Characteristics of included studies

Bedrossian 1974
Methods	Study design: Quasi-randomized controlled series Exclusions after allocation: None Losses to follow-up: None Intention-to-treat: All participants were analyzed in the group to which they were assigned. Sample size calculations: Not reported
Participants	Country: USA Dates: Not reported Number allocated: 58 consecutive patients alternately assigned to treatment group after classification based on the size of initial hyphema. Age: Not reported Sex: Not reported Race: Not reported Sickle cell disease: Not reported Participants appeared to be balanced with respect to baseline characteristics. Inclusion criteria: Non-total traumatic hyphema
Interventions	Cycloplegics (n = 28): 1% atropine ointment Miotics (n = 30): 2% pilocarpine ointment (or eserine ointment) Treatment for both groups included: Topical anesthetic if needed; Bed rest; Head of bed elevated between 30 and 90 degrees; Binocular patching or pinhole glasses; No reading or watching television; Metal shield over injured eye; Soft, non-chew diet; Laxatives; Room with other individuals; and Sedation.
Outcomes	Primary outcome: Time to resolution of primary hemorrhage Secondary outcomes: Risk of secondary hemorrhage; and Risk of iridodialysis Follow-up: days 1 to 7
Notes	Funding source not reported
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	No	Allocation was not randomized; alternately assigned patients to treatment groups based on the blood level in the anterior chamber.
Allocation concealment?	No	Allocation was assigned on an alternate basis.
Blinding? Participants	No	Masking was not reported.
Blinding? Personnel and outcome assessors	No	Masking was not reported.
Incomplete outcome data addressed? Primary outcome	Yes	All participants were analyzed in the group to which they were assigned.
Incomplete outcome data addressed? Secondary outcomes	Yes	All participants were analyzed in the group to which they were assigned.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes
Christianson 1979
Methods	Study design: Randomized, double-masked, placebo-controlled clinical trial Exclusions after randomization: None reported Losses to follow-up: None reported Intention-to-treat: All participants were analyzed in the group to which they were randomly assigned. Sample size calculations: Not reported
Participants	Country: USA Dates: Not reported Number randomized: 45 Age: Not reported Sex: Not reported Race: Not reported Sickle cell disease: Not reported Inclusion criteria: Traumatic hyphema Exclusion criteria: Not reported
Interventions	Treatment (n = 22): Loading dose 75 mg/kg oral aminocaproic acid, followed by 60 mg/kg every 4 hours; length of treatment not reported. Control (n = 23): Placebo, presumably every 4 hours
Outcomes	Primary outcome: Risk of secondary hemorrhage, details not reported Secondary outcomes: Time to resolution of primary hyphema, details not reported
Notes	Abstract of unpublished study
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Unclear	Method of randomization not reported.
Allocation concealment?	Unclear	Method of allocation concealment not reported.
Blinding? Participants	Yes	Authors used a placebo control and stated that the study was double- masked.
Blinding? Personnel and outcome assessors	Yes	Authors used a placebo control and stated that the study was double- masked.
Incomplete outcome data addressed? Primary outcome	Yes	Unclear if number randomized equaled the number reported and analyzed in the abstract, but no exclusions or losses to follow-up were reported.
Incomplete outcome data addressed? Secondary outcomes	Yes	Unclear if number randomized equaled the number reported and analyzed in the abstract, but no exclusions or losses to follow-up were reported.
Free of selective reporting?	Unclear	Few study details available in the abstract and no full version was published.
Free of other bias?	Unclear	Few study details available in the abstract and no full version was published.
Crouch 1976
Methods	Study design: Randomized, double-masked, placebo-controlled clinical trial Exclusions after randomization: None Losses to follow-up: None Intention-to-treat: All participants were analyzed in the group to which they were randomly assigned. Sample size calculations: Not reported
Participants	Country: USA Dates: September 1972 to October 1974 Number randomized: 59 Age: 83% of all study participants were between the ages of 6 and 30 years. Sex: 83% of study participants were male. Race: 65% of study participants were black and 35% were white. Sickle cell disease: 8/59 (14%) of all study participants had sickle cell trait. Participants appeared to be balanced with respect to baseline characteristics. Inclusion criteria: Traumatic hyphema Exclusion criteria: Penetrating injury; Total hyphema; History of a bleeding disorder; and Pregnancy.
Interventions	Treatment (n =32): 100 mg/kg oral aminocaproic acid every 4 hours for 5 days. Control (n = 27): Placebo (200 mL of aromatic elixir (5% glucose, water, and ethanol) in 1,000 mL sterile water) every 4 hours for 5 days. Treatment for both groups included: Moderate ambulation; No reading; Head of bed elevated to 45 degrees; Patching of affected eye; No mydriatics, miotics, corticosteroids, or other topical medication; and No salicylates.
Outcomes	Primary outcome: Risk of secondary hemorrhage, assessed by daily slit lamp examination, and documented by three observers. Secondary outcomes: Time to resolution of primary hemorrhage; Time to secondary hemorrhage; Final visual acuity, with follow-up ranging between 6 months and 2.5 years; IOP assessed daily by applanation tonometry; and Risk of complications and adverse events. Follow-up: 1 week, 1, 2, 3, 6, 12, 18, and 24 months
Notes	Funded by the National Eye Institute, National Institutes of Health
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Yes	Study participants assigned to treatment groups using computerized randomization.
Allocation concealment?	Unclear	Method of allocation concealment not reported.
Blinding? Participants	Yes	Authors used a placebo control and stated that the study was double- masked.
Blinding? Personnel and outcome assessors	Yes	Authors used a placebo control and stated that the study was double- masked.
Incomplete outcome data addressed? Primary outcome	Yes	There were no exclusions and losses to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Incomplete outcome data addressed? Secondary outcomes	Yes	There were no exclusions and losses to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes
Crouch 1997
Methods	Study design: Randomized, double-masked clinical trial Exclusions after randomization: One individual assigned to oral aminocaproic acid and topical placebo excluded based on side-effect of drug (vomiting). Losses to follow-up: None Intention-to-treat: All participants were analyzed in the group to which they were randomly assigned. Sample size calculations: Sample size was determined to be between 25 and 30 participants in each of the three groups based on alpha of 0.05 and power of 80%. Additional comments: The investigators also studied a control group that did not receive either topical or systemic aminocaproic acid and had refused randomization. We did not include these patients in our analyses.
Participants	Country: USA Dates: March 1990 to May 1996 Number randomized: 64: 29 assigned to oral aminocaproic acid and topical placebo, and 35 to oral placebo and topical aminocaproic acid. Additional 54 patients included as control group. Age: 72% of study population was younger than 21 years. Sex: 67% of study population was male. Race: 50% of study population was black, 49% was white, and 1% (one participant) was Asian. Sickle cell disease: 2/35 (6%) of participants assigned to topical aminocaproic acid, and 2/29 (7%) of participants assigned to oral aminocaproic acid had sickle cell trait. Participants appeared to be balanced with respect to baseline characteristics. Inclusion criteria: Traumatic hyphema. Exclusion criteria: Penetrating ocular injury; History of anticoagulant or antiplatelet agent within 7 days of ocular trauma; Oral or topical corticosteroid use within 48 hours of study; History of a coagulopathy; History of renal or hepatic insufficiency; Previous intraocular surgery; History of sensitivity to any component of topical aminocaproic acid; Pregnancy; and Participation in any investigational drug trial within last 4 weeks.
Interventions	Treatment: 0.2 ml of 30% aminocaproic acid in 2% carboxymethylene gel applied to inferior fornix every 6 hours plus oral placebo solution every 4 hours, for 5 days. Control: 50 mg/kg oral aminocaproic acid (up to 30 g/day) plus placebo gel every 4 hours, for 5 days. Treatment for both groups included: Moderate ambulation; Head of bed elevated to 30 degrees; Shield on affected eye; No aspirin, corticosteroids, non-steroidal anti-inflammatory or antiplatelet agents; and Topical timolol maleate, apraclonidine hydrochloride, dipivefrin hydrochloride or oral acetazolamide if IOP > 22 mmHg.
Outcomes	Primary outcome: Risk of secondary hemorrhage, assessed by daily slit lamp examination, and documented by a sketch each day. Secondary outcomes: Visual acuity, measured daily and at the end of the 5 days (final visual acuity); Cell and flare, assessed daily for 5 days; Corneal blood staining and toxicity, assessed daily by slit lamp examination for 5 days; IOP assessed daily for 5 days by applanation tonometry; and Risk of complications and adverse events.
Notes	Funded in part by the Lions Medical Eye Bank and Research Center of Eastern Virginia
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Yes	Study participants assigned to treatment groups using computerized randomization.
Allocation concealment?	Unclear	Method of allocation concealment not reported.
Blinding? Participants	Yes	Authors used a placebo control and stated that the study was double- masked. Placebo pills were given to the topical group and placebo gel administered to the systemic group to make both regimens similar.
Blinding? Personnel and outcome assessors	Yes	Authors used a placebo control and stated that the study was double- masked. “Data were compiled by observers who did not know what patients were in the treated and untreated control groups.”
Incomplete outcome data addressed? Primary outcome	Yes	One patient was excluded: one individual assigned to oral aminocaproic acid and topical placebo excluded based on side-effect of drug (vomiting). The remaining participants were analyzed in the group to which they were randomly assigned.
Incomplete outcome data addressed? Secondary outcomes	Yes	One patient was excluded: one individual assigned to oral aminocaproic acid and topical placebo excluded based on side-effect of drug (vomiting). The remaining participants were analyzed in the group to which they were randomly assigned.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes
Edwards 1973
Methods	Study design: Quasi-randomized controlled series Exclusions after allocation: Patients over 20 years old were excluded from the study because of the small number enrolled. Losses to follow-up: None Intention-to-treat: Participants aged 20 and younger were analyzed in the group to which they were assigned. Sample size calculations: Not reported
Participants	Country: USA Dates: 1969 to 1971 Number allocated: 64 consecutive patients alternately assigned to treatment group. Age: Mean was 10 years (up to 20 years) Sex: 61 (95%) men and 3 (5%) women Race: Not reported Sickle cell disease: Not reported Participants appeared to be balanced with respect to baseline characteristics. Inclusion criteria: Traumatic hyphema Exclusion criteria: Patients over 20 years of age.
Interventions	Treatment: Monocular patching (n =35) Control: Binocular patching (n = 29) Treatment for both groups included: Standard regimen (including position in bed, sedation and diet); Acetazolamide for severe secondary glaucoma; and No topical medications.
Outcomes	Primary outcome: Not reported Secondary outcomes: Risk of secondary hemorrhage; Duration of rebleeding; Complication rates; and Final visual acuity Follow-up: days 1 to 7
Notes	Funded by Research to Prevent Blindness Inc., Public Health Service Training Grant, and the National Institutes of Health
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	No	Allocation was not randomized; an independent study director assigned patients to treatment groups on an alternate basis by turning a card. Occasionally the card was not turned each time which led to an uneven number of patients in each group.
Allocation concealment?	No	Allocation was assigned on an alternate basis.
Blinding? Participants	No	Masking of patients was not possible with the interventions being studied.
Blinding? Personnel and outcome assessors	Unclear	Authors reported study to be double-masked, although this statement is not clear. The study investigators seldom participated in patient care to allow other examiners with less experience in monocular patching to collect data in hopes of minimizing observation bias.
Incomplete outcome data addressed? Primary outcome	Unclear	Patients over 20 years of age were excluded after allocation to treatment group.
Incomplete outcome data addressed? Secondary outcomes	Unclear	Patients over 20 years of age were excluded after allocation to treatment group.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes
Farber 1991
Methods	Study design: Randomized, double-masked clinical trial Exclusions after randomization: 6 participants in the aminocaproic acid group were excluded; 4 were administered prednisone instead of aminocaproic acid (treatment crossover), 1 participant had an unrelated seizure, and 1 developed thrombocytopenia. 1 participant in the prednisone group was administered aminocaproic acid instead of prednisone (treatment crossover) and was excluded. Losses to follow-up: 2 participants in the aminocaproic acid group and 1 participant in the prednisone group withdrew from the study. Intention-to-treat: The participants lost to follow-up or excluded were not included in the analyses and the intention-to-treat principle was not followed in the analyses. Sample size calculations: Not reported Additional comments: The authors noted that there were no secondary hemorrhages in the individuals who had been excluded or withdrew from the study.
Participants	Country: USA Dates: July 1985 to March 1990 Number randomized: 122: 64 assigned to aminocaproic acid and 58 to prednisone. Age: Mean age in aminocaproic acid group = 23.8 ± 13.8 years (range = 4 to 64 years); mean age in the prednisone group = 23.3 ± 13.4 years (range = 1.5 to 62 years). Sex: 79% of total study population was male. Race: 53% of study population was black, 27% was white, 22% was Hispanic, and 3% was of another ethnic or racial group. Study groups were not balanced by race: there were 57% of blacks and 20% of whites in the aminocaproic acid group compared with 48% of blacks and 25% of whites in the prednisone group. Sickle cell disease: None; excluded Inclusion criteria: Traumatic hyphema Exclusion criteria: Penetrating ocular injury; Need for immediate surgery; Sickle cell trait or disease; History of intravascular coagulopathy; History of gastric ulcer; History of diabetes mellitus; Pregnancy; Intoxication; Presence of detectable blood in stool.
Interventions	Treatment: 50 mg/kg oral aminocaproic acid (up to 30 g per day) every 4 hours plus 2 doses placebo, for 5 days. Control: 40 mg/day oral prednisone in two doses plus 6 doses placebo; children and adults weighing less than 60 kg were given 0.6 mg/kg/day prednisone, for 5 days. Treatment for both groups included: Moderate ambulation; No reading; Head of bed elevated to 30 degrees; Patch and shield on affected eye; Topical 1% atropine sulfate 4 times a day; Oral acetaminophen up to 650 mg per day, no aspirin; Topical timolol maleate 0.25% or 0.50% and/or oral acetazolamide if IOP > 25 mmHg; and Prochlorperazine edisylate (5 or 10 mg) if vomiting or nausea.
Outcomes	Primary outcome: Risk of secondary hemorrhage, recorded daily by slitlamp examination, documented by measuring height in mm and defined as a definite increase in level of presence of “fresh” blood visible over darker clotted blood. Secondary outcomes: Visual acuity, initial and final (5 days); IOP measured daily using applanation tonometry; and Risk of complications and adverse events.
Notes	Funded by the National Eye Institute of the National Institutes of Health, Bethesda, Md, and Research to Prevent Blindness
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Unclear	Randomized, but method of allocation not reported.
Allocation concealment?	Unclear	Method of allocation concealment not reported.
Blinding? Participants	Yes	Authors used a double dummy placebo design and stated that the study was double-masked.
Blinding? Personnel and outcome assessors	Yes	Authors used a double dummy placebo design and stated that the study was double-masked. “All of the treating physicians and nurses were masked to the identity of the treatment.”
Incomplete outcome data addressed? Primary outcome	Unclear	The participants lost to follow-up or excluded were not included in the analyses and the intention to treat principle was not followed in the analyses.
Incomplete outcome data addressed? Secondary outcomes	Unclear	The participants lost to follow-up or excluded were not included in the analyses and the intention to treat principle was not followed in the analyses.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes
Karkhaneh 2003
Methods	Study design: Randomized, double-masked clinical trial Exclusions after randomization: None Losses to follow-up: 23 participants lost to follow-up; 4 in the group assigned to cycloplegic drops and topical aminocaproic acid gel, 5 in group assigned to cycloplegic drops and topical placebo gel, and 14 in group assigned to cycloplegic drops only. Intention-to-treat: The participants lost to follow-up were not included in the analyses and the intention to treat principle was not followed in the analyses. Sample size calculations: Not reported
Participants	Country: Iran Dates: 1998 to 1999 Number randomized: 155: 45 assigned to cycloplegic drops and topical aminocaproic acid gel, 44 to cycloplegic drops and placebo gel, and 66 to cycloplegic drops only. Age: Age range of study population (4 to 30). Sex: 87% of study population (not including those lost to follow-up) was male. Race: Not reported Sickle cell disease: Not reported Participants appeared to be balanced with respect to baseline characteristics. Inclusion criteria: Non-pentrating traumatic hyphema and emergency room outpatient of Farabi Eye Hospital. Exclusion criteria: Penetrating ocular injury; Total hyphema; Microscopic hyphema; More than 24 hours since trauma; History of bleeding disorder; Previous ocular surgery in affected eye; Recent aspirin or anticoagulant ingestion; Pregnancy; and Trauma to affected eye during follow up.
Interventions	Treatment 1: 2 drops of 25% aminocaproic acid in 2% carboxymethylene gel applied to inferior fornix of affected eye every 6 hours plus homotropine eye drops 3 times per day, for 5 days. Control 1: 2 drops 2% carboxymethylene (placebo) gel applied to inferior fornix of affected eye every 6 hours plus homotropine eye drops 3 times per day, for 5 days. Control 2: Homotropine eye drops 3 times per day, for 5 days. Treatment for all groups included: No reading; Head of bed elevated to 30 degrees; Shield on affected eye; Oral acetaminophen; No aspirin.
Outcomes	Primary outcome: Risk of secondary hemorrhage, assessed daily by slit lamp examination for 7 days, and then at day 14. Method for documentation and definition not reported. Secondary outcomes: All measured daily for 7 days and at day 14 Time to resolution of primary hemorrhage; Time to secondary hemorrhage; Visual acuity; final visual acuity at day 14; IOP measured using applanation tonometry; Corneal blood staining; Drug toxicity; and Risk of complications and adverse events.
Notes	Conducted with support from Sina Darou (an ophthalmic pharmaceutical company in Iran), who provided the aminocaproic acid preparation.
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Unclear	Randomized, but method of allocation was not reported
Allocation concealment?	Yes	Allocation was concealed from investigators by use of coded bottles.
Blinding? Participants	Unclear	Authors used coded bottles to mask participants for the topical medication, but the group assigned to cycloplegic drops and no topical medication was not masked.
Blinding? Personnel and outcome assessors	Yes	Authors used coded bottles to mask healthcare providers and outcomes assessors. “The ophthalmologist who examined the patients did not know if they were treated or not.”
Incomplete outcome data addressed? Primary outcome	Unclear	The participants lost to follow-up were not included in the analyses and the intention-to-treat principle was not followed in the analyses. There were 23 participants lost to follow-up: 4 in the group assigned to cycloplegic drops and topical aminocaproic acid gel, 5 in group assigned to cycloplegic drops and topical placebo gel, and 14 in group assigned to cycloplegic drops only.
Incomplete outcome data addressed? Secondary outcomes	Unclear	The participants lost to follow-up were not included in the analyses and the intention to treat principle was not followed in the analyses. There were 23 participants lost to follow-up: 4 in the group assigned to cycloplegic drops and topical aminocaproic acid gel, 5 in group assigned to cycloplegic drops and topical placebo gel, and 14 in group assigned to cycloplegic drops only.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Unclear	Conducted with support from Sina Darou (an ophthalmic pharmaceutical company in Iran), who provided the aminocaproic acid preparation.
Kraft 1987
Methods	Study design: Randomized, double-masked clinical trial Exclusions after randomization: None Losses to follow-up: None Intention-to-treat: All participants were analyzed in the group to which they were randomly assigned. Sample size calculations: Not reported
Participants	Country: Canada Dates: May 1978 to December 1984 Number randomized: 49: 24 assigned to oral aminocaproic acid and 25 to placebo. Age: Age range of study population was 3 to 18 years. Mean age in aminocaproic acid group was 10.6, and in placebo group 11.2. Sex: 73% of study population was male. Race: There were 3 black participants in the aminocaproic acid group and 1 in the placebo group. The ethnicity or race of the other study participants was not reported. Sickle cell disease: None; excluded Participants appeared to be balanced with respect to baseline characteristics. Inclusion criteria: Children with non-penetrating traumatic hyphema treated at the Hospital for Sick Children in Toronto, Canada. Exclusion criteria: Penetrating ocular injury; More than 24 hours since trauma; Requirement for immediate surgical intervention; Positive sickle cell test or abnormal hematologic parameter; History of bleeding disorder; Ingestion of aspirin-containing medication within 7 days of admission; and Pregnancy.
Interventions	Treatment: 100 mg/kg oral aminocaproic acid every 4 hours, for 5 days. Control: Placebo every 4 hours, for 5 days. Treatment for both groups included: Bed rest with bathroom privileges; Head of bed elevated 15 degrees; Patch on affected eye; No topical eye medications except antibiotic ointment for corneal abrasions; Oral acetaminophen (10 to 20 mg/kg every 4 hours, up to 650 mg per dose); No aspirin-containing medications; Up to 0.5 mg/kg per day diazepam for sedation if needed; Topical timolol maleate 0.50% if IOP > 25 mmHg; Dimenhydrinate (Gravol) 6.25 to 12.5 mg every 6 hours if vomiting or nausea.
Outcomes	Primary outcome: Risk of secondary hemorrhage, assessed daily by slit lamp examination; documented by two observers and defined as definite increase in amount of blood compared with amount at admission or fresh red blood over darker clotted blood. Secondary outcomes: Outcomes measured daily during hospitalization (up to 5 days), then at 6 weeks, and 3, 6, 12, and 18 months after discharge. Time to resolution of primary hemorrhage; Visual acuity; IOP assessed using applanation tonometry; and Risk of complications and adverse events.
Notes
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Yes	Study participants assigned to treatment groups using computerized randomization.
Allocation concealment?	Unclear	Method of allocation concealment not reported.
Blinding? Participants	Yes	Authors used a placebo control and stated that the study was double- masked.
Blinding? Personnel and outcome assessors	Yes	Authors used a placebo control and stated that the study was double- masked.
Incomplete outcome data addressed? Primary outcome	Yes	There was no loss to follow-up and all participants were analyzed in the group to which they were randomly assigned.
Incomplete outcome data addressed? Secondary outcomes	Yes	There was no loss to follow-up and all participants were analyzed in the group to which they were randomly assigned.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes
Kutner 1987
Methods	Study design: Randomized, double-masked clinical trial Exclusions after randomization: One participant was excluded from the aminocaproic acid group due to systemic hypotension attributable to the study drug. Losses to follow-up: None Intention-to-treat: The participant excluded from the study was not included in the analyses and the intention to treat principle was not followed in the analyses. Sample size calculations: Not reported
Participants	Country: USA Dates: November 1983 to January 1986 Number randomized: 34: 21 to the aminocaproic acid group and 13 to the placebo group. Age: mean age in the aminocaproic acid group was 18.9±7.7 years and in the placebo group it was 22.8±7.6 years. Sex: 88% of the study population was male. Race: 85% of the study population was white. Sickle cell disease: None; excluded Participants appeared to be balanced with respect to baseline characteristics. Inclusion criteria: Non-penetrating traumatic hyphema Exclusion criteria: Penetrating ocular injury; More than 48 hours since trauma; Age less than 7 years; Sickle cell anemia; History of intravascular coagulopathy; History of blood dyscrasia; History of renal disease; History of ocular disease that could increase the susceptibility to intraocular hemorrhage; Recent anticoagulant, aspirin or oral contraceptive use; and Pregnancy.
Interventions	Treatment: 100 mg/kg oral aminocaproic acid every 4 hours (up to 5 g/dose and 30 g/day), for 5 days. Control: Placebo every 4 hours, for 5 days. Treatment for both groups included: Quiet activities; No reading; No patch or shield; No ocular medications; Oral acetaminophen (10 to 20 mg/kg every 4 hours, up to 650 mg per dose); No aspirin or alcohol; 5 mg diazepam every 6 hours for sedation if needed; Topical timolol maleate 0.5% with IOP > 35 mmHg; and Prochloroperazine 5 to 10 mg if vomiting or nausea.
Outcomes	Primary outcome: Risk of secondary hemorrhage, assessed daily by slit lamp examination, for 6 days and one week after discharge. Defined as a definite increase in the amount of blood in the anterior chamber compared with that noted on the previous day’s examination. Secondary outcomes: Time to resolution of primary hemorrhage; Visual acuity, measured daily for 6 days and one week after discharge; IOP measured daily using applanation tonometry for 6 days and one week after discharge; and Risk of complications and adverse events.
Notes
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Yes	Study participants assigned to treatment groups using computerized randomization.
Allocation concealment?	Unclear	Method of allocation concealment not reported.
Blinding? Participants	Yes	Authors used a placebo control and stated that the study was double- masked.
Blinding? Personnel and outcome assessors	Yes	Authors used a placebo control and stated that the study was double- masked. Assignment codes maintained by a central data evaluator who had no clinical contact with any patient. “Physicians caring for study patients did not have access to the cumulative data until the code was broken.”
Incomplete outcome data addressed? Primary outcome	Unclear	One participant was excluded from the aminocaproic acid group due to systemic hypotension attributable to the study drug. It was reported that this patient did not rebleed.
Incomplete outcome data addressed? Secondary outcomes	Unclear	One participant was excluded from the aminocaproic acid group due to systemic hypotension attributable to the study drug. Data for this patient was analyzed until time of study withdrawal.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes
Liu 2002
Methods	Study design: Randomized clinical trial Exclusions after randomization: None Losses to follow-up: None Intention-to-treat: All participants were analyzed in the group to which they were randomly assigned. Sample size calculations: Not reported
Participants	Country: China Dates: December 1997 to December 2000 Number randomized: 92: 60 to aminomethylbenzoic acid group and 32 to the control group. Age: The mean age of the aminomethylbenzoic acid group was 32.7±11.25 years and that of the control group was 33.4±10.75 years. Sex: 75% of the study population were male. Race: Not reported Sickle cell disease: Not reported Participants appeared to be balanced with respect to baseline characteristics. Inclusion criteria: Traumatic hyphema Exclusion criteria: More than 48 hours since trauma; Use of anticoagulants; History of risk of clot formation; History of diabetes.
Interventions	Treatment: 0.5 g oral aminomethylbenzoic acid plus 20 mg oral vitamin B1 3 times a day, for 6 days. For children, the dosage of aminomethylbenzoic acid was modified to “follow age-recommended dose”; the vitamin B1 dosage remained the same. Control: 20 mg oral vitamin B1 3 times a day, for 6 days Treatment for both groups included 0.3% ofloxacin eye drops 4 times a day, for 6 days.
Outcomes	Primary outcome: Risk of secondary hemorrhage, details not reported. Secondary outcomes: Risk of complications and adverse events
Notes
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Unclear	Randomized, but method of allocation not reported.
Allocation concealment?	Unclear	Method of allocation concealment not reported.
Blinding? Participants	Unclear	The authors do not state whether masking was used.
Blinding? Personnel and outcome assessors	Unclear	The authors do not state whether masking was used.
Incomplete outcome data addressed? Primary outcome	Yes	No exclusions or loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Incomplete outcome data addressed? Secondary outcomes	Yes	No exclusions or loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Free of selective reporting?	Unclear	Study outcomes of interest not clearly stated.
Free of other bias?	Unclear	Poor description of study methods in publication.
Marcus 1988
Methods	Study design: Randomized clinical trial Exclusions after randomization: None Losses to follow-up: None Intention-to-treat: All participants were analyzed in the group to which they were randomly assigned. Sample size calculations: Not reported
Participants	Country: Israel Dates: not reported Number randomized: 51: 23 assigned to aspirin group and 28 to observation. Age: Mean age of study population = 20 years Sex: Not reported Race: Not reported Sickle cell disease: Not reported Author stated that participants were balanced with respect to baseline characteristics. Inclusion criteria: Traumatic hyphema Exclusion criteria: Age less than 7 years; Diastolic blood pressure over 100 mmHg; Current use of anticoagulants; Current use of antihypertensive medication; Peptic ulcer; “Restless”.
Interventions	Treatment: 500 mg aspirin 3 times a day for 5 days. Control: observation Treatment for both groups included: Bed rest; Topical atropine 1% and dexamycin 0.1% 4 times a day; and Topical timolol or oral acetazolamide if IOP > 25 mmHg.
Outcomes	Primary outcome: Risk of secondary hemorrhage, assessed daily. Documented by estimating percentage involvement and plotting diagrammatically; definition not reported. Secondary outcomes: Visual acuity, assessed daily for 7 days; and IOP assessed daily for 7 days; details not reported.
Notes
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Unclear	Randomized, but method of allocation not reported.
Allocation concealment?	Yes	Allocation was concealed from investigators by use of sequentially numbered envelopes.
Blinding? Participants	No	The study participants were not masked to treatment. No placebo was given to the control group.
Blinding? Personnel and outcome assessors	No	The health care providers were not masked to treatment. No placebo was given to the control group.
Incomplete outcome data addressed? Primary outcome	Yes	No exclusions or loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Incomplete outcome data addressed? Secondary outcomes	Yes	No exclusions or loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Free of selective reporting?	Unclear	Only report results for secondary hemorrhage.
Free of other bias?	Unclear	Poor description of study methods and results in publication.
McGetrick 1983
Methods	Study design: Randomized, double-masked clinical trial Exclusions after randomization: The chart of 1 participant in the placebo group was “lost” was this participant was excluded. Losses to follow-up: None Intention-to-treat: The excluded participant was not included in the analyses and the intention to treat principle was not followed in the analyses. Sample size calculations: Not reported
Participants	Country: USA Dates: August 1980 to February 1982 Number randomized: 50: 28 assigned to aminocaproic acid and 22 to placebo. Age: 86% of the study population was between the ages of 6 and 40 years. Sex: 81% of the study population was male. Race: 69% of the study population was black, 21% Hispanic and 10% white. Sickle cell disease: None; excluded Participants appeared to be balanced with respect to baseline characteristics. Inclusion criteria: Non-penetrating traumatic hyphema Exclusion criteria: Penetrating ocular injury; Requirement for immediate surgical intervention; Sickle cell hemoglobin; History of intravascular coagulopathy; Pregnancy.
Interventions	Treatment:100 mg/kg oral aminocaproic acid (up to 5 g per dose and 30 g per day) every 4 hours, for 5 days. Control: Placebo every 4 hours, for 5 days. Treatment for both groups included: Quiet activities; No reading; Patch and shield on affected eye; Topical 1% atropine sulfate 4 times a day; Oral acetaminophen up to 650 mg per day; No aspirin; and Topical timolol maleate 0.25% or 0.5% and oral acetazolamide, if IOP > 35 mmHg.
Outcomes	Primary outcome: Risk of secondary hemorrhage, assessed daily by slit lamp examination. Defined as a definite increase in the amount of blood in the anterior chamber following admission. Secondary outcomes: Time to resolution of primary hemorrhage; Time to secondary hemorrhage; Visual acuity (final) with follow-up ranging from 0 to 9 months; IOP assessed daily by applanation tonometry for 5 days; Length of hospitalization; and Risk of complications and adverse events.
Notes	Funded by the National Eye Institute, National Institutes of Health, Bethesda, Md and Research to Prevent Blindness, Inc.
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Yes	Study participants assigned to treatment groups using computerized randomization.
Allocation concealment?	Unclear	Method of allocation concealment not reported.
Blinding? Participants	Yes	Authors used a placebo control and stated that the study was double- masked.
Blinding? Personnel and outcome assessors	Yes	Authors used a placebo control and stated that the study was double- masked. Assignment codes were not broken until the study was terminated.
Incomplete outcome data addressed? Primary outcome	Unclear	The chart of 1 participant in the placebo group was “lost” and this participant was excluded. The excluded participant was not included in the analyses and the intention to treat principle was not followed in the analyses.
Incomplete outcome data addressed? Secondary outcomes	Unclear	The chart of 1 participant in the placebo group was “lost” and this participant was excluded. The excluded participant was not included in the analyses and the intention to treat principle was not followed in the analyses.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes
Palmer 1986
Methods	Study design: Randomized, double-masked clinical trial Exclusions after randomization: Two participants were excluded: one from the low dose aminocaproic acid group due to need for surgery and one from the usual dose aminocaproic acid group due to severe hypotension. Losses to follow-up: None Intention-to-treat: The intention-to-treat principle was followed only for analyses of adverse events. The 2 excluded participants were not included in the analyses and the intention to treat principle was not followed in the analyses. Sample size calculations: Not reported
Participants	Country: USA Dates: July 1982 to December 1983 Number randomized: 59: 26 assigned to low dose aminocaproic acid and 33 to standard dose aminocaproic acid. Age: The mean age of the low dose aminocaproic acid group was 20 years (range = 4 to 46 years) and for the standard aminocaproic acid group, it was 22.8 years (range = 3 to 50 years). Sex: 23 (88%) of the low dose aminocaproic acid group and 27 (82%) of the standard aminocaproic acid group was male. Race: There were 13 (50%) black, 7 (27%) white, and 5 (19%) Hispanic in the low dose aminocaproic acid group; the race of the excluded participant was not reported. There were 17 (52%) black, 7 (27%) white, and 9 (21%) Hispanic in the standard dose aminocaproic acid group. Sickle cell disease: None; excluded Participants appeared to be balanced with respect to baseline characteristics. Inclusion criteria: Traumatic hyphema, including both primary and secondary hemorrhages Exclusion criteria: Requirement for immediate surgical intervention; Sickle cell hemoglobin; History of intravascular coagulopathy; Pregnancy.
Interventions	Treatment: Low dose (50 mg/kg) oral aminocaproic acid (up to 5 g per dose or 30 g per day) every 4 hours, for 5 days. Control: Standard dose (100 mg/kg) oral aminocaproic acid (up to 5 g per dose or 30 g per day) every 4 hours, for 5 days. Treatment for both groups included: Quiet activities; No reading; Head of bed elevated to 30 degrees; Patch and shield on affected eye; Topical 1% atropine sulfate 4 times a day; Oral acetaminophen up to 650 mg per day; No aspirin; Topical timolol maleate 0.25% or 0.5% and oral acetazolamide if IOP > 25 mmHg; Oral prochlorperazine edisylate (5 or 10 mg) if nausea or vomiting; and Steroids on recommendation of admitting physician.
Outcomes	Primary outcome: Incidence of secondary hyphema, assessed daily by slit lamp examination. Documented by level in mm and percentage of anterior chamber filled with blood. Defined as a definite increase in the amount of fresh blood in the anterior chamber over level at admission. Secondary outcomes: Time to resolution of primary hemorrhage; Time to secondary hemorrhage; Visual acuity; “final” visual acuity not defined; IOP assessed daily using applanation tonometry; Length of hospitalization; Incidence of complications and adverse events.
Notes	Funded by the National Eye Institute, National Institutes of Health, Bethesda, Md, Research to Prevent Blindness, Inc., and Lederle-Cyanamid Laboratories for serum assays.
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Yes	Assignments determined by computerized randomization in the pharmacy.
Allocation concealment?	Yes	Allocation was possibly concealed from investigators by pharmacy preparation of drugs.
Blinding? Participants	Yes	Participants masked by preparation of drugs by pharmacy. “The treating physicians and the patients were not told of the admission dose in order to maintain the double-masked status.”
Blinding? Personnel and outcome assessors	Yes	Healthcare providers and outcomes assessors masked by preparation of drugs by pharmacy. “The treating physicians and the patients were not told of the admission dose in order to maintain the double-masked status.”
Incomplete outcome data addressed? Primary outcome	Unclear	Two participants were excluded: one from the low dose aminocaproic acid group due to need for surgery and one from the standard dose aminocaproic acid group due to severe hypotension. The study authors noted that excluding the patient from the full-dose group did not affect the statistical results.
Incomplete outcome data addressed? Secondary outcomes	Unclear	Two participants were excluded: one from the low dose aminocaproic acid group due to need for surgery and one from the standard dose aminocaproic acid group due to severe hypotension. The intention to treat principle was followed only for analyses of adverse events.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes
Pieramici 2003
Methods	Study design: Randomized, double-masked, placebo-controlled clinical trial Exclusions after randomization: None Losses to follow-up: None Intention-to-treat: All participants were analyzed in the group to which they were randomly assigned. Sample size calculations: 124 study participants based on secondary hemorrhage rate of 15% and 3% in placebo and aminocaproic acid treated participants, respectively, with alpha = 0.05, power = 80%, and one-tailed test of significance; study terminated due to slow enrollment. Notes: Multi-center study with 8 centers.
Participants	Country: USA Dates: Not reported, although study was conducted over 14 months. Number randomized: 51: 24 assigned to aminocaproic acid and 27 to placebo Age: The mean age of the aminocaproic acid group was 24±4 years (range = 4 to 73 years) and for the placebo group, it was 23±3 years (range = 6 to 48 years). Sex: 21 (88%) of the aminocaproic acid group and 23 (85%) of the placebo group was male. Race: There were 15 (63%) white, 8 (33%) black, and 1 (1%) other in the aminocaproic acid group. There were 13 (48%) white, 11 (41%) black, and 3 (11%) other in the placebo group. Sickle cell disease: 2/24 (8%) of participants assigned to topical aminocaproic acid and 1/27 (4%)% of participants assigned to oral aminocaproic acid had sickle cell trait. Participants appeared to be balanced with respect to baseline characteristics except for race and size of primary hyphema with larger hyphemas found in the placebo group. Inclusion criteria: traumatic hyphema Exclusion criteria: Total hyphema or unlayered microscopic hyphema; More than 36 hours since trauma; Age less than 4 years; History of clinically significant coagulopathy; History of renal insufficiency; History of hepatic insufficiency; Hypersensitivity or idiosyncratic reaction of proparacaine hydrochloride 0.5%, aminocaproic acid or carboxymethylene; Evidence of any clinically significant cardiac, endocrine, gastrointestinal, hematologic, or immunologic abnormalities or disease (sickle cell disease was allowed); Ingestion of anticoagulant or antiplatelet agent within the previous 7 days or any nonsteroidal anti-inflammatory drug within previous 24 hours; Pregnancy; Participation in investigational drug trial within 4 weeks before randomization; Unable to complete trial.
Interventions	Treatment: Following 1 drop of 0.05% proparacaine hydrochloride, 30% aminocaproic acid in 2% gel instilled in inferior fornix every 6 hours, for 5 days. Control: Following 1 drop of 0.05% proparacaine hydrochloride, placebo gel instilled in inferior fornix every 6 hours, for 5 days. Treatment for both groups included: No reading or video games; Head of bed elevated to 30 degrees; Shield on affected eye; Topical 2% homotropine sulfate 3 times a day; No topical steroids; and If IOP elevated, treatment at discretion of physician.
Outcomes	Primary outcome: Risk of secondary hemorrhage, assessed daily by slit lamp examination for 7 days; defined as increase in height of hyphema of at least 0.5 mm above darker blood, colour change of blood of at least 0.5 mm, obvious new “trickle” of blood on iris, or reappearance of blood after resolution. Secondary outcomes: Time to resolution of primary hemorrhage; Time to secondary hemorrhage; Visual acuity, final visual acuity assessed at 7 days (end of treatment); Risk of complications and adverse events.
Notes	Funded by Orphan Medical Inc., Covance Inc, National Eye Institute, National Institutes of health, Bethesda, Md, and Research to Prevent Blinding
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Yes	Study participants assigned to treatment groups using computerized randomization.
Allocation concealment?	Yes	Allocation was concealed from investigators in that treatment assignments were based on a trial number obtained from a contract research organization.
Blinding? Participants	Yes	Authors used a placebo control and stated that the study was double- masked. “The investigators and patients were masked to the treatment arm.”
Blinding? Personnel and outcome assessors	Yes	Authors used a placebo control and stated that the study was double- masked. “The investigators and patients were masked to the treatment arm.”
Incomplete outcome data addressed? Primary outcome	Yes	No exclusions or loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Incomplete outcome data addressed? Secondary outcomes	Yes	No exclusions or loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Unclear	“There were a number of protocol violations noted in both study groups.” “During the course of the study, only 8 of the original 13 sites enrolled patients, and at 14 months a total of 51 patients were enrolled overall. The study was terminated at this point by Orphan Medical, the manufacturer, against the advice of the principal investigators, because of slow enrollment.”
Rahmani 1999
Methods	Study design: Randomized, placebo-controlled clinical trial Exclusions after randomization: 6; 2 participants in the tranexamic acid group, 3 in the prednisone group, and 1 in the placebo group left the hospital before the end of the study and were excluded. Losses to follow-up: none Intention-to-treat: The excluded participants were not included in the analyses and the intention-to-treat principle was not followed in the analyses. Sample size calculations: Not reported
Participants	Country: Iran Dates: January 1991 to May 1992 Number randomized: 244: 82 assigned to tranexamic acid, 81 assigned to prednisone, and 81 assigned to placebo. Age: Median age in tranexamic acid group was 11 years (range = 1 to 65 years); in the prednisone group, it was 11.5 years (range = 1 to 50 years), and in the placebo group, it was 12 years (range = 1 to 58 years). Sex: 63 (79%) of the tranexamic acid group, 58 (73%) of the prednisone group, and 66 (82%) of the placebo group were male. Race: All study participants were white. Sickle cell disease: Not reported, but all white study population. Participants appeared to be balanced with respect to baseline characteristics. Inclusion criteria: Traumatic hyphema Exclusion criteria: Penetrating ocular injury; Total hyphema or unlayered microscopic hyphema; Definite secondary hemorrhage before entry; More than 48 hours since trauma; Requirement for immediate surgical intervention; History of renal insufficiency; Acid peptic disease; Recent ingestion of aspirin or anticoagulant; Use of topical steroids after trauma; Pregnancy.
Interventions	Treatment 1: 75 mg/kg oral tranexamic acid per day, divided into 3 doses per day, for 5 days. Treatment 2: 0.75 mg/kg oral prednisolone per day, divided into 2 doses per day, for 5 days. Control: Placebo administered 3 times per day. Treatment for all groups included: Limited ambulation; Head of bed elevated; Patch and shield on affected eye; Topical cyclopentolate for examination of the retina if necessary; Oral acetaminophen for pain; No aspirin or topical steroids; Topical timolol and oral acetazolamide, if elevated IOP; and Oral promethazine if nausea or vomiting.
Outcomes	Primary outcome: Risk of secondary hemorrhage, assessed daily by slit lamp examination for 5 days. Defined as definite increase in size of level of blood or appearance of fresh blood over darker clotted blood in the anterior chamber. Secondary outcomes: Visual acuity, measured at day 5 (discharge); and Risk of complications and adverse events.
Notes
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Yes	Randomization was based on a randomization list.
Allocation concealment?	Unclear	Study participants assigned to treatment groups using a randomization list, but not clear whether list was revealed before allocation to individuals enrolling study participants.
Blinding? Participants	Unclear	Participants partially masked in that authors used a placebo control for the tranexamic acid, but not for prednisone.
Blinding? Personnel and outcome assessors	Yes	Healthcare providers partially masked in that authors used a placebo control for the tranexamic acid, but not for prednisone; however, ophthalmologists and outcome assessors were masked.
Incomplete outcome data addressed? Primary outcome	Unclear	Six patients were excluded from the study: 2 participants in the tranexamic acid group, 3 in the prednisone group, and 1 in the placebo group left the hospital before the end of the study and were excluded. The excluded participants were not included in the analyses and the intention to treat principle was not followed in the analyses.
Incomplete outcome data addressed? Secondary outcomes	Unclear	Six patients were excluded from the study: 2 participants in the tranexamic acid group, 3 in the prednisone group, and 1 in the placebo group left the hospital before the end of the study and were excluded. The excluded participants were not included in the analyses and the intention to treat principle was not followed in the analyses.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes
Rakusin 1972
Methods	Study design: Quasi-randomized controlled series Exclusions after allocation: 59 patients in the series with large hyphemas underwent surgery and were not included in the analysis. Losses to follow-up: 20 patients were lost to follow-up. Intention-to-treat: All participants were not accounted for in the final analyses, thus intention-to-treat analysis was not followed. Sample size calculations: Not reported
Participants	Country: South Africa Dates: 1966 to 1969 Number allocated: 390 consecutive patients Age: Not reported Sex: Not reported Sickle cell disease: Not reported Race: 90% African origin and 10% Asiatic origin. Inclusion criteria: Traumatic hyphema Exclusion criteria: Surgical treatment indicated
Interventions	Series of comparisons based on 6 variable factors: Bed rest (n = 26) versus ambulatory treatment (n = 26); Eye pads: bilateral eye pads (n = 27) versus single eye pads (n = 26) versus no eye pads (n = 10); Topical antibiotics (0.5% chloramphenicol, n = 21) versus corticosteroids, 0.5% hydrocortisone acetate (n = 13) versus neither (n = 3); Mydriatics (1% homatropine, n = 17) versus miotics (4% pilocarpine, n = 17) versus neither (n = 19) versus both (n = 17); Enzymes: oral trypsin (n = 15) versus oral papase (n = 18) versus neither (n = 10); Ocular hypotensive agents: 250 mg acetazolamide (n = 18) versus 1 mL/kg oral glycerol (n = 18) versus neither (n = 10). Treatment and control groups followed the same regime except even-numbered patients received the variable, and odd-numbered patients did not. Excluding the variable factor for each series, all patients received bed rest, single pad over the injured eye, and topical chloramphenicol or chloromycetin.
Outcomes	Primary outcomes: Speed of absorption of blood from the anterior chamber; Risk of secondary hemorrhage; Complications of the hyphema; and Final visual acuity. Follow-up: Range 1 to 2 weeks, to 3 years
Notes	Funded by the University of Witwatersrand, the South African Medical Research Council, Leo Laboratories, Mer-National, and Warner Pharmaceutical Co. In the third comparison group, antibiotics versus corticosteroids, 3 patient were assigned to receive neither treatment, but this group was discontinued after all 3 patients developed a mucous conjunctival discharge.
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	No	Method of allocation unclear, not all patients in the series were allocated to the 6 comparisons under study; 59 patients were selected for surgery. Also even and odd patient number allocation is not applicable to comparison with three treatment groups.
Allocation concealment?	No	Method of allocation concealment not reported, not randomized.
Blinding? Participants	No	Masking of patients was not possible for some variables (i.e., bed rest and eye patching). Use of placebo for other variables was not mentioned.
Blinding? Personnel and outcome assessors	Unclear	Masking was not reported.
Incomplete outcome data addressed? Primary outcome	Unclear	79 participants were not included in the analyses and the intention to treat principle was not followed.
Incomplete outcome data addressed? Secondary outcomes	Unclear	79 participants were not included in the analyses and the intention to treat principle was not followed.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Unclear	The primary interventions of interest for this study are not clear. Although the majority of the patients in the series were assigned to one of six conservative treatment comparison groups, 59 recruited patients were selected for surgery.
Read 1974
Methods	Study design: Quasi-randomized controlled series Exclusions after allocation: None Losses to follow-up: None Intention-to-treat: All participants were analyzed in the groups to which they were assigned. Sample size calculations: Not reported
Participants	Country: USA Dates: February 1970 to July 1972 Number allocated: 137 consecutive patients Age: Mean 15.9 years Sex: 108 men and 29 women; 78% male Race: 101 (74%) African-American Sickle cell disease: Not reported Participants were similar in regards to baseline characteristics. Inclusion criteria: Traumatic hyphema Exclusion criteria: Associated penetrating ocular injury; Surgical exploration for suspected rupture of the globe; Bodily injury; Recurrent ocular injury; Personal or family history of diabetes or bleeding disorders.
Interventions	Medical treatment #1 (n = 66): Bed rest with elevation of head to 30 degrees, bilateral ocular patches and shield over injured eye, and sedation. Medical treatment #2 (n = 71): Moderate ambulatory activity in the hospital, patching and shielding of the traumatized eye only, and no sedation. Eye drops were not administered in either medical treatment regimen. On day 5 patients with remaining major primary or secondary hyphemas (n = 16) were alternately assigned to continue with medical treatment or to receive surgical intervention (ab externo corneal section with clot expression).
Outcomes	Primary outcome: Not reported Secondary outcomes: Changes or presence of IOP; Duration of primary hyphema; Risk of secondary hemorrhage; Risk of corneal staining; Need for surgical intervention; Complications of the hyphema; and Final visual acuity. Follow-up: 1 week, 1, 3, and 6 months (range 3 months to 2.5 years; average was 16.5 months).
Notes	Funded by a grant from the Research to Prevent Blindness, Inc.
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	No	Allocation was not randomized; alternately assigned patients to treatment groups at time of admission. Imbalance in number assigned to each group (66 versus 71) makes it appear alternation was not systematic.
Allocation concealment?	No	Allocation was assigned on an alternate basis.
Blinding? Participants	No	Masking of patients was not possible with the interventions being studied.
Blinding? Personnel and outcome assessors	No	All patients were treated by the primary investigator in order to standardize therapy and record results as accurately as possible.
Incomplete outcome data addressed? Primary outcome	Yes	All participants were analyzed in the group to which they were assigned.
Incomplete outcome data addressed? Secondary outcomes	Yes	All participants were analyzed in the group to which they were assigned.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	No	A subset of patients with major hyphema on day 5 were alternately allocated to either continue with medical treatment as originally assigned or undergo surgical intervention. Thus the patients that had surgery were censored on day 5 from their medical treatment outcomes.
Spaeth 1966
Methods	Study design: Randomized, double-masked, placebo-controlled clinical trial Exclusions after randomization: None Losses to follow-up: None Intention-to-treat: All participants were analyzed in the group to which they were randomly assigned. Sample size calculations: not reported
Participants	Country: USA Dates: 1963 to 1964 Number randomized: 85: 39 assigned to estrogen and 46 to placebo. Age: Mean age in the estrogen group = 16.2 years (range 2 to 62 years), and in the placebo group, it was 18.9 years (range 0.5 to 65 years). Sex: 80% of the estrogen group and 85% of the placebo group was male. Race: 72% of the estrogen group and 70% of the placebo group was black; remaining study participants were white. Sickle cell disease: Not reported Participants appeared to be balanced with respect to baseline characteristics. Inclusion criteria: Traumatic hyphema Exclusion criteria: Penetrating ocular injury; More than 24 hours since trauma; History of ocular disease; Failure to co-operate.
Interventions	Treatment: Conjugated estrogen, 5 mg intramuscularly for children < 5 years; 10 mg for children 5 or older but < 10; and 20 mg intravenously for children 10 or older and adults, for 5 days. Control: Placebo, for 5 days. Treatment for both groups included: Complete bed rest; Head of bed elevated; Patches on both eyes; No ophthalmic drops; and Sedation and analgesics as needed.
Outcomes	Primary outcome: Risk of secondary hemorrhage, assessed daily by “complete ocular examination” for 5 days. Documentation and definition not reported. Secondary outcomes: Time to secondary hemorrhage; Visual acuity measured at day 5 (discharge); and Risk of complications and adverse events.
Notes	Placebo and conjugated estrogen supplied by Ayerst Laboratory
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Unclear	Randomized, but method of allocation not reported
Allocation concealment?	Yes	Allocation was concealed from investigators by use of coded bottles.
Blinding? Participants	Yes	Authors used coded bottles to mask participants. “Neither the person administering nor the patient receiving the medications knew whether estrogen or placebo was being given.”
Blinding? Personnel and outcome assessors	Yes	Authors used coded bottles to mask healthcare providers and outcomes assessors. “Neither the person administering nor the patient receiving the medications knew whether estrogen or placebo was being given.”
Incomplete outcome data addressed? Primary outcome	Yes	There were no exclusions and no loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Incomplete outcome data addressed? Secondary outcomes	Yes	There were no exclusions and no loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes
Spoor 1980
Methods	Study design: Randomized, double-masked, placebo-controlled clinical trial Exclusions after randomization: None Losses to follow-up: None Intention-to-treat: All participants were analyzed in the group to which they were randomly assigned. Sample size calculations: Not reported
Participants	Country: USA Dates: September 1975 to December 1977 Number randomized: 43: 23 assigned to prednisone, and 20 to placebo. Age: The mean age of the prednisone group was 20.1 (range = 5 to 61) and that of the placebo group was 21.2 (range 9 to 51). Sex: 16 (70%) of the prednisone group and 16 (80%) of the placebo group were male. Race: There were 14 (61%) white, 6 (26%) Hispanic, and 3 (13%) black in the prednisone group. There were 11 (55%) white, 7 (35%) Hispanic, and 2 (10%) black in the placebo group. Sickle cell disease: Not reported Participants appeared to be balanced with respect to baseline characteristics. Inclusion criteria: Traumatic hyphema Exclusion criteria: Penetrating ocular injury; More than 24 hours since trauma; Treated before entry; Not available for 6 months follow-up.
Interventions	Treatment: Oral prednisone, 40 mg/day for adults and children > 10 years; 15 mg/day for children between 4 and 10 years; and 10 mg/day for children between 18 months up to 4 years, for 7 days. Control: Lactose placebo capsules administered daily for 7 days. Treatment for both groups included: Bed rest; Head of bed elevated between 30 and 45 degrees; Patch on affected eye; No topical medications; Sedation as needed; No aspirin; and Oral acetazolamide if IOP > 24 mmHg.
Outcomes	Primary outcome: Risk of secondary hemorrhage, assessed daily for 7 days, using slit lamp examination, documented by drawings or photography. Secondary outcomes: Time to resolution of primary hemorrhage; Time to secondary hemorrhage; Visual acuity (followed up to 6 months); IOP assessed daily for 7 days using applanation tonometry; Risk of complications and adverse events.
Notes
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Unclear	Randomized, but method of allocation not reported.
Allocation concealment?	Yes	Allocation was concealed from investigators by use of encoded capsules prepared by pharmacy.
Blinding? Participants	Yes	Participants by use of encoded capsules prepared by pharmacy. “Neither the doctor nor the patient knew which capsule the patient was receiving until the conclusion of the course of treatment and follow-up.”
Blinding? Personnel and outcome assessors	Yes	Healthcare providers and outcomes assessors by use of encoded capsules prepared by pharmacy. “Neither the doctor nor the patient knew which capsule the patient was receiving until the conclusion of the course of treatment and follow-up.”
Incomplete outcome data addressed? Primary outcome	Yes	There were no exclusions and no loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Incomplete outcome data addressed? Secondary outcomes	Yes	There were no exclusions and no loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes
Sukumaran 1988
Methods	Study design: Quasi-randomized controlled series Exclusions after allocation: None Losses to follow-up: None Intention-to-treat: All participants were analyzed in the group to which they were assigned. Sample size calculations: Not reported
Participants	Country: Malaysia Dates: Not reported Number allocated: 35 consecutive patients Age: 80% below 30 years old Sex: 35 men Race: Not reported Sickle cell disease: Not reported Inclusion criteria: Traumatic hyphema Exclusion criteria: Other serious ocular or facial injuries; Hyphema greater than 7 mm.
Interventions	Treatment (n =17): 25 mg/kg oral tranexamic acid (cyklokapron) divided into 3 doses for 7 days in addition to routine treatment. Control (n = 18): Routine treatment Routine treatment for both groups included: Bilateral patching; Bed rest; Sedation; Analgesics when required; and Topical steroid drops from the third day for a week.
Outcomes	Primary outcomes: Risk of secondary hemorrhage; Speed of recovery; and Final visual acuity Follow-up: At least 1 week
Notes	Funding source not reported
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	No	Method of allocation unclear, not randomized.
Allocation concealment?	No	Method of allocation concealment not reported, not randomized.
Blinding? Participants	No	No placebo was used for the control group.
Blinding? Personnel and outcome assessors	Unclear	Masking was not reported.
Incomplete outcome data addressed? Primary outcome	Yes	All participants were analyzed in the group to which they were assigned.
Incomplete outcome data addressed? Secondary outcomes	Yes	All participants were analyzed in the group to which they were assigned.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes
Teboul 1995
Methods	Study design: Randomized, double-masked, placebo-controlled clinical trial Exclusions after randomization: None Losses to follow-up: None Intention-to-treat: All participants were analyzed in the group to which they were randomly assigned. Sample size calculations: Authors reported that sample sizes were not calculated because the rate of secondary hemorrhage in children was unknown and that of other populations was too variable to estimate.
Participants	Country: Canada Dates: November 1987 to February 1994 Number randomized: 94: 48 assigned to aminocaproic acid and 46 to placebo. Age: The mean age of the aminocaproic acid group was 8.2 years, while that of the placebo group was 10.6 years. Sex: 42 (88%) of the aminocaproic acid group, and 39 (85%) of the placebo group were male. Race: 43 (90%) of the aminocaproic acid group, and 42 (91%) of the placebo group was white. Sickle cell disease: None; excluded Participants appeared to be balanced with respect to baseline characteristics, except for mean age where the aminocaproic acid group was younger (8.2 to 10.6 years). Inclusion criteria: Traumatic hyphema Exclusion criteria: Penetrating ocular injury; Total hyphema; More than 24 hours since trauma; Requirement for immediate surgical intervention; History of sickle cell anemia; History of renal disease; History of hepatic disease; History of cardiac disease; History of coagulopathy; Recent ingestion of aspirin up to 1 week before entry; Pregnancy.
Interventions	Treatment: 100 mg/kg oral aminocaproic acid every 4 hours (up to 30 g per day), for 5 days. Control: Placebo every 4 hours. for 5 days. Treatment for both groups included: Bed rest; Head of bed elevated to 45 degrees; Patch on affected eye; 1% atropine ointment nightly and garsone drops 2 times a day; Oral acetaminophen for pain; No aspirin; Topical timolol maleate 0.5% 2 times a day and oral acetazolamide if IOP > 25 mmHg; and Dimenhydrinate (Gravol) if nausea or vomiting.
Outcomes	Primary outcome: Risk of secondary hemorrhage, assessed by daily slit lamp examination for 5 days; documented by drawing of hyphema with distinction between fresh and clotted blood. Secondary outcomes: Time to resolution of primary hemorrhage; Time to secondary hemorrhage; Visual acuity at final visit (follow-up ranged from 5 days to 3.4 years); IOP measured daily for 5 days using applanation tonometry; Length of hospitalization; and Risk of complications and adverse events.
Notes
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Unclear	Randomized, but method of allocation not reported
Allocation concealment?	Yes	Allocation was concealed from investigators by preparation of drugs by pharmacy; statement that investigators were unaware of next treatment assignment.
Blinding? Participants	Yes	Participants by use of medications prepared by pharmacy.
Blinding? Personnel and outcome assessors	Yes	Healthcare providers and outcomes assessors by use of medications prepared by pharmacy. “The double-blind code was not broken until completion of the study.”
Incomplete outcome data addressed? Primary outcome	Yes	There were no exclusions and no loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Incomplete outcome data addressed? Secondary outcomes	Yes	There were no exclusions and no loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes	“The authors have no proprietary interest in aminocaproic acid or any competing drug.”
Vangsted 1983
Methods	Study design: Randomized clinical trial Exclusions after randomization: None Losses to follow-up: None Intention-to-treat: All participants were analyzed in the group to which they were randomly assigned. Sample size calculations: Not reported
Participants	Country: Sweden Dates: November 1978 to May 1981 Number randomized: 112: 59 assigned to tranexamic acid, and 53 to bed rest. Age: The mean age of the tranexamic acid group was 23.5 years (range = 9 to 60), and that of the bed rest group was 23.5 years (range 9 to 67 years). Sex: The ratio of male: female of the study population was 4:1. Race: Not reported. Sickle cell disease: Not reported Participants appeared to be balanced with respect to baseline characteristics. Inclusion criteria: Traumatic hyphema Exclusion criteria: Penetrating ocular injury; Microscopic hyphema; More than 24 hours since trauma; Younger than 8 years of age; History of renal disease with creatine > 115 micromol/l; Serious blood dyscrasia or earlier thrombotic disease; Pregnancy.
Interventions	Treatment: 25 mg/kg oral tranexamic acid 3 times a day, for 7 days. Control: Complete bed rest, for 6 days. Treatment for both groups included: Patch on affected eye 1% atropine once a day; Dexamethosone 3 times a day; No aspirin; and Oral acetazolamide if IOP > 25 mmHg.
Outcomes	Primary outcome: Risk of secondary hemorrhage, assessed daily by slit lamp examination at days 2 and 7. Documentation and definition not reported. Secondary outcomes: Time to resolution of primary hemorrhage; Visual acuity measured at day 2 and 7; IOP measured using applanation tonometry at day 2 and 7; Length of hospitalization; and Risk of complications and adverse events.
Notes
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Unclear	Randomized, but method of allocation not reported
Allocation concealment?	Unclear	Method of allocation concealment not reported.
Blinding? Participants	No	Participants were not masked to treatment assignment (bed rest compared with tranexamic acid).
Blinding? Personnel and outcome assessors	No	Healthcare providers and outcome assessors were not masked to treatment assignment (bed rest compared with tranexamic acid).
Incomplete outcome data addressed? Primary outcome	Yes	There were no exclusions and no loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Incomplete outcome data addressed? Secondary outcomes	Yes	There were no exclusions and no loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes
Varnek 1980
Methods	Study design: Quasi-randomized controlled series Exclusions after allocation: None Losses to follow-up: None Intention-to-treat: All participants were analyzed in the group to which they were assigned. Sample size calculations: Not reported
Participants	Country: Denmark Dates: March 1978 to November 1979 Number allocated: 232 consecutive patients from 4 study centers Age: Mean 24.4 years Sex: 188 men and 44 women; 81% male Race: All were white Sickle cell disease: Not reported, but all white study population. Inclusion criteria: Traumatic hyphema with sedimented hyphema or visible clots in the anterior chamber; and Admitted less than 24 hours after sustaining injury. Exclusion criteria: Patients with hemorrhagic flare only; Pregnancy; Perforating eye injuries.
Interventions	Treatment (n =102): 25 mg/kg oral tranexamic acid divided into 3 doses for 6 days. Control (n = 130): Conservative treatment Treatment for both groups included: Hospitalization; Bed rest; and Stenopaeic glasses for 5 days.
Outcomes	Primary outcomes: Risk of secondary hemorrhage; Speed of absorption of primary hemorrhage; Final visual acuity; and Length of hospitalization. Follow-up: Days 5 and 12
Notes	Funding source not reported Method used to calculate mean visual acuity not reported
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	No	Allocation was not randomized; assigned patients to treatment groups based on date of admission.
Allocation concealment?	No	Method of allocation based on even versus odd admission dates.
Blinding? Participants	No	No placebo was used for the control group.
Blinding? Personnel and outcome assessors	No	Masking was not done because of the noticeable delay in resolution time between treatment groups. Tranexamic acid was considered to induce persistence of the primary clot a priori.
Incomplete outcome data addressed? Primary outcome	Yes	All participants were analyzed in the group to which they were assigned.
Incomplete outcome data addressed? Secondary outcomes	Yes	All participants were analyzed in the group to which they were assigned.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes
Welsh 1983
Methods	Study design: Randomized, double-masked, placebo-controlled clinical trial Exclusions after randomization: None Losses to follow-up: None Intention-to-treat: All participants were analyzed in the group to which they were randomly assigned. Sample size calculations: Not reported
Participants	Country: South Africa Dates: Not reported Number randomized: 39: 19 assigned to tranexamic acid, and 20 to placebo. Age: The mean age of the tranexamic acid group was 25.2 years (range = 15 to 38), and that of the placebo group was 25.2 years (range 14 to 52). Sex: 15 (79%) of the tranexamic acid group, and 17 (85%) of the placebo group were male. Race: All study participants were black. Sickle cell disease: Not reported Participants appeared to be balanced with respect to baseline characteristics. Three of 39 patients had a hyphema due to cataract surgery; 2 in the in the tranexamic group and one in the control group. Inclusion criteria: Hyphema; either non-perforated, or if perforated, then the wound was sutured and treated as closed injury. Exclusion criteria: More than 5 days since onset; Age 14 or older; Presence of hypertension; History of thrombocytic event; Diabetes; Renal impairment; Uremia; Presence of coma; Pregnancy.
Interventions	Treatment: 3 500 mg tablets of oral tranexamic acid 3 times a day for 7 days, for an overall total of 31.5 g tranexamic acid. Control: 3 tablets of placebo 3 times a day for 7 days Treatment for both groups included: Bed rest; Patch on affected eye; 1% atropine once a day; 4% pilocarpine once a day; Cortisone eye drops once a day.
Outcomes	Primary outcome: Risk of secondary hemorrhage, assessed daily by visual examination. Documentation and definition not reported. Secondary outcomes: Percentage area of hyphema, measured daily; IOP measured daily; and Risk of complications and adverse events.
Notes	Tranexamic acid and placebo supplied by Adcock Ingram Laboratories.
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Unclear	Randomized, but method of allocation not reported
Allocation concealment?	Yes	Allocation was concealed from investigators by preparation of drugs by pharmacy; statement that investigators were unaware of next treatment assignment.
Blinding? Participants	Yes	Participants by use of medications prepared by pharmacy. “Neither patient nor staff knew which tablet the patient was receiving and the code was broken by the pharmaceutical firm at the end of the trial.”
Blinding? Personnel and outcome assessors	Yes	Healthcare providers and outcomes assessors by use of medications prepared by pharmacy. “Neither patient nor staff knew which tablet the patient was receiving and the code was broken by the pharmaceutical firm at the end of the trial.”
Incomplete outcome data addressed? Primary outcome	Yes	There were no exclusions and no loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Incomplete outcome data addressed? Secondary outcomes	Yes	There were no exclusions and no loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Unclear	Cyklokapron and placebo tablets were supplied by Adcock Ingram Laboratories.
Zetterstrom 1969
Methods	Study design: Quasi-randomized controlled series Exclusions after allocation: None Losses to follow-up: None Intention-to-treat: All participants were analyzed in the group to which they were assigned Sample size calculations: Not reported
Participants	Country: Sweden Dates: September 1967 to September 1968 Number allocated: 117 consecutive patients Age: Mean was 22.0 years (range 5 to 57) Sex: 102 men and 17 women (as reported); 86% male Race: Not reported Sickle cell disease: Not reported Inclusion criteria: Traumatic hyphema Exclusion criteria: Perforation of the eyeball
Interventions	Treatment (n = 58): Topical atropine with Decadron (cortisone) eye drops five times daily and moderate ambulatory activity within hospital. Control (n = 59): Conservative treatment of complete bed rest without pinhole glasses or simultaneous local therapy. Treatment for both groups included in-patient care until visual acuity in the injured eye was satisfactory, the hyphema was absorbed, and intraocular pressure did not deviate from normal.
Outcomes	Primary outcomes: Length of hospitalization; Final visual acuity; Risk of secondary hemorrhage; and Complication rates. Follow-up: Followed until discharge; some patients with iritis were seen as out-patients after discharge.
Notes	Funding source not reported Method used to calculate mean visual acuity not reported
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	No	Allocation was not randomized; alternately assigned patients to treatment groups based on order of admission.
Allocation concealment?	No	Method of allocation based on order of admission.
Blinding? Participants	No	Masking of patients was not possible with the interventions being studied.
Blinding? Personnel and outcome assessors	Unclear	Masking was not reported, but unlikely because of the types of interventions being studied.
Incomplete outcome data addressed? Primary outcome	Yes	All participants were analyzed in the group to which they were assigned.
Incomplete outcome data addressed? Secondary outcomes	Yes	All participants were analyzed in the group to which they were assigned.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes
Zi 1999
Methods	Study design: Randomized controlled series Exclusions after allocation: None Losses to follow-up: None Intention-to-treat: All participants were analyzed in the group to which they were assigned. Sample size calculations: Not reported
Participants	Country: China Dates: September 1990 to 1997 Number randomized: 79 patients Age: Mean was 24.5 years (range 7 to 43) Sex: 70 men and 4 women (as reported); 95% male Race: Not reported Sickle cell disease: Not reported Inclusion criteria: Hyphema Exclusion criteria: Not reported
Interventions	Treatment (n = 39): Alternatively right and left lateral position. Control (n = 35): Semi-reclined position
Outcomes	Primary outcomes: time to resolution by severity. Secondary outcomes: Discomfort; Complications. Follow-up: Not reported
Notes	Funding source not reported
Risk of bias table
Item	Authors’ judgement	Support for judgement
Adequate sequence generation?	Unclear	Randomized, but method of allocation not reported
Allocation concealment?	Unclear	Method of allocation concealment not reported.
Blinding? Participants	No	Participants were not masked to treatment assignment (lying either semireclining or on side)
Blinding? Personnel and outcome assessors	No	Healthcare providers and outcome assessors were not masked.
Incomplete outcome data addressed? Primary outcome	Yes	All participants were analyzed in the group to which they were assigned.
Incomplete outcome data addressed? Secondary outcomes	Yes	All participants were analyzed in the group to which they were assigned.
Free of selective reporting?	Yes	Reported results for primary and secondary outcomes.
Free of other bias?	Yes

g: gram

IOP: intraocular pressure

kg: kilogram

l: liter

mg: milligram

micromol: micromole

mL: microliter

mm: millimeter

mmHg: millimeters of mercury

n: number of participants