POINT: PeriOcular and INTravitreal Corticosteroids for Uveitic Macular Edema Trial

• Sponsor: JHSPH Center for Clinical Trials (Other)
• Overall Status: Completed
• CT.gov ID: NCT02374060
• Collaborator: National Eye Institute (NEI) (NIH)
• Enrollment: 192
• Locations: 26
• Arms: 3
• Actual Duration (Months): 30.7
• Patients Per Site: 7.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To evaluate the relative efficacy of three commonly utilized regional corticosteroids for the regional treatment of uveitic macular edema: periocular triamcinolone acetonide; intravitreal triamcinolone acetonide; intravitreal dexamethasone implant. The primary efficacy measure will be percent change in central subfield thickness as measured by OCT at 8 weeks. Participants will continue in the study for 24 weeks in order to evaluate relative effects of the 3 treatment strategies on the duration of treatment effects, requirement for additional injections, and adverse effects.

Note: The planned sample size for the POINT Trial was 267 subjects. On 17 July 2017, with 192 subjects enrolled, the Data and Safety Monitoring Committee (DSMC) reviewed the planned interim analysis and recommended that the goals of the trial could be accomplished by completing follow-up of enrolled subjects without the recruitment of additional subjects. Per the DSMC recommendations, recruitment was suspended and follow-up of enrolled subjects was completed according to the protocol.

Condition or Disease	Intervention/Treatment	Phase
Macular Edema; Uveitis	Drug: Periocular triamcinolone 40 mg; Drug: Intravitreal triamcinolone 4 mg; Drug: Dexamethasone intravitreal implant	Phase 3

Detailed Description

Macular edema is the most common structural complication and leading cause of visual loss in patients with uveitis. Regional injections of corticosteroids are the most frequently used treatments specifically for uveitic macular edema but there is a lack of high quality evidence to guide choice of drug (e.g., triamcinolone acetonide, dexamethasone) and route of administration (e.g. periocular, intravitreal). The question of how to approach regional treatment of uveitic macular edema is a key question for ophthalmologists treating these patients. The Periocular and Intravitreal Corticosteroids for Uveitic Macular Edema (POINT) Trial is a randomized trial designed to compare the relative efficacy of three regional corticosteroids commonly utilized for the initial regional treatment of uveitic macular edema, periocular triamcinolone (Kenalog® , Bristol-Myers Squibb Company, Princeton, NJ), intravitreal triamcinolone (Triesence™, Alcon Pharmaceuticals, Fort Worth, TX), and the intravitreal dexamethasone implant (Ozurdex®, Allergan, Irvine CA) will be conducted by the MUST Research Group clinical centers throughout the U.S. and one each in Australia and the UK. After signing informed consent and undergoing eligibility evaluation, eligible patients will be randomized to one of the three study treatments to be administered at the first study visit. Randomization is by participant, if both eyes meet eligibility requirements then both eyes receive assigned treatment. The design outcome is the percent change in central subfield macular thickness on OCT from baseline to the 8 week visit. After assessment of the primary outcome at 8 weeks, second injections and best medical judgment will be used if macular edema has not improved as follows:

Eye(s) meeting trial eligibility criteria receive initial injection of assigned treatment at P01 visit.

Second injection of assigned treatment permitted at 8 week visit for periocular triamcinolone and intravitreal triamcinolone and at 12 week visit for intravitreal dexamethasone 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

And the following repeat injection criterion are met:

• IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents;

Eyes demonstrating no improvement or worsening of ME as measured by the central submacular thickness on OCT (at week 12 for periocular and intravitreal triamcinolone arms and at week 20 for intravitreal dexamethasone arm) are considered primary treatment non-responders.

Study Design

• Study Type: Interventional
• Actual Enrollment: 192 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: PeriOcular and INTravitreal Corticosteroids for Uveitic Macular Edema Trial
• Actual Study Start Date: Jun 16, 2015
• Actual Primary Completion Date: Aug 30, 2017
• Actual Study Completion Date: Jan 4, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Periocular triamcinolone 40mg Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents;	Drug: 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.; Other Names: Kenalog
Active Comparator: Intravitreal triamcinolone 4mg (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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents;	Drug: 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.; Other Names: Triescence (in U.S); Kenalog allowed at non-U.S. clinics
Active Comparator: Dexamethasoneintravitreal implant Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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;	Drug: Dexamethasone intravitreal implant; • Standard preparation as described for intravitreal injections.; Other Names: Ozurdex

Outcome Measures

Primary Outcome Measures

1. Proportion of Baseline Central Subfield Thickness Observed at 8 Weeks [At baseline and 8 weeks]

   The primary outcome is the change in central subfield thickness 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. The time point of 8 weeks 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.

Secondary Outcome Measures

1. Proportion of Baseline Central Subfield Thickness Observed at 24 Weeks [At baseline and the 24 week visit]

   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.

2. Proportion of Eyes With >= 20% Reduction in Macular Thickness (or Normalization Even if <20% Reduction) at 8 Weeks [Over 8 weeks of follow-up]

   Proportion of eyes with >=20% reduction in macular thickness (or normalization of macular thickness even if there is <20% reduction) at 8 weeks.

3. Proportion of Eyes With >= 20% Reduction in Macular Thickness (or Normalization Even if <20% Reduction) at 24 Weeks [Over 24 weeks of follow-up]

   Proportion of eyes with >=20% reduction in macular thickness (or normalization of macular thickness even if there is <20% reduction) at 24 weeks

4. Proportion of Eyes With Resolution of Macular Edema at 8 Weeks [Over 8 weeks of follow-up]

   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.

5. Proportion of Eyes With Resolution of Macular Edema at 24 Weeks [Over 24 weeks of follow-up]

   Proportion of eyes with resolution of macular edema defined as normalization of the macular thickness (i.e., <260 um on the standard scale) at 24 weeks.

6. Change in Best-corrected Visual Acuity at 8 Weeks [Over 8 weeks of follow-up]

   Mean change in best-corrected visual acuity from baseline to 8 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.

7. Change in Best-corrected Visual Acuity at 24 Weeks [Over 24 weeks of follow-up]

   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.

8. Number of Eyes With Vitreous Hemorrhage [During 24 weeks of follow-up]

   Count of eyes with vitreous hemorrhage as an immediate complication of injection.

9. Number of Eyes With Retinal Tear or Detachment [During 24 weeks of follow-up]

   Count of eyes with retinal tears or detachments during the course of follow-up.

10. Number of Eyes With Endophthalmitis [During 24 weeks of folllow-ip]

    Count of eyes with an occurrence of endophthalmitis

11. Cumulative Proportion of Eyes With Severe Vision Loss [During 24 weeks of follow-up]

    Cumulative proportion of eyes with uveitic macular edema who experience severe vision loss (>= 15 standard letters) during the 24 weeks of follow-up.

12. Cumulative Proportion of Eyes With an IOP Elevation of >=10 mm Hg Over Baseline [During 24 weeks of follow-up]

    Cumulative proportion of eyes with uveitic macular edema that experience an IOP elevation of >=10 mm Hg higher than the baseline level during 24 weeks of follow-up.

13. Cumulative Proportion of Eyes With an IOP Elevation >=24 mm Hg [During 24 weeks of follow-up]

    Cumulative proportion of eyes with uveitic macular edema that experience elevated IOP to >=24 mm Hg during 24 weeks of follow-up.

14. Cumulative Proportion of Eyes With an IOP Elevation >=30 mm Hg [During 24 weeks of follow-up]

    Cumulative proportion of eyes with uveitic macular edema that experience elevated IOP to >=30 mm Hg during 24 weeks of follow-up.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Eye level inclusion criteria - at least one eye must meet all of the following conditions:

• Non-infectious anterior, intermediate, posterior or panuveitis; either active or inactive uveitis is acceptable;

• Macular edema (ME) defined as the presence of central subfield macular thickness greater than the normal range for the OCT machine being used, regardless of the presence of cysts, as assessed by study ophthalmologist;

• Best corrected visual acuity (BCVA) 5/200 or better;

• Baseline intraocular pressure > 5 mm Hg and ≤ 21 mm Hg (current use of 3 or fewer intraocular pressure-lowering medications and/or prior glaucoma surgery are acceptable);

• Baseline fluorescein angiogram that is gradable for leakage in the central subfield

• Pupillary dilation sufficient to allow OCT testing.

Exclusion Criteria:

Patient level exclusion criteria:

-History of infectious uveitis, or of scleritis, keratitis, or infectious endophthalmitis in either eye;

History of central serous retinopathy in either eye;

• For women of childbearing potential: pregnancy, breastfeeding, or a positive pregnancy test; unwilling to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for duration of trial;

• Use of oral acetazolamide or other systemic carbonic anhydrase inhibitor at baseline;

• Oral prednisone dose > 10 mg per day (or of an alternative corticosteroid at a dose higher than that equipotent to prednisone 10 mg per day) OR oral prednisone dose ≤ 10 mg per day that has not been stable for at least 4 weeks(note that if patient is off of oral prednisone at baseline (P01 visit), dose stability requirement for past 4 weeks does not apply);

• Systemic immunosuppressive drug therapy that has not been stable for at least 4 weeks;

• Known allergy or hypersensitivity to any component of the study drugs;

Eye level exclusion criteria - at least one eye that meets all inclusion criteria cannot have any of the following conditions:

• History of severe glaucoma as defined by optic nerve damage (cup/disc ratio of ≥ 0.9 or any notching of optic nerve to the rim);

• Media opacity causing inability to assess fundus or perform OCT;

• Presence of an epiretinal membrane noted clinically or by OCT that per the judgment of study ophthalmologist may be significant enough to limit improvement of ME (i.e., causing substantial wrinkling of the retinal surface)81;

• Torn or ruptured posterior lens capsule;

• Presence of silicone oil;

• Periocular or intravitreal corticosteroid injection in past 8 weeks;

• Injection of dexamethasone intravitreal implant in past 12 weeks;

• Placement of fluocinolone acetonide implant (Retisert) in past 3 years;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jules Stein Eye Institute, UCLA	Los Angeles	California	United States	90095
2	University of California, San Francisco	San Francisco	California	United States	94143
3	Anne Bates Leach Eye Hospital, University of Miami Miller School of Medicine	Miami	Florida	United States	33136
4	University of South Florida	Tampa	Florida	United States	33612
5	Emory University	Atlanta	Georgia	United States	30322
6	Northwestern University	Chicago	Illinois	United States	60611
7	Rush University Medical Center	Chicago	Illinois	United States	60612
8	University of Iowa	Iowa City	Iowa	United States	52242
9	Johns Hopkins University	Baltimore	Maryland	United States	21287
10	National Eye Institute, NIH	Bethesda	Maryland	United States	20892
11	Massachusetts Eye and Ear Infirmary	Boston	Massachusetts	United States	02114
12	Ophthalmic Consultants of Boston	Boston	Massachusetts	United States	02114
13	Kellogg Eye Center, University of Michigan	Ann Arbor	Michigan	United States	48105
14	MAYO Clinic	Rochester	Minnesota	United States	55905
15	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
16	New York Eye and Ear Infirmary	New York	New York	United States	10016
17	Duke Eye Center, Duke University	Durham	North Carolina	United States	27710
18	Scheie Eye Institute, University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
19	Wills Eye Hospital	Philadelphia	Pennsylvania	United States	19107
20	Unniversity of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
21	Vitreoretinal Consultants	Houston	Texas	United States	77030
22	John A. Moran Eye Center, University of Utah	Salt Lake City	Utah	United States	84132
23	University of Washington	Seattle	Washington	United States	98104
24	Royal Victorian Eye & Ear Hospital	East Melbourne		Australia
25	McGill University	Montreal	Quebec	Canada	H4A 3s5
26	Moorfields Eye Hospital	London		United Kingdom	EC1V 9EL

Sponsors and Collaborators

• JHSPH Center for Clinical Trials
• National Eye Institute (NEI)

Investigators

• Study Chair: Douglas A Jabs, MD, MBA, Icahn School of Medicine, Noutn Sinai, New York, NY

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Feb 16, 2017

More Information

Publications

None provided.

• Responsible Party: JHSPH Center for Clinical Trials
• ClinicalTrials.gov Identifier: NCT02374060
• Other Study ID Numbers: IRB00006139; 1U10EY024527-01
• First Posted: Feb 27, 2015
• Last Update Posted: Dec 4, 2018
• Last Verified: May 1, 2018

• Additional relevant MeSH terms: Macular Edema; Uveitis; Edema; Dexamethasone; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Triamcinolone diacetate

Study Results

Participant Flow

Arm/Group Title	Periocular Triamcinolone 40mg	Intravitreal Triamcinolone 4mg	Dexamethasoneintravitreal Implant
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.	(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.	Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.
Period Title: Overall Study
STARTED	65	63	64
COMPLETED	63	62	61
NOT COMPLETED	2	1	3

Baseline Characteristics

Arm/Group Title	Periocular Triamcinolone 40mg	Intravitreal Triamcinolone 4mg	Dexamethasoneintravitreal Implant	Total
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.	(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.	Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.	Total of all reporting groups
Overall Participants	65	63	64	192
Overall Eyes with macular edema	74	82	79	235
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	55	56	55	55
Sex: Female, Male (Count of Participants)
Female	39 60%	40 63.5%	40 62.5%	119 62%
Male	26 40%	23 36.5%	24 37.5%	73 38%
Race/Ethnicity, Customized (Count of Participants)
White	46 70.8%	37 58.7%	39 60.9%	122 63.5%
Hispanic	1 1.5%	3 4.8%	5 7.8%	9 4.7%
Black	11 16.9%	19 30.2%	17 26.6%	47 24.5%
Other	7 10.8%	4 6.3%	3 4.7%	14 7.3%
Intraocular pressure (mm Hg) [Median (Full Range) ]
Median (Full Range) [mm Hg]	14	14	13	14
Visual acuity (Standard letters) [Median (Full Range) ]
Median (Full Range) [Standard letters]	68	63	64	64
Retinal thickness at the center subfield (um) [Median (Full Range) ]
Median (Full Range) [um]	438	485	449	462
Concomitant systemic medication (Count of Participants)
Count of Participants [Participants]	24 36.9%	23 36.5%	23 35.9%	70 36.5%

Outcome Measures

1. Primary Outcome

Title	Proportion of Baseline Central Subfield Thickness Observed at 8 Weeks
Description	The primary outcome is the change in central subfield thickness 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. The time point of 8 weeks 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.
Time Frame	At baseline and 8 weeks

Outcome Measure Data

Analysis Population Description

All eyes with uveitic macular edema at randomization according to assigned treatment ("as randomized")

Arm/Group Title	Periocular Triamcinolone 40mg	Intravitreal Triamcinolone 4mg	Dexamethasoneintravitreal Implant
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.	(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.	Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.
Measure Participants	65	63	64
Measure Eyes with uveitis macular edema	74	82	79
Mean (99.87% Confidence Interval) [proportion of baseline retinal thickness]	.77	.61	.54

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Intravitreal Triamcinolone 4mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Two sided type I error threshold was 0.00132 since recruitment was halted after the single pre-planned interim analysis
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Ratio of the proportion of BL
	Estimated Value	0.79
	Confidence Interval	(2-Sided) 99.87%; .65 to .96
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratio of intravitreal over periocular

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	the 2 sided type 1 error threshold was 0.000132 since recruitment was halted after the single preplanned interim analysis
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Ratio of the proportion of BL
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 99.87%; 0.56 to 0.86
	Parameter Dispersion	Type: Value:
	Estimation Comments	ratio of dexamethasone over periocular

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Intravitreal Triamcinolone 4mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	The non inferiority margin was 1.16
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the proportion of BL
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 99.87%; .71 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments	A mixed effects model was used to create the confidence interval for testing non-inferiority. The direction is the ratio of dexamethasone over intravitreal

2. Secondary Outcome

Title	Proportion of Baseline Central Subfield Thickness Observed at 24 Weeks
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.
Time Frame	At baseline and the 24 week visit

Outcome Measure Data

Analysis Population Description

All eyes with uveitic macular edema at randomization according to assigned treatment ("as randomized")

Arm/Group Title	Periocular Triamcinolone 40mg	Intravitreal Triamcinolone 4mg	Dexamethasoneintravitreal Implant
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.	(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.	Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.
Measure Participants	65	63	64
Measure Eyes with uveitis macular edema	74	82	79
Mean (99.87% Confidence Interval) [proportion of baseline retinal thickness]	0.68	0.64	0.61

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Intravitreal Triamcinolone 4mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.35
	Comments	Two sided type I error threshold was 0.00132 since recruitment was halted after the single Two sided type I error threshold was 0.00132 since recruitment was halted after the single preplanned interim analysis
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Ratio of the proportion of BL
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 99.87%; 0.77 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	Ratio of intravitreal over periocular

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments	the 2 sided type 1 error threshold was 0.000132 since recruitment was halted after the single preplanned interim analysis
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Ratio of the proportion of BL
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 99.87%; 0.72 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	ratio of dexamethasone over periocular

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Intravitreal Triamcinolone 4mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	The non inferiority margin was 1.16
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of the proportion of BL
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 99.87%; 0.77 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	A mixed effects model was used to create the confidence interval for testing non-inferiority. The direction is the ratio of dexamethasone over intravitreal

3. Secondary Outcome

Title	Proportion of Eyes With >= 20% Reduction in Macular Thickness (or Normalization Even if <20% Reduction) at 8 Weeks
Description	Proportion of eyes with >=20% reduction in macular thickness (or normalization of macular thickness even if there is <20% reduction) at 8 weeks.
Time Frame	Over 8 weeks of follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Periocular Triamcinolone 40mg	Intravitreal Triamcinolone 4mg	Dexamethasoneintravitreal Implant
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.	(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.	Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.
Measure Participants	65	63	64
Measure Eyes with uveitis macular edema	74	82	79
Number (95% Confidence Interval) [Proportion of eyes]	0.41	0.79	0.84

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Intravitreal Triamcinolone 4mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in proportion
	Estimated Value	0.39
	Confidence Interval	(2-Sided) 95%; 0.24 to 0.53
	Parameter Dispersion	Type: Value:
	Estimation Comments	Intravitreal - periocular

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in proportion
	Estimated Value	0.44
	Confidence Interval	(2-Sided) 95%; 0.29 to 0.59
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone - periocular

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Intravitreal Triamcinolone 4mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.45
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in proportion
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone - intravitreal

4. Secondary Outcome

Title	Proportion of Eyes With >= 20% Reduction in Macular Thickness (or Normalization Even if <20% Reduction) at 24 Weeks
Description	Proportion of eyes with >=20% reduction in macular thickness (or normalization of macular thickness even if there is <20% reduction) at 24 weeks
Time Frame	Over 24 weeks of follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Periocular Triamcinolone 40mg	Intravitreal Triamcinolone 4mg	Dexamethasoneintravitreal Implant
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.	(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.	Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.
Measure Participants	65	63	64
Measure Eyes with uveitis macular edema	74	82	79
Number (95% Confidence Interval) [Proportion of eyes]	0.61	0.73	0.74

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Intravitreal Triamcinolone 4mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in proportion
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 95%; -0.03 to 0.27
	Parameter Dispersion	Type: Value:
	Estimation Comments	Intravitreal - Periocular

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in proportion
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 95%; -0.03 to 0.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone - Periocular

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Intravitreal Triamcinolone 4mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.98
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in proportion
	Estimated Value	0.002
	Confidence Interval	(2-Sided) 95%; -0.16 to 0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone - Intravitreal

5. Secondary Outcome

Title	Proportion of Eyes With Resolution of Macular Edema at 8 Weeks
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.
Time Frame	Over 8 weeks of follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Periocular Triamcinolone 40mg	Intravitreal Triamcinolone 4mg	Dexamethasoneintravitreal Implant
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.	(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.	Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.
Measure Participants	65	63	64
Measure Eyes with uveitis macular edema	74	82	79
Number (95% Confidence Interval) [Proportion of eyes]	0.20	0.47	0.61

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Intravitreal Triamcinolone 4mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in proportion
	Estimated Value	0.27
	Confidence Interval	(2-Sided) 95%; 0.11 to 0.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	Intravitreal - periocular

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in proportion
	Estimated Value	0.40
	Confidence Interval	(2-Sided) 95%; 0.25 to 0.56
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone - periocular

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Intravitreal Triamcinolone 4mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in proportion
	Estimated Value	0.13
	Confidence Interval	(2-Sided) 95%; -0.04 to 0.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone - intravitreal

6. Secondary Outcome

Title	Proportion of Eyes With Resolution of Macular Edema at 24 Weeks
Description	Proportion of eyes with resolution of macular edema defined as normalization of the macular thickness (i.e., <260 um on the standard scale) at 24 weeks.
Time Frame	Over 24 weeks of follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Periocular Triamcinolone 40mg	Intravitreal Triamcinolone 4mg	Dexamethasoneintravitreal Implant
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.	(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.	Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.
Measure Participants	65	63	64
Measure Eyes with uveitis macular edema	74	82	79
Number (95% Confidence Interval) [Proportion of eyes]	0.35	0.36	0.41

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Intravitreal Triamcinolone 4mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.96
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in proportion
	Estimated Value	0.004
	Confidence Interval	(2-Sided) 95%; -0.16 to 0.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	Intravitreal - periocular

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.51
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in proportion
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone - periocular

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Intravitreal Triamcinolone 4mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.54
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in proportion
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.12 to 0.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone - intravitreal

7. Secondary Outcome

Title	Change in Best-corrected Visual Acuity at 8 Weeks
Description	Mean change in best-corrected visual acuity from baseline to 8 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.
Time Frame	Over 8 weeks of follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Periocular Triamcinolone 40mg	Intravitreal Triamcinolone 4mg	Dexamethasoneintravitreal Implant
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.	(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.	Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.
Measure Participants	65	63	64
Measure Eyes with uveitis macular edema	74	82	79
Mean (95% Confidence Interval) [Standard letters]	4.37	9.70	9.53

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Intravitreal Triamcinolone 4mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in mean change from BL
	Estimated Value	5.32
	Confidence Interval	(2-Sided) 95%; 1.82 to 8.82
	Parameter Dispersion	Type: Value:
	Estimation Comments	Intravitreal - periocular

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in mean change from BL
	Estimated Value	5.16
	Confidence Interval	(2-Sided) 95%; 1.60 to 8.72
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone - periocular

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Intravitreal Triamcinolone 4mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in mean change from BL
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 95%; -3.67 to 3.34
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone - intravitreal

8. Secondary Outcome

Title	Change in Best-corrected Visual Acuity at 24 Weeks
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.
Time Frame	Over 24 weeks of follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Periocular Triamcinolone 40mg	Intravitreal Triamcinolone 4mg	Dexamethasoneintravitreal Implant
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.	(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.	Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.
Measure Participants	65	63	64
Measure Eyes with uveitis macular edema	74	82	79
Mean (95% Confidence Interval) [Standard letters]	4.07	9.60	9.21

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Intravitreal Triamcinolone 4mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in mean change from BL
	Estimated Value	5.53
	Confidence Interval	(2-Sided) 95%; 1.14 to 9.92
	Parameter Dispersion	Type: Value:
	Estimation Comments	Intravitreal - periocular

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.019
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in mean change from BL
	Estimated Value	5.14
	Confidence Interval	(2-Sided) 95%; 0.84 to 9.44
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone - periocular

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Intravitreal Triamcinolone 4mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.84
	Comments
	Method	mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Difference in mean change from BL
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -4.16 to 3.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone-intravitreal

9. Secondary Outcome

Title	Number of Eyes With Vitreous Hemorrhage
Description	Count of eyes with vitreous hemorrhage as an immediate complication of injection.
Time Frame	During 24 weeks of follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Periocular Triamcinolone 40mg	Intravitreal Triamcinolone 4mg	Dexamethasoneintravitreal Implant
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.	(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.	Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.
Measure Participants	65	63	64
Measure Eyes with uveitis macular edema	74	82	79
Number [Eyes with uveitic macular edema]	1	0	1

10. Secondary Outcome

Title	Number of Eyes With Retinal Tear or Detachment
Description	Count of eyes with retinal tears or detachments during the course of follow-up.
Time Frame	During 24 weeks of follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Periocular Triamcinolone 40mg	Intravitreal Triamcinolone 4mg	Dexamethasoneintravitreal Implant
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.	(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.	Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.
Measure Participants	65	63	64
Measure Eyes with uveitis macular edema	74	82	79
Number [Eyes with uveitic macular edema]	1	0	0

11. Secondary Outcome

Title	Number of Eyes With Endophthalmitis
Description	Count of eyes with an occurrence of endophthalmitis
Time Frame	During 24 weeks of folllow-ip

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Periocular Triamcinolone 40mg	Intravitreal Triamcinolone 4mg	Dexamethasoneintravitreal Implant
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.	(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.	Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.
Measure Participants	65	63	64
Measure Eyes with uveitis macular edema	74	82	79
Number [Eyes with uveitic macular edema]	1	0	0

12. Secondary Outcome

Title	Cumulative Proportion of Eyes With Severe Vision Loss
Description	Cumulative proportion of eyes with uveitic macular edema who experience severe vision loss (>= 15 standard letters) during the 24 weeks of follow-up.
Time Frame	During 24 weeks of follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Periocular Triamcinolone 40mg	Intravitreal Triamcinolone 4mg	Dexamethasoneintravitreal Implant
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.	(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.	Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.
Measure Participants	65	63	64
Measure Eyes with uveitis macular edema	74	81	78
Number (95% Confidence Interval) [Cumulative proportion of eyes at 24 wks]	0.11	0.10	0.05

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Intravitreal Triamcinolone 4mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.33
	Confidence Interval	(2-Sided) 95%; 0.09 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments	Intravitreal/Periocular

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.20
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.46
	Confidence Interval	(2-Sided) 95%; 0.14 to 1.50
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone/Periocular

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Intravitreal Triamcinolone 4mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.62
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95%; 0.34 to 6.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone/Intravitreal

13. Secondary Outcome

Title	Cumulative Proportion of Eyes With an IOP Elevation of >=10 mm Hg Over Baseline
Description	Cumulative proportion of eyes with uveitic macular edema that experience an IOP elevation of >=10 mm Hg higher than the baseline level during 24 weeks of follow-up.
Time Frame	During 24 weeks of follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Periocular Triamcinolone 40mg	Intravitreal Triamcinolone 4mg	Dexamethasoneintravitreal Implant
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.	(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.	Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.
Measure Participants	65	63	64
Measure Eyes with uveitis macular edema	74	81	78
Number (95% Confidence Interval) [Cumulative proportion of eyes at 24 wks]	0.14	0.26	0.39

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Intravitreal Triamcinolone 4mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.92
	Confidence Interval	(2-Sided) 95%; 0.86 to 4.29
	Parameter Dispersion	Type: Value:
	Estimation Comments	Intravitreal/Periocular

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.85
	Confidence Interval	(2-Sided) 95%; 1.30 to 6.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone/Intravitreal

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Intravitreal Triamcinolone 4mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.30
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.43
	Confidence Interval	(2-Sided) 95%; 0.72 to 2.81
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone/intravitreal

14. Secondary Outcome

Title	Cumulative Proportion of Eyes With an IOP Elevation >=24 mm Hg
Description	Cumulative proportion of eyes with uveitic macular edema that experience elevated IOP to >=24 mm Hg during 24 weeks of follow-up.
Time Frame	During 24 weeks of follow-up

Outcome Measure Data

Analysis Population Description

As randomized

Arm/Group Title	Periocular Triamcinolone 40mg	Intravitreal Triamcinolone 4mg	Dexamethasoneintravitreal Implant
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.	(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.	Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.
Measure Participants	65	63	64
Measure Eyes with uveitis macular edema	74	81	78
Number (95% Confidence Interval) [Cumulative proportion of eyes at 24 wks]	0.20	0.30	0.41

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Intravitreal Triamcinolone 4mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.09
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.83
	Confidence Interval	(2-Sided) 95%; 0.91 to 3.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	Intravitreal/periocular

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.52
	Confidence Interval	(2-Sided) 95%; 1.29 to 4.91
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone/periocular

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Intravitreal Triamcinolone 4mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95%; 0.72 to 2.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone/intravitreal

15. Secondary Outcome

Title	Cumulative Proportion of Eyes With an IOP Elevation >=30 mm Hg
Description	Cumulative proportion of eyes with uveitic macular edema that experience elevated IOP to >=30 mm Hg during 24 weeks of follow-up.
Time Frame	During 24 weeks of follow-up

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Periocular Triamcinolone 40mg	Intravitreal Triamcinolone 4mg	Dexamethasoneintravitreal Implant
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.	(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.	Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.
Measure Participants	65	63	64
Measure Eyes with uveitis macular edema	74	81	78
Number (95% Confidence Interval) [Cumulative proportion of eyes at 24 wks]	0.06	0.06	0.04

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Intravitreal Triamcinolone 4mg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.92
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.28 to 4.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	Intravitreal/Periocular

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Periocular Triamcinolone 40mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95%; 0.16 to 3.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamethasone/Periocular

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Intravitreal Triamcinolone 4mg, Dexamethasoneintravitreal Implant
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.53
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.64
	Confidence Interval	(2-Sided) 95%; 0.16 to 2.59
	Parameter Dispersion	Type: Value:
	Estimation Comments	Dexamthasone/Intravitreal

Adverse Events

Time Frame	24 weeks of follow-up
Arm/Group Title	Periocular Triamcinolone 40mg		Intravitreal Triamcinolone 4mg		Dexamethasoneintravitreal Implant
Arm/Group Description	Periocular triamcinolone acetonide (Kenalog), 40 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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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 efficacy; the approach to the periocular injection will be recorded for analysis if needed.		(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; IOP of ≤21 or mm Hg and treatment with ≤3 IOP-lowering agents; 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.		Dexamethasone intravitreal implant (Ozurdex) (0.7 mg) 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; Dexamethasone intravitreal implant: • Standard preparation as described for intravitreal injections.
All Cause Mortality
	Periocular Triamcinolone 40mg		Intravitreal Triamcinolone 4mg		Dexamethasoneintravitreal Implant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/65 (0%)		0/63 (0%)		0/64 (0%)
Serious Adverse Events
	Periocular Triamcinolone 40mg		Intravitreal Triamcinolone 4mg		Dexamethasoneintravitreal Implant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/65 (9.2%)		5/63 (7.9%)		6/64 (9.4%)
Eye disorders
Choroidal	0/65 (0%)	0	0/63 (0%)	0	1/64 (1.6%)	1
Ocular hypertension	1/65 (1.5%)	1	0/63 (0%)	0	0/64 (0%)	0
uveitis	0/65 (0%)	0	0/63 (0%)	0	1/64 (1.6%)	1
Vitreous haemorrhage	0/65 (0%)	0	0/63 (0%)	0	1/64 (1.6%)	1
Gastrointestinal disorders
colitis	1/65 (1.5%)	1	0/63 (0%)	0	0/64 (0%)	0
gastric polyps	0/65 (0%)	0	0/63 (0%)	0	1/64 (1.6%)	1
General disorders
injection site injury	1/65 (1.5%)	1	0/63 (0%)	0	0/64 (0%)	0
Infections and infestations
pneumonia	0/65 (0%)	0	0/63 (0%)	0	1/64 (1.6%)	1
Investigations
Intraocular pressure increased	0/65 (0%)	0	2/63 (3.2%)	2	0/64 (0%)	0
mediastinoscopy	0/65 (0%)	0	1/63 (1.6%)	1	0/64 (0%)	0
Investigation	1/65 (1.5%)	1	0/63 (0%)	0	0/64 (0%)	0
Musculoskeletal and connective tissue disorders
bursitis	1/65 (1.5%)	2	0/63 (0%)	0	0/64 (0%)	0
Respiratory, thoracic and mediastinal disorders
chronic obstructive pulmonary disease	0/65 (0%)	0	1/63 (1.6%)	1	0/64 (0%)	0
pulmonary hypertension	0/65 (0%)	0	1/63 (1.6%)	1	0/64 (0%)	0
Surgical and medical procedures
knee arthroplasty	1/65 (1.5%)	1	0/63 (0%)	0	0/64 (0%)	0
shoulder arthroplasty	0/65 (0%)	0	0/63 (0%)	0	1/64 (1.6%)	1
Other (Not Including Serious) Adverse Events
	Periocular Triamcinolone 40mg		Intravitreal Triamcinolone 4mg		Dexamethasoneintravitreal Implant
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/65 (0%)		0/63 (0%)		0/64 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.