Clinical Efficacy of Topical Hydrocortisone 0.335% (Softacort®) in Patients With Chronic Dry Eye Disease and Associated Ocular Surface Inflammation

Study Overview
=================
Brief Summary
-----------------
Dry eye disease (DED) is a highly prevalent ocular condition and induces a significant burden to the affected patients. Regardless of the underlying etiology, DED is associated with increased inflammation of the entire ocular surface including the adnexa, conjunctiva and cornea. As such, there is evidence from in vitro, animal and clinical studies that this inflammatory response of the ocular surface plays a pathophysiological key role in the development of DED. The Dry Eye Workshop 2007 (DEWS) therefore suggests the use of anti-inflammatory drugs such as corticosteroids, cyclosporine or others when topical lubricants alone are not sufficient. Recently, Softacort® eye drops containing 0.335% hydrocortisone have gained marketing authorization for the treatment of ocular surface inflammation. This formulation offers several advantages that make them potentially interesting for the treatment of DED. First, the formulation is preservative-free, which is of special importance in patients with DED, since it has been shown that preservatives are detrimental for the ocular surface. Further, hydrocortisone has the advantage that in comparison to other glucocorticoid derivatives, it features poor solubility. This means that corneal penetration is low, which is a desired effect in the treatment of ocular surface inflammation. Because of the poor penetration through thecornea, elevation of intraocular pressure and cataract formation, which are common side effect of corticosteroid treatment, have not been observed with Softacort® to date, also favoring the use of this agent in DED. The aim of the present study is to investigate whether treatment with Softacort® improves ocular surface inflammation as well as clinical signs and symptoms associated with DED in patients who are already taking topical lubricants for at least three months.

Official Title
-----------------
Clinical Efficacy of Topical Hydrocortisone 0.335% (Softacort®) in Patients With Chronic Dry Eye Disease and Associated Ocular Surface Inflammation

Conditions
-----------------
Dry Eye

Intervention / Treatment
-----------------
* Drug: Softacort


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Age ≥ 18 years Normal ophthalmic findings except dry eye disease Ametropy ≤ 6 diopters Chronic dry eye defined as longer than six months since diagnosis OSDI ≥ 22 Conjunctival Hyperemia ≥ Grade 3 (Efron Scale) Current use of topical lubricants since at least 3 months Exclusion criteria: Best far corrected visual acuity < 1/10 Severe Dry Eye associated with: Eyelid malposition Sjogren Syndrome Steven Johnson Syndrome Corneal dystrophy Ocular neoplasia Filamentous keratitis Corneal neovascularisation Orbital radiotherapy History of any of the following within last 3 months: Systemic treatment of dry eye Systemic treatment of MGD Isotretinoide, Cyclosporine, Tacrolimus, Siromilus, Pimecrolimus Punctual plugs Anti-glaucoma treatment History of any of the following within previous six months: ocular trauma ocular infection, ocular allergy History of any of the following within last 12 months: inflammatory corneal ulcer Herpetic eye infection or uveitis Ocular surgery History of IOP increase caused by systemic or topical treatment with corticosteroids IOP > 22mmHg Glaucoma in the medical history Known hypersensitivity to any of the components of the IMP under investigation or other study medication Allergic rhinitis; active or susceptible to reactivation during the study Pregnant or breast-feeding woman. Woman of childbearing potential (neither menopausal, nor hysterectomized, nor sterilized) not using effective contraception (oral contraceptives, intrauterine device, contraceptive implant or condoms) Inability of patient to understand the investigation procedures and thus inability to give valid, informed consent. Non-compliant patient (e.g. not willing to attend the follow-up visits, way of life interfering with compliance) Participation in another clinical study or clinical investigation at the same time as the present investigation Participation to the present clinical investigation during the exclusion period of another clinical study Patient already included once in this clinical investigation Patient under guardianship

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: intense<br>Patients have been randomized to receive Softacort eye drops for 12 days 4 times daily followed by 2 days twice daily treatment resulting in a total time of 14 days | Drug: Softacort<br>* Group 1: 4 times daily for the first 12 days of the treatment period and then 2 times daily for 2 additional days Group 2: 3 times daily for the first 8 days of the treatment period and then 2 times daily for 3 additional days<br>|
| Experimental: standard<br>Patients have been randomized to receive Softacort eye drops for 8 days 3 times daily followed by 3 days twice daily treatment resulting in a treatment time of 11 days total | Drug: Softacort<br>* Group 1: 4 times daily for the first 12 days of the treatment period and then 2 times daily for 2 additional days Group 2: 3 times daily for the first 8 days of the treatment period and then 2 times daily for 3 additional days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conjunctival hyperemia | Conjunctival hyperemia will be graded according to the Efron Scale: 0=none, 1=trace, 2 = mild, 3 = moderate, 4 = severe | 5 minutes |