Medical interventions for traumatic hyphema

What is the aim of this review?
The aim of this Cochrane Review was to find out what medical treatments are effective for traumatic hyphema, a condition in which blood collects in the eye following trauma, usually a blow to the eye. We collected and analyzed all relevant studies to answer this question.

Key messages
We found no evidence that any medical intervention affected vision, whether measured within a few weeks or longer. We also found that no medical intervention resulted in fewer complications from the hyphema itself, although this evidence is weak because few events occurred. We found limited evidence that antifibrinolytics, drugs that affect how blood is clotted, reduced the risk of new bleeding in the eye.

What was studied in the review?
It was important to evaluate current medication interventions for traumatic hyphema because complications from the condition can affect final vision. We found 27 studies with a total of 2643 participants addressing this question. Studies were from the USA, Canada, Sweden, Denmark, China, South Africa, Malysia, Iran, and Israel. The studies included more males than females, and participants tended to be children or young adults. Interventions included antifibrinolytic agents taken orally or applied directly to the eye (aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid), oral or topical corticosteroids, other kinds of eyedrops, aspirin, estrogens, traditional Chinese medicine, patching, elevation of the head, and bed rest. Most studies looked at how often fresh bleeding occurred, because this secondary bleeding is often associated with more complications. Other outcomes examined included visual acuity and the length of time it took for the blood in the eye to be absorbed.

What are the main results of the review?
We found no evidence that any medical intervention affected final vision, but we graded the evidence as generally of low certainty. Antifibrinolytic agents did appear to reduce the risk of new bleeding in the eye, but participants taking oral aminocaproic acid (an antifibrinolytic agent) appeared to have more nausea and vomiting compared with participants in the control group. It was unclear whether antifibrinolytics reduced complications of secondary bleeding, because these events were infrequent in the studies. We found no evidence for effectiveness of any other medical intervention in reducing the rate of fresh bleeding or the number of complications, but the evidence for a beneficial effect of any of these interventions was uncertain because the numbers of participants and events were small.

How up-to-date is this review?
We reviewed studies published up to 28 June 2018.

Authors' conclusions: 

We found no evidence of an effect on visual acuity by any of the interventions evaluated in this review. Although evidence was limited, it appears that people with traumatic hyphema who receive aminocaproic acid or tranexamic acid are less likely to experience secondary hemorrhaging. However, hyphema took longer clear in people treated with systemic aminocaproic acid.

There is no good evidence to support the use of antifibrinolytic agents in the management of traumatic hyphema other than possibly to reduce the rate of secondary hemorrhage. Similarly, there is no evidence to support the use of corticosteroids, cycloplegics, or non-drug interventions (such as binocular patching, bed rest, or head elevation) in the management of traumatic hyphema. As these multiple interventions are rarely used in isolation, further research to assess the additive effect of these interventions might be of value.

Read the full abstract...
Background: 

Traumatic hyphema is the entry of blood into the anterior chamber (the space between the cornea and iris) subsequent to a blow or a projectile striking the eye. Hyphema uncommonly causes permanent loss of vision. Associated trauma (e.g. corneal staining, traumatic cataract, angle recession glaucoma, optic atrophy, etc.) may seriously affect vision. Such complications can lead to permanent impairment of vision. People with sickle cell trait/disease may be particularly susceptible to increases of elevated intraocular pressure. If rebleeding occurs, the rates and severity of complications increase.

Objectives: 

To assess the effectiveness of various medical interventions in the management of traumatic hyphema.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 6); MEDLINE Ovid; Embase.com; PubMed (1948 to June 2018); the ISRCTN registry; ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). The date of the search was 28 June 2018.

Selection criteria: 

Two review authors independently assessed the titles and abstracts of all reports identified by the electronic and manual searches. In this review, we included randomized and quasi-randomized trials that compared various medical (non-surgical) interventions versus other medical intervention or control groups for the treatment of traumatic hyphema following closed-globe trauma. We applied no restrictions regarding age, gender, severity of the closed-globe trauma, or level of visual acuity at the time of enrollment.

Data collection and analysis: 

Two review authors independently extracted the data for the primary outcomes, visual acuity and time to resolution of primary hemorrhage, and secondary outcomes including: secondary hemorrhage and time to rebleed; risk of corneal blood staining, glaucoma or elevated intraocular pressure, optic atrophy, or peripheral anterior synechiae; adverse events; and duration of hospitalization. We entered and analyzed data using Review Manager 5. We performed meta-analyses using a fixed-effect model and reported dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD).

Main results: 

We included 20 randomized and seven quasi-randomized studies with a total of 2643 participants. Interventions included antifibrinolytic agents (systemic and topical aminocaproic acid, tranexamic acid, and aminomethylbenzoic acid), corticosteroids (systemic and topical), cycloplegics, miotics, aspirin, conjugated estrogens, traditional Chinese medicine, monocular versus bilateral patching, elevation of the head, and bed rest.

We found no evidence of an effect on visual acuity for any intervention, whether measured within two weeks (short term) or for longer periods. In a meta-analysis of two trials, we found no evidence of an effect of aminocaproic acid on long-term visual acuity (RR 1.03, 95% confidence interval (CI) 0.82 to 1.29) or final visual acuity measured up to three years after the hyphema (RR 1.05, 95% CI 0.93 to 1.18). Eight trials evaluated the effects of various interventions on short-term visual acuity; none of these interventions was measured in more than one trial. No intervention showed a statistically significant effect (RRs ranged from 0.75 to 1.10). Similarly, visual acuity measured for longer periods in four trials evaluating different interventions was also not statistically significant (RRs ranged from 0.82 to 1.02). The evidence supporting these findings was of low or very low certainty.

Systemic aminocaproic acid reduced the rate of recurrent hemorrhage (RR 0.28, 95% CI 0.13 to 0.60) as assessed in six trials with 330 participants. A sensitivity analysis omitting two studies not using an intention-to-treat analysis reduced the strength of the evidence (RR 0.43, 95% CI 0.17 to 1.08). We obtained similar results for topical aminocaproic acid (RR 0.48, 95% CI 0.20 to 1.10) in two studies with 121 participants. We assessed the certainty of these findings as low and very low, respectively. Systemic tranexamic acid had a significant effect in reducing the rate of secondary hemorrhage (RR 0.31, 95% CI 0.17 to 0.55) in five trials with 578 participants, as did aminomethylbenzoic acid as reported in one study (RR 0.10, 95% CI 0.02 to 0.41). The evidence to support an associated reduction in the risk of complications from secondary hemorrhage (i.e. corneal blood staining, peripheral anterior synechiae, elevated intraocular pressure, and development of optic atrophy) by antifibrinolytics was limited by the small number of these events. Use of aminocaproic acid was associated with increased nausea, vomiting, and other adverse events compared with placebo. We found no evidence of an effect in the number of adverse events with the use of systemic versus topical aminocaproic acid or with standard versus lower drug dose. 

The number of days for the primary hyphema to resolve appeared to be longer with the use of systemic aminocaproic acid compared with no use, but this outcome was not altered by any other intervention.

The available evidence on usage of systemic or topical corticosteroids, cycloplegics, or aspirin in traumatic hyphema was limited due to the small numbers of participants and events in the trials.

We found no evidence of an effect between a single versus binocular patch or ambulation versus complete bed rest on the risk of secondary hemorrhage or time to rebleed.

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