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: 10443803
• 负责人: JOHN H KEMPEN
• 金额: $ 66.99万
• 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/10443803
• 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; Poverty; Poverty Areas; 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.

沙眼是世界上导致失明的主要传染病，主要影响#年最贫穷的人。 流行区和女性多于男性。沙眼性倒睫(TT)是一种慢性 沙眼引起的瘢痕形成，是导致沙眼失明的关键机制。因为这个原因， TT的大规模矫正眼皮手术治疗是一项核心的全球规划战略。目前，有 在全球开展这种手术的伟大方案活动，这提供了极大的希望 减少这一古老灾祸造成的视力损害，包括失明。不幸的是，TT术后复发 手术(术后TT)很常见，可能发生在超过20%的情况下，手术是由 根据世界卫生组织(WHO)建议培训的综合眼科护理人员外科医生 在程序化的背景下。以20%的数字和公布的320万人需要TT的估计为例 手术后，将产生约64万例术后TT。术后TT难以控制 治疗；世卫组织建议在再次手术时转诊至熟悉该问题的眼科医生 需要的。然而，这种眼科医生服务在偏远、贫困地区很少。 受沙眼的影响，使绝大多数患者术后TT处于高危状态 有失明和疼痛的风险。减少术后TT发生率的实用策略有可能 减少沙眼引起的低视力和失明。因为围手术期局部使用的皮质类固醇 有效地限制了各种眼科手术的术后炎症和疤痕形成，我们的小组 探讨0.1%氟米松滴眼液作为围手术期辅助治疗的安全性和可能的益处 在一项初步随机试验中，将三种候选剂量与安慰剂进行比较，共154只眼/上眼 154例沙眼患者的眼睑情况。0.1%氟米松可用于局部眼表的治疗 炎症，但眼内效果差，预计在无眼内时具有安全优势 效果是想要的。它也是一种可广泛获得的低成本仿制药，我们预计使用它是可行的 在计划性的背景下。我们的初步研究发现，大约三分之一的TT复发减少 三个积极治疗组与安慰剂治疗眼和对侧未治疗眼进行比较， 最小的安全问题。确认或反驳0.1%氟米隆滴眼液是否辅助性治疗 将是一种值得广泛采用的编程有用的策略，我们建议进行一项全面的 随机现场试验比较0.1%氟米松滴眼液每日两次的疗效和安全性。 安慰剂作为TT手术的辅助药物治疗。临床试验结果的成本-效果分析将 指导治疗方案的价值。这项研究(N=2254名患者)被提供了检测减少的动力 在术后TT从20%到15%，效果阈值对应于大约16万例减少 全球TT复发，失明风险和慢性疼痛相应减少。