Dry Eye
Conditions
Brief summary
This 6 month study seeks to compare the use of Intracanalicular Dexamethasone in conjunction with Restasis (cyclosporine ophthalmic emulsion) for the treatment of signs and symptoms of dry eye disease as compared to Restasis with Lotemax (loteprednol etabonate ophthalmic suspension 0.5%) and Restasis monotherapy.
Interventions
DRUGCyclosporine
Used to increase tear production in patients who have dry eye caused by inflammation
Used to treat inflammation of the eye
DRUGDexamethasone Ophthalmic 0.4 Mg Ophthalmic Insert
Used to treat inflammation of the eye
Sponsors
Thomas Chester, OD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
10 subjects will receive Restasis and Dextenza 10 subjects will receive Restasis and Lotemax 10 subjects will receive Restasis
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 18 years of age or older * Signs and symptoms of Dry Eye Disease * Consent to treat with topical immunomodulator * Willing and able to comply with clinic visits and study related procedures * Willing and able to sign the informed consent form
Exclusion criteria
* Patients under the age of 18. * Pregnancy (must be ruled out in women of child-bearing age with pregnancy test) * Active infectious systemic disease * Active infectious ocular or extraocular disease * Altered nasolacrimal flow of either acquired, induced, or congenital origin * Hypersensitivity to dexamethasone * Patients who have been on topical immunomodulating agents in the previous 3 months to their baseline visit * Patient being treated with either topical, oral, or intravenous immunosuppressive agents, immunomodulating agents, or steroid (including NSAIDS) * Patients with severe disease that warrants critical attention, deemed unsafe for the study by the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Ocular Surface Staining From Baseline | Baseline to Week 4, Week 8 and Week 12 | The primary outcome measure was the mean corneal surface staining (guided by use of fluorescein and lissamine green) at weeks 4, 8 and 12 from baseline based on the National Eye Institute grading scale. Corneal fluorescein staining was scored from 0 to 3 on the scale (none, better to heavy, worse) in five regions of the cornea and summed for a total score of 0-15. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Schirmer Tear Test 1 Score | Baseline to Week 4, Week 8 and Week 12 | Schirmer Tear Test 1 score, measuring tear production, as measured by a Schirmer's test strip with anesthetic (mm/5min on a strip 0-35mm. 0 mm is worse, \>15 indicates normal production) at week 4, 8 and 12 from Baseline. |
| Tear Breakup Time (Seconds) | Baseline to Week 4, Week 8 and Week 12 | The time it takes (in seconds) for the tear film to break after blinking at Week 4, 8 and 12 from Baseline |
| Mean Conjunctival Staining | Baseline to Week 4, Week 8 and Week 12 | The mean conjunctival staining (guided by use of lissamine green) at weeks 4, 8 and 12 from baseline based on the National Eye Institute grading scale. Conjunctival staining was scored from 0 to 3 on the scale (none, better to heavy, worse) in six regions of the cornea and summed for a total score of 0-18. |
| Meibomian Gland Scores | Baseline to Week 4, Week 8 and Week 12 | Meibomian gland scoring on a scale of 1-4 (1 represents clear, liquid secretions and 4 is no secretions) in three regions (nasal, central, temporal) and summed for a single score between 3-12 at Week 4, 8 and 12 from baseline |
| DEQ-5 Score | Baseline to Week 4, Week 8 and Week 12 | Dry Eye Questionnaire-5 (5 questions about dry eye symptoms rated from 0, or never to 5, or constantly) total score of 0-22 with higher scores representing worse symptoms at weeks 4, 8 and 12 from baseline |
| Tear Osmolarity | Baseline to Week 4, Week 8 and Week 12 | Tear osmolarity as measured by TearLab (275-307 is considered homeostatic range) at Week 4, 8 and 12 from Baseline. |
Countries
United States
Participant flow
Pre-assignment details
Thirty patients were enrolled in the study. 10 patients in each treatment group.
Participants by arm
| Arm | Count |
|---|---|
| Restasis and Lotemax 10 subjects will be receiving Restasis ophthalmic solution twice a day in both eyes and Lotemax ophthalmic solution twice a day in both eyes.
Cyclosporine: Used to increase tear production in patients who have dry eye caused by inflammation
Loteprednol Etabonate: Used to treat inflammation of the eye | 10 |
| Restasis and Dextenza 10 subjects will be receiving Restasis ophthalmic solution twice a day in both eyes, as well as receiving Dextenza insertion in both lower lids.
Cyclosporine: Used to increase tear production in patients who have dry eye caused by inflammation
Dexamethasone Ophthalmic 0.4 Mg Ophthalmic Insert: Used to treat inflammation of the eye | 10 |
| Restasis 10 subjects will be receiving Restasis ophthalmic solution twice a day in both eyes
Cyclosporine: Used to increase tear production in patients who have dry eye caused by inflammation | 10 |
| Total | 30 |
Baseline characteristics
| Characteristic | Restasis and Lotemax | Total | Restasis | Restasis and Dextenza |
|---|---|---|---|---|
| Age, Continuous | 59 years | 58 years | 62 years | 55 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 25 Participants | 7 Participants | 8 Participants |
| Region of Enrollment United States | 10 participants | 30 participants | 10 participants | 10 participants |
| Sex: Female, Male Female | 8 Participants | 23 Participants | 9 Participants | 6 Participants |
| Sex: Female, Male Male | 2 Participants | 7 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 2 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Mean Ocular Surface Staining From Baseline
The primary outcome measure was the mean corneal surface staining (guided by use of fluorescein and lissamine green) at weeks 4, 8 and 12 from baseline based on the National Eye Institute grading scale. Corneal fluorescein staining was scored from 0 to 3 on the scale (none, better to heavy, worse) in five regions of the cornea and summed for a total score of 0-15.
Time frame: Baseline to Week 4, Week 8 and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Restasis and Lotemax | Mean Ocular Surface Staining From Baseline | Baseline | 0.8 Score on a scale | Standard Deviation 1.5 |
| Restasis and Lotemax | Mean Ocular Surface Staining From Baseline | Week 4 | 0.9 Score on a scale | Standard Deviation 0.9 |
| Restasis and Lotemax | Mean Ocular Surface Staining From Baseline | Week 8 | 0.0 Score on a scale | Standard Deviation 0 |
| Restasis and Lotemax | Mean Ocular Surface Staining From Baseline | Week 12 | 0.6 Score on a scale | Standard Deviation 1 |
| Restasis and Dextenza | Mean Ocular Surface Staining From Baseline | Week 12 | 0.7 Score on a scale | Standard Deviation 1.4 |
| Restasis and Dextenza | Mean Ocular Surface Staining From Baseline | Baseline | 0.6 Score on a scale | Standard Deviation 1 |
| Restasis and Dextenza | Mean Ocular Surface Staining From Baseline | Week 8 | 0.5 Score on a scale | Standard Deviation 1.1 |
| Restasis and Dextenza | Mean Ocular Surface Staining From Baseline | Week 4 | 0.6 Score on a scale | Standard Deviation 1 |
| Restasis | Mean Ocular Surface Staining From Baseline | Week 12 | 0.5 Score on a scale | Standard Deviation 0.7 |
| Restasis | Mean Ocular Surface Staining From Baseline | Week 4 | 1.1 Score on a scale | Standard Deviation 1.4 |
| Restasis | Mean Ocular Surface Staining From Baseline | Week 8 | 0.3 Score on a scale | Standard Deviation 0.6 |
| Restasis | Mean Ocular Surface Staining From Baseline | Baseline | 0.5 Score on a scale | Standard Deviation 0.5 |
Secondary
DEQ-5 Score
Dry Eye Questionnaire-5 (5 questions about dry eye symptoms rated from 0, or never to 5, or constantly) total score of 0-22 with higher scores representing worse symptoms at weeks 4, 8 and 12 from baseline
Time frame: Baseline to Week 4, Week 8 and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Restasis and Lotemax | DEQ-5 Score | Baseline | 14.4 Score on a scale | Standard Deviation 2.4 |
| Restasis and Lotemax | DEQ-5 Score | Week 4 | 11.0 Score on a scale | Standard Deviation 2.4 |
| Restasis and Lotemax | DEQ-5 Score | Week 8 | 9.1 Score on a scale | Standard Deviation 4 |
| Restasis and Lotemax | DEQ-5 Score | Week 12 | 10.2 Score on a scale | Standard Deviation 3.8 |
| Restasis and Dextenza | DEQ-5 Score | Week 12 | 10.3 Score on a scale | Standard Deviation 6.3 |
| Restasis and Dextenza | DEQ-5 Score | Baseline | 14.1 Score on a scale | Standard Deviation 4 |
| Restasis and Dextenza | DEQ-5 Score | Week 8 | 11.3 Score on a scale | Standard Deviation 4.5 |
| Restasis and Dextenza | DEQ-5 Score | Week 4 | 10.6 Score on a scale | Standard Deviation 4.6 |
| Restasis | DEQ-5 Score | Week 12 | 9.4 Score on a scale | Standard Deviation 3.1 |
| Restasis | DEQ-5 Score | Week 4 | 12.2 Score on a scale | Standard Deviation 2.2 |
| Restasis | DEQ-5 Score | Week 8 | 10.6 Score on a scale | Standard Deviation 2.6 |
| Restasis | DEQ-5 Score | Baseline | 14.4 Score on a scale | Standard Deviation 3.7 |
Secondary
Mean Conjunctival Staining
The mean conjunctival staining (guided by use of lissamine green) at weeks 4, 8 and 12 from baseline based on the National Eye Institute grading scale. Conjunctival staining was scored from 0 to 3 on the scale (none, better to heavy, worse) in six regions of the cornea and summed for a total score of 0-18.
Time frame: Baseline to Week 4, Week 8 and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Restasis and Lotemax | Mean Conjunctival Staining | Baseline | 1.5 Score on a scale | Standard Deviation 1.8 |
| Restasis and Lotemax | Mean Conjunctival Staining | Week 4 | 0.9 Score on a scale | Standard Deviation 1.4 |
| Restasis and Lotemax | Mean Conjunctival Staining | Week 8 | 0.8 Score on a scale | Standard Deviation 1.8 |
| Restasis and Lotemax | Mean Conjunctival Staining | Week 12 | 1.0 Score on a scale | Standard Deviation 1.6 |
| Restasis and Dextenza | Mean Conjunctival Staining | Week 12 | 0.8 Score on a scale | Standard Deviation 1.7 |
| Restasis and Dextenza | Mean Conjunctival Staining | Baseline | 0.5 Score on a scale | Standard Deviation 1.8 |
| Restasis and Dextenza | Mean Conjunctival Staining | Week 8 | 0.4 Score on a scale | Standard Deviation 0.8 |
| Restasis and Dextenza | Mean Conjunctival Staining | Week 4 | 0.3 Score on a scale | Standard Deviation 0.6 |
| Restasis | Mean Conjunctival Staining | Week 12 | 0.7 Score on a scale | Standard Deviation 1.4 |
| Restasis | Mean Conjunctival Staining | Week 4 | 0.5 Score on a scale | Standard Deviation 0.7 |
| Restasis | Mean Conjunctival Staining | Week 8 | 0.3 Score on a scale | Standard Deviation 0.6 |
| Restasis | Mean Conjunctival Staining | Baseline | 0.4 Score on a scale | Standard Deviation 0.6 |
Secondary
Mean Schirmer Tear Test 1 Score
Schirmer Tear Test 1 score, measuring tear production, as measured by a Schirmer's test strip with anesthetic (mm/5min on a strip 0-35mm. 0 mm is worse, \>15 indicates normal production) at week 4, 8 and 12 from Baseline.
Time frame: Baseline to Week 4, Week 8 and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Restasis and Lotemax | Mean Schirmer Tear Test 1 Score | Baseline | 10.3 Score on a scale | Standard Deviation 7.2 |
| Restasis and Lotemax | Mean Schirmer Tear Test 1 Score | Week 4 | 12.9 Score on a scale | Standard Deviation 9.1 |
| Restasis and Lotemax | Mean Schirmer Tear Test 1 Score | Week 8 | 12.4 Score on a scale | Standard Deviation 8.4 |
| Restasis and Lotemax | Mean Schirmer Tear Test 1 Score | Week 12 | 10.1 Score on a scale | Standard Deviation 6 |
| Restasis and Dextenza | Mean Schirmer Tear Test 1 Score | Week 12 | 12.3 Score on a scale | Standard Deviation 7.1 |
| Restasis and Dextenza | Mean Schirmer Tear Test 1 Score | Baseline | 14.9 Score on a scale | Standard Deviation 10.3 |
| Restasis and Dextenza | Mean Schirmer Tear Test 1 Score | Week 8 | 15.8 Score on a scale | Standard Deviation 9.4 |
| Restasis and Dextenza | Mean Schirmer Tear Test 1 Score | Week 4 | 15.4 Score on a scale | Standard Deviation 10.1 |
| Restasis | Mean Schirmer Tear Test 1 Score | Week 12 | 9.6 Score on a scale | Standard Deviation 5.5 |
| Restasis | Mean Schirmer Tear Test 1 Score | Week 4 | 10.1 Score on a scale | Standard Deviation 8.5 |
| Restasis | Mean Schirmer Tear Test 1 Score | Week 8 | 10.8 Score on a scale | Standard Deviation 6.4 |
| Restasis | Mean Schirmer Tear Test 1 Score | Baseline | 11.6 Score on a scale | Standard Deviation 10.5 |
Secondary
Meibomian Gland Scores
Meibomian gland scoring on a scale of 1-4 (1 represents clear, liquid secretions and 4 is no secretions) in three regions (nasal, central, temporal) and summed for a single score between 3-12 at Week 4, 8 and 12 from baseline
Time frame: Baseline to Week 4, Week 8 and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Restasis and Lotemax | Meibomian Gland Scores | Week 8 | 6.3 Score on a scale | Standard Deviation 2.6 |
| Restasis and Lotemax | Meibomian Gland Scores | Week 12 | 6.0 Score on a scale | Standard Deviation 2.3 |
| Restasis and Lotemax | Meibomian Gland Scores | Baseline | 7.1 Score on a scale | Standard Deviation 2.1 |
| Restasis and Lotemax | Meibomian Gland Scores | Week 4 | 6.7 Score on a scale | Standard Deviation 2.5 |
| Restasis and Dextenza | Meibomian Gland Scores | Week 4 | 7.6 Score on a scale | Standard Deviation 1.8 |
| Restasis and Dextenza | Meibomian Gland Scores | Week 8 | 8.3 Score on a scale | Standard Deviation 2 |
| Restasis and Dextenza | Meibomian Gland Scores | Baseline | 8.7 Score on a scale | Standard Deviation 2.4 |
| Restasis and Dextenza | Meibomian Gland Scores | Week 12 | 8.7 Score on a scale | Standard Deviation 2 |
| Restasis | Meibomian Gland Scores | Week 4 | 7.2 Score on a scale | Standard Deviation 1.4 |
| Restasis | Meibomian Gland Scores | Week 12 | 7.3 Score on a scale | Standard Deviation 1.4 |
| Restasis | Meibomian Gland Scores | Baseline | 9.2 Score on a scale | Standard Deviation 2.6 |
| Restasis | Meibomian Gland Scores | Week 8 | 8.2 Score on a scale | Standard Deviation 2.2 |
Secondary
Tear Breakup Time (Seconds)
The time it takes (in seconds) for the tear film to break after blinking at Week 4, 8 and 12 from Baseline
Time frame: Baseline to Week 4, Week 8 and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Restasis and Lotemax | Tear Breakup Time (Seconds) | Basline | 5.4 Seconds | Standard Deviation 1.5 |
| Restasis and Lotemax | Tear Breakup Time (Seconds) | Week 4 | 6.1 Seconds | Standard Deviation 2.8 |
| Restasis and Lotemax | Tear Breakup Time (Seconds) | Week 8 | 6.2 Seconds | Standard Deviation 2.2 |
| Restasis and Lotemax | Tear Breakup Time (Seconds) | Week 12 | 6.1 Seconds | Standard Deviation 2.4 |
| Restasis and Dextenza | Tear Breakup Time (Seconds) | Week 12 | 7.7 Seconds | Standard Deviation 2.5 |
| Restasis and Dextenza | Tear Breakup Time (Seconds) | Basline | 6.6 Seconds | Standard Deviation 2.2 |
| Restasis and Dextenza | Tear Breakup Time (Seconds) | Week 8 | 7.7 Seconds | Standard Deviation 3.1 |
| Restasis and Dextenza | Tear Breakup Time (Seconds) | Week 4 | 8.0 Seconds | Standard Deviation 3.6 |
| Restasis | Tear Breakup Time (Seconds) | Week 12 | 7.3 Seconds | Standard Deviation 3.6 |
| Restasis | Tear Breakup Time (Seconds) | Week 4 | 7.4 Seconds | Standard Deviation 3.7 |
| Restasis | Tear Breakup Time (Seconds) | Week 8 | 7.1 Seconds | Standard Deviation 3.4 |
| Restasis | Tear Breakup Time (Seconds) | Basline | 5.7 Seconds | Standard Deviation 3.3 |
Secondary
Tear Osmolarity
Tear osmolarity as measured by TearLab (275-307 is considered homeostatic range) at Week 4, 8 and 12 from Baseline.
Time frame: Baseline to Week 4, Week 8 and Week 12
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Restasis and Lotemax | Tear Osmolarity | Week 8 | 300.1 mOsM/L | Standard Deviation 19.2 |
| Restasis and Lotemax | Tear Osmolarity | Baseline | 311.3 mOsM/L | Standard Deviation 19.8 |
| Restasis and Lotemax | Tear Osmolarity | Week 12 | 304.4 mOsM/L | Standard Deviation 28.7 |
| Restasis and Lotemax | Tear Osmolarity | Week 4 | 307.7 mOsM/L | Standard Deviation 17.3 |
| Restasis and Dextenza | Tear Osmolarity | Week 8 | 303.9 mOsM/L | Standard Deviation 22.1 |
| Restasis and Dextenza | Tear Osmolarity | Week 4 | 304.4 mOsM/L | Standard Deviation 30.1 |
| Restasis and Dextenza | Tear Osmolarity | Week 12 | 299.5 mOsM/L | Standard Deviation 16.2 |
| Restasis and Dextenza | Tear Osmolarity | Baseline | 295.5 mOsM/L | Standard Deviation 17.4 |
| Restasis | Tear Osmolarity | Week 12 | 304.6 mOsM/L | Standard Deviation 19.6 |
| Restasis | Tear Osmolarity | Baseline | 306.9 mOsM/L | Standard Deviation 28.4 |
| Restasis | Tear Osmolarity | Week 4 | 307.9 mOsM/L | Standard Deviation 24.2 |
| Restasis | Tear Osmolarity | Week 8 | 295.3 mOsM/L | Standard Deviation 20.7 |