Clinical trial in Ethiopia targets the trachoma scourge

John Kempen, MD, MPH, PhD, MHS, Director of Epidemiology for Ophthalmology at Mass Eye and Ear and Harvard Medical School, is the lead author of a paper published in The Lancet Global Health, “Evaluation of fluorometholone as adjunctive medical therapy for trachomatous trichiasis surgery (FLAME): a parallel, double-blind, randomised controlled field trial in the Jimma Zone, Ethiopia.”

Q: Why is trachoma important?

Trachoma is the leading cause of infectious blindness in the world, predominantly affecting low-income individuals, and women more than men. It’s most common in Africa, with Ethiopia being the most affected country.

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.

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.

Q: How would you summarize your study for a lay audience?

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

Q: What question were you investigating and how did you approach answering it? 

We were evaluating whether fluorometholone 0.1% suspension given just before surgery and postoperatively for 4 weeks would reduce the risk of recurrence of postoperative TT.

Our study, which was supported by the National Eye Institute of the NIH, 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, our research team would often travel on motorcycles—or even walk—to the remote sites where surgeries were performed. The study also gave us 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).   

Q: What did you find, and what are the implications of the results? 

Our 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 4 weeks is generally safe. That is an important finding for the use of fluorometholone for other diseases.

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 we accumulated, we plan to conduct additional, secondary analyses. 

Q: What are the next steps? 

It will 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 has 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, our 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.

Authorship: In addition to Kempen, Mass General Brigham authors include Ahlam Awad Mohammed. Additional authors included Aida Abashawl, Sarity Dodson, Wondu Alemayehu, Fangming Jin, Alemu Gemechu, Aemero Abateneh Mengesha, Dereje Adugna Kumsa, Yineng Chen, Kathleen McWilliams, Berhanu Tulu, Genemo Abdela, Alemayehu Megersa, Tolossa Cheru, Gadisa Mohammad, Tony Succar, Vatinee Y Bunya, K Davina Frick, Maureen G Maguire, Matthew J Burton, and Gui-Shuang Ying of the Center for Preventive Ophthalmology and Biostatistics of the University of Pennsylvania, which has the FLAME trial data repository.

Paper cited: Kempen JH, et al. “Evaluation of fluorometholone as adjunctive medical therapy for trachomatous trichiasis surgery (FLAME): a parallel, double-blind, randomised controlled field trial in the Jimma Zone, Ethiopia.” Lancet Global Health. DOI: 10.1016/S2214-109X(25)00493-0

Funding: This study was supported by National Eye Institute (NIH) grants (UG1EY030420 for Chair grant) and (UG1EY030419 for Data Center grant). Additional funding was from the Mass Eye and Ear Global Surgery Program, Sight for Souls and Research to Prevent Blindness. The FLAME Trial received donations of fluorometholone 0.1% suspension brand name FML from Allergan (an AbbVie company; Dublin, Ireland) as the active treatment for the study.