Supplementary Online Content

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1 Supplementary Online Content Caldeira D, Canastro M, Barra M, et al. Risk of substantial intraocular bleeding with novel oral anticoagulants: systematic review and meta-analysis. JAMA Ophthalmol. Published online May 7, doi: /jamaophthalmol emethods etable. Characteristics of Included Studies efigure 1. Flowchart of Study Selection efigure 2. Risk of Bias Graft efigure 3. Funnel Plot This supplementary material has been provided by the authors to give readers additional information about their work.

2 emethods. Search strategy Database(s): EBM Reviews - Cochrane Central Register of Controlled Trials November 2014, Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations and Ovid MEDLINE(R) 1946 to Present Search Strategy: # Searches Results 1 exp eye hemorrhage/ intraocular hemorrhage.af intraocular bleeding.af Choroid Hemorrhage.af Hyphema.af Retinal Hemorrhage.af Vitreous Hemorrhage.af exp Choroid Hemorrhage/ exp Hyphema/ exp Retinal Hemorrhage/ exp Vitreous Hemorrhage/ hemovitreous.af or 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9 or 10 or 11 or dabigatran.af rivaroxaban.af apixaban.af edoxaban.af pradaxa.af xarelto.af eliquis.af lixiana.af noacs.af noac.af new oral anticoagulant*.af non-vitamin K oral anticoagulant.af non-vitamin K antagonist oral anticoagulant.af. 5

3 27 darexaban.af or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or and 28 3 Web of Science TM Web Of Science: Science Citation Index Expanded, Social Sciences Citation Index, Arts & Humanities Citation Index, Conference Proceedings Citation Index Science, Conference Proceedings Citation Index - Social Science & Humanities, Current Chemical Reactions, Index Chemicus - November 2014 Search Strategy: # Searches 1 TS=((intraocular bleeding OR intraocular hemorrhage OR intraocular haemorrhage OR ocular bleeding OR ocular hemorrhage OR ocular haemorrhage OR hyphema OR Choroid Hemorrhage OR Retinal Hemorrhage OR Vitreous Hemorrhage) AND (noacs OR noac OR non vitamin k oral anticoagulant OR apixaban OR rivaroxaban OR edoxaban OR dabigatran OR eliquis OR xarelto OR savaysa OR lixiana OR pradaxa)) SciELO collections through Web of Science Search Strategy: # Searches 1 TS=((intraocular bleeding OR intraocular hemorrhage OR intraocular haemorrhage OR ocular bleeding OR ocular hemorrhage OR ocular haemorrhage OR hyphema OR Choroid Hemorrhage OR Retinal Hemorrhage OR Vitreous Hemorrhage) AND (noacs OR noac OR non vitamin k oral anticoagulant OR apixaban OR rivaroxaban OR edoxaban OR dabigatran OR eliquis OR xarelto OR savaysa OR lixiana OR pradaxa))

4 etable. Characteristics of included studies. Study Mean Age NOAC Control Follow up Post-orthopedical surgery ADVANCE patients with 2.5 mg of Apixaban BID ADVANCE patients with 2.5 mg of apixaban BID ADVANCE patients with 2.5 mg of apixaban BID RECORD patients Rivaroxaban 10 RE-MOBILIZE patients Dabigatran 220 ; 871 patients Dabigatran 150. VTE 1588 patients Enoxaparin patients with 40 mg of subcutaneous enoxaparin OD 2659 patients with 40 mg of subcutaneous enoxaparin OD 2224 patients Enoxaparin patients Enoxaparin days after anticoagulation period 60 days after anticoagulation period 60 days after anticoagulation period 30 to 35 days 3 months AMPLIFY patients Apixaban 10 mg BID for 7 days, and then 5 mg BID for 6 months AMPLIFY-EXT patients Apixaban 2.5 ; 813 patients Apixaban 5 mg BID EINSTEIN PE patients Rivaroxaban given 15 mg BID for 3 weeks, followed by patients VKA OD 6 months 829 Placebo 1 year 2405 patients VKA According to intended treatment duration: 3 months (5%), 6 months (57%), and 1 year (38%) RE-COVER patients Dabigatran 150 RE-COVER II patients Dabigatran patients 1289 patients 30 days 6 months

5 RE-MEDY 55 RE-MEDY: 1430 patients Dabigatran 150 RE-MEDY: 1426 patients RE-MEDY: 6 months; Atrial Fibrillation ARISTOTLE patients Apixaban 5mg BID AVERROES patients Apixaban 5mg BID ENGAGE-AF patients Edoxaban 60 ; 7034 patients Edoxaban 30 J-ROCKET patients Rivaroxaban 15 RE-LY patients Dabigatran 110; 6076 patients Dabigatran 150 ROCKET-AF patients Rivaroxaban patients dose adjusted Warfarin 2791 patients Aspirin 81mg to 324mg per day patients patients 3.0; except >70 years INR patients patients years 1.1 years 2.8 years >1 year 2 years 23 months AF: Atrial Fibrillation; BID: Twice daily; CrCl: Creatinine Clearance; INR: International Normalized Ratio; OD: Once daily; VKA: Vitamin K Antagonist; VTE: Venous Thromboembolism;

6 efigure 1. Flowchart of studies selection.

7 efigure 2. Risk of bias graph.

8 efigure 3. Funnel plot. As standard error increases (y axis), there is not any trend to risk ratio to be higher or lower, thus trials with smaller precision were published irrespective of the treatment direction and effect size.