The Utility of IVCM to Assess Cellular Response and Efficacy of Long-term Topical Steroid Treatment in Patients With DED

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)

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.

Study Overview

• Status: Completed
• Conditions: Dry Eye Disease
• Intervention / Treatment: Drug: Lotemax; Diagnostic test: In Vivo Confocal Microscopy (IVCM); Drug: Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears)

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.

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Lotemax; Lotemax (loteprednol etabonate) 0.5% is a prescription-only, preserved ophthalmic suspension supplied by Bausch & Lomb, Inc. Lotemax (loteprednol etabonate) 0.5% has been approved by the FDA for treatment of ocular inflammation with a maximum dosing frequency of 24 drops per eye per day. It is a C-20 ester-based corticosteroid, with a potent anti-inflammatory efficacy, but decreased impact on intraocular pressure (IOP) compared to other corticosteroids, which may increase IOP. The medication will be applied topically to both eyes for 6 weeks with the following regimen: four times a day for 2 weeks, twice daily for 2 weeks, and once daily for 2 weeks.	Drug: Lotemax; Lotemax (loteprednol etabonate) 0.5% will be applied topically to both eyes for 6 weeks with the following regimen: four times a day for 2 weeks, twice daily for 2 weeks, and once daily for 2 weeks.; Other Names: Lotemax (loteprednol etabonate) 0.5%; Diagnostic test: In Vivo Confocal Microscopy (IVCM); In vivo confocal microscopy (IVCM) is a new imaging method, which allows visualization of the corneal structures at the cellular level. With a magnification of 800 times, it makes it possible to detect and quantify changes in the epithelial layers and sub-basal nerve plexus.
Active Comparator: Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears); Soothe Tired Eyes Lubricant Eye Drop (Bausch & Lomb Inc.) is a preserved artificial tear which is used to relieve the dryness of the eye and to prevent further irritation. Its active ingredient is glycerin 1%. The artificial tear will be applied topically to both eyes for 6 weeks with the following regimen: four times a day for 2 weeks, twice daily for 2 weeks, and once daily for 2 weeks.	Diagnostic test: In Vivo Confocal Microscopy (IVCM); In vivo confocal microscopy (IVCM) is a new imaging method, which allows visualization of the corneal structures at the cellular level. With a magnification of 800 times, it makes it possible to detect and quantify changes in the epithelial layers and sub-basal nerve plexus.; Drug: Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears); Soothe Tired Eyes Lubricant Eye Drop will be applied topically to both eyes for 6 weeks with the following regimen: four times a day for 2 weeks, twice daily for 2 weeks, and once daily for 2 weeks.; Other Names: Soothe Tired Eyes Lubricant Eye Drop (Bausch & Lomb Inc.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IVCM for Density of Corneal Immune Dendritiform Cells	Density (in cells/mm2) of Corneal Immune Dendritiform Cells	2 Weeks
IVCM for Density of Corneal Immune Dendritiform Cells	Density (in cells/mm2) of corneal immune dendritiform cells	6 Weeks
IVCM for Corneal Immune Dendritiform Cell (DC) Morphology	Morphology (in cells/mm2) of Corneal Immune Dendritiform Cells	2 Weeks
IVCM for Corneal Immune Dendritiform Cell (DC) Morphology	Morphology (in cells.mm2) of Corneal Immune Dendritiform Cells	6 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ocular Signs: Corneal Epitheliopathy	Corneal Fluorescein Staining Using the National Eye Institute (NEI) Grading Scheme Minimum score-0 Maximum score-15 Higher score means worse outcome	2 Weeks
Ocular Signs: Corneal Epitheliopathy	Corneal Fluorescein Staining Using the National Eye Institute (NEI) Grading Scheme Minimum score-0 Maximum score-15 Higher score means worse outcome	6 Weeks
Ocular Signs: Conjunctival Epitheliopathy	Conjunctival Lissamine Green Staining Using National Eye Institute (NEI) Grading Scheme Minimum score-0 Maximum score-18 Higher score means worse outcome	2 Weeks
Ocular Signs: Conjunctival Epitheliopathy	Conjunctival Lissamine Green Staining Using National Eye Institute (NEI) Grading Scheme Minimum score-0 Maximum score-18 Higher score means worse outcome	6 Weeks
Ocular Symptoms: Ocular Surface Disease Index (OSDI) Questionnaire	Total Score of the Ocular Surface Disease Index (OSDI) Questionnaire Minimum score- 0 Maximum score-100 Higher score means worse outcome	2 Weeks
Ocular Symptoms: Ocular Surface Disease Index (OSDI) Questionnaire	Total Score of the Ocular Surface Disease Index (OSDI) Questionnaire Minimum score- 0 Maximum score-100 Higher score means worse outcome	6 Weeks
Ocular Signs: Intraocular Pressure (IOP) by Measure of Applanation Tonometry	Intraocular Pressure (IOP) will be measured via Applanation and the result will have these units: mmHg	2 Weeks
Ocular Signs: Intraocular Pressure (IOP) by Measure of Applanation Tonometry	Intraocular Pressure (IOP) will be measured via Applanation and the result will have these units: mmHg	6 Weeks
Ocular Signs: Tear Break Up Time (TBUT)	Tear Break Up Time (TBUT) will be recorded in seconds	2 Weeks
Ocular Signs: Tear Break Up Time (TBUT)	Tear Break Up Time (TBUT) will be recorded in seconds	6 Weeks
Ocular Signs: Schirmer's Test With Anesthesia	The Schirmer's Test (performed using Anesthesia) will be measured in mm.	2 Weeks
Ocular Signs: Schirmer's Test With Anesthesia	The Schirmer's Test (performed using Anesthesia) will be measured in mm.	6 Weeks

Collaborators and Investigators

• Sponsor: Tufts Medical Center

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): January 28, 2018

Study Registration Dates

• First Submitted: February 12, 2014
• First Submitted That Met QC Criteria: April 18, 2014
• First Posted (Estimate): April 22, 2014

Study Record Updates

• Last Update Posted (Actual): March 23, 2022
• Last Update Submitted That Met QC Criteria: February 24, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Dry Eye
• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Anti-Allergic Agents; Pharmaceutical Solutions; Loteprednol Etabonate; Ophthalmic Solutions; Lubricant Eye Drops
• Other Study ID Numbers: 13-150H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No