What is the role of topical aminocaproic acid (ACA) in the treatment of hyphema?

Updated: Jan 18, 2019
  • Author: David L Nash, MD; Chief Editor: Andrew A Dahl, MD, FACS  more...
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For systemically administered ACA to be effective, it must penetrate the anterior segment in sufficient concentration to retard fibrinolysis. To directly determine the concentration of ACA in the aqueous humor following systemic administration, using an animal model, the authors compared plasma and aqueous humor concentrations of ACA following intravenous (IV) administration of 50 mg/kg and 100 mg/kg, as well as after constant infusion of 25 mg/kg/h. [42] After IV administration, plasma levels were 10-fold higher than levels in the aqueous humor. Antifibrinolytic activity correlated directly with ACA concentration in plasma or the aqueous humor. The time to clot dissolution was greatest (2.5 times control) when the ACA concentration in the aqueous humor reached 30-35 mg/dL, which, thus, became the target concentration to achieve with topical therapy.

The authors' long-range goal is to improve the management of hyphema by decreasing the incidence of secondary hemorrhage using topical drug therapy that is more effective, less toxic, and better accepted by both patients and ophthalmologists than the currently available oral therapy with ACA.

Seven topical preparations containing ACA were studied to assess which could deliver the required amount of ACA into the aqueous humor. [43] The greatest ACA concentrations were obtained using either polyvinyl alcohol or carboxypolymethylene (CPM), 51 mg/dL and 58 mg/dL, respectively. The latter had a longer duration of action. Using an experimental model for hyphema, ACA in CPM was applied topically every 6 hours for 6 days or until a secondary hemorrhage occurred. [44] Compared to no treatment or the administration of a placebo (eg, vehicle without ACA), topical application of ACA significantly decreased the incidence of rebleeds from 33% to 10% (P < 0.05). No ocular adverse effects occurred after topical application of either formulation.

Additional studies have been performed to optimize the concentration of the vehicle and the drug. [45] The optimal combination is 30% ACA to 2% CPM. However, this combination did not lead to an increase in the duration of action using hyaluronic acid (Healon) or collagen shields as a depot. [46] The gel is administered in a glass syringe 4 times per day for 7 days. The gel is well tolerated by patients, including children.

Studies of 25% ACA have not seen a significant benefit in reducing rebleeding rates and increased the time to clot resolution. [47] However, a study concluded ACA was beneficial in treating patients with hyphema. [48]

The authors established a prospective, multicenter, double-masked, randomized clinical trial comparing oral and topical ACA. [49]

In the trial, 64 patients with traumatic hyphema treated with topical or systemic ACA were compared with 54 control patients with hyphema. Compared with the control group, topical and systemic ACA were statistically significant in preventing secondary hemorrhage. Only 3% (2/64) of the patients who received topical ACA (35 patients) or systemic ACA (29 patients) had secondary hemorrhage, compared with 22% (12/54) of the control group (P=0.002). Final visual acuity was 20/40 or better in 30 patients (86%) in the topical ACA group, compared with 23 patients (43%) in the control group (P=0.001). Final visual acuity was 20/40 or better in 20 patients (69%) in the systemic ACA group, compared with 23 patients (43%) in the control group (P=0.04). A final visual acuity of 20/40 or better was regained by 86% of patients in the topical ACA group, compared with 69% of patients in the systemic ACA group. [49]

Topical ACA, although unapproved in the United States, appears to be a safe, effective treatment to prevent secondary hemorrhage in patients with traumatic hyphema. It is as effective as systemic ACA in reducing secondary hemorrhage, and no systemic adverse effects were observed with topical use. Topical ACA provides an effective outpatient treatment for traumatic hyphemas.

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