Dry Eye Disease
Conditions
Keywords
Dry Eye
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.
Interventions
DRUGLotemax
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.
DRUGSoothe 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.
DIAGNOSTIC_TESTIn 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.
Sponsors
Tufts Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 89 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| IVCM for Density of Corneal Immune Dendritiform Cells | 2 Weeks | Density (in cells/mm\^2) of Corneal Immune Dendritiform Cells |
| IVCM for Corneal Immune Dendritiform Cell (DC) Morphology | 2 Weeks | Morphology (in cells/mm\^2) of Corneal Immune Dendritiform Cells |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ocular Symptoms: Ocular Surface Disease Index (OSDI) Questionnaire | 2 Weeks | 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 | 2 Weeks | Intraocular Pressure (IOP) will be measured via Applanation and the result will have these units: mmHg |
| Ocular Signs: Corneal Epitheliopathy | 2 Weeks | Corneal Fluorescein Staining Using the National Eye Institute (NEI) Grading Scheme Minimum score-0 Maximum score-15 Higher score means worse outcome |
| Ocular Signs: Schirmer's Test With Anesthesia | 2 Weeks | The Schirmer's Test (performed using Anesthesia) will be measured in mm. |
| Ocular Signs: Tear Break Up Time (TBUT) | 2 Weeks | Tear Break Up Time (TBUT) will be recorded in seconds |
| Ocular Signs: Conjunctival Epitheliopathy | 2 Weeks | Conjunctival Lissamine Green Staining Using National Eye Institute (NEI) Grading Scheme Minimum score-0 Maximum score-18 Higher score means worse outcome |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lotemax Lotemax (loteprednol etabonate) 0.5% is a prescription-only, preserved ophthalmic suspension. Lotemax 0.5% is FDA approved 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. Lotemax 0.5% will be applied topically to both eyes for 6 weeks with the following regimen: four times daily for 2 weeks, twice daily for 2 weeks, and once daily for 2 weeks.
In Vivo Confocal Microscopy (IVCM): 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. | 17 |
| Lotemax Lotemax (loteprednol etabonate) 0.5% is a prescription-only, preserved ophthalmic suspension. Lotemax 0.5% is FDA approved 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. Lotemax 0.5% will be applied topically to both eyes for 6 weeks with the following regimen: four times daily for 2 weeks, twice daily for 2 weeks, and once daily for 2 weeks.
In Vivo Confocal Microscopy (IVCM): 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. | 28 |
| 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.
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.
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. | 20 |
| 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.
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.
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. | 34 |
| Total | 99 |
Baseline characteristics
| Characteristic | Lotemax | Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears) | Total |
|---|---|---|---|
| Age, Continuous | 57.29 years STANDARD_DEVIATION 12.62 | 55.35 years STANDARD_DEVIATION 15.78 | 56.24 years STANDARD_DEVIATION 14.25 |
| Corneal fluorescein staining at Baseline | 3.39 Score STANDARD_DEVIATION 2.5 | 4.06 Score STANDARD_DEVIATION 3.27 | 3.76 Score STANDARD_DEVIATION 2.94 |
| Corneal immune dendritiform cell (DC) density at Baseline | 26.83 cells/mm^2 STANDARD_DEVIATION 14.98 | 34.59 cells/mm^2 STANDARD_DEVIATION 29.15 | 30.97 cells/mm^2 STANDARD_DEVIATION 23.76 |
| Corneal immune dendritiform cell (DC) morphology at Baseline | 90.79 cells/mm2 STANDARD_DEVIATION 16.67 | 92.29 cells/mm2 STANDARD_DEVIATION 23.82 | 91.59 cells/mm2 STANDARD_DEVIATION 20.64 |
| Intraocular Pressure (IOP) at Baseline | 14.50 mmHG STANDARD_DEVIATION 3.18 | 14.97 mmHG STANDARD_DEVIATION 2.46 | 14.76 mmHG STANDARD_DEVIATION 2.79 |
| Lissamine Green at Baseline | 3.57 Score STANDARD_DEVIATION 2.71 | 5.74 Score STANDARD_DEVIATION 4.26 | 4.76 Score STANDARD_DEVIATION 3.78 |
| Ocular Symptoms Disease Index (OSDI) at Baseline | 56.93 Score STANDARD_DEVIATION 29.36 | 38.46 Score STANDARD_DEVIATION 20.34 | 47.18 Score STANDARD_DEVIATION 26.35 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Schirmer's at Baseline | 10.44 mm STANDARD_DEVIATION 8.94 | 10.57 mm STANDARD_DEVIATION 9.35 | 10.51 mm STANDARD_DEVIATION 9.09 |
| Sex: Female, Male Female | 12 Participants | 17 Participants | 29 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 8 Participants |
| Tear Break-Up Time (TBUT) at Baseline | 3.99 Seconds STANDARD_DEVIATION 2.18 | 4.17 Seconds STANDARD_DEVIATION 3.3 | 4.09 Seconds STANDARD_DEVIATION 2.82 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 20 |
| other Total, other adverse events | 0 / 17 | 0 / 20 |
| serious Total, serious adverse events | 0 / 17 | 0 / 20 |
Outcome results
Primary
IVCM for Corneal Immune Dendritiform Cell (DC) Morphology
Morphology (in cells/mm\^2) of Corneal Immune Dendritiform Cells
Time frame: 6 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotemax | IVCM for Corneal Immune Dendritiform Cell (DC) Morphology | 102.31 Cells/mm^2 | Standard Deviation 26.25 |
| Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears) | IVCM for Corneal Immune Dendritiform Cell (DC) Morphology | 89.34 Cells/mm^2 | Standard Deviation 24.73 |
Primary
IVCM for Corneal Immune Dendritiform Cell (DC) Morphology
Morphology (in cells/mm\^2) of Corneal Immune Dendritiform Cells
Time frame: 2 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotemax | IVCM for Corneal Immune Dendritiform Cell (DC) Morphology | 109.50 cells/mm^2 | Standard Deviation 40.56 |
| Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears) | IVCM for Corneal Immune Dendritiform Cell (DC) Morphology | 97.95 cells/mm^2 | Standard Deviation 30.92 |
Primary
IVCM for Density of Corneal Immune Dendritiform Cells
Density (in cells/mm\^2) of corneal immune dendritiform cells
Time frame: 6 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotemax | IVCM for Density of Corneal Immune Dendritiform Cells | 9.80 cells/mm^2 | Standard Deviation 5.1 |
| Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears) | IVCM for Density of Corneal Immune Dendritiform Cells | 34.03 cells/mm^2 | Standard Deviation 31.92 |
Primary
IVCM for Density of Corneal Immune Dendritiform Cells
Density (in cells/mm\^2) of Corneal Immune Dendritiform Cells
Time frame: 2 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotemax | IVCM for Density of Corneal Immune Dendritiform Cells | 9.47 cells/mm^2 | Standard Deviation 5.13 |
| Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears) | IVCM for Density of Corneal Immune Dendritiform Cells | 28.60 cells/mm^2 | Standard Deviation 26.09 |
Secondary
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
Time frame: 2 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotemax | Ocular Signs: Conjunctival Epitheliopathy | 3.79 Score | Standard Deviation 3.47 |
| Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears) | Ocular Signs: Conjunctival Epitheliopathy | 4.50 Score | Standard Deviation 4.13 |
Secondary
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
Time frame: 6 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotemax | Ocular Signs: Conjunctival Epitheliopathy | 2.46 Score | Standard Deviation 1.86 |
| Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears) | Ocular Signs: Conjunctival Epitheliopathy | 3.44 Score | Standard Deviation 3.55 |
Secondary
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
Time frame: 2 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotemax | Ocular Signs: Corneal Epitheliopathy | 1.86 Score | Standard Deviation 2.12 |
| Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears) | Ocular Signs: Corneal Epitheliopathy | 3.18 Score | Standard Deviation 2.55 |
Secondary
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
Time frame: 6 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotemax | Ocular Signs: Corneal Epitheliopathy | 2.00 Score | Standard Deviation 1.98 |
| Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears) | Ocular Signs: Corneal Epitheliopathy | 3.59 Score | Standard Deviation 2.75 |
Secondary
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
Time frame: 6 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotemax | Ocular Signs: Intraocular Pressure (IOP) by Measure of Applanation Tonometry | 16.88 mmHg | Standard Deviation 2.3 |
| Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears) | Ocular Signs: Intraocular Pressure (IOP) by Measure of Applanation Tonometry | 13.76 mmHg | Standard Deviation 3.32 |
Secondary
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
Time frame: 2 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotemax | Ocular Signs: Intraocular Pressure (IOP) by Measure of Applanation Tonometry | 15.52 mmHg | Standard Deviation 2.87 |
| Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears) | Ocular Signs: Intraocular Pressure (IOP) by Measure of Applanation Tonometry | 14.50 mmHg | Standard Deviation 3.32 |
Secondary
Ocular Signs: Schirmer's Test With Anesthesia
The Schirmer's Test (performed using Anesthesia) will be measured in mm.
Time frame: 2 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotemax | Ocular Signs: Schirmer's Test With Anesthesia | 7.98 mm | Standard Deviation 4.98 |
| Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears) | Ocular Signs: Schirmer's Test With Anesthesia | 6.88 mm | Standard Deviation 5.92 |
Secondary
Ocular Signs: Schirmer's Test With Anesthesia
The Schirmer's Test (performed using Anesthesia) will be measured in mm.
Time frame: 6 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotemax | Ocular Signs: Schirmer's Test With Anesthesia | 8.16 mm | Standard Deviation 4.78 |
| Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears) | Ocular Signs: Schirmer's Test With Anesthesia | 8.18 mm | Standard Deviation 6.06 |
Secondary
Ocular Signs: Tear Break Up Time (TBUT)
Tear Break Up Time (TBUT) will be recorded in seconds
Time frame: 2 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotemax | Ocular Signs: Tear Break Up Time (TBUT) | 5.20 Seconds | Standard Deviation 3.48 |
| Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears) | Ocular Signs: Tear Break Up Time (TBUT) | 3.93 Seconds | Standard Deviation 1.91 |
Secondary
Ocular Signs: Tear Break Up Time (TBUT)
Tear Break Up Time (TBUT) will be recorded in seconds
Time frame: 6 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotemax | Ocular Signs: Tear Break Up Time (TBUT) | 4.83 Seconds | Standard Deviation 3.68 |
| Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears) | Ocular Signs: Tear Break Up Time (TBUT) | 3.44 Seconds | Standard Deviation 2.04 |
Secondary
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
Time frame: 6 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotemax | Ocular Symptoms: Ocular Surface Disease Index (OSDI) Questionnaire | 46.63 Score | Standard Deviation 29.15 |
| Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears) | Ocular Symptoms: Ocular Surface Disease Index (OSDI) Questionnaire | 36.04 Score | Standard Deviation 23.3 |
Secondary
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
Time frame: 2 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lotemax | Ocular Symptoms: Ocular Surface Disease Index (OSDI) Questionnaire | 47.25 Score | Standard Deviation 27.36 |
| Soothe Tired Eyes Lubricant Eye Drop (Artificial Tears) | Ocular Symptoms: Ocular Surface Disease Index (OSDI) Questionnaire | 33.16 Score | Standard Deviation 23.55 |