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

This study has been completed.
Sponsor:
Collaborator:
Alcon Research
Information provided by (Responsible Party):
TearLab Corporation
ClinicalTrials.gov Identifier:
NCT00848198
First received: February 18, 2009
Last updated: April 13, 2016
Last verified: April 2016
  Purpose
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
Keratoconjunctivitis Sicca

Study Type: Observational
Study Design: 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.

Resource links provided by NLM:


Further study details as provided by TearLab Corporation:

Primary Outcome Measures:
  • Diagnostic Test Data for Disease Using Tear Osmolarity Threshold > 308 mOsm/L [ Time Frame: Single visit ] [ Designated as safety issue: No ]

    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).


  • Diagnostic Test Data for Disease Using Schirmer Test Threshold < 7 mm [ Time Frame: Single visit ] [ Designated as safety issue: No ]

    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).


  • Diagnostic Test Data for Disease Using Tear Film Breakup Time Threshold < 5 Seconds [ Time Frame: Single visit ] [ Designated as safety issue: No ]
    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).

  • Diagnostic Test Data for Disease Using Corneal Staining Threshold > Grade 4/15 [ Time Frame: Single visit ] [ Designated as safety issue: No ]
    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).

  • Diagnostic Test Data for Disease Using Conjunctival Staining Threshold > Grade 3/12 [ Time Frame: Single visit ] [ Designated as safety issue: No ]
    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).

  • Diagnostic Test Data for Disease Using Meibomian Gland Grading Threshold > Grade 5/27 [ Time Frame: Single visit ] [ Designated as safety issue: No ]
    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).

  • Diagnostic Test Data for Disease Using Ocular Surface Disease Index Threshold > 15/100 [ Time Frame: Single visit ] [ Designated as safety issue: No ]
    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:
  • Referent Values for Tear Osmolarity [ Time Frame: Single visit ] [ Designated as safety issue: No ]
  • Referent Values for Schirmer Test [ Time Frame: Single visit ] [ Designated as safety issue: No ]
  • Referent Values for Tear Film Breakup Time [ Time Frame: Single visit ] [ Designated as safety issue: No ]
  • Referent Values for Corneal Staining [ Time Frame: Single visit ] [ Designated as safety issue: No ]
    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.

  • Referent Values for Conjunctival Staining [ Time Frame: Single visit ] [ Designated as safety issue: No ]
    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.

  • Referent Values for Meibomian Gland Grading [ Time Frame: Single visit ] [ Designated as safety issue: No ]
    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.

  • Referent Values for Ocular Surface Disease Index [ Time Frame: Single visit ] [ Designated as safety issue: No ]
    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.


Enrollment: 314
Study Start Date: February 2009
Study Completion Date: March 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts
Normal
Subjects with no objective signs of Dry Eye Disease
Dry Eye Disease
Subjects with objective signs of Dry Eye Disease

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.
  Eligibility

Ages Eligible for Study:   18 Years to 79 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Ophthalmology and Optometry Clinics
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00848198

Locations
United States, California
Gordon Binder Weiss Vision Institute
San Diego, California, United States, 92130
United States, Kentucky
Kentucky Lion Eye Center
Louisville, Kentucky, United States, 40202
United States, Missouri
Pepose Vision Institute
Chesterfield, Missouri, United States, 63017
Tauber Eye Clinic
Kansas City, Missouri, United States, 63017
United States, North Carolina
Mundorf Eye Center
Charlotte, North Carolina, United States, 28204
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
France
Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
Paris, France
Germany
University of Wurzburg
Wurzburg, Germany
Spain
Hospital Clinico San Carlos
Madrid, Spain
United Kingdom
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
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: TearLab Corporation
ClinicalTrials.gov Identifier: NCT00848198     History of Changes
Other Study ID Numbers: TP00007 OTO 
Study First Received: February 18, 2009
Results First Received: April 5, 2011
Last Updated: April 13, 2016
Health Authority: United States: Institutional Review Board
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Data was published in AJO May 2011 and IOVS Dec.2010.

Keywords provided by TearLab Corporation:
Dry Eye Disease
Dry Eye Syndrome
Dry Eye

Additional relevant MeSH terms:
Keratoconjunctivitis Sicca
Dry Eye Syndromes
Eye Diseases
Keratoconjunctivitis
Conjunctivitis
Conjunctival Diseases
Keratitis
Corneal Diseases
Lacrimal Apparatus Diseases

ClinicalTrials.gov processed this record on July 28, 2016