Study shows no benefit of anti-inflammatory therapy in trachomatous trichiasis surgery

Study shows no benefit of anti-inflammatory therapy in trachomatous trichiasis surgery

John Kempen, MD, MPH, PhD, MHS, director of ophthalmology epidemiology at Mass Eye and Ear and Harvard Medical School, is the lead author of an article published inThe Lancet Global Health“Evaluation of fluorometholone as adjunctive medical therapy in trachomatous trichiasis surgery (FLAME): a parallel, double-blind, randomized controlled field trial in Jimma zone, Ethiopia.”

Q: Why is trachoma important?

Trachoma is the leading cause of infectious blindness worldwide and primarily affects low-income people, with women being affected more often than men. It is most common in Africa, with Ethiopia being the most affected country.

Trachoma causes scarring on the surface of the eye, including the inner surface of the eyelids. The latter causes the eyelashes to curl, the cornea to be scratched and lead to blindness due to corneal damage and secondary infections. This leads not only to blindness, but also to constant suffering as the eyelashes constantly scratch the surface of the cornea.

The World Health Organization (WHO) has put in place a plan to try to eliminate blindness from trachoma, including by performing surgery on eyes with inverted upper eyelashes (a condition known as trachomatous trichiasis, or "TT"). Since it is not uncommon for TT surgery to fail, which is difficult to resolve, improving surgical outcomes is very important. The FLAME study is part of an initiative to improve the quality of surgical procedures to better prevent blindness and improve the quality of life of 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 of a preliminary study comparing three doses of a low-risk topical anti-inflammatory treatment called fluorometholone with placebo. In this first trial, the risk of postoperative TT was reduced by about a third in all three groups.

However, as our new study reports, the FLAME trial failed to confirm the promising preliminary results. Given the much larger sample size of FLAME, we are confident in the “negative” results and interpret them to mean that anti-inflammatory therapy is unlikely to advance this field.

Q: What question did you examine and how did you go about answering it?

We investigated whether 0.1% fluorometholone suspension administered immediately before surgery and postoperatively for 4 weeks would reduce the risk of recurrence of postoperative TT.

Our study, supported by the NIH National Eye Institute, was a randomized controlled clinical trial in which more than 2,400 participants received active or placebo treatment (artificial tears). Because this disease affects very disadvantaged people in remote areas, our research team often traveled by motorcycle or even on foot to the remote locations where surgeries were performed. The study also gave us the opportunity to offer free treatment to almost 3,000 people (including those who presented for treatment and did not qualify for or did not consent to enrollment in the study).

Q: What did you find and what implications do the results have?

Our results convincingly demonstrated no difference between treatment with active fluorometholone and placebo, with results almost identical between groups. In terms of safety, the results were also similar, suggesting that taking fluorometholone twice daily for 4 weeks is generally safe. This is an important finding for the use of fluorometholone in other diseases.

The results, together with the negative results of another study, suggest that the use of anti-inflammatory therapy along with all surgery is unlikely to help improve the outcomes of TT surgery. However, due to the extensive data set we have collected, we plan to conduct additional secondary analyses.

Q: What are the next steps?

It is best to shift the focus to other ideas for improving the outcomes of TT surgery, and there are some promising new possibilities. A published secondary analysis of the FLAME trial found that outcomes of either of the two WHO-recommended surgical techniques resulted in approximately 70% fewer recurrent or postoperative TT. This confirmed the results of a previous clinical study showing that postoperative TT is approximately 50% lower with the Posterior Lamellar Tarsal Rotation (PLTR) technique (also known as the Trabut technique) than with the Bilamellar Tarsal Rotation technique.

Furthermore, our group has also demonstrated that refresher training in a structured supportive mentoring context can significantly reduce the risk of postoperative TT.

In general, focusing on quality assurance in TT operations seems to be the key concept to make the results as favorable as possible. General prevention efforts aimed at antibiotics, facial cleansing and environmental improvement also remain very important.

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