ROP screening guideline is paramount. This is why the number of infants missed by international screening criteria is concerning. While screening criteria are being lowered across the world (with general guidelines in the US being lowered to 30 weeks and 1500g in 2013 and UK guidelines being lowered to 32 weeks in 2022 from the 32 weeks and 1500g), our findings support a broadening of these parameters in our region.(22) The variation of screening criteria by region has been recommended before, as it was found that low and lower middle-income regions tended to find ROP in older and heavier babies. Sub optimal neonatal care services may be to blame for this disparity, as it has been consistently noted that countries lower on the human development index require guidelines more extensive than the standard 32 weeks and 1500g and require extensive studies and data to fine tune these guidelines to suit their populations needs. (23) This is why the Ophthalmological Society of Pakistan (OSP, December 2019) recommends screening at ≤ 35 weeks or ≤ 2000g, which our findings heavily support (20).
We found zones of ROP to be significantly associated with GA, BW along with treatment required. We found babies weighing over 2000 grams and with a gestational age of > 35 weeks were more likely to have zone 2 ROP and receive laser therapy as their initial treatment. In contrast, babies with zone 1 disease typically had lower birth weights (< 1500 grams or 1500–2000 grams) and earlier gestational ages (< 32 weeks), making them more likely to receive anti-VEGF treatment initially. Other studies also found higher birth weight and age leading to zone 2 ROP and laser therapy and zone 1 disease got anti-VEGF.(17, 18) Real world data reports that Anti-VEGF is preferred for zone 1 ROP and zone 2 posterior disease, while laser is better for zone 2 ROP.(24) Although studies such as the BEAT-ROP have found anti-VEGF treatment to be more effective in zone 1 than zone 2 ROP, we found no significant difference in disease regression after initial anti-VEGF in both zones.(9) Two-thirds of zone 1 ROP and three-fourth of zone 2 ROP babies initially treated with anti-VEGF failed to achieve disease regression and required laser treatment on follow up. No significant difference between the two groups was noted.
We found that 68.6% of babies initially treated with anti-VEGF required additional laser therapy on follow up, while all babies initially treated with laser achieved disease regression. Similar findings were observed in other studies 25). However, across the board, a majority of the babies initially treated with anti-VEGF, needed further laser intervention. This highlights the importance of robust follow-up programs during anti-VEGF ROP treatment.
Overall, it is very encouraging that all of the babies treated for type 1 ROP in our centre managed to achieve disease regression. The main strength of this study is that we studied a large population compared to previous studies, offering important insights into ROP incidence and evaluation of screening practices.
Our study has several limitations, Firstly, the relatively small sample size of 89 participants limits the generalizability of our findings. The single-centre design introduces potential selection bias, restricting the applicability of our findings to other settings with different neonatal care practices and screening protocols. The short follow up duration may have been insufficient to fully evaluate the long-term implications and sustainability of the treatment modalities examined. It should be noted that we employed ranibizumab as the anti-VEGF treatment in our study. Recent network meta-analysis has noted that ranibizumab has significantly lower success rate than bevacizumab, future studies should take into account the effectiveness of different anti-VEGF agents (26).