Dry Eye
Conditions
Keywords
ocular surface disease, dexamethasone, ophthalmic steroids, keratoconjuntivitis sicca, dry eye
Brief summary
To determine efficacy and safety profile of dexamethasone 0.4mg lacrimal insert in dry eye related ocular surface inflammation.
Detailed description
Previous studies showed that dexamethasone and loteprednol topical drops have led to favorable results. However, the requirement of frequent instillation of drops by the patients is problematic causing discomfort and blurring of vision and requires remembering and dexterity for instillation, poor compliance is not uncommon. In addition Investigators believe that instillation of drops disturbs the homeostasis of the natural tear film due to physical and chemical trauma due to large drop volume (50 microliters) hammering on the eye surface (which can only hold 7 to 10 microliters). Particularly washing away of the mucin layer that holds all the good ingredients in the tears is harmful to the ocular surface. Therefore, dropless treatment of dry eye is desirable. Dextenza® (dexamethasone ophthalmic insert, Ocular Therapeutix Inc., Bedford, MA) is a corticosteroid intracanalicular insert approved by US-FDA in November 2018 for the treatment of post-surgical ocular inflammation and pain. It is inserted into the lower lacrimal punctum and into the canaliculus. A single insert releases a 0.4 mg dose of dexamethasone for up to 30 days following insertion. Dextenza® is resorbable and does not require removal. Investigators hypothesize that Dextenza® could mimic short-term topical steroid use in a tapering manner in patients with clinically significant dry eye and show efficacy in improving its symptoms and signs, as was previously shown with other steroid preparations. If proven, the use of Dextenza® may shift paradigms in the management of the clinically significant ocular surface disease. To test this hypothesis, investigators propose to study the effects of Dextenza® in the treatment of clinically significant dry eye.
Interventions
DRUGSustained Release Dexamethasone, 0.4 mg
dexamethasone 0.4mg lacrimal insert
OTHERE-Caprolactone-L-Lactide copolymer (PCL) punctal plug
Control eye will receive a tear duct plug without the dexamethasone (EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG made of E-Caprolactone-L-Lactide copolymer (PCL). Absorbs in 60 to 180 days. Size 0.5mm which is comparable to the study treatment)
Sponsors
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
The patient and the examining physician/outcomes accessor will be masked. The treating physician cannot be masked.
Intervention model description
Prospective, Double Masked, Interventional Study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
Yes
Inclusion criteria
A patient's study eye must meet the following criteria to be eligible for inclusion in the study: * Male or Female Age 18-100 * Capacity to give informed consent * Ability to follow study direction and complete all study visits * A previous or current diagnosis of dry eye by an eye care specialist, whereas treatment is requiring the use of a topical steroid * Able to have a lacrimal plug placement into both lower puncta. If lower puncta are already plugged or cauterized/sealed, upper puncta will be used * Females of childbearing potential unwilling to use reliable form(s) of birth control throughout study period * Clinical diagnosis of dry eye syndrome (DES) or keratoconjunctivitis sicca (KCS), in which the following has been bilaterally documented in the ophthalmic and medical histories: i. history/diagnosis of dry eye ii. has taken or is on prescription drops (including but not limited to topical steroids, cyclosporine or lifitegrast) * Presence of all of the following in both eyes at Baseline (Day 1): i. Total OSS of 3 or more with at least 2+ corneal staining (0-6) ii. Unanesthetized Schirmer level of \<10 mm at 5 minutes iii. Presence of significant symptoms defined as 30mm or higher score of (1) eye dryness, or (2) eye fatigue, or (3) eye discomfort as measured using VAS, in both eyes. At the baseline visit, the most bothersome symptom (of the three) will be determined and used as the main symptom outcome measure throughout the study.
Exclusion criteria
A patient who meets any of the following criteria will be excluded from the study: * Use of Contact lenses within 1 week of screening visit or during the study * Any ocular surgery (including tear duct cauterization) within the 3 months * Inability to place a lacrimal device into upper or lower puncta of both eyes (if upper in R eye should be upper in the left eye and vice versa) * Inability to participate in the wash out period * Use of topical glaucoma medications (With exception of rescue medication) * Pregnancy, nursing or intention of pregnancy or nursing in the study period. * Monocular patients * Uncontrolled systemic disease (defined as frequent or recent change in the medication regimen) * Patients who are currently on with stable doses of oral steroids, topical cyclosporine or lifitigrast, topical tacrolimus or pimecrolimus are eligible as long as there has been no change in the dose in the last 3 months * Patients who are on topical steroids (With exception of rescue medication) (Patients who have used steroids recently but have been off for at least 2 weeks will be eligible.) * Current enrollment in any other investigational drug or device study or participation of study within 30 days of baseline visit. * Known allergy or sensitivity to any of the clinical or experimental drugs used in this study including history of steroid response.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | 28 days | OSS will be graded according to the Sjögren's International Collaborative Clinical Alliance (SICCA) grading system. Maximum possible fluorescein score (the punctate epithelial erosions grade + any extra points for modifiers \[central staining, confluent staining, and filaments\]) will be 6 and minimum of 0. Maximum possible conjunctival staining score (the punctate epithelial erosions grade on the temporal and nasal sides) will be 6 and minimum of 0. The total possible maximum OSS, derived by summing the corneal and conjunctival scores, will be 12 for each eye, and minimum OSS will be 0. Higher corneal, conjunctival, and staining scores represent worse outcomes. The difference between the average corneal staining in the treated arm versus the average corneal staining in the sham arm will be compared statistically. |
| Patient Reported Symptom | 28 Days | (1)eye dryness, (2)eye discomfort, or (3)eye fatigue will be measured using visual analogue scale (0 to 100). The difference between the average bothersome symptom in the treated arm versus the average most bothersome symptom in the sham arm will be compared statistically. Higher VAS scores indicate worse eye dryness, discomfort, or fatigue. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects Achieving 2 Severity Grade Improvement in Corneal Staining | 42 days | Corneal staining responder analysis. Responder is defined as two full severity grade improvement in corneal staining. The percentage of subjects achieving two severity grades improvement in corneal staining (responders) in the treated arm versus sham arm will be compared statistically. |
| Percentage of Subjects Achieving Improvement in Their Most Bothersome Symptom | 42 days | Symptom responder analysis. Responder is defined as 30% or more improvement in the most bothersome symptom (VAS score is decreased by 30 points or more). The percentage of subjects achieving a 30% improvement in their most bothersome symptom (responders) in the treated arm versus the sham arm will be compared statistically. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Intraocular Pressure Increase | At day 30 and day 42 | Intraocular Pressure (IOP) measurement obtained using applanation tonometry |
Countries
United States
Participant flow
Recruitment details
Single-center, participant- and outcome assessor-masked, randomized controlled trial at the Ocular Surface Disease Clinic of Wilmer Eye Institute, The Johns Hopkins University School of Medicine in Baltimore, Maryland, USA.
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants All participants received treatment and control.
Treatment:
Commercially available Sustained Release Dexamethasone, 0.4 mg intracannalicular insert (DEXTENZA® - Ocular Therapeutix, Bedford, MA) Sustained Release Dexamethasone, 0.4 mg: dexamethasone 0.4mg lacrimal insert
Control:
FCIProlong® made of E-Caprolactone-L-Lactide copolymer (PCL) (FCI Ophthalmics Inc., Pembroke, MA) E-Caprolactone-L-Lactide copolymer (PCL) punctal plug: Control eye will receive a tear duct plug without the dexamethasone (EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG made of E-Caprolactone-L-Lactide copolymer (PCL). Absorbs in 60 to 180 days. Size 0.5mm which is comparable to the study treatment) | 75 |
| All Study Participants All participants received treatment and control.
Treatment:
Commercially available Sustained Release Dexamethasone, 0.4 mg intracannalicular insert (DEXTENZA® - Ocular Therapeutix, Bedford, MA) Sustained Release Dexamethasone, 0.4 mg: dexamethasone 0.4mg lacrimal insert
Control:
FCIProlong® made of E-Caprolactone-L-Lactide copolymer (PCL) (FCI Ophthalmics Inc., Pembroke, MA) E-Caprolactone-L-Lactide copolymer (PCL) punctal plug: Control eye will receive a tear duct plug without the dexamethasone (EXTENDED WEAR SYNTHETIC ABSORBABLE PUNCTAL PLUG made of E-Caprolactone-L-Lactide copolymer (PCL). Absorbs in 60 to 180 days. Size 0.5mm which is comparable to the study treatment) | 150 |
| Total | 225 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 3 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Customized Age Categories of Participants 18-29 years | 2 Participants |
| Age, Customized Age Categories of Participants 30-39 years | 8 Participants |
| Age, Customized Age Categories of Participants 40-49 years | 10 Participants |
| Age, Customized Age Categories of Participants 50-59 years | 19 Participants |
| Age, Customized Age Categories of Participants 60-69 years | 23 Participants |
| Age, Customized Age Categories of Participants 70-79 years | 12 Participants |
| Age, Customized Age Categories of Participants 80 years or older | 1 Participants |
| Anterior Blepharitis No | 44 Participants |
| Anterior Blepharitis Yes | 31 Participants |
| Conjunctival Scarring/Punctal stenosis No | 69 Participants |
| Conjunctival Scarring/Punctal stenosis Yes | 6 Participants |
| Corneal Haze/Scarring No | 72 Participants |
| Corneal Haze/Scarring Yes | 3 Participants |
| Corneal Vascularization No | 74 Participants |
| Corneal Vascularization Yes | 1 Participants |
| History of Corneal Ulceration No | 73 Participants |
| History of Corneal Ulceration Yes | 2 Participants |
| Posterior Blepharitis No | 6 Participants |
| Posterior Blepharitis Yes | 69 Participants |
| Pseudophakia No | 60 Participants |
| Pseudophakia Yes | 15 Participants |
| Punctal plugs No | 48 Participants |
| Punctal plugs Yes | 27 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 55 Participants |
| Sex: Female, Male Female | 65 Participants |
| Sex: Female, Male Male | 10 Participants |
| Sjögren's No | 48 Participants |
| Sjögren's Yes | 27 Participants |
| Visually Significant Cataract No | 40 Participants |
| Visually Significant Cataract Yes | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 77 | 0 / 77 |
| other Total, other adverse events | 19 / 77 | 10 / 77 |
| serious Total, serious adverse events | 1 / 77 | 1 / 77 |
Outcome results
Primary
Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS)
OSS will be graded according to the Sjögren's International Collaborative Clinical Alliance (SICCA) grading system. Maximum possible fluorescein score (the punctate epithelial erosions grade + any extra points for modifiers \[central staining, confluent staining, and filaments\]) will be 6 and minimum of 0. Maximum possible conjunctival staining score (the punctate epithelial erosions grade on the temporal and nasal sides) will be 6 and minimum of 0. The total possible maximum OSS, derived by summing the corneal and conjunctival scores, will be 12 for each eye, and minimum OSS will be 0. Higher corneal, conjunctival, and staining scores represent worse outcomes. The difference between the average corneal staining in the treated arm versus the average corneal staining in the sham arm will be compared statistically.
Time frame: 28 days
Population: Only 75 (150 eyes) patients' data were analyzed as 2 patients were lost to follow-up before 28 days.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Corneal Staining Mean Staining - Subgroup 60+ | 2.13 score on a scale | Standard Deviation 0.36 |
| Treatment Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Conjunctival Staining Mean Staining | 3.01 score on a scale | Standard Deviation 1.89 |
| Treatment Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Corneal Staining Mean Staining - Subgroup 18-59 | 2.14 score on a scale | Standard Deviation 1.29 |
| Treatment Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Conjunctival Staining Mean Staining - Subgroup 18-59 | 3.50 score on a scale | Standard Deviation 2.35 |
| Treatment Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Corneal Staining Subgroup analysis by Sjögren's status - Yes | 2.54 score on a scale | Standard Deviation 1.2 |
| Treatment Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Conjunctival Staining Mean Staining - Subgroup 60+ | 2.69 score on a scale | Standard Deviation 1.89 |
| Treatment Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Conjunctival Staining Subgroup analysis by Sjögren's status - Yes | 3.31 score on a scale | Standard Deviation 2.39 |
| Treatment Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Corneal Staining Subgroup analysis by Sjögren's status - No | 1.82 score on a scale | Standard Deviation 1.43 |
| Treatment Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Conjunctival Staining Subgroup analysis by Sjögren's status - No | 2.88 score on a scale | Standard Deviation 1.93 |
| Treatment Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Corneal Staining Mean Staining | 2.15 score on a scale | Standard Deviation 1.31 |
| Control Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Conjunctival Staining Subgroup analysis by Sjögren's status - No | 3.59 score on a scale | Standard Deviation 1.41 |
| Control Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Corneal Staining Mean Staining | 2.70 score on a scale | Standard Deviation 1.33 |
| Control Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Corneal Staining Mean Staining - Subgroup 18-59 | 2.64 score on a scale | Standard Deviation 1.55 |
| Control Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Corneal Staining Mean Staining - Subgroup 60+ | 3.06 score on a scale | Standard Deviation 1.12 |
| Control Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Corneal Staining Subgroup analysis by Sjögren's status - Yes | 3.23 score on a scale | Standard Deviation 1.42 |
| Control Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Corneal Staining Subgroup analysis by Sjögren's status - No | 2.59 score on a scale | Standard Deviation 1.23 |
| Control Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Conjunctival Staining Mean Staining | 3.69 score on a scale | Standard Deviation 1.69 |
| Control Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Conjunctival Staining Mean Staining - Subgroup 18-59 | 2.69 score on a scale | Standard Deviation 1.89 |
| Control Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Conjunctival Staining Mean Staining - Subgroup 60+ | 3.88 score on a scale | Standard Deviation 1.41 |
| Control Arm | Efficacy Endpoint as Assessed by Dry Eye Sign Using Ocular Surface Scale (OSS) | Day 28 Conjunctival Staining Subgroup analysis by Sjögren's status - Yes | 4.09 score on a scale | Standard Deviation 1.55 |
Comparison: Corneal staining sub-group analysis, day 28, 60+ year old subgroup.p-value: 0.04795% CI: [-1.86, -0.02]t-test, 2 sided
Comparison: Corneal staining sub-group analysis, day 28, Sjogren's subgroup.p-value: 0.0895% CI: [-1.49, 0.1]t-test, 2 sided
Comparison: Corneal staining analysis, day 28.p-value: 0.00395% CI: [-0.91, -0.19]t-test, 2 sided
Comparison: Corneal staining sub-group analysis, day 28, 18-59 year old subgroup.p-value: 0.1995% CI: [-1.28, 0.28]t-test, 2 sided
Comparison: Corneal staining sub-group analysis, day 28, non-Sjogren's subgroup.p-value: 0.0995% CI: [-1.67, 0.14]t-test, 2 sided
Comparison: Conjunctival staining analysis, day 28p-value: <0.00195% CI: [-1.05, -0.3]t-test, 2 sided
Comparison: Conjunctival staining sub-group analysis, day 28, 18-59 year old subgroup.p-value: 0.5895% CI: [-1.04, 0.61]t-test, 2 sided
Comparison: Conjunctival staining sub-group analysis, day 28, 60+ year old subgroup.p-value: 0.02195% CI: [-2.17, -0.21]t-test, 2 sided
Comparison: Conjunctival staining sub-group analysis, day 28, Sjogren's subgroup.p-value: 0.1695% CI: [-1.88, 0.34]t-test, 2 sided
Comparison: Conjunctival staining sub-group analysis, day 28, non-Sjogren's subgroup.p-value: 0.09795% CI: [-1.55, 0.14]t-test, 2 sided
Primary
Patient Reported Symptom
(1)eye dryness, (2)eye discomfort, or (3)eye fatigue will be measured using visual analogue scale (0 to 100). The difference between the average bothersome symptom in the treated arm versus the average most bothersome symptom in the sham arm will be compared statistically. Higher VAS scores indicate worse eye dryness, discomfort, or fatigue.
Time frame: 28 Days
Population: Only 75 (150 eyes) patients' data were analyzed as 2 patients were lost to follow-up before 28 days.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment Arm | Patient Reported Symptom | Day 28 Eye Fatigue VAS Mean Score | 43.7 units on a scale | Standard Deviation 27.5 |
| Treatment Arm | Patient Reported Symptom | Day 28 Eye Dryness VAS Mean Score | 49.3 units on a scale | Standard Deviation 26.4 |
| Treatment Arm | Patient Reported Symptom | Day 28 Eye Discomfort VAS Mean Score | 50.3 units on a scale | Standard Deviation 27.7 |
| Control Arm | Patient Reported Symptom | Day 28 Eye Dryness VAS Mean Score | 54.8 units on a scale | Standard Deviation 23 |
| Control Arm | Patient Reported Symptom | Day 28 Eye Discomfort VAS Mean Score | 50.6 units on a scale | Standard Deviation 26 |
| Control Arm | Patient Reported Symptom | Day 28 Eye Fatigue VAS Mean Score | 45.0 units on a scale | Standard Deviation 26.7 |
Comparison: Eye dryness, day 28p-value: 0.06995% CI: [-11.4, 0.4]t-test, 2 sided
Comparison: VAS Eye discomfort, Day 28p-value: 0.9295% CI: [-7, 6.3]t-test, 2 sided
Comparison: VAS eye fatigue, day 28p-value: 0.5595% CI: [-5.8, 3.1]t-test, 2 sided
Secondary
Percentage of Subjects Achieving 2 Severity Grade Improvement in Corneal Staining
Corneal staining responder analysis. Responder is defined as two full severity grade improvement in corneal staining. The percentage of subjects achieving two severity grades improvement in corneal staining (responders) in the treated arm versus sham arm will be compared statistically.
Time frame: 42 days
Population: 74 (148 eyes) patients' data were analyzed as 3 patients were lost to follow-up before 42 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Arm | Percentage of Subjects Achieving 2 Severity Grade Improvement in Corneal Staining | 32 Percentage of responders |
| Control Arm | Percentage of Subjects Achieving 2 Severity Grade Improvement in Corneal Staining | 26 Percentage of responders |
p-value: 0.4295% CI: [0.8, 2]McNemar
Secondary
Percentage of Subjects Achieving Improvement in Their Most Bothersome Symptom
Symptom responder analysis. Responder is defined as 30% or more improvement in the most bothersome symptom (VAS score is decreased by 30 points or more). The percentage of subjects achieving a 30% improvement in their most bothersome symptom (responders) in the treated arm versus the sham arm will be compared statistically.
Time frame: 42 days
Population: 74 (148 eyes) patients' data were analyzed as 3 patients were lost to follow-up before 42 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Arm | Percentage of Subjects Achieving Improvement in Their Most Bothersome Symptom | 38 Percentage of responders |
| Control Arm | Percentage of Subjects Achieving Improvement in Their Most Bothersome Symptom | 37 Percentage of responders |
p-value: 195% CI: [0.76, 1.42]McNemar
Other Pre-specified
Percentage of Participants With Intraocular Pressure Increase
Intraocular Pressure (IOP) measurement obtained using applanation tonometry
Time frame: At day 30 and day 42
Population: 75 (150 eyes) patients' data were analyzed at day 30. 74 (148 eyes) patients' data were analyzed at day 42.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment Arm | Percentage of Participants With Intraocular Pressure Increase | Day 30 : Raised intraocular pressure (increase by 5-10 mm Hg from baseline) | 12 percentage of subjects with IOP increase |
| Treatment Arm | Percentage of Participants With Intraocular Pressure Increase | Day 30 : Raised intraocular pressure (increase by >10 mm Hg from baseline) | 0 percentage of subjects with IOP increase |
| Treatment Arm | Percentage of Participants With Intraocular Pressure Increase | Day 42 : Raised intraocular pressure (increase by 5-10 mm Hg from baseline) | 11 percentage of subjects with IOP increase |
| Treatment Arm | Percentage of Participants With Intraocular Pressure Increase | Day 42 : Raised intraocular pressure (increase by >10 mm Hg from baseline) | 3 percentage of subjects with IOP increase |
| Control Arm | Percentage of Participants With Intraocular Pressure Increase | Day 42 : Raised intraocular pressure (increase by >10 mm Hg from baseline) | 1 percentage of subjects with IOP increase |
| Control Arm | Percentage of Participants With Intraocular Pressure Increase | Day 30 : Raised intraocular pressure (increase by 5-10 mm Hg from baseline) | 1 percentage of subjects with IOP increase |
| Control Arm | Percentage of Participants With Intraocular Pressure Increase | Day 42 : Raised intraocular pressure (increase by 5-10 mm Hg from baseline) | 4 percentage of subjects with IOP increase |
| Control Arm | Percentage of Participants With Intraocular Pressure Increase | Day 30 : Raised intraocular pressure (increase by >10 mm Hg from baseline) | 0 percentage of subjects with IOP increase |