The Effects of Cyclosporin A in a Low Humidity Environment, on the Ocular Surface

Study Overview
=================
Brief Summary
-----------------
This study will test that hypothesis that topical administration of the FDA approved immunomodulatory agent cyclosporin A emulsion will minimize irritation and ocular surface disease that results from a short term low humidity environmental stress

Detailed Description
-----------------
This is a pilot study designed to evaluate the effect of two conventional dry eye therapies, artificial tears to hydrate and cyclosporine A as an anti-inflammatory, on the irritation symptoms and ocular surface disease of dry eye patients who will be exposed to a low humidity environment for 90 minutes. Patients with dry eye will be enrolled in this study and complete a validated symptom questionnaire and then undergo a complete ocular surface and tear examination to characterize their disease. Enrolled subjects will be exposed to a low humidity environment at the initial evaluation prior to any treatment and will be exposed to a low humidity environment for a second time. They will be randomized to receive either artificial tears or 0.05% cyclosporine A emulsion drop four times a day for 6 weeks.

Official Title
-----------------
The Effects of Cyclosporin A Emulsion, (Restasis), on the Ocular Surface in Response to Low Humidity Environment in Patients With Dry Eye

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

Intervention / Treatment
-----------------
* Drug: Cyclosporin 0.05% emulsion
* Drug: Endura, Refresh artificial tears


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signature on the written informed consent form Patient willingness and ability to return for all visits during the study Rapid tear film break up time of seven seconds or less in at least one eye AND Both cornea fluorescein staining score greater than or equal to 3 and conjunctival lissamine green staining greater than or equal to 3 in at least one eye Ocular Surface Disease Index Symptom Severity score of twenty or greater Tear meniscus height less than or equal to 230um Intact corneal sensitivity Willingness to discontinue use of any current dry eye treatment (except artificial tears) for four weeks prior to enrollment, and during the course of the study Exclusion Criteria: Compromised cognitive ability which may be expected to interfere with study compliance Uncontrolled or poorly controlled diabetes or heart or pulmonary disease that could, in the judgment of the investigator, jeopardize subject safety or interfere with the interpretation of the results of the study Known hypersensitivity to any components of the artificial tears or cyclosporin A eye drops Anticipated contact lens wear during the study History of corneal transplant Active ocular infection, uveitis or non-KCS related inflammation History of cataract surgery within 3 months prior to enrollment History of pterygium removal within 6 months prior to enrollment Reduced corneal sensitivity Initiation, discontinuation or change in dosage of hormone replacement therapy (HRT), fish oil, evening primrose, flaxseed, or black current seed oil supplements, antihistamines, cholinergic agents, beta-blocking agents, tricyclic or SSRI antidepressants, phenothiazines, or topical or systemic acne rosacea medications in two months prior to enrollment, or anticipated change in dosage during course of study Topical ophthalmic medications within prior 4 weeks, or anticipated use of same during the study (except artificial tears) Occlusion of the lacrimal puncta either surgically or with temporary collagen punctal plugs within three months prior to study, or anticipated use of same during study

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyclosporin 0.05% emulsion<br>used in the eye 4 times a day | Drug: Cyclosporin 0.05% emulsion<br>* Topical therapy for dry eye<br>* Other names: Dry Eyes;|
| Active Comparator: Endura Refresh, Artificial Tears<br>Over the Counter artificial tears used in the eye 4 times a day | Drug: Endura, Refresh artificial tears<br>* Over the counter therapy for dry eye, used 4 times a day<br>* Other names: Artificial Tears;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corneal Fluorescein Staining | The mean difference in corneal staining using the adjusted CCLR global staining score before and after the environmental challenge at visits baseline and Visit 3/Day 42 when patients were subjected to a 90-minute low humidity stress. Corneal fluorescein staining was graded 0-100 in 5 zones on the cornea. The scores ranged from 0 (minimum) to 500 (maximum). A higher score indicates there was greater cornea disease induced by the low humidity stress on Day 42 | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eye Irritation Symptoms | The mean difference in subject's scoring of eye irritation symptoms using a VAS (visual analog scale) questionnaire before and after the environmental challenge after treatment at Visit 3/Day 42 when patients were subjected to a 90-minute low humidity stress. Symptoms were graded on a 4 question VAS 0-5 for each question, with scores summed for all questions for a total score that ranges from 0 (minimum) to 20 (maximum) for the pre and post challenge questionnaires. The outcome measure is the difference in the post to pre total score ranging from -20 (maximum improvement) to 20 (maximum worsening). A minus difference indicated the subject had lower irritation symptoms following the lower humidity challenge, while a positive difference indicated the subject had greater irritation following the low humidity challenge on Day 42. | 6 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Dry eye, environmental stress, artificial tears, cyclosporin, Restasis