Dry Eye, Meibomian Gland Dysfunction
Conditions
Brief summary
The pilot study objective is to evaluate the potential benefits of LipiFlow® System treatment of contact lens wearers with meibomian gland dysfunction and evaporative dry eye by assessing for improvement in meibomian gland function and reduction of dry eye symptoms in comparison to an untreated control.
Detailed description
This is a prospective, non-significant risk, open-label, randomized clinical trial of LipiFlow® treatment of contact lens wearers with meibomian gland dysfunction and evaporative dry eye. All subjects undergo examination to determine study eligibility and to capture the Baseline status. Subjects are randomized to receive LipiFlow® treatment (Treatment Group) or no LipiFlow® treatment (Untreated Control Group). The Treatment group is evaluated one month after receiving LipiFlow® treatment. Study endpoints are evaluated at 3 Months by comparing the Treatment Group to the Untreated Group. To facilitate subject recruitment, the Untreated Control group receives Crossover LipiFlow® treatment (Crossover Treatment Group) at 3 Months. The Crossover Treatment group is evaluated one month after receiving LipiFlow® treatment (4 Months visit).
Interventions
DEVICELipiFlow treatment
The LipiFlow® Thermal Pulsation System is a prescription device intended for the application of localized heat and pressure therapy in adult patients with chronic cystic conditions of the eyelids, including meibomian gland dysfunction, also known as evaporative dry eye or lipid deficiency dry eye.
Sponsors
TearScience, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of meibomian gland dysfunction and dry eye * At least 18 years of age * Willing to comply with randomization, attend all study visits and follow patient instructions * Habitual soft contact lens wearer 2 to 18 hours/day and 4 to 7 days/week * No change in contact lens type or dimensions for the past 3 months * Clinician assessment of acceptable contact lens fit and disinfecting solution * Tear film interferometry of 100 units or less
Exclusion criteria
* Systemic disease conditions that cause dry eye * Use of systemic medications known to cause dryness * History of any of the following ocular conditions in the past 3 months: surgery, trauma, Herpes infection, recurrent inflammation, punctal plug insertion or punctal occlusion * Presence of any of the following active conditions: ocular infection, ocular inflammation, moderate to severe allergic conjunctivitis, severe eyelid inflammation, eyelid abnormality that affects lid function, or ocular surface abnormality that compromises corneal integrity * Use of other treatments for meibomian gland dysfunction or dry eye except over the counter lubricants or dietary supplements * Participation in another ophthalmic drug or device trial in the past month * Employee, relative of employee or associate of the clinical site
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Meibomian Gland Score From Baseline at 3 Months | 3 Months | The Primary Endpoint was intended to assess for improvement in meibomian gland function in symptomatic contact lens wearers after LipiFlow treatment in comparison to an untreated control.The Primary Endpoint was defined as the mean change in meibomian gland score in the LipiFlow Treatment group compared to Untreated Control group from Baseline to 3 Months. To determine the meibomian gland score, secretion characteristics of 15 meibomian glands along the lower eyelid were evaluated including five glands each in the temporal, central and nasal regions of the lower eyelid. For each gland, secretion characteristics were graded as 3 (clear liquid), 2 (cloudy liquid), 1 (inspissated/ toothpaste consistency) and 0 (no secretion). The total meibomian gland score is the sum of the grades for all 15 glands with a range between 0 and 45. A higher score reflects less meibomian gland dysfunction. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Dry Eye Questionnaire Score From Baseline at 3 Months | 3 Months | The Secondary Endpoint was intended to assess for reduction in dry eye symptoms in symptomatic contact lens after LipiFlow treatment in comparison to an untreated control using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. The Secondary Endpoint was defined as the mean change in SPEED score in the LipiFlow Treatment group compared to Untreated Control group from Baseline to 3 Months. Dry eye symptoms evaluated were dryness, grittiness or scratchiness; soreness or irritation; burning or watering; and eye fatigue. Symptom frequency and severity were assessed. The SPEED score is the sum of frequency and severity scores with a range from 0 to 28. A lower SPEED score represents less frequent and/or less severe symptoms. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Comfortable Contact Lens Wear Time From Baseline at 3 Months | 3 Months | Subjects reported how long they wore their contact lenses per day (total contact lens wear time) and how long the contact lenses were comfortable (comfortable contact lens wear time). A pre-specified exploratory analysis was to compare the mean change in comfortable contact lens wear time between Baseline and 3 Months for the LipiFlow group vs. untreated control. |
| Mean Change in Meibomian Gland Score From Baseline at 1 Month | 1 Month | The mean change in meibomian gland score from Baseline was also evaluated at 1 Month post-LipiFlow treatment for the LipiFlow and Crossover LipiFlow Groups. The LipiFlow Group was assessed at the 1-Month visit. The Crossover LipiFlow Group was assessed at the 4-Month visit (one month after receiving crossover LipiFlow treatment). There was no planned statistical analysis comparison between the LipiFlow and Crossover LipiFlow groups at 1 Month. To determine the meibomian gland score, secretion characteristics of 15 meibomian glands along the lower eyelid were evaluated including five glands each in the temporal, central and nasal regions of the lower eyelid. For each gland, secretion characteristics were graded as 3 (clear liquid), 2 (cloudy liquid), 1 (inspissated/ toothpaste consistency) and 0 (no secretion). The total meibomian gland score is the sum of the grades for all 15 glands with a range between 0 and 45. A higher score reflects less meibomian gland dysfunction. |
| Mean Change in Dry Eye Questionnaire From Baseline at 1 Month | 1 Month | The mean change in dry eye symptoms from Baseline based on the SPEED questionnaire score was also evaluated at 1 Month post-LipiFlow treatment for the LipiFlow and Crossover LipiFlow Groups. The LipiFlow Group was assessed at the 1-Month visit. The Crossover LipiFlow Group was assessed at the 4-Month visit (one month after receiving cossover LipiFlow treatment). There was no planned statistical analysis comparison between the LipiFlow and Crossover LipiFlow groups at 1 Month. Dry eye symptoms evaluated were dryness, grittiness or scratchiness; soreness or irritation; burning or watering; and eye fatigue. Symptom frequency and severity were assessed. The SPEED score is the sum of frequency and severity scores with a range from 0 to 28. A lower SPEED score represents less frequent and/or less severe symptoms. |
| Mean Change in Comfortable Contact Lens Wear Time From Baseline at 1 Month | 1 Month | Subjects reported how long they wore their contact lenses per day (total contact lens wear time) and how long the contact lenses were comfortable (comfortable contact lens wear time). The mean change in comfortable contact lens wear time from Baseline was also evaluated at 1 Month post-LipiFlow treatment for the LipiFlow and Crossover LipiFlow Groups. The LipiFlow Group was assessed at the 1-Month visit. The Crossover LipiFlow Group was assessed at the 4-Month visit (one month after receiving cossover LipiFlow treatment). There was no planned statistical analysis comparison between the LipiFlow and Crossover LipiFlow groups at 1 Month. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LipiFlow Single 12-minute LipiFlow treatment
LipiFlow treatment: The LipiFlow® Thermal Pulsation System is a prescription device intended for the application of localized heat and pressure therapy in adult patients with chronic cystic conditions of the eyelids, including meibomian gland dysfunction, also known as evaporative dry eye or lipid deficiency dry eye. | 29 |
| LipiFlow Single 12-minute LipiFlow treatment
LipiFlow treatment: The LipiFlow® Thermal Pulsation System is a prescription device intended for the application of localized heat and pressure therapy in adult patients with chronic cystic conditions of the eyelids, including meibomian gland dysfunction, also known as evaporative dry eye or lipid deficiency dry eye. | 58 |
| Untreated Control Untreated Control (No Intervention) | 26 |
| Untreated Control Untreated Control (No Intervention) | 52 |
| Total | 165 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Randomized Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | LipiFlow | Total | Untreated Control |
|---|---|---|---|
| Age, Continuous | 40.0 years STANDARD_DEVIATION 13.1 | 41.7 years STANDARD_DEVIATION 14.5 | 43.5 years STANDARD_DEVIATION 15.9 |
| Comfortable Contact Lens Wear Time | 5.4 hours per day STANDARD_DEVIATION 3.4 | 4.9 hours per day STANDARD_DEVIATION 3.3 | 4.3 hours per day STANDARD_DEVIATION 3.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 54 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Meibomian Gland Score | 8.0 units on a scale STANDARD_DEVIATION 3.5 | 8.1 units on a scale STANDARD_DEVIATION 3.8 | 8.2 units on a scale STANDARD_DEVIATION 4.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 12 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 9 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 17 Participants | 33 Participants | 16 Participants |
| Region of Enrollment Canada | 8 Participants | 16 Participants | 8 Participants |
| Region of Enrollment United States | 21 Participants | 39 Participants | 18 Participants |
| Sex: Female, Male Female | 25 Participants | 47 Participants | 22 Participants |
| Sex: Female, Male Male | 4 Participants | 8 Participants | 4 Participants |
| SPEED Score | 14.5 units on a scale STANDARD_DEVIATION 4.8 | 14.9 units on a scale STANDARD_DEVIATION 4.6 | 15.3 units on a scale STANDARD_DEVIATION 4.5 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 26 | 0 / 25 |
| other Total, other adverse events | 0 / 29 | 0 / 26 | 0 / 25 |
| serious Total, serious adverse events | 0 / 29 | 0 / 26 | 0 / 25 |
Outcome results
Primary
Mean Change in Meibomian Gland Score From Baseline at 3 Months
The Primary Endpoint was intended to assess for improvement in meibomian gland function in symptomatic contact lens wearers after LipiFlow treatment in comparison to an untreated control.The Primary Endpoint was defined as the mean change in meibomian gland score in the LipiFlow Treatment group compared to Untreated Control group from Baseline to 3 Months. To determine the meibomian gland score, secretion characteristics of 15 meibomian glands along the lower eyelid were evaluated including five glands each in the temporal, central and nasal regions of the lower eyelid. For each gland, secretion characteristics were graded as 3 (clear liquid), 2 (cloudy liquid), 1 (inspissated/ toothpaste consistency) and 0 (no secretion). The total meibomian gland score is the sum of the grades for all 15 glands with a range between 0 and 45. A higher score reflects less meibomian gland dysfunction.
Time frame: 3 Months
Population: Intent to Treat (ITT) Population of all randomized subjects.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LipiFlow | Mean Change in Meibomian Gland Score From Baseline at 3 Months | 12.4 units on a scale |
| Untreated Control | Mean Change in Meibomian Gland Score From Baseline at 3 Months | 1.4 units on a scale |
p-value: <0.000195% CI: [8, 14]t-test, 2 sided
Secondary
Mean Change in Dry Eye Questionnaire Score From Baseline at 3 Months
The Secondary Endpoint was intended to assess for reduction in dry eye symptoms in symptomatic contact lens after LipiFlow treatment in comparison to an untreated control using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire. The Secondary Endpoint was defined as the mean change in SPEED score in the LipiFlow Treatment group compared to Untreated Control group from Baseline to 3 Months. Dry eye symptoms evaluated were dryness, grittiness or scratchiness; soreness or irritation; burning or watering; and eye fatigue. Symptom frequency and severity were assessed. The SPEED score is the sum of frequency and severity scores with a range from 0 to 28. A lower SPEED score represents less frequent and/or less severe symptoms.
Time frame: 3 Months
Population: Intent to Treat (ITT) Population of all randomized subjects.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LipiFlow | Mean Change in Dry Eye Questionnaire Score From Baseline at 3 Months | -8.4 units on a scale |
| Untreated Control | Mean Change in Dry Eye Questionnaire Score From Baseline at 3 Months | -0.7 units on a scale |
p-value: <0.000195% CI: [-10.2, -5.2]t-test, 2 sided
Other Pre-specified
Mean Change in Comfortable Contact Lens Wear Time From Baseline at 1 Month
Subjects reported how long they wore their contact lenses per day (total contact lens wear time) and how long the contact lenses were comfortable (comfortable contact lens wear time). The mean change in comfortable contact lens wear time from Baseline was also evaluated at 1 Month post-LipiFlow treatment for the LipiFlow and Crossover LipiFlow Groups. The LipiFlow Group was assessed at the 1-Month visit. The Crossover LipiFlow Group was assessed at the 4-Month visit (one month after receiving cossover LipiFlow treatment). There was no planned statistical analysis comparison between the LipiFlow and Crossover LipiFlow groups at 1 Month.
Time frame: 1 Month
Population: Intent to Treat (all randomized subjects)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LipiFlow | Mean Change in Comfortable Contact Lens Wear Time From Baseline at 1 Month | 4.0 hours per day |
| Untreated Control | Mean Change in Comfortable Contact Lens Wear Time From Baseline at 1 Month | 3.7 hours per day |
Other Pre-specified
Mean Change in Comfortable Contact Lens Wear Time From Baseline at 3 Months
Subjects reported how long they wore their contact lenses per day (total contact lens wear time) and how long the contact lenses were comfortable (comfortable contact lens wear time). A pre-specified exploratory analysis was to compare the mean change in comfortable contact lens wear time between Baseline and 3 Months for the LipiFlow group vs. untreated control.
Time frame: 3 Months
Population: Intent to Treat (ITT) of all randomized subjects
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LipiFlow | Mean Change in Comfortable Contact Lens Wear Time From Baseline at 3 Months | 3.7 hours per day |
| Untreated Control | Mean Change in Comfortable Contact Lens Wear Time From Baseline at 3 Months | -0.3 hours per day |
p-value: <0.000195% CI: [2.5, 5.4]t-test, 2 sided
Other Pre-specified
Mean Change in Dry Eye Questionnaire From Baseline at 1 Month
The mean change in dry eye symptoms from Baseline based on the SPEED questionnaire score was also evaluated at 1 Month post-LipiFlow treatment for the LipiFlow and Crossover LipiFlow Groups. The LipiFlow Group was assessed at the 1-Month visit. The Crossover LipiFlow Group was assessed at the 4-Month visit (one month after receiving cossover LipiFlow treatment). There was no planned statistical analysis comparison between the LipiFlow and Crossover LipiFlow groups at 1 Month. Dry eye symptoms evaluated were dryness, grittiness or scratchiness; soreness or irritation; burning or watering; and eye fatigue. Symptom frequency and severity were assessed. The SPEED score is the sum of frequency and severity scores with a range from 0 to 28. A lower SPEED score represents less frequent and/or less severe symptoms.
Time frame: 1 Month
Population: Intent to Treat (All randomized subjects)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LipiFlow | Mean Change in Dry Eye Questionnaire From Baseline at 1 Month | -8.3 units on a scale |
| Untreated Control | Mean Change in Dry Eye Questionnaire From Baseline at 1 Month | -8.1 units on a scale |
Other Pre-specified
Mean Change in Meibomian Gland Score From Baseline at 1 Month
The mean change in meibomian gland score from Baseline was also evaluated at 1 Month post-LipiFlow treatment for the LipiFlow and Crossover LipiFlow Groups. The LipiFlow Group was assessed at the 1-Month visit. The Crossover LipiFlow Group was assessed at the 4-Month visit (one month after receiving crossover LipiFlow treatment). There was no planned statistical analysis comparison between the LipiFlow and Crossover LipiFlow groups at 1 Month. To determine the meibomian gland score, secretion characteristics of 15 meibomian glands along the lower eyelid were evaluated including five glands each in the temporal, central and nasal regions of the lower eyelid. For each gland, secretion characteristics were graded as 3 (clear liquid), 2 (cloudy liquid), 1 (inspissated/ toothpaste consistency) and 0 (no secretion). The total meibomian gland score is the sum of the grades for all 15 glands with a range between 0 and 45. A higher score reflects less meibomian gland dysfunction.
Time frame: 1 Month
Population: Intent to Treat (All randomized subjects)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LipiFlow | Mean Change in Meibomian Gland Score From Baseline at 1 Month | 11.7 units on a scale |
| Untreated Control | Mean Change in Meibomian Gland Score From Baseline at 1 Month | 14.3 units on a scale |