Clinical trial NCT02120079: The Utility of IVCM to Assess Cellular Response and Efficacy of Long-term Topical Steroid Treatment in Patients With DED
Official title: The Utility of in Vivo Confocal Microscopy (IVCM) to Assess Cellular Response and Efficacy of Long-term Topical Steroid Treatment in Patients With Dry Eye Disease (DED)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Dry Eye Disease
Keywords: Dry Eye
Lead sponsor: Tufts Medical Center
Sponsor class: OTHER
First posted: 2014-04-22
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This research study is looking to see if in vivo confocal microscopy (IVCM) imaging can be used to confirm clinical findings (which are noted by the doctor during an eye exam) and measure the immune response to the inflammation in the subject's cornea (the front part of the eyeball).

Additionally, this study is trying to determine the effectiveness of two eye-drops, Lotemax and artificial tears, in treating the inflammation associated with DED by measuring changes in immune cells with IVCM imaging. The subject will be treated with either Lotemax (loteprednol) or artificial tears (a lubricating eye drop with no medication). Lotemax is an FDA-approved steroid eye-drop that is often used to treat inflammation associated with DED. Artificial tears are approved by the FDA for treatment of dryness associated with DED.

Thus, this study is designed to determine the effects of the administration of a topical steroid, Lotemax, over a treatment period of 6 weeks, using novel methods of detecting efficacy. In order to achieve the aforementioned goal, subjects will be prospectively randomized to one of two treatment arms - Lotemax or artificial tear. Both groups will follow the same study schedule.

Detailed description: IVCM is a non-invasive imaging technique that images the cornea at a cellular level with 800x magnification, using a scanning laser. The laser is used to map the cornea, and will not damage or harm the subject's eye. Studies have shown that IVCM can be used to study cells and nerves within the cornea, providing a better understanding of how the cornea reacts to irritants. IVCM has recently been used by the investigator to assess the extent of eye inflammation in cases of dry eye patients.

Current steroid therapy in dry eye disease (DED) is comprised of a 2 week duration of pulse therapy, administered twice daily (to avoid adverse effects associated with long-term steroid use). This time frame is often too short to meaningfully resolve the inflammation associated with DED. DED often occurs when there is a decrease in the eye's tear production or if there is an increase in the evaporation of the tear film (a thin layer of tears that keep the eye moist). Eye irritation and inflammation (swelling) is often associated with DED because the surface of the eye is unable to maintain a normal level of moisture.

Eligibility criteria: Inclusion Criteria:

* Age 18-89 years.
* Willing and able to provide written informed consent.
* Willing and able to comply with study assessments for the full duration of the study.
* In good stable overall health.
* Corneal dendritiform cell count by confocal microscopy of \>=75/mm2 (13 immune cells per image)
* Diagnosis of dry eye disease based on the followings:
* Symptoms of dry eye disease such as foreign body sensation, burning, stinging, light sensitivity for at least 6 months.
* Two or more of the following objective signs:
* Schirmer test with anesthesia \<10 mm at 5 minutes \[mean Schirmer between eyes.
* Tear break-up time (TBUT) of \<10 seconds.
* Corneal fluorescein staining of 4 (NEI grading scheme, 0-15) in at least one eye
* Lissamine green staining of the nasal and temporal conjunctiva (NEI grading scheme, 0-18) in at least one eye

Exclusion Criteria:

* Central corneal subbasal dendritic cell count by in vivo confocal microscopy of \<75/mm2 in both eyes
* Active ocular allergies
* Active allergies to steroids, aminoglycosides, or benzalkonium chloride (BAK)
* History of contact lens wear within 3 months before enrollment.
* Intraocular surgery or ocular laser surgery within 3 months before enrollment.
* History of ocular infection within 3 months before enrollment.
* History of topical (for ophthalmic use) or systemic steroid treatment (Loteprednol (other than Lotemax suspension used in our study), Difluprednate, Fluorometholone, Prednisolone, Dexamethasone, Triamcinolone, Rimexolone, Medrysone) within 1 month before enrollment. In case of topical ophthalmic steroid use, a wash-out period of 1 month is required.
* History of increased intraocular pressure after using topical steroids (steroid responsive)
* Change in systemic immunosuppression medication in the past 3 months.
* History of any change in the frequency of topical cyclosporine or oral tetracycline compounds (tetracycline, doxycycline, and minocycline) within 1 month before enrollment.
* Any condition (including language barrier) that precludes subject's ability to comply with study requirements including completion of study.

Primary outcomes:
measure: IVCM for Density of Corneal Immune Dendritiform Cells
timeFrame: 2 Weeks
measure: IVCM for Density of Corneal Immune Dendritiform Cells
timeFrame: 6 Weeks
measure: IVCM for Corneal Immune Dendritiform Cell (DC) Morphology
timeFrame: 2 Weeks
measure: IVCM for Corneal Immune Dendritiform Cell (DC) Morphology
timeFrame: 6 Weeks
Secondary outcomes:
measure: Ocular Signs: Corneal Epitheliopathy
timeFrame: 2 Weeks
measure: Ocular Signs: Corneal Epitheliopathy
timeFrame: 6 Weeks
measure: Ocular Signs: Conjunctival Epitheliopathy
timeFrame: 2 Weeks
measure: Ocular Signs: Conjunctival Epitheliopathy
timeFrame: 6 Weeks
measure: Ocular Symptoms: Ocular Surface Disease Index (OSDI) Questionnaire
timeFrame: 2 Weeks
measure: Ocular Symptoms: Ocular Surface Disease Index (OSDI) Questionnaire
timeFrame: 6 Weeks
measure: Ocular Signs: Intraocular Pressure (IOP) by Measure of Applanation Tonometry
timeFrame: 2 Weeks
measure: Ocular Signs: Intraocular Pressure (IOP) by Measure of Applanation Tonometry
timeFrame: 6 Weeks
measure: Ocular Signs: Tear Break Up Time (TBUT)
timeFrame: 2 Weeks
measure: Ocular Signs: Tear Break Up Time (TBUT)
timeFrame: 6 Weeks
measure: Ocular Signs: Schirmer's Test With Anesthesia
timeFrame: 2 Weeks
measure: Ocular Signs: Schirmer's Test With Anesthesia
timeFrame: 6 Weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
Study officials:
affiliation: Tufts Medical Center
name: Pedram Hamrah, MD
role: PRINCIPAL_INVESTIGATOR
References: