Clinical trial NCT01775540: Systane Ultra Versus Maxidex Versus Saline
Official title: Study to Evaluate the Ocular Surface Healing Action of the Artificial Tear Systane ULTRA Using Both Positive (Maxidex) and Negative (Saline Solution) Controls
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dry Eye Disease
Keywords: Dry eye
Artificial tears
Ocular surface inflammation
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: Alcon Research
First posted: 2013-01-25
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was to evaluate the healing action on the eye surface of the artificial tear Systane® ULTRA as compared to two other eyedrops: Maxidex and Saline solution. Dry eye disease leads to inflammation of the eye surface and treating dry eyes with artificial tears may lead to reduction in this inflammation and improvement of symptoms and signs.

Detailed description: For all patients who present to the office with a history of dry eyes:

1. Consent forms will be obtained from every patient. Informed consent will be discussed with the patient in detail. Every topic will be addressed separately. All risks, benefits, and alternatives will be discussed. Patient will be allowed to ask questions, and all questions will be answered. The assessment will be made after that conversation, whether or not the patient understood the consent as described above. Each subject will be allowed as much time as needed to review and sign the consent forms.
2. All patients will be asked to fill out the Ocular Surface Discomfort Index (OSDI) questionnaire to ensure they meet the inclusion criteria. If patients score meets eligibility requirements a general and ocular history will be taken. (Time: 10 min)
3. A pregnancy test will be given to all female subjects of child bearing age. A standard eye exam will be performed to rule out any other ocular pathology besides refractive error. This allows for confirmation that all study subjects have dry eye disease. Topical fluorescein and lissamine dye will be used to record staining on the cornea and conjunctiva of subjects as well as the tear film break-up time (TFBUT). Both of these dyes are used as standard-of-care in eye exams around the country. TFBUT will first be determined through application of sodium fluorescein onto the eye using DET strip. Following triplicate evaluation of TFBUT in each eye, ocular staining will be determined with liquid fluorescein and lissamine dyes administered in liquid form. (Time 15 min).
4. Patients will be given Alcon questionnaires to fill out, inquiring about past treatments, daily symptoms and distress associated with their dry eye disease. (Time:15 minutes) This also serves as a waiting period for some of the dye to wash out.
5. Using a graduated disposable 5 µl microcapillary tube (Wiretol-Micropipettes, Drummond Scientific Co., Broomall, PA, USA) up to 5 µl of tears / eye will be collected from the inferior temporal tear meniscus of each participant, without corneal anesthesia, taking care to ensure that the lid margin and corneal surface were not touched. A maximum of 5 minutes will be allowed per eye for collection of minimal 5 uL of tear. Tears will be immediately dispensed into pre-labeled Eppendorf tubes and placed on dry ice until transferred to -80oC for storage. (Time: 10 minutes)
6. A technique known as Impression Cytology (IC) will be used to isolate epithelial cells from the conjunctiva. Anesthetic drops will be administered to each eye before the procedure. Blunted forceps are used to gently press a piece of filter paper against the patient's conjunctiva. The paper is gently lifted off, and sent to the Mount Sinai Laboratory for analyses. (Estimated collection time: 15 minutes). A total of 6 pieces per patient (3 pieces per eye) will be collected on each scheduled visit. For HLA-DR analysis, 2 pieces from each eye will be held at room temperature in a vial containing fixative until assay. The remaining 1 piece from each eye will be pooled together in one vial for RT-PCR assays in the following order: (1) immediately merged into a pre-labeled Eppendorf tube with 600 µL of TriZol Reagent; (2) Vortex for 30 seconds; (3) sealed with Saran Wrap; (4) transfer to -80C for storage until assay.
7. Measurement of Intraocular pressure using Tonopen.
8. As a part of the substudy we intend to treat patients with Systane ULTRA®, Maxidex, (both of which are FDA approved ophthalmic solutions), or the saline solution placebo. Subjects will be assigned to one of the three groups as per randomization sequence and the corresponding eye drop will be dispensed.
9. The patient's response to treatment will be assessed after approximately 4 weeks (+/- 5 days) using the same diagnostic tests in order to assess the sensitivity of these diagnostic tests to detect the response to medical treatment of dry eye disease. In addition to baseline and 4 week visits, safety evaluations will be performed at a 2 week (+/- 5 days) visit. All the procedures done during the baseline visit will be repeated except pregnancy test, tear collection and impression cytology.

Eligibility criteria: Inclusion Criteria:

* A score of at least 15 on the Ocular Surface Discomfort Index (OSDI) symptom questionnaire.
* Moderate vital staining, fluorescein (for corneal evaluation, 3-15 on the NEI scale) OR lissamine (for conjunctival evaluation, score of 2-6; temporal and nasal areas, each graded 0-3).
* Willingness to use study drugs 4 times per day in both eyes.
* Willingness to discontinue use of other artificial tear products.
* Patient must provide written informed consent
* Patient must understand the scope of the study including completion of worksheet and be willing to follow instructions and return for all required study visits
* An intraocular pressure less than or equal to 22 mmHg in both eyes

Exclusion Criteria:

* Contact Lens wearers
* Pregnant and/or lactating women
* Those with moderate to severe Meibomian Gland Disease i.e. plugging of 3 or more glands and/or pasty secretion from 3 or more glands or presence of obstructed glands out of a total of 10 glands evaluated in the central portion of the lower lid.
* Uncontrolled systemic or ocular disease
* Dry eye due to seasonal allergic conjunctivitis, contact lens related conjunctivitis or other acute or seasonal diagnosis.
* Are monocular and/or legally blind
* Had ocular surgery or trauma within last six months
* Participation in an ophthalmic drug or device research study within 30 days prior to entry in this study
* Current use of any eye drops other than artificial tears
* Use of Restasis within three months prior to entry in this study

Primary outcomes:
measure: OSDI score
timeFrame: at Baseline
measure: OSDI score
timeFrame: visit 2 (at 2 weeks)
measure: OSDI score
timeFrame: at visit 3 (at 4 weeks)
Secondary outcomes:
measure: Tear Film break up time
timeFrame: at Baseline
measure: Tear Film break up time
timeFrame: at visit 2 (at 2 weeks)
measure: Tear Film break up time
timeFrame: at visit 3 (at 4 weeks)
measure: Corneal Staining
timeFrame: at Baseline
measure: Corneal Staining
timeFrame: at visit 2 (at 2 weeks)
measure: Corneal Staining
timeFrame: at visit 3 (at 4 weeks)
measure: Conjunctival Staining
timeFrame: at Baseline
measure: Conjunctival Staining
timeFrame: at visit 2 (at 2 weeks)
measure: Conjunctival Staining
timeFrame: at visit 3 (at 4 weeks)
measure: Best corrected visual acuity
timeFrame: at Baseline
measure: Best corrected visual acuity
timeFrame: at visit 2 (at 2 weeks)
measure: Best corrected visual acuity
timeFrame: at visit 3 (at 4 weeks)
measure: Tear Cytokines
timeFrame: At baseline
measure: Tear Cytokines
timeFrame: At visit 3 (at 4 weeks)
measure: mRNA for HLA-DR
timeFrame: At baseline
measure: mRNA for HLA-DR
timeFrame: At visit 3 (at 4 weeks)
measure: HLA-DR expression
timeFrame: At baseline
measure: HLA-DR expression
timeFrame: At visit 3 (at 4 weeks)
measure: IDEEL questionnaire
timeFrame: At baseline
measure: IDEEL questionnaire
timeFrame: At visit 2 (at 2 weeks)
measure: IDEEL questionnaire
timeFrame: At visit 3 (at 4 weeks)
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Penny Asbell, MD, MBA, FACS
role: PRINCIPAL_INVESTIGATOR
References: