The ocular surface disease index (OSDI) questionnaire is a 12-item assessment of ocular symptoms and their impact on vision-related functioning. Each of the 12 items of the OSDI are graded on a scale of 0 to 4, where 0 indicates none of the time; 1 some of the time; 2 half of the time; 3, most of the time; and 4 all of the time. The total OSDI score is then calculated by the sum of scores for all questions answered, multiplied by 100. This integer is then divided by [total number of questions answered) x 4]. The highest possible score on OSDI questionnaire being 100, represents most severe symptoms, whereas lower OSDI score represent lower symptom severity.

The Ocular Pain Assessment Survey (OPAS) is a 27-item quantitative questionnaire designed to provide an assessment of the symptoms and quality of life effect of ocular pain. Each of the 27 items is graded on a scale of 0-10, or a scale of 0% to 100%, where 0 indicates none and 10 or 100 indicate maximum. The OPAS questionnaire assess quality of life dimensions by addressing ocular pain intensity, interference with daily activities, aggravating factors and associated symptoms, as well as non-ocular pain. Higher scores indicate greater impact on quality of life, whereas lower scores indicate less interference on quality of life dimensions.

Pain score on the Visual Analog Scale graded from 0 to 10, where 0 is no pain and 10 is the worst pain one can imagine before and after a topical drop of hyperosmolar solution is applied to both eyes.

Pain score on the Visual Analog Scale graded from 0 to 10, where 0 is no pain and 10 is the worst pain one can imagine before and after a topical anesthetic drop (proparacaine) is applied to both eyes. Peripheral pain will be assessed by percent decrease in pain VAS score after topical proparacaine eye drop. Partial (greater than or equal to 50% decrease in pain VAS) or total pain relief with anesthetic drop is indicative of peripheral pain and no response to topical proparacaine is indicative of centralized neuropathic pain. Changes in pain VAS score reported after proparacaine drop from baseline to 16 weeks will be assessed.

Change in dendritic cell density on in vivo confocal microscopy from baseline to 4 weeks, and at 16 weeks.

Change in dendritic cell density on in vivo confocal microscopy from baseline and 4 weeks measure, at 8 and 16 weeks.

The Schirmer's test will be performed 5 minutes after a drop of topical anesthesia with 0.5% proparacaine (Alcon Inc., Ft Worth TX) is applied to the eye. The Schirmer test is performed by placing a narrow filter-paper strip (5 x 35 mm strip of Whatman #41 filter paper) in the inferior cul-de-sac. The resultant Schirmer strip value will be reported after 5 minutes. Aqueous tear production will be measured by the length in millimeters that the strip wets during 5 minutes. Values less than 10 mm / 5 minutes indicate tear production insufficiency. Values greater than 25 mm / 5 minutes indicate normal tear production as expected from a healthy eye.

The standard Tear Break Up Time measurement will be performed by dropping a fluorescein drop to the inferior tarsal conjunctiva and waiting 30 seconds. After several blinks, the tear film will be examined using a broad beam of the slit lamp with a blue filter. The time lapse between the last blink and the appearance of the first randomly distributed dark discontinuity in the fluorescein stained tear film will be measured three times and the mean value of the measurements will be calculated. Break-up times less than 10 seconds are considered abnormal. A positive change from baseline (increase in amount of seconds it take tear film to break up / show discontinuity) indicates improvement.

Corneal fluorescein staining will be performed after 2 minutes of application of a fluorescein drop. The entire cornea will be then examined using slit-lamp evaluation with cobalt blue illumination. Staining will be graded using the NEI grading scheme, with a total range of 0-15. Each corneal quadrant (central, superior, temporal, nasal, and inferior) will be graded for severity of staining on a scale of 0-3, 0 being no staining, 1 being mild staining, 2 being moderate staining, and 3 being severe staining. The total of all 5 corneal quadrants will be added together to get the resultant score per eye out of 15. 15/15 represents the most severe staining, whereas 0/15 represents no staining and greater ocular surface integrity and homeostasis.