Randomized Controlled Trial of Long-term Treatment Effectiveness for Meibomian Gland Dysfunction (MGD) and Dry Eye

• Sponsor: TearScience, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01521507
• Collaborator: (none)
• Enrollment: 200
• Locations: 9
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 22.2
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The study objective is to evaluate the long-term treatment effectiveness for adult patients with meibomian gland dysfunction (MGD) and evaporative dry eye by: 1) comparing the LipiFlow® System to a standardized daily warm compress and eyelid hygiene control therapy over a duration of 3 Months; and 2) evaluating the LipiFlow® alone and in combination with other MGD and dry eye treatments over a duration of up to 12 Months.

This is a post-market, non-significant risk, prospective and multi-center clinical trial divided into two stages. The first stage from enrollment to 3 Months is an open-label, randomized controlled design to compare the effectiveness of a single LipiFlow® System treatment to a standardized daily warm compress and eyelid hygiene Control therapy with Crossover LipiFlow® treatment of the Control subjects at 3 Months. The second stage, occurring between 3 and 12 Months, is an observational design to evaluate the effectiveness of LipiFlow® alone and in combination with other MGD and dry eye treatments over a duration of up to 12 Months. Subjects are entered into the following subgroups based on the subject's self-assessment of the adequacy of symptom relief and protocol-defined criteria for additional treatment.

1. One LipiFlow® Treatment: Subjects who receive only one LipiFlow® treatment.

2. Two LipiFlow® Treatments: Subjects who receive a second LipiFlow® treatment.

3. Combination Treatment: Subjects who receive one or two LipiFlow® treatments followed by other MGD or dry eye treatment, as prescribed by the physician.

Condition or Disease	Intervention/Treatment	Phase
Meibomian Gland Dysfunction; Dry Eye	Device: LipiFlow System; Device: Warm Compress Therapy + Lid Scrub	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 200 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Controlled Trial of Long-term Treatment Effectiveness for Meibomian Gland Dysfunction (MGD) and Dry Eye
• Study Start Date: Jan 1, 2012
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Jan 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LipiFlow System Treatment with LipiFlow System at randomization in Stage 1 of study	Device: LipiFlow System; In-office device treatment for meibomian gland dysfunction by a physician
Active Comparator: Warm Compress and Lid Hygiene Control group receiving warm compress therapy and lid hygiene at randomization in Stage 1 of study and crossover LipiFlow System treatment in Stage 2 of study	Device: LipiFlow System; In-office device treatment for meibomian gland dysfunction by a physician; Device: Warm Compress Therapy + Lid Scrub; At-home daily warm compress therapy and lid hygiene; Other Names: EyeGiene Warm Compress Therapy OCuSOFT Lid Scrub

Outcome Measures

Primary Outcome Measures

1. Stage 1 Mean Change in Total Meibomian Gland Score From Baseline to 3 Months [Baseline and 3 Months]

   To assess the meibomian glands, the secretion characteristics from 15 gland orifices along the lower eyelid were evaluated under a slit lamp biomicrosope using a handheld instrument, Meibomian Gland Evaluator, to apply gentle standardized pressure to the eyelid margin. Expressed secretion characteristics were graded on a scale of 3 (clear liquid secretion), 2 (cloudy liquid secretion), 1 (inspissated/toothpaste consistency), and 0 (no secretion). Total meibomian gland score was calculated based on the sum of the secretion grades for all 15 glands over a range from 0 to 45 with a higher score reflecting less meibomian gland dysfunction. To be eligible for the study, the Baseline total meibomian gland score must have been 12 or less in each eye. Change = 3 Month score - Baseline Score.

2. Stage 2 Mean Total Meibomian Gland Score at 12 Months [12 Months]

   To assess the meibomian glands, the secretion characteristics from 15 gland orifices along the lower eyelid were evaluated under a slit lamp biomicrosope using a handheld instrument, Meibomian Gland Evaluator, to apply gentle standardized pressure to the eyelid margin. Expressed secretion characteristics were graded on a scale of 3 (clear liquid secretion), 2 (cloudy liquid secretion), 1 (inspissated/toothpaste consistency), and 0 (no secretion). Total meibomian gland score was calculated based on the sum of the secretion grades for all 15 glands over a range from 0 to 45 with a higher score reflecting less meibomian gland dysfunction. The total meibomian gland score at 12 Months was compared across subgroups, as defined below.

Secondary Outcome Measures

1. Stage 1 Mean Change in Total OSDI Score From Baseline to 3 Months [Baseline, 3 Months]

   Dry eye symptoms assessed using the OSDI questionnaire were sensitivity to light, grittiness, pain or soreness, blurred vision and poor vision. The questionnaire evaluated the frequency problems with the eyes limited performance in reading, driving at night, working with a computer or bank machine, and watching television. Also, the frequency that eyes felt uncomfortable was assessed in windy conditions, areas with low humidity, and air-conditioned areas. The frequency scale was 0 (none of the time), 1 (some of the time), 2 (half of the time), 3 (most of the time), and 4 (all of the time). The total OSDI score was calculated as the sum of frequency scores for all symptoms multiplied by 25 and divided by the number of questions answered with a range from 0 to 100. A lower total OSDI score represents less disability from dry eye symptoms. To be eligible for the study, the Baseline total OSDI score must have been 13 points or higher in each eye. Change=3 Months score-Baseline score.

2. Stage 2 Mean Total OSDI Score at 12 Months [12 Months]

   Dry eye symptoms assessed using the OSDI questionnaire were sensitivity to light, grittiness, pain or soreness, blurred vision and poor vision. The questionnaire evaluated the frequency problems with the eyes limited performance in reading, driving at night, working with a computer or bank machine, and watching television. Also, the frequency that eyes felt uncomfortable was assessed in windy conditions, areas with low humidity, and air-conditioned areas. Frequency scale was 0 (none of the time), 1 (some of the time), 2 (half of the time), 3 (most of the time), and 4 (all of the time). The total OSDI score was calculated as the sum of frequency scores for all symptoms multiplied by 25 and divided by the number of questions answered with a range from 0 to 100. A lower total OSDI score represents less disability from dry eye symptoms. The total OSDI score at 12 Months was compared across subgroups, as defined below.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• At least 18 years old

• Tear film assessment that qualifies in both eyes

• Evidence of meibomian gland dysfunction and dry eye in both eyes

• Willingness to comply with study protocol

Exclusion Criteria:

• Systemic disease condition or medication that causes dry eye

• Use of other treatments for MGD or dry eye

• Ocular surgery, trauma, herpes infection, punctal plug insertion or punctal occlusion within past 3 months

• Active eye infection

• Active eye inflammation or recurrent inflammation within past 3 months

• Moderate to severe allergic conjunctivitis

• Severe eyelid inflammation

• Eyelid abnormality that affects lid function

• Ocular surface abnormality that may compromise corneal integrity

• Pregnant or nursing women

• Participation in another ophthalmic clinical trial within past 30 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	McDonald Eye Associates	Fayetteville	Arkansas	United States	72703
2	Harvard Eye Associates	Laguna Hills	California	United States	92653
3	Center for Excellence in Eye Care	Miami	Florida	United States	33176
4	Chicago Cornea Consultants, Ltd.	Hoffman Estates	Illinois	United States	60169
5	Jackson Eye	Lake Villa	Illinois	United States	50046
6	Cincinnati Eye Institute - Northern Kentucky	Edgewood	Kentucky	United States	41017
7	Charles River Eye Associates	Winchester	Massachusetts	United States	01890
8	Associated Eye Care	Stillwater	Minnesota	United States	55082
9	Ophthalmology Consultants, Ltd.	St. Louis	Missouri	United States	63131

Sponsors and Collaborators

• TearScience, Inc.

Investigators

• Study Director: Christy Stevens, O.D., TearScience, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: TearScience, Inc.
• ClinicalTrials.gov Identifier: NCT01521507
• Other Study ID Numbers: LF-004
• First Posted: Jan 30, 2012
• Last Update Posted: Feb 23, 2015
• Last Verified: Feb 1, 2015

• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Meibomian Gland Dysfunction

Study Results

Participant Flow

Recruitment Details	Between February 19, 2012 and October 15, 2012, this study enrolled subjects with meibomian gland dysfunction (MGD) and evaporative dry eye from nine ophthalmic practices in the United States.
Pre-assignment Detail	A total of 274 subjects were consented and 200 subjects were randomized. Of the 74 subjects who were not randomized, 52 subjects did not meet the study eligibility criteria and 22 subjects elected not to participate prior to randomization or had not yet attended the Baseline visit when study enrollment was completed.

Arm/Group Title	LipiFlow Treatment	Warm Compress & Lid Hygiene, Then Crossover LipiFlow Treatment
Arm/Group Description	Subjects received a single, 12-minute, in-office treatment of both eyes for MGD with the LipiFlow System after randomization in Stage 1 of study. In Stage 2, subjects were entered into subgroups based on the subject's assessment of adequacy of symptom relief: One LipiFlow Treatment - After subjects received one LipiFlow treatment at randomization, no other MGD or dry eye treatment was prescribed for the study duration. Two LipiFlow Treatments - Subjects received a second LipiFlow treatment during Stage 2. No other MGD or dry eye treatment was prescribed for the study duration. Combination Treatment - After subjects received one or two LipiFlow treatments, they received other MGD or dry eye treatment, as prescribed by the physician.	Subjects received twice-daily, standardized warm compress therapy and lid hygiene in both eyes from randomization to 3 months in Stage 1. Then, subjects received a single, 12-minute crossover LipiFlow treatment of both eyes. In Stage 2, subjects were entered into subgroups based on the subject's assessment of adequacy of symptom relief: One LipiFlow Treatment - After subjects received one LipiFlow treatment at crossover, no other MGD or dry eye treatment was prescribed for the study duration. Two LipiFlow Treatments - Subjects received a second LipiFlow treatment during Stage 2. No other MGD or dry eye treatment was prescribed for the study duration. Combination Treatment - After subjects received one or two LipiFlow treatments, they received other MGD or dry eye treatment, as prescribed by the physician.
Period Title: Stage 1: Randomized Design
STARTED	101	99
Received Initial Treatment (Tx)	99	98
COMPLETED	98	94
NOT COMPLETED	3	5
Period Title: Stage 1: Randomized Design
STARTED	98	94
Received Crossover LipiFlow Tx	0	93
Received Only One LipiFlow Tx at 12 Mo	81	82
Received Other MGD Treatment at 12 Mo	11	9
Received 2nd LipiFlow Tx at 12 Mo	2	1
COMPLETED	94	92
NOT COMPLETED	4	2

Baseline Characteristics

Arm/Group Title	LipiFlow Treatment	Warm Compress & Lid Hygiene	Total
Arm/Group Description	Subjects received a single, 12-minute, in-office treatment of both eyes for MGD with the LipiFlow System after randomization in Stage 1 of study.	Subjects received twice-daily, standardized warm compress therapy and lid hygiene in both eyes from randomization to 3-month visit in Stage 1.	Total of all reporting groups
Overall Participants	101	99	200
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.3 (15.9)	56.1 (14.7)	56.2 (15.3)
Sex: Female, Male (Count of Participants)
Female	74 73.3%	68 68.7%	142 71%
Male	27 26.7%	31 31.3%	58 29%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 6.9%	7 7.1%	14 7%
Not Hispanic or Latino	94 93.1%	92 92.9%	186 93%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1%	0 0%	1 0.5%
Asian	2 2%	3 3%	5 2.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	98 97%	96 97%	194 97%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	101 100%	99 100%	200 100%
Baseline Total Meibomian Gland Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6.2 (3.7)	6.3 (3.7)	6.2 (3.7)
Baseline Total OSDI Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	45.6 (21.2)	51.8 (23.1)	48.7 (22.4)
Duration of Dry Eye Symptoms (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	6.9 (6.8)	8.7 (7.7)	7.8 (7.3)
Duration of MGD or Dry Eye Diagnosis (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	5.3 (6.2)	5.5 (5.9)	5.4 (6.0)

Outcome Measures

1. Primary Outcome

Title	Stage 1 Mean Change in Total Meibomian Gland Score From Baseline to 3 Months
Description	To assess the meibomian glands, the secretion characteristics from 15 gland orifices along the lower eyelid were evaluated under a slit lamp biomicrosope using a handheld instrument, Meibomian Gland Evaluator, to apply gentle standardized pressure to the eyelid margin. Expressed secretion characteristics were graded on a scale of 3 (clear liquid secretion), 2 (cloudy liquid secretion), 1 (inspissated/toothpaste consistency), and 0 (no secretion). Total meibomian gland score was calculated based on the sum of the secretion grades for all 15 glands over a range from 0 to 45 with a higher score reflecting less meibomian gland dysfunction. To be eligible for the study, the Baseline total meibomian gland score must have been 12 or less in each eye. Change = 3 Month score - Baseline Score.
Time Frame	Baseline and 3 Months

Outcome Measure Data

Analysis Population Description

Intent to Treat Population (All Participants who were randomized and received at least partial LipiFlow treatment or used warm compress therapy at least once and had data available at 3 Months).

Arm/Group Title	LipiFlow Treatment	Warm Compress & Lid Hygiene
Arm/Group Description	Subjects received a single, 12-minute, in-office treatment of both eyes for MGD with the LipiFlow System after randomization in Stage 1 of study.	Subjects received twice-daily, standardized warm compress therapy and lid hygiene in both eyes from randomization to 3-month visit in Stage 1.
Measure Participants	98	94
Mean (95% Confidence Interval) [units on a scale]	11.6	4.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LipiFlow Treatment, Warm Compress & Lid Hygiene
	Comments	The null and alternative hypotheses are H0: µt ≤ µc vs. Ha: µt > µc, where µt and µc are the mean changes in total meibomian gland scores from Baseline to 3 Months for the LipiFlow (test) and Warm Compress and Lid Hygiene (active control) groups, respectively. For the Stage 1 Primary Outcome, the minimum sample size was 24 subjects per group with a power of 90% and a one-sided alpha of 0.025.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Stage 1 primary and secondary outcomes were tested in order under a closed form testing method. Secondary outcome was tested only if primary outcome was statistically significant. If both outcomes were significant, overall study alpha was 0.025.
	Method	z-statistic
	Comments	p-value was based on z-statistic of the sum of weighted average of difference in scores between groups at each site divided by the sum of the weights.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LipiFlow Treatment, Warm Compress & Lid Hygiene
	Comments	Supportive multivariate mixed model was also performed for this outcome controlling for significant demographic and baseline characteristics.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0020
	Comments
	Method	Mixed Models Analysis
	Comments

2. Primary Outcome

Title	Stage 2 Mean Total Meibomian Gland Score at 12 Months
Description	To assess the meibomian glands, the secretion characteristics from 15 gland orifices along the lower eyelid were evaluated under a slit lamp biomicrosope using a handheld instrument, Meibomian Gland Evaluator, to apply gentle standardized pressure to the eyelid margin. Expressed secretion characteristics were graded on a scale of 3 (clear liquid secretion), 2 (cloudy liquid secretion), 1 (inspissated/toothpaste consistency), and 0 (no secretion). Total meibomian gland score was calculated based on the sum of the secretion grades for all 15 glands over a range from 0 to 45 with a higher score reflecting less meibomian gland dysfunction. The total meibomian gland score at 12 Months was compared across subgroups, as defined below.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

Intent to Treat Population (All participants who received at least partial LipiFlow or Crossover LipiFlow treatment and had data available at 12 Months). Two LipiFlow treatments subgroup was not analyzed because sample size was too small (n<5) for meaningful analysis.

Arm/Group Title	LipiFlow Arm: One LipiFlow Treatment Subgroup	LipiFlow Arm: Combination Treatment Subgroup	Warm Compress/Hygiene Arm: One LipiFlow Treatment Subgroup	Warm Compress/Hygiene Arm: Combination Treatment Subgroup
Arm/Group Description	Subjects received a single, 12-minute, in-office LipiFlow treatment of both eyes after randomization in Stage 1. In Stage 2, subjects were entered into subgroups based on the subject's assessment of adequacy of symptom relief. In the One LipiFlow Treatment subgroup, no other MGD or dry eye treatment was prescribed for the study duration.	Subjects received a single, 12-minute, in-office LipiFlow treatment of both eyes after randomization in Stage 1. In Stage 2, subjects were entered into subgroups based on the subject's assessment of adequacy of symptom relief. In the Combination Treatment subgroup, subjects received one LipiFlow treatment (at randomization) followed by other MGD or dry eye treatment, as prescribed by the physician.	After 3 months of using standardized warm compress therapy and lid hygiene, subjects received a single, 12-minute crossover LipiFlow treatment of both eyes. In Stage 2, subjects were entered into subgroups based on the subject's assessment of adequacy of symptom relief. In the One LipiFlow Treatment subgroup, no other MGD or dry eye treatment was prescribed for the study duration.	After 3 months of using standardized warm compress therapy and lid hygiene, subjects received a single, 12-minute crossover LipiFlow treatment of both eyes. In Stage 2, subjects were entered into subgroups based on the subject's assessment of adequacy of symptom relief. In the Combination Treatment subgroup, subjects received one LipiFlow treatment (at crossover) or two LipiFlow treatments followed by other MGD or dry eye treatment, as prescribed by the physician.
Measure Participants	81	11	82	9
Mean (95% Confidence Interval) [units on a scale]	17.3	17.9	18.4	17.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LipiFlow Treatment, Warm Compress & Lid Hygiene, Warm Compress/Hygiene Arm: One LipiFlow Treatment Subgroup, Warm Compress/Hygiene Arm: Combination Treatment Subgroup
	Comments	The null and alternative hypotheses for the Stage 2 Primary Outcome was: H0: µi= µj for all i and j where i≠j versus Ha: µi ≠ µj for at least one i and j, where µi is the mean total meibomian gland score at 12 Months for the ith subgroup. The null hypothesis was tested with a two-sided test at alpha=0.05. Since Stage 2 was an observational design, no minimum sample size was calculated for Stage 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9098
	Comments
	Method	Mixed Models Analysis
	Comments	Stage 2 Primary Outcome was analyzed with a multivariate mixed model with the subgroup as a fixed effect while controlling for other covariates.

3. Secondary Outcome

Title	Stage 1 Mean Change in Total OSDI Score From Baseline to 3 Months
Description	Dry eye symptoms assessed using the OSDI questionnaire were sensitivity to light, grittiness, pain or soreness, blurred vision and poor vision. The questionnaire evaluated the frequency problems with the eyes limited performance in reading, driving at night, working with a computer or bank machine, and watching television. Also, the frequency that eyes felt uncomfortable was assessed in windy conditions, areas with low humidity, and air-conditioned areas. The frequency scale was 0 (none of the time), 1 (some of the time), 2 (half of the time), 3 (most of the time), and 4 (all of the time). The total OSDI score was calculated as the sum of frequency scores for all symptoms multiplied by 25 and divided by the number of questions answered with a range from 0 to 100. A lower total OSDI score represents less disability from dry eye symptoms. To be eligible for the study, the Baseline total OSDI score must have been 13 points or higher in each eye. Change=3 Months score-Baseline score.
Time Frame	Baseline, 3 Months

Outcome Measure Data

Analysis Population Description

Intent to Treat Population (All participants who were randomized and received at least partial device treatment or used warm compress at least once and had data available at 3 Months).

Arm/Group Title	LipiFlow Treatment	Warm Compress & Lid Hygiene
Arm/Group Description	Subjects received a single, 12-minute, in-office treatment of both eyes for MGD with the LipiFlow System after randomization in Stage 1 of study.	Subjects received twice-daily, standardized warm compress therapy and lid hygiene in both eyes from randomization to 3-month visit in Stage 1.
Measure Participants	98	94
Mean (95% Confidence Interval) [units on a scale]	-23.4	-17.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LipiFlow Treatment, Warm Compress & Lid Hygiene
	Comments	The null and alternative hypotheses are H0: µt ≤ µc vs. Ha: µt > µc, where µt and µc are the mean changes in total OSDI scores from Baseline to 3 Months for the LipiFlow (test) and Warm Compress and Lid Hygiene (active control) groups, respectively. For the Stage 1 Secondary Outcome, the minimum sample size was 84 per group with a power of 80% and a one-sided alpha of 0.025.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0068
	Comments	Stage 1 primary and secondary outcomes were tested in order under a closed form testing method. Secondary outcome was tested only if primary outcome was statistically significant. If both outcomes were significant, overall study alpha was 0.025.
	Method	t-test, 2 sided
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LipiFlow Treatment, Warm Compress & Lid Hygiene
	Comments	Supportive multivariate mixed model was also performed for this outcome controlling for significant demographic and baseline characteristics.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0419
	Comments
	Method	Mixed Models Analysis
	Comments

4. Secondary Outcome

Title	Stage 2 Mean Total OSDI Score at 12 Months
Description	Dry eye symptoms assessed using the OSDI questionnaire were sensitivity to light, grittiness, pain or soreness, blurred vision and poor vision. The questionnaire evaluated the frequency problems with the eyes limited performance in reading, driving at night, working with a computer or bank machine, and watching television. Also, the frequency that eyes felt uncomfortable was assessed in windy conditions, areas with low humidity, and air-conditioned areas. Frequency scale was 0 (none of the time), 1 (some of the time), 2 (half of the time), 3 (most of the time), and 4 (all of the time). The total OSDI score was calculated as the sum of frequency scores for all symptoms multiplied by 25 and divided by the number of questions answered with a range from 0 to 100. A lower total OSDI score represents less disability from dry eye symptoms. The total OSDI score at 12 Months was compared across subgroups, as defined below.
Time Frame	12 Months

Outcome Measure Data

Analysis Population Description

Intent to Treat (All participants who received at least a partial LipiFlow treatment or Crossover LipiFlow treatment and had data available at 12 Months). The Two LipiFlow treatments subgroup was not analyzed because the sample size (n<5) was too small for meaningful analysis.

Arm/Group Title	LipiFlow Arm: One LipiFlow Treatment Subgroup	LipiFlow Arm: Combination Treatment Subgroup	Warm Compress/Hygiene Arm: One LipiFlow Treatment Subgroup	Warm Compress/Hygiene Arm: Combination Treatment Subgroup
Arm/Group Description	Subjects received a single, 12-minute, in-office treatment of both eyes for MGD with the LipiFlow System after randomization in Stage 1 of study. In Stage 2, subjects were entered into subgroups based on the subject's assessment of adequacy of symptom relief. In the One LipiFlow Treatment subgroup, no other MGD or dry eye treatment was prescribed for the study duration.	Subjects received a single, 12-minute, in-office treatment of both eyes for MGD with the LipiFlow System after randomization in Stage 1 of study. In Stage 2, subjects were entered into subgroups based on the subject's assessment of adequacy of symptom relief. In the Combination Treatment subgroup, subjects received one LipiFlow treatment (at randomization) followed by other MGD or dry eye treatment, as prescribed by the physician.	After 3 months of using standardized warm compress therapy and lid hygiene, subjects received a single, 12-minute crossover LipiFlow treatment of both eyes. In Stage 2, subjects were entered into subgroups based on the subject's assessment of adequacy of symptom relief. In the One LipiFlow Treatment subgroup, no other MGD or dry eye treatment was prescribed for the study duration.	After 3 months of using standardized warm compress therapy and lid hygiene, subjects received a single, 12-minute crossover LipiFlow treatment of both eyes. In Stage 2, subjects were entered into subgroups based on the subject's assessment of adequacy of symptom relief. In the Combination Treatment subgroup, subjects received one LipiFlow treatment (at crossover) or two LipiFlow treatments followed by other MGD or dry eye treatment, as prescribed by the physician.
Measure Participants	81	11	82	9
Mean (95% Confidence Interval) [units on a scale]	21.6	35.8	24.0	42.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LipiFlow Treatment, Warm Compress & Lid Hygiene, Warm Compress/Hygiene Arm: One LipiFlow Treatment Subgroup, Warm Compress/Hygiene Arm: Combination Treatment Subgroup
	Comments	The null and alternative hypotheses for the Stage 2 Secondary Outcome was: H0: µi= µj for all i and j where i≠j versus Ha: µi ≠ µj for at least one i and j, where µi is the mean total OSDI score at 12 Months for the ith subgroup. The null hypothesis was tested with a two-sided test at alpha=0.05. Since Stage 2 was an observational design, no minimum sample size was calculated for Stage 2.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0237
	Comments	Stage 2 Secondary Outcome was analyzed with a multivariate mixed model with the subgroup as a fixed effect while controlling for other covariates.
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	Adverse events were collected over 1 year.
Adverse Event Reporting Description	Device-related adverse events were evaluated by arm/group. Events occurring during Stage 1 were assessed based on relationship to the LipiFlow Treatment or Warm Compress Therapy and Lid Hygiene. Events occurring in Stage 2 were assessed based on relationship to LipiFlow Treatment or Crossover LipiFlow Treatment.
Arm/Group Title	LipiFlow Treatment		Warm Compress & Lid Hygiene		Crossover LipiFlow Treatment
Arm/Group Description	Subjects received a single, 12-minute, in-office treatment of both eyes for MGD with the LipiFlow System after randomization in Stage 1 of study.		Subjects received twice-daily, standardized warm compress therapy and lid hygiene in both eyes from randomization to 3-month visit in Stage 1.		After using twice-daily, standardized warm compress therapy and lid hygiene for 3 months, subjects received a single, 12-minute crossover LipiFlow treatment of both eyes.
All Cause Mortality
	LipiFlow Treatment		Warm Compress & Lid Hygiene		Crossover LipiFlow Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LipiFlow Treatment		Warm Compress & Lid Hygiene		Crossover LipiFlow Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/101 (0%)		0/99 (0%)		0/94 (0%)
Other (Not Including Serious) Adverse Events
	LipiFlow Treatment		Warm Compress & Lid Hygiene		Crossover LipiFlow Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/101 (5.9%)		7/99 (7.1%)		4/94 (4.3%)
Eye disorders
Anterior Staphylococcal Blepharitis	1/101 (1%)	2	0/99 (0%)	0	0/94 (0%)	0
Blurry Vision	1/101 (1%)	1	1/99 (1%)	2	0/94 (0%)	0
Burning Sensation	0/101 (0%)	0	1/99 (1%)	2	1/94 (1.1%)	2
Chalazion	1/101 (1%)	1	0/99 (0%)	0	0/94 (0%)	0
Eye/Eyelid Discomfort/Pain	3/101 (3%)	4	1/99 (1%)	2	1/94 (1.1%)	2
Eyelid Edema/Swelling	1/101 (1%)	2	1/99 (1%)	2	1/94 (1.1%)	2
Eyelid Erythema/Redness	0/101 (0%)	0	1/99 (1%)	2	0/94 (0%)	0
Eyelid Irritation	0/101 (0%)	0	1/99 (1%)	2	0/94 (0%)	0
Eyelid Itching	1/101 (1%)	1	1/99 (1%)	1	0/94 (0%)	0
Eyelid Dermatitis	0/101 (0%)	0	2/99 (2%)	3	0/94 (0%)	0
Flashes/Ocular Migraine	1/101 (1%)	1	0/99 (0%)	0	0/94 (0%)	0
Gritty Sensation	0/101 (0%)	0	1/99 (1%)	2	0/94 (0%)	0
Hordeolum	1/101 (1%)	1	0/99 (0%)	0	0/94 (0%)	0
Increase/Worsening of MGD	0/101 (0%)	0	1/99 (1%)	2	0/94 (0%)	0
Increase/Worsening of Ocular Dryness	0/101 (0%)	0	1/99 (1%)	2	2/94 (2.1%)	4
Photophobia/Light Sensitivity	0/101 (0%)	0	1/99 (1%)	2	1/94 (1.1%)	1
Tearing	0/101 (0%)		1/99 (1%)	2	1/94 (1.1%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor can review communications for at least 30 days prior to public release with an extension for up to 45 additional days, if the Sponsor notifies the Investigator that the publication contains patentable material or Proprietary Information other than the study results. Upon Sponsor's written request, Investigator agrees to delete any Proprietary Information.