Fluorometholone as Adjunctive Therapy for Trachomatous Trichiasis Surgery

氟米龙作为沙眼倒睫手术的辅助治疗

• 批准号: 10018022
• 负责人: JOHN H KEMPEN
• 金额: $ 107.15万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10018022
• 关键词: Adoption; Adrenal Cortex Hormones; Affect; Anti-Inflammatory Agents; Area; Back; Blindness; Caring; Chronic; Cicatrix; Complication; Contralateral; Cost Effectiveness Analysis; Country; Data; Developing Countries; Dose; Drops; Ethiopia; Eye; Eyedrops; Eyelash; Eyelid structure; Female; Fluorometholone; Generic Drugs; Incidence; Individual; Inflammation; Location; Medical; Modeling; Newly Diagnosed; Operative Surgical Procedures; Ophthalmologist; Outcome; Pain; Pathogenesis; Pathway interactions; Patients; Peer Review; Perioperative; Placebos; Play; Postoperative Period; Prevalence; Publishing; Randomized; Recommendation; Recurrence; Regimen; Relapse; Repeat Surgery; Reporting; Resources; Risk; Role; Rotation; Rural; Safety; Savings; Scourge; Services; Surgeon; Time; Topical Corticosteroids; Trachoma; Training; Treatment Effectiveness; Vision; Visual impairment; Woman; World Health Organization; active method; base; chronic pain; clinical trial analysis; comparative efficacy; cost; cost effective; cost effectiveness; dosage; health economics; high risk; incremental cost-effectiveness; male; ocular pain; ocular surface; prevent; programs; randomized trial; treatment group; trial comparing; uptake

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.

沙眼是世界上最主要的致盲传染病，主要影响世界上最贫穷的人， 女性多于男性。沙眼性倒睫（TT）是一种慢性 沙眼引起的疤痕，并且是导致沙眼失明的关键机制。基于这个理由， 大规模眼睑矫正手术治疗TT是一项核心的全球方案战略。目前， 在全球范围内开展这种手术的伟大计划活动，这为极大地 减少视力损害，包括失明，从这个古老的祸害。不幸的是，TT复发后， 手术（术后TT）是常见的，可能发生在超过20%的情况下，当手术是由 根据世界卫生组织（WHO）的建议培训综合眼科护理工作者外科医生 in the programmatic程序setting设置.以20%的数字和公布的估计数字320万需要TT 手术后将产生约64万例术后TT。术后TT难以 治疗;世界卫生组织建议转诊到眼科医生熟悉的问题时，再次手术是 needed.然而，在偏远，贫困地区很少有这样的眼科医生服务 受到沙眼的影响，使绝大多数术后TT患者处于高的困境 失明和疼痛的风险。降低术后TT发生率的实用策略具有以下潜力： 减少沙眼引起的视力低下和失明。因为围手术期外用皮质类固醇 有效地限制了广泛的眼科手术的术后炎症和瘢痕形成，我们的小组 探讨了0.1%氟米龙滴眼液作为围手术期辅助治疗的安全性和可能的益处 在154只眼睛/上方的三种候选剂量与安慰剂相比的初步随机试验中， 对154例沙眼患者的眼睑进行了观察。0.1%氟米龙可用于治疗局部眼表 炎症，但具有差的眼内效果，这预期在没有眼内刺激时提供安全性优势。 效果是想要的。它也是一种广泛可用的低成本仿制药，我们预计使用它是可行的 在方案背景下。我们的初步研究发现TT复发率降低了约三分之一， 三个活性治疗组与安慰剂治疗的眼睛和对侧未治疗的眼睛相比， 最小的安全问题。确认或反驳是否为0.1%氟米龙滴眼液治疗 将是一个值得广泛采用的编程有用的战略，我们建议进行全面的 一项随机田间试验，比较了0.1%氟米龙滴眼液每日两次与 安慰剂作为TT手术的连续药物治疗。临床试验结果的成本效益分析将 指导方案的治疗价值。该研究（N=2254例患者）有把握度检测到 在术后TT从20%到15%，效应阈值对应于大约160，000例 在全球范围内，复发性TT的失明风险和慢性疼痛相应降低。