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

Primary Purpose

Dry Eye Disease

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Lotemax
Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears)
In Vivo Confocal Microscopy (IVCM)
Sponsored by
Tufts Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dry Eye Disease focused on measuring Dry Eye

Eligibility Criteria

18 Years - 89 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Tufts Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Lotemax

Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

IVCM for Density of Corneal Immune Dendritiform Cells
Density (in cells/mm2) of Corneal Immune Dendritiform Cells
IVCM for Density of Corneal Immune Dendritiform Cells
Density (in cells/mm2) of corneal immune dendritiform cells
IVCM for Corneal Immune Dendritiform Cell (DC) Morphology
Morphology (in cells/mm2) of Corneal Immune Dendritiform Cells
IVCM for Corneal Immune Dendritiform Cell (DC) Morphology
Morphology (in cells.mm2) of Corneal Immune Dendritiform Cells

Secondary Outcome Measures

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
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
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
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
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
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
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
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
Ocular Signs: Tear Break Up Time (TBUT)
Tear Break Up Time (TBUT) will be recorded in seconds
Ocular Signs: Tear Break Up Time (TBUT)
Tear Break Up Time (TBUT) will be recorded in seconds
Ocular Signs: Schirmer's Test With Anesthesia
The Schirmer's Test (performed using Anesthesia) will be measured in mm.
Ocular Signs: Schirmer's Test With Anesthesia
The Schirmer's Test (performed using Anesthesia) will be measured in mm.

Full Information

First Posted
February 12, 2014
Last Updated
February 24, 2022
Sponsor
Tufts Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT02120079
Brief Title
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

2. Study Status

Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
February 2014 (undefined)
Primary Completion Date
April 2017 (Actual)
Study Completion Date
January 28, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tufts Medical Center

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dry Eye Disease
Keywords
Dry Eye

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
38 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lotemax
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Lotemax
Other Intervention Name(s)
Lotemax (loteprednol etabonate) 0.5%
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears)
Other Intervention Name(s)
Soothe Tired Eyes Lubricant Eye Drop (Bausch & Lomb Inc.)
Intervention Description
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.
Intervention Type
Diagnostic Test
Intervention Name(s)
In Vivo Confocal Microscopy (IVCM)
Intervention Description
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.
Primary Outcome Measure Information:
Title
IVCM for Density of Corneal Immune Dendritiform Cells
Description
Density (in cells/mm2) of Corneal Immune Dendritiform Cells
Time Frame
2 Weeks
Title
IVCM for Density of Corneal Immune Dendritiform Cells
Description
Density (in cells/mm2) of corneal immune dendritiform cells
Time Frame
6 Weeks
Title
IVCM for Corneal Immune Dendritiform Cell (DC) Morphology
Description
Morphology (in cells/mm2) of Corneal Immune Dendritiform Cells
Time Frame
2 Weeks
Title
IVCM for Corneal Immune Dendritiform Cell (DC) Morphology
Description
Morphology (in cells.mm2) of Corneal Immune Dendritiform Cells
Time Frame
6 Weeks
Secondary Outcome Measure Information:
Title
Ocular Signs: Corneal Epitheliopathy
Description
Corneal Fluorescein Staining Using the National Eye Institute (NEI) Grading Scheme Minimum score-0 Maximum score-15 Higher score means worse outcome
Time Frame
2 Weeks
Title
Ocular Signs: Corneal Epitheliopathy
Description
Corneal Fluorescein Staining Using the National Eye Institute (NEI) Grading Scheme Minimum score-0 Maximum score-15 Higher score means worse outcome
Time Frame
6 Weeks
Title
Ocular Signs: Conjunctival Epitheliopathy
Description
Conjunctival Lissamine Green Staining Using National Eye Institute (NEI) Grading Scheme Minimum score-0 Maximum score-18 Higher score means worse outcome
Time Frame
2 Weeks
Title
Ocular Signs: Conjunctival Epitheliopathy
Description
Conjunctival Lissamine Green Staining Using National Eye Institute (NEI) Grading Scheme Minimum score-0 Maximum score-18 Higher score means worse outcome
Time Frame
6 Weeks
Title
Ocular Symptoms: Ocular Surface Disease Index (OSDI) Questionnaire
Description
Total Score of the Ocular Surface Disease Index (OSDI) Questionnaire Minimum score- 0 Maximum score-100 Higher score means worse outcome
Time Frame
2 Weeks
Title
Ocular Symptoms: Ocular Surface Disease Index (OSDI) Questionnaire
Description
Total Score of the Ocular Surface Disease Index (OSDI) Questionnaire Minimum score- 0 Maximum score-100 Higher score means worse outcome
Time Frame
6 Weeks
Title
Ocular Signs: Intraocular Pressure (IOP) by Measure of Applanation Tonometry
Description
Intraocular Pressure (IOP) will be measured via Applanation and the result will have these units: mmHg
Time Frame
2 Weeks
Title
Ocular Signs: Intraocular Pressure (IOP) by Measure of Applanation Tonometry
Description
Intraocular Pressure (IOP) will be measured via Applanation and the result will have these units: mmHg
Time Frame
6 Weeks
Title
Ocular Signs: Tear Break Up Time (TBUT)
Description
Tear Break Up Time (TBUT) will be recorded in seconds
Time Frame
2 Weeks
Title
Ocular Signs: Tear Break Up Time (TBUT)
Description
Tear Break Up Time (TBUT) will be recorded in seconds
Time Frame
6 Weeks
Title
Ocular Signs: Schirmer's Test With Anesthesia
Description
The Schirmer's Test (performed using Anesthesia) will be measured in mm.
Time Frame
2 Weeks
Title
Ocular Signs: Schirmer's Test With Anesthesia
Description
The Schirmer's Test (performed using Anesthesia) will be measured in mm.
Time Frame
6 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
89 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pedram Hamrah, MD
Organizational Affiliation
Tufts Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tufts Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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