Dry Eye
Conditions
Keywords
Dry eye, environmental stress, artificial tears, cyclosporin, Restasis
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.
Interventions
DRUGCyclosporin 0.05% emulsion
Topical therapy for dry eye
DRUGEndura, Refresh artificial tears
Over the counter therapy for dry eye, used 4 times a day
Sponsors
Allergan
Baylor College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Corneal Fluorescein Staining | 6 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Eye Irritation Symptoms | 6 weeks | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Conjunctival Goblet Cells | 6 weeks | The number of conjunctival goblet cells measured in impression cytology at screening/baseline before and after low humidity exposure at the baseline and Day 42 visits. No (zero) subjects were analyzed because the assay was not performed and data was not collected because the study was terminated due to loss of funding. |
Countries
United States
Participant flow
Recruitment details
Recruitment process occurred at the medical clinic of the primary investigator. Recruitment began July 2014 and ended December 2015.
Pre-assignment details
There were no pre-assignment details.
Participants by arm
| Arm | Count |
|---|---|
| Cyclosporin 0.05% Emulsion used in the eye 4 times a day
Cyclosporin 0.05% emulsion: Topical therapy for dry eye | 2 |
| Endura Refresh, Artificial Tears Over the Counter artificial tears used in the eye 4 times a day
Endura, Refresh artificial tears: Over the counter therapy for dry eye, used 4 times a day | 2 |
| Total | 4 |
Baseline characteristics
| Characteristic | Endura Refresh, Artificial Tears | Cyclosporin 0.05% Emulsion | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 4 Participants |
| Age, Continuous | 58 years STANDARD_DEVIATION 4.2 | 51 years STANDARD_DEVIATION 9.9 | 54.5 years STANDARD_DEVIATION 7.4 |
| Region of Enrollment United States | 2 participants | 2 participants | 4 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 0 / 2 | 0 / 2 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 |
Outcome results
Primary
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
Time frame: 6 weeks
Population: Due to loss of funding, this study was not completed and enrollment ended. Data from only 2 subjects per group was analyzed
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cyclosporin 0.05% Emulsion | Corneal Fluorescein Staining | 21.5 units on a scale | Standard Deviation 13.44 |
| Endura Refresh, Artificial Tears | Corneal Fluorescein Staining | 29 units on a scale | Standard Deviation 15.6 |
Secondary
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.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cyclosporin 0.05% Emulsion | Eye Irritation Symptoms | 1.5 units on a scale | Standard Deviation 2.1 |
| Endura Refresh, Artificial Tears | Eye Irritation Symptoms | 1 units on a scale | Standard Deviation 0 |
Other Pre-specified
Conjunctival Goblet Cells
The number of conjunctival goblet cells measured in impression cytology at screening/baseline before and after low humidity exposure at the baseline and Day 42 visits. No (zero) subjects were analyzed because the assay was not performed and data was not collected because the study was terminated due to loss of funding.
Time frame: 6 weeks