A Phase II, Multicenter, Randomized, Placebo-Controlled, Double-Masked Trial of a Topical Estradiol Ophthalmic Formulation in Postmenopausal Women with Moderate-to-Severe Dry Eye Disease.

INTRODUCTION

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

CLINICAL TRIAL REGISTRATION

Clinicaltrials.gov registry NCT03821415.