CVS: TearLab Core Validation Study to Establish Referent Values for Dry Eye Disease

• Sponsor: TearLab Corporation (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00848198
• Collaborator: Alcon Research (Industry)
• Enrollment: 314
• Locations: 10
• Duration (Months): 24.9
• Patients Per Site: 31.4
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

This is a prospective, observational case series to determine the clinical utility of tear osmolarity and other commonly used objective tests to diagnose dry eye disease, as well as to establish referent values for objective tests of the disease.

Condition or Disease	Intervention/Treatment	Phase
Keratoconjunctivitis Sicca

Detailed Description

This is a prospective, observational case series to determine the clinical utility of tear osmolarity, tear film breakup time, corneal fluorescein staining, conjunctival lissamine green staining, Schirmer's test without anesthesia, Bron/Foulks meibomian glan grading and the ocular surface disease index to diagnose dry eye disease, as well as to establish referent values for objective tests of the disease. Patients were recruited across sites in the EU and US from the general clinical population.

Study Design

• Study Type: Observational
• Actual Enrollment: 314 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: A Prospective Study to Establish Normative Values, Demographic Variations, Referent Diagnostic Values and Disease Severity Correlations for Dry Eye Disease and TearLab Osmometry.
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Normal Subjects with no objective signs of Dry Eye Disease
Dry Eye Disease Subjects with objective signs of Dry Eye Disease

Outcome Measures

Primary Outcome Measures

1. Diagnostic Test Data for Disease Using Tear Osmolarity Threshold > 308 mOsm/L [Single visit]

   Tear osmolarity was measured with a laboratory-on-a-chip, to simultaneously collect and analyze the electrical impedance of a 50 nL tear sample from the interior lateral meniscus (TearLab Osmolarity System). A cutoff threshold of more than 308 mOsm/L was used for differentiating normal from mild to moderate subjects. The clinical tools most commonly used in grading dry eye severity are symptomatology (e.g. questionnaires such as the Ocular Surface Disease Index (OSDI) or McMonnies Dry Eye Questionnaire), tear osmolarity, tear film breakup time (TBUT), fluoresceine or lissamine green staining of the cornea and conjunctiva, meibomiam secretion scoring, and the Schirmer test.To convert all the various clinical measurements into a common unit system, based on their breakpoints provided by the Dry Eye Workshop (DEWS), a composite score was created. Its scale being between 0 (representing the least evidence of disease) and 1 (representing the most evidence of disease).

2. Diagnostic Test Data for Disease Using Schirmer Test Threshold < 7 mm [Single visit]

   A 5-minute Schirmer test was performed with sterile strips without anesthetic (Tear Flo). The cutoff threshold of <7mm was used to differentiating normal from mild subjects. The clinical tools most commonly used in grading dry eye severity are symptomatology (e.g. questionnaires such as the Ocular Surface Disease Index (OSDI) or McMonnies Dry Eye Questionnaire), tear osmolarity, tear film breakup time (TBUT), fluoresceine or lissamine green staining of the cornea and conjunctiva, meibomiam secretion scoring, and the Schirmer test. To convert all the various clinical measurements into a common unit system, based on their breakpoints provided by the Dry Eye Workshop (DEWS), a composite score was created. Its scale being between 0 (representing the least evidence of disease) and 1 (representing the most evidence of disease).

3. Diagnostic Test Data for Disease Using Tear Film Breakup Time Threshold < 5 Seconds [Single visit]

   Tear film breakup time was measured by instilling 5μL of a 2% sodium fluoresceine solution and calculating the average of three consecutive breakup times, manually determined with a stopwatch. The cutoff of <5 seconds was used to differentiate normal from dry eye subjects. The clinical tools most commonly used in grading dry eye severity are symptomatology (e.g. questionnaires such as the Ocular Surface Disease Index (OSDI) or McMonnies Dry Eye Questionnaire), tear osmolarity, tear film breakup time (TBUT), fluoresceine or lissamine green staining of the cornea and conjunctiva, Meibomiann secretion scoring, and the Schirmer test. To convert all the various clinical measurements into a common unit system, based on their breakpoints provided by the Dry Eye Workshop (DEWS), a composite score was created. Its scale being between 0 (representing the least evidence of disease) and 1 (representing the most evidence of disease).

4. Diagnostic Test Data for Disease Using Corneal Staining Threshold > Grade 4/15 [Single visit]

   Corneal Staining was evaluated under cobalt blue illumination 2.5 to 3.0 minutes after fluorescein instillation. Staining amplitude followed the National Eye Institute/Industry Workshop scale. The cutoff threshold >4/15 was used to differentiate normals from dry eye subjects. The clinical tools most commonly used in grading dry eye severity are symptomatology (e.g. questionnaires such as the Ocular Surface Disease Index (OSDI) or McMonnies Dry Eye Questionnaire), tear osmolarity, tear film breakup time (TBUT), fluoresceine or lissamine green staining of the cornea and conjunctiva, meibomiam secretion scoring, and the Schirmer test.To convert all the various clinical measurements into a common unit system, based on their breakpoints provided by the Dry Eye Workshop (DEWS), a composite score was created. Its scale being between 0 (representing the least evidence of disease) and 1 (representing the most evidence of disease).

5. Diagnostic Test Data for Disease Using Conjunctival Staining Threshold > Grade 3/12 [Single visit]

   Conjunctival staining was performed 2.5 to 3.0 minutes after instillation of 10 μL of a 1% sodium lissamine green dye. Conjunctival staining followed the National Eye Institute/Industry Workshop scale. A cutoff threshold of grade >3/12 was used to differentiate normal from dry eye subjects. The clinical tools most commonly used in grading dry eye severity are symptomatology (e.g. questionnaires such as the Ocular Surface Disease Index (OSDI) or McMonnies Dry Eye Questionnaire), tear osmolarity, tear film breakup time (TBUT), fluoresceine or lissamine green staining of the cornea and conjunctiva, meibomiam secretion scoring, and the Schirmer test. To convert all the various clinical measurements into a common unit system, based on their breakpoints provided by the Dry Eye Workshop (DEWS), a composite score was created. Its scale being between 0 (representing the least evidence of disease) and 1 (representing the most evidence of disease).

6. Diagnostic Test Data for Disease Using Meibomian Gland Grading Threshold > Grade 5/27 [Single visit]

   Meibomian dysfunction was assessed to grade the quality, expressibility, and volume of gland secretion, according to Bron/Foulks scoring system. A cutoff threshold of grade 5/27 was used to differentiate normal from dry eye subjects. The clinical tools most commonly used in grading dry eye severity are symptomatology (e.g. questionnaires such as the Ocular Surface Disease Index (OSDI) or McMonnies Dry Eye Questionnaire), tear osmolarity, tear film breakup time (TBUT), fluoresceine or lissamine green staining of the cornea and conjunctiva, meibomiam secretion scoring, and the Schirmer test.To convert all the various clinical measurements into a common unit system, based on their breakpoints provided by the Dry Eye Workshop (DEWS), a composite score was created. Its scale being between 0 (representing the least evidence of disease) and 1 (representing the most evidence of disease).

7. Diagnostic Test Data for Disease Using Ocular Surface Disease Index Threshold > 15/100 [Single visit]

   Ocular Surface Disease Index (OSDI) Questionnaire was used for symptoms assessment. A cutoff of 15/100 score was used to differentiate between normal and dry eye subjects. The clinical tools most commonly used in grading dry eye severity are symptomatology (e.g. questionnaires such as the Ocular Surface Disease Index (OSDI) or McMonnies Dry Eye Questionnaire), tear osmolarity, tear film breakup time (TBUT), fluoresceine or lissamine green staining of the cornea and conjunctiva, meibomiam secretion scoring, and the Schirmer test.To convert all the various clinical measurements into a common unit system, based on their breakpoints provided by the Dry Eye Workshop (DEWS), a composite score was created. Its scale being between 0 (representing the least evidence of disease) and 1 (representing the most evidence of disease).

Secondary Outcome Measures

1. Referent Values for Tear Osmolarity [Single visit]

2. Referent Values for Schirmer Test [Single visit]

3. Referent Values for Tear Film Breakup Time [Single visit]

4. Referent Values for Corneal Staining [Single visit]

   Corneal Staining is used to identify and evaluate ocular surface and corneal damages. It was evaluated under cobalt blue illumination 2.5 to 3.0 minutes after fluorescein instillation. Staining amplitude followed the National Eye Institute/Industry Workshop scale. The cutoff threshold >4/15 was used to differentiate normals from dry eye subjects. A score of 0 indicates no damage of ocular surface/cornea, while the maximum for the most severe damage is 15.

5. Referent Values for Conjunctival Staining [Single visit]

   Conjunctival staining is used to identify and evaluate dead or injured conjunctival cells. Conjunctival staining was performed 2.5 to 3.0 minutes after instillation of 10 μL of a 1% sodium lissamine green dye. Conjunctival staining followed the National Eye Institute/Industry Workshop scale. A cutoff threshold of grade >3/12 was used to differentiate normal from dry eye subjects. A score of 0 indicates no damage of conjunctival cells, while the maximum for the most severe damage is 12.

6. Referent Values for Meibomian Gland Grading [Single visit]

   Meibomian gland dysfunction was assessed to grade the quality, expressibility, and volume of gland secretion, according to Bron/Foulks scoring system. A score of 0 indicates full integrity of these glands while the maximum of 27, is used for severe damage.

7. Referent Values for Ocular Surface Disease Index [Single visit]

   Ocular Surface Disease Index (OSDI) Questionnaire was used for symptoms assessment and the index is calculated based on the responses given by the subject. A cutoff of 15/100 score was used to differentiate between normal and dry eye subjects. A score of 0 confirms no dry eye symptoms are present, while a maximum of 100 indicates the maximum severity of symptoms experienced by subjects.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Be between the ages of 18 and 79 years of age.

• Must understand and be able, willing and likely to fully comply with study procedures and restrictions.

Exclusion Criteria:

• Clinically significant eyelid deformity or eyelid movement disorder that is caused by conditions such as notch deformity, incomplete lid closure, entropion, ectropion, hordeola or chalazia..

• Previous ocular disease leaving sequelae or requiring current topical eye therapy other than for Dry Eye Disease, including, but not limited to: active corneal or conjunctival infection of the eye and ocular surface scarring.

• Active ocular allergy.

• LASIK or PRK surgery that was performed within one year of Visit 1.

• Started or changed the dose of chronic ocular medication within 30 days of visit 1.

• Contact lens worn within the past eight (8) hours.

• Any ophthalmologic drops within 2 hours of screening and visit 1 procedures.

• Pregnancy or lactation.

• Abnormality of nasolacrimal drainage (by history).

• Punctual plugs placement or cauterization within 30 days of Visit 1

• Started or changed the dose of chronic systemic medication known to affect tear production including, but not limited to antihistamines, antidepressants, diuretics, corticosteroids or immunomodulators within 30 days of Visit 1.

• Systemic disease known to affect tear production or loss including, but not limited to thyroid eye disease, that has been diagnosed or has not been stable within 30 days of Visit 1.

• Known hypersensitivity to any of the agents used in testing i.e. sodium fluorescein, lissamine green, oxybuprocaine or proparacaine.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Gordon Binder Weiss Vision Institute	San Diego	California	United States	92130
2	Kentucky Lion Eye Center	Louisville	Kentucky	United States	40202
3	Pepose Vision Institute	Chesterfield	Missouri	United States	63017
4	Tauber Eye Clinic	Kansas City	Missouri	United States	63017
5	Mundorf Eye Center	Charlotte	North Carolina	United States	28204
6	Ohio State University	Columbus	Ohio	United States	43210
7	Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts	Paris		France
8	University of Wurzburg	Wurzburg		Germany
9	Hospital Clinico San Carlos	Madrid		Spain
10	Division of Vision Sciences	Glasgow	Scotland	United Kingdom

Sponsors and Collaborators

• TearLab Corporation
• Alcon Research

Investigators

• Study Chair: Gary Foulks, MD, Kentucky Lions Eye Center, University of Louisville

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: TearLab Corporation
• ClinicalTrials.gov Identifier: NCT00848198
• Other Study ID Numbers: TP00007 OTO
• First Posted: Feb 20, 2009
• Last Update Posted: May 16, 2016
• Last Verified: Apr 1, 2016

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by TearLab Corporation: Dry Eye Disease; Dry Eye Syndrome; Dry Eye
• Additional relevant MeSH terms: Dry Eye Syndromes; Keratoconjunctivitis Sicca; Eye Diseases; Keratoconjunctivitis

Study Results

Participant Flow

Recruitment Details	Subjects between the ages of 18 and 82 years were included in the study. Participants were chosen from 10 sites in the E.U. and U.S. from the general patient population. 314 total subjects were enrolled.
Pre-assignment Detail	Of the first 314 subjects enrolled, only 299 (n = 218 female, n = 81 male), were used in the analysis with the remainder disqualified for incomplete case report forms and lack of data from the single visit.

Arm/Group Title	Total Number of Participants
Arm/Group Description	All participants who were tested using common signs and symptoms for dry eye disease
Period Title: Overall Study
STARTED	314
COMPLETED	299
NOT COMPLETED	15

Baseline Characteristics

Arm/Group Title	Total Number of Participants
Arm/Group Description	All participants who were tested using common signs and symptoms for dry eye disease
Overall Participants	314
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	269 85.7%
>=65 years	45 14.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	46.3 (16.9)
Sex: Female, Male (Count of Participants)
Female	233 74.2%
Male	81 25.8%
Region of Enrollment (participants) [Number]
France	50 15.9%
United States	139 44.3%
Spain	50 15.9%
Germany	50 15.9%
United Kingdom	25 8%

Outcome Measures

1. Primary Outcome

Title	Diagnostic Test Data for Disease Using Tear Osmolarity Threshold > 308 mOsm/L
Description	Tear osmolarity was measured with a laboratory-on-a-chip, to simultaneously collect and analyze the electrical impedance of a 50 nL tear sample from the interior lateral meniscus (TearLab Osmolarity System). A cutoff threshold of more than 308 mOsm/L was used for differentiating normal from mild to moderate subjects. The clinical tools most commonly used in grading dry eye severity are symptomatology (e.g. questionnaires such as the Ocular Surface Disease Index (OSDI) or McMonnies Dry Eye Questionnaire), tear osmolarity, tear film breakup time (TBUT), fluoresceine or lissamine green staining of the cornea and conjunctiva, meibomiam secretion scoring, and the Schirmer test.To convert all the various clinical measurements into a common unit system, based on their breakpoints provided by the Dry Eye Workshop (DEWS), a composite score was created. Its scale being between 0 (representing the least evidence of disease) and 1 (representing the most evidence of disease).
Time Frame	Single visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants With Dry Eye Disease	Participants Without Dry Eye Disease (Normal)
Arm/Group Description	Presence of dry eye disease as defined by positive reference test	Absence of dry eye disease as defined by negative reference test
Measure Participants	224	75
Positive diagnostic test	177 56.4%	14 NaN
Negative diagnostic test	47 15%	61 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With Dry Eye Disease
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity
	Estimated Value	87.1
	Confidence Interval	(2-Sided) 95%; 83.2 to 90.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants Without Dry Eye Disease (Normal)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Specificity
	Estimated Value	72.0
	Confidence Interval	(2-Sided) 95%; 66.9 to 77.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Diagnostic Test Data for Disease Using Schirmer Test Threshold < 7 mm
Description	A 5-minute Schirmer test was performed with sterile strips without anesthetic (Tear Flo). The cutoff threshold of <7mm was used to differentiating normal from mild subjects. The clinical tools most commonly used in grading dry eye severity are symptomatology (e.g. questionnaires such as the Ocular Surface Disease Index (OSDI) or McMonnies Dry Eye Questionnaire), tear osmolarity, tear film breakup time (TBUT), fluoresceine or lissamine green staining of the cornea and conjunctiva, meibomiam secretion scoring, and the Schirmer test. To convert all the various clinical measurements into a common unit system, based on their breakpoints provided by the Dry Eye Workshop (DEWS), a composite score was created. Its scale being between 0 (representing the least evidence of disease) and 1 (representing the most evidence of disease).
Time Frame	Single visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants With Dry Eye Disease	Participants Without Dry Eye Disease (Normal)
Arm/Group Description	Presence of dry eye disease as defined by positive reference test	Absence of dry eye disease as defined by negative reference test
Measure Participants	224	75
Positive diagnostic test	89 28.3%	13 NaN
Negative diagnostic test	135 43%	62 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With Dry Eye Disease
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity
	Estimated Value	39.7
	Confidence Interval	(2-Sided) 95%; 34.2 to 45.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants Without Dry Eye Disease (Normal)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Specificity
	Estimated Value	82.7
	Confidence Interval	(2-Sided) 95%; 78.4 to 87.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Diagnostic Test Data for Disease Using Tear Film Breakup Time Threshold < 5 Seconds
Description	Tear film breakup time was measured by instilling 5μL of a 2% sodium fluoresceine solution and calculating the average of three consecutive breakup times, manually determined with a stopwatch. The cutoff of <5 seconds was used to differentiate normal from dry eye subjects. The clinical tools most commonly used in grading dry eye severity are symptomatology (e.g. questionnaires such as the Ocular Surface Disease Index (OSDI) or McMonnies Dry Eye Questionnaire), tear osmolarity, tear film breakup time (TBUT), fluoresceine or lissamine green staining of the cornea and conjunctiva, Meibomiann secretion scoring, and the Schirmer test. To convert all the various clinical measurements into a common unit system, based on their breakpoints provided by the Dry Eye Workshop (DEWS), a composite score was created. Its scale being between 0 (representing the least evidence of disease) and 1 (representing the most evidence of disease).
Time Frame	Single visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants With Dry Eye Disease	Participants Without Dry Eye Disease (Normal)
Arm/Group Description	Presence of dry eye disease as defined by positive reference test	Absence of dry eye disease as defined by negative reference test
Measure Participants	224	75
Positive diagnostic test	161 51.3%	13 NaN
Negative diagnostic test	63 20.1%	62 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With Dry Eye Disease
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity
	Estimated Value	71.9
	Confidence Interval	(2-Sided) 95%; 66.8 to 77.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants Without Dry Eye Disease (Normal)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Specificity
	Estimated Value	82.7
	Confidence Interval	(2-Sided) 95%; 78.4 to 87.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	Diagnostic Test Data for Disease Using Corneal Staining Threshold > Grade 4/15
Description	Corneal Staining was evaluated under cobalt blue illumination 2.5 to 3.0 minutes after fluorescein instillation. Staining amplitude followed the National Eye Institute/Industry Workshop scale. The cutoff threshold >4/15 was used to differentiate normals from dry eye subjects. The clinical tools most commonly used in grading dry eye severity are symptomatology (e.g. questionnaires such as the Ocular Surface Disease Index (OSDI) or McMonnies Dry Eye Questionnaire), tear osmolarity, tear film breakup time (TBUT), fluoresceine or lissamine green staining of the cornea and conjunctiva, meibomiam secretion scoring, and the Schirmer test.To convert all the various clinical measurements into a common unit system, based on their breakpoints provided by the Dry Eye Workshop (DEWS), a composite score was created. Its scale being between 0 (representing the least evidence of disease) and 1 (representing the most evidence of disease).
Time Frame	Single visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants With Dry Eye Disease	Participants Without Dry Eye Disease (Normal)
Arm/Group Description	Presence of dry eye disease as defined by positive reference test	Absence of dry eye disease as defined by negative reference test
Measure Participants	224	75
Positive diagnostic test	61 19.4%	1 NaN
Negative diagnostic test	163 51.9%	74 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With Dry Eye Disease
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity
	Estimated Value	27.2
	Confidence Interval	(2-Sided) 95%; 22.2 to 32.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants Without Dry Eye Disease (Normal)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Specificity
	Estimated Value	98.7
	Confidence Interval	(2-Sided) 95%; 97.4 to 100.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Primary Outcome

Title	Diagnostic Test Data for Disease Using Conjunctival Staining Threshold > Grade 3/12
Description	Conjunctival staining was performed 2.5 to 3.0 minutes after instillation of 10 μL of a 1% sodium lissamine green dye. Conjunctival staining followed the National Eye Institute/Industry Workshop scale. A cutoff threshold of grade >3/12 was used to differentiate normal from dry eye subjects. The clinical tools most commonly used in grading dry eye severity are symptomatology (e.g. questionnaires such as the Ocular Surface Disease Index (OSDI) or McMonnies Dry Eye Questionnaire), tear osmolarity, tear film breakup time (TBUT), fluoresceine or lissamine green staining of the cornea and conjunctiva, meibomiam secretion scoring, and the Schirmer test. To convert all the various clinical measurements into a common unit system, based on their breakpoints provided by the Dry Eye Workshop (DEWS), a composite score was created. Its scale being between 0 (representing the least evidence of disease) and 1 (representing the most evidence of disease).
Time Frame	Single visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants With Dry Eye Disease	Participants Without Dry Eye Disease (Normal)
Arm/Group Description	Presence of dry eye disease as defined by positive reference test	Absence of dry eye disease as defined by negative reference test
Measure Participants	224	75
Positive diagnostic test	115 36.6%	4 NaN
Negative diagnostic test	109 34.7%	71 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With Dry Eye Disease
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity
	Estimated Value	51.3
	Confidence Interval	(2-Sided) 95%; 45.7 to 57.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants Without Dry Eye Disease (Normal)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Specificity
	Estimated Value	94.7
	Confidence Interval	(2-Sided) 95%; 92.1 to 97.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Primary Outcome

Title	Diagnostic Test Data for Disease Using Meibomian Gland Grading Threshold > Grade 5/27
Description	Meibomian dysfunction was assessed to grade the quality, expressibility, and volume of gland secretion, according to Bron/Foulks scoring system. A cutoff threshold of grade 5/27 was used to differentiate normal from dry eye subjects. The clinical tools most commonly used in grading dry eye severity are symptomatology (e.g. questionnaires such as the Ocular Surface Disease Index (OSDI) or McMonnies Dry Eye Questionnaire), tear osmolarity, tear film breakup time (TBUT), fluoresceine or lissamine green staining of the cornea and conjunctiva, meibomiam secretion scoring, and the Schirmer test.To convert all the various clinical measurements into a common unit system, based on their breakpoints provided by the Dry Eye Workshop (DEWS), a composite score was created. Its scale being between 0 (representing the least evidence of disease) and 1 (representing the most evidence of disease).
Time Frame	Single visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants With Dry Eye Disease	Participants Without Dry Eye Disease (Normal)
Arm/Group Description	Presence of dry eye disease as defined by positive reference test	Absence of dry eye disease as defined by negative reference test
Measure Participants	224	75
Positive diagnostic test	137 43.6%	16 NaN
Negative diagnostic test	87 27.7%	59 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With Dry Eye Disease
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity
	Estimated Value	61.2
	Confidence Interval	(2-Sided) 95%; 55.6 to 66.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants Without Dry Eye Disease (Normal)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Specificity
	Estimated Value	78.7
	Confidence Interval	(2-Sided) 95%; 74.0 to 83.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Primary Outcome

Title	Diagnostic Test Data for Disease Using Ocular Surface Disease Index Threshold > 15/100
Description	Ocular Surface Disease Index (OSDI) Questionnaire was used for symptoms assessment. A cutoff of 15/100 score was used to differentiate between normal and dry eye subjects. The clinical tools most commonly used in grading dry eye severity are symptomatology (e.g. questionnaires such as the Ocular Surface Disease Index (OSDI) or McMonnies Dry Eye Questionnaire), tear osmolarity, tear film breakup time (TBUT), fluoresceine or lissamine green staining of the cornea and conjunctiva, meibomiam secretion scoring, and the Schirmer test.To convert all the various clinical measurements into a common unit system, based on their breakpoints provided by the Dry Eye Workshop (DEWS), a composite score was created. Its scale being between 0 (representing the least evidence of disease) and 1 (representing the most evidence of disease).
Time Frame	Single visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants With Dry Eye Disease	Participants Without Dry Eye Disease (Normal)
Arm/Group Description	Presence of dry eye disease as defined by positive reference test	Absence of dry eye disease as defined by negative reference test
Measure Participants	224	75
Positive diagnostic test	131 41.7%	20 NaN
Negative diagnostic test	93 29.6%	55 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Participants With Dry Eye Disease
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Sensitivity
	Estimated Value	58.5
	Confidence Interval	(2-Sided) 95%; 52.9 to 64.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Participants Without Dry Eye Disease (Normal)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Specificity
	Estimated Value	73.3
	Confidence Interval	(2-Sided) 95%; 68.3 to 78.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Referent Values for Tear Osmolarity
Time Frame	Single visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants With Severe Dry Eye Disease	Participants With Mild/Moderate Dry Eye Disease	Participants Without Dry Eye Disease (Normal)
Arm/Group Description	Subjects with composite severity score less than 0.20	Subjects with composite severity score between 0.20 and 0.35	Subjects with composite severity score greater than 0.35
Measure Participants	75	149	75
Mean (Standard Deviation) [mOsm/L]	336.4 (22.3)	315.0 (11.4)	302.2 (8.3)

9. Secondary Outcome

Title	Referent Values for Schirmer Test
Time Frame	Single visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants With Severe Dry Eye Disease	Participants With Mild/Moderate Dry Eye Disease	Participants Without Dry Eye Disease (Normal)
Arm/Group Description	Subjects with composite severity score less than 0.20	Subjects with composite severity score between 0.20 and 0.35	Subjects with composite severity score greater than 0.35
Measure Participants	75	149	75
Mean (Standard Deviation) [mm]	8.2 (8.4)	13.9 (9.5)	19.3 (10.4)

10. Secondary Outcome

Title	Referent Values for Tear Film Breakup Time
Time Frame	Single visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants With Severe Dry Eye Disease	Participants With Mild/Moderate Dry Eye Disease	Participants Without Dry Eye Disease (Normal)
Arm/Group Description	Subjects with composite severity score less than 0.20	Subjects with composite severity score between 0.20 and 0.35	Subjects with composite severity score greater than 0.35
Measure Participants	75	149	75
Mean (Standard Deviation) [seconds]	2.7 (1.5)	6.1 (4.9)	11.8 (6.4)

11. Secondary Outcome

Title	Referent Values for Corneal Staining
Description	Corneal Staining is used to identify and evaluate ocular surface and corneal damages. It was evaluated under cobalt blue illumination 2.5 to 3.0 minutes after fluorescein instillation. Staining amplitude followed the National Eye Institute/Industry Workshop scale. The cutoff threshold >4/15 was used to differentiate normals from dry eye subjects. A score of 0 indicates no damage of ocular surface/cornea, while the maximum for the most severe damage is 15.
Time Frame	Single visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants With Severe Dry Eye Disease	Participants With Mild/Moderate Dry Eye Disease	Participants Without Dry Eye Disease (Normal)
Arm/Group Description	Subjects with composite severity score less than 0.20	Subjects with composite severity score between 0.20 and 0.35	Subjects with composite severity score greater than 0.35
Measure Participants	75	149	75
Mean (Standard Deviation) [Grade]	5.1 (4.1)	1.7 (1.9)	0.4 (0.9)

12. Secondary Outcome

Title	Referent Values for Conjunctival Staining
Description	Conjunctival staining is used to identify and evaluate dead or injured conjunctival cells. Conjunctival staining was performed 2.5 to 3.0 minutes after instillation of 10 μL of a 1% sodium lissamine green dye. Conjunctival staining followed the National Eye Institute/Industry Workshop scale. A cutoff threshold of grade >3/12 was used to differentiate normal from dry eye subjects. A score of 0 indicates no damage of conjunctival cells, while the maximum for the most severe damage is 12.
Time Frame	Single visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants With Severe Dry Eye Disease	Participants With Mild/Moderate Dry Eye Disease	Participants Without Dry Eye Disease (Normal)
Arm/Group Description	Subjects with composite severity score less than 0.20	Subjects with composite severity score between 0.20 and 0.35	Subjects with composite severity score greater than 0.35
Measure Participants	75	149	75
Mean (Standard Deviation) [Grade]	5.9 (3.6)	2.6 (1.9)	1.1 (1.4)

13. Secondary Outcome

Title	Referent Values for Meibomian Gland Grading
Description	Meibomian gland dysfunction was assessed to grade the quality, expressibility, and volume of gland secretion, according to Bron/Foulks scoring system. A score of 0 indicates full integrity of these glands while the maximum of 27, is used for severe damage.
Time Frame	Single visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants With Severe Dry Eye Disease	Participants With Mild/Moderate Dry Eye Disease	Participants Without Dry Eye Disease (Normal)
Arm/Group Description	Subjects with composite severity score less than 0.20	Subjects with composite severity score between 0.20 and 0.35	Subjects with composite severity score greater than 0.35
Measure Participants	75	149	75
Mean (Standard Deviation) [Grade]	10.4 (5.2)	5.6 (4.7)	2.6 (2.7)

14. Secondary Outcome

Title	Referent Values for Ocular Surface Disease Index
Description	Ocular Surface Disease Index (OSDI) Questionnaire was used for symptoms assessment and the index is calculated based on the responses given by the subject. A cutoff of 15/100 score was used to differentiate between normal and dry eye subjects. A score of 0 confirms no dry eye symptoms are present, while a maximum of 100 indicates the maximum severity of symptoms experienced by subjects.
Time Frame	Single visit

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Participants With Severe Dry Eye Disease	Participants With Mild/Moderate Dry Eye Disease	Participants Without Dry Eye Disease (Normal)
Arm/Group Description	Subjects with composite severity score less than 0.20	Subjects with composite severity score between 0.20 and 0.35	Subjects with composite severity score greater than 0.35
Measure Participants	75	149	75
Mean (Standard Deviation) [Score]	41.2 (21.6)	21.0 (19.2)	5.5 (7.4)

Adverse Events

Time Frame	Time of the single visit
Adverse Event Reporting Description	No side effects were reported or observed.
Arm/Group Title	Total Number of Participants
Arm/Group Description	All participants who were tested using common signs and symptoms for dry eye disease
All Cause Mortality
	Total Number of Participants
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Total Number of Participants
	Affected / at Risk (%)	# Events
Total	0/314 (0%)
Other (Not Including Serious) Adverse Events
	Total Number of Participants
	Affected / at Risk (%)	# Events
Total	0/314 (0%)

Limitations/Caveats

95/299 subjects were using topical medication at the time of measurement, potentially lowering the diagnostic performance of osmolarity (osmolarity is lowered and responds before the other tests during therapy) and compressing the referent spread.

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.