Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Óbudai Egészségügyi Centrum (OEC), Budapest, Hungary.
Adv Ther. 2021 Apr;38(4):1975-1986. doi: 10.1007/s12325-021-01680-3. Epub 2021 Mar 12.
Dry eye disease (DED) is a multifactorial disorder of the ocular surface. The current phase II study was performed to assess the safety and dose regimen of a recently developed topical estradiol formulation for the treatment of DED.
A total of 104 postmenopausal women suffering from moderate-to-severe DED were included. Topical 17-β-estradiol-3-phosphate eye drops were administered in three different dosage groups (group 1, 0.05% twice daily; group 2, 0.1% morning, vehicle in the evening; group 3, 0.1% twice daily) and vehicle twice daily as control group for a total period of 3 months. Clinical signs including Schirmer's test and corneal staining were assessed at baseline and at days 14, 30, 60, and 90. Symptoms of DED were measured using the symptom assessment in dry eye (SANDE) test at the same time points. Safety was assessed via frequency of adverse events.
Schirmer's test II wetting distance significantly increased in all four groups from baseline to day 90 without significant difference between groups (group 1, + 5.6 ± 6.7 mm/5 min; group 2, + 3.7 ± 4.2 mm/5 min; group 3, + 4.8 ± 4.5 mm/5 min; group 4, + 4.0 ± 5.3 mm/5 min). Statistical significance versus baseline was reached earlier in the treatment groups versus the control group. Corneal staining was significantly reduced after the 3-month treatment period with no significant difference between treatment groups. Staining of the inferior cornea, however, showed a significantly more pronounced decrease in the highest dose group compared to vehicle (p = 0.0463). Symptoms score as assessed with the SANDE test decreased at the end of the treatment period in all four groups. Estradiol eye drops showed a favorable safety profile.
Our results show that both estradiol eye drops and vehicle are safe and reduce signs and symptoms in postmenopausal women with moderate-to-severe DED. Although the study failed to reach the primary outcome to demonstrate a significant difference between the estradiol eye drops and vehicle in Schirmer's test, improvement occurred earlier in the active groups compared to the control group. The data of the current study will serve as a basis for a larger phase III study to establish a potential therapeutic effect of topical estradiol eye drops.
Clinicaltrials.gov registry NCT03821415.
干眼（DED）是一种眼表多因素疾病。本 II 期研究旨在评估一种新开发的局部雌二醇制剂治疗 DED 的安全性和剂量方案。
共纳入 104 例绝经后中重度 DED 女性。局部 17-β-雌二醇-3-磷酸滴眼剂分为三组（组 1：0.05%，每日两次；组 2：0.1%，晨用，晚上用载体；组 3：0.1%，每日两次）和每日两次载体作为对照组，共治疗 3 个月。在基线和第 14、30、60 和 90 天评估临床体征，包括 Schirmer 试验和角膜染色。同时在同一时间点使用干眼症状评估（SANDE）测试评估 DED 症状。通过不良事件的频率评估安全性。
从基线到第 90 天，所有四组的 Schirmer 试验 II 湿距均显著增加，组间无显著差异（组 1：+5.6±6.7mm/5min；组 2：+3.7±4.2mm/5min；组 3：+4.8±4.5mm/5min；组 4：+4.0±5.3mm/5min）。与对照组相比，治疗组更早达到与基线相比的统计学意义。3 个月治疗后，角膜染色显著减少，各组间无显著差异。然而，与载体相比，最高剂量组的下角膜染色明显减少（p=0.0463）。SANDE 测试评估的症状评分在治疗期末所有四组均下降。雌二醇滴眼剂具有良好的安全性。
我们的研究结果表明，雌二醇滴眼剂和载体均安全，可减少绝经后中重度 DED 妇女的体征和症状。尽管该研究未能达到显示雌二醇滴眼剂与载体在 Schirmer 试验中存在显著差异的主要终点，但与对照组相比，早期治疗组的改善更早。本研究的数据将为更大规模的 III 期研究奠定基础，以确定局部雌二醇滴眼剂的潜在治疗效果。
Clinicaltrials.gov 注册号 NCT03821415。
