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

NCT00848198 | Completed Results

• 1 other identifier: TP00007 OTO
• Study Type: observational
• Target: 314
• Locations: 5 countries
• Sites: 10

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.

Conditions

Keratoconjunctivitis Sicca

Keywords

Dry Eye Disease; Dry Eye Syndrome; Dry Eye

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (7)

• 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

  Single visit

• Referent Values for Conjunctival Staining

  Single visit

Study Arms (2)

Normal

Subjects with no objective signs of Dry Eye Disease

Dry Eye Disease

Subjects with objective signs of Dry Eye Disease

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Ophthalmology and Optometry Clinics

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• TearLab Corporation: lead
• Alcon Research: collaborator

Study Sites (10)

Gordon Binder Weiss Vision Institute

San Diego, California, 92130, United States

Location

Kentucky Lion Eye Center

Louisville, Kentucky, 40202, United States

Location

Pepose Vision Institute

Chesterfield, Missouri, 63017, United States

Location

Tauber Eye Clinic

Kansas City, Missouri, 63017, United States

Location

Mundorf Eye Center

Charlotte, North Carolina, 28204, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts

Paris, France

Location

University of Wurzburg

Würzburg, Germany

Location

Hospital Clinico San Carlos

Madrid, Spain

Location

Division of Vision Sciences

Glasgow, Scotland, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 21310379 RESULT

• 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.

  PMID: 20631232 RESULT

• 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.

  PMID: 22378109 DERIVED

MeSH Terms

Conditions

Keratoconjunctivitis Sicca; Dry Eye Syndromes

Condition Hierarchy (Ancestors)

Keratoconjunctivitis; Conjunctivitis; Conjunctival Diseases; Eye Diseases; Keratitis; Corneal Diseases; Lacrimal Apparatus Diseases

Limitations and 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.

Results Point of Contact

• Title: Michael Berg, VP of Regulatory
• Organization: TearLab, Inc.

mberg@TearLab.com

858-795-6887

Study Officials

• Gary Foulks, MD

  Kentucky Lions Eye Center, University of Louisville

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2009
• First Posted: February 20, 2009
• Study Start: February 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: May 16, 2016
• Results First Posted: April 14, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will share

Locations

US (6); DE (1); FR (1); ES (1); GB (1)