SCORE.

Study characteristics
Methods	Study design: parallel‐group, randomized controlled trial Number randomized: Total: 271 Per group: 92 IVTA 1 mg; 91 IVTA 4 mg; 88 observation Unit of randomization: one eye per participant Exclusions after randomization: Total: none reported Per group: none reported Losses to follow‐up: Total: 33 Per group: 9 IVTA 1 mg; 9 IVTA 4 mg; 15 observation Number analyzed: Total: 238 at 12 months Per group: 83 IVTA 1 mg; 82 IVTA 4 mg; 73 observation Unit of analysis: one eye per participant Analysis of outcomes: "The primary analysis of the SCORE‐CRVO trial is based on an observed case analysis that analyzed participants based on the arm to which they were randomized (consistent with the intention‐to‐treat principle) and treated missing 12‐month observations as missing completely at random. To be included in the primary analysis, a study participant must have had 12‐month visual acuity within a window ranging from 2 months before the target date to 3 months after the target date, with the target date defined as 12 months after the date of randomization." Sample size calculation: "target sample size of 630 participants to be divided equally across three treatment arms. Due to slow recruitment, adjust to 486 participants. When it was determined about only half of the sample size was enrolled, a series of conditional power calculations were presented to the DSMB which determined the trial should continue."
Participants	Country: 66 clinical sites in the USA Study period: recruitment November 2004 to February 2008 with follow‐up and study close‐out through February 2009 Age (mean): 68 years (range 27 to 93 years) Gender (% male): 55% Underlying conditions: 62 (23%) participants had diabetes mellitus; 197 (73%) had hypertension; 56 (21%) had coronary artery disease; and 58 (21%) had a history of cancer Inclusion criteria: best‐corrected ETDRS visual acuity letter score ≤ 73 (approximate Snellen equivalent, 20/40 or worse) and ≥ 19 (20/400 or better) center‐involved macular edema secondary to CRVO present on clinical examination mean central subfield retinal thickness of 2 OCT fast macular scans, ≥ 250 μm media clarity, pupillary dilation, and participant cooperation sufficient for adequate fundus photographs Exclusion criteria: macular edema due to a cause other than CRVO any ocular condition such that visual acuity would not improve from resolution of the edema (e.g., foveal atrophy) substantial cataract estimated to have reduced visual acuity by 3 lines or more prior treatment with intravitreal corticosteroids at any time or peribulbar steroid injection within 6 months prior to randomization history of focal or grid macular photocoagulation within 15 weeks (3.5 months), panretinal photocoagulation within 4 months prior to randomization, or anticipated need for panretinal photocoagulation within the 4 months following randomization prior pars plana vitrectomy major ocular surgery (including cataract extraction) within prior 6 months or anticipated within the next 6 months following randomization yttrium aluminum garnet capsulotomy performed within 2 months prior to randomization IOP ≥ 25 mm Hg, open‐angle glaucoma (either primary open‐angle glaucoma or other cause of open‐angle glaucoma), steroid‐induced IOP elevation that required IOP‐lowering treatment, or pseudoexfoliation aphakia Equivalence of baseline characteristics? yes
Interventions	Intervention 1: intravitreal triamcinolone acetonide 1 mg; preservative‐free, single‐use, 0.05 mL dose injected into the vitreous cavity via the pars plana 3 to 4 mm posterior to the limbus Intervention 2: intravitreal triamcinolone acetonide 4 mg; preservative‐free, single‐use, 0.05 mL dose injected into the vitreous cavity via the pars plana 3 to 4 mm posterior to the limbus Control: observation Eyes assigned to observation could receive intravitreal triamcinolone when there was a loss from baseline in BCVA letter score of 15 or more that was present at 2 consecutive 4‐month–interval visits. The decrease in visual acuity had to be a result of persistent or recurrent macular edema (not because of cataract or other abnormality) that was documented on OCT. If the above criteria were met, eyes assigned to observation could receive (but were not required to receive) intravitreal triamcinolone (4 mg dose, study formulation). Length of follow up: Planned: the prespecified primary efficacy evaluation was performed at month 12 Actual: 4‐month intervals through 12 months, then annually through 36 months
Outcomes	Primary outcome, as defined in the study: the proportion of participants who experienced a gain in visual acuity of 15 letters or more from baseline to month 12, as assessed by electronic‐ETDRS Secondary outcomes, as defined in the study: mean change in visual acuity from baseline to 12 months. Additional secondary analyses were conducted to determine the consistency of the primary results which included a last‐observation‐carried‐forward analysis and a per protocol analysis that included only study eyes with 12‐month visual acuity data and excluded participants who, before 12 months, received an alternative treatment (i.e., treatment crossovers) or a non‐protocol treatment, who did not meet the eligibility criteria, or who did not receive the treatment assigned at randomization. Measurement of outcomes in the study: BCVA was measured using the electronic‐ETDRS method at 3 meters by a masked certified tester Other outcomes: other visual acuity measures included loss in visual acuity of 15 letters or more; imaging outcomes included OCT‐measured center point thickness (study eye only) and disc areas of fluorescein leakages Intervals at which outcomes were assessed: Participants were evaluated every 4 months through first 12 months and annually through 36 months. Additional safety visits were scheduled 4 days and 4 weeks after intravitreal triamcinolone injections. Stereoscopic color fundus photographs (7 fields) were taken of the study eye at baseline and at the annual visits. Three‐field photographs were taken of the study eye at the month 4, 8, 16, 20, 28, and 32 visits, and of the fellow eye at the baseline and annual visits. Fluorescein angiograms were performed at baseline and at the month 4, 12, and 24 visits. All images were sent to the reading center and graded by a masked observer. Outcomes related to cost of interventions: not reported Outcomes related to quality of life: not reported
Notes	Full study name: Standard Care vs COrticosteroid for REtinal Vein Occlusion Publication types: all types (journal articles, conference abstracts, regulatory documents, and trial registry information) Trial registration number: NCT00106132 Source of funding: National Eye Institute (USA) grants 5U10EY014351, 5U10EY014352, and 5U10EY014404. Allergan, Inc. donated investigational drug, partially funded site monitoring visits, and performed secondary data analyses. Declarations of interest: "The authors have no proprietary or commercial interest in any of the materials discussed in this article" Subgroup analyses: according to eyes with the following baseline characteristics: pseudophakic, duration of macular edema, visual acuity letter score, and OCT‐measured center point thickness
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"participants were randomly assigned centrally through a Web‐based data entry system maintained at the data coordinating center (EMMES Corporation, Rockville, Maryland), with equal probability to receive standard care (observation group), 1 mg of intravitreal triamcinolone, or 4 mg of intravitreal triamcinolone using a permuted blocks design with random block sizes"
Allocation concealment (selection bias)	Low risk	"participants were randomly assigned centrally through a Web‐based data entry system"
Masking of participants and personnel of the allocated intervention during the study (performance bias)	High risk	"Participants and physicians were masked to the intravitreal triamcinolone dose (1 mg vs 4 mg) but not to the treatment assignment of observation vs intravitreal triamcinolone."
Masking of outcome assessors during follow‐up examination (detection bias)	Low risk	Fluorescein angiograms and OCT results were assessed by a masked observer at the reading center. Visual acuity was measured at each visit by a masked technician.
Incomplete outcome data (attrition bias) All outcomes	High risk	Proportion of participants with missing data at the 12‐month visit (which was the basis of the primary outcome analysis) was identical in both 1 mg and 4 mg triamcinolone intravitreal injection arms (10%). In the observation arm, 17% of participants had missing data compared with the 6.8% observed risk for the primary outcome. Reasons for missing data were not reported. Data were analyzed assuming all missing data were missing at random.
Selective reporting (reporting bias)	Low risk	Primary analysis reported as described in methods paper. All secondary analyses were reported according to prespecified methods as well.
Other bias	Unclear risk	Study drugs provided by pharmaceutical company (Allergan, Inc.) which also provided funding for study site visits, and conducted the secondary analyses.

BCVA: best‐corrected visual acuity
BRVO: branch retinal vein occlusion
CRVO: central retinal vein occlusion
DEX: dexamethasone
ETDRS: Early Treatment Diabetic Retinopathy Study
IOP: intraocular pressure
IVTA: intravitreal triamcinolone acetonide
OCT: optical coherence tomography