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

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).

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).

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).

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).

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).

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).

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).

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.

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.

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.

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.