Topical Aminocaproic Acid in the Treatment

of Traumatic Hyphema
Earl R. Crouch, Jr, MD; Patricia B. Williams, PhD; M. Kevin Gray, MD;
Eric R. Crouch; Michael Chames, MD

Objectives: To determine whether topically applied
aminocaproic acid, like systemic aminocaproic acid,
effectively reduces secondary hemorrhage after hyphe-
mas and to compare the safety and effectiveness of
topical application with those of systemic use and a
control group.
Design: A prospective, randomized, double-masked,
multicenter
study.
Patients: Sixty-four patients with traumatic hyphema
treated with topical or systemic aminocaproic acid and
compared with 54 control patients with hyphema. Daily
slitlamp examinations for hyphema grading and cor-
neal clarity, initial and final visual acuity, applanation to-
the patients who received topical or systemic aminoca-
proic acid had secondary hemorrhage compared with 22%
(12/54) of the control group (P=.002). Final visual acu-
ity was 20/40 or better in 30 patients (86%) in the topi-
cal group compared with 23 patients (43%) in the con-
trol group (P<.001). Final visual acuity was 20/40 or
better in 20 patients (69%) in the systemic aminoca-
proic acid group compared with 23 patients (43%) in the
control group (P=.04). The topical aminocaproic acid
group had a final visual acuity of 20/40 or better in 86%
of patients, compared with 69% of patients in the sys-
temic group.
Conclusions: Topical aminocaproic acid appears to be
a safe, effective treatment to prevent secondary hemor-

nometry, and fundus indirect ophthalmoscopy were stud-
ied. Follow-up was 6 months to 5\m=1/2\years (mean, 2.96
years).
Results: Compared with the control group, topical and
systemic aminocaproic acid was statistically significant
in preventing secondary hemorrhage. Only 3% (2/64) of
rhage in traumatic hyphema. It is as effective as sys-
temic aminocaproic acid in reducing secondary hemor-
rhage. No systemic side effects were observed with topical
use. Topical aminocaproic acid provides an effective out\x=req-\
patient treatment for traumatic hyphemas.
Arch Ophthalmol. 1997;115:1106-1112

From theDepartment of
Ophthalmology, Eastern
Virginia Medical School,
Norfolk (Drs Crouch, Williams,
and Chames and Mr Crouch);
and Department of
Ophthalmology, University
of Tennessee, Memphis
(Dr Gray).
SECONDARY
hemorrhage oc¬ double-masked, prospective study, the
curs after traumatic hy¬ incidence of secondary hemorrhage was
phema in 9% to 38% of un¬ reduced to 3% compared with an inci¬
treated patients 2 to 5 days dence of 33% in placebo-treated eyes.10
after the initial injury.1"9 Sec¬ Other studies have demonstrated that
ondary hemorrhage significantly in¬ the incidence of secondary hemorrhage
creases the risk of visual impairment in the was reduced to 3% to 5% in patients
traumatized eye. Generally, secondary treated with aminocaproic acid com¬
hemorrhage is more severe than the ini¬ pared with 28% to 33% of the placebo
tial hemorrhage and confers a worse vi¬ group (P<.01).1415
sual prognosis. The incidences of corneal
blood staining, elevated intraocular pres¬ For editorial comment
sure with resultant optic atrophy, poste¬
rior synechiae, and anterior synechiae are seepage 1189
all increased with secondary hemor¬ Secondary hemorrhage results from
rhage.1·913 lysis and retraction of the fibrin plug
an antifibrino- that produced an occlusion of the trau¬
Aminocaproic acid,
lytic agent, was shown by Crouch and matized blood vessel.710 Treatment with
Frenkel10 to significantly reduce the systemic aminocaproic acid for 5 days
incidence of rebleeding when 100 injured blood vessel to more
allows the
mg/kg was given orally every 4 hours permanently repair its integrity before
for 5days (P<.01). In a randomized, the mobilization of the primary fibrin

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 PATIENTS AND METHODS
Patients with nonpenetrating traumatic hyphema were ad¬
mitted to the prospective, randomized, double-masked mul-
ticenter study to evaluate topical and systemic aminoca¬
proic acid compared with an untreated control group.
Patients were computer randomized to receive either
systemic aminocaproic acid and a placebo topical gel, or
the topical aminocaproic acid in 2% carboxypolymethyl-
ene gel and an oral placebo for 5 full days of treatment. A
third group of patients with traumatic hyphema com¬
posed the control group in the multicenter study, ie, these
patients did not receive either topical or systemic amino¬
caproic acid. Patients enrolled in the control group had re¬
fused entry into the randomized study group for treat¬
ment with aminocaproic acid.
Patients randomized to the group receiving systemic
therapy received aminocaproic acid orally, 50 mg/kg ev¬
ery 4 hours with a maximum dose of 30 g/d. Patients in
the topical therapy group received doses of 30% aminoca¬
proic acid in 2% carboxypolymethylene gel, 0.2 mL ap¬
plied in the inferior fomix of the involved eye every 6 hours.
The control group was studied contemporaneously by in¬
dependent observers. Data were compiled by observers who
did not know what patients were in the treated and un¬
treated control groups. The procedures and timing for treat¬
ment were the same for both treated and untreated groups.
Patients received either a placebo topical gel or a placebo
oral syrup with their active treatment. Treatment for pa¬
tients in both the medicated and the control groups con¬
sisted of 30° of head elevation, protection of the involved
eye with a metal shield, and moderate ambulation. In¬
formed consent was obtained from patients or the paren¬
tal guardian before they entered the study. The study pro¬
tocol and consent form were approved by the institutional
review board in this multicenter study.
Patients excluded from this study included those who
had 1 or more of the following conditions: penetrating ocu¬
lar trauma, previous intraocular surgery, history of coagu-
lopathy, history of renal or hepatic insufficiency, preg¬
nancy (a pregnancy test was performed on all females aged
12 years and older), history of anticoagulant or antiplate-
let agents within 7 days of ocular trauma, history of sen¬
sitivity to any component of the topical aminocaproic acid
gel, history of oral or topical corticosteroid use within 48
hours of the study, and participation in any investiga-
tional drug trial within 4 weeks.
Patients with sickle cell trait and disease represent a
special subgroup of patients who have unique complica¬
tions of traumatic hyphema and were included in the study.
A sickle cell test was conducted before the study on all black
patients; if positive, hemoglobin electrophoresis was con¬
ducted.
The 6-year study was initiated March 1,1990, and con¬
cluded May 1, 1996. Patients remained hospitalized for 5
full days of treatment. Clinical and demographic informa¬
tion obtained for analysis included age, sex, race, sickle
clot.7 Theantifibrinolytic activity of aminocaproic acid
administered systemically has also been demonstrated
in renal and neurological surgery to decrease the inci¬
dence of secondary hemorrhage.7
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cell status, mechanism of injury, initial and final visual
acuity, associated ocular and orbital injuries, history of sa-
licylate and corticosteroid usage, treatment, and compli¬
cations (ocular and systemic).
All patients underwent a complete ophthalmologic
examination. Blood pressure was recorded on admission
to study and before each dosing; blood pressure mea¬
the
surements were taken with the patient sitting upright and
lying flat, and hypertension and hypotension were docu¬
mented. Patients were asked about dizziness, headaches,
and nausea and vomiting at the time of vital signs mea¬
surements. Laboratory assessments included partial throm-
boplastin time, prothrombin time, complete blood cell count,
differential count, serum urea nitrogen, creatinine (before
and after study), and serum pregnancy test (females aged
12 years and older). Admitting orders included bed rest with
the head of the bed elevated 30°, protection of the in¬
volved eye with a metal shield, and moderate ambulation.
Patients were not allowed to receive aspirin, nonsteroid anti-
inflammatory drugs, antiplatelet products, or systemic or
topical corticosteroids during the 5 days of hospital treat¬
ment. Patients received topical timolol maléate, apracloni-
dine hydrochloride, dipivefrin hydrochloride, and oral
methazolamide for intraocular pressure greater than 22
mm Hg.
Patients in the study underwent daily examinations
by the ophthalmologists that included visual acuity; slit-
lamp examination for grading of hyphema (with sketch),
cell and flare, evidence of secondary hemorrhage, and/or
corneal blood staining; slitlamp examination with fluores¬
cein to examine for evidence of corneal toxicity; applana-
tion tonometry; recording objective and subjective re¬
ports of adverse ocular and systemic effects; and fundus
indirect ophthalmoscopy. (B-scan ultrasonography was per¬
formed initially when details of the fundus were ob¬
scured.)
Patients in the treatment groups had blood drawn (2.5
mL) 1 hour after the fifth dose (25 hours after the first dose),
and 1 hour after the 13th dose (73 hours after the first dose)
of the initial medication with date and time of collection
noted. Serum aminocaproic acid levels were analyzed by
the Eastern Virginia Medical School Pharmacology Depart¬
ment, Norfolk, by means of a high-performance liquid Chro¬
matographie assay.1618·19
The sample size required for this study was calcu¬
lated to be between 25 and 30 patients in each of the 3 groups
(topical aminocaproic acid, systemic aminocaproic acid, and
control). The sample size justification was calculated on
the basis of an c< level (type 1 error rate) of 0.05 and a power
of 80%.
Statistical evaluation was performed with the un¬
paired 2 and Fisher exact tests for independent samples.
A value of .05 or less was considered statistically signifi¬
cant.
By computer evaluation, each variable was compared
with every other variable between treated and control
groups, including initial and final visual acuities, inci¬
dence of complications, and secondary hemorrhage.
Systemic side effects of systemic aminocaproic acid
therapy include nausea, vomiting, dizziness, and hypo¬
tension.7·1415 Topical aminocaproic acid in 2% carboxy-
polymethylene gel (Carbopol) has been shown to be ef-
 Table 1. Incidence of Secondary Hemorrhage* Table 3. Initial Size of Hyphema*

No. (%) of Group, No. (%)

Secondary
Treatment Group Hemorrhage Fraction of Anterior Topical and
1 (3)
Chamber Filled Systemic ACA Control
Topical ACA (n=35) .01
Grade_With Blood_(n=64)_(n=54)
Oral ACA (n=29) 1 (3) .03
2 (3) I <Vs 44(69) 35(65)
Total (n=64) .002
II Vs to 1/2 6(9) 6(11)
III V2 to near total 8(13) 8(15)
*P values were calculated for the treatment groups vs the control group
(n=54) in which 12 patients had secondary hemorrhage. ACA indicates
IV Total 6(9) 5(9)
aminocaproic acid.
*ACA indicates aminocaproic acid.

caproic acid, only 1 (3%) of the 35 patients in the

Table 2. Patient Demographics*
topical group and 1 (3%) of the 29 patients in the sys¬
temic group developed secondary hemorrhage
Group, No. (%) (Table I ; P=.01 and P=.03, respectively, vs controls).
-1
Topical ACA Systemic ACA Control The overall incidence of secondary hemorrhage in the
Variable_(n=35)_(n=29) (n=54) 2 treated groups was 2 (3%) of 64 (P=.002). Reduc¬
Sex tion in the incidence of secondary hemorrhage com¬
M 24(69) 19(65) 39(72) pared with the control group was statistically signifi¬
F 11(31) 10(35) 15(28) cant in both the topical (P .01) and the systemic
=

Race (P=.03) aminocaproic acid groups.

Black 17(49) 15(52) 31(57)
White
The topical and systemic aminocaproic acid group
17(49) 14(48) 23(43) included 43 males (67%) and 21 females (33%); the con¬
Asian 1 (2) 0 (0) 0 (0)
Positive SA hemoglobin 2/17(12) 2/15(13) 5/31(16) trol group consisted of 39 males (72%) and 15 females
or SS hemoglobin (28%). There was no statistically significant difference
in blacks between topical aminocaproic acid, systemic aminoca¬
*ACA indicates aminocaproic acid.
proic acid, and the control group in patient sex, race, and
SS or SA hemoglobin (sickle cell trait or disease)
(Table 2). In the treated groups, black patients (N=32)
fective in reducing secondary
the incidence of represented 50% of the study and white patients (N=31),
hemorrhage prospective, double-masked, controlled
in 49%. One patient (1%) was Asian. Three (9%) of 32 black
laboratory studies using New Zealand white rabbits patients were positive for SA hemoglobin, and 1 black
with traumatic hyphema.16"19 Aqueous humor concen¬ patient in the treated group (3%) had SS hemoglobin. In
trations of aminocaproic acid after topical administra¬ the control group, black patients (N=31) represented 57%
tion are comparable with those achieved with systemic of the study and white patients (N=23), 43%. Five (16%)
therapy.161819 The adverse effects after systemic admin¬ of 31 black patients were positive for SA hemoglobin. In
istration of aminocaproic acid are thought to be related the topical and systemic aminocaproic acid group, 46 pa¬
to serum levels of the drug. The substantial reduction in tients (72%) were younger than 21 years. Factors were
serum aminocaproic acid levels achieved with topical equally distributed between the treated groups and the
application should decrease the incidence or eliminate control group as determined by statistical analysis. There
these adverse effects.16"19 was no statistically significant difference between the topi¬
The purposes of this study were to ( 1 ) establish the cal and systemic aminocaproic acid-treated groups and
efficacy of topical aminocaproic acid in 2% carboxypoly- the untreated control groups in the size of the initial hy¬
methylene gel in prevention of secondary hemorrhage phema (Table 3).
after traumatic hyphema, (2) compare the effectiveness The topical aminocaproic acid group had initial vi¬
of topical aminocaproic acid with that of systemic ami¬ sual acuity of 20/40 or better in 10 (29%) compared with
nocaproic acid in prevention of secondary hemorrhage 11 (38%)in the systemic aminocaproic acid group and
in the treatment of traumatic hyphema, and (3) deter¬ 16 (32%)in the control group (Table 4). Final visual
mine whether known adverse effects of systemic amino¬ acuity was 20/40 or better in 30 patients (86%) of the
caproic acid, such as nausea and vomiting, dizziness, and topical group compared with 23 patients (43%) in the
hypotension, can be reduced by topical application of ami¬ control group (P<.001) (Table 4). Final visual acuity was
nocaproic acid. 20/40 or better in 20 patients (69%) in the systemic ami¬
nocaproic acid group compared with 23 patients (43%)
RESULTS in the control group (P=.04). The topical aminocaproic
acid group had a final visual acuity of 20/40 or better in
A total of 64 patients were treated with either topical 30 patients (86%), compared with 20 patients (69%) in
(N 35)
=
systemic (N 29) aminocaproic acid, and
or = the systemic aminocaproic acid group.
there were 54 patients in the control group. In the 54 Table 5 lists the complications secondary to the
control patients, the secondary hemorrhage rate was trauma and secondary hemorrhage in the total study.
12 (22%) of 54. Of the 64 patients treated with amino- There was no statistically significant difference in the in-

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 Table 4. Initial and Final Visual Acuity in the Topical ACA, Systemic ACA, and Control Hyphema Groups*
Group, No. (%)
Topical ACA Systemic ACA Control
(n=35) (n=29) (n=54)
-1 -1
Visual Acuity Initial Final Initial Final Initial Final
20/20-20/40 10(29) 30 (86)t 11(38) 20 (69)+. 16(30) 23(43)
20/50-20/100 10(29) 2(6) 7(24) 4(14) 6(11) 7(13)
20/200-20/400 2(6) 2(6) 3(10) 2(7) 5(9) 4(7)
Finger counting 1(3) 1(2) 2(7) 1(3) 6(11) 6(11)
Hand motions 8(23) 0 (0)§ 4(14) 2(7) 12(22) 6(11)
Light perception with projection 4(10) 0 (0)§ 2(7) 0(0)+· 9(17) 8(15)
*ACA indicates aminocaproic acid.
t Topical vs control, P<.001.
XSystemic vs control, P<.05.
^Topical vs control, ?<.05.

Table 5. Complications of Ocular Trauma* Table 6. Incidence of Optic Atrophy and Corneal Blood
Staining in the Treatment and Control Groups and Final
Group, No. (%) Visual Acuity in the Control Group*

Topical and No. (%)

Systemic ACA Control
Complication (n=64) (n=54) Corneal
Optic Blood
Eyelid laceration 5(8) 7(13)
Corneal abrasion 17 (27) 9(17) Group Atrophy Staining
Corneal blood staining 0 (0) 3 (6) Topical ACA (n=35) 0(0) 0(0)
Iritis 48 (75) 39 (72) Systemic ACA (n=29) 0(0) 0(0)
Angle recession glaucoma 6 (9) 0 (0) Control (n=54) 5(9) 3(6)
Iridodialysis 4 (6) 3 (6)
Final Visual Acuity of Control Group
Peripheral anterior synechiae 4 (6) 3 (6)
Light perception and projection 3 (5) 1(2)
Sphincter rupture 8(12) 1(2) Counting fingers 2 (4) 1(2)
Posterior synechiae 4 (6) 3 (6)
20/400 0 (0) 1(2)
Cataract 8(12) 5(9) Total 5 (9) 3(6)
Subluxated lens 3 (5) 2 (4)
Cyclodialysis 2 (3) 0 (0)
Vitreous hemorrhage *ACA indicates aminocaproic acid.
13(20) 14(26)
Macular edema (commotio retinae) 19 (30) 8 (15)
Retinal detachment/tear 2 (3) 3 (6)
Macular scar 4 (6) 0 (0) COMMENT
Subretinal hemorrhage 2 (3) 2 (4)
Choroidal rupture 3 (5) 4 (7) In the previous prospective study by Crouch and Fren-
Scierai ectasia 0 (0) 0 (0) kel10 well as 2 additional studies,1415 patient groups
as
Optic atrophy 0 (0) 5 (9) treated with systemic aminocaproic acid and placebo were
Orbit wall fracture 6(9) 9(16) randomized and the studies were double masked. Ami¬
*ACA indicates aminocaproic acid. nocaproic acid in a dosage of 50 mg/kg every 4 hours was
as effective as 100 mg/kg every 4 hours orally for 5 days,
with fewer systemic side effects.14 The maximum dos¬
cidence of complications between the topical and sys¬ age of aminocaproic acid was 5 g every 4 hours, not to
temic aminocaproic acid-treated groups and the con¬ exceed 30 g/d.7
trol group. However, the complications of optic atrophy Some ophthalmologists have been reluctant to
(5 patients [9%]) and corneal blood staining (3 patients prescribe aminocaproic acid systemically because of
[6%]) in the control group accounted for notable vision potential systemic side effects.10·14·15 Other ophthal¬
loss in 8 (15%) of 54 control patients (Table 6); these mologists observe patients with hyphema until sec¬
complications occurred in none of the aminocaproic ondary hemorrhage occurs before initiating systemic
acid-treated patients. Systemic side effects of systemic aminocaproic acid treatment to prevent additional
aminocaproic acid appear to' be related to the plasma hemorrhage.7 By concentrating the aminocaproic acid
level of aminocaproic acid. The mean (±SEM) serum in the aqueous humor, a topical aminocaproic acid
level of aminocaproic acid was 61.87±4.2 pg/mL in the preparation decreases the systemic concentration of
systemic aminocaproic acid-treated group. In the topi¬ aminocaproic acid associated with many of the adverse
cal aminocaproic acid-treated group, the mean effects. Aminocaproic acid should not be used by preg¬
(±SEM) serum aminocaproic acid level was 6.03 ±1.4 nant patients or those with renal or hepatic impair¬
pg/mL (P<.001). ment.7

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 For systemically administered aminocaproic acid to
be effective, it must penetrate into the anterior segment
in sufficient concentration to retard fibrinolysis. To di¬
rectly determine the concentration of aminocaproic acid
in aqueous humor after systemic administration, we com¬
pared plasma and aqueous humor concentrations of ami¬
nocaproic acid after intravenous administration of 50
mg/kg and 100 mg/kg as well as after constant infusion
of 25 mg/kg per hour.16 Plasma levels after intravenous
administration were 10-fold higher than in the aqueous
humor. Antifibrinolytic activity correlated directly with
aminocaproic acid concentration in plasma or aqueous
humor.16
AMINOCAPROIC
ACID retards clot lysis by
preventing plasmin from binding to ly¬
sine molecules in the fibrin clot. Amino¬
caproic acid, a lysine analogue, competi¬
tively inactivates plasmin by occupying
the lysine binding site on plasmin that would normally
bind to fibrin. In addition, aminocaproic acid binds to
plasminogen, so that, when activated to plasmin, it can¬
not attach to fibrin. These effects stabilize the clot-
vessel wall interface, decreasing the potential for second¬
ary hemorrhage.7·9"11
Based on the work of Ablondi and associates20 and
Alkjaersig and coworkers,21 a concentration of amino¬
caproic acid of 10 to 32.5 pg/mL is required to produce
antifibrinolytic effects. These concentrations are
achieved in aqueous humor after systemic administra¬
tion.16 In a previous study, the optimum concentration
for topical drug delivery was determined to be 30% ami¬
nocaproic acid to 2% carboxypolymethylene.19 Using
different assumptions and a different approach, Camp¬
bell and associates22 also determined that a similar con¬
centration of aminocaproic acid would be required but
would have a limited duration of action. Through ma¬
nipulation of the vehicle and incorporation of a perme¬
ation enhancer to facilitate penetration of the corneal
epithelium, we determined that the duration could be
extended to permit clinically relevant dosages of greater
than 10 pg/mL at intervals of 6 hours.19 Attempts to fur¬
ther increase the duration of action by means of hyal-
uronic acid (Healon) or collagen shields as a depot were
ineffective.23
Seven topically applied preparations containing
aminocaproic acid of different compositions were pre¬
pared to assess the ability of aminocaproic acid to
penetrate into the aqueous humor.17 The greatest
aqueous aminocaproic acid concentrations were
obtained with the use of carboxypolymethylene. The
topical preparation containing carboxypolymethylene
had a duration of action of greater than 6 hours. In
addition, pretreatment with proparacaine significantly
increased aminocaproic acid concentration in the
aqueous humor.19
In an experimental model for hyphema, aminoca¬
proic acid in carboxypolymethylene was applied topi¬
cally every 6 hours for 5 days or until a secondary
hemorrhage occurred.18 Compared with no treatment
or the administration of a placebo (eg, carboxypoly-
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méthylène vehicle without aminocaproic acid), topical
application of aminocaproic acid significantly
decreased the incidence of secondary hemorrhage
from 33% to 10% (P<.05).18 There were no serious
ocular side effects after the topical application. Aque¬
ous humor concentrations of aminocaproic acid after
topical administration were comparable with those
achieved with systemic therapy.
In the present study, 64 patients were treated with
systemic or topical aminocaproic acid. Only 2 (3%) of
64 patients developed secondary hemorrhage (P=.002).
One patient of 29 treated with systemic aminocaproic acid
developed a secondary hemorrhage on day 3. There was
an increase in bright anterior chamber blood from 15%
to 30%. Final visual acuity was 20/20. One patient in the
topical aminocaproic acid-treated group (N=35) devel¬
oped secondary hemorrhage on day 5 with an increase
in anterior chamber blood from 25% to 40%. Final vi¬
sual acuity was 20/20.
There were no significant ocular complications from
topical aminocaproic acid except that 4 patients re¬
ported a conjunctival or corneal foreign body sensation.
Transient punctate corneal staining was observed in 3 of
these patients. One adult patient (3%) of 35 patients tak¬
ing topical aminocaproic acid had dizziness, nausea, and
vomiting on 2 occasions. However, no antiemetic medi¬
cation was required. No patients taking topical amino¬
caproic acid developed postural hypotension.
Five (17%) of 29 patients taking systemic amino¬
caproic acid had dizziness, nausea, and vomiting that
was relieved by promethazine hydrochloride (Phener-
gan). All 5 patients were older than 21 years. One pa¬
tient taking systemic aminocaproic acid had to be re¬
moved from the study on day 3 because of repeated
nausea and vomiting despite antiemetic therapy. Only 1
(3%) of 35 patients taking topical aminocaproic acid
had nausea and vomiting or dizziness. The 10.3-fold in¬
crease of serum levels in the systemic aminocaproic
acid group (mean±SEM, 61.87±4.2 pg/mL) compared
with the topical aminocaproic acid-treated group
(mean±SEM, 6.03±1.4 pg/mL) accounts for the sys¬
temic side effects observed with systemic aminocaproic
acid (P<.001). Only 1 of the 46 patients younger than
21 years developed nausea and vomiting while taking
systemic or topical therapy. None had systemic hypo¬
tension or dizziness. This younger patient population
(72% of the aminocaproic acid-treated groups) ap¬
peared to tolerate both topical and systemic aminoca¬
proic acid without major side effects.
In the control group of 54 patients, there were 12
patients with secondary hemorrhage. Ten (83%) of these
patients were black. Ten (32%) of 31 black patients in
the control group had secondary hemorrhage. Four (40%)
of the 10 black patients with secondary hemorrhage had
positive SA hemoglobin. Other reports have observed a
higher incidence of complications and secondary hem¬
orrhage in the black population.7·9·11·24·25 In our previous
series, 3 (37%) of 8 blacks with positive SA hemoglobin
had secondary hemorrhage.9 Four patients in the ami¬
nocaproic acid-treated groups who required surgical in¬
tervention were black (4 of 32 patients [12%]), and 2 had
positive SA hemoglobin.
 In the present series, 2 patients with positive SA he¬
moglobin required surgical intervention. One patient had
a hyphema that occupied 20% of the anterior chamber
and intraocular pressure became elevated at greater than
40 mm Hg for 48 hours despite antiglaucomatous therapy
with timolol maléate, dipivefrin hydrochloride, and
methazolamide. Visual acuity was reduced to 20/100. An¬
terior chamber paracentesis and irrigation were per¬
formed. Final visual acuity was 20/25. The second pa¬
tient positive for SA hemoglobin had a hyphema that
occupied 25% of the anterior chamber. Initial visual acu¬
ity was 20/200, and intraocular pressure was elevated at
54 mm Hg. The intraocular pressure remained elevated
at 46 mm Hg despite treatment with timolol, apracloni-
dine hydrochloride, and methazolamide antiglaucoma
medications for 48 hours. After surgical irrigation and
aspiration, the intraocular pressure was 10 mm Hg. Fi¬
nal visual acuity was 20/20.
In the topical and systemic aminocaproic acid
groups, 2 patients of 6 with total hyphemas required
surgical intervention on day 4 because of elevated intra¬
ocular pressure with maximum antiglaucoma medica¬
tions. Final visual acuity was 20/30 in both patients.
The other 3 patients with total hyphemas had intraocu¬
lar pressure controlled and did not require surgical
intervention.
In the control group, 5 patients had a hy¬
total
phema initially. All required surgical intervention on day
4 or 5 because of elevated intraocular pressure not con¬
trolled by timolol, apraclonidine, dipivefrin, and metha¬
zolamide.
No patients developed corneal blood staining or op¬
tic atrophy in the aminocaproic acid groups. Five pa¬
tients in the control hyphema group had optic atrophy
related to secondary hemorrhage and elevated intraocu¬
lar pressure and 3 patients had corneal blood staining af¬
ter secondary hemorrhage and total hyphemas.
In patients with traumatic hyphema, the severity of
the trauma is frequently related to the final visual out¬
come. Lens opacities, choroidal rupture, vitreous hem¬
orrhage, angle recession glaucoma, and retinal detach¬
ment are commonly associated with traumatic hyphema,
compromising the final visual result.7 Fourteen percent
of patients have poor visual results from associated trauma,
ie, glaucoma, vitreous hemorrhage, retinal detachment,
and scierai rupture. Poor visual outcome in traumatic hy¬
phema can be attributed directly to the hyphema in 11%
of patients.7·"·26 This frequently may be the result of sec¬
ondary hemorrhage associated with optic atrophy or cor¬
neal blood staining.7·11·26
The major cause of loss of vision in the 64 patients
in the topical and systemic aminocaproic acid groups
was related to associated ocular trauma, especially com-
motio retinae in 19 patients (30%), choroidal rupture
with resultant macular scarring in 4 patients (6%), sub¬
retinal hemorrhage in 2 patients (3%), choroidal rup¬
ture in 3 patients (5%), and vitreous hemorrhage in 13
patients (20%) (Table 5). The major causes of reduced
vision in the control group of 54 patients were corneal
blood staining in 3 patients (6%) and optic atrophy in 5
patients (9%) and account for 15% of patients in the
control group.
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No patients developed optic atrophy or corneal
blood staining in our present study in the groups
treated with topical or systemic aminocaproic acid. In
our previous series of 196 patients, we observed corneal
blood staining in 11 patients (5.6%).711 All 11 patients
had hyphemas that occupied greater than 50% of the
anterior chamber for 3 days or more. Optic atrophy
with visual acuity reduction to less than 20/400 oc¬
curred in 10 (5.1%) of 196 patients. Two of the 10 pa¬
tients who developed optic atrophy were positive for SA
hemoglobin. One patient with sickle cell trait had intra¬
ocular pressure that ranged between 35 and 39 mm Hg
for only 2 days, and the other patient's intraocular pres¬
sure ranged between 35 and 40 mm Hg for 4 days. The
prognosis for visual recovery in traumatic hyphema ap¬
pears to be directly related to 3 factors: (1) the amount
of associated damage to other ocular structures, ie, cho¬
roidal rupture or macular scarring, (2) whether second¬
ary hemorrhage occurs, and (3) whether complications
of glaucoma, corneal blood staining, or optic atrophy
occur.7 Treatment modalities should be directed at re¬
ducing the incidence of secondary hemorrhage and re¬
ducing the risk of corneal blood staining and optic atro¬
phy. A low incidence of side effects is important in
treatment.
Because of its efficacy and favorable side effects pro¬
file, the use of topical aminocaproic acid has potential
use in the outpatient treatment of hyphema. Several stud¬
ies showed no significant differences in final visual acu¬
ities in patients treated at home and those treated in the
hospital.7 26"29 With the increased emphasis on reducing
hospital admissions and cost containment, outpatient
treatment of hyphemas occupying less than half the an¬
terior chamber is a viable option. Potentially, hyphemas
that occupy less than 50% of the anterior chamber could
be managed safely on an outpatient basis with topical ami¬
nocaproic acid therapy. This represents 78% of all hy¬
phemas.7·11
Accepted for publication March 6, 1997.
This research project was supported in part by the Li¬
ons Medical Eye Bank and Research Center of Eastern Vir¬
ginia, Norfolk.
Drs Crouch and Williams were awarded 2 patents in
May 1996 related to topical aminocaproic acid.
We thank Paul Kolm, PhD, statistician, Eastern Vir¬
ginia Medical School, who performed statistical analysis on
the study patient data; John H. Key, Jr, for technical assis¬
tance; Susan Drady, RPh, for preparation of the drugs and
maintenance of the randomization scheme; and Cy Carlton
for manuscript preparation.
Reprints: Earl R. Crouch, Jr, MD, Department of
Ophthalmology, Eastern Virginia Medical School, 880
Kempsville Rd, Suite 2500, Norfolk, VA 23502 (e-mail:
crouch@picard. evms.edu).
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"Pupil-
Error in Title. In the Letter to the Editor titled
lary Block, Angle-closure Glaucoma Produced by an An-
terior Chamber Air Bubble in a Nanophthalmic Eye," pub-
lished in the March Archives (1997;115:432), the term
"nanophthalmic" was misspelled in the title. We truly
regret the error.

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