Topical ketorolac and nepafenac prophylaxis in early retinopathy of prematurity: real-world clinical evidence from a multicenter care network in Colombia

Every year, thousands of babies are born too early, their bodies still unfinished and their eyes still developing. For these infants, a condition called retinopathy of prematurity is a constant threat. It happens when the blood vessels in the back of the eye, which should grow steadily to fill the retina, instead grow in a chaotic, disordered way. This abnormal growth can lead to scarring, detachment of the retina, and permanent blindness. The risk is highest for the smallest and most fragile babies, particularly those who have spent time on oxygen support. While doctors have effective treatments for severe cases, such as laser therapy or injections, the real challenge often lies in the period before the disease becomes severe. In many parts of the world, getting a baby to a specialist for frequent eye exams is difficult due to distance, cost, or a lack of available experts. If a baby's condition worsens between visits, the window to prevent blindness can close before help arrives. This gap between diagnosis and reliable treatment has led some doctors to wonder if a simple, topical medication could act as a safety net, slowing down the disease just long enough to keep the baby safe until a specialist can intervene.

In a large network of hospitals across Colombia, researchers set out to examine a real-world attempt to fill this gap. They looked at data from preterm infants who were diagnosed with early stages of this eye disease. Instead of waiting to see if the condition would get worse, some doctors began applying eye drops containing nonsteroidal anti-inflammatory drugs, specifically ketorolac and nepafenac, to the babies' eyes. These drops are commonly used to reduce pain and inflammation in adults, but here they were being used off-label, meaning outside their standard approved use, with the hope of calming the eye's internal signals that drive abnormal blood vessel growth. The study compared the outcomes of these treated infants against a group of babies from previous years who received only standard monitoring, where doctors watched the eyes closely but did not use any medication to try to stop the disease progression. The goal was not to declare a new cure, but to see if this emerging practice showed enough promise to warrant serious, controlled testing.

The researchers analyzed records from 192 infants across fourteen different medical centers. The group was split into three: those who received ketorolac drops, those who received nepafenac drops, and a historical group that received no drops at all. The results offered a clear signal that the medication might be doing something beneficial. Among the babies who received ketorolac, only about one in five went on to develop the severe form of the disease that requires invasive treatment. In the group that received nepafenac, the number was slightly higher but still well below the historical group, where nearly half of the infants progressed to a stage needing intervention. This difference was significant enough to suggest that for every four babies treated with these drops, one case of severe disease was potentially prevented.

Beyond just preventing the worst outcomes, the treated babies also fared better in other ways. They required fewer follow-up visits to the eye specialist, which is a major relief for families who often struggle with transportation and time away from work. The eyes of the treated infants also returned to a healthy, stable state faster than those of the untreated group. The study found no major safety issues with the drops; the only side effects noted were minor redness of the eye surface, which cleared up quickly when the drops were paused. However, the researchers were careful to note that the two drugs did not behave exactly the same way in their statistical analysis. While both showed promise in the raw numbers, the evidence remained stronger and more consistent for ketorolac after accounting for other factors like the baby's birth weight and overall health.

The study does not claim that these eye drops are a proven solution ready for immediate global adoption. The researchers emphasize that their work is a snapshot of what happened in routine care, not a definitive proof of cause and effect. The historical comparison group came from a different time period, and even though the doctors tried to match the groups as closely as possible, differences in how babies were cared for in the hospital over the years could have influenced the results. Furthermore, the study was not a randomized trial where babies were randomly assigned to get drops or not; it was an observation of what doctors actually did in their practice. This means that while the results are encouraging, they are not yet a final verdict.

What this research truly accomplishes is to validate a question that has been circulating in medical communities. It shows that the idea of using simple eye drops to protect vulnerable infants is not just a theory, but a practice that has been tested in the real world with measurable results. The findings suggest that in settings where specialist care is hard to reach, this approach could be a valuable tool to buy time and reduce the risk of blindness. However, the authors are clear that before this becomes standard practice, larger and more rigorous studies are needed to confirm that the drops are truly responsible for the improvement and to ensure they are safe for every type of premature baby. Until then, the use of these medications remains an experimental strategy, one that has shown enough potential to justify the next step: a carefully designed clinical trial to find out if this simple intervention can truly change the future for the world's most fragile patients.