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Postinjury accumulation of blood in the anterior chamber is one of the most

challenging clinical problems encountered by the ophthalmologist. Even a


small hyphema can be a sign of major intraocular trauma with associated
damage to vascular and other intraocular tissues.
Blunt trauma to the eye may result in injury to the iris, papillary sphincter,
angle structures, lens, zonules, retina, vitreous, optic nerve, and other
intraocular structures. Blunt trauma associated with a rapid, marked elevation
in intraocular pressure with sudden distortion of intraocular structures
produces the dynamic changes responsible for hyphema formation.
The lack of an ideal therapeutic program, the potential for secondary
hemorrhage, and the secondary onset of glaucoma all threaten to turn an eye
with an initially good visual prognosis into a complex therapeutic problem with
a poor final visual result.
Classification and characteristics
Traumatic hyphema is encountered in children and adults. Hyphema is
usually the result of a projectile or deliberate punch that hits the exposed
portion of the eye despite the protection of the bony orbital rim. Various
missiles and objects have been incriminated, including balls, rocks, projectile
toys, air gun pellets, BB gun pellets, hockey pucks, bungee cords, paint balls,
and the human fist.
[1, 2, 3]
More recently, air gun pellets and BB gun pellets
have been made of plastic polymers. There have even been cases involving
objects larger than the orbit, such as soccer balls.
[4]
Slow motion photography
has demonstrated deformation of the soccer balls as impact occurs with the
orbital rim, thereby causing the hyphema. With the increase of child abuse,
fists and belts have started to play a prominent role. Males are involved in
three fourths of cases.
[5, 6]

Hyphema can also occur intraoperatively or postoperatively. Surgical
hyphema is a known complication of intraocular surgery and should be
managed in a similar manner as traumatic hyphema.
Rarely, spontaneous hyphemas may occur and be confused with traumatic
hyphemas. Spontaneous hyphemas are secondary to neovascularization (eg,
diabetes mellitus, ischemia, cicatrix formation), ocular neoplasms (eg,
retinoblastoma), uveitis, and vascular anomalies (eg, juvenile
xanthogranuloma). Vascular tufts that exist at the pupillary border have been
implicated in spontaneous hyphemas.
[7]

The following clinical grading system for traumatic hyphemas is preferred:
Grade 1 - Layered blood occupying less than one third of the anterior
chamber
Grade 2 - Blood filling one third to one half of the anterior chamber
Grade 3 - Layered blood filling one half to less than total of the anterior
chamber
Grade 4 - Total clotted blood, often referred to as blackball or 8-ball
hyphema

Most hyphemas fill less than one third of the anterior chamber. When
hyphemas are divided into 4 groups according to the amount of filling of the
anterior chamber, 58% involve less than one third of the anterior chamber,
20% involve one third to one half of the anterior chamber, 14% involve one
half to less than total of the anterior chamber, and 8% are total hyphemas.
Slightly fewer than one half of all hyphemas settle inferiorly to form a level;
approximately 40% form a definite clot, usually adherent to the iris stroma;
and 10% have a dark clot in contact with the endothelium. This last form may
portend a poor outcome and corneal staining.
An alternative method of grading hyphemas involves measuring (in
millimeters) the hyphema from the inferior 6-o'clock limbus. This method may
help in monitoring the progress of resolution or the occurrence of rebleeding.
Digital imaging analysis is also useful and objective but is available in only a
few research or academic facilities.
The cause of an anterior chamber hemorrhage in contusion injuries is thought
to be related to the posterior displacement of tissue or to the resultant fluid
wave in the aqueous humor and the vitreous. This sudden dynamic shift
stretches the limbal vessels and displaces the iris and the lens. This
displacement may result in a tear at the iris or the ciliary body, usually at the
angle structures.
[8]
A tear at the anterior aspect of the ciliary body is the most
common site of bleeding and occurs in about 71% of cases.
[9]
The blood exits
from the anterior chamber via the trabecular meshwork and the Schlemm
canal or the juxtacanalicular tissue.
The usual duration of an uncomplicated hyphema is 5-6 days. The mean
duration of elevated intraocular pressure is 6 days.
Pathophysiology
Hyphema describes the condition of the aqueous humor when red blood cells
form a suspension in it.
The choroid and the iris contain a rich complex of vessels. The pupil is
outlined and controlled by a complex set of iridial muscles, sphincters, and
dilators. These muscles can be ruptured by sharp and/or blunt trauma. This is
a frequent source of intraocular hemorrhage (hyphema). In addition, the iris
root and/or the ciliary spur is a common location of bleeding from blunt
trauma.
Surgical intervention into the eye for anterior segment procedures is
accomplished routinely through various approaches. The most commonly
used approaches in modern small incision surgery are via the limbus and/or
the clear cornea. Clear cornea surgery markedly reduces the risk of bleeding
from limbal vessels since the cornea in its healthy state is avascular. Scleral
tunnel incision is subject to unpredictable hemorrhage, and the incision must
be closed carefully with sutures.
Hyphema can occur as a result of intraocular surgery, as follows:
Intraoperative bleeding - Ciliary body or iris injury seen during a peripheral
iridectomy, cataract extraction, cyclodialysis, and filtration procedure (laser
peripheral iridectomy, especially with YAG laser than with argon laser; argon
laser trabeculoplasty [ALT] not very common)
Early postoperative bleeding (a traumatized uveal vessel that was in spasm
and suddenly dilates; conjunctival bleeding that makes its way into the
anterior chamber via a corneoscleral wound or sclerostomy)
Late postoperative bleeding (new vessels growing across the corneoscleral
wound that bleed when manipulated; a uveal wound that is reopened; an
intraocular lens [IOL] that causes chronic iris erosion)
Frequency
In the United States, the incidence of hyphema is 17-20 per 100,000 people
per year.
Differentials
Herpes Simplex
Herpes Zoster
Juvenile Xanthogranuloma
Keratoconjunctivitis, Atopic
Melanoma, Choroidal
Melanoma, Ciliary Body
Melanoma, Iris
Retinoblastoma
Uveitis, Fuchs Heterochromic
Other problems to be considered
Trauma
Intraocular surgery
Spontaneous hyphema
Iris microhemangiomas, iris varix, and pupillary microhemangiomas
Iris neovascularization
Clotting disorders
Following laser trabeculoplasty
[10]
or iridotomy
Anticoagulation therapy, such as warfarin (Coumadin), clopidogrel bisulfate
(Plavix), or aspirin
Increased intraocular pressures may accompany hyphemas of any size.
Elevated intraocular pressures (>22 mm Hg) may be anticipated in
approximately 32% of all patients with hyphemas at some time during their
course.
[9]
Higher, more prolonged elevations of intraocular pressure are more
commonly associated with near total or total hyphemas. Patients predisposed
to glaucoma or with preexisting glaucoma and decreased facility of trabecular
outflow are also more likely to develop glaucoma with a hyphema.
These highly elevated intraocular pressures occur during the acute phase of
the hyphema and are separate from those related to angle recession.
[11]
In
patients with pressure elevations, abnormal tonometric readings are
frequently detected during the first 24 hours after injury. This initial period of
elevated intraocular pressure is often followed by a period of normal or below
normal pressure from the second day to the sixth day. Careful monitoring of
the intraocular pressure is important and may determine the course of
treatment.
[12]
The early period of elevated intraocular pressure is probably the
result of trabecular plugging by erythrocytes and fibrin. The following period of
reduced pressure is most likely due to reduced aqueous production and
uveitis, and it may actually increase the chance of secondary hemorrhage.
This period of hypotony is commonly followed by a subsequent rise in
intraocular pressure, probably coincidental with the recovery of the
ciliarybody.
Intraocular hypertension then subsides with recovery of the trabecular
meshwork and disappearance of the hyphema.
Exceptions include patients with a hyphema occupying greater than 75% of
the anterior chamber and those with a total hyphema, in whom pressure
elevation frequently has its onset simultaneously with the initial hyphema and
remains continually elevated until the hyphema has had considerable
resolution. When large segments of the anterior chamber angle are
irreparably damaged and/or when organization of the fibrin or clot produces
extensive peripheral anterior synechiae, the intraocular hypertension
continues, becoming intractable glaucoma.
Ghost cell glaucoma with hyphema and vitreous hemorrhage may cause
elevated intraocular pressure 2 weeks to 3 months after the initial
injury.
[13]
Gradual clearing of the hyphema occurs, with erythrocytes losing
hemoglobin and becoming so-called ghost cells in the vitreous cavity. The
ghost cells then circulate forward into the anterior chamber, with resultant
trabecular blockage due to the distorted, bulky configuration of the crenated
red blood cell. Considerable delayed elevation of intraocular pressure may
occur with ghost cell glaucoma, particularly in patients with poor facility of
outflow.

Secondary bleeding into the anterior chamber results in a markedly worse
prognosis. Eventual visual recovery to a visual acuity of 20/50 (6/15) or better
occurs in approximately 64% of patients with secondary hemorrhage as
compared with 79.5% of patients in whom no rebleeding occurred.
[5, 9]
True
secondary bleeding into the anterior chamber is indicated by an obvious
increase in the amount of blood in the anterior chamber. Secondary
hemorrhage occurs in approximately 25% (range, 7-38%) of all patients with
hyphema.
[5, 9]
The incidence of secondary hemorrhage is higher in hyphemas
classified as Grades 3 and 4.
[6]

With near total to total hyphemas, in which the blood is dark and clotted,
bright red blood often begins to appear at the periphery of the clot on the
fourth day to the sixth day. This probably results from early dissolution of the
clot and does not necessarily indicate a secondary hemorrhage. A large
proportion (33%) of patients younger than 6 years has secondary
hemorrhages; the likelihood of secondary hemorrhages decreases with age.
Secondary hemorrhage usually occurs on the third day or the fourth day, but it
may occur from the second day to the seventh day after trauma.
[5, 14]

Secondary hemorrhage is probably due to lysis and retraction of the clot and
fibrin aggregates that have occluded the initially traumatized vessel.
[9]
The
secondary bleeding may result in increased intraocular pressure and corneal
staining and is associated with a poorer visual prognosis.
[15, 16]

Several studies have documented that secondary hemorrhage occurs more
frequently in African American patients. In 1990, Spoor et al observed
secondary hemorrhage in 24.2% of African American patients and in only
4.5% of white patients.
[17]
Two other studies demonstrated greater rates of
secondary hemorrhage in African American patients that are highly significant
(P < 0.05).
[18, 19]
In the initial systemic aminocaproic acid (ACA) study, African
American patients comprised 66.2% of the population
[9]
; 34% of African
American patients in the placebo group developed secondary hemorrhage,
and 20% of them had positive sickle cell trait by hemoglobin electrophoresis.
There have also been studies showing a higher incidence of rebleeding in
cases of hemophilia.
[20]

Early postsurgical hyphemas can be caused by bleeding from the ciliary body,
from cut ends of the Schlemm canal, from the iris or iris root, and from the
corneoscleral wounds. Wounds located more posteriorly tend to bleed more.
Iris neovascularization can also result in a hyphema due to fragile iris vessels
that can bleed from intraoperative manipulation.
Late-onset postsurgical hyphemas occur from the fine arborizing neovascular
vessels that form in the inner aspect of the cataract incision site. These
vessels are fragile and bleed spontaneously after minor trauma. Hyphemas in
this setting may be caused by posterior chamber intraocular lens (PCIOL)
haptics eroding the ciliary sulcus. Anterior chamber intraocular lens (ACIOL)
haptics also may cause bleeding by chafing the iris surface.
Rubeosis, or iris neovascularization, can also be a source of late
postoperative hyphema.
Uveitis-glaucoma-hyphema (UGH) syndrome is seen weeks to months after
surgery. Postoperative hyphema may also occur after laser procedures.
After ALT, bleeding may occur from an inadvertent laser treatment of the iris
root vessel or from reflux of blood in the Schlemm canal.
After a laser iridotomy, bleeding may occur from an inadvertent laser
treatment of the iris root vessel. The physician should apply pressure with the
focusing lens to reduce the rate of bleeding and the size of hyphema
formation if promptly recognized.

Complications of traumatic hyphema may be directly attributed to the retention of
blood in the anterior chamber. The four most significant complications include
posterior synechiae, peripheral anterior synechiae, corneal bloodstaining, and optic
atrophy.
[9, 21]

Posterior synechiae
Posterior synechiae may form in patients with traumatic hyphema. This complication
is secondary to iritis or iridocyclitis. However, they are relatively rare complications
in patients who are medically treated. Posterior synechiae occur more frequently in
patients who have had surgical evacuation of the hyphema.
Peripheral anterior synechiae
Peripheral anterior synechiae occur frequently in medically treated patients in whom
the hyphema has remained in the anterior chamber for a prolonged period, typically 9
or more days. The pathogenesis of peripheral anterior synechiae may be due to a
prolonged iritis associated with the initial trauma and/or chemical iritis resulting from
blood in the anterior chamber. Alternately, the clot in the chamber angle may
subsequently organize, producing trabecular meshwork fibrosis that closes the angle.
Both mechanisms are likely to be involved.
[5, 9]

Corneal bloodstaining
Corneal bloodstaining primarily occurs in patients with a total hyphema and
associated elevation of intraocular pressure. The following factors may increase the
likelihood of corneal bloodstaining; all of these factors affect endothelial integrity:
Initial state of the corneal endothelium; decreased viability resulting from
trauma or advanced age (eg, cornea guttata)
Surgical trauma to the endothelium
Large amount of formed clot in contact with the endothelium
Prolonged elevation of intraocular pressure
Corneal bloodstaining may occur with low or normal intraocular pressure; rarely, it
may also occur in less than total hyphemas. However, these latter 2 instances
probably can be anticipated only in eyes with a severely damaged or compromised
endothelium. Corneal bloodstaining is more likely to occur in patients who have a
total hyphema that remains for at least 6 days with concomitant, continuous
intraocular pressures of greater than 25 mm Hg.
[5]
Clearing of the corneal bloodstains
may require several or many months. Generally, the corneal bloodstains form
centrally and then spread to the periphery of the corneal endothelium. During
resolution, corneal bloodstaining clears peripherally and then centrally, reversing the
sequence of the initial staining process.
Optic atrophy
Optic atrophy may result from either acute, transiently elevated intraocular pressure
or chronically elevated intraocular pressure; each occurrence was studied in a series
of patients with hyphema in an attempt to identify predisposing factors.
[9, 22]

Nonglaucomatous optic atrophy in patients with hyphema may be due to either the
initial trauma or the transient periods of markedly elevated intraocular pressure.
Diffuse optic pallor (and not glaucomatous cupping) is the result of transient periods
of markedly elevated intraocular pressure. Pallor occurs with constant pressure of 50
mm Hg or higher for 5 days or 35 mm Hg or higher for 7 days.
[5, 9]

The authors have observed numerous patients with sickle cell trait who developed a
nonglaucomatous optic atrophy with relatively low elevations of intraocular pressure
of 35-39 mm Hg for 2-4 days.
[5]
In spite of maximum medical therapy, final visual
acuity was less than 20/400 in all patients. The authors continue to observe optic
atrophy in patients with sickle cell trait who are referred to their institution and who
have not had vigorous control of intraocular pressure and/or delay in paracentesis.
Other studies indicate that patients with sickle cell hemoglobinopathies and anterior
chamber hyphemas have more sickled erythrocytes in their anterior chambers than in
their circulating venous blood.
[23]
The sickled erythrocytes obstruct the trabecular
meshwork more effectively than healthy cells, and a consequent elevation of
intraocular pressure occurs with lesser amounts of hyphema.
Systemic hypotensive agents, such as acetazolamide and methazolamide, may not
always be successful in reducing the intraocular pressure. In fact, they may be
contraindicated in high or repeated dose regimens because of their possible
contribution to intravascular hemoconcentration and increased microvascular
sludging, both of which are detrimental in sickle cell hemoglobinopathy.
The increased intraocular pressure may not be tolerated well in these patients because
of the increased susceptibility to impaired vascular perfusion within the optic nerve
and the retina. Indeed, moderate elevation of intraocular pressure in patients with
sickle cell hemoglobinopathy may produce rapid deterioration of visual function
because of profound reduction of central retinal artery and posterior ciliary artery
perfusion.
[24, 25]
For African American patients, the prevention of secondary
hemorrhage is a critical factor.
Other complications associated with hyphema involve disruption of the posterior
segment. These complications include, but are not limited to, choroidal rupture,
macular scarring, retinal detachment, vitreous hemorrhage, and zonular dialysis. Even
a case of sympathetic ophthalmia following hyphema has been reported
Recognizing that the prognosis for visual recovery is directly related to the
following 3 factors is important:
Amount of associated damage to other ocular structures (ie, choroidal
rupture, macular scarring)
Whether secondary hemorrhage occurs
Whether complications of glaucoma, corneal bloodstaining, or optic atrophy
occur
Treatment modalities should be directed at reducing both the incidence of
secondary hemorrhage and the risk of corneal bloodstaining and optic
atrophy.
The success of hyphema treatment, as judged by the recovery of visual
acuity, is good in approximately 75% of patients. Approximately 80% of those
with less than one third filling of the anterior chamber regain visual acuity of
20/40 (6/12) or better. Approximately 60% of those with a hyphema occupying
greater than one half but less than total of the anterior chamber regain visual
acuity of 20/40 (6/12) or better, while only approximately 35% of those with an
initially total hyphema or a Grade 4 hyphema have good visual results.
Approximately 60% of patients younger than 6 years have good visual results;
older age groups have progressively higher percentages of good visual
recovery.
The severity of the trauma is frequently related to the final visual outcome.
Lens opacities, choroidal rupture, vitreous hemorrhage, angle-recession
glaucoma, secondary macular edema, and retinal detachment are commonly
associated with traumatic hyphema, compromising the final visual result.
Of patients with hyphema, 14% have poor visual results from associated
trauma, including such complications as glaucoma, vitreous hemorrhage,
retinal detachment, choroidal rupture, or scleral rupture. Poor visual outcome
in traumatic hyphema can be directly attributed to the hyphema in 11% of
patients
[22, 9]
; the poor visual outcome is usually the result of secondary
hemorrhage associated with optic atrophy or corneal bloodstaining.
For excellent patient education resources, visit eMedicineHealth's Eye and
Vision Center. Also, see eMedicineHealth's patient education
articles Hyphema (Bleeding in Eye) and Eye Injuries.
Lab studies
In African American patients, a sickle cell prep should be ordered if a hyphema is
seen because the presence of a hyphema in patients with sickle cell trait or disease can
produce significant ocular complications. Sickled red blood cells can more easily
obstruct the trabecular meshwork and result in a high IOP, even in the presence of a
relatively small hyphema. In addition, ischemic complications of the retina and the
optic nerve are greater in patients with sickle cell trait and disease.
A hemoglobin electrophoresis is also helpful. It helps distinguish sickle cell trait from
disease once the sickle cell prep is positive.
Imaging studies
Infrequently, a B-scan and/or a CT scan may be necessary to rule out anintraocular
tumor or a foreign body if a thorough examination is not possible and the reasons for
postoperative hyphema are not clear.
Other tests
Rarely, an iris fluorescein angiogram may be needed if early iris neovascularization is
suspected as an underlying cause of the hyphema.
Gonioscopy
Examination of the angle structures is critical to understanding the extent of the blunt
trauma precipitating a hyphema. This can be delayed until after the critical 5-day,
high-risk, re-bleed period, particularly dynamic gonioscopy. Angle abnormalities,
synechiae, and recession may commonly be found. Rarely, a focus of bleeding can be
photocoagulated with the argon laser on low-power settings, up to 300 mW with a
200-m spot size.
The customary treatment of patients with traumatic hyphema has included
hospitalization, bed rest, bilateral patching, topical cycloplegics, topical
steroids, systemic steroids, and sedation.
[27]
However, studies have not
indicated that rigidly following this regimen is necessary to achieve acceptable
therapeutic results. These studies provide evidence that no statistically
significant difference exists in most areas of comparison between patients
treated with bed rest, bilateral patches, and sedation and those treated with
ambulation, a patch and shield on the injured eye only, and no sedation.
[9, 28,
29, 30]
The authors recommend ambulation and a patch and shield for the
injured eye. Sedation is recommended only in the extremely apprehensive
individual. Hospitalization may be warranted in cases of severe trauma and
rebleeding.
If analgesics are required for pain relief, acetaminophen (Tylenol) with or
without codeine, depending on the severity of the pain, is preferred. The
antiplatelet effect of aspirin tends to increase the incidence of rebleeding in
patients with traumatic hyphema and should be strictly
avoided.
[15]
Nonsteroidal anti-inflammatory drugs (NSAIDs) with analgesic
activity, such as mefenamic acid (Ponstel) or naproxen (Aleve), share this
deleterious antiplatelet effect.
In any therapeutic regimen, the injured globe requires adequate protection
with a patch and shield.
[31]
Elevating the head of the bed 30-45 facilitates
settling of the hyphema in the inferior anterior chamber and aids in classifying
the hyphema. Inferior settling facilitates more rapid improvement of visual
acuity, earlier evaluation of the posterior pole, and greater clearing of the
anterior chamber angle. A better estimate of the decrease or increase in the
amount of blood in the anterior chamber is also possible during subsequent
biomicroscope examinations.
Various topical medications have been recommended for treating patients
with traumatic hyphema, including cycloplegics for traumatic iridocyclitis and
miotics to increase the surface area of the iris to enhance resorption of the
hyphema.
[16, 32, 33]
Topical corticosteroids and estrogens
[33, 34]
have been
recommended with contradictory results.
[34]

Investigations conducted by the authors of patients with traumatic hyphema
excluded the use of topical medications because of a lack of definite evidence
of their advantages.
[5, 22]
One recommendation regarding topical medication is
that the topical use of steroids after the third day or the fourth day of retained
hyphema may be advantageous to decrease the associated iridocyclitis and
to prevent or deter the development of peripheral anterior synechiae or
posterior synechiae. Secondly, topical atropine (1%) is indicated in hyphemas
occupying more than 50% of the anterior chamber to break the pupillary
block.
Several double-masked studies clearly establish the value of systemic
aminocaproic acid (ACA, AMICAR) in the prevention of recurrent
hemorrhages.
[5, 35]
If secondary hemorrhages are the result of lysis and
retraction of a clot that has produced an occlusion of the traumatized vessel,
then prevention of normally occurring clot lysis for 5-6 days should be
advantageous to allow the injured blood vessel to more completely repair its
integrity.
[5]
The antifibrinolytic activity of ACA given systemically has been
demonstrated in other areas of the body to decrease the incidence of
secondary hemorrhage.
ACA retards clot lysis by preventing plasmin from binding to the lysine in the
fibrin clot. As a lysine analog, ACA competitively inactivates plasmin by
occupying the site on plasmin that would normally bind to fibrin. In a similar
manner, ACA binds to plasminogen, so that when activated to plasmin, it
cannot attach to fibrin.
When ACA was administered orally in a dosage of 100 mg/kg every 4 hours
for 5 days, a statistically significant reduction in the incidence of rebleeding of
traumatic hyphemas was observed.
[5]
Systemic ACA should be used in
hyphemas occupying 75% or less of the anterior chamber because the clot
may persist in the anterior chamber for an increased period during
administration of the drug. The continued retention of the clot in the anterior
chamber could be a potential disadvantage with larger Grade 4 hyphemas.
In a prospective study by the authors, as well as 2 additional studies, patient
groups treated with ACA and placebo were randomized and double-
masked.
[5, 18, 36, 35]
In the ACA-treated group, the incidence of secondary
hemorrhage varied 3-4%.
[5, 18, 36, 35]
In the placebo-treated group, the incidence
was 28-33%. ACA in a dosage of 50 mg/kg every 4 hours is equally as
effective as 100 mg/kg every 4 hours, orally, for 5 days.
[18]
The total dosage of
ACA should not exceed 30 grams per day.
Systemic ACA should not be used in patients who are pregnant or those with
renal or hepatic insufficiency.
Since systemic ACA significantly reduces the incidence of secondary
hemorrhage, a topical preparation could decrease the incidence of adverse
effects. By concentrating the drug in the aqueous humor, a topical preparation
would decrease the systemic concentration of ACA associated with many of
the adverse effects.
For systemically administered ACA to be effective, it must penetrate into 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.
[37]
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.
[38]
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.
[39]
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.
[40]
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.
[41]
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.
[42]
However, a study concluded
ACA was beneficial in treating patients with hyphema.
[43]

The authors established a prospective, multicenter, double-masked,
randomized clinical trial comparing oral and topical ACA.
[44]

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.
[44]

Topical ACA 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.
Although not approved for ophthalmic use in the United States, another lysine
analog, tranexamic acid, also has antifibrinolytic properties. In a series of
children treated with tranexamic acid (25 mg/kg/d), the incidence of secondary
hemorrhage was significantly reduced.
[45]
Like ACA, tranexamic acid has been
associated with nausea, vomiting, and hypotension. Unlike ACA, tranexamic
acid is associated with visual abnormalities, which could complicate the
ophthalmologic evaluation of the patient. In addition, some patients in this
study were treated with other drugs, including topical steroids. One study
found that tranexamic acid was better than oral steroids in preventing
rebleeding rates.
[46]
A meta-analysis of hyphema literature determined
antifibrinolytics had a significant impact on hyphema rebleeding.
[47]
The
authors suggested antifibrinolytics use in patients at high risk for associated
hyphema complications.
Other investigators have suggested that systemic steroids decrease the
incidence of secondary hemorrhage. Initial studies supporting this claim were
neither randomized nor double-masked.
[32, 48]
In 1980, a randomized, double-
masked, prospective study by Spoor and associates observed a secondary
hemorrhage rate of 20% in controls and 13% in treated patients, which was
not statistically significant.
[17]
In 1991, Farber and colleagues compared
treatment with oral ACA with oral prednisone in a well-controlled trial.
[49]
Their
study suggested that both drugs decrease the incidence of secondary
hemorrhage by a similar amount, albeit by different mechanisms. Because of
the small number of rebleeds, the confidence limits were large and may have
masked a real difference.
Other studies have recommended oral steroids combined with traditional
treatments to reduce rebleeding rates.
[46, 31]
A randomized, comparative study
of ACA versus oral steroids found no significant difference in the outcomes
between the 2 treatments.
[49]

The major difficulty with this study was that controls were not used. The lack
of a true control population is unfortunate in comparing the 2 groups. In
addition, the study excluded all patients with sickle cell trait. These patients
are one group that should be considered for systemic ACA or systemic
corticosteroid treatment. In addition, patients with gastric ulcer or diabetes
mellitus and those who were intoxicated or had bleeding were excluded. The
mode of action of prednisone is unclear and may be related to an anti-
inflammatory influence on traumatized blood vessels with reduced
engorgement and a propensity for rebleeding. Additional randomized studies
with controls would be extremely helpful in determining whether or not a
significant reduction of secondary hemorrhage occurs with systemic
prednisone in comparison with systemic ACA.
Some studies have investigated the application of intracameral tissue
plasminogen activator (t-PA) in the management of traumatic
hyphema.
[50]
However, these studies have been neither large nor randomized.
A potential problem with t-PA is the associated risk of rebleeding of the initial
wound.
Application of t-PA has been considered in resolving hyphemas that either fail
to clear spontaneously or are associated with malignant intraocular
pressure,
[51]
although the actual timing of t-PA administration from the initial
injury has yet to be determined.
Topical antiglaucomatous medications usually lower intraocular pressure.
With the advent of newer glaucoma modalities, initiating therapy incrementally
with brimonidine tartrate (Alphagan, Allergan), followed by latanoprost
(Xalatan, Pharmacia) and timolol maleate (Timoptic-XE, Merck), is
recommended. If intraocular pressure is still elevated, a topical carbonic
anhydrase inhibitor should be added. In patients with sickle cell trait or sickle
cell disease, methazolamide and topical beta-blockers should be
substituted.
[8, 52]

If intraocular pressure is still uncontrolled, systemic medication should be
given during the acute phase of the hyphema. Acetazolamide (20 mg/kg/d)
may be administered in 4 divided doses for intraocular pressure of greater
than 22 mm Hg. However, acetazolamide can increase the concentration of
anterior chamber ascorbate, lower the pH of human plasma, and exacerbate
sickling of erythrocytes. Therefore, methazolamide (10 mg/kg/d), administered
in 4 divided doses, is preferred in pediatric patients with sickle cell trait or
sickle cell disease.
[5, 23]

Osmotic agents (preferably mannitol) should be considered for intraocular
pressure above 35 mm Hg in spite of topical medications. Orally administered
glycerol is effective; however, nausea and vomiting are often associated with
its administration in patients with elevated intraocular pressure. Mannitol is
administered intravenously, 1.5 g/kg (usually in a 10% solution), over a period
of approximately 45 minutes. This agent may be given 2 times a day (or every
8 hours in patients with extremely high pressure) in attempt to keep the
intraocular pressure below 35 mm Hg. Renal output, blood urea nitrogen, and
electrolyte values should be monitored in all patients in whom such therapy is
continued for several days.
With increasing emphasis on cost containment, outpatient management of
hyphema has become more popular in recent years. Several studies have
demonstrated no significant difference in final visual acuities in patients with
smaller hyphemas treated at home or those treated in hospitals.
[53, 41, 54, 55, 35,
56]

Microhyphemas can be treated on an outpatient basis, unless secondary
hemorrhage occurs or elevated intraocular pressure is uncontrolled. Patients
with traumatic hyphema occupying less than one third of the anterior chamber
can be treated on an outpatient basis with systemic or topical ACA. If the
hyphema occupies more than one third of the anterior chamber, intraocular
pressure is elevated beyond 30 mm Hg, or both, hospitalization is
recommended. The decision to hospitalize also depends on the cooperation
of the patient, family members, and the extent of ocular injury. For outpatients,
daily ocular examinations, including an evaluation of the amount of hyphema
and intraocular pressure, should be performed. Daily ophthalmic sketches are
helpful in estimating the amount and the rate of resolution or rebleeding.
Applanation tonometry must be performed at least once daily and twice daily
in patients with elevated intraocular pressures.
Minimal bloodstaining is often difficult to detect against a background of blood
in the anterior chamber. Under such circumstances, the cornea often
assumes a yellowish cast, which is reflected from the yellowish fibrinous
coagulum in the anterior chamber. The most typical early sign of corneal
bloodstaining is the presence of tiny yellowish granules that initially appear in
the posterior third of the corneal stroma. An additional finding is a lack of
definition or a blurred appearance of the ordinarily sharply defined fibrillar
structure of the involved corneal stroma. The latter is independent of the
yellowish color transmitted to the stroma by the contents of the anterior
chamber.
The authors have found this sign to be useful in recognizing the very early
stages of corneal bloodstaining. These biomicroscopic signs of corneal
bloodstaining usually precede gross staining by only 24-36 hours. Surgical
treatment in this early stage may prevent gross staining, and the cornea may
clear in 4-6 months. However, once grossly visible staining develops, many
months may elapse before clearing is complete.
Generally, medical management seems to produce the best visual results for
patients with less than total hyphemas. Certainly, other causes of
inflammation or bleeding should be ruled out, particularly when the history of
trauma is questionable.
[57]

For several reasons, surgical management is fraught with
complication.
[35]
First, surgery is chosen for the most severe presentations of
hyphema, thus selecting out the most difficult cases. Surgical intervention is
rarely indicated for hyphemas that occupy less than one half of the anterior
chamber; these lesser hyphemas (either primary or secondary) usually
resolve spontaneously under any medical regimen and require no surgical
intervention.
In 2 prospective series totaling 196 patients, no corneal bloodstaining or optic
atrophy was noted in hyphemas of 50% or less.
[5, 9]
Corneal bloodstaining,
with rare exceptions, only occurs in patients with hyphemas that are total at
some time during their course. The results of surgical evacuation to improve
secondary glaucoma in small hyphemas (75% or less) are disappointing. The
ocular hypertension in these instances results more frequently from damage
to the trabecular structures than from plugging by red cells and fibrin. Surgical
evacuation in these instances may produce only temporary postsurgical
hypotony, with a rapid return to preoperative intraocular pressure.
The authors believe that most hyphemas, including total hyphemas, should be
medically treated for the first 4 days. Spontaneous resolution of the hyphema
occurs quite rapidly during this period, and these cases have the best
prognosis. In one series of 20 eyes with total hyphemas, 4 of these 20 eyes
(20%) cleared sufficiently by day 4 to rule out surgery.
[22]
An additional 4 eyes
resolved spontaneously on medical treatment over a longer period.
Surgical intervention is usually indicated on or after the fourth day. Overall,
indications for surgical intervention are outlined below.
[5, 22]

Four days after onset of total hyphema
Microscopic corneal bloodstaining (at any time)
Total hyphema with intraocular pressures of 50 mm Hg or more for 4 days
(to prevent optic atrophy)
Total hyphemas or hyphemas filling greater than 75% of the anterior
chamber present for 6 days with pressures of 25 mm Hg or more (to prevent
corneal bloodstaining)
Hyphemas filling greater than 50% of the anterior chamber retained longer
than 8-9 days (to prevent peripheral anterior synechiae)
In patients with sickle cell trait or sickle cell disease who have hyphemas of
any size that are associated with intraocular pressures of greater than 35
mm Hg for more than 24 hours
If intraocular pressure remains elevated at 50 mm Hg or more for 4 days,
surgery should not be delayed. One study noted optic atrophy in 50% of
patients with total hyphemas when surgery was delayed. Corneal
bloodstaining occurred in 43% of patients.
[58]

Patients with sickle cell hemoglobinopathies and even those with sickle cell
trait require surgical intervention if intraocular pressure is not controlled within
24 hours.
[5, 23]

Surgery for patients with hyphema should be cautiously approached. In 2
series involving 196 patients, surgery was performed in only 14 patients
(7.1%).
[5, 9]
Risks of surgery include damage to the corneal endothelium, the
lens, and/or the iris; prolapse of the intraocular contents; rebleeding; and
increased synechiae formation. With the exception of patients with sickle cell
trait, no patients in these series required surgery if the hyphema occupied less
than 50% of the anterior chamber. Total hyphema evacuation by vitrectomy
instrumentation, peripheral iridectomy, and trabeculectomy has been
recommended.
Generally, the authors recommend the type of surgical intervention with which
the surgeon is most familiar. Hyphema surgery should be preceded by
intravenous acetazolamide and mannitol if the intraocular pressure is
elevated. The operation should be performed under general anesthesia in all
patients. The operating microscope should be used in all instances. Presently,
the 4 major approaches include the following:
Hyphema evacuation with closed vitrectomy instrumentation
Paracentesis
Irrigation and aspiration through a small incision
Clot irrigation with trabeculectomy
Currently, the preferred technique is evacuation of the hyphema with
vitrectomy instrumentation. The initial clear corneal incision is made with a
diamond blade. To avoid both the iris and the lens, the blade is oriented and
pushed into the anterior chamber in such a manner that it is parallel to the
plane of the iris. A 20-gauge Ocutome or similar guillotine instrument,
attached to an infusion line of balanced salt solution plus (BSS-Plus), is gently
placed into the anterior chamber. The bottle of BSS-Plus should be 30-40 cm
above the eye to maintain normal intraocular pressure. With the Ocutome
cutting port half open and the infusion line in place, irrigating and aspirating
free blood from the formed clot are possible. The suction mode is initially set
at 4, and the cutting speed is set at 150 for the procedure. An anterior
chamber maintainer can help stabilize fluctuations in intraocular pressure
during clot evacuation.
[59]

Extreme care is required to avoid any contact with the iris, the lens, or the
corneal endothelium. Directing the guillotine port anteriorly and keeping the
port in view at all times generally avoids intraoperative uveal tissue injury.
This operative procedure is used to remove the central portion of the clot.
Removing the entire clot in the periphery of the anterior chamber is not
necessary.
If a secondary hemorrhage occurs during the operative procedure, the
authors recommend tamponade of the bleeding by elevation of the infusion
bottle to approximately 70 cm above the eye for several minutes. If the
bleeding continues, filling the anterior chamber with an air bubble after
evacuating the clot is helpful. If bleeding persists, bimanual bipolar diathermy
is extremely helpful when the bleeding site is visible.
[60]
At the end of the
surgical procedure, filling the anterior chamber with an air bubble is helpful.
This also helps to control any secondary bleeding. The corneal incision is
closed with two 10-0 nylon sutures. The response in lowering intraocular
pressure with the Ocutome instrumentation has been quite successful. Each
eye operated on with this technique has shown an initial decrease in
intraocular pressure associated with the surgery.
Paracentesis causes little surgical trauma and relieves the elevated
intraocular pressure. Paracentesis is especially beneficial in patients with
sickle cell trait or sickle cell disease. However, the decrease in intraocular
pressure may be transient, and appreciable reduction may not occur in the
amount of the formed clot.
Irrigation by a single or double needle technique has the advantage of a small
incision. The authors prefer using a diamond blade and entering at the 1-
o'clock position in the right eye and at the 11-o'clock position in the left eye.
The entry should be through clear cornea. The irrigating needle should extend
just through the corneal endothelium, and a slow push-pull maneuver with the
single needle technique washes out the erythrocytes from the anterior
chamber clot, often leaving the fibrin matrix. To reduce the likelihood of
rebleeding during the operative procedure, care should be undertaken not to
produce violent alterations in the anterior chamber pressure. If rebleeding
does occur, an air bubble can be effectively introduced for tamponade. After a
5-minute wait, irrigation maneuvers can be resumed. Using the single or
double needle technique, the surgeon must be particularly careful to have
direct visualization of the anterior chamber.
This technique has some disadvantages. Sometimes, maintaining the position
of the needle tip in the anterior chamber during the procedure is difficult. A
hazardous situation is created when the collar-button type of formed clot
occupies both the anterior and posterior chambers. This produces pupillary
block with anterior displacement of the iris-lens diaphragm.
Generally, trabeculectomy is not used in smaller hyphemas. However, in
patients with total hyphema, trabeculectomy with peripheral iridectomy should
be considered. Trabeculectomy is performed with gentle irrigation of the
anterior chamber hyphema. This surgery is relatively safe and should be
performed early for patients with total hyphema unless the elevated
intraocular pressure is medically controlled and resolution of the hyphema is
clearly imminent.
The authors currently perform trabeculectomy on patients with total hyphema
persisting to day 4 and find it superior to clot evacuation. Several patients
referred to the authors' institution have had attempts at clot evacuation. One
patient sustained complete iridodialysis related to attempted clot evacuation.
In addition, the authors have treated other patients who have been referred
after optic atrophy developed with total hyphemas.
When trabeculectomy is performed, the authors use a partial-thickness
lamellar technique. Superficial episcleral vessels are coagulated with the
bipolar cautery. A superficial lamellar flap is developed through one-third
scleral thickness, creating a 3 X 3-mm trap door hinged at the limbal area. A 1
X 4-mm window through the scleral root and the trabecular meshwork into the
anterior chamber is fashioned with a diamond knife. Peripheral iridectomy is
performed, followed by gentle irrigation of the clot in the area of the
trabeculectomy site. Two 10-0 nylon scleral flap sutures are used to close the
trabeculectomy site. First the Tenon capsule and then the conjunctiva are
closed with a running 8-0 or 9-0 Vicryl suture in a layered, anatomical fashion.
Once the conjunctiva has healed, the nylon scleral suture(s) can be lasered to
open up the trabeculectomy site (when necessary). This technique has been
invaluable in difficult total hyphema cases.
Topically applied mitomycin-C may be a useful adjunct in the prevention of
long-term trabeculectomy failure, particularly in patients with trauma and,
therefore, a predisposition to inflammation.
Because each of these surgical procedures has its own set of complications,
the surgeon should approach each patient with caution and individualize the
surgical strategy. Postoperative care should include meticulous control of
nausea and emesis to avoid significant fluctuations in intraocular pressure.
Postoperative hyphemas may be seen at the time of surgery or within the first
2-3 days after surgery. If bleeding is identified intraoperatively, it must be
identified and coagulated if it does not cease on its own. The surgeon can
reduce postsurgical hyphemas by creating internal sclerostomy as anteriorly
as possible to reduce bleeding during filtration surgery. In uveitis-glaucoma-
hyphema (UGH) syndrome associated with archaic design anterior chamber
IOLs and sulcus posterior chamber IOLs, the treatment may require removal
of the lens that is causing the problem and replacing it with another lens.

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