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

A Prospective Study to Establish Normative Values, Demographic Variations, Referent Diagnostic Values and Disease Severity Correlations for Dry Eye Disease and TearLab Osmometry.

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.

Study Overview

• Status: Completed
• Conditions: 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 Type: Observational
• Enrollment (Actual): 314

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Ophthalmology and Optometry Clinics

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Normal; Subjects with no objective signs of Dry Eye Disease
Dry Eye Disease; Subjects with objective signs of Dry Eye Disease

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic Test Data for Disease Using Tear Osmolarity Threshold > 308 mOsm/L	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).	Single visit
Diagnostic Test Data for Disease Using Schirmer Test Threshold < 7 mm	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).	Single visit
Diagnostic Test Data for Disease Using Tear Film Breakup Time Threshold < 5 Seconds	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).	Single visit
Diagnostic Test Data for Disease Using Corneal Staining Threshold > Grade 4/15	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).	Single visit
Diagnostic Test Data for Disease Using Conjunctival Staining Threshold > Grade 3/12	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).	Single visit
Diagnostic Test Data for Disease Using Meibomian Gland Grading Threshold > Grade 5/27	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).	Single visit
Diagnostic Test Data for Disease Using Ocular Surface Disease Index Threshold > 15/100	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).	Single visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Referent Values for Tear Osmolarity		Single visit
Referent Values for Schirmer Test		Single visit
Referent Values for Tear Film Breakup Time		Single visit
Referent Values for Corneal Staining	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.	Single visit
Referent Values for Conjunctival Staining	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.	Single visit
Referent Values for Meibomian Gland Grading	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.	Single visit
Referent Values for Ocular Surface Disease Index	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.	Single visit

Collaborators and Investigators

• Sponsor: TearLab Corporation
• Collaborators: Alcon Research
• Investigators: Study Chair: Gary Foulks, MD, Kentucky Lions Eye Center, University of Louisville

Publications and helpful links

General Publications

• Sullivan BD, Whitmer D, Nichols KK, Tomlinson A, Foulks GN, Geerling G, Pepose JS, Kosheleff V, Porreco A, Lemp MA. An objective approach to dry eye disease severity. Invest Ophthalmol Vis Sci. 2010 Dec;51(12):6125-30. doi: 10.1167/iovs.10-5390. Epub 2010 Jul 14.
• Lemp MA, Bron AJ, Baudouin C, Benitez Del Castillo JM, Geffen D, Tauber J, Foulks GN, Pepose JS, Sullivan BD. Tear osmolarity in the diagnosis and management of dry eye disease. Am J Ophthalmol. 2011 May;151(5):792-798.e1. doi: 10.1016/j.ajo.2010.10.032. Epub 2011 Feb 18.
• Lemp MA, Crews LA, Bron AJ, Foulks GN, Sullivan BD. Distribution of aqueous-deficient and evaporative dry eye in a clinic-based patient cohort: a retrospective study. Cornea. 2012 May;31(5):472-8. doi: 10.1097/ICO.0b013e318225415a.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: February 18, 2009
• First Submitted That Met QC Criteria: February 19, 2009
• First Posted (Estimate): February 20, 2009

Study Record Updates

• Last Update Posted (Estimate): May 16, 2016
• Last Update Submitted That Met QC Criteria: April 13, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Dry Eye; Dry Eye Syndrome; Dry Eye Disease
• Additional Relevant MeSH Terms: Lacrimal Apparatus Diseases; Conjunctivitis; Conjunctival Diseases; Keratitis; Corneal Diseases; Eye Diseases; Dry Eye Syndromes; Keratoconjunctivitis Sicca; Keratoconjunctivitis
• Other Study ID Numbers: TP00007 OTO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data was published in AJO May 2011 and IOVS Dec.2010.