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    Postinjury accumulation of blood in the anterior chamber is one of the mostchallenging clinical problems encountered by the ophthalmologist. Even asmall hyphema can be a sign of major intraocular trauma with associateddamage to vascular and other intraocular tissues.

    Blunt trauma to the eyemay result in injury to the iris, papillary sphincter,angle structures, lens, zonules, retina, vitreous, optic nerve, and otherintraocular structures. Blunt trauma associated with a rapid, marked elevationin intraocular pressure with sudden distortion of intraocular structuresproduces the dynamic changes responsible for hyphema formation.

    The lack of an ideal therapeutic program, the potential for secondaryhemorrhage, and the secondary onset ofglaucomaall threaten to turn an eyewith an initially good visual prognosis into a complex therapeutic problem witha poor final visual result.

    Classification and characteristics

    Traumatic hyphema is encountered in children and adults. Hyphema isusually the result of a projectile or deliberate punch that hits the exposedportion of the eye despite the protection of the bony orbital rim. Variousmissiles and objects have been incriminated, including balls, rocks, projectiletoys, 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 pelletshave been made of plastic polymers. There have even been cases involvingobjects larger than the orbit, such as soccer balls.[4] Slow motion photographyhas demonstrated deformation of the soccer balls as impact occurs with theorbital rim, thereby causing the hyphema. With the increase of child abuse,

    fists and belts have started to play a prominent role. Males are involved inthree fourths of cases.[5, 6]

    Hyphema can also occur intraoperatively or postoperatively. Surgicalhyphema is a known complication of intraocular surgery and should bemanaged in a similar manner as traumatic hyphema.

    Rarely, spontaneous hyphemas may occur and be confused with traumatichyphemas. Spontaneous hyphemas are secondary to neovascularization (eg,diabetes mellitus, ischemia, cicatrix formation), ocular neoplasms (eg,retinoblastoma), uveitis, and vascular anomalies (eg, juvenilexanthogranuloma). Vascular tufts that exist at the pupillary border have beenimplicated 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 anteriorchamber

    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

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    Most hyphemas fill less than one third of the anterior chamber. Whenhyphemas are divided into 4 groups according to the amount of filling of theanterior chamber, 58% involve less than one third of the anterior chamber,20% involve one third to one half of the anterior chamber, 14% involve onehalf 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 mayportend a poor outcome and corneal staining.

    An alternative method of grading hyphemas involves measuring (inmillimeters) the hyphema from the inferior 6-o'clock limbus. This method mayhelp in monitoring the progress of resolution or the occurrence of rebleeding.Digital imaging analysis is also useful and objective but is available in only afew research or academic facilities.

    The cause of an anterior chamber hemorrhage in contusion injuries is thoughtto be related to the posterior displacement of tissue or to the resultant fluidwave in the aqueous humor and the vitreous. This sudden dynamic shiftstretches the limbal vessels and displaces the iris and the lens. Thisdisplacement may result in a tear at the iris or the ciliary body, usually at theangle structures.[8]A tear at the anterior aspect of the ciliary body is the mostcommon site of bleeding and occurs in about 71% of cases.[9] The blood exitsfrom the anterior chamber via the trabecular meshwork and the Schlemmcanal or the juxtacanalicular tissue.

    The usual duration of an uncomplicated hyphema is 5-6 days. The meanduration of elevated intraocular pressure is 6 days.

    Pathophysiology

    Hyphema describes the condition of the aqueous humor when red blood cellsform a suspension in it.

    The choroid and the iris contain a rich complex of vessels. The pupil isoutlined and controlled by a complex set of iridial muscles, sphincters, anddilators. These muscles can be ruptured by sharp and/or blunt trauma. This isa frequent source of intraocular hemorrhage (hyphema). In addition, the irisroot and/or the ciliary spur is a common location of bleeding from blunttrauma.

    Surgical intervention into the eye for anterior segment procedures isaccomplished routinely through various approaches. The most commonlyused approaches in modern small incision surgery are via the limbus and/orthe clear cornea. Clear cornea surgery markedly reduces the risk of bleedingfrom limbal vessels since the cornea in its healthy state is avascular. Scleraltunnel incision is subject to unpredictable hemorrhage, and the incision mustbe 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 peripheraliridectomy, cataract extraction, cyclodialysis, and filtration procedure (laser

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    peripheral iridectomy, especially with YAG laser than with argon laser; argonlaser trabeculoplasty [ALT] not very common)

    Early postoperative bleeding (a traumatized uveal vessel that was in spasmand suddenly dilates; conjunctival bleeding that makes its way into theanterior chamber via a corneoscleral wound or sclerostomy)

    Late postoperative bleeding (new vessels growing across the corneoscleralwound that bleed when manipulated; a uveal wound that is reopened; anintraocular lens [IOL] that causes chronic iris erosion)

    Frequency

    In the United States, the incidence of hyphema is 17-20 per 100,000 peopleper 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 inapproximately 32% of all patients with hyphemas at some time during theircourse.[9] Higher, more prolonged elevations of intraocular pressure are more

    commonly associated with near total or total hyphemas. Patients predisposed

    http://emedicine.medscape.com/article/1195788-overviewhttp://emedicine.medscape.com/article/1195788-overviewhttp://emedicine.medscape.com/article/783223-overviewhttp://emedicine.medscape.com/article/783223-overviewhttp://emedicine.medscape.com/article/1209681-overviewhttp://emedicine.medscape.com/article/1209681-overviewhttp://emedicine.medscape.com/article/1194480-overviewhttp://emedicine.medscape.com/article/1194480-overviewhttp://emedicine.medscape.com/article/1190564-overviewhttp://emedicine.medscape.com/article/1190564-overviewhttp://emedicine.medscape.com/article/1208487-overviewhttp://emedicine.medscape.com/article/1208487-overviewhttp://emedicine.medscape.com/article/1208624-overviewhttp://emedicine.medscape.com/article/1208624-overviewhttp://emedicine.medscape.com/article/1222849-overviewhttp://emedicine.medscape.com/article/1222849-overviewhttp://emedicine.medscape.com/article/1208706-overviewhttp://emedicine.medscape.com/article/1208706-overviewhttp://emedicine.medscape.com/article/1208706-overviewhttp://emedicine.medscape.com/article/1222849-overviewhttp://emedicine.medscape.com/article/1208624-overviewhttp://emedicine.medscape.com/article/1208487-overviewhttp://emedicine.medscape.com/article/1190564-overviewhttp://emedicine.medscape.com/article/1194480-overviewhttp://emedicine.medscape.com/article/1209681-overviewhttp://emedicine.medscape.com/article/783223-overviewhttp://emedicine.medscape.com/article/1195788-overview
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    to glaucoma or with preexisting glaucoma and decreased facility of trabecularoutflow are also more likely to developglaucoma with a hyphema.

    These highly elevated intraocular pressures occur during the acute phase ofthe hyphema and are separate from those related toangle recession.[11] In

    patients with pressure elevations, abnormal tonometric readings arefrequently detected during the first 24 hours after injury. This initial period ofelevated intraocular pressure is often followed by a period of normal or belownormal pressure from the second day to the sixth day. Careful monitoring ofthe intraocular pressure is important and may determine the course oftreatment.[12] The early period of elevated intraocular pressure is probably theresult of trabecular plugging by erythrocytes and fibrin. The following period ofreduced pressure is most likely due to reduced aqueous production anduveitis, and it may actually increase the chance of secondary hemorrhage.This period of hypotony is commonly followed by a subsequent rise inintraocular pressure, probably coincidental with the recovery of the

    ciliarybody.

    Intraocular hypertensionthen subsides with recovery of the trabecularmeshwork and disappearance of the hyphema.

    Exceptions include patients with a hyphema occupying greater than 75% ofthe anterior chamber and those with a total hyphema, in whom pressureelevation frequently has its onset simultaneously with the initial hyphema andremains continually elevated until the hyphema has had considerableresolution. When large segments of the anterior chamber angle areirreparably damaged and/or when organization of the fibrin or clot producesextensive peripheral anterior synechiae, the intraocular hypertensioncontinues, becoming intractable glaucoma.

    Ghost cell glaucoma with hyphema and vitreous hemorrhage may causeelevated intraocular pressure 2 weeks to 3 months after the initialinjury.[13] Gradual clearing of the hyphema occurs, with erythrocytes losinghemoglobin and becoming so-called ghost cells in the vitreous cavity. Theghost cells then circulate forward into the anterior chamber, with resultanttrabecular blockage due to the distorted, bulky configuration of the crenatedred blood cell. Considerable delayed elevation of intraocular pressure mayoccur with ghost cell glaucoma, particularly in patients with poor facility ofoutflow.

    Secondary bleeding into the anterior chamber results in a markedly worseprognosis. Eventual visual recovery to a visual acuity of 20/50 (6/15) or betteroccurs in approximately 64% of patients with secondary hemorrhage ascompared with 79.5% of patients in whom no rebleeding occurred.[5, 9] Truesecondary bleeding into the anterior chamber is indicated by an obviousincrease in the amount of blood in the anterior chamber. Secondaryhemorrhage occurs in approximately 25% (range, 7-38%) of all patients withhyphema.[5, 9] The incidence of secondary hemorrhage is higher in hyphemasclassified as Grades 3 and 4.[6]

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    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 thefourth day to the sixth day. This probably results from early dissolution of theclot and does not necessarily indicate a secondary hemorrhage. A largeproportion (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 itmay 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 andfibrin aggregates that have occluded the initially traumatized vessel.[9] Thesecondary bleeding may result in increased intraocular pressure and cornealstaining and is associated with a poorer visual prognosis.[15, 16]

    Several studies have documented that secondary hemorrhage occurs morefrequently in African American patients. In 1990, Spoor et al observedsecondary hemorrhage in 24.2% of African American patients and in only4.5% of white patients.[17] Two other studies demonstrated greater rates ofsecondary hemorrhage in African American patients that are highly significant(P < 0.05).[18, 19] In the initial systemic aminocaproic acid (ACA) study, AfricanAmerican patients comprised 66.2% of the population[9] ; 34% of AfricanAmerican 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 incases 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 thecorneoscleral wounds. Wounds located more posteriorly tend to bleed more.

    Iris neovascularization can also result in a hyphema due to fragile iris vesselsthat can bleed from intraoperative manipulation.

    Late-onset postsurgical hyphemas occur from the fine arborizing neovascularvessels that form in the inner aspect of thecataractincision site. Thesevessels are fragile and bleed spontaneously after minor trauma. Hyphemas inthis 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 latepostoperative hyphema.

    Uveitis-glaucoma-hyphema (UGH) syndrome is seen weeks to months aftersurgery. Postoperative hyphema may also occur after laser procedures.

    After ALT, bleeding may occur from an inadvertent laser treatment of the irisroot vessel or from reflux of blood in the Schlemm canal.

    After a laser iridotomy, bleeding may occur from an inadvertent lasertreatment of the iris root vessel. The physician should apply pressure with the

    focusing lens to reduce the rate of bleeding and the size of hyphemaformation if promptly recognized.

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    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 synechiaeoccur 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 pressureCorneal 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 formcentrally 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 atrophymay 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

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    Approximately 60% of patients younger than 6 years have good visual results;older age groups have progressively higher percentages of good visualrecovery.

    The severity of the trauma is frequently related to the final visual outcome.

    Lens opacities, choroidal rupture, vitreous hemorrhage, angle-recessionglaucoma, secondary macular edema, and retinal detachment are commonlyassociated with traumatic hyphema, compromising the final visual result.

    Of patients with hyphema, 14% have poor visual results from associatedtrauma, including such complications as glaucoma, vitreous hemorrhage,retinal detachment, choroidal rupture, or scleral rupture. Poor visual outcomein traumatic hyphema can be directly attributed to the hyphema in 11% ofpatients[22, 9] ; the poor visual outcome is usually the result of secondaryhemorrhage associated with optic atrophy or corneal bloodstaining.

    For excellent patient education resources, visit eMedicineHealth'sEye and

    Vision Center. Also, see eMedicineHealth's patient educationarticlesHyphema (Bleeding in Eye)andEye 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 withsickle cell trait or diseasecan

    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 fromdisease once the sickle cell prep is positive.

    Imaging studies

    Infrequently, a B-scan and/or a CT scan may be necessary to rule out an intraocular

    tumor or a foreign bodyif 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, topicalsteroids, systemic steroids, and sedation.[27] However, studies have not

    http://www.emedicinehealth.com/collections/SU311.asphttp://www.emedicinehealth.com/collections/SU311.asphttp://www.emedicinehealth.com/collections/SU311.asphttp://www.emedicinehealth.com/collections/SU311.asphttp://www.emedicinehealth.com/articles/13637-1.asphttp://www.emedicinehealth.com/articles/13637-1.asphttp://www.emedicinehealth.com/articles/13637-1.asphttp://www.emedicinehealth.com/articles/14478-1.asphttp://www.emedicinehealth.com/articles/14478-1.asphttp://www.emedicinehealth.com/articles/14478-1.asphttp://emedicine.medscape.com/article/1918423-overviewhttp://emedicine.medscape.com/article/1918423-overviewhttp://emedicine.medscape.com/article/1918423-overviewhttp://emedicine.medscape.com/article/1230338-overviewhttp://emedicine.medscape.com/article/1230338-overviewhttp://emedicine.medscape.com/article/1230338-overviewhttp://emedicine.medscape.com/article/1230338-overviewhttp://emedicine.medscape.com/article/1230338-overviewhttp://emedicine.medscape.com/article/1918423-overviewhttp://www.emedicinehealth.com/articles/14478-1.asphttp://www.emedicinehealth.com/articles/13637-1.asphttp://www.emedicinehealth.com/collections/SU311.asphttp://www.emedicinehealth.com/collections/SU311.asp
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    indicated that rigidly following this regimen is necessary to achieve acceptabletherapeutic results. These studies provide evidence that no statisticallysignificant difference exists in most areas of comparison between patientstreated with bed rest, bilateral patches, and sedation and those treated withambulation, 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 theinjured eye. Sedation is recommended only in the extremely apprehensiveindividual. Hospitalization may be warranted in cases of severe trauma andrebleeding.

    If analgesics are required for pain relief, acetaminophen (Tylenol) with orwithout codeine, depending on the severity of the pain, is preferred. Theantiplatelet effect of aspirin tends to increase the incidence of rebleeding inpatients with traumatic hyphema and should be strictlyavoided.[15] Nonsteroidal anti-inflammatory drugs (NSAIDs) with analgesicactivity, such as mefenamic acid (Ponstel) or naproxen (Aleve), share this

    deleterious antiplatelet effect.

    In any therapeutic regimen, the injured globe requires adequate protectionwith a patch and shield.[31] Elevating the head of the bed 30-45 facilitatessettling of the hyphema in the inferior anterior chamber and aids in classifyingthe hyphema. Inferior settling facilitates more rapid improvement of visualacuity, earlier evaluation of the posterior pole, and greater clearing of theanterior chamber angle. A better estimate of the decrease or increase in theamount of blood in the anterior chamber is also possible during subsequentbiomicroscope examinations.

    Various topical medications have been recommended for treating patientswith traumatic hyphema, including cycloplegics for traumatic iridocyclitis andmiotics to increase the surface area of the iris to enhance resorption of thehyphema.[16, 32, 33] Topical corticosteroids and estrogens[33, 34] have beenrecommended with contradictory results.[34]

    Investigations conducted by the authors of patients with traumatic hyphemaexcluded the use of topical medications because of a lack of definite evidenceof their advantages.[5, 22] One recommendation regarding topical medication isthat the topical use of steroids after the third day or the fourth day of retainedhyphema may be advantageous to decrease the associated iridocyclitis andto prevent or deter the development of peripheral anterior synechiae or

    posterior synechiae. Secondly, topical atropine (1%) is indicated in hyphemasoccupying more than 50% of the anterior chamber to break the pupillaryblock.

    Several double-masked studies clearly establish the value of systemicaminocaproic acid (ACA, AMICAR) in the prevention of recurrenthemorrhages.[5, 35] If secondary hemorrhages are the result of lysis andretraction of a clot that has produced an occlusion of the traumatized vessel,then prevention of normally occurring clot lysis for 5-6 days should beadvantageous to allow the injured blood vessel to more completely repair itsintegrity.[5] The antifibrinolytic activity of ACA given systemically has been

    demonstrated in other areas of the body to decrease the incidence ofsecondary hemorrhage.

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    ACA retards clot lysis by preventing plasmin from binding to the lysine in thefibrin clot. As a lysine analog, ACA competitively inactivates plasmin byoccupying the site on plasmin that would normally bind to fibrin. In a similarmanner, ACA binds to plasminogen, so that when activated to plasmin, itcannot attach to fibrin.

    When ACA was administered orally in a dosage of 100 mg/kg every 4 hoursfor 5 days, a statistically significant reduction in the incidence of rebleeding oftraumatic hyphemas was observed.[5] Systemic ACA should be used inhyphemas occupying 75% or less of the anterior chamber because the clotmay persist in the anterior chamber for an increased period duringadministration of the drug. The continued retention of the clot in the anteriorchamber could be a potential disadvantage with larger Grade 4 hyphemas.

    In a prospective study by the authors, as well as 2 additional studies, patientgroups treated with ACA and placebo were randomized and double-masked.[5, 18, 36, 35] In the ACA-treated group, the incidence of secondaryhemorrhage varied 3-4%.[5, 18, 36, 35] In the placebo-treated group, the incidencewas 28-33%. ACA in a dosage of 50 mg/kg every 4 hours is equally aseffective as 100 mg/kg every 4 hours, orally, for 5 days.[18] The total dosage ofACA should not exceed 30 grams per day.

    Systemic ACA should not be used in patients who are pregnant or those withrenal or hepatic insufficiency.

    Since systemic ACA significantly reduces the incidence of secondaryhemorrhage, a topical preparation could decrease the incidence of adverseeffects. By concentrating the drug in the aqueous humor, a topical preparation

    would decrease the systemic concentration of ACA associated with many ofthe adverse effects.

    For systemically administered ACA to be effective, it must penetrate into theanterior segment in sufficient concentration to retard fibrinolysis. To directlydetermine the concentration of ACA in the aqueous humor following systemicadministration, using an animal model, the authors compared plasma andaqueous humor concentrations of ACA following intravenous (IV)administration of 50 mg/kg and 100 mg/kg, as well as after constant infusionof 25 mg/kg/h.[37]After IV administration, plasma levels were 10-fold higherthan levels in the aqueous humor. Antifibrinolytic activity correlated directly

    with ACA concentration in plasma or the aqueous humor. The time to clotdissolution was greatest (2.5 times control) when the ACA concentration inthe aqueous humor reached 30-35 mg/dL, which, thus, became the targetconcentration to achieve with topical therapy.

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

    Seven topical preparations containing ACA were studied to assess whichcould deliver the required amount of ACA into the aqueous humor.[38] Thegreatest ACA concentrations were obtained using either polyvinyl alcohol orcarboxypolymethylene (CPM), 51 mg/dL and 58 mg/dL, respectively. The

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    latter had a longer duration of action. Using an experimental model forhyphema, ACA in CPM was applied topically every 6 hours for 6 days or untila secondary hemorrhage occurred.[39] Compared to no treatment or theadministration of a placebo (eg, vehicle without ACA), topical application ofACA significantly decreased the incidence of rebleeds from 33% to 10% (P