Fluorometholone as Adjunctive Therapy for Trachomatous Trichiasis Surgery

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Trachoma, the leading infectious cause of blindness in the world, mainly affects the poorest of the poor in endemic areas and females more than males. Trachomatous trichiasis (TT) is a complication of the chronic trachoma-induced scarring, and is a key mechanism leading to blindness from trachoma. For this reason, mass corrective eyelid surgical treatment of TT is a core global programmatic strategy. Presently, there is great programmatic activity globally in carrying out such surgery, which provides the promise of greatly reducing visual impairment including blindness from this ancient scourge. Unfortunately, recurrence of TT after surgery (postoperative TT) is common, probably occurring in over 20% of cases when surgery is performed by integrated eye care worker surgeons trained according to World Health Organization (WHO) recommendations in the programmatic setting. Taking the 20% figure, and the published estimate that 3.2 million need TT surgery, approximately 640,000 cases of postoperative TT will be generated. Postoperative TT is difficult to treat; the WHO recommends referral to an ophthalmologist familiar with the problem when reoperation is needed. However, such ophthalmologist services are seldom available in the remote, impoverished regions affected by trachoma, leaving the large majority of patients with postoperative TT in the predicament of high risk of blindness and pain. Practical strategies to reduce the incidence of postoperative TT hold the potential to reduce low vision and blindness arising from trachoma. Because perioperative topical corticosteroids are effective in limiting postoperative inflammation and scarring for a wide range of ophthalmic surgeries, our group explored the safety and possible benefits of fluorometholone 0.1% eyedrops as ancillary perioperative therapy in a preliminary randomized trial of three candidate doses in comparison with placebo in 154 eyes/upper eyelids of 154 patients with trachoma. Fluorometholone 0.1% is useful for treating local ocular surface inflammation but has poor intraocular effect, which is expected to give a safety advantage when no intraocular effect is wanted. It also is a widely available, low-cost generic drug, which we expect would be feasible to use in a programmatic context. Our preliminary study found an approximate one-third reduction in TT recurrence in the three active treatment groups compared with both placebo-treated eyes and contralateral untreated eyes, with minimal safety issues. To confirm or refute whether adjunctive fluorometholone 0.1% eyedrop treatment would be a programmatically useful strategy worthy of widespread adoption, we propose to conduct a full-scale randomized field trial comparing the efficacy and safety of fluorometholone 0.1% eyedrops twice daily vs. placebo as adjunctive medical therapy for TT surgery. Cost-effectiveness analysis of clinical trial results will guide programs as to the value of the treatment. The study (N=2254 patients) is powered to detect a reduction in postoperative TT from 20% to 15%, an effect threshold corresponding to roughly 160,000 fewer cases of recurrent TT globally with corresponding reductions in blindness risk and chronic pain.