Lotemax® Gel 0.5% and Restasis 0.05% in Participants With Mild or Moderate Keratoconjunctivitis Sicca (Dry Eye Disease)

OSDI is a 12-item questionnaire developed to assess severity of DED. There are 3 question types: "Have you experienced any of following (light sensitivity, eye feel gritty, sore eyes, blurred vision, and poor vision) during last week?"(items 1-5); "Have problems with your eyes limited you in performing any of following (reading, driving at night, working with computer, and watching TV) during last week?" (items 6-9); and "Have your eyes felt uncomfortable in any of following situations (windy, low humidity, air conditioned) during the last week?" (items 10-12). Response of each of these questions were graded on a scale (that relate to the frequency of ocular surface disease effects) of 0 (none of the time) to 4 (all of the time).Total OSDI score was calculated using following formula: OSDI=([sum of scores for all questions answered] × 100)/([total number of questions answered] * 4). Total OSDI score ranged from 0 to 100, with higher scores representing greater disability.

Fluorescein Corneal Staining indicates the damage to the corneal epithelium (corneal epitheliopathy). Punctate corneal staining with fluorescein was evaluated and graded according to the NEI grading method. The cornea was divided into 5 regions: central, superior, inferior, nasal and temporal. Each of these 5 regions was graded from scores 0 to 3, where 0 indicated no staining (absent) and 3 maximal staining (severe damage). The total score was the sum of all these regions, ranged from 0 (absence of corneal epitheliopathy) to 15 (severe corneal epitheliopathy).

Participants eligible for enrollment rated the severity of dry eye symptoms at Baseline (Day 0) on a 5-point grading scale (ranged from 0 [no problem] to 4 [continuous or severe discomfort; intolerable]) for each of 8 symptoms in the following symptom list prior to enrollment and then selected their most bothersome symptom: Photophobia, itchiness or scratchiness, grittiness or sandiness, foreign body sensation, haziness or blurriness, eye discomfort, burning or stinging, or photopsia (sensation of light or light flashes). Participants subsequently rated their dry eye symptom severity on the same 5-point grading scale at Week 2-Week 12 for study eye for the worst symptom identified at Baseline.

LG staining is useful for monitoring evidence of eye dryness in conjunctival tissue. Scoring of conjunctival staining was done using Oxford conjunctival grading scale. The investigator instilled an ophthalmic dye (LG stain) on the eye and rated staining in 2 areas (nasal and temporal conjunctiva). Staining was rated on a 6-point scale from 0 (absent) to 5 (severe). The total score ranged from 0 (improvement; no conjunctival damage) to 12 (worsening; severe conjunctival damage).

Tear osmolarity was measured with the TearLab Osmolarity System. The TearLab instrument measures the impedance of 50 nanoliters (nL) tear samples taken with a disposable lab-on-a-chip device. Tear samples from enrolled participants were taken at Weeks 2, 4, and 12 from each eye in duplicate with a tear sampler according to the manufacturer's instructions, and the tear osmolarity for each sample was read with the TearLab instrument. Osmolarity values were provided by the TearLab instrument in 3-digit units of milliosmoles (mOsm). Change from mean baseline values for all participants within a treatment group was calculated using a participant's worst eye value at Week 12.

Tear osmolarity was measured with the TearLab Osmolarity System. The TearLab instrument measures the impedance of 50 nL tear samples taken with a disposable lab-on-a-chip device. Tear samples from enrolled participants were taken at Weeks 2, 4, and 12 from each eye in duplicate with a tear sampler according to the manufacturer's instructions, and the tear osmolarity for each sample was read with the TearLab instrument. Osmolarity values were provided by the TearLab instrument in 3-digit units of mOsm. Change from mean baseline values for all participants within a treatment group was calculated for the difference between average values between 2 eyes at Week 12.

An ocular comfort assessment questionnaire was administered at weeks 2, 4, and 12 to participants. The assessment of the degree of dry eye discomfort experienced by the participant was conducted using an adapted and validated 12-item ocular comfort questionnaire ( to measure the frequency and intensity of 6 common dry eye symptoms: dryness, grittiness, stinging, eye tiredness, pain, and itching) based upon the ocular comfort index of Johnson and Murphy. Each item (question) was graded from 0 to 4, where 0 = Not at all, 1 = Seldom; perceptible but not intense, 2 = Sometimes; intermittent with easily tolerable intensity, 3 = Frequently; often but with tolerable intensity, 4 = Constantly; constant or intolerable intensity. Total score was calculated and normalized to a score of 0 (no discomfort)-100 (more ocular discomfort) by the formula: Normalized comfort grade = ([Total Comfort Grade] * 100)/48.

The 5-item Dry Eye Questionnaire (DEQ-5) is a validated questionnaire for discriminating self-assessed severity of dry eye diagnoses. The participants rated the frequency on a scale of 0 (never) to 4 (constant) with which they have experienced 3 symptoms (watery eyes, discomfort and dryness). The participant was also asked to rate the increase in intensity of discomfort and dryness throughout the day on a scale of 0 (never have it) to 5 (very intense). Participant rated the overall severity of dry eye symptoms on a scale of 0 (no problem) to 4 (intolerable; unable to perform my daily tasks). Total DEQ-5 score was the sum of scores for frequency and intensity of dryness and discomfort plus frequency of watery eyes. A DEQ-5 total score >6 was indicative of DED and a score >12 is indicative of Sjögren's syndrome.

The TFBUT was defined as the interval between the last complete blink and the first appearance of dark zones or spots, or disruption in the tear film. Tear film breakup time is a measure of the stability of the tear film protecting the cornea and bulbar conjunctiva. 5 microliters (μL) of fluorescein solution was instilled in the participant's eye, after which the participant blinked several times, then kept the eye open. The cornea was visualized through the slit lamp using appropriate barrier filters for the white light source.

TFBUT was counted using a stopwatch. Three consecutive measurements were taken and averaged for actual TFBUT. TFBUT at Baseline (Day 0) was subtracted from TFBUT at Week 12 (Day 84) and reported as change. A higher number represented a lengthening in the TFBUT. A longer TFBUT indicated a more stable tear film.

The tear film breakup time was defined as the interval between the last complete blink and the first appearance of dark zones or spots, or disruption in the tear film. Tear film examination using any non-invasive method analyzes optical reflections from the cornea. Reflections that become distorted are characteristic of tear film breakup. Circular images were projected onto the corneal surface using an Oculus Keratograph 5M instrument, and the tear film reflection was observed on a computer. NIKBUT (initial break-up time [NIKBUTi] and average break-up time [NIKBUTav]) were determined and recorded for each eye in duplicate after participant blink 2 times. NIKBUT at Baseline (Day 0) was subtracted from NIKBUT at Week 12 (Day 84) and reported as change. A higher number represented a lengthening in the NIKBUT. A longer NIKBUT indicated a more stable tear film.

Schirmer's test measures the aqueous component of tear secretion. The Schirmer's test (anesthetized) is a measure of the tonic secretion of the aqueous component of tears. A Schirmer's test (with anaesthesia) was performed for both eyes of a participant using Schirmer's test strips. After instillation of an ophthalmic anaesthetic, Schirmer's test strips for each eye were left in place for 5 minutes with participant eyelids closed. After 5 minutes, the Schirmer's test strips were removed with forceps and the distance to where each strip was wetted was recorded in millimeters (mm). Lesser wetting of strips (low levels of tear production) were associated with dry eye.

Amount of averaged daily soothe lubricant eye drops (Bausch + Lomb) used was reported.

Participants and investigators independently rated the overall change from baseline in dry eye conditions for each participant on a 7-point Likert scale at Week 12. The scale ranged from +3 to -3, where +3 = Substantial improvement in dry eye; little or no awareness of dry eye, +2 = Some improvement in dry eye, +1 = Little improvement in dry eye, 0 = No improvement in dry eye, -1 = Slight worsening of dry eye, -2 = Some worsening of dry eye, and -3 = Substantial worsening of dry eye.

The Investigator subjectively rated the degree of eye redness on a 4-point (0-3) grading scale prior to any objective grading of eye redness for a participant, where score 0 = none absent; no redness present in the white of the eyes, 1 = mild, slightly dilated blood vessels seen in some portion of the white of the eyes; the color of vessels was typically pink, 2 = moderate more apparent dilation of blood vessels in the white of the eyes; vessel color was more intense (redder) and involves the majority of the vessel bed, 3 = severe numerous obvious dilated blood vessels throughout the white of the eyes; the vessel color was deep red.

The objective redness scoring assessment was conducted by automated means using an Oculus Keratograph 5M. Duplicate digital photographs of bulbar and limbal conjunctiva were taken with the Oculus Keratograph 5M instrument for each eye of a participant and the images were analyzed using R-Scan classification software to numerically rate the severity of ocular redness (bulbar and limbal redness) on a 4-point (0-3) grading scale, where score 0 = none absent; no redness present in the white of the eyes, 1 = mild, slightly dilated blood vessels seen in some portion of white of the eyes; color of vessels was typically pink, 2 = moderate more apparent dilation of blood vessels in the white of the eyes; vessel color was more intense (redder) and involves the majority of the vessel bed, 3 = severe numerous obvious dilated blood vessels throughout the white of the eyes; the vessel color was deep red. Keratograph 5M ocular redness grading results were averaged for each eye and for both eyes.