Trial Outcomes & Findings for TearLab Core Validation Study to Establish Referent Values for Dry Eye Disease (NCT NCT00848198)

NCT ID: NCT00848198

Last Updated: 2016-05-16

Results Overview

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).

• Recruitment status: COMPLETED
• Target enrollment: 314 participants
• Primary outcome timeframe: Single visit
• Results posted on: 2016-05-16

Participant Flow

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.

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.

Participant milestones

Measure	Total Number of Participants All participants who were tested using common signs and symptoms for dry eye disease
Overall Study STARTED	314
Overall Study COMPLETED	299
Overall Study NOT COMPLETED	15

Reasons for withdrawal

Measure	Total Number of Participants All participants who were tested using common signs and symptoms for dry eye disease
Overall Study Incomplete Case Report Forms	15

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Total Number of Participants n=314 Participants All participants who were tested using common signs and symptoms for dry eye disease
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	269 Participants n=5 Participants
Age, Categorical >=65 years	45 Participants n=5 Participants
Age, Continuous	46.3 years STANDARD_DEVIATION 16.9 • n=5 Participants
Sex: Female, Male Female	233 Participants n=5 Participants
Sex: Female, Male Male	81 Participants n=5 Participants
Region of Enrollment France	50 participants n=5 Participants
Region of Enrollment United States	139 participants n=5 Participants
Region of Enrollment Spain	50 participants n=5 Participants
Region of Enrollment Germany	50 participants n=5 Participants
Region of Enrollment United Kingdom	25 participants n=5 Participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Measure	Participants Without Dry Eye Disease (Normal) Subjects with composite severity score greater than 0.35	Participants With Dry Eye Disease n=224 Participants Presence of dry eye disease as defined by positive reference test	Participants Without Dry Eye Disease (Normal) n=75 Participants Absence of dry eye disease as defined by negative reference test
Diagnostic Test Data for Disease Using Tear Osmolarity Threshold > 308 mOsm/L Positive diagnostic test	—	177 participants	14 participants
Diagnostic Test Data for Disease Using Tear Osmolarity Threshold > 308 mOsm/L Negative diagnostic test	—	47 participants	61 participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Measure	Participants Without Dry Eye Disease (Normal) Subjects with composite severity score greater than 0.35	Participants With Dry Eye Disease n=224 Participants Presence of dry eye disease as defined by positive reference test	Participants Without Dry Eye Disease (Normal) n=75 Participants Absence of dry eye disease as defined by negative reference test
Diagnostic Test Data for Disease Using Schirmer Test Threshold < 7 mm Positive diagnostic test	—	89 participants	13 participants
Diagnostic Test Data for Disease Using Schirmer Test Threshold < 7 mm Negative diagnostic test	—	135 participants	62 participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Measure	Participants Without Dry Eye Disease (Normal) Subjects with composite severity score greater than 0.35	Participants With Dry Eye Disease n=224 Participants Presence of dry eye disease as defined by positive reference test	Participants Without Dry Eye Disease (Normal) n=75 Participants Absence of dry eye disease as defined by negative reference test
Diagnostic Test Data for Disease Using Tear Film Breakup Time Threshold < 5 Seconds Positive diagnostic test	—	161 participants	13 participants
Diagnostic Test Data for Disease Using Tear Film Breakup Time Threshold < 5 Seconds Negative diagnostic test	—	63 participants	62 participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Measure	Participants Without Dry Eye Disease (Normal) Subjects with composite severity score greater than 0.35	Participants With Dry Eye Disease n=224 Participants Presence of dry eye disease as defined by positive reference test	Participants Without Dry Eye Disease (Normal) n=75 Participants Absence of dry eye disease as defined by negative reference test
Diagnostic Test Data for Disease Using Corneal Staining Threshold > Grade 4/15 Positive diagnostic test	—	61 participants	1 participants
Diagnostic Test Data for Disease Using Corneal Staining Threshold > Grade 4/15 Negative diagnostic test	—	163 participants	74 participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Measure	Participants Without Dry Eye Disease (Normal) Subjects with composite severity score greater than 0.35	Participants With Dry Eye Disease n=224 Participants Presence of dry eye disease as defined by positive reference test	Participants Without Dry Eye Disease (Normal) n=75 Participants Absence of dry eye disease as defined by negative reference test
Diagnostic Test Data for Disease Using Conjunctival Staining Threshold > Grade 3/12 Positive diagnostic test	—	115 participants	4 participants
Diagnostic Test Data for Disease Using Conjunctival Staining Threshold > Grade 3/12 Negative diagnostic test	—	109 participants	71 participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Measure	Participants Without Dry Eye Disease (Normal) Subjects with composite severity score greater than 0.35	Participants With Dry Eye Disease n=224 Participants Presence of dry eye disease as defined by positive reference test	Participants Without Dry Eye Disease (Normal) n=75 Participants Absence of dry eye disease as defined by negative reference test
Diagnostic Test Data for Disease Using Meibomian Gland Grading Threshold > Grade 5/27 Positive diagnostic test	—	137 participants	16 participants
Diagnostic Test Data for Disease Using Meibomian Gland Grading Threshold > Grade 5/27 Negative diagnostic test	—	87 participants	59 participants

PRIMARY outcome

Timeframe: 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).

Outcome measures

Measure	Participants Without Dry Eye Disease (Normal) Subjects with composite severity score greater than 0.35	Participants With Dry Eye Disease n=224 Participants Presence of dry eye disease as defined by positive reference test	Participants Without Dry Eye Disease (Normal) n=75 Participants Absence of dry eye disease as defined by negative reference test
Diagnostic Test Data for Disease Using Ocular Surface Disease Index Threshold > 15/100 Positive diagnostic test	—	131 participants	20 participants
Diagnostic Test Data for Disease Using Ocular Surface Disease Index Threshold > 15/100 Negative diagnostic test	—	93 participants	55 participants

SECONDARY outcome

Timeframe: Single visit

Outcome measures

Measure	Participants Without Dry Eye Disease (Normal) n=75 Participants Subjects with composite severity score greater than 0.35	Participants With Dry Eye Disease n=75 Participants Presence of dry eye disease as defined by positive reference test	Participants Without Dry Eye Disease (Normal) n=149 Participants Absence of dry eye disease as defined by negative reference test
Referent Values for Tear Osmolarity	302.2 mOsm/L Standard Deviation 8.3	336.4 mOsm/L Standard Deviation 22.3	315.0 mOsm/L Standard Deviation 11.4

SECONDARY outcome

Timeframe: Single visit

Outcome measures

Measure	Participants Without Dry Eye Disease (Normal) n=75 Participants Subjects with composite severity score greater than 0.35	Participants With Dry Eye Disease n=75 Participants Presence of dry eye disease as defined by positive reference test	Participants Without Dry Eye Disease (Normal) n=149 Participants Absence of dry eye disease as defined by negative reference test
Referent Values for Schirmer Test	19.3 mm Standard Deviation 10.4	8.2 mm Standard Deviation 8.4	13.9 mm Standard Deviation 9.5

SECONDARY outcome

Timeframe: Single visit

Outcome measures

Measure	Participants Without Dry Eye Disease (Normal) n=75 Participants Subjects with composite severity score greater than 0.35	Participants With Dry Eye Disease n=75 Participants Presence of dry eye disease as defined by positive reference test	Participants Without Dry Eye Disease (Normal) n=149 Participants Absence of dry eye disease as defined by negative reference test
Referent Values for Tear Film Breakup Time	11.8 seconds Standard Deviation 6.4	2.7 seconds Standard Deviation 1.5	6.1 seconds Standard Deviation 4.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Participants Without Dry Eye Disease (Normal) n=75 Participants Subjects with composite severity score greater than 0.35	Participants With Dry Eye Disease n=75 Participants Presence of dry eye disease as defined by positive reference test	Participants Without Dry Eye Disease (Normal) n=149 Participants Absence of dry eye disease as defined by negative reference test
Referent Values for Corneal Staining	0.4 Grade Standard Deviation 0.9	5.1 Grade Standard Deviation 4.1	1.7 Grade Standard Deviation 1.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Participants Without Dry Eye Disease (Normal) n=75 Participants Subjects with composite severity score greater than 0.35	Participants With Dry Eye Disease n=75 Participants Presence of dry eye disease as defined by positive reference test	Participants Without Dry Eye Disease (Normal) n=149 Participants Absence of dry eye disease as defined by negative reference test
Referent Values for Conjunctival Staining	1.1 Grade Standard Deviation 1.4	5.9 Grade Standard Deviation 3.6	2.6 Grade Standard Deviation 1.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Participants Without Dry Eye Disease (Normal) n=75 Participants Subjects with composite severity score greater than 0.35	Participants With Dry Eye Disease n=75 Participants Presence of dry eye disease as defined by positive reference test	Participants Without Dry Eye Disease (Normal) n=149 Participants Absence of dry eye disease as defined by negative reference test
Referent Values for Meibomian Gland Grading	2.6 Grade Standard Deviation 2.7	10.4 Grade Standard Deviation 5.2	5.6 Grade Standard Deviation 4.7

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Participants Without Dry Eye Disease (Normal) n=75 Participants Subjects with composite severity score greater than 0.35	Participants With Dry Eye Disease n=75 Participants Presence of dry eye disease as defined by positive reference test	Participants Without Dry Eye Disease (Normal) n=149 Participants Absence of dry eye disease as defined by negative reference test
Referent Values for Ocular Surface Disease Index	5.5 Score Standard Deviation 7.4	41.2 Score Standard Deviation 21.6	21.0 Score Standard Deviation 19.2

Adverse Events

Total Number of Participants

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Michael Berg, VP of Regulatory

TearLab, Inc.

Phone: 858-795-6887

Email: mberg@TearLab.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place