MedPath

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

Completed
Conditions
Keratoconjunctivitis Sicca
Registration Number
NCT00848198
Lead Sponsor
TearLab Corporation
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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
314
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Diagnostic Test Data for Disease Using Meibomian Gland Grading Threshold > Grade 5/27Single 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).

Diagnostic Test Data for Disease Using Tear Osmolarity Threshold > 308 mOsm/LSingle 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).

Diagnostic Test Data for Disease Using Schirmer Test Threshold < 7 mmSingle 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).

Diagnostic Test Data for Disease Using Tear Film Breakup Time Threshold < 5 SecondsSingle 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).

Diagnostic Test Data for Disease Using Conjunctival Staining Threshold > Grade 3/12Single 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).

Diagnostic Test Data for Disease Using Ocular Surface Disease Index Threshold > 15/100Single 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).

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

Secondary Outcome Measures
NameTimeMethod
Referent Values for Tear OsmolaritySingle visit
Referent Values for Tear Film Breakup TimeSingle visit
Referent Values for Meibomian Gland GradingSingle 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.

Referent Values for Ocular Surface Disease IndexSingle 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.

Referent Values for Schirmer TestSingle visit
Referent Values for Corneal StainingSingle 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.

Referent Values for Conjunctival StainingSingle 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.

Trial Locations

Locations (10)

University of Wurzburg

🇩🇪

Wurzburg, Germany

Hospital Clinico San Carlos

🇪🇸

Madrid, Spain

Mundorf Eye Center

🇺🇸

Charlotte, North Carolina, United States

Pepose Vision Institute

🇺🇸

Chesterfield, Missouri, United States

Division of Vision Sciences

🇬🇧

Glasgow, Scotland, United Kingdom

Ohio State University

🇺🇸

Columbus, Ohio, United States

Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts

🇫🇷

Paris, France

Gordon Binder Weiss Vision Institute

🇺🇸

San Diego, California, United States

Kentucky Lion Eye Center

🇺🇸

Louisville, Kentucky, United States

Tauber Eye Clinic

🇺🇸

Kansas City, Missouri, United States

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