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    Clinical Trial Results:
    Periocular and Intravitreal Corticosteroids for Uveitic Macular Edema (POINT) Trial

    Summary
    EudraCT number
    		 2016-000304-29
    Trial protocol
    		 GB  
    Global end of trial date
    04 Jan 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    12 Nov 2021
    First version publication date
    12 Nov 2021
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    140840
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02374060
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    MUST Coordinating Centre Johns Hopkins Bloomberg School of Public Health
    Sponsor organisation address
    415 N. Washington St, 2nd Floor, Baltimore, MD, United States, 21231
    Public contact
    Sue Lightman, University College London, 44 02075662266, s.lightman@ucl.ac.uk
    Scientific contact
    Sue Lightman, University College London, 44 02075662266, s.lightman@ucl.ac.uk
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    04 Jan 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    04 Jan 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Jan 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To find out which therapy for uveitic macular oedema (swelling of the macula at the back of the eye due to inflammation in the eye) offers the best balance of effectiveness and tolerability, specifically by comparing the relative efficacy and safety of three commonly used treatments for macular oedema: periocular steroid (triamcinolone acetonide); intravitreal steroid (triamcinolone acetonide); and intravitreal slow release steroid implant (dexamethasone implant - Ozurdex®) for the treatment of uveitic macular edema. The primary outcome measure will be change in macular thickness (i.e. decreased swelling of the macula) at the 8 week visit.
    Protection of trial subjects
    The injection procedures, dosage of medication and treatment algorithm within the study were consistent with standard clinical treatment. To minimize risks associated with increased ocular pressure post-injection, patients with uncontrolled ocular hypertension or glaucomatous changes were excluded from the trial. Patients in the trial were not exposed to risk beyond what they would be exposed to with standard clinical care for their condition.
    Background therapy
    		 -
    Evidence for comparator
    		 Active Comparator: Periocular triamcinolone 40 mg injection (by posterior sub-Tenon's or orbital approach): A Johns Hopkins Medical Institution study of 126 patients (156 eyes) with uveitic ME who received a single periocular injection of corticosteroid reported clinical resolution of ME among 53% and 57% of eyes at 1 month and 3 months respectively. 46 Of the 83 eyes that had resolution of ME at 1 month, 50 (60%) had no recurrence of the ME at 3 months after the first periocular corticosteroid injection. Forty eyes were treated with more than one periocular injection due to persistence of ME one month following the first injection. Of the 21 eyes treated with a second periocular injection, 81% and 43% had no ME at one and 3 months, respectively, after the second injection. Overall, a 3-line improvement in visual acuity was observed in 52% at one month and in 57% at 3-months. Active Comparator: Intravitreal triamcinolone 4 mg injection A study of intravitreal triamcinolone acetonide in patients with uveitic ME was performed at Moorfields Eye Hospital. This retrospective case series of 65 eyes in 54 patients found an improvement in ME and visual acuity in 83% of eyes and a mean 12-letter gain (2.4 lines) in BCVA with intravitreal triamcinolone acetonide with a mean follow-up of 8 months Active Comparator: Intravitreal triamcinolone 4 mg injection Active Comparator: Dexamethasone intravitreal (0.7 mg) The HURON study (a sham controlled clinical trial among 229 participants) compared the safety and efficacy of a single intravitreal injection of two dexamethasone implant doses (0.7mg and 0.35mg). While both implant doses were shown to be effective in controlling vitreous inflammation and in improving visual acuity, the higher dose implant proved to have a longer duration of action. At 8 weeks, 43% of treated eyes versus 7% in the sham group had at least a 15 letter improvement from baseline BCVA. The central macular thickness was significantly lowe
    Actual start date of recruitment
    01 Jun 2015
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 42
    Country: Number of subjects enrolled
    United States: 133
    Country: Number of subjects enrolled
    Australia: 11
    Country: Number of subjects enrolled
    Canada: 6
    Worldwide total number of subjects
    192
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    144
    From 65 to 84 years
    45
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 391 screened, 192 randomized Excluded 199 Major reasons for exclusion were No macular edema (central subfield macular thickness within the normal range for the OCT machine (>300 μm for Zeiss Cirrus/Topcon 3DOCT or >320 μm for Heidelberg Spectralis) - 19% Visual acuity >20/40 or <5/200 (13%) Patient preference -16%

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    Reading center graders assessing primary outcome and visual acuity examiners masked to treatment

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Periocular triamcinolone 40mg
    Arm description
    		 Periocular triamcinolone acetonide (Kenalog® , Bristol-Myers Squibb Company, Princeton, NJ), ), 40 mg Initial injection at Week 0 Periocular triamcinolone acetonide, 40 mg injection may be given either by posterior sub-Tenon's approach or by the orbital floor approach, as both appear to have similar efficacy; the approach to the periocular injection will be recorded for analysis if needed
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Periocular triamcinolone 40mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Emulsion for injection
    Routes of administration
    Injection
    Dosage and administration details
    Periocular triamcinolone 40 mg: Periocular triamcinolone acetonide, 40 mg injection may be given either by posterior sub-Tenon’s approach or by the orbital floor approach, as both appear to have similar efficac

    Arm title
    		 Intravitreal triamcinolone 4mg
    Arm description
    		 Intravitreal triamcinolone (Triesence™, Alcon Pharmaceuticals, Fort Worth, TX)(preservative-free preparation, Triescence at U.S. clinics; Triesence preferred at non-U.S. clinics but Kenalog allowed) (4 mg) Initial injection at Week 0 Second injection permitted at Week 8 IF: • Eye does not meet the improvement definition (a 20% decrease in central subfield thickness of the macula) OR eye has a normal central subfield thickness but has cystoid spaces in the 1 mm central subfield OR ME is worse after initial improvement; Intravitreal triamcinolone acetonide, 4 mg injection procedures should be carried out under controlled aseptic conditions which include the use of sterile gloves and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide such as betadine, applied to the periocular skin, eyelid and ocular surface are required prior to an intravitreal injection.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Intravitreal triamcinolone (Triesence™, Alcon Pharmaceuticals, Fort Worth, TX)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Emulsion for injection
    Routes of administration
    Injection
    Dosage and administration details
    Intravitreal triamcinolone 4 mg: Intravitreal triamcinolone acetonide, 4 mg injection procedures should be carried out under controlled aseptic conditions which include the use of sterile gloves and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide such as betadine, applied to the periocular skin, eyelid and ocular surface are required prior to an intravitreal injection

    Arm title
    		 Dexamethasone intravitreal implant (Ozurdex) (0.7 mg)
    Arm description
    		 Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) implant (Ozurdex®, Allergan, Irvine CA) Initial injection at Week 0 Second injection permitted at Week 12 IF: • Eye does not meet the improvement definition (a 20% decrease in central subfield thickness of the macula) OR eye has a normal central subfield thickness but has cystoid spaces in the 1 mm central subfield OR ME is worse after initial improvement; • IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents;
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) implant
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Implant in pre-filled syringe
    Routes of administration
    Implantation
    Dosage and administration details
    Standard preparation Initial injection at Week 0 Second injection permitted at Week 12 IF: • Eye does not meet the improvement definition (a 20% decrease in central subfield thickness of the macula) OR eye has a normal central subfield thickness but has cystoid spaces in the 1 mm central subfield OR ME is worse after initial improvement; • IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents

    Number of subjects in period 1
    		Periocular triamcinolone 40mg Intravitreal triamcinolone 4mg Dexamethasone intravitreal implant (Ozurdex) (0.7 mg)
    Started
    65
    63
    64
    week 8
    65
    63
    64
    Completed
    65
    63
    64

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Periocular triamcinolone 40mg
    Reporting group description
    		 Periocular triamcinolone acetonide (Kenalog® , Bristol-Myers Squibb Company, Princeton, NJ), ), 40 mg Initial injection at Week 0 Periocular triamcinolone acetonide, 40 mg injection may be given either by posterior sub-Tenon's approach or by the orbital floor approach, as both appear to have similar efficacy; the approach to the periocular injection will be recorded for analysis if needed

    Reporting group title
    Intravitreal triamcinolone 4mg
    Reporting group description
    		 Intravitreal triamcinolone (Triesence™, Alcon Pharmaceuticals, Fort Worth, TX)(preservative-free preparation, Triescence at U.S. clinics; Triesence preferred at non-U.S. clinics but Kenalog allowed) (4 mg) Initial injection at Week 0 Second injection permitted at Week 8 IF: • Eye does not meet the improvement definition (a 20% decrease in central subfield thickness of the macula) OR eye has a normal central subfield thickness but has cystoid spaces in the 1 mm central subfield OR ME is worse after initial improvement; Intravitreal triamcinolone acetonide, 4 mg injection procedures should be carried out under controlled aseptic conditions which include the use of sterile gloves and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide such as betadine, applied to the periocular skin, eyelid and ocular surface are required prior to an intravitreal injection.

    Reporting group title
    Dexamethasone intravitreal implant (Ozurdex) (0.7 mg)
    Reporting group description
    		 Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) implant (Ozurdex®, Allergan, Irvine CA) Initial injection at Week 0 Second injection permitted at Week 12 IF: • Eye does not meet the improvement definition (a 20% decrease in central subfield thickness of the macula) OR eye has a normal central subfield thickness but has cystoid spaces in the 1 mm central subfield OR ME is worse after initial improvement; • IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents;

    Reporting group values
    		 Periocular triamcinolone 40mg Intravitreal triamcinolone 4mg Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) Total
    Number of subjects
    		 65 63 64 192
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 55 (22 to 87) 56 (18 to 86) 55 (19 to 85) -
    Gender categorical
    Units: Subjects
        Female
    		 39 40 40 119
        Male
    		 26 23 24 73
    Retinal thickness at the center subfield
    Retinal thickness at the center subfield measured by OCT
    Units: um
        median (full range (min-max))
    		 -
    Visual acuity
    easure Description: Participants' visual acuity was measured by certified examiners with best refractive correction in place.Participants were challenged with reading letters on lines of the standard ETDRS eye chart (5 letters per line). Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until no more meaningful readings could be made and were scored by how many letters could be correctly identified. More letters read is associated with higher visual acuity.
    Units: standard letters
        median (full range (min-max))
    		 -
    Intraocular pressure (IOP)
    Units: mm Hg
        median (full range (min-max))
    		 -
    Subject analysis sets

    Subject analysis set title
    Macular edema eyes from Arm 1 (Periocular triamcinolone)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Eyes with macular edema from Arm 1 (Periocular triamcinolone acetonide (Kenalog® , Bristol-Myers Squibb Company, Princeton, NJ), ), 40 mg )Initial injection

    Subject analysis set title
    Macular edema eyes from Arm 2 (Intravitreal triamcinolone)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Macular edema eyes from Arm 2 (Intravitreal triamcinolone (Triesence™, Alcon Pharmaceuticals, Fort Worth, TX)(preservative-free preparation, Triescence at U.S. clinics; Triesence preferred at non-U.S. clinics but Kenalog allowed) (4 mg)

    Subject analysis set title
    Macular edema eyes from Arm 3 (Dexamethasone implant)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Macular edema eyes from Arm 3 (Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) implant (Ozurdex®, Allergan, Irvine CA))

    Subject analysis sets values
    		 Macular edema eyes from Arm 1 (Periocular triamcinolone) Macular edema eyes from Arm 2 (Intravitreal triamcinolone) Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects
    74
    82
    79
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    Units: years
        median (full range (min-max))
    Gender categorical
    Units: Subjects
        Female
        Male
    Retinal thickness at the center subfield
    Retinal thickness at the center subfield measured by OCT
    Units: um
        median (full range (min-max))
    438 (278 to 922)
    485 (236 to 824)
    449 (243 to 1300)
    Visual acuity
    easure Description: Participants' visual acuity was measured by certified examiners with best refractive correction in place.Participants were challenged with reading letters on lines of the standard ETDRS eye chart (5 letters per line). Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until no more meaningful readings could be made and were scored by how many letters could be correctly identified. More letters read is associated with higher visual acuity.
    Units: standard letters
        median (full range (min-max))
    68 (25 to 91)
    63 (13 to 88)
    64 (23 to 86)
    Intraocular pressure (IOP)
    Units: mm Hg
        median (full range (min-max))
    14 (6 to 20)
    14 (7 to 21)
    13 (6 to 20)

    End points

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    End points reporting groups
    Reporting group title
    Periocular triamcinolone 40mg
    Reporting group description
    		 Periocular triamcinolone acetonide (Kenalog® , Bristol-Myers Squibb Company, Princeton, NJ), ), 40 mg Initial injection at Week 0 Periocular triamcinolone acetonide, 40 mg injection may be given either by posterior sub-Tenon's approach or by the orbital floor approach, as both appear to have similar efficacy; the approach to the periocular injection will be recorded for analysis if needed

    Reporting group title
    Intravitreal triamcinolone 4mg
    Reporting group description
    		 Intravitreal triamcinolone (Triesence™, Alcon Pharmaceuticals, Fort Worth, TX)(preservative-free preparation, Triescence at U.S. clinics; Triesence preferred at non-U.S. clinics but Kenalog allowed) (4 mg) Initial injection at Week 0 Second injection permitted at Week 8 IF: • Eye does not meet the improvement definition (a 20% decrease in central subfield thickness of the macula) OR eye has a normal central subfield thickness but has cystoid spaces in the 1 mm central subfield OR ME is worse after initial improvement; Intravitreal triamcinolone acetonide, 4 mg injection procedures should be carried out under controlled aseptic conditions which include the use of sterile gloves and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide such as betadine, applied to the periocular skin, eyelid and ocular surface are required prior to an intravitreal injection.

    Reporting group title
    Dexamethasone intravitreal implant (Ozurdex) (0.7 mg)
    Reporting group description
    		 Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) implant (Ozurdex®, Allergan, Irvine CA) Initial injection at Week 0 Second injection permitted at Week 12 IF: • Eye does not meet the improvement definition (a 20% decrease in central subfield thickness of the macula) OR eye has a normal central subfield thickness but has cystoid spaces in the 1 mm central subfield OR ME is worse after initial improvement; • IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents;

    Subject analysis set title
    Macular edema eyes from Arm 1 (Periocular triamcinolone)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Eyes with macular edema from Arm 1 (Periocular triamcinolone acetonide (Kenalog® , Bristol-Myers Squibb Company, Princeton, NJ), ), 40 mg )Initial injection

    Subject analysis set title
    Macular edema eyes from Arm 2 (Intravitreal triamcinolone)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Macular edema eyes from Arm 2 (Intravitreal triamcinolone (Triesence™, Alcon Pharmaceuticals, Fort Worth, TX)(preservative-free preparation, Triescence at U.S. clinics; Triesence preferred at non-U.S. clinics but Kenalog allowed) (4 mg)

    Subject analysis set title
    Macular edema eyes from Arm 3 (Dexamethasone implant)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Macular edema eyes from Arm 3 (Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) implant (Ozurdex®, Allergan, Irvine CA))

    Primary: Change in central subfield thickness at 8 weeks measured as the proportion of the baseline central subfield thickness

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    End point title
    		 Change in central subfield thickness at 8 weeks measured as the proportion of the baseline central subfield thickness
    End point description
    The primary outcome is the change in central subfield thickness assessed with OCT by masked readers from baseline to 8 weeks measured on a relative scale as the the proportion of the baseline central subfield thickness. Values less than 1 indicate a decrease in retinal thickness with lower values indicating greater decreases. Smaller values are better.
    End point type
    Primary
    End point timeframe
    The time point of 8 weeks from randomization was chosen for assessment of the primary outcome because it encompasses the window for maximum benefit for all three treatment strategies. Retinal thickness was evaluated using masked assessments of OCT images
    End point values
    		 Macular edema eyes from Arm 1 (Periocular triamcinolone) Macular edema eyes from Arm 2 (Intravitreal triamcinolone) Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects analysed
    74
    82
    79
    Units: Proportion of Baseline Central Subfield
        arithmetic mean (confidence interval 95%)
    .77 (.67 to .89)
    .61 (.53 to .70)
    .54 (.46 to .63)
    Statistical analysis title
    		 Intravitreal over Periocular
    Statistical analysis description
    Proportion of Baseline Central Subfield Thickness Observed at 8 Weeks. Compare Intravitreal Triamcinolone 4mg to periocular Triamcinolone 40mg,
    Comparison groups
    Macular edema eyes from Arm 1 (Periocular triamcinolone) v Macular edema eyes from Arm 2 (Intravitreal triamcinolone)
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 < 0.0001
    Method
    		 Mixed effects model
    Parameter type
    		 Ratio of the proportion of BL
    Point estimate
    0.79
    Confidence interval
         level
    		 99.87%
         sides
    2-sided
         lower limit
    		 0.65
         upper limit
    		 0.96
    Notes
    [1] - Two sided type I error threshold was 0.00132 since recruitment was halted after the single pre-planned interim analysis
    Statistical analysis title
    		 Dexamethasone implant over Periocular Triamcinolon
    Comparison groups
    Macular edema eyes from Arm 1 (Periocular triamcinolone) v Macular edema eyes from Arm 3 (Dexamethasone implant) v Macular edema eyes from Arm 2 (Intravitreal triamcinolone)
    Number of subjects included in analysis
    235
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Ratio of the proportion of BL
    Point estimate
    0.69
    Confidence interval
         level
    		 99.87%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 0.86
    Statistical analysis title
    		 Dexamethasone implant over intravitreal
    Comparison groups
    Macular edema eyes from Arm 3 (Dexamethasone implant) v Macular edema eyes from Arm 1 (Periocular triamcinolone) v Macular edema eyes from Arm 2 (Intravitreal triamcinolone)
    Number of subjects included in analysis
    235
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority
    Method
    Parameter type
    		 Ratio of the proportion of BL
    Point estimate
    0.88
    Confidence interval
         level
    		 99.87%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.08

    Secondary: Change in central subfield thickness at 24 weeks measured as the proportion of the baseline central subfield thickness

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    End point title
    		 Change in central subfield thickness at 24 weeks measured as the proportion of the baseline central subfield thickness
    End point description
    The primary outcome is the change in central subfield thickness from baseline to 24 weeks measured on a relative scale as the the proportion of the baseline central subfield thickness. Values less than 1 indicate a decrease in retinal thickness with lower values indicating greater decreases. Smaller values are better. The time point of 24 weeks was chosen to evaluate the duration of response and the need for additional injections. Retinal thickness was evaluated using masked assessments of OCT images
    End point type
    Secondary
    End point timeframe
    At baseline and the 24 week visit
    End point values
    		 Macular edema eyes from Arm 1 (Periocular triamcinolone) Macular edema eyes from Arm 2 (Intravitreal triamcinolone) Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects analysed
    74
    82
    79
    Units: proportion of the baseline central subfi
        arithmetic mean (confidence interval 99.87%)
    0.68 (0.59 to 0.79)
    0.64 (0.56 to 0.74)
    0.61 (0.52 to 0.71)
    Statistical analysis title
    		 Ratio of intravitreal over periocular
    Statistical analysis description
    Two sided type I error threshold was 0.00132 since recruitment was halted after the single preplanned interim analysis
    Comparison groups
    Macular edema eyes from Arm 1 (Periocular triamcinolone) v Macular edema eyes from Arm 2 (Intravitreal triamcinolone) v Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects included in analysis
    235
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.35
    Method
    		 Mixed models analysis
    Parameter type
    		 Ratio of the proportion of BL
    Point estimate
    0.95
    Confidence interval
         level
    		 99.87%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 1.16
    Statistical analysis title
    		 Ratio of dexamethasone over periocular
    Statistical analysis description
    he 2 sided type 1 error threshold was 0.000132 since recruitment was halted after the single preplanned interim analysis
    Comparison groups
    Macular edema eyes from Arm 1 (Periocular triamcinolone) v Macular edema eyes from Arm 2 (Intravitreal triamcinolone) v Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects included in analysis
    235
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.07
    Method
    		 Mixed models analysis
    Parameter type
    		 Ratio of the proportion of BL
    Point estimate
    0.89
    Confidence interval
         level
    		 99.87%
         sides
    2-sided
         lower limit
    		 0.72
         upper limit
    		 1.1
    Statistical analysis title
    		 Ratio of dexamethasone over intravitreal
    Comparison groups
    Macular edema eyes from Arm 1 (Periocular triamcinolone) v Macular edema eyes from Arm 2 (Intravitreal triamcinolone) v Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects included in analysis
    235
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    		 Mixed models analysis
    Parameter type
    		 Ratio of the proportion of BL
    Point estimate
    0.94
    Confidence interval
         level
    		 99.87%
         sides
    2-sided
         lower limit
    		 0.77
         upper limit
    		 1.16
    Notes
    [2] - The noninferiority margin for the comparison between dexamethasone and intravitreal treatment was 1.16, that is, dexamethasone is considered noninferior if the upper boundary of the 99.87% CI is less than 1.16.

    Secondary: Proportion of Eyes With >= 20% Reduction in Macular Thickness (or Normalization Even if <20% Reduction) at 8 Weeks

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    End point title
    		 Proportion of Eyes With >= 20% Reduction in Macular Thickness (or Normalization Even if <20% Reduction) at 8 Weeks
    End point description
    Proportion of eyes with >=20% reduction in macular thickness (or normalization of macular thickness even if there is <20% reduction) at 8 weeks.
    End point type
    Secondary
    End point timeframe
    Over 8 weeks of follow-up
    End point values
    		 Macular edema eyes from Arm 1 (Periocular triamcinolone) Macular edema eyes from Arm 2 (Intravitreal triamcinolone) Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects analysed
    74
    82
    79
    Units: proportion of eyes
        arithmetic mean (confidence interval 95%)
    0.41 (0.29 to 0.52)
    0.79 (0.7 to 0.88)
    0.84 (0.74 to 0.94)
    Statistical analysis title
    		 Intravitreal over Periocular
    Comparison groups
    Macular edema eyes from Arm 1 (Periocular triamcinolone) v Macular edema eyes from Arm 2 (Intravitreal triamcinolone)
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in proportion
    Point estimate
    0.39
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.24
         upper limit
    		 0.53
    Statistical analysis title
    		 Dexamethasone implant over Periocular Triamcinolon
    Comparison groups
    Macular edema eyes from Arm 1 (Periocular triamcinolone) v Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in proportion
    Point estimate
    0.44
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.29
         upper limit
    		 0.59
    Statistical analysis title
    		 Dexamethasone implant over Intravitre Triamcinolon
    Statistical analysis description
    Dexamethasone - intravitreal
    Comparison groups
    Macular edema eyes from Arm 2 (Intravitreal triamcinolone) v Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects included in analysis
    161
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.45
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in proportion
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.09
         upper limit
    		 0.19

    Secondary: Proportion of Eyes With >= 20% Reduction in Macular Thickness (or Normalization Even if <20% Reduction) at 24 Weeks

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    End point title
    		 Proportion of Eyes With >= 20% Reduction in Macular Thickness (or Normalization Even if <20% Reduction) at 24 Weeks
    End point description
    Proportion of eyes with >=20% reduction in macular thickness (or normalization of macular thickness even if there is <20% reduction) at 24 week
    End point type
    Secondary
    End point timeframe
    24 weeks
    End point values
    		 Macular edema eyes from Arm 1 (Periocular triamcinolone) Macular edema eyes from Arm 2 (Intravitreal triamcinolone) Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects analysed
    74
    82
    79
    Units: Proportion of eyes
        arithmetic mean (confidence interval 95%)
    0.61 (0.50 to 0.72)
    0.73 (0.63 to 0.83)
    0.74 (0.61 to 0.85)
    Statistical analysis title
    		 Intravitreal over Periocular
    Statistical analysis description
    Intravitreal - Periocular
    Comparison groups
    Macular edema eyes from Arm 1 (Periocular triamcinolone) v Macular edema eyes from Arm 2 (Intravitreal triamcinolone)
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.01
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in proportion
    Point estimate
    0.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.03
         upper limit
    		 0.27
    Statistical analysis title
    		 Dexamethasone implant over Periocular Triamcinolon
    Statistical analysis description
    Dexamethasone implant - Periocular Triamcinolone
    Comparison groups
    Macular edema eyes from Arm 1 (Periocular triamcinolone) v Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.11
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in proportion
    Point estimate
    0.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.03
         upper limit
    		 0.28
    Statistical analysis title
    		 Dexamethasone implant over Intravit Triamcinolon
    Statistical analysis description
    Dexamethasone implant - Intravitreal Triamcinolone
    Comparison groups
    Macular edema eyes from Arm 2 (Intravitreal triamcinolone) v Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects included in analysis
    161
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.98
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in proportion
    Point estimate
    0.002
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.16
         upper limit
    		 0.16

    Secondary: Proportion of Eyes With Resolution of Macular Edema at 8 Weeks

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    End point title
    		 Proportion of Eyes With Resolution of Macular Edema at 8 Weeks
    End point description
    Proportion of eyes with resolution of macular edema defined as normalization of the macular thickness (i.e., < 260 um on the standardized scale) at 8 weeks. The greater the proportion the more eyes achieved resolution of macular edema.
    End point type
    Secondary
    End point timeframe
    Over 8 weeks of follow-up
    End point values
    		 Macular edema eyes from Arm 1 (Periocular triamcinolone) Macular edema eyes from Arm 2 (Intravitreal triamcinolone) Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects analysed
    74
    82
    79
    Units: Proportion of eyes
        arithmetic mean (confidence interval 95%)
    .20 (.12 to .30)
    .47 (.34 to .60)
    .61 (.48 to .73)
    Statistical analysis title
    		 Intravitreal over Periocular
    Statistical analysis description
    Intravitreal - Periocular
    Comparison groups
    Macular edema eyes from Arm 1 (Periocular triamcinolone) v Macular edema eyes from Arm 2 (Intravitreal triamcinolone)
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0005
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in proportion
    Point estimate
    0.27
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.11
         upper limit
    		 0.43
    Statistical analysis title
    		 Dexamethasone implant over Periocular Triamcinolon
    Statistical analysis description
    Dexamethasone implant - Periocular Triamcinolone
    Comparison groups
    Macular edema eyes from Arm 3 (Dexamethasone implant) v Macular edema eyes from Arm 1 (Periocular triamcinolone)
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in proportion
    Point estimate
    0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.25
         upper limit
    		 0.56
    Statistical analysis title
    		 Dexamethasone implant over Intravit Triamcinolon
    Statistical analysis description
    Dexamethasone implant - Intravitreal Triamcinolone
    Comparison groups
    Macular edema eyes from Arm 3 (Dexamethasone implant) v Macular edema eyes from Arm 2 (Intravitreal triamcinolone)
    Number of subjects included in analysis
    161
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.12
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in proportion
    Point estimate
    0.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.04
         upper limit
    		 0.3

    Secondary: Proportion of Eyes With Resolution of Macular Edema at 24 Weeks

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    End point title
    		 Proportion of Eyes With Resolution of Macular Edema at 24 Weeks
    End point description
    End point type
    Secondary
    End point timeframe
    Over 24 weeks of follow up
    End point values
    		 Macular edema eyes from Arm 1 (Periocular triamcinolone) Macular edema eyes from Arm 2 (Intravitreal triamcinolone) Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects analysed
    74
    82
    79
    Units: Proportion of eyes
        arithmetic mean (confidence interval 95%)
    0.35 (0.24 to 0.47)
    0.36 (0.24 to 0.48)
    0.41 (0.28 to 0.54)
    Statistical analysis title
    		 Intravitreal over Periocular
    Statistical analysis description
    Intravitreal - Periocular
    Comparison groups
    Macular edema eyes from Arm 1 (Periocular triamcinolone) v Macular edema eyes from Arm 2 (Intravitreal triamcinolone)
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.96
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in proportion
    Point estimate
    0.004
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.16
         upper limit
    		 0.17
    Statistical analysis title
    		 Dexamethasone implant over Periocular Triamcinolon
    Statistical analysis description
    Dexamethasone implant - Periocular Triamcinolone
    Comparison groups
    Macular edema eyes from Arm 1 (Periocular triamcinolone) v Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.51
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in proportion
    Point estimate
    0.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.11
         upper limit
    		 0.23
    Statistical analysis title
    		 Dexamethasone implant over Intravit Triamcinolon
    Statistical analysis description
    Dexamethasone implant over IntravitrealTriamcinolone
    Comparison groups
    Macular edema eyes from Arm 2 (Intravitreal triamcinolone) v Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects included in analysis
    161
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.54
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in proportion
    Point estimate
    0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.12
         upper limit
    		 0.22

    Secondary: Change in Best-corrected Visual Acuity at 8 Week

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    End point title
    		 Change in Best-corrected Visual Acuity at 8 Week
    End point description
    End point type
    Secondary
    End point timeframe
    Over 8 weeks of follow-up
    End point values
    		 Macular edema eyes from Arm 1 (Periocular triamcinolone) Macular edema eyes from Arm 2 (Intravitreal triamcinolone) Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects analysed
    74
    82
    79
    Units: Stamdard letters
        arithmetic mean (confidence interval 95%)
    4.37 (1.86 to 6.89)
    9.70 (7.26 to 12.13)
    9.53 (7.01 to 12.05)
    Statistical analysis title
    		 Intravitreal over Periocular
    Comparison groups
    Macular edema eyes from Arm 1 (Periocular triamcinolone) v Macular edema eyes from Arm 2 (Intravitreal triamcinolone)
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in mean change from baseline
    Point estimate
    5.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.82
         upper limit
    		 8.82
    Statistical analysis title
    		 Dexamethasone implant over Periocular Triamcinolon
    Statistical analysis description
    Dexamethasone implant -Periocular Triamcinolone
    Comparison groups
    Macular edema eyes from Arm 3 (Dexamethasone implant) v Macular edema eyes from Arm 1 (Periocular triamcinolone)
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.004
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in mean change from baseline
    Point estimate
    5.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.6
         upper limit
    		 8.72
    Statistical analysis title
    		 Dexamethasone implant over Intravit Triamcinolon
    Statistical analysis description
    Dexamethasone implant - Intravitreal Triamcinolone
    Comparison groups
    Macular edema eyes from Arm 2 (Intravitreal triamcinolone) v Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects included in analysis
    161
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.93
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in mean change from baseline
    Point estimate
    -0.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.67
         upper limit
    		 3.34

    Secondary: Change in Best-corrected Visual Acuity at 24 Weeks

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    End point title
    		 Change in Best-corrected Visual Acuity at 24 Weeks
    End point description
    Mean change in best-corrected visual acuity from baseline to 24 weeks. Participants' visual acuity was measured by certified examiners with best refractive correction in place. Participants were challenged with reading letters on lines of the standard ETDRS eye chart (5 letters per line). Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until no more meaningful readings could be made and were scored by how many letters could be correctly identified. More letters read is associated with higher visual acuity
    End point type
    Secondary
    End point timeframe
    Over 24 weeks of follow-up
    End point values
    		 Macular edema eyes from Arm 1 (Periocular triamcinolone) Macular edema eyes from Arm 2 (Intravitreal triamcinolone) Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects analysed
    74
    82
    79
    Units: standard letters
        arithmetic mean (confidence interval 95%)
    4.07 (0.64 to 7.51)
    9.60 (6.87 to 12.34)
    9.21 (6.62 to 11.80)
    Statistical analysis title
    		 Intravitreal over Periocular
    Comparison groups
    Macular edema eyes from Arm 1 (Periocular triamcinolone) v Macular edema eyes from Arm 2 (Intravitreal triamcinolone)
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.13
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in mean change from baseline
    Point estimate
    5.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.14
         upper limit
    		 9.92
    Statistical analysis title
    		 Dexamethasone implant over Periocular Triamcinolon
    Comparison groups
    Macular edema eyes from Arm 1 (Periocular triamcinolone) v Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.019
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in mean change from baseline
    Point estimate
    5.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 9.44
    Statistical analysis title
    		 Dexamethasone implant over Intravitre Triamcinolon
    Statistical analysis description
    Dexamethasone implant Intravitreal Triamcinolone
    Comparison groups
    Macular edema eyes from Arm 2 (Intravitreal triamcinolone) v Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects included in analysis
    161
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.84
    Method
    		 Mixed models analysis
    Parameter type
    		 Difference in mean change from baseline
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.16
         upper limit
    		 3.37

    Secondary: Cumulative Proportion of Eyes With an IOP Elevation >=30 mm Hg

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    End point title
    		 Cumulative Proportion of Eyes With an IOP Elevation >=30 mm Hg
    End point description
    End point type
    Secondary
    End point timeframe
    During 24 weeks of follow-up
    End point values
    		 Macular edema eyes from Arm 1 (Periocular triamcinolone) Macular edema eyes from Arm 2 (Intravitreal triamcinolone) Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects analysed
    74
    82
    79
    Units: Cumulative proportion of eyes
        number (confidence interval 95%)
    0.06 (0.00 to 0.12)
    0.06 (0.01 to 0.12)
    0.04 (0.00 to 0.08)
    Statistical analysis title
    		 Intravitreal over Periocular
    Comparison groups
    Macular edema eyes from Arm 2 (Intravitreal triamcinolone) v Macular edema eyes from Arm 1 (Periocular triamcinolone)
    Number of subjects included in analysis
    156
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.92
    Method
    		 Regression, Cox
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.28
         upper limit
    		 4.01
    Statistical analysis title
    		 Dexamethasone implant over Periocular Triamcinolon
    Comparison groups
    Macular edema eyes from Arm 1 (Periocular triamcinolone) v Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects included in analysis
    153
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.65
    Method
    		 Regression, Cox
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.16
         upper limit
    		 3.11
    Statistical analysis title
    		 Dexamethasone implant over Intravit Triamcinolon
    Comparison groups
    Macular edema eyes from Arm 2 (Intravitreal triamcinolone) v Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects included in analysis
    161
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.53
    Method
    		 Regression, Cox
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.16
         upper limit
    		 2.59

    Secondary: Cumulative Proportion of Eyes With Severe Vision Loss

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    End point title
    		 Cumulative Proportion of Eyes With Severe Vision Loss
    End point description
    Cumulative proportion of eyes with uveitic macular edema who experience severe vision loss (>= 15 standard letters) during the 24 weeks of follow-up.
    End point type
    Secondary
    End point timeframe
    During 24 weeks of follow up
    End point values
    		 Macular edema eyes from Arm 1 (Periocular triamcinolone) Macular edema eyes from Arm 2 (Intravitreal triamcinolone) Macular edema eyes from Arm 3 (Dexamethasone implant)
    Number of subjects analysed
    74
    81
    78
    Units: cumulative proportion of eyes at 24 week
        number (confidence interval 95%)
    0.11 (0.04 to 0.18)
    0.10 (0.0 to 0.22)
    0.05 (0.05 to 0.10)
    Statistical analysis title
    		 Intravitreal triamc over Periocular triamcinolone
    Statistical analysis description
    Intravitreal triamcinolone over Periocular triamcinolone - cumulative proportion of eyes with severe vison loss
    Comparison groups
    Macular edema eyes from Arm 2 (Intravitreal triamcinolone) v Macular edema eyes from Arm 1 (Periocular triamcinolone)
    Number of subjects included in analysis
    155
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1
    Method
    		 Regression, Cox
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.09
         upper limit
    		 1.24
    Statistical analysis title
    		 Dexamethasone over periocular triamcinolone
    Statistical analysis description
    Dexamethasone over periocular triamcinolone. Cumulative Proportion of Eyes With Severe Vision Loss
    Comparison groups
    Macular edema eyes from Arm 3 (Dexamethasone implant) v Macular edema eyes from Arm 1 (Periocular triamcinolone)
    Number of subjects included in analysis
    152
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2
    Method
    		 Regression, Cox
    Parameter type
    		 Cox proportional hazard
    Point estimate
    0.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.14
         upper limit
    		 1.5
    Statistical analysis title
    		 Dexamethasone over intravitreal triamcinolone
    Statistical analysis description
    Dexamethasone over intravitreal triamcinolone - Cumulative Proportion of Eyes With Severe Vision Loss
    Comparison groups
    Macular edema eyes from Arm 3 (Dexamethasone implant) v Macular edema eyes from Arm 2 (Intravitreal triamcinolone)
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.62
    Method
    		 Regression, Cox
    Parameter type
    		 Cox proportional hazard
    Point estimate
    1.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.34
         upper limit
    		 6.26

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Serious adverse events were reported to coordinating center within 72 hours and immediately referred to safety officer. Non-serious adverse events were reported monthly on the case report form as responses to questions about specific ocular events
    Adverse event reporting additional description
    Serious adverse event defined as an event that results in any of the following outcomes: Death, Life-threatening adverse event, Hospitalization , inpatient, Disability or permanent damage, Congenital anomaly/birth defect, other significant medical events. Also reported were ocular events that could be related to study treatment or procedures.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.1
    Reporting groups
    Reporting group title
    Periocular triamcinolone 40mg
    Reporting group description
    		 Periocular triamcinolone acetonide (Kenalog® , Bristol-Myers Squibb Company, Princeton, NJ), ), 40 mg Initial injection at Week 0 Periocular triamcinolone acetonide, 40 mg injection may be given either by posterior sub-Tenon's approach or by the orbital floor approach, as both appear to have similar efficacy; the approach to the periocular injection will be recorded for analysis if needed

    Reporting group title
    Intravitreal triamcinolone 4mg
    Reporting group description
    		 Intravitreal triamcinolone (Triesence™, Alcon Pharmaceuticals, Fort Worth, TX)(preservative-free preparation, Triescence at U.S. clinics; Triesence preferred at non-U.S. clinics but Kenalog allowed) (4 mg) Initial injection at Week 0 Second injection permitted at Week 8 IF: • Eye does not meet the improvement definition (a 20% decrease in central subfield thickness of the macula) OR eye has a normal central subfield thickness but has cystoid spaces in the 1 mm central subfield OR ME is worse after initial improvement; Intravitreal triamcinolone acetonide, 4 mg injection procedures should be carried out under controlled aseptic conditions which include the use of sterile gloves and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide such as betadine, applied to the periocular skin, eyelid and ocular surface are required prior to an intravitreal injection.

    Reporting group title
    Dexamethasone intravitreal implant (Ozurdex) (0.7 mg)
    Reporting group description
    		 Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) implant (Ozurdex®, Allergan, Irvine CA) Initial injection at Week 0 Second injection permitted at Week 12 IF: • Eye does not meet the improvement definition (a 20% decrease in central subfield thickness of the macula) OR eye has a normal central subfield thickness but has cystoid spaces in the 1 mm central subfield OR ME is worse after initial improvement; • IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents;

    Serious adverse events
    		 Periocular triamcinolone 40mg Intravitreal triamcinolone 4mg Dexamethasone intravitreal implant (Ozurdex) (0.7 mg)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    6 / 65 (9.23%)
    5 / 63 (7.94%)
    6 / 64 (9.38%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Investigations
    Intraocular pressure increased
         subjects affected / exposed
    0 / 65 (0.00%)
    2 / 63 (3.17%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mediastinoscopy
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Knee arthroplasty
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Shoulder arthroplasty
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Injection site injury
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    choroidal effusion
         subjects affected / exposed
    0 / 65 (0.00%)
    0 / 63 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ocular hypertension
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vitreous haemorrhage
         subjects affected / exposed
    0 / 65 (0.00%)
    0 / 63 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uveitis
         subjects affected / exposed
    0 / 65 (0.00%)
    0 / 63 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric polyps
         subjects affected / exposed
    0 / 65 (0.00%)
    0 / 63 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    0 / 65 (0.00%)
    1 / 63 (1.59%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Bursitis
         subjects affected / exposed
    1 / 65 (1.54%)
    0 / 63 (0.00%)
    0 / 64 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 65 (0.00%)
    0 / 63 (0.00%)
    1 / 64 (1.56%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 Periocular triamcinolone 40mg Intravitreal triamcinolone 4mg Dexamethasone intravitreal implant (Ozurdex) (0.7 mg)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    1 / 65 (1.54%)
    10 / 63 (15.87%)
    0 / 64 (0.00%)
    General disorders and administration site conditions
    Injection site reaction
    Additional description: Increase in interocular pressure to > 30 mmHg immediately following injection. (Temporary reaction to ocular injection of fluid)
    alternative assessment type: Systematic
         subjects affected / exposed
    1 / 65 (1.54%)
    10 / 63 (15.87%)
    0 / 64 (0.00%)
         occurrences all number
    1
    13
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/30269924
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