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.

沙眼是世界上导致失明的主要传染性疾病，主要影响世界上最贫穷的人 流行地区女性多于男性。沙眼性倒睫（TT）是一种慢性沙眼倒睫的并发症。 沙眼引起的疤痕，是导致沙眼失明的关键机制。为此原因， TT 的大规模矫正眼睑手术治疗是一项核心的全球规划策略。目前，有 在全球范围内进行此类手术的伟大计划活动，这提供了极大的希望 减少视力障碍，包括这种古老祸害造成的失明。不幸的是，TT 复发后 手术（术后 TT）很常见，可能在 20% 以上的病例中发生 根据世界卫生组织 (WHO) 建议接受培训的综合眼保健工作者外科医生 在程序设置中。以 20% 的数字为例，公布的估计有 320 万人需要 TT 手术后，大约会产生64万例术后TT。术后TT很难 对待;世界卫生组织建议在再次手术时转诊给熟悉问题的眼科医生 需要。然而，这样的眼科服务在偏远贫困地区却很少见 受沙眼的影响，使得绝大多数术后TT患者处于高风险的困境 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。因为围手术期局部皮质类固醇 我们的团队可有效限制各种眼科手术的术后炎症和疤痕 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 在一项初步随机试验中，对 154 只眼睛/上肢进行了三种候选剂量与安慰剂的比较 154 名沙眼患者的眼睑。 0.1% 氟米龙可用于治疗局部眼表 炎症但眼内效果差，预计在无眼内注射时具有安全性优势 想要效果。它也是一种广泛使用的低成本仿制药，我们预计使用它是可行的 在程序化环境中。我们的初步研究发现，TT 复发率大约减少了三分之一 三个积极治疗组与安慰剂治疗的眼睛和对侧未治疗的眼睛进行比较， 安全问题最小化。确认或反驳是否辅助0.1%氟米龙滴眼液治疗 将是一个值得广泛采用的、有计划性的、有用的战略，我们建议进行全面的 随机现场试验，比较 0.1% 氟米龙滴眼液（每日两次）与 0.1% 氟米龙滴眼液（每日两次）的功效和安全性。 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益分析将 关于治疗价值的指导计划。该研究（N = 2254 名患者）有能力检测到减少 术后 TT 从 20% 降至 15%，效果阈值相当于减少了约 160,000 例 全球复发性 TT 相应降低失明风险和慢性疼痛。