HMN 2026: How Clinical trial targets the trachoma scourge

Trachoma is the leading cause of infectious blindness in the world, with Ethiopia the most impacted country in Africa. In a clinical trial of more than 2,400 individuals, researchers led by Dr. John Kempen of Mass Eye and Ear found a topical anti-inflammatory treatment, fluorometholone, was not effective at reducing postoperative trachomatous trichiasis. Their research is published in The Lancet Global Health.

Trachoma causes scarring on the ocular surface, including the inner surface of the eyelids. The latter causes the eyelashes to turn in, scratching the cornea and leading to blindness through corneal damage and secondary infections. Thus, it not only causes blindness, but also constant misery with the lashes always scratching on the corneal surface.

WHO strategies and the FLAME trial

The World Health Organization (WHO) has established a plan to try to clear blindness from trachoma, in part by conducting surgery on eyes with inturned upper eyelashes (a condition known as trachomatous trichiasis, or “TT”). Because it’s not uncommon for TT surgery to fail, which is hard to fix, improving the outcomes of surgery is very important. The FLAME Trial is part of an initiative to improve the quality of surgery to better prevent blindness and improve quality of life for those affected.

The FLAME Trial was a large-scale field trial in Ethiopia designed to confirm (or refute) the impressive results from a preliminary trial comparing three doses of a low-risk, topical anti-inflammatory treatment called fluorometholone to placebo. In this initial trial, all three groups experienced about a one-third reduction in the risk of postoperative TT.

However, as a new study reports, the FLAME trial could not confirm the promising preliminary results. Given the far larger sample size of FLAME, researchers are confident in its “negative” results, and interpret them to mean that anti-inflammatory therapy is unlikely to advance this field.

Details of the clinical trial

The team evaluated whether fluorometholone 0.1% suspension given just before surgery and postoperatively for four weeks would reduce the risk of recurrence of postoperative TT.

The study was a randomized controlled clinical trial in which more than 2,400 participants received an active or placebo (artificial tears) treatment. Because this disease affects very disadvantaged individuals in remote areas, the research team would often travel on motorcycles—or even walk—to the remote sites where surgeries were performed. The study also gave the team an opportunity to provide free treatment to nearly 3,000 people (including those presenting for care who did not qualify for or consent to study enrollment).

The results convincingly showed no difference between the active fluorometholone treatment and placebo, with near-identical results between groups. In terms of safety, results were similar as well, suggesting that taking fluorometholone twice daily for four weeks is generally safe. That is an important finding for the use of fluorometholone for other diseases.

Implications and future directions

The results, along with negative results from a different trial, suggest that the use of anti-inflammatory therapy along with all surgeries is not likely to help improve TT surgery outcomes. However, because of the rich dataset the team accumulated, the researchers plan to conduct additional, secondary analyses.

It would be best to shift focus to other ideas for improving TT surgery outcomes, and there are some promising new opportunities. A published secondary analysis from the FLAME Trial has found that the results of one of the two WHO-endorsed surgical techniques reflect about 70% less recurrent or postoperative TT. This confirmed results from a previous clinical trial showing about a 50% reduction in postoperative TT with the Posterior Lamellar Tarsal Rotation (PLTR) technique (also known as the Trabut technique) than with the Bilamellar Tarsal Rotation technique.

In addition, the group has also shown that refresher training in a structured supportive mentorship context can reduce the risk of postoperative TT substantially.

In general, focusing on quality assurance for TT surgery seems to be the key concept to make outcomes as favorable as possible. General preventive efforts targeting antibiotics, face washing and environmental improvement also remain very important.

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