Austrian study targets dry eye disease in postmenopausal women
Investigators find that oestradiol drops can ease signs and symptoms for 3 months.
Reviewed by Dr Gerhard Garhöfer.
A novel treatment for dry eye disease (DED) in the form of topical oestradiol can reduce signs and symptoms of DED in postmenopausal women for at least 3 months, according to Dr Gerhard Garhöfer, associate professor at Medical University of Vienna, Department of Clinical Pharmacology, Vienna, Austria. Dr Garhöfer served as lead investigator for a randomised, controlled, parallel-group study of the therapeutic formulation of oestradiol candidate RP101 (Redwood Pharma).
“Sex hormone receptors or oestrogen receptors have been found to be present on the ocular surface in several tissues, such as the conjunctiva, cornea and Meibomian glands,” Dr Garhöfer said. “The pronounced contrast in dry eye prevalence between men and women, especially women who are postmenopausal, points towards an involvement of sex hormones in the disease process. Furthermore, anti-oestrogen treatment seems to disrupt tear production.”
RP101 contains 17-beta-estradiol as the active ingredient and a sterile isotonic thermogelling (IntelliGel) solution as the drug delivery system. This thermosensitive, supramolecular hydrogel becomes a gel at eye temperature, allowing for a long period of residency on the ocular surface and thus permitting sustained drug delivery.
Dr Garhöfer and his co-investigators enrolled 104 patients in the study, with 77 completing the study according to the protocol. Five patients requested withdrawal, 21 withdrew due to adverse events and one withdrew for other reasons.
The study aimed to determine the optimal dosing regimen of RP101 and to evaluate its safety in postmenopausal women with moderate-to-severe DED. The four arms of the study included 0.05% twice daily, 0.1% morning and vehicle (isotonic thermogelling solution) in the evening, 0.1% twice daily and a control group who received the vehicle twice daily. The treatment period was 3 months.
Investigators used Schirmer’s test II and grading of corneal fluorescein staining, taking measurements at baseline and at various points during treatment: Day 14, Day 30, Day 60 and Day 90 (treatment completion). Patients reported outcomes for various DED symptoms via the Symptom Assessment Questionnaire iN Dry Eye (SANDE) and the Visual Analogue Scales (VAS).
Corneal fluorescein staining score significantly decreased during the 3-month treatment period(P < 0.001 vs baseline). Investigators found no significant difference between treatment groups. The staining of the inferior cornea, however, showed a significantly more pronounced reduction in the highest-dose group compared with vehicle (P = 0.0463).
Schirmer’s test II showed an increase in tear production, reaching maximum effect after 90 days of treatment. “Schirmer’s Test II increased significantly after 14 days of treatment in the active groups and after 1 month of treatment in the control group and remained significantly elevated until the end of the study,” Dr Garhöfer explained.
The SANDE symptom score, a frequently used standardised questionnaire for assessing the severity and frequency of dry eye symptoms, showed a decrease at the end of the treatment period in all groups. Moreover, patient-reported outcome via VAS in all four treatment arms showed a decrease in symptoms of DED, such as foreign body sensation; burning/stinging; itching; pain; sticky feeling; redness; and tearing.
The eye drops were well tolerated on the ocular surface and showed a favourable safety profile. “Most treatment-related adverse events were eye-related and mostly mild or moderate,” Dr Garhöfer said. “The most frequent … (more than 5% in at least one treatment group) were blurred vision; eye pain; eye irritation; ocular hyperaemia; eyelid swelling; or foreign body sensation. All these adverse events had resolved at the end of the study.”
According to Dr Garhöfer, at this time therapy data are limited to use in postmenopausal women. “Further studies are needed to investigate whether other target populations would benefit from topical oestrogen treatment.” He added that the next step will be a Phase 3 study, which will be designed based on the data obtained from the Phase 2 study.
“Our data show that all dosages of RP101 were safe and improved signs and symptoms of DED at the end of the observation period,” he said. “We think the topical approach would make the most sense in dry eye patients as it can reach higher levels on the ocular surface while not needing high plasma levels, which would be the case when oestrogen is given systemically.”
Dr Garhöfer did point out, however, that the thermosensitive hydrogel solution that served as a control in the study also had an impact on signs and symptoms of DED. He said that systemic oestrogen is not a preferred option to treat DED in postmenopausal women because it has been linked to serious systemic adverse effects. He concluded, though, that “with a topical formulation, systemic uptake of oestradiol is very low, which limits the risk of systemic side effects.”
