Tolerability, Safety and Efficacy of Lubricin Versus Sodium Hyaluronate Eye Drops in Patients With Moderate Dry Eye

A global ocular tolerability score was determined using a 100 mm Visual Analogue Scale (VAS) on which 0 meant no symptoms and 100 meant the worst possible discomfort. This evaluation was to be performed before any ophthalmic assessment at each scheduled visit. Specific ocular symptoms were measured with the VAS included: foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision, photophobia. The patients evaluated their symptoms using the VAS giving the value they were feeling from none to an extreme value. The VAS scale was a straight horizontal line of fixed length (100 mm). The ends were defined as the extreme limits of the parameter.

Please note that Ophthalmological evaluations were performed for both eyes. Hence both the eyes - right and left - were "study-eyes".

TEAEs included all AEs occurring or worsening after the first dose of the IMD. These comprise AEs during the treatment and follow-up period. For TEAE the number of events was provided.

The corneal fluorescein staining was graded by using the Oxford scheme to assess cornea and conjunctiva epithelium damage. The Oxford grading scale divides corneal staining into six groups according to severity from 0 (absent) to 5 (severe). The examiner compared the overall appearance of the patient's corneal staining with a reference figure, simulating the pattern of staining encountered in dry eye disease. No attempt was made to count the dots or to assess the position or confluence of the dots. The examiner selected the appropriate grade that best represented the state of corneal staining. The grading system recommended by NEI divides the cornea into five zones (central, superior, temporal, nasal, and inferior) and for each zone, the severity of corneal fluorescein staining is graded on a scale from 0 to 3 based on reference figures. Therefore, the maximum score (worst outcome) was 15, the minimum (best outcome) was 0.

Please note: both the eyes, right & left, were "study-eyes".

The Schirmer test type I (without anaesthesia) was performed to measure aqueous tear secretion prior to the instillation of any dilating or anaesthetic eye drops.The rounded bent end of a sterile strip was inserted into the lower conjunctival sac over the temporal one-third of the lower eyelid margin. After 5 minutes had elapsed, the Schirmer"s test strip was removed and the length of the tear absorption on the strip was measured (millimeters/5 minutes). Changes from baseline in values of Schirmer's test type I were summarised by eye and evaluation visit, and stratified by severity level. The longer the wetted length, the healthier the status of the eye.

Please note that Ophthalmological evaluations were performed for both eyes. Hence both the eyes - right and left - were "study-eyes".

The SANDE (Symptom Assessment in Dry Eye) questionnaire was a short questionnaire to evaluate both dry eye frequency and severity by using a 100 mm VAS.

For the assessment, the subjects marked on the 100 mm VAS line the point that they felt represented their perception of their current state. The VAS score was determined by measuring in millimetres from the left hand end of the line to the point that the subject marked. The SANDE scores was then evaluated for the 2 questions severity (0-100) and frequency (0-100), where 0 was the best condition and 100 marked the worst condition.

Please note that ophthalmological evaluations were performed for both eyes. Hence both the eyes - right and left - were "study-eyes".

The SANDE (Symptom Assessment in Dry Eye) questionnaire was a short questionnaire to evaluate both dry eye severity and frequency by using a 100 mm VAS.

For the assessment, the subjects marked on the 100 mm VAS line the point that they felt represented their perception of their current state. The VAS score was determined by measuring in millimetres from the left hand end of the line to the point that the subject marked. The SANDE scores were evaluated for the 2 questions severity (0-100) and frequency (0-100), where 0 was the best condition and 100 marked the worst condition.

Please note that ophthalmological evaluations were performed for both eyes. Hence both the eyes - right and left - were "study-eyes".

OPI was used to quantify the interaction between tear film break-up time and blink intervals of a subject. It was based on the idea that, even when the TBUT was normal, if the blink interval was too slow it may cause breakage of tear film due to increased evaporation. The OPI was calculated by dividing TFBUT by inter blink interval (IBI). A visual count of the number of blinks per minute was performed while the subject read the ETDRS chart. ETDRS charts had five Sloan letters on each line; the lines were of equal difficulty, and there was a geometric progression in letter size from line to line. If the IBI and TBUT was same, dividing both give a value of 1.0. If TFBUT was more than IBI, dividing both, gave a value more than 1.0, so dryness would not occur. If TFBUT was less than IBI, dividing both gave a value less than 1.0. A subject was at risk of developing dry eye if the OPI was < 1.0; so the higher the score the better the outcome. Both eyes - right and left - were "study-eyes".

TFBUT was measured by determining the time to tear break-up. The TFBUT test was performed after instillation of 5 µl of 2% preservative-free sodium fluorescein solution into the inferior conjunctival cul-de-sac of each eye. With the aid of a slit lamp at 10X magnification using cobalt blue illumination, the examiner monitored the integrity of the tear film, noting the time it took to form lacunae (clear spaces in the tear film) from the time that the eye was opened after the last blink. This measurement was performed within 10 seconds maximum. The TFBUT was measured twice during the first minute after the instillation of the fluorescein. If the 2 readings differed by more than 2 seconds, a third reading was taken. The TFBUT value was the average of the 2 or 3 measurements. Generally, a TFBUT value of 10-35 seconds was considered normal. A value of less than 10 seconds was usually suspicious and may indicate tear film instability. Both the eyes - right and left - were "study-eyes".

BCDVA was determined by careful refraction according to the standard protocol for refraction. Chart 1 was used for testing the VA of the right eye; Chart 2 for the left eye; and Chart R for refraction only. Retroilluminated standard Early Treatment of Diabetic Retinopathy Study (ETDRS) charts were used. They had 5 Sloan letters on each line of equal difficulty, and there was a geometric progression in letter size from line to line.VAS awarded one point for every letter correctly guessed. A distance of 4 meters (m) was required between the subject's eyes and the VA chart. When a subject cannot read at least 20 letters on the chart at 4 m, the subject was tested at 1 m. If 20 or more letters were read at 4 m, the VAS for that eye was recorded as the no of letters correct at 4 m plus 30. Otherwise, the VAS was the no of letters read correctly at 1 m plus the no read at 4 m. The higher the score the better the outcome. Both eyes - right and left - were "study-eyes".

The Slit Lamp Examination was used to examine the structures of the eye (eyelids, lashes, conjunctiva, cornea, lens, iris and anterior chamber) according to different scales: Eyelid - Meibomian glands (from 0-none to 3-severe), Eyelid - Erythema (from 0-none to 4-very severe), Eyelid - Oedema (from 0-none to 4-very severe), Lashes (0-normal 1-abnormal), Conjunctiva - Erythema (from 0-none to 3-severe), Conjunctiva - Oedema (from 0-none to 4-very severe), Lens (from 0-no opacification to 3-severe lens opacification), Iris (0-normal 1-abnormal), Anterior chamber inflammation (from 0-none to 3-severe), Cornea transparency (from 0-completely transparent to 4-complete cornea opacity), Cornea neovascularization (0-absence of neovascularization to 4-neovascularization between 270° and 360°). The higher the score the worse the outcome. There was not a total score.

Please note: ophthalmological evaluations were performed for both eyes. Hence both eyes - right and left - were "study-eyes".

The intraocular pressure (IOP) of the eye was determined by the balance between the amount of aqueous humor that the eye marked and the ease with which it leaved the eye. IOP was performed using Goldmann applanation tonometry after the instillation of a topical anaesthetic. The Goldmann applanation tonometer measured the force necessary to flatten a corneal area of 3.06 mm diameter. At this diameter, the resistance of the cornea to flattening was counterbalanced by the capillary attraction of the tear film meniscus for the tonometer head. The IOP (in mm Hg) equals the flattening force (in grams) multiplied by 10. IOP was measured in both eyes after completion of all other SLEs to avoid potential interference with the other evaluations. Both eyes were tested. Normal eye pressure was between 10 to 21 mm Hg. High intraocular pressure was greater than 21 mm Hg.

Please note: ophthalmological evaluations were performed for both eyes. Hence both eyes - right and left - were "study-eyes".

The number of daily instillations of test and comparator IMD from from Visit 3 - Day 7±1 to Visit 4 - Day 14±1