Intervention Review

You have free access to this content

Medical interventions for traumatic hyphema

  1. Almutez Gharaibeh1,
  2. Howard I Savage2,
  3. Roberta W Scherer3,*,
  4. Morton F Goldberg4,
  5. Kristina Lindsley5

Editorial Group: Cochrane Eyes and Vision Group

Published Online: 3 DEC 2013

Assessed as up-to-date: 30 AUG 2013

DOI: 10.1002/14651858.CD005431.pub3


How to Cite

Gharaibeh A, Savage HI, Scherer RW, Goldberg MF, Lindsley K. Medical interventions for traumatic hyphema. Cochrane Database of Systematic Reviews 2013, Issue 12. Art. No.: CD005431. DOI: 10.1002/14651858.CD005431.pub3.

Author Information

  1. 1

    Faculty of Medicine, The University of Jordan, Department of Special Surgery-Ophthalmology, Amman, Jordan

  2. 2

    Kaiser Permanente Largo Medical Center, Largo, Maryland, USA

  3. 3

    Johns Hopkins University Bloomberg School of Public Health, Center for Clinical Trials, Baltimore, MD, USA

  4. 4

    Johns Hopkins University School of Medicine, Wilmer Eye Institute, Baltimore, Maryland, USA

  5. 5

    Johns Hopkins Bloomberg School of Public Health, Department of Epidemiology, Baltimore, Maryland, USA

*Roberta W Scherer, Center for Clinical Trials, Johns Hopkins University Bloomberg School of Public Health, Room W5010, 615 N. Wolfe St., Baltimore, MD, 21205, USA. rscherer@jhsph.edu.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 3 DEC 2013

SEARCH

 
Characteristics of included studies [ordered by study ID]
Bedrossian 1974

MethodsStudy 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.


ParticipantsCountry: 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: Nontotal traumatic hyphema.


InterventionsCycloplegics (n = 28): 1% atropine ointment.

Miotics (n = 30): 2% pilocarpine ointment (or eserine ointment).

Treatment for both groups included:

  1. Topical anesthetic if needed;
  2. Bed rest;
  3. Head of bed elevated 30-90°;
  4. Binocular patching or pinhole glasses;
  5. No reading or watching television;
  6. Metal shield over injured eye;
  7. Soft, nonchew diet;
  8. Laxatives;
  9. Room with other individuals; and
  10. Sedation.


OutcomesPrimary outcome: Time to resolution of primary hemorrhage.

Secondary outcomes:

  1. Risk of secondary hemorrhage; and
  2. Risk of iridodialysis.


Follow-up: days 1 to 7.


NotesFunding source not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskAllocation was not randomized; alternately assigned patients to treatment groups based on the blood level in the anterior chamber.

Allocation concealment (selection bias)High riskAllocation was assigned on an alternate basis.

Blinding (performance bias and detection bias)
Participants
High riskMasking was not reported.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
High riskMasking was not reported.

Incomplete outcome data (attrition bias)
Primary outcome
Low riskAll participants were analyzed in the group to which they were assigned.

Incomplete outcome data (attrition bias)
Secondary outcomes
Low riskAll participants were analyzed in the group to which they were assigned.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasLow riskNo other sources of potential bias were identified.

Christianson 1979

MethodsStudy 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.


ParticipantsCountry: 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.


InterventionsTreatment (n = 22): Oral aminocaproic acid, loading dose 75 mg/kg, followed by 60 mg/kg every 4 hours; length of treatment not reported.

Control (n = 23): Placebo, presumably every 4 hours.


OutcomesPrimary outcome: Risk of secondary hemorrhage, details not reported.

Secondary outcomes: Time to resolution of primary hyphema, details not reported.


NotesAbstract of unpublished study.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of randomization not reported.

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported.

Blinding (performance bias and detection bias)
Participants
Low riskAuthors used a placebo control and stated that the study was double-masked.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
Low riskAuthors used a placebo control and stated that the study was double-masked.

Incomplete outcome data (attrition bias)
Primary outcome
Low riskUnclear 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 (attrition bias)
Secondary outcomes
Low riskUnclear if number randomized equaled the number reported and analyzed in the abstract, but no exclusions or losses to follow-up were reported.

Selective reporting (reporting bias)Unclear riskFew study details available in the abstract and no full version was published.

Other biasUnclear riskFew study details available in the abstract and no full version was published.

Crouch 1976

MethodsStudy 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.


ParticipantsCountry: USA.

Dates: September 1972 to October 1974.

Number randomized: 59.

Age: 83% ages 6-30 years.

Sex: 83% male.

Race: 65% black people, 35% white people.

Sickle cell disease: 8/59 (14%) had sickle cell trait.

Participants appeared to be balanced with respect to baseline characteristics.

Inclusion criteria: Traumatic hyphema.

Exclusion criteria:

  1. Penetrating injury;
  2. Total hyphema;
  3. History of a bleeding disorder; and
  4. Pregnancy.


InterventionsTreatment (n = 32): Oral aminocaproic acid 100 mg/kg every 4 hours for 5 days.

Control (n = 27): Placebo (200 mL of aromatic elixir (5% glucose, water, and ethanol) in 1000 mL sterile water) every 4 hours for 5 days.

Treatment for both groups included:

  1. Moderate ambulation;
  2. No reading;
  3. Head of bed elevated to 45°;
  4. Patching of affected eye;
  5. No mydriatics, miotics, corticosteroids, or other topical medication; and
  6. No salicylates.


OutcomesPrimary outcome: Risk of secondary hemorrhage, assessed by daily slit lamp exam, and documented by 3 observers.

Secondary outcomes:

  1. Time to resolution of primary hemorrhage;
  2. Time to secondary hemorrhage;
  3. Final VA, with follow-up ranging between 6 months and 2.5 years;
  4. IOP assessed daily by applanation tonometry; and
  5. Risk of complications and adverse events.


Follow-up: 1 week, 1, 2, 3, 6, 12, 18, and 24 months.


NotesFunded by the National Eye Institute, National Institutes of Health.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskParticipants assigned to treatment groups using computerized randomization.

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported.

Blinding (performance bias and detection bias)
Participants
Low riskAuthors used a placebo control and stated that the study was double-masked.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
Low riskAuthors used a placebo control and stated that the study was double-masked.

Incomplete outcome data (attrition bias)
Primary outcome
Low riskThere were no exclusions and losses to follow-up. All participants were analyzed in the group to which they were randomly assigned.

Incomplete outcome data (attrition bias)
Secondary outcomes
Low riskThere were no exclusions and losses to follow-up. All participants were analyzed in the group to which they were randomly assigned.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasLow riskNo other sources of potential bias were identified.

Crouch 1997

MethodsStudy design: Randomized, double-masked clinical trial.

Exclusions after randomization: 1 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 25-30 participants in each of the 3 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.


ParticipantsCountry: USA.

Dates: March 1990 to May 1996.

Number randomized: 64: 29 to oral aminocaproic acid plus topical placebo, 35 to oral placebo plus topical aminocaproic acid. Additional 54 participants included as control group.

Age: 72% younger than 21 years.

Sex: 67% male.

Race: 50% black people, 49% white people, and 1% (1 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:

  1. Penetrating ocular injury;
  2. History of anticoagulant or antiplatelet agent within 7 days of ocular trauma;
  3. Oral or topical corticosteroid use within 48 hours of study;
  4. History of a coagulopathy;
  5. History of renal or hepatic insufficiency;
  6. Previous intraocular surgery;
  7. History of sensitivity to any component of topical aminocaproic acid;
  8. Pregnancy; and
  9. Participation in any investigational drug trial within last 4 weeks.


InterventionsTreatment: 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: Oral aminocaproic acid 50 mg/kg (up to 30 g/day) plus placebo gel every 4 hours, for 5 days.

Treatment for both groups included:

  1. Moderate ambulation;
  2. Head of bed elevated to 30°;
  3. Shield on affected eye;
  4. No aspirin, corticosteroids, nonsteroidal anti-inflammatory, or antiplatelet agents; and
  5. Topical timolol maleate, apraclonidine hydrochloride, dipivefrin hydrochloride, or oral acetazolamide if IOP > 22 mmHg.


OutcomesPrimary outcome: Risk of secondary hemorrhage, assessed by daily slit lamp exam, and documented by a sketch each day.

Secondary outcomes:

  1. VA, measured daily and at the end of the 5 days (final VA);
  2. Cell and flare, assessed daily for 5 days;
  3. Corneal bloodstaining and toxicity, assessed daily by slit lamp exam for 5 days;
  4. IOP assessed daily for 5 days by applanation tonometry; and
  5. Risk of complications and adverse events.


NotesFunded in part by the Lions Medical Eye Bank and Research Center of Eastern Virginia.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskParticipants assigned to treatment groups using computerized randomization.

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported.

Blinding (performance bias and detection bias)
Participants
Low riskAuthors 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 (performance bias and detection bias)
Personnel and outcome assessors
Low riskAuthors 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 (attrition bias)
Primary outcome
Unclear risk1 patient was excluded: 1 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 (attrition bias)
Secondary outcomes
Unclear risk1 patient was excluded: 1 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.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasLow riskNo other sources of potential bias were identified.

Edwards 1973

MethodsStudy 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 years and younger were analyzed in the group to which they were assigned.

Sample size calculations: Not reported.


ParticipantsCountry: USA.

Dates: 1969-1971.

Number allocated: 64 consecutive patients alternately assigned to treatment group.

Age: Mean 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.


InterventionsTreatment: Monocular patching (n = 35)

Control: Binocular patching (n = 29)

Treatment for both groups included:

  1. Standard regimen (including position in bed, sedation, and diet);
  2. Acetazolamide for severe secondary glaucoma; and
  3. No topical medications.


OutcomesPrimary and secondary outcomes not specified.

Measured outcomes:

  1. Risk of secondary hemorrhage;
  2. Duration of rebleeding;
  3. Complication rates; and
  4. Final VA.


Follow-up: days 1-7.


NotesFunded by Research to Prevent Blindness Inc., Public Health Service Training Grant, and the National Institutes of Health.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskAllocation 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 (selection bias)High riskAllocation was assigned on an alternate basis.

Blinding (performance bias and detection bias)
Participants
High riskMasking of patients was not possible with the interventions being studied.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
Unclear riskAuthors reported study to be double-masked, although this statement was 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 (attrition bias)
Primary outcome
Unclear riskPatients over 20 years of age were excluded after allocation to treatment group.

Incomplete outcome data (attrition bias)
Secondary outcomes
Unclear riskPatients over 20 years of age were excluded after allocation to treatment group.

Selective reporting (reporting bias)Low riskReported results for all outcomes.

Other biasLow risk No other sources of potential bias were identified.

Farber 1991

MethodsStudy 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 cross-over), 1 participant had an unrelated seizure, and 1 developed thrombocytopenia. 1 participant in the prednisone group was administered aminocaproic acid instead of prednisone (treatment cross-over) 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.


ParticipantsCountry: USA.

Dates: July 1985 to March 1990.

Number randomized: 122: 64 to aminocaproic acid, 58 to prednisone.

Age: Mean age in aminocaproic acid group: 23.8 ± 13.8 years (range 4-64 years); in prednisone group: 23.3 ± 13.4 years (range 1.5-62 years).

Sex: 79% male.

Race: 53% black people, 22% white people, 22% Hispanic people, and 3% of other ethnic or racial group. Study groups were not balanced by race: 57% of black people and 20% of white people in aminocaproic acid group vs. 48% of black people and 25% of white people in prednisone group.

Sickle cell disease: None; excluded

Inclusion criteria: Traumatic hyphema

Exclusion criteria:

  1. Penetrating ocular injury;
  2. Need for immediate surgery;
  3. Sickle cell trait or disease;
  4. History of intravascular coagulopathy;
  5. History of gastric ulcer;
  6. History of diabetes mellitus;
  7. Pregnancy;
  8. Intoxication;
  9. Presence of detectable blood in stool.


InterventionsTreatment: Oral aminocaproic acid 50 mg/kg (up to 30 g/day) every 4 hours plus 2 doses placebo, for 5 days.

Control: Oral prednisone 40 mg/day in 2 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:

  1. Moderate ambulation;
  2. No reading;
  3. Head of bed elevated to 30°;
  4. Patch and shield on affected eye;
  5. Topical 1% atropine sulfate 4 times/day;
  6. Oral acetaminophen (paracetamol) up to 650 mg/day, no aspirin;
  7. Topical timolol maleate 0.25% or 0.50% with or without oral acetazolamide if IOP > 25 mmHg; and
  8. Prochlorperazine edisylate (5 or 10 mg) if vomiting or nausea.


OutcomesPrimary outcome: Risk of secondary hemorrhage, recorded daily by slit lamp exam, 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:

  1. VA, initial and final (5 days);
  2. IOP measured daily using applanation tonometry; and
  3. Risk of complications and adverse events.


NotesFunded by the National Eye Institute of the National Institutes of Health, Bethesda, MD, and Research to Prevent Blindness.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomized, but method of allocation not reported.

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported.

Blinding (performance bias and detection bias)
Participants
Low riskAuthors used a double-dummy placebo design and stated that the study was double-masked.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
Low riskAuthors 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 (attrition bias)
Primary outcome
Unclear riskThe 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 (attrition bias)
Secondary outcomes
Unclear riskThe 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.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasLow riskNo other sources of potential bias were identified.

Karkhaneh 2003

MethodsStudy design: Randomized, double-masked clinical trial.

Exclusions after randomization: None.

Losses to follow-up: 23; 4 to homatropine drops plus topical aminocaproic acid gel, 5 to homatropine drops plus topical placebo gel, 14 to homatropine 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


ParticipantsCountry: Iran

Dates: 1998-1999

Number randomized: 155: 45 to homatropine drops plus topical aminocaproic acid gel, 44 to homatropine drops plus placebo gel, 66 to homatropine drops only.

Age: 4-30 years.

Sex: 87% (not including those lost to follow-up) male.

Race: Not reported.

Sickle cell disease: Not reported.

Participants appeared to be balanced with respect to baseline characteristics.

Inclusion criteria: Nonpentrating traumatic hyphema and emergency room outpatient of Farabi Eye Hospital.

Exclusion criteria:

  1. Penetrating ocular injury;
  2. Total hyphema;
  3. Microscopic hyphema;
  4. More than 24 hours since trauma;
  5. History of bleeding disorder;
  6. Previous ocular surgery in affected eye;
  7. Recent aspirin or anticoagulant ingestion;
  8. Pregnancy; and
  9. Trauma to affected eye during follow-up.


InterventionsTreatment 1: 2 drops of 25% aminocaproic acid in 2% carboxymethylene gel applied to inferior fornix of affected eye every 6 hours plus homatropine eyedrops 3 times/day, for 5 days.

Control 1: 2 drops 2% carboxymethylene (placebo) gel applied to inferior fornix of affected eye every 6 hours plus homatropine eyedrops 3 times/day, for 5 days.

Control 2: Homatropine eyedrops 3 times/day, for 5 days.

Treatment for all groups included:

  1. No reading;
  2. Head of bed elevated to 30°;
  3. Shield on affected eye;
  4. Oral acetaminophen (paracetamol);
  5. No aspirin.


OutcomesPrimary outcome: Risk of secondary hemorrhage, assessed daily by slit lamp exam 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:

  1. Time to resolution of primary hemorrhage;
  2. Time to secondary hemorrhage;
  3. VA; final VA at day 14;
  4. IOP measured using applanation tonometry;
  5. Corneal blood staining;
  6. Drug toxicity; and
  7. Risk of complications and adverse events.


NotesConducted with support from Sina Darou (an ophthalmic pharmaceutical company in Iran), who provided the aminocaproic acid preparation.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomized, but method of allocation was not reported.

Allocation concealment (selection bias)Low riskAllocation was concealed from investigators by use of coded bottles.

Blinding (performance bias and detection bias)
Participants
Unclear riskAuthors used coded bottles to mask participants for the topical medication, but the group assigned to homatropine drops and no topical medication was not masked.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
Low riskAuthors 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 (attrition bias)
Primary outcome
Unclear riskThe participants lost to follow-up were not included in the analyses and the intention-to-treat principle was not followed in the analyses. 23 participants lost to follow-up: 4 to homatropine drops plus topical aminocaproic acid gel, 5 to homatropine drops plus topical placebo gel, 14 to homatropine drops only.

Incomplete outcome data (attrition bias)
Secondary outcomes
Unclear riskThe participants lost to follow-up were not included in the analyses and the intention-to-treat principle was not followed in the analyses. 23 participants lost to follow-up: 4 to homatropine drops plus topical aminocaproic acid gel, 5 to homatropine drops plus topical placebo gel, 14 to homatropine drops only.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasUnclear riskConducted with support from Sina Darou (an ophthalmic pharmaceutical company in Iran), who provided the aminocaproic acid preparation.

Kraft 1987

MethodsStudy 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.


ParticipantsCountry: Canada

Dates: May 1978 to December 1984

Number randomized: 49: 24 to oral aminocaproic acid; 25 to placebo.

Age: 3-18 years. Mean age: aminocaproic acid group 10.6 years, placebo group 11.2 years.

Sex: 73% male.

Race: 3 black participants in the aminocaproic acid group; 1 in the placebo group. The ethnicity or race of the other participants was not reported.

Sickle cell disease: None; excluded.

Participants appeared to be balanced with respect to baseline characteristics.

Inclusion criteria: Children with nonpenetrating traumatic hyphema treated at the Hospital for Sick Children in Toronto, Canada.

Exclusion criteria:

  1. Penetrating ocular injury;
  2. More than 24 hours since trauma;
  3. Requirement for immediate surgical intervention;
  4. Positive sickle cell test or abnormal hematologic parameter;
  5. History of bleeding disorder;
  6. Ingestion of aspirin-containing medication within 7 days of admission; and
  7. Pregnancy.


InterventionsTreatment: Oral aminocaproic acid 100 mg/kg every 4 hours, for 5 days.

Control: Placebo every 4 hours, for 5 days.

Treatment for both groups included:

  1. Bed rest with bathroom privileges;
  2. Head of bed elevated 15°;
  3. Patch on affected eye;
  4. No topical eye medications except antibiotic ointment for corneal abrasions;
  5. Oral acetaminophen (paracetamol) (10-20 mg/kg every 4 hours, up to 650 mg/dose);
  6. No aspirin-containing medications;
  7. Up to 0.5 mg/kg per day diazepam for sedation if needed;
  8. Topical timolol maleate 0.5% if IOP > 25 mmHg;
  9. Dimenhydrinate (Gravol) 6.25-12.5 mg every 6 hours if vomiting or nausea.


OutcomesPrimary outcome: Risk of secondary hemorrhage, assessed daily by slit lamp exam; documented by 2 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.

  1. Time to resolution of primary hemorrhage;
  2. VA;
  3. IOP assessed using applanation tonometry; and
  4. Risk of complications and adverse events.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskParticipants assigned to treatment groups using computerized randomization.

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported.

Blinding (performance bias and detection bias)
Participants
Low riskAuthors used a placebo control and stated that the study was double-masked.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
Low riskAuthors used a placebo control and stated that the study was double-masked.

Incomplete outcome data (attrition bias)
Primary outcome
Low riskThere was no loss to follow-up and all participants were analyzed in the group to which they were randomly assigned.

Incomplete outcome data (attrition bias)
Secondary outcomes
Low riskThere was no loss to follow-up and all participants were analyzed in the group to which they were randomly assigned.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasLow riskNo other sources of potential bias were identified.

Kutner 1987

MethodsStudy design: Randomized, double-masked clinical trial

Exclusions after randomization: 1 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.


ParticipantsCountry: USA.

Dates: November 1983 to January 1986.

Number randomized: 34: 21 to aminocaproic acid, 13 placebo.

Age: Mean age: aminocaproic acid 18.9 ± 7.7 years, placebo 22.8 ± 7.6 years.

Sex: 88% male.

Race: 85% white people.

Sickle cell disease: None; excluded.

Participants appeared to be balanced with respect to baseline characteristics.

Inclusion criteria: Nonpenetrating traumatic hyphema.

Exclusion criteria:

  1. Penetrating ocular injury;
  2. More than 48 hours since trauma;
  3. Age less than 7 years;
  4. Sickle cell anemia;
  5. History of intravascular coagulopathy, blood dyscrasia, or renal disease;
  6. History of ocular disease that could increase the susceptibility to intraocular hemorrhage;
  7. Recent anticoagulant, aspirin, or oral contraceptive use; and
  8. Pregnancy.


InterventionsTreatment: Oral aminocaproic acid 100 mg/kg 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:

  1. Quiet activities;
  2. No reading;
  3. No patch or shield;
  4. No ocular medications;
  5. Oral acetaminophen 9paracetamol) (10-20 mg/kg every 4 hours, up to 650 mg/dose);
  6. No aspirin or alcohol;
  7. Diazepam 5 mg every 6 hours for sedation if needed;
  8. Topical timolol maleate 0.5% with IOP > 35 mmHg; and
  9. Prochloroperazine 5-10 mg if vomiting or nausea.


OutcomesPrimary outcome: Risk of secondary hemorrhage, assessed daily by slit lamp exam, for 6 days and 1 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 exam.

Secondary outcomes:

  1. Time to resolution of primary hemorrhage;
  2. VA, measured daily for 6 days and 1 week after discharge;
  3. IOP measured daily using applanation tonometry for 6 days and 1 week after discharge; and
  4. Risk of complications and adverse events.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskParticipants assigned to treatment groups using computerized randomization.

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported.

Blinding (performance bias and detection bias)
Participants
Low riskAuthors used a placebo control and stated that the study was double-masked.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
Low riskAuthors 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 (attrition bias)
Primary outcome
Unclear riskOne 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 (attrition bias)
Secondary outcomes
Unclear riskOne 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.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasLow riskNo other sources of potential bias were identified.

Liu 2002

MethodsStudy 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.


ParticipantsCountry: China

Dates: December 1997 to December 2000

Number randomized: 92: 60 to aminomethylbenzoic acid, 32 to control.

Age: Mean age: aminomethylbenzoic acid 32.7 ± 11.25 years, control 33.4 ± 10.75 years.

Sex: 75% 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:

  1. More than 48 hours since trauma;
  2. Use of anticoagulants;
  3. History of risk of clot formation;
  4. History of diabetes.


InterventionsTreatment: Oral aminomethylbenzoic acid 0.5 g plus oral vitamin B1 20 mg 3 times/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: Oral vitamin B1 20 mg 3 times/day, for 6 days.

Treatment for both groups included 0.3% ofloxacin eyedrops 4 times/day, for 6 days.


OutcomesPrimary outcome: Risk of secondary hemorrhage, details not reported.

Secondary outcomes: Risk of complications and adverse events.


NotesPoor description of study methods in publication.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomized, but method of allocation not reported.

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported.

Blinding (performance bias and detection bias)
Participants
Unclear riskThe authors do not state whether masking was used.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
Unclear riskThe authors do not state whether masking was used.

Incomplete outcome data (attrition bias)
Primary outcome
Low riskNo exclusions or loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.

Incomplete outcome data (attrition bias)
Secondary outcomes
Low riskNo exclusions or loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.

Selective reporting (reporting bias)Unclear riskStudy outcomes of interest not clearly stated.

Other biasLow riskNo other sources of potential bias were identified.

Marcus 1988

MethodsStudy 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.


ParticipantsCountry: Israel.

Dates: Not reported.

Number randomized: 51: 23 to aspirin, 28 to observation.

Age: Mean age: 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:

  1. Age < 7 years;
  2. Diastolic blood pressure > 100 mmHg;
  3. Current use of anticoagulants;
  4. Current use of antihypertensive medication;
  5. Peptic ulcer;
  6. "Restless".


InterventionsTreatment: Aspirin 500 mg 3 times/day for 5 days.

Control: Observation

Treatment for both groups included:

  1. Bed rest;
  2. Topical atropine 1% and dexamycin 0.1% 4 times/day; and
  3. Topical timolol or oral acetazolamide if IOP > 25 mmHg.


OutcomesPrimary outcome: Risk of secondary hemorrhage, assessed daily. Documented by estimating percentage involvement and plotting diagrammatically; definition not reported.

Secondary outcomes:

  1. VA, assessed daily for 7 days; and
  2. IOP assessed daily for 7 days; details not reported.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomized, but method of allocation not reported.

Allocation concealment (selection bias)Low riskAllocation was concealed from investigators by use of sequentially numbered envelopes.

Blinding (performance bias and detection bias)
Participants
High riskThe participants were not masked to treatment. No placebo was given to the control group.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
High riskThe healthcare providers were not masked to treatment. No placebo was given to the control group.

Incomplete outcome data (attrition bias)
Primary outcome
Low riskNo exclusions or loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.

Incomplete outcome data (attrition bias)
Secondary outcomes
Low riskNo exclusions or loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.

Selective reporting (reporting bias)Unclear riskOnly report results for secondary hemorrhage.

Other biasLow riskPoor description of study methods and results in publication.

McGetrick 1983

MethodsStudy design: Randomized, double-masked clinical trial.

Exclusions after randomization: The chart of 1 participant in the placebo group was "lost" and 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.


ParticipantsCountry: USA.

Dates: August 1980 to February 1982.

Number randomized: 50: 28 to aminocaproic acid, 22 to placebo.

Age: 86% ages 6-40 years.

Sex: 81% male.

Race: 69% black people, 21% Hispanic people, and 10% white people.

Sickle cell disease: None; excluded.

Participants appeared to be balanced with respect to baseline characteristics.

Inclusion criteria: Nonpenetrating traumatic hyphema.

Exclusion criteria:

  1. Penetrating ocular injury;
  2. Requirement for immediate surgical intervention;
  3. Sickle cell hemoglobin;
  4. History of intravascular coagulopathy;
  5. Pregnancy.


InterventionsTreatment: Oral aminocaproic acid 100 mg/kg (up to 5 g/dose and 30 g/day) every 4 hours, for 5 days.

Control: Placebo every 4 hours, for 5 days.

Treatment for both groups included:

  1. Quiet activities;
  2. No reading;
  3. Patch and shield on affected eye;
  4. Topical 1% atropine sulfate 4 times/day;
  5. Oral acetaminophen (paracetamol) up to 650 mg/day;
  6. No aspirin; and
  7. Topical timolol maleate 0.25% or 0.5% and oral acetazolamide, if IOP > 35 mmHg


OutcomesPrimary outcome: Risk of secondary hemorrhage, assessed daily by slit lamp exam. Defined as a definite increase in the amount of blood in the anterior chamber following admission.

Secondary outcomes:

  1. Time to resolution of primary hemorrhage;
  2. Time to secondary hemorrhage;
  3. VA (final) with follow-up ranging from 0 to 9 months;
  4. IOP assessed daily by applanation tonometry for 5 days;
  5. Length of hospitalization; and
  6. Risk of complications and adverse events.


NotesFunded by the National Eye Institute, National Institutes of Health, Bethesda, MD and Research to Prevent Blindness, Inc.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskParticipants assigned to treatment groups using computerized randomization.

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported.

Blinding (performance bias and detection bias)
Participants
Low riskAuthors used a placebo control and stated that the study was double-masked.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
Low riskAuthors 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 (attrition bias)
Primary outcome
Unclear riskThe 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 (attrition bias)
Secondary outcomes
Unclear riskThe 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.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasLow riskNo other sources of potential bias were identified.

Palmer 1986

MethodsStudy design: Randomized, double-masked clinical trial.

Exclusions after randomization: 2 participants were excluded: 1 from the low-dose aminocaproic acid group due to need for surgery and 1 from the standard-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.


ParticipantsCountry: USA.

Dates: July 1982 to December 1983.

Number randomized: 59: 26 to low-dose aminocaproic acid, 33 to standard-dose aminocaproic acid.

Age: Mean age: low-dose aminocaproic acid 20 years (range 4-46 years), standard-dose aminocaproic acid 22.8 years (range 3-50 years).

Sex: 23 (88%) of low-dose aminocaproic acid and 27 (82%) of standard-dose aminocaproic acid were male.

Race: 13 (50%) black people, 7 (27%) white people, and 5 (19%) Hispanic people in the low-dose aminocaproic acid group, the race of the excluded participant was not reported; and 17 (52%) black people, 7 (27%) white people, and 9 (21%) Hispanic people 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:

  1. Requirement for immediate surgical intervention;
  2. Sickle cell hemoglobin;
  3. History of intravascular coagulopathy;
  4. Pregnancy.


InterventionsTreatment: Low-dose (50 mg/kg) oral aminocaproic acid (up to 5 g/dose or 30 g/day) every 4 hours, for 5 days.

Control: Standard-dose (100 mg/kg) oral aminocaproic acid (up to 5 g/dose or 30 g/day) every 4 hours, for 5 days.

Treatment for both groups included:

  1. Quiet activities;
  2. No reading;
  3. Head of bed elevated to 30°;
  4. Patch and shield on affected eye;
  5. Topical 1% atropine sulfate 4 times/day;
  6. Oral acetaminophen (paracetamol) up to 650 mg/day;
  7. No aspirin;
  8. Topical timolol maleate 0.25% or 0.5% and oral acetazolamide if IOP > 25 mmHg;
  9. Oral prochlorperazine edisylate (5 or 10 mg) if nausea or vomiting; and
  10. Steroids on recommendation of admitting physician.


OutcomesPrimary outcome: Incidence of secondary hyphema, assessed daily by slit lamp exam. 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:

  1. Time to resolution of primary hemorrhage;
  2. Time to secondary hemorrhage;
  3. VA; "final" VA not defined;
  4. IOP assessed daily using applanation tonometry;
  5. Length of hospitalization;
  6. Incidence of complications and adverse events.


NotesFunded 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

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskAssignments determined by computerized randomization in the pharmacy.

Allocation concealment (selection bias)Low riskAllocation was possibly concealed from investigators by pharmacy preparation of drugs.

Blinding (performance bias and detection bias)
Participants
Low riskParticipants 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 (performance bias and detection bias)
Personnel and outcome assessors
Low riskHealthcare 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 (attrition bias)
Primary outcome
Unclear risk2 participants were excluded: 1 from the low-dose aminocaproic acid group due to need for surgery and 1 from the standard-dose aminocaproic acid group due to severe hypotension. The study authors noted that excluding the patient from the standard group did not affect the statistical results.

Incomplete outcome data (attrition bias)
Secondary outcomes
Unclear risk2 participants were excluded: 1 from the low-dose aminocaproic acid group due to need for surgery and 1 from the standard-dose aminocaproic acid group due to severe hypotension. The intention-to-treat principle was followed only for analyses of adverse events.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasLow riskNo other sources of potential bias were identified.

Pieramici 2003

MethodsStudy 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 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: Multicenter study with 8 centers.


ParticipantsCountry: USA.

Dates: Not reported, although study was conducted over 14 months.

Number randomized: 51: 24 to aminocaproic acid, 27 to placebo

Age: Mean age: aminocaproic acid group 24 ± 4 years (range 4-73 years), placebo group 23 ± 3 years (range 6-48 years).

Sex: 21 (88%) of aminocaproic acid group and 23 (85%) of placebo group were male.

Race: 15 (63%) white people, 8 (33%) black people, and 1 (1%) other in aminocaproic acid group and 13 (48%) white people, 11 (41%) black people, and 3 (11%) other in placebo group.

Sickle cell disease: 2/24 (8%) of participants in aminocaproic acid group and 1/27 (4%) of participants in placebo group 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:

  1. Total hyphema or unlayered microscopic hyphema;
  2. More than 36 hours since trauma;
  3. Age less than 4 years;
  4. History of clinically significant coagulopathy, renal insufficiency, or hepatic insufficiency;
  5. Hypersensitivity or idiosyncratic reaction of proparacaine hydrochloride 0.5%, aminocaproic acid, or carboxymethylene;
  6. Evidence of any clinically significant cardiac, endocrine, gastrointestinal, hematologic, or immunologic abnormalities or disease (sickle cell disease was allowed);
  7. Ingestion of anticoagulant or antiplatelet agent within the previous 7 days or any nonsteroidal anti-inflammatory drug within previous 24 hours;
  8. Pregnancy;
  9. Participation in investigational drug trial within 4 weeks before randomization;
  10. Unable to complete trial.


InterventionsTreatment: 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:

  1. No reading or video games;
  2. Head of bed elevated to 30°;
  3. Shield on affected eye;
  4. Topical 2% homatropine sulfate 3 times/day;
  5. No topical steroids; and
  6. If IOP elevated, treatment at discretion of physician.


OutcomesPrimary outcome: Risk of secondary hemorrhage, assessed daily by slit lamp exam for 7 days; defined as increase in height of hyphema of at least 0.5 mm above darker blood, color change of blood of at least 0.5 mm, obvious new "trickle" of blood on iris, or reappearance of blood after resolution.

Secondary outcomes:

  1. Time to resolution of primary hemorrhage;
  2. Time to secondary hemorrhage;
  3. VA, final VA assessed at 7 days (end of treatment);
  4. Risk of complications and adverse events.


NotesFunded by Orphan Medical Inc., Covance Inc, National Eye Institute, National Institutes of health, Bethesda, MD, and Research to Prevent Blinding.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskParticipants assigned to treatment groups using computerized randomization.

Allocation concealment (selection bias)Low riskAllocation was concealed from investigators in that treatment assignments were based on a trial number obtained from a contract research organization.

Blinding (performance bias and detection bias)
Participants
Low riskAuthors used a placebo control and stated that the study was double-masked. "The investigators and patients were masked to the treatment arm."

Blinding (performance bias and detection bias)
Personnel and outcome assessors
Low riskAuthors 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 (attrition bias)
Primary outcome
Low riskNo exclusions or loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.

Incomplete outcome data (attrition bias)
Secondary outcomes
Low riskNo exclusions or loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasUnclear risk"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

MethodsStudy 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.


ParticipantsCountry: Iran.

Dates: January 1991 to May 1992.

Number randomized: 244: 82 to tranexamic acid, 81 to prednisone, 81 to placebo.

Age: Median age: tranexamic acid 11 years (range 1-65 years); prednisone 11.5 years (range 1-50 years), placebo 12 years (range 1-58 years).

Sex: 63 (79%) of tranexamic acid group, 58 (73%) of prednisone group, and 66 (82%) of placebo group were male.

Race: 100% white people.

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:

  1. Penetrating ocular injury;
  2. Total hyphema or unlayered microscopic hyphema;
  3. Definite secondary hemorrhage before entry;
  4. More than 48 hours since trauma;
  5. Requirement for immediate surgical intervention;
  6. History of renal insufficiency;
  7. Acid peptic disease;
  8. Recent ingestion of aspirin or anticoagulant;
  9. Use of topical corticosteroids after trauma;
  10. Pregnancy.


InterventionsTreatment 1: Oral tranexamic acid 75 mg/kg per day, divided into 3 doses/day, for 5 days.

Treatment 2: Oral prednisolone 0.75 mg/kg per day, divided into 2 doses/day, for 5 days.

Control: Placebo administered 3 times/day.

Treatment for all groups included:

  1. Limited ambulation;
  2. Head of bed elevated;
  3. Patch and shield on affected eye;
  4. Topical cyclopentolate for exam of the retina if necessary;
  5. Oral acetaminophen (paracetamol) for pain;
  6. No aspirin or topical corticosteroids;
  7. Topical timolol and oral acetazolamide, if elevated IOP; and
  8. Oral promethazine if nausea or vomiting.


OutcomesPrimary outcome: Risk of secondary hemorrhage, assessed daily by slit lamp exam 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:

  1. VA, measured at day 5 (discharge); and
  2. Risk of complications and adverse events.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomization was based on a randomization list.

Allocation concealment (selection bias)Unclear riskParticipants assigned to treatment groups using a randomization list, but not clear whether list was revealed before allocation to individuals enrolling participants.

Blinding (performance bias and detection bias)
Participants
Unclear riskParticipants partially masked in that authors used a placebo control for the tranexamic acid, but not for prednisone.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
Low riskHealthcare 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 (attrition bias)
Primary outcome
Unclear risk6 patients were excluded from the study: 2 in tranexamic acid group, 3 in prednisone group, and 1 in 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 (attrition bias)
Secondary outcomes
Unclear risk6 patients were excluded from the study: 2 in tranexamic acid group, 3 in prednisone group, and 1 in 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.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasLow riskNo other sources of potential bias were identified.

Rakusin 1972

MethodsStudy 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.

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.


ParticipantsCountry: South Africa.

Dates: 1966-1969.

Number allocated: 390 consecutive patients.

Age: Not reported.

Sex: Not reported.

Sickle cell disease: Not reported.

Race: 90% African origin, 10% Asiatic origin.

Inclusion criteria: Traumatic hyphema.

Exclusion criteria: Surgical treatment indicated.


InterventionsSeries of comparisons based on 6 variable factors:

  1. Bed rest (n = 26) vs. ambulatory treatment (n = 26);
  2. Eye pads: bilateral eye pads (n = 27) vs. single eye pads (n = 26) vs. no eye pads (n = 10);
  3. Topical antibiotics (0.5% chloramphenicol, n = 21) vs. corticosteroids, 0.5% hydrocortisone acetate (n = 13) vs. neither (n = 3);
  4. Mydriatics (1% homatropine, n = 17) vs. miotics (4% pilocarpine, n = 17) vs. neither (n = 19) vs. both (n = 17);
  5. Enzymes: oral trypsin (n = 15) vs. oral papase (n = 18) vs. neither (n = 10);
  6. Ocular hypotensive agents: acetazolamide 250 mg (n = 18) vs. oral glycerol 1 mL/kg (n = 18) vs. neither (n = 10).


Treatment and control groups followed the same regimen except even-numbered patients received the variable factor, 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.


OutcomesPrimary outcomes:

  1. Speed of absorption of blood from the anterior chamber;
  2. Risk of secondary hemorrhage;
  3. Complications of the hyphema; and
  4. Final VA.


Follow-up: Range 1-2 weeks to 3 years


NotesFunded 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

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskMethod 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 3 treatment groups.

Allocation concealment (selection bias)High riskMethod of allocation concealment not reported, not randomized.

Blinding (performance bias and detection bias)
Participants
High riskMasking 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 (performance bias and detection bias)
Personnel and outcome assessors
Unclear riskMasking was not reported.

Incomplete outcome data (attrition bias)
Primary outcome
Unclear risk79 participants were not included in the analyses and the intention-to-treat principle was not followed.

Incomplete outcome data (attrition bias)
Secondary outcomes
Unclear risk79 participants were not included in the analyses and the intention-to-treat principle was not followed.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasUnclear riskThe primary interventions of interest for this study were not clear. Although the majority of the patients in the series were assigned to 1 of 6 conservative treatment comparison groups, 59 recruited patients were selected for surgery.

Read 1974

MethodsStudy 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.


ParticipantsCountry: USA.

Dates: February 1970 to July 1972.

Number allocated: 137 consecutive patients.

Age: Mean 15.9 years.

Sex: 108 men and 29 women; 79% 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:

  1. Associated penetrating ocular injury;
  2. Surgical exploration for suspected rupture of the globe;
  3. Bodily injury;
  4. Recurrent ocular injury;
  5. Personal or family history of diabetes or bleeding disorders.


InterventionsMedical treatment #1 (n = 66): Bed rest with elevation of head to 30°, 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.

Eyedrops 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).


OutcomesPrimary and secondary outcomes not specified.

Measured outcomes:

  1. Changes or presence of IOP;
  2. Duration of primary hyphema;
  3. Risk of secondary hemorrhage;
  4. Risk of corneal staining;
  5. Need for surgical intervention;
  6. Complications of the hyphema; and
  7. Final VA.


Follow-up: 1 week, 1, 3, and 6 months (range 3 months to 2.5 years; mean 16.5 months).


NotesFunded by a grant from the Research to Prevent Blindness, Inc.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskAllocation was not randomized; alternately assigned patients to treatment groups at time of admission. Imbalance in number assigned to each group (66 vs. 71) makes it appear alternation was not systematic.

Allocation concealment (selection bias)High riskAllocation was assigned on an alternate basis.

Blinding (performance bias and detection bias)
Participants
High riskMasking of patients was not possible with the interventions being studied.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
High riskAll patients were treated by the primary investigator in order to standardize therapy and record results as accurately as possible.

Incomplete outcome data (attrition bias)
Primary outcome
Low riskAll participants were analyzed in the group to which they were assigned.

Incomplete outcome data (attrition bias)
Secondary outcomes
Low riskAll participants were analyzed in the group to which they were assigned.

Selective reporting (reporting bias)Low riskReported results for all outcomes.

Other biasHigh riskA 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

MethodsStudy 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.


ParticipantsCountry: USA.

Dates: 1963-1964.

Number randomized: 85: 39 to estrogen, 46 to placebo.

Age: Mean age: estrogen 16.2 years (range 2-62 years), placebo 18.9 years (range 0.5-65 years).

Sex: 80% of estrogen group, 85% of placebo group were male.

Race: 72% of estrogen group, 70% of placebo group were black people; remaining participants were white people.

Sickle cell disease: Not reported

Participants appeared to be balanced with respect to baseline characteristics.

Inclusion criteria: Traumatic hyphema.

Exclusion criteria:

  1. Penetrating ocular injury;
  2. More than 24 hours since trauma;
  3. History of ocular disease;
  4. Failure to co-operate.


InterventionsTreatment: Conjugated estrogen, 5 mg intramuscularly for children < 5 years; 10 mg intramuscularly for children 5 years or older but < 10 years; and 20 mg intravenously for children 10 years or older and adults, for 5 days.

Control: Placebo, for 5 days.

Treatment for both groups included:

  1. Complete bed rest;
  2. Head of bed elevated;
  3. Patches on both eyes;
  4. No ophthalmic drops; and
  5. Sedation and analgesics as needed.


OutcomesPrimary outcome: Risk of secondary hemorrhage, assessed daily by "complete ocular examination" for 5 days. Documentation and definition not reported.

Secondary outcomes:

  1. Time to secondary hemorrhage;
  2. VA measured at day 5 (discharge); and
  3. Risk of complications and adverse events.


NotesPlacebo and conjugated estrogen supplied by Ayerst Laboratory.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomized, but method of allocation not reported.

Allocation concealment (selection bias)Low riskAllocation was concealed from investigators by use of coded bottles.

Blinding (performance bias and detection bias)
Participants
Low riskAuthors 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 (performance bias and detection bias)
Personnel and outcome assessors
Low riskAuthors 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 (attrition bias)
Primary outcome
Low riskThere 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 (attrition bias)
Secondary outcomes
Low riskThere were no exclusions and no loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasLow riskNo other sources of potential bias were identified.

Spoor 1980

MethodsStudy 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.


ParticipantsCountry: USA.

Dates: September 1975 to December 1977.

Number randomized: 43: 23 to prednisone, 20 to placebo.

Age: Mean age: prednisone group 20.1 years (range 5-61 years), placebo group 21.2 years (range 9-51 years).

Sex: 16 (70%) of prednisone group, 16 (80%) of placebo group were male.

Race: There were 14 (61%) white people, 6 (26%) Hispanic people, and 3 (13%) black people in prednisone group. There were 11 (55%) white people, 7 (35%) Hispanic people, and 2 (10%) black people in placebo group.

Sickle cell disease: Not reported.

Participants appeared to be balanced with respect to baseline characteristics.

Inclusion criteria: Traumatic hyphema.

Exclusion criteria:

  1. Penetrating ocular injury;
  2. More than 24 hours since trauma;
  3. Treated before entry;
  4. Not available for 6 months follow-up.


InterventionsTreatment: Oral prednisone 40 mg/day for adults and children > 10 years; 15 mg/day for children ages 4-10 years; and 10 mg/day for children ages 18 months to 4 years, for 7 days.

Control: Lactose placebo capsules administered daily for 7 days.

Treatment for both groups included:

  1. Bed rest;
  2. Head of bed elevated 30-45°;
  3. Patch on affected eye;
  4. No topical medications;
  5. Sedation as needed;
  6. No aspirin; and
  7. Oral acetazolamide if IOP > 24 mmHg.


OutcomesPrimary outcome: Risk of secondary hemorrhage, assessed daily for 7 days, using slit lamp exam, documented by drawings or photography.

Secondary outcomes:

  1. Time to resolution of primary hemorrhage;
  2. Time to secondary hemorrhage;
  3. VA (followed up to 6 months);
  4. IOP assessed daily for 7 days using applanation tonometry;
  5. Risk of complications and adverse events.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomized, but method of allocation not reported.

Allocation concealment (selection bias)Low riskAllocation was concealed from investigators by use of encoded capsules prepared by pharmacy.

Blinding (performance bias and detection bias)
Participants
Low riskParticipants 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 (performance bias and detection bias)
Personnel and outcome assessors
Low riskHealthcare 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 (attrition bias)
Primary outcome
Low riskThere 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 (attrition bias)
Secondary outcomes
Low riskThere were no exclusions and no loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasLow riskNo other sources of potential bias were identified.

Sukumaran 1988

MethodsStudy 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.


ParticipantsCountry: 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:

  1. Other serious ocular or facial injuries;
  2. Hyphema greater than 7 mm.


InterventionsTreatment (n = 17): oral tranexamic acid (cyklokapron) 25 mg/kg divided into 3 doses for 7 days in addition to routine treatment.

Control (n = 18): Routine treatment.

Routine treatment for both groups included:

  1. Bilateral patching;
  2. Bed rest;
  3. Sedation;
  4. Analgesics when required; and
  5. Topical corticosteroid drops from the third day for 1 week.


OutcomesPrimary outcomes:

  1. Risk of secondary hemorrhage;
  2. Speed of recovery; and
  3. Final VA


Follow-up: At least 1 week


NotesFunding source not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskMethod of allocation unclear, not randomized.

Allocation concealment (selection bias)High riskMethod of allocation concealment not reported, not randomized.

Blinding (performance bias and detection bias)
Participants
High riskNo placebo was used for the control group.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
Unclear riskMasking was not reported.

Incomplete outcome data (attrition bias)
Primary outcome
Low riskAll participants were analyzed in the group to which they were assigned.

Incomplete outcome data (attrition bias)
Secondary outcomes
Low riskAll participants were analyzed in the group to which they were assigned.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasLow risk No other sources of potential bias were identified.

Teboul 1995

MethodsStudy 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.


ParticipantsCountry: Canada.

Dates: November 1987 to February 1994.

Number randomized: 94: 48 to aminocaproic acid, 46 to placebo.

Age: Mean age: aminocaproic acid group 8.2 years, placebo group 10.6 years.

Sex: 42 (88%) of aminocaproic acid group, 39 (85%) of placebo group were male.

Race: 43 (90%) of aminocaproic acid group, 42 (91%) of placebo group were 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:

  1. Penetrating ocular injury;
  2. Total hyphema;
  3. More than 24 hours since trauma;
  4. Requirement for immediate surgical intervention;
  5. History of sickle cell anemia, renal disease, hepatic disease, cardiac disease, or coagulopathy;
  6. Recent ingestion of aspirin up to 1 week before entry;
  7. Pregnancy.


InterventionsTreatment: Oral aminocaproic acid 100 mg/kg every 4 hours (up to 30 g/day), for 5 days.

Control: Placebo every 4 hours, for 5 days.

Treatment for both groups included:

  1. Bed rest;
  2. Head of bed elevated to 45°;
  3. Patch on affected eye;
  4. 1% atropine ointment nightly and garsone drops 2 times/day;
  5. Oral acetaminophen (paracetamol) for pain;
  6. No aspirin;
  7. Topical timolol maleate 0.5% 2 times/day and oral acetazolamide if IOP > 25 mmHg; and
  8. Dimenhydrinate (Gravol) if nausea or vomiting.


OutcomesPrimary outcome: Risk of secondary hemorrhage, assessed by daily slit lamp exam for 5 days; documented by drawing of hyphema with distinction between fresh and clotted blood.

Secondary outcomes:

  1. Time to resolution of primary hemorrhage;
  2. Time to secondary hemorrhage;
  3. VA at final visit (follow-up range 5 days to 3.4 years);
  4. IOP measured daily for 5 days using applanation tonometry;
  5. Length of hospitalization; and
  6. Risk of complications and adverse events.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomized, but method of allocation not reported.

Allocation concealment (selection bias)Low riskAllocation was concealed from investigators by preparation of drugs by pharmacy; statement that investigators were unaware of next treatment assignment.

Blinding (performance bias and detection bias)
Participants
Low riskParticipants by use of medications prepared by pharmacy.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
Low riskHealthcare 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 (attrition bias)
Primary outcome
Low riskThere 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 (attrition bias)
Secondary outcomes
Low riskThere were no exclusions and no loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasLow risk"The authors have no proprietary interest in aminocaproic acid or any competing drug."

Vangsted 1983

MethodsStudy 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.


ParticipantsCountry: Sweden.

Dates: November 1978 to May 1981.

Number randomized: 112: 59 to tranexamic acid, 53 to bed rest.

Age: Mean age: tranexamic acid group 23.5 years (range 9-60 years), bed rest group 23.5 years (range 9-67 years).

Sex: Ratio of male:female 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:

  1. Penetrating ocular injury;
  2. Microscopic hyphema;
  3. More than 24 hours since trauma;
  4. Younger than 8 years of age;
  5. History of renal disease with creatine > 115 micromol/L;
  6. Serious blood dyscrasia or earlier thrombotic disease;
  7. Pregnancy.


InterventionsTreatment: Oral tranexamic acid 25 mg/kg 3 times/day, for 7 days.

Control: Complete bed rest, for 6 days.

Treatment for both groups included:

  1. Patch on affected eye;
  2. 1% atropine once/day;
  3. Dexamethasone 3 times/day;
  4. No aspirin; and
  5. Oral acetazolamide if IOP > 25 mmHg.


OutcomesPrimary outcome: Risk of secondary hemorrhage, assessed daily by slit lamp exam at days 2 and 7. Documentation and definition not reported.

Secondary outcomes:

  1. Time to resolution of primary hemorrhage;
  2. VA measured at day 2 and 7;
  3. IOP measured using applanation tonometry at day 2 and 7;
  4. Length of hospitalization; and
  5. Risk of complications and adverse events.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomized, but method of allocation not reported.

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported.

Blinding (performance bias and detection bias)
Participants
High riskParticipants were not masked to treatment assignment (bed rest vs. tranexamic acid).

Blinding (performance bias and detection bias)
Personnel and outcome assessors
High riskHealthcare providers and outcome assessors were not masked to treatment assignment (bed rest vs. tranexamic acid).

Incomplete outcome data (attrition bias)
Primary outcome
Low riskThere 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 (attrition bias)
Secondary outcomes
Low riskThere were no exclusions and no loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasLow riskNo other sources of potential bias were identified.

Varnek 1980

MethodsStudy 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.


ParticipantsCountry: Denmark.

Dates: March 1978 to November 1979.

Number allocated: 232 consecutive patients from 4 study centers.

Age: Mean 24.4 years.

Sex: 188 men, 44 women; 81% male.

Race: 100% white people.

Sickle cell disease: Not reported, but all white study population.

Inclusion criteria:

  1. Traumatic hyphema with sedimented hyphema or visible clots in the anterior chamber; and
  2. Admitted less than 24 hours after sustaining injury.


Exclusion criteria:

  1. Patients with hemorrhagic flare only;
  2. Pregnancy;
  3. Perforating eye injuries.


InterventionsTreatment (n = 102): oral tranexamic acid 25 mg/kg divided into 3 doses for 6 days.

Control (n = 130): Conservative treatment.

Treatment for both groups included:

  1. Hospitalization;
  2. Bed rest; and
  3. Stenopaeic glasses for 5 days.


OutcomesPrimary outcomes:

  1. Risk of secondary hemorrhage;
  2. Speed of absorption of primary hemorrhage;
  3. Final VA; and
  4. Length of hospitalization.


Follow-up: Days 5 and 12.


NotesFunding source not reported.

Method used to calculate mean VA not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskAllocation was not randomized; assigned patients to treatment groups based on date of admission.

Allocation concealment (selection bias)High riskMethod of allocation based on even versus odd admission dates.

Blinding (performance bias and detection bias)
Participants
High riskNo placebo was used for the control group.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
High riskMasking 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 (attrition bias)
Primary outcome
Low riskAll participants were analyzed in the group to which they were assigned.

Incomplete outcome data (attrition bias)
Secondary outcomes
Low riskAll participants were analyzed in the group to which they were assigned.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasLow risk No other sources of potential bias were identified.

Wang 1994

MethodsStudy 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.


ParticipantsCountry: China.

Dates: Not reported.

Number randomized: 83: 45 in treatment group, 38 in control group.

Age: Range 4-49 years.

Sex: 56 (67%) men, 27 (33%) women.

Race: Not reported.

Sickle cell disease: Not reported.

Participants appeared to be balanced with respect to baseline characteristics (P value > 0.05 for between-group comparisons for anterior chamber blood volume, IOP, gender, and age). Severity of hyphema not reported; however, in the treatment group, 29 (64%) participants were given the medicine within 24 hours after the trauma, 13 (29%) cases were given the medicine within 3 days after the trauma, and 3 (7%) cases were given the medicine at day 5 after the trauma; for the control group, 31 (82%) participants were given the medicine (Carbazochrome or Etamsylate) within 24 hours after the trauma, and 7 (18%) cases were given the medicine within 3 days after the trauma.

Inclusion criteria: Any degree of traumatic hyphema.

Exclusion criteria: Not reported.


InterventionsTreatment (n = 45): Yunnan Baiyao (a traditional Chinese medicine) was given to the participants in the treatment group. The participants were assigned to take 0.5 g of the medicine 4 times/day orally, accompanied by vitamin C and vitamin K also taken orally, and with 0.5% vinegar eyedrops [醋考眼药水]. The length of treatment was up to 5 days (until complete resolution).

Control (n = 38): participants in the control group were given medicines such as Carbazochrome or Etamsylate to help with stopping bleeding

Follow-up: 1 week.


OutcomesPrimary outcome: Number of participants "cured", defined as complete resolution within 5 days, VA of 0.7 or better, and no rebleed within 1 week.

Secondary outcomes: None reported.


NotesFunding source not reported.

Poor description of study methods and outcomes in publication.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomized, but method of allocation not reported.

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported.

Blinding (performance bias and detection bias)
Participants
Unclear riskMasking of participants was not reported.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
Unclear riskMasking of outcome assessors was not reported.

Incomplete outcome data (attrition bias)
Primary outcome
Low riskThere 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 (attrition bias)
Secondary outcomes
Low riskThere were no exclusions and no loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.

Selective reporting (reporting bias)Unclear riskStudy outcomes of interest not clearly stated.

Other biasHigh risk2 different control interventions were described, but method used to decide which participants received which control intervention not stated. Why 'vinegar eyedrops' were used in the experimental group not described. Length of time between onset of hyphema and initiation of treatment differed between treatment groups.

Welsh 1983

MethodsStudy 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.


ParticipantsCountry: South Africa.

Dates: Not reported.

Number randomized: 39: 19 to tranexamic acid, 20 to placebo.

Age: Mean age: tranexamic acid group 25.2 years (range 15-38 years), placebo group 25.2 years (range 14-52 years).

Sex: 15 (79%) of tranexamic acid group, 17 (85%) of placebo group were male.

Race: 100% black people.

Sickle cell disease: Not reported.

Participants appeared to be balanced with respect to baseline characteristics. 3 of 39 patients had a hyphema due to cataract surgery; 2 in the tranexamic group and 1 in the control group.

Inclusion criteria: Hyphema; either nonperforated, or if perforated, then the wound was sutured and treated as closed injury.

Exclusion criteria:

  1. More than 5 days since onset;
  2. Age 14 or older;
  3. Presence of hypertension;
  4. History of thrombocytic event;
  5. Diabetes;
  6. Renal impairment;
  7. Uremia;
  8. Presence of coma;
  9. Pregnancy.


InterventionsTreatment: 3 x 500 mg tablets of oral tranexamic acid 3 times/day for 7 days, for an overall total of 31.5 g of tranexamic acid.

Control: 3 tablets of placebo 3 times/day for 7 days.

Treatment for both groups included:

  1. Bed rest;
  2. Patch on affected eye;
  3. 1% atropine once/day;
  4. 4% pilocarpine once/day;
  5. Cortisone eyedrops once/day.


OutcomesPrimary outcome: Risk of secondary hemorrhage, assessed daily by visual exam. Documentation and definition not reported.

Secondary outcomes:

  1. Percentage area of hyphema, measured daily;
  2. IOP measured daily; and
  3. Risk of complications and adverse events.


NotesTranexamic acid and placebo supplied by Adcock Ingram Laboratories.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomized, but method of allocation not reported.

Allocation concealment (selection bias)Low riskAllocation was concealed from investigators by preparation of drugs by pharmacy; statement that investigators were unaware of next treatment assignment.

Blinding (performance bias and detection bias)
Participants
Low riskParticipants 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 (performance bias and detection bias)
Personnel and outcome assessors
Low riskHealthcare 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 (attrition bias)
Primary outcome
Low riskThere 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 (attrition bias)
Secondary outcomes
Low riskThere were no exclusions and no loss to follow-up. All participants were analyzed in the group to which they were randomly assigned.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasUnclear riskCyklokapron and placebo tablets were supplied by Adcock Ingram Laboratories.

Zetterstrom 1969

MethodsStudy 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.


ParticipantsCountry: Sweden.

Dates: September 1967 to September 1968.

Number allocated: 117 consecutive patients.

Age: Mean: 22.0 years (range 5-57 years).

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.


InterventionsTreatment (n = 58): Topical atropine with Decadron (cortisone) eyedrops 5 times/day 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 inpatient care until VA in the injured eye was satisfactory, the hyphema was absorbed, and IOP did not deviate from normal.


OutcomesPrimary outcomes:

  1. Length of hospitalization;
  2. Final VA;
  3. Risk of secondary hemorrhage; and
  4. Complication rates.


Follow-up: Followed until discharge; some patients with iritis were seen as outpatients after discharge.


NotesFunding source not reported.

Method used to calculate mean VA not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskAllocation was not randomized; alternately assigned patients to treatment groups based on order of admission.

Allocation concealment (selection bias)High riskMethod of allocation based on order of admission.

Blinding (performance bias and detection bias)
Participants
High riskMasking of patients was not possible with the interventions being studied.

Blinding (performance bias and detection bias)
Personnel and outcome assessors
Unclear riskMasking was not reported, but unlikely because of the types of interventions being studied.

Incomplete outcome data (attrition bias)
Primary outcome
Low riskAll participants were analyzed in the group to which they were assigned.

Incomplete outcome data (attrition bias)
Secondary outcomes
Low riskAll participants were analyzed in the group to which they were assigned.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasLow risk No other sources of potential bias were identified.

Zi 1999

MethodsStudy 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.


ParticipantsCountry: China.

Dates: September 1990 to 1997.

Number randomized: 79.

Age: Mean: 24.5 years (range 7-43 years).

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.


InterventionsTreatment (n = 39): Alternatively right and left lateral position.

Control (n = 35): Semi-reclined position.


OutcomesPrimary outcomes: Time to resolution by severity.

Secondary outcomes:

  1. Discomfort; and
  2. Complications.


Follow-up: Not reported.


NotesFunding source not reported.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomized, but method of allocation not reported.

Allocation concealment (selection bias)Unclear riskMethod of allocation concealment not reported.

Blinding (performance bias and detection bias)
Participants
High riskParticipants were not masked to treatment assignment (laying either semi-reclining or on side).

Blinding (performance bias and detection bias)
Personnel and outcome assessors
High riskHealthcare providers and outcome assessors were not masked.

Incomplete outcome data (attrition bias)
Primary outcome
Low riskAll participants were analyzed in the group to which they were assigned.

Incomplete outcome data (attrition bias)
Secondary outcomes
Low riskAll participants were analyzed in the group to which they were assigned.

Selective reporting (reporting bias)Low riskReported results for primary and secondary outcomes.

Other biasLow riskNo other sources of potential bias were identified.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Amirova 1991Included nontraumatic hyphema cases in trial and could not determine outcomes in traumatic hyphema cases separately; the method of choosing the control group was not mentioned.

Anderson 1971Not a clinical trial, case reports.

Berrios 1995Review of traumatic hyphema, no original data.

Bramsen 1977Not a clinical trial, used historical controls.

Bramsen 1980Review of previously published studies, no original data.

Campana 1969Not a clinical trial, case reports and experimental studies in rabbits.

Cherkasov 1989Did not include traumatic hyphema cases, all had vitreous hemorrhage.

Crawford 1976Not a clinical trial, retrospective cohort study.

Dralands 1981Not a clinical trial, used historical controls.

Dumitrache 2011Not a clinical trial, case reports.

Gabler 2002Review of treatment strategies for ocular emergencies, no original data.

Gastaldi 1970Review of treatments for traumatic hyphema, no original data.

Ghisolfi 1972Included nontraumatic hyphema cases in trial and could not determine outcomes in traumatic hyphema cases separately.

Gilbert 1973Not a clinical trial, used historical controls.

Gillan 1961Not a clinical trial, used historical controls.

Goldberg 1960Not a clinical trial, cohort study using chart review.

Gundorova 1985Not a clinical trial. There were only 3 patients with post-traumatic hyphema and no obvious control group was defined.

Guseva 2010Included nontraumatic hyphema cases and could not determine outcomes in traumatic hyphema cases separately; the method of choosing treatment groups was not mentioned.

Heath 1966Not a clinical trial, case reports.

Jrasnov 1986Not a clinical trial, all patients on same drug therapy, compared those who ended up having surgery vs. those who did not.

Kirschner 2012Summary of review, no original data.

Kotas 1990Not a clinical trial, case report.

Krasnov 1971aThere were only 6 patients with post-traumatic hyphema without surgery or penetrating injuries; patients with different types of glaucoma were classified and treated with glycerin alone or with glycerin and thromboplatin accordingly.

Krasnov 1971bNot a clinical trial, 2 case series and 1 report of an animal study.

Latinovic 1981Interventional case series, no control group.

Li 1997Included nontraumatic hyphema cases in trial and could not determine outcomes in traumatic hyphema cases separately.

Li 2009Not a clinical trial, cohort study.

Logai 1974Not a clinical trial, case series of 74 eyes with hyphema, 28 had nonpenetrating traumatic hyphema.

Mathis 1987Not a clinical trial, case reports.

Missotten 1977Not a clinical trial, used historical controls

Mortensen 1978Not a clinical trial, used historical controls.

Munoz Negrete 1989Interventional case series, no control group.

Murzin 1966Not a clinical trial, appears to be without a control group and the author tested 2 different drugs in various combinations for various types of bleeds in the eye, which occurred at various times before the onset of treatment.

Ohrstrom 1972Not a clinical trial, cohort study.

Oksala 1967Not a clinical trial, cohort study.

Pierse 1964Not a clinical trial, case reports.

Pogorel'skii 1966Not a clinical trial, cohort study comparing patients with hemophthalmos treated with chemotrypsin vs. patients with hemorrhage into the eye cavity treated with resorption therapy.

Polychronakos 1967Not a clinical trial, case reports.

Rakusin 1971Not eligible, surgical interventions.

Roberts 2006Editorial calling for trial for traumatic hyphema to be done, no original data.

Romano 1986Review of corticosteroids for the treatment of traumatic hyphema, no original data.

Romashchenko 19853 groups of patients with bleeds in the eye: group 1 was a mix of post-traumatic and postoperative hyphemas (no clear group with post-traumatic hyphemas); the control group was taken from a retrospective study of case notes from 1979 to 1981 and those patients had received an entirely different set of drugs as treatment for their bleeds in the eye.

Rouher 1966Not a clinical trial, report of 10 cases, only some of patients had hyphema.

Spoor 1990Not a clinical trial, cohort study.

Stepanov 2002Not a clinical trial, no control group.

Surel 1987Not a clinical trial, used historical controls.

Tartakovskaia 1972Not a clinical trial, no control group.

Travkin 1997Included nontraumatic hyphema cases in trial and could not determine outcomes in traumatic hyphema cases separately.

Uusitalo 1988Not a clinical trial, used historical controls.

Volpe 1991Combined randomized and nonrandomized patients into one cohort.

Wang 2010Not related to medical treatments for hyphema, compared satisfaction in 2 groups based on whether or not they received education about having glaucoma secondary to traumatic hyphema.

Watkins 1974Not a clinical trial, animal study and case reports.

Welsh 1971Not a clinical trial, case reports.

Williams 1993Not a clinical trial, interventional case series.

Williamson 1973Not a clinical trial, report of 4 cases.

Wilson 1990Not a clinical trial, cohort study.

Wright 1964Included nontraumatic hyphema cases in trial and could not determine outcomes in traumatic hyphema cases separately.

Yan 2012Included participants who may have been treated surgically prior to study enrollment.

Yasuna 1974Not a clinical trial, used historical controls.

Zhou 1982Not a clinical trial, groups were selected based on severity of injury.

Zobina 1987Not a clinical trial, case series, no control group.

Zobina 1996Not a clinical trial, description of therapy with observational findings.

 
Comparison 1. Oral aminocaproic acid versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Long-term visual acuity between 20/20 and 20/402108Odds Ratio (M-H, Fixed, 95% CI)1.11 [0.47, 2.61]

 2 Short-term visual acuity from 20/20 to 20/401Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Final visual acuity between 20/20 and 20/402143Odds Ratio (M-H, Fixed, 95% CI)1.56 [0.53, 4.56]

 4 Time to resolution of primary hemorrhage (days)Other dataNo numeric data

 5 Risk of secondary hemorrhage6330Odds Ratio (M-H, Fixed, 95% CI)0.25 [0.11, 0.57]

 6 Time to rebleed (days)Other dataNo numeric data

 7 Risk of corneal bloodstain1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 8 Risk of glaucoma or elevated intraocular pressure (IOP)283Odds Ratio (M-H, Fixed, 95% CI)0.35 [0.06, 1.98]

 9 Risk of glaucoma or increases in IOPOther dataNo numeric data

    9.1 Transient increase in IOP
Other dataNo numeric data

    9.2 Persistent increase in IOP
Other dataNo numeric data

 10 Risk of optic atrophy1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 11 Adverse effects: nausea or vomiting3131Odds Ratio (M-H, Fixed, 95% CI)11.76 [2.59, 53.46]

 12 Duration of hospitalization (days)Other dataNo numeric data

 
Analysis 1.4 Comparison 1 Oral aminocaproic acid versus placebo, Outcome 4 Time to resolution of primary hemorrhage (days).
Time to resolution of primary hemorrhage (days)

StudyMean (SD) time to resolution in drug treated groupNumber of participants in drug treated groupMean (SD) time to resolution in control groupNumber of participants in control group

Christianson 1979NR22NR23

Crouch 19764.1 days (4.0 days in study participants without secondary hemorrhage)32 (31 without a secondary hemorrhage)3.8 days (2.8 days in study participants without secondary hemorrhage)27 (18 without a secondary hemorrhage)

Kraft 19878 days (5.3 days in study participants without secondary hemorrhage)24 (22 without a secondary hemorrhage)5 days (2.6 days in study participants without a secondary hemorrhage)25 (24 without a secondary hemorrhage)

Kutner 19874.8 days in all study participants21 (no participant had a secondary hemorrhage2.4 days in all study participants10 study participants without a secondary hemorrhage

McGetrick 19834.5 days in all study participants28 (1 study participant had a secondary hemorrhage)6.3 days in all study participants21 (7 study participants had a secondary hemorrhage)

Teboul 19956.7 days in all study participants48 (1 study participant had a secondary hemorrhage)2.6 days in all study participants46 (2 study participants had a secondary hemorrhage)

 
Analysis 1.6 Comparison 1 Oral aminocaproic acid versus placebo, Outcome 6 Time to rebleed (days).
Time to rebleed (days)

StudyNumber of rebleeds in drug treated groupTime to rebleed in drug treated groupNumber of rebleeds in control groupTime to rebleed in control group

Christianson 19792 of 22NR1 of 23NR

Crouch 19761 of 32Day 19 of 27Days 2 to 7: 2 on day 2; 2 on day 3; 4 on day 4; and 1 on day 7

Kraft 19872 of 24Days 3 and 41 of 25Day 4

Kutner 19870 of 21NA3 of 13All rebled on Day 2

McGetrick 19831 of 28Day 47 of 21Days 3 to 6: 5 on day 3; 1 on day 5; and 1 on day 6

Teboul 19951 of 48Day 62 of 46Days 2 and 7

 
Analysis 1.9 Comparison 1 Oral aminocaproic acid versus placebo, Outcome 9 Risk of glaucoma or increases in IOP.
Risk of glaucoma or increases in IOP

StudyOdds Ratio [95% CI]Total patients (N)Definition of outcomePatients with sickle cell/trait

Transient increase in IOP

Teboul 19950.96 [0.18, 5.00]94Transient IOP greater than 25 mmHg, all patients had normal IOP at discharge (5 days)None (excluded)

Persistent increase in IOP

Kraft 19871.04 [0.06, 17.69]49IOP greater than 25 mmHg at follow-up (6 weeks to 18 months)None (excluded)

Kutner 19870.17 [0.02, 1.81]34Elevated IOP at time of discharge (6 days)None (excluded)

 
Analysis 1.12 Comparison 1 Oral aminocaproic acid versus placebo, Outcome 12 Duration of hospitalization (days).
Duration of hospitalization (days)

StudyMean (SD) duration of hospitalization for drug treated groupNumber of participants in drug treated groupMean (SD) duration of hospitalization in control groupNumber of participants in control group

McGetrick 19835.7 days287.3 days20

Teboul 19957.3 days485.4 days46

 
Comparison 2. Topical aminocaproic acid versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term visual acuity from 20/20 to 20/401Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Time to resolution of primary hemorrhage (days)Other dataNo numeric data

 3 Risk of secondary hemorrhage2131Odds Ratio (M-H, Fixed, 95% CI)0.42 [0.16, 1.10]

 4 Time to rebleed (days)Other dataNo numeric data

 5 Risk of glaucoma or elevated intraocular pressure (IOP)1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Analysis 2.2 Comparison 2 Topical aminocaproic acid versus placebo, Outcome 2 Time to resolution of primary hemorrhage (days).
Time to resolution of primary hemorrhage (days)

StudyMean (SD) time to resolution in drug treated groupNumber of participants in drug treated groupMean (SD) time to resolution in control groupNumber of participants in control group

Karkhaneh 200311.1 (4.7) days41+ Placebo gel: 9.3 (4.2) days

No placebo gel: 9.5 (3.9) days
+ Placebo gel: 39

No placebo gel: 52

Pieramici 2003Reported as "no difference between treatment groups"24Reported as "no difference between treatment groups"27

 
Analysis 2.4 Comparison 2 Topical aminocaproic acid versus placebo, Outcome 4 Time to rebleed (days).
Time to rebleed (days)

StudyNumber of rebleeds in drug treated groupTime to rebleed in drug treated groupNumber of rebleeds in control groupTime to rebleed in control group

Karkhaneh 20035 of 41Days 2 to 4: Mean = 3.2 days; SD = 0.5+ Placebo gel: 7 of 39

No placebo gel: 8 of 52
+ Placebo gel: Mean = 3 days; SD = 0.8

No placebo gel: Mean = 3 days; SD = 0.8

Pieramici 20032 of 24Days 3 and 68 of 27Days 2 to 6: 3 on day 2; 1 on day 3; 2 on day 4; and 2 on day 6

 
Comparison 3. Low-dose versus standard-dose aminocaproic acid

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Unspecified time for visual acuity between 20/20 and 20/401Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Time to resolution of primary hemorrhage (days)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 3 Risk of secondary hemorrhage1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 4 Time to rebleed (days)Other dataNo numeric data

 5 Risk of glaucoma or elevated intraocular pressure (IOP)1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 6 Adverse effects1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

    6.1 Nausea or vomiting
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 Dizziness or hypotension
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.3 Syncope
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.4 Diarrhea
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.5 Rash or pruritis
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.6 Hot flashes
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.7 Dry mouth or nose
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 7 Duration of hospitalization (days)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 
Analysis 3.4 Comparison 3 Low-dose versus standard-dose aminocaproic acid, Outcome 4 Time to rebleed (days).
Time to rebleed (days)

StudyNumber of rebleeds in the low dose groupTime to rebleed in the low dose groupNumber of rebleeds in the standard dose groupTime to rebleed in the standard dose group

Palmer 19861 of 25Day 45 of 32Days 2 to 6: 1 on day 2; 2 on day 3; and 2 on day 6

 
Comparison 4. Oral versus topical aminocaproic acid

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term visual acuity from 20/20 to 20/401Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Risk of secondary hemorrhage1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Time to rebleed (days)Other dataNo numeric data

 4 Risk of corneal bloodstain1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 5 Risk of optic atrophy1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 6 Adverse effects1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

    6.1 Conjunctival corneal foreign body sensation
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.2 Transient punctate corneal staining
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

    6.3 Dizziness, nausea, vomiting
1Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Analysis 4.3 Comparison 4 Oral versus topical aminocaproic acid, Outcome 3 Time to rebleed (days).
Time to rebleed (days)

StudyNumber of rebleeds in oral treated groupTime to rebleed in oral treated groupNumber of rebleeds in topical treated groupTime to rebleed in topical treated group

Crouch 19971Day 31Day 5

 
Comparison 5. Tranexamic acid versus control

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term visual acuity from 20/20 to 20/403303Odds Ratio (M-H, Fixed, 95% CI)1.65 [0.91, 2.99]

 2 Time to resolution of primary hemorrhage (days)Other dataNo numeric data

 3 Risk of secondary hemorrhage5578Odds Ratio (M-H, Fixed, 95% CI)0.25 [0.13, 0.49]

 4 Time to rebleed (days)Other dataNo numeric data

 5 Risk of corneal bloodstain2Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 6 Risk of glaucoma or elevated intraocular pressure (IOP)4543Odds Ratio (M-H, Fixed, 95% CI)1.23 [0.70, 2.16]

 7 Risk of optic atrophy1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 8 Adverse effects: nausea or vomiting2Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 9 Duration of hospitalization (days)Other dataNo numeric data

 
Analysis 5.2 Comparison 5 Tranexamic acid versus control, Outcome 2 Time to resolution of primary hemorrhage (days).
Time to resolution of primary hemorrhage (days)

StudyMean (SD) time to resolution in drug treated groupNumber of participants in drug treated groupMean (SD) time to resolution in control groupNumber of participants in control group

Rahmani 19994.0 (2.2) days in study participants without secondary hemorrhage723.7 (1.6) days in study participants without secondary hemorrhage59

Sukumaran 19884.6 (2.4) days in all study participants17 (2 study participants had a secondary hemorrhage)3.9 (2.4) days in all study participants18 (6 study participants had a secondary hemorrhage)

Vangsted 1983Reported as delayed59NR53

Varnek 1980NR102NR130

Welsh 1983NR19NR20

 
Analysis 5.4 Comparison 5 Tranexamic acid versus control, Outcome 4 Time to rebleed (days).
Time to rebleed (days)

StudyNumber of rebleeds in drug treated groupTime to rebleed in drug treated groupNumber of rebleeds in control groupTime to rebleed in control group

Rahmani 19998 of 80Days 2 to 4: Mean = 3.4 days; SD = 0.721 of 80Days 2 to 6: Mean = 3.8 days; SD = 1.0

Sukumaran 19882 of 17Days 2 to 36 of 18Days 2 to 3

Vangsted 19830 of 59NA0 of 53NA

Varnek 19802 of 102Day 312 of 130Days 2 to 7: 5 occurred on Day 4

Welsh 19831 of 19NR6 of 20NR

 
Analysis 5.9 Comparison 5 Tranexamic acid versus control, Outcome 9 Duration of hospitalization (days).
Duration of hospitalization (days)

StudyMean (SD) duration of hospitalization for drug treated groupNumber of participants in drug treated groupMean (SD) duration of hospitalization in control groupNumber of participants in control group

Rahmani 19996.0 (1.6) days806.3 (1.8) days80

Vangsted 19836 days597 days53

Varnek 19806.8 days1026.5 days130 ( Analysis 8.7)

 
Comparison 6. Aminomethylbenzoic acid versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Risk of secondary hemorrhage1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 7. Oral corticosteroids versus control

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term (5-14 day) visual acuity from 20/20 to 20/401Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Visual acuity between 20/20 and 20/50 at resolution of hyphema1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Time to resolution of primary hemorrhage (days)Other dataNo numeric data

 4 Risk of secondary hemorrhage2201Odds Ratio (M-H, Fixed, 95% CI)0.61 [0.31, 1.22]

 5 Time to rebleed (days)Other dataNo numeric data

 6 Risk of corneal bloodstain1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 7 Risk of peripheral anterior synechiae1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 8 Risk of glaucoma or elevated intraocular pressure (IOP)2201Odds Ratio (M-H, Fixed, 95% CI)0.75 [0.31, 1.81]

 9 Duration of hospitalization (days)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 
Analysis 7.3 Comparison 7 Oral corticosteroids versus control, Outcome 3 Time to resolution of primary hemorrhage (days).
Time to resolution of primary hemorrhage (days)

StudyTime to resolution in drug groupNumber of participants in drug groupTime to resolution in control groupNumber of participants in control group

Rahmani 19993.5 days (SD = 1.8) in study participants without a secondary hemorrhage643.7 days (SD = 1.6) in study participants without a secondary hemorrhage59

Spoor 19804.45 days (4.01 days in study participants without a secondary hemorrhage)23 (20 without a secondary hemorrhage)4.48 days (3.60 days in study participants without a secondary hemorrhage)20 (16 without a secondary hemorrhage)

 
Analysis 7.5 Comparison 7 Oral corticosteroids versus control, Outcome 5 Time to rebleed (days).
Time to rebleed (days)

StudyNumber of rebleeds in the drug groupMean time to rebleed in the drug groupNumber of rebleeds in the control groupMean time to rebleed in the control group

Rahmani 199914 of 783.2 days (SD = 0.8)21 of 803.8 days (SD = 1.0)

Spoor 19803 of 232.3 days4 of 202.6 days

 
Comparison 8. Topical corticosteroids versus control

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term (5-14 day) visual acuity from 20/20 to 20/401Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Time to resolution of primary hemorrhage (days)Other dataNo numeric data

 3 Risk of secondary hemorrhage2151Odds Ratio (M-H, Fixed, 95% CI)0.27 [0.05, 1.61]

 4 Risk of corneal bloodstain1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 5 Risk of glaucoma or elevated intraocular pressure (IOP)1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 6 Risk of optic atrophy1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 7 Duration of hospitalization (days)Other dataNo numeric data

 
Analysis 8.2 Comparison 8 Topical corticosteroids versus control, Outcome 2 Time to resolution of primary hemorrhage (days).
Time to resolution of primary hemorrhage (days)

StudyTime to resolution in drug groupNumber of participants in drug groupTime to resolution in control groupNumber of participants in control group

Rakusin 197210 resolved within 7 days13 (1 study participant had a secondary hemorrhage)16 resolved within 7 days21 (2 study participants had a secondary hemorrhage)

 
Analysis 8.7 Comparison 8 Topical corticosteroids versus control, Outcome 7 Duration of hospitalization (days).
Duration of hospitalization (days)

StudyMean (SD) duration of hospitalization for drug treated groupNumber of participants in drug treated groupMean (SD) duration of hospitalization in control groupNumber of participants in control group

Zetterstrom 19695.9 days (SD not reported)588.9 days (SD not reported)59

 
Comparison 9. Aminocaproic acid versus prednisone

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term (5-14 day) visual acuity from 20/20 to 20/401Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Risk of secondary hemorrhage1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Adverse effect: any adverse event1112Odds Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 10. Conjugated estrogen versus placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Risk of secondary hemorrhage1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Risk of corneal bloodstain1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 11. Cycloplegics versus miotics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term visual acuity1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Time to resolution of primary hemorrhage (days)1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 3 Risk of secondary hemorrhage292Odds Ratio (M-H, Fixed, 95% CI)1.03 [0.14, 7.53]

 4 Time to rebleed (days)Other dataNo numeric data

 
Analysis 11.4 Comparison 11 Cycloplegics versus miotics, Outcome 4 Time to rebleed (days).
Time to rebleed (days)

StudyNumber of rebleeds in the cycloplegic groupMean time to rebleed in the cycloplegic groupNumber of rebleeds in the miotic groupMean time to rebleed in the miotic group

Bedrossian 19741 of 282 days0 of 30NA

 
Comparison 12. Aspirin versus observation

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Risk of secondary hemorrhage1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 13. Monocular versus binocular patching

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term visual acuity1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Variable time length 'final' visual acuity1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 3 Risk of secondary hemorrhage2117Odds Ratio (M-H, Fixed, 95% CI)0.72 [0.26, 2.00]

 4 Time to rebleed (days)Other dataNo numeric data

 5 Risk of corneal bloodstain1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 6 Risk of glaucoma or elevated intraocular pressure (IOP)1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Analysis 13.4 Comparison 13 Monocular versus binocular patching, Outcome 4 Time to rebleed (days).
Time to rebleed (days)

StudyNumber of rebleeds in monocular patching groupTime to rebleed in monocular patching groupNumber of rebleeds in binocular patching groupTime to rebleed in binocular patching group

Edwards 19738 of 35Mean 3 days8 of 29Mean 3 days

 
Comparison 14. Ambulatory versus conservative treatment

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Short-term visual acuity1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 2 Time to resolution of primary hemorrhageOther dataNo numeric data

 3 Risk of secondary hemorrhage2189Odds Ratio (M-H, Fixed, 95% CI)1.36 [0.62, 2.99]

 4 Risk of corneal bloodstain1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 5 Risk of glaucoma or elevated intraocular pressure (IOP)1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Analysis 14.2 Comparison 14 Ambulatory versus conservative treatment, Outcome 2 Time to resolution of primary hemorrhage.
Time to resolution of primary hemorrhage

StudyTime to resolution in ambulatory groupNumber of participants in ambulatory groupTime to resolution in control groupNumber of participants in control group

Read 19745.8 days5.6 days

 
Table 1. Summary of outcomes* reported by intervention

InterventionsPrimary outcomesSecondary outcomesAdverse effectsDuration of hospitalization or quality of life outcomes


VATime to resolution of primary hemorrhageSecondary hemorrhageRisk of corneal bloodstainingRisk of PAS formationRisk of pathologic increase in IOP or glaucomaRisk of optic atrophy

Risk of rebleedTime to rebleed

Aminocaproic acid vs. placebo

Oral aminocaproic acid

Christianson 1979Not reportedPartially reported**Risk of rebleed reportedNot reportedNot reportedNot reportedNot reportedNot reportedNot reportedNot reported

Crouch 1976Long-term VA reportedDays to resolution reportedRisk of rebleed reportedTime to rebleed reportedRisk of corneal bloodstaining reportedPartially reported**Not reportedRisk of optic atrophy reportedNot reportedNot reported

Kraft 1987Long-term VA reportedDays to resolution reportedRisk of rebleed reportedTime to rebleed reportedNot reportedNot reportedPersistent increases in IOP reportedNot reportedAdverse effects reportedNot reported

Kutner 1987Short-term VA reportedDays to resolution reportedRisk of rebleed reportedTime to rebleed reportedNot reportedNot reportedPersistent increases in IOP reportedNot reportedAdverse effects reportedNot reported

McGetrick 1983Final VA reportedDays to resolution reportedRisk of rebleed reportedTime to rebleed reportedNot reportedNot reportedNot reportedNot reportedAdverse effects reportedPartially reported**

Teboul 1995Final VA reportedDays to resolution reportedRisk of rebleed reportedTime to rebleed reportedNot reportedNot reportedTransient increases in IOP reportedNot reportedNot reportedDuration of hospitalization reported

Topical aminocaproic acid

Karkhaneh 2003Reported as NSDays to resolution reportedRisk of rebleed reportedTime to rebleed reportedNot reportedNot reportedReported as NSNot reportedNot reportedNot reported

Pieramici 2003Short-term VA reportedReported as NSRisk of rebleed reportedTime to rebleed reportedNot reportedNot reportedTransient increases in IOP reportedNot reportedAdverse effects reportedNot reported

Low-dose vs. standard-dose aminocaproic acid

Palmer 1986Final VA reportedDays to resolution reportedRisk of rebleed reportedTime to rebleed reportedNot reportedNot reportedTransient increases in IOP reportedNot reportedAdverse effects reportedDuration of hospitalization reported

Oral vs. topical aminocaproic acid

Crouch 1997Final VA reportedNot reportedRisk of rebleed reportedTime to rebleed reportedRisk of corneal bloodstaining reportedPartially reported**Not reportedRisk of optic atrophy reportedAdverse effects reportedNot reported

Tranexamic acid vs. control

Rahmani 1999Short-term VA reportedDays to resolution reportedRisk of rebleed reportedTime to rebleed reportedNot reportedNot reportedTransient increases in IOP reportedNot reportedAdverse effects reportedDuration of hospitalization reported

Sukumaran 1988Short-term VA reportedDays to resolution reportedRisk of rebleed reportedTime to rebleed reportedNot reportedNot reportedNot reportedNot reportedNot reportedNot reported

Vangsted 1983Short-term VA reportedPartially reported**Risk of rebleed reportedNo rebleeds occurredRisk of corneal bloodstaining reportedNot reportedTransient increases in IOP reportedNot reportedNot reportedDuration of hospitalization and days off work reported

Varnek 1980Partially reported**Not reportedRisk of rebleed reportedTime to rebleed reportedRisk of corneal bloodstaining reportedNot reportedTransient increases in IOP reportedRisk of optic atrophy reportedNot reportedDuration of hospitalization reported

Welsh 1983Not reportedPartially reported**Risk of rebleed reportedNot reportedNot reportedNot reportedTransient increases in IOP reportedNot reportedAdverse effects reportedNot reported

Aminomethylbenzoic acid vs. placebo

Liu 2002Not reportedNot reportedRisk of rebleed reportedNot reportedNot reportedNot reportedNot reportedNot reportedAdverse effects reportedNot reported

Corticosteroids vs. control

Oral corticosteroids

Rahmani 1999Short-term VA reportedDays to resolution reportedRisk of rebleed reportedTime to rebleed reportedNot reportedNot reportedTransient increases in IOP reportedNot reportedAdverse effects reportedDuration of hospitalization reported

Spoor 1980Final VA reportedDays to resolution reportedRisk of rebleed reportedTime to rebleed reportedRisk of corneal bloodstaining reportedRisk of PAS formation reportedTransient increases in IOP reportedNot reportedNot reportedNot reported

Topical corticosteroids

Rakusin 1972Short-term VA reportedPartially reported**Risk of rebleed reportedNot reportedPartially reported**Partially reported**Not reportedNot reportedNot reportedNot reported

Zetterstrom 1969Short-term VA reportedNot reportedRisk of rebleed reportedNot reportedRisk of corneal bloodstaining reportedNot reportedTransient increases in IOP reportedRisk of optic atrophy reportedNot reportedDuration of hospitalization reported

Oral aminocaproic acid vs. oral prednisone

Farber 1991Short-term VA reportedPartially reported**Risk of rebleed reportedNot reportedNot reportedNot reportedReported as NSNot reportedNot reportedNot reported

Conjugated estrogen vs. placebo

Spaeth 1966Partially reported**Not reportedRisk of rebleed reportedPartially reported**Risk of corneal bloodstaining reportedPartially reported**Partially reported**Not reportedNot reportedNot reported

Cycloplegics vs. miotics

Bedrossian 1974Not reportedDays to resolution reportedRisk of rebleed reportedTime to rebleed reportedNot reportedNot reportedNot reportedNot reportedNot reportedNot reported

Rakusin 1972Short-term VA reportedPartially reported**Risk of rebleed reportedNot reportedReported as NSReported as NSNot reportedNot reportedNot reportedNot reported

Aspirin vs. observation

Marcus 1988Not reportedNot reportedRisk of rebleed reportedNot reportedNot reportedNot reportedNot reportedNot reportedNot reportedNot reported

Traditional Chinese medicine vs. control treatment

Wang 1994Partially reported**Partially reported**Partially reported**Not reportedNot reportedNot reportedNot reportedNot reportedNot reportedNot reported

Monocular vs. binocular patching

Edwards 1973Final VA reportedNot reportedRisk of rebleed reportedTime to rebleed reportedRisk of corneal bloodstaining reportedNot reportedRisk of secondary glaucoma reportedNot reportedNot reportedQuality of life outcomes reported

Rakusin 1972Short-term VA reportedPartially reported**Risk of rebleed reportedNot reportedReported as NSReported as NSNot reportedNot reportedNot reportedNot reported

Ambulatory vs. conservative treatment

Rakusin 1972Short-term VA reportedPartially reported**Risk of rebleed reportedNot reportedReported as NSReported as NSNot reportedNot reportedNot reportedNot reported

Read 1974Partially reportedDays to resolution reportedRisk of rebleed reportedPartially reported**Risk of corneal bloodstaining reportedNot reportedTransient increases in IOP reportedNot reportedNot reportedNot reported

Elevation of the head vs. control

Zi 1999Not reportedDays to resolution reportedNot reportedNot reportedNot reportedNot reportedRisk of secondary glaucoma reportedNot reportedNot reportedNot reported

 *See Types of outcome measures for detailed descriptions of outcomes.
**Noted as "partially reported" if some information was reported, but it was insufficient for quantitative data analyses.
IOP: intraocular pressure; NS: not significant; PAS: peripheral anterior synechiae; VA: visual acuity.
 
Table 2. Outcomes by initial hyphema severity

StudySeverity scaleReported severitySecondary hemorrhageOther outcomes

Oral aminocaproic acid vs. control

Christianson 1979NRNRNRTime to resolution of the primary hyphema was significantly longer (P value < 0.05) for patients receiving drug in which the hyphema filled more than ½ of the anterior chamber

Crouch 1976Blood filling < ⅓ of anterior chamberReported no statistically significant differences across groupsNRNR

Blood filling ⅓ to ½ of anterior chamber

Blood filling > ½ to ¾ of anterior chamber

Blood filling > ¾ to total of anterior chamber, but excluded total hyphema

Kraft 1987Blood filling < ⅓ of anterior chamber30/49 (61%) participants; 13/24 (54%) in drug group; 17/25 (68%) in placebo group1/3 (33%) secondary hemorrhage (in placebo group)Excluding secondary hemorrhages, mean time to resolution of 3.4 days in drug group (range 1-11 days); mean time to resolution of 2.2 days in placebo group (range 1-4 days)

Blood filling ⅓ to ½ of anterior chamber14/49 (29%) participants; 9/24 (37.5%) in drug group; 5/25 (20%) in placebo group1/3 (33%) secondary hemorrhage (in drug group)Excluding secondary hemorrhages, mean time to resolution of 7.1 days in drug group (range 6-9 days); mean time to resolution of 4.0 days in placebo group (range 3-4 days)

Blood filling ½ or more of anterior chamber5/49 (10%) participants; 2/24 (8.3%) in drug group; 3/25 (12%) in placebo group1/3 (33%) secondary hemorrhage (in drug group)Excluding secondary hemorrhages, time to resolution of 10 days in drug group: mean of placebo 4.3 days (range 3-5 days)

Kutner 1987Mean hyphema height2.2 mm (SD 1.7, n = 21) in drug group; 1.7 mm (SD 1.0, n = 13) in placebo group"All who rebled had initial hyphemas of 15% or less"NR

McGetrick 1983;Mean hyphema height100% (28/28) hyphemas in drug group were < 25% of anterior chamber; 86% (18/21) hyphemas in placebo group were < 25% of anterior chamber1 secondary hemorrhage in drug group; 6 secondary hemorrhages in placebo groupNR

Teboul 1995Blood filling < ⅓ of anterior chamber88/94 (94%) participants; 44/48 (92%) in drug group; 44/46 (96%) in placebo group1 secondary hemorrhages in drug group and 2 in placebo groupNR

Blood filling ⅓ to ½ of anterior chamber6/94 (6%) participants; 4/48 (8%) in aminocaproic acid group; 2/46 (4%) in placebo groupNo rebleedsNR

Topical aminocaproic acid vs. control

Karkhaneh 2003Blood filling < ¼ of anterior chamber; excluded microscopic hyphemas65/80 (81%) participants; 34/41 (83%) in drug group; 31/39 (79.5%) in placebo groupReported no effect of hyphema size on secondary hyphema (RR 0.7, 95% CI 0.2 to 2.5)NR

Blood filled ¼ to ½ of anterior chamber14/80 (18%) participants; 7/41 (17%) in drug group; 7/39 (18%) in placebo group

blood filling > ½ of anterior chamber; excluded total or blackball hyphemas1/80 (1%) participants; 0/41 in drug group; 1/39 (2.5%) in placebo group

Pieramici 2003Mean hyphema height in mm1 mm (SE 0) in drug group (range 0-4 mm); 2 mm (SE 0) in placebo group (range 0-8 mm)Size of primary hyphema in 2 participants with secondary hemorrhages in drug group: 0.3 and 1 mm; in 8 participants in the placebo group: 0.8, 0.9, 1, 1.4, 1.8, 2, 2, and 4.5 mmNR

Low-dose vs. standard-dose aminocaproic acid

Palmer 1986Mean hyphema height in mm1.7 mm (SD 2.0, range 0.1-9.9) in low-dose group (n = 25); 1.5 mm (SD 2.2, range 0.1-9.9) in standard-dose group; 1.5 mm in standard-dose group (n = 33)1 secondary hemorrhage in low-dose group; 5 secondary hemorrhages in standard-dose groupNR

Oral vs. topical aminocaproic acid

Crouch 1997Blood filling < ⅓ of anterior chamber44/64 (69%) participantsNRNR

Blood filling ⅓ to ½ of anterior chamber6/64 (9%) participants

Blood filling > ½ to ¾ of anterior chamber8/64 (13%) participants

Blood filling > ¾ to total of anterior chamber6/64 (9%) participants

Tranexamic acid vs. control

Rahmani 1999Microscopic, but excluding patients with unlayered microscopic hyphemas17/238 (7%) participants; 6/80 (7%) in aminocaproic acid group; 4/78 (5%) in prednisolone group; 7/80 (9%) in placebo group2/43 (5%) secondary hemorrhagesNR

Blood filling < ¼ of anterior chamber173/238 (72%) participants; 56/80 (70%) in aminocaproic acid group; 61/78 (78%) in prednisolone group; 56/80 (70%) in placebo group30/43 (70%) secondary hemorrhages

Blood filling ¼ to ½ of anterior chamber36/238 (15%) participants; 13/80 (16%) in aminocaproic acid group; 10/78 (13%) in prednisolone group; 13/80 (16%) in placebo group7/43 (16%) secondary hemorrhages

Blood filling >½ of anterior chamber; excluded total hyphemas12/238 (5%) participants; 5/80 (6%) in aminocaproic acid group; 3/78 (4%) in prednisolone group; 4/80 (5%) in placebo group4/43 (9%) secondary hemorrhages

Sukumaran 1988Hyphema height of 0-1 mm8/35 (23%) participants; 4/17 (24%) in drug group; 4/18 (22%) in control groupNRNR

Hyphema height of 2-3 mm12/35 (34%) participants; 6/17 (35%) in drug group; 6/18 (33%) in control group

Hyphema height of 4-5 mm10/35 (29%) participants; 5/17 (29%) in drug group; 5/18 (28%) in control group

Hyphema height of 6-7 mm5/35 (14%) participants; 2/17 (12%) in drug group; 3/18 (17%) in control group

Vangsted 1983Hyphema height of 1 mm10/112 (9%) participants; 8/59 (14%) in drug group; 2/53 (4%) in control groupNRNR

Hyphema height of 2 mm33/112 (29%) participants; 15/59 (25%) in drug group; 18/53 (34%) in control group

Hyphema height of 3 mm37/112 (33%) participants; 18/59 (31%) in drug group; 19/53 (36%) in control group

Hyphema height of 4 mm18/112 (16%) participants; 9/59 (15%) in drug group; 9/53 (17%) in control group

Hyphema height of 5 mm9/112 (8%) participants; 6/59 (10%) in drug group; 3/53 (6%) in control group

Hyphema height of 6 mm4/112 (4%) participants; 3/59 (5%) in drug group; 1/53 (2%) in control group

Hyphema height of 7 mmNone in either group

Hyphema height of 8 mm1/112 (1%) participants; 0/59 (0%) in drug group; 1/53 (2%) in control group

Varnek 1980Mean hyphema height in mm2.0 mm in drug group (n = 102); 2.1 mm in control group (n = 130)1.0 mm in 2 participants in drug group with a secondary hemorrhage; 2.2 mm in 12 participants in control group with a secondary hemorrhageNR

Welsh 1983Mean of proportion of anterior chamber area filled with blood68% in drug group (n = 19); 63% in placebo group (n = 20)NRNR

Aminomethylbenzoic acid vs. control

Liu 2002Blood filling < ⅓ of anterior chamber and level is lower than the inferior boarder of pupil47/92 (51%) participants; 31/60 (52%) in drug group; 16/32 (50%) in control groupNRNR

Blood filling ½ of anterior chamber and level is higher than the inferior border of the pupil, but not exceeding the median line30/92 (33%) participants; 19/60 (32%) in drug group; 11/32 (34%) in control group

Blood filling > ½ of anterior chamber or filling the entire anterior chamber15/92 (16%) participants; 10/60 (17%) in drug group; 5/32 (16%) in control group

Oral corticosteroids vs. control

Spoor 19800-33% of anterior chamber area filled with blood38/43 (88%) participants; 21/23 (91%) in prednisone group; 17/20 (85%) in placebo group2/4 (50%) secondary hemorrhages1. 30 hyphemas resolved in 5 days or less; 8 hyphemas resolved in more than 5 days

2. 34 patients with final visual acuity between 20/20 and 20/50

> 33% to 75% of anterior chamber filled with blood5/43 (12%) participants; 2/23 (9%) in prednisone group; 3/20 (15%) in placebo group2/4 (50%) secondary hemorrhages1. 1 hyphema resolved in 5 days or less; 4 hyphemas resolved in more than 5 days

2. 5 patients with final visual acuity between 20/20 and 20/50

Rahmani 1999See above under "Tranexamic acid vs. control"


Topical corticosteroids

Zetterstrom 1969Mean hyphema height in mm2.5 mm in topical corticosteroid group (n = 58); 3.5 mm in control group (n = 59)No patient with secondary hemorrhage in topical corticosteroid group; 4 patients with secondary hemorrhage in control groupNR

Antifibrinolytics vs. oral corticosteroids

Farber 1991Microscopic24/112 (21%) participants; 11/56 (20%) in aminocaproic acid group; 13/56 (23%) in prednisone group,3/8 (38%) secondary hemorrhages; 2 in aminocaproic acid group; 1 in prednisone groupNR

Hyphema height 0.1-3.9 mm80/112 (71%) participants; 41/56 (73%) in aminocaproic acid group; 39/56 (70%) in prednisone group4/8 (50%) secondary hemorrhages; 1 in aminocaproic acid group; 3 in prednisone group

Hyphema height 4.0-5.9 mm4/112 (4%) participants; 3/56 (6%) in aminocaproic acid group; 1/56 (2%) in prednisone groupNo secondary hemorrhages in either group

Hyphema height 6.0-11 mm2/112 (2%) participants; 0/56 (0%) in aminocaproic acid group; 2/56 (4%) in prednisone groupNo secondary hemorrhages in either group

Total hyphema2/112 (2%) participants; 1/56 (2%) in aminocaproic acid group; 1/56 (2%) in prednisone group1/8 (12%) secondary hemorrhage; 1 in aminocaproic acid group; none in prednisone group

Rahmani 1999See above under "Tranexamic acid vs. control"


Conjugated estrogens vs. control

Spaeth 1966Blood filling < 20% of anterior chamber55/85 (65%) participants; 28/39 (72%) in estrogen group; 27/46 (59%) in control group13/20 (65%) secondary hemorrhages; 8 in estrogen group; 5 in control groupNR

Blood filling 20-40% of anterior chamber17/85 (20%) participants; 5/39 (13%) in estrogen group; 12/46 (26%) in control group4/20 (20%) secondary hemorrhages; 1 in estrogen group; 3 in control group

Blood filling 40-60% of anterior chamber5/85 (6%) participants; 2/39 (5%) in estrogen group; 3/46 (7%) in control group1/20 (5%) secondary hemorrhage; 0 in estrogen group; 1 in control group

Blood filling 60-80% of anterior chamber2/85 (2%) participants; 1/39 (3%) in estrogen group; 1/46 (2%) in control groupNo secondary hemorrhages in either group

Blood filling > 80% of anterior chamber6/85 (7%) participants; 3/39 (8%) in estrogen group; 3/46 (7%) in control group2/20 (10%) secondary hemorrhages; 1 in estrogen group; 1 in control group

Cycloplegics vs. miotics

Bedrossian 1974Hyphema height of 1 mm20/58 (34%) participants; 10/28 (36%) in the cycloplegic group; 10/30 (33%) in the miotic group1/1 (100%) secondary hemorrhage (in cycloplegic group)Mean time to resolution in cycloplegic group of 1.9 days (SD 1.4); mean time to resolution in miotic group of 2.5 days (SD 1)

Hyphema height of 2 mm22/58 (38%) participants; 10/28 (36%) in the cycloplegic group; 12/30 (40%) in the miotic groupNo secondary hemorrhages in either groupMean time to resolution in cycloplegic group of 3.3 days (SD 1.8); mean time to resolution in miotic group of 4.2 days (SD 1.3)

Hyphema height of 3 mm12/58 (21%) participants; 6/28 (21%) in the cycloplegic group; 6/30 (20%) in the miotic groupNo secondary hemorrhages in either groupMean time to resolution in cycloplegic group of 3.2 days (SD 1.9); mean time to resolution in miotic group of 4.0 days (SD 1.1)

Hyphema height of 4 mm4/58 (7%) participants; 2/28 (7%) in the cycloplegic group; 2/30 (7%) in the miotic groupNo secondary hemorrhages in either groupMean time to resolution in cycloplegic group of 2.5 days (1 resolved on day 2 and 1 on day 3); mean time to resolution in miotic group of 4.0 days (1 resolved on day 3 and 1 on day 5)

Aspirin vs. no aspirin

Marcus 1988Reported that "the two groups were comparable with respect to age, cause, and extent of hyphema" and that 2 of 3 eyes with a secondary hemorrhage in the aspirin group (n = 23) had an initial total hyphema, while of the 2 eyes with a secondary hemorrhage in the control group (n = 28), 1 had 30% and 1 had almost total hyphema           NR



Traditional Chinese medicine vs. control treatment

Wang 1994Any levelNo significant differences between groupsNRProportion of patients who were "cured" (defined as the resolution of the primary hemorrhage after 5 days of treatment, visual acuity of 0.7 or better after resolution of the primary hemorrhage, and no recurrence of bleeding for 1 week following resolution of the primary hemorrhage) was 29/45 (64%) in the TCM group and 10/38 (26%) in the control group

Monocular vs. binocular patching

Edwards 1973Blood filling < ⅓ of anterior chamber42/64 (66%) participants; 21/35 (60%) in the monocular patching group; 21/29 (72%) in the binocular patching group7/14 (50%) secondary hemorrhages; 4 in the monocular group; 3 in the binocular group62% (13/21) of patients with final visual acuity of 20/50 or better in the monocular group; 71% (15/21) of patients with final visual acuity of 20/50 or better in the binocular group

Blood filling ⅓ to ½ of anterior chamber14/64 (22%) participants; 9/35 (26%) in the monocular patching group; 5/29 (17%) in the binocular patching group7/14 (50%) secondary hemorrhages; 4 in the monocular group; 3 in the binocular group57% (8/14) of patients with final visual acuity of 20/50 or better in the monocular group; 62% (5/8) of patients with final visual acuity of 20/50 or better in the binocular group

Blood filling ½ or more of anterior chamber8/64 (12%) participants; 5/35 (14%) in the monocular patching group; 3/29 (10%) in the binocular patching group

Ambulatory vs. conservative treatment

Read 1974Blood filling < ⅓ of anterior chamber79/137 (58%) participants; 47/71 (66%) in the ambulatory group; 32/66 (48%) in the conservative group16/30 (53%) secondary hemorrhages; 9 in the ambulatory group; 7 in the conservative groupNR

Blood filling ⅓ to ½ of anterior chamber28/137 (20%) participants; 11/71 (16%) patients in the ambulatory group; 17/66 (26%) patients in the conservative group5/30 (17%) secondary hemorrhages; 4 in the ambulatory group; 1 in the conservative group

Blood filling ½ but not total anterior chamber19/137 (14%) participants; 8/71 (11%) patients in the ambulatory group; 11/66 (17%) patients in the conservative group6/30 (20%) secondary hemorrhages; 3 in the ambulatory group; 3 in the conservative group

Total hyphema11/137 (8%) participants; 5/71 (7%) patients in the ambulatory group; 6/66 (9%) patients in the conservative group3/30 (10%) secondary hemorrhages; 2 in the ambulatory group; 1 in the conservative group

Elevation of head vs. laying flat

Zi 1999Blood filling < ½ of anterior chamber and level was lower than the inferior boarder of pupil36/74 (49%) participants; 18/35 (51%) patients with elevation of the head; 18/39 (46%) patients laying flatNRNR

Blood filling ½ of anterior chamber and level was higher than the inferior border of the pupil19/74 (26%) participants; 6/35 (17%) patients with elevation of the head; 13/39 (33%) patients laying flatNRNR

Blood filling > ½ of anterior chamber or filling the entire anterior chamber19/74 (26%) participants; 11/35 (31%) patients with elevation of the head; 8/39 (21%) patients laying flatNRNR

Other

Rakusin 1972 *Blood filling < ½ of anterior chamber213 participantsNR1. 4% (8/213) of patients with elevated intraocular pressure across all patients

2. 22% (47/213) of patients with complications

3. 78% (166/213) of patients with final visual acuity better than 20/60

Blood filling > ½ of anterior chamber157 participantsNR1. 85% (133/157) of patients with elevated intraocular pressure across all patients

2. 78% (123/157) of patients with complications

3. 28% (44/157) of patients with final visual acuity better than 20/60

 * Rakusin 1972 reported severity for entire study population rather than by trials of topical corticosteroids, cycloplegics vs. miotics, monocular vs. binocular patching, and ambulatory vs. conservative treatment. See under "Other".
CI: confidence interval; n: number of participants; NR: not reported; RR: risk ratio; SD: standard deviation; SE: standard error.
 
Table 3. Risk of corneal bloodstaining

StudyTest interventionNo. with outcome/No. in groupControl interventionNo. with outcomeTotal No./No. with outcome

Aminocaproic acid

Crouch 1976Oral aminocaproic acid0/32Placebo2/272/59

Crouch 1997Oral aminocaproic acid0/29Topical aminocaproic acid0/350/64

Tranexamic acid

Vangsted 1983Tranexamic acid0/59Bed rest only0/530/112

Varnek 1980Tranexamic acid1/102Conservative treatment0/1301/232

Prednisone/cortisone

Spoor 1980Oral prednisoneNRPlaceboNR1/43

Zetterstrom 1969Atropine plus cortisone eyedrops0/58Conservative treatment1/591/117

Estrogen

Spaeth 1966Estrogen2/39Placebo2/464/85

Nondrug medical interventions

Edwards 1973Monocular patching1/35Binocular patching1/292/64

Read 1974Moderate ambulatory activity, patching and shielding of injured eye5/71Bed rest with elevation of the head, bilateral patches and eye shield4/669/137

 NR: not reported.
 
Table 4. Risk of peripheral anterior synechiae

StudyTest interventionNo. with outcome/No. in groupControl interventionNo. with outcomeTotal No./No. with outcome

Aminocaproic acid

Crouch 1997Oral aminocaproic acidNRTopical aminocaproic acidNR4/64

Prednisone

Spoor 1980Oral prednisone0/23Placebo0/200/43

Conjugated estrogen

Spaeth 1966Conjugated estrogensNRPlaceboNR15/85

Nondrug medical interventions

Read 1974Moderate ambulatory activity, patching and shielding of injured eyeNRBed rest with elevation of the head, bilateral patches and eye shieldNR9/137

 NR: not reported
 
Table 5. Risk of elevated intraocular pressure

StudyTest interventionNo. with outcome/No. in groupControl interventionNo. with outcomeTotal No./No. with outcome

Aminocaproic acid

Kraft 1987Oral aminocaproic acid1/24Placebo1/252/49

Kutner 1987Oral aminocaproic acid1/21Placebo3/134/34

Teboul 1995Oral aminocaproic acid3/48Placebo3/466/94

Pieramici 2003Topical aminocaproic acid2/24Placebo1/273/51

Palmer 1986Standard-dose oral aminocaproic acid2/33Low-dose oral aminocaproic acid0/262/59

Tranexamic acid

Vangsted 1983Tranexamic acid8/59Bed rest only6/5314/112

Varnek 1980Tranexamic acid8/102Conservative treatment7/13015/232

Rahmani 1999Tranexamic acid12/80Placebo12/8024/160

Welsh 1983Tranexamic acid1/19Placebo2/203/39

Prednisone/cortisone

Spoor 1980Oral prednisone0/23Placebo0/200/43

Rahmani 1999Oral prednisone9/78Placebo12/8021/158

Zetterstrom 1969Atropine plus cortisone eyedrops3/58Conservative treatment2/595/117

Nondrug medical interventions

Edwards 1973Monocular patching3/35Binocular patching0/293/64

Read 1974Ambulation17/71Bed rest19/6636/137

Zi 1999Laying on right and left lateral position7/39Laying in semi-reclining position8/3515/74

 NR: not reported.
 
Table 6. Risk of optic atrophy

StudyTest interventionNo. with outcome/No. in groupControl interventionNo. with outcomeTotal No./No. with outcome

Aminocaproic acid

Crouch 1976Oral aminocaproic acid0/32Placebo2/272/59

Crouch 1997Oral aminocaproic acid0/29Topical aminocaproic acid0/350/64

Tranexamic acid

Varnek 1980Tranexamic acid1/102Conservative treatment0/1301/232

Cortisone

Zetterstrom 1969Atropine plus cortisone eyedrops0/58Conservative treatment1/591/117

Nondrug medical interventions

Read 1974Moderate ambulatory activity, patching and shielding of injured eyeNRBed rest with elevation of the head, bilateral patches and eye shieldNR8/137

 NR: not reported.
 
Table 7. Risk of other ocular events

StudyOutcomeTest interventionNo. with outcome/No. in groupControl interventionNo. with outcomeTotal No./No. with outcome

Aminocaproic acid

Crouch 1997Conjunctival/corneal foreign body sensationTopical aminocaproic acid4/35Oral aminocaproic acid0/294/64

Transient punctate corneal stainingTopical aminocaproic acid3/35Oral aminocaproic acid0/293/64

Tranexamic acid

Varnek 1980Vitreous and retinal hemorrhageTranexamic acid5/102Conservative treatment5/13010/232

Traumatic cataractTranexamic acid2/102Conservative treatment0/1302/232

Nondrug medical intervention

Read 1974Traumatic cataractModerate ambulatory activity, patching and shielding of injured eyeNRBed rest with elevation of the head, bilateral patches and eye shieldNR8/137

Vitreous hemorrhageModerate ambulatory activity, patching and shielding of injured eyeNRBed rest with elevation of the head, bilateral patches and eye shieldNR11/137

Commotio retinaeModerate ambulatory activity, patching and shielding of injured eyeNRBed rest with elevation of the head, bilateral patches and eye shieldNR4/137

Occluded pupilModerate ambulatory activity, patching and shielding of injured eyeNRBed rest with elevation of the head, bilateral patches and eye shieldNR2/137

Optic atrophy with nasalization of optic cupModerate ambulatory activity, patching and shielding of injured eyeNRBed rest with elevation of the head, bilateral patches and eye shieldNR4/137

Optic atrophy without nasalization of optic cupModerate ambulatory activity, patching and shielding of injured eyeNRBed rest with elevation of the head, bilateral patches and eye shieldNR8/137

 NR: not reported.
 
Table 8. Risk of nonocular adverse effects

Study IDComparisonType of complicationResults

Aminocaproic acid

Kraft 1987Oral aminocaproic acid vs. placeboNauseaDrug group: 8 of 24; placebo group 1 of 25

Kutner 1987Oral aminocaproic acid vs. placeboNausea or vomitingDrug group: 6 of 21; placebo group: 0 of 13

Light headednessDrug group: 7 of 21; placebo group: 1 of 13

Systemic hypotensionDrug group: 4 of 21; placebo group: 1 of 13

Total complicationsDrug group: 10 of 21; placebo group: 1 of 13

McGetrick 1983Oral aminocaproic acid vs. placeboNausea or vomitingDrug group: 6 of 28; placebo group: 0 of 20

DiarrheaDrug group: 2 of 28; placebo group: 0 of 20

Muscle crampsDrug group: 1 of 28; placebo group: 0 of 20

Pieramici 2003Topical aminocaproic acid vs. placeboSystemic hypotensionDrug group: 3 of 24; placebo group: 3 of 27

Crouch 1997Oral vs. topical aminocaproic acidDizziness, nausea, vomitingOral group: 5 of 29; topical group: 1 of 35

Palmer 1986Low-dose vs. standard-dose oral aminocaproic acidNausea or vomitingLow-dose group: 5 of 25; standard-dose group: 9 of 33

Dizziness and hypotensionLow-dose group: 0 of 25; standard-dose group: 5 of 33

SyncopeLow-dose group: 0 of 25; standard-dose group: 2 of 33

DiarrheaLow-dose group: 1 of 25; standard-dose group: 0 of 33

Rash or pruritisLow-dose group: 1 of 25; standard-dose group: 2 of 33

Hot flashesLow-dose group: 1 of 25; standard-dose group: 0 of 33

Dry mouth or noseLow-dose group: 1 of 25; standard-dose group: 0 of 33

Farber 1991Oral aminocaproic acid vs. oral prednisoneAny adverse eventAminocaproic acid group: 0 of 56; prednisone group; 0 of 56

Tranexamic acid

Welsh 1983Tranexamic acid vs. placeboNauseaDrug group: 1 of 19; placebo group: 0 of 20

Rahmani 1999Tranexamic acid vs. placeboNauseaDrug group: 0 of 80; placebo group: 0 of 80

Aminomethylbenzoic acid

Liu 2002Oral aminomethylbenzoic acid vs. placeboNausea and vomitingDrug group: 7 of 60; placebo group: NR

 NR: not reported.