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Topics in Compan An Med 30 (2015) 97–106

Topical Review

Hyphema: Considerations in the Small Animal Patient


Mary Rebecca Telle, DVMa, Caroline Betbeze, DVM, MS, Dipl. ACVOb,n

Keywords: Classification, diagnosis, and treatment of hemorrhage into the anterior chamber of the eye, or hyphema,
hyphema
can be a challenging and frustrating process for many practitioners, especially in emergency situations.
emergency
This review outlines an inclusive list of causes, diagnostics, and treatments for traumatic and
canine
feline nontraumatic hyphema in both canine and feline patients. The review is tailored to small animal
hemorrhage practitioners, especially in emergency practice, and is designed to provide concise but thorough
bleeding descriptions on investigating underlying causes of hyphema and treating accordingly.
Published by Elsevier Inc.
a
Small Animal Clinical Sciences, College of
Veterinary Medicine, University of Tennessee
Veterinary Medical Center, Knoxville, TN, USA
b
Department of Clinical Sciences, College of
Veterinary Medicine, Mississippi State
University, Mississippi State, MS, USA
n
Address reprint requests to: Caroline
Betbeze, DVM, MS, Dipl. ACVO, Department
of Clinical Sciences, College of Veterinary
Medicine, Mississippi State University, PO
Box 6100, Mississippi State, MS 39762, USA.
E-mail: [email protected]
(C. Betbeze)

Introduction reduces the chance of hyphema, although trauma directly in the


area of the orbit or soft tissues may result in damage to the globe
Hyphema, blood in the anterior chamber of the eye, usually and uveal tissues4-6 (Fig 2). A study investigated traumatic ocular
occurs following damage to and bleeding of the retinal or uveal proptosis in 84 dogs and cats and included patients suffering from
vasculature.1,2 The blood may be characterized in several different dog bites, vehicular accidents, animal fights, and unknown
ways: clotted or unclotted, free or associated with fibrin or trauma. Hyphema was the second most common ocular finding
hypopyon, and by the amount of the anterior chamber volume it in cats presenting for ocular proptosis, and was found in some of
occupies3 (Fig 1). Hyphema can be the result of numerous disease the more severe canine cases.6 Hyphema is generally considered
processes that may disrupt the blood-ocular barrier, including to be a poor prognostic indicator in patients with proptosis,
trauma, coagulopathies, neoplasia, infectious diseases, systemic resulting in enucleation in most cases. Another study investigated
hypertension, congenital anomalies, uveitis, retinal detachments, traumatic hyphema in animals and found they had suffered gunshot
and immune-mediated diseases.1,4 Severe sequelae to hyphema wounds, canine bites, vehicular impacts, feline scratches, and blunt
commonly include cataract formation, phthisis bulbi, secondary trauma from a closing door, a horse kick, a high-rise fall, and a rock
glaucoma, corneal blood staining, and posterior synechiae.2 thrown from a lawn mower. These cases had hyphema that
Although there are many known traumatic and nontraumatic inhibited ophthalmic examination beyond the iris, and ocular ultra-
causes of hyphema, finding the underlying cause and treating sonography was performed to investigate other ocular abnormal-
the condition can still be rather difficult, especially in emergency ities.5 This is especially important because retinal detachment can
situations. This review highlights the most common etiologies result from blunt force trauma to the eye and lead to hyphema.
associated with hyphema and provides guidelines to approach Traumatic hyphema is relatively easy to diagnose, especially
hyphema both diagnostically and therapeutically. with an adequate history and thorough physical and ophthalmic
examination. When traumatic hyphema is suspected, other diag-
nostics including radiography, ultrasonography, and bloodwork
Etiologies are recommended to investigate other possible injuries resulting
from the traumatic event.
Trauma

Blunt force head trauma and penetrating eye wounds are some Coagulopathies and Bleeding Disorders
of the most common veterinary emergencies, typically caused by
vehicular accidents and animal fights. These patients may present Systemic bleeding disorders commonly responsible for causing
with severe clinical signs such as skull fractures or inappropriate hyphema include thrombocytopenia, hemolytic and nonhemo-
mentation or more inconspicuous clinical signs, such as hyphema. lytic anemia, and clotting disorders. Although inherited coagulo-
Protection by the bony orbit and soft tissues surrounding the eye pathies are seen infrequently in emergency situations, acquired

http://dx.doi.org/10.1053/j.tcam.2015.07.008
1527-3369/ & 2015 Topics in Companion Animal Medicine. Published by Elsevier Inc.
98 M.R. Telle, C. Betbeze / Topics in Companion An Med 30 (2015) 97–106

Fig. 1. Anterior chamber containing unclotted blood. Unclotted hyphema often


indicates continued bleeding or lack of the ability to form a clot. (Image courtesy of Fig. 3. Petechiae present in a patient with immune-mediated thrombocytopenia. It
Ellen Belknap.) is important to perform a full physical examination on any patient presenting for
hyphema because subtle findings of petechiae or ecchymoses may prompt further
investigation of underlying systemic coagulation disorders. (Image courtesy of
coagulopathies present more commonly as an emergency. Coagu- Andrew Mackin.)
lopathies result from disruptions of the intrinsic, common, or
extrinsic clotting pathways, and are generally classified as primary tion and include immune-mediated, sepsis-related, and drug-
or secondary hemostatic conditions. Primary hemostatic defects related thrombocytopenia as well as inflammatory and infectious
usually result in petechiae (Fig 3) and ecchymoses, whereas causes.7,11 As is the case in humans, ophthalmic disorders are
secondary hemostatic defects typically result in large or major reported in cases with thrombocytopenia in small animals, espe-
hemorrhages, usually into body cavities or larger organ systems.7 cially with infectious and neoplastic diseases. The prevalence
Any disturbance in the clotting cascade may cause hyphema or and severity of ocular lesions with thrombocytopenia cases have
hemorrhage into the eye. been found to be more significant than ocular lesions associated
In emergency cases, acquired coagulopathies from anticoagu- with anemia cases.11 Because platelets play such a vital role in
lant rodenticide intoxication are diagnosed frequently. Anticoagu- primary hemostasis, a platelet deficiency can easily lead to
lant rodenticides, known to cause deficiency in vitamin K ocular hemorrhage, including hyphema and subconjunctival,
coagulation factors (II, VII, IX, and X), are the most commonly retinal, or intravitreal hemorrhage (Fig 4). Secondary ocular
reported rodenticide toxicities in multiple studies.8,9 Without diseases, such as glaucoma or uveitis, often follow these bleed-
these factors, coagulation is severely impaired and results in ing events.11 Determination of the etiology of thrombocytopenia
multiple clinical signs related to hemorrhage, including hyphema.8 is important, as treatment of immune-mediated thrombocyto-
Other possible causes of coagulopathies include neoplasia penia involves the use of glucocorticoids, which can inhibit
(hemangiosarcoma and lymphoma), infectious diseases, snake diagnosis of underlying disease processes such as lymphoma.
and insect bites, and any other condition that may cause dissemi- Glucocorticoids at immunosuppressive dosages can also worsen
nated intravascular coagulation.7,8,10 certain infectious diseases.8,12 For these reasons, further inves-
Thrombocytopenia is the most common cause of spontaneous tigation of thrombocytopenia should be performed in all
bleeding in dogs and can be the result of decreased platelet patients presenting with hyphema to properly manage the
production, increased platelet destruction, increased platelet underlying cause.
consumption, and increased platelet sequestration.7 The most Patients experiencing moderate to severe anemia may also
common etiologies of thrombocytopenia involve platelet destruc- present with retinal hemorrhages and hyphema. When the patient

Fig. 2. An “8-ball” appearance of hyphema following vehicular trauma. The


hyphema has a blue or black appearance, which is typical of clot formation and Fig. 4. Shih Tzu with immune-mediated thrombocytopenia. The right eye has
may lead to secondary glaucoma. The cornea is perforated at the medial limbus and hyphema and aqueous flare. Platelet disorders are a common cause of hyphema
there is severe exophthalmos due to retrobulbar and subconjunctival hemorrhage. especially if vasculitis is present or the platelets are extremely low. (Image courtesy
A corneal ulcer has developed owing to globe exposure. of Andrew Mackin.)
M.R. Telle, C. Betbeze / Topics in Companion An Med 30 (2015) 97–106 99

Fig. 5. Hyphema present in association with multicentric lymphoma and anterior Fig. 6. This is the same patient as seen in Fig 5. All palpable lymph nodes were
uveitis in a 6-year-old pit bull terrier. Aqueous flare with a small amount of enlarged and firm.
hyphema is present in both eyes.

lymphoma presented with hemorrhage and uveitis, whereas 15%


is severely anemic, the retinal vasculature may experience hypoxia of all patients with lymphoma presented with some type of
due to decreased blood flow to the tissues and may become more intraocular hemorrhage.18 Additionally, animals with stage V
permeable, leading to hemorrhage.13 As there are several causes of disease were significantly more likely to have intraocular hemor-
anemia in the small animal patient, evaluating the patient's clinical rhage or uveitis. These patients with ocular lesions were also more
signs and bloodwork abnormalities are crucial in determining a likely to have lymphoblastic lymphoma vs. lymphocytic
possible cause, including performing a reticulocyte count to classify lymphoma.18
the anemia as regenerative or nonregenerative.7 Although ocular
lesions are well documented in anemic humans, a study showed Infectious Diseases
little association between anemia and ocular lesions in dogs. The
lack of ocular signs in dogs may be a species difference or may be Several infectious diseases can lead to widespread vasculitis in
correlated with varying degrees of anemia in each study designated the body, resulting in the extravasation of blood from the vascular
by higher or lower cutoff packed cell volumes.11 tunic of the eye and manifesting as hyphema. Some of the most
Because acquired coagulopathies are fairly common in small common conditions include Rocky Mountain spotted fever
animal emergency medicine, laboratory tests including prothrom- (RMSF), brucellosis, leptospirosis, and ehrlichiosis in endemic
bin time, partial prothromboplastin time, packed cell volume, areas. Other conditions such as protothecosis (caused by a green
platelet count, and blood smear are essential when hyphema is algae known as Prototheca)19,20 and aspergillosis (caused by
present.1,7,8,10 Aspergillus spp.)21 have been reported to cause ocular lesions,
including hyphema as well.
Neoplasia Ehrlichia canis is a tick-borne disease that causes a condition
known as canine monocytic ehrlichiosis (CME). Clinical signs
Both primary and secondary neoplasias are differentials for including depression, lethargy, lymphadenopathy, vasculitis, and
hyphema, especially in older dogs and susceptible breeds. ocular signs, most commonly hyphema and uveitis, are common
Although lymphoma or other types of intraocular neoplasia are with this disease.22-24 Bleeding abnormalities seen with CME are
not necessarily emergencies, these patients often present as an associated with thrombocytopenia, platelet dysfunction, and
emergency for signs of uveitis or secondary glaucoma. serum anti-platelet antibodies.23 Some studies report that up to
Primary intraocular tumors usually affect only one eye, making 50% of infected dogs developed ocular lesions from CME, with the
unilateral hyphema more common in these cases. In cases of most common clinical sign reported as anterior uveitis usually
intraocular melanoma, hyphema is reported to mask the presence with hyphema.22,23 Ocular abnormalities are commonly associated
of the tumor.14,15 Secondary neoplasms such as lymphoma or with CME and in many, ocular lesions, including hyphema or
multiple myeloma, however, are commonly bilateral conditions. retinal hemorrhages,22 may be the only presenting complaint with
There are several mechanisms in which neoplasia can cause no other clinical signs. Diagnosis of CME is based on clinical signs
hyphema; however, with primary intraocular neoplasms, the and blood smears demonstrating morulae, detection of E. canis
tumors may secrete growth factors that develop new vasculature antibodies, or polymerase chain reaction (PCR) amplification.22
and cause growth of the tumor. This new vasculature is usually Anterior uveitis and hyphema are known to be present in dogs
fragile and leaky, and can lead to hemorrhage, hence the mani- with Brucella canis infections.25 The disease can cause severe
festation of hyphema.4 anterior uveitis, leading to loss of integrity of the blood-aqueous
Lymphoma is one of the most common neoplasms of dogs, and barrier, which can then lead to bleeding into the anterior chamber.
commonly presents with ophthalmic manifestations. Ocular com- This condition should be suspected in intact, sexually mature
ponents occur with both primary ocular lymphoma and multi- animals in endemic areas, most commonly the rural southeastern
centric lymphoma in cats, whereas ophthalmic disease is more United States.26 Although B. canis' zoonotic potential to humans is
common with multicentric lymphoma in dogs. Clinical signs low, the condition has been reported to cause undulant fever in
include hyphema, hypopyon, ocular or orbital masses, anterior humans and usually has greater potential to affect immunocom-
uveitis, retinal detachment, epiphora, and blepharospasm16 promised individuals.26 For these reasons, diagnosis of the con-
(Figs 5 and 6). Hyphema and uveitis are listed as common clinical dition is particularly important. Diagnosis can be made by using
signs in animals with substage B lymphoma, or those that display serology, agglutination tests, and indirect fluorescent antibody and
clinical signs.17 A study reported that 6% of patients with enzyme-linked immunosorbent assay tests.26
100 M.R. Telle, C. Betbeze / Topics in Companion An Med 30 (2015) 97–106

RMSF should also be considered in dogs with hyphema, subcon- Collie eye anomaly is an inherited disorder described in both
junctival hemorrhage, anterior uveitis, and inflammatory cell infil- rough and smooth collies that involves incomplete development
trates, especially in endemic areas.27 Additionally, these dogs may of the choroid, defects of the optic nerve, retinal detachment, or
not be on flea and tick prevention, as it is a tick-borne disease thinning of the sclera. This condition is recessively inherited and
caused by Rickettsia rickettsia, which is transmitted by the American there are genetic tests available for breeders and buyers.1,4 Retinal
dog tick (Dermacentor variabilis), Rocky Mountain wood tick detachment is a common sequelae to these changes and subse-
(Dermacentor andersoni), and the brown dog tick (Rhipicephalus quently leads to hyphema in most of these instances.
sanguineus).28 Other common clinical signs appreciated in dogs with Vitreoretinal dysplasia has also been associated with retinal
RMSF include fever, lethargy, ecchymoses, and retinal hemor- detachment, which then leads to hemorrhage into the anterior
rhages.28 Diagnosis can be made by assessing titers, which may take chamber. This condition has been described in several breeds,
a considerable amount of time, so if suspected, treatment may be including Labrador retrievers, Bedlington terriers, Springer span-
warranted before definitive diagnosis, especially in endemic areas.28 iels, and Sealyham terriers. Puppies of the aforementioned breeds
should be considered especially susceptible to this condition and
Systemic Hypertension should be thoroughly examined for the deformities when
hyphema is present. Glaucoma is a common result of hyphema
Hypertensive retinopathy is the most common ocular clinical in these cases.1,4
sign associated with systemic hypertension, but hyphema may During embryonic development of the eye, the hyaloid artery is
also be a presenting sign with this disease. Because of the the primary arterial blood supplier providing nutrients to the lens
autoregulation of the vasculature of the eyes, central nervous and retina.32 Failure of this artery to regress normally results in a
system, heart, and kidneys, these organs are known as end persistent hyaloid artery. The persistence of this vascular structure
organs29 and are commonly associated with significant damage can lead to rupture and result in bleeding into the lens, the
from systemic hypertension.29,30 vitreous, and anterior chamber, resulting in hyphema.4,32
Because the choroid and retina are extremely vascular, these
structures respond to systemic hypertension by arteriolar vaso- Retinal Detachment
constriction, thus leading to disruption of the integrity of the
vasculature and increased vascular permeability due to arterial Retinal detachments can be described either as primary or as
endothelial cell damage.30 This vascular permeability can lead to secondary in small animal patients. Secondary retinal detach-
retinal hemorrhage, edema, retinal detachment, secondary glau- ments caused by infectious diseases, inflammation, neoplasia,
coma, and hyphema.30 systemic hypertension, and congenital abnormalities are far more
Essential (primary) systemic hypertension tends to be rare in common than primary retinal detachments, which are rare in
dogs and cats; therefore, several underlying disease processes veterinary medicine.2,4
should be investigated when systemic hypertension is sus- Subretinal or intraretinal edema is a common mechanism of
pected.30,31 Some of the most common underlying etiologies retinal detachment and may result from a number of causes.2 Any
causing systemic hypertension in both dogs and cats include renal cause of retinal detachment can lead to hemorrhage due to
failure (acute and chronic), protein-losing nephropathies, hyper- damage of retinal vasculature.2 Common causes of retinal detach-
thyroidism (cats), hyperadrenocorticism, pheochromocytoma, and ment in dogs and cats are associated with systemic diseases
diabetes mellitus.30,31 Assessing blood pressure of all patients (nonrhegmatogenous)4,33 or with a retinal hole or tear (rhegma-
presenting with hyphema is extremely important, especially if togenous).33 Both types of detachment can be associated with
one of the underlying disease processes is present (Fig 7). intraocular hemorrhage.2
Retinal detachments can also be caused by trauma, and they
are commonly seen in animals that have suffered blunt force
Congenital Anomalies
trauma to the head or to the globe. Penetrating trauma can also
cause retinal detachment.33 Because these incidents can cause
A congenital ocular disorder should be suspected in young
direct detachment of the retina, the retinal vessels may become
animals presenting with hyphema with no known traumatic
leaky and bleed directly into the vitreous or anterior chamber
cause. Disorders to consider include Collie eye anomaly, persistent
traveling anteriorly, which may manifest as hyphema. This is a
hyaloid artery, and vitreoretinal dysplasia.1,4
particularly important cause of hyphema in the small animal
patient, especially in emergency situations.

Anterior Uveitis

Anterior uveitis (iridocyclitis) is inflammation of the uveal tract


of the eye and is one of the most common causes of blindness in
small animal patients. Some of the more common signs of uveitis
include hyphema, miosis, hypopyon, aqueous flare, conjunctival
hyperemia, corneal edema, chorioretinitis, and hypotony.1,4,34 The
presence of preiridal fibrovascular membranes has also been
described to cause hyphema owing to the fragility of these newly
formed blood vessels.2 This process occurs commonly in animals
with chronic uveitis or retinal detachments (and several other
diseases) and leads to neovascularization in certain areas of the
eye, most commonly the anterior surface of the iris. The neo-
vascularization is most likely due to angiogenic stimulating factors
Fig. 7. Doppler blood pressure measurement in a 13-year-old domestic shorthaired
triggered by hypoxia. Because the junctions between the vessels
cat. If hyphema is seen, blood pressure measurement is indicated as part of a are poorly developed, the vessels become leaky and can lead to
thorough examination. hemorrhage, manifesting as hyphema.2,35
M.R. Telle, C. Betbeze / Topics in Companion An Med 30 (2015) 97–106 101

Anterior uveitis as a cause of hyphema is discussed more


thoroughly in the neoplasia and infectious disease sections, as
they are the most common causes of anterior uveitis with
hyphema in the small animal patient.

Diagnostics

History

As with all small animal emergencies, obtaining an accurate


and thorough history from the client is one of the most helpful
and useful diagnostic tools at a veterinarian's disposal.
Vaccination status and parasite control protocols are extremely
pertinent pieces of information, and can help guide the
diagnostic plan.
The breed and signalment of the animal can play a significant Fig. 8. Hyphema and anterior uveitis in a 4-year-old German shepherd dog that
role in finding an underlying cause of the hyphema. In a young, was presented with loss of vision. History indicated previous treatment with
trimethoprim sulfa for a urinary tract infection and toxicity was suspected as the
otherwise healthy animal, congenital anomalies should always be
cause of uveitis. This patient made a complete recovery.
considered, especially in certain breeds.1 Other etiologies to
consider in any patient, especially young animals, include inges-
tion of toxins such as anticoagulant rodenticide and xylitol. Geo- when there is blood in the anterior chamber that precludes a full
graphic location, travel history, and other clinical signs are very ophthalmic examination.36 A positive consensual reflex or dazzle
useful when considering tick-borne, fungal, and infectious dis- reflex can suggest proper retinal function in the eye.1,36
eases, and patients with significant histories should be assessed Although a Schirmer tear test may not be indicated in all cases
for these conditions. It is important to investigate parasite control presenting for hyphema, the test should be performed as a part of
as well. Acquiring a complete list of current and past medications a comprehensive ophthalmic examination if the patient appears
is essential, as these medications may be contributing to the stable. If the animal does not appear stable, this test can be
hyphema.36 Potentiated sulfonamides have been reported to cause performed at a later time, as tear film abnormalities are unlikely to
uveitis and hyphema in human and canine patients37 (Fig 8). be the primary inciting factor for hyphema. Performing a fluo-
Hyphema has also been a presenting clinical sign associated with rescein stain or a Seidel test in the affected eye is important to
an overdose of phenylpropanolamine in a 4-year-old dog because determine the integrity of the cornea and rule out leakage of
of systemic hypertension.38 Typically older patients are more aqueous humor from a possible penetrating trauma (Fig 10).
likely to acquire hyphema from conditions such as neoplasia and Perhaps one of the most important aspects of the ophthalmic
systemic hypertension. examination in these cases is tonometry. In most cases of
Making a differential diagnosis list may be considerably easier hyphema and anterior uveitis, intraocular pressure (IOP) tends to
if the time at which the hyphema first formed can be noted, as be low, or hypotonic.1 If IOP is measured and is normal to high,
some conditions such as ocular neoplasia and trauma usually secondary glaucoma should be suspected and adjunctive glau-
cause acute hyphema, whereas other conditions such as anti- coma therapy should be implemented in the treatment plan. A
coagulant rodenticide toxicity may take several days to develop.36 finding of increased IOP could also discourage use of mydriatic
agents (i.e., atropine) in management of patients with hyphema
Physical Examination (Fig 11). Hyphema leading to secondary glaucoma is associated
with a poor prognosis in most cases.1 Secondary glaucoma
Although the cause of hyphema may seem obvious in some because of obstruction of the iridocorneal angle by erythro-
cases such as trauma, a thorough physical examination should cytes or from infiltration of phagocytic macrophages is the
always be performed. Examining the entire animal is extremely most commonly reported side effect of hyphema reported in a
important in these situations to find the appropriate diagnosis. study.2
Auscultation of the heart and lungs coupled with abdominal
palpation may reveal evidence of bleeding in other systems in
the body. Additionally, animals with bleeding disorders may have
areas of petechiae or bruising and offer other clues as to the
underlying cause of the hyphema7 (Fig 9). As mentioned previ-
ously, systemic hypertension commonly causes ocular lesions;
therefore, measuring blood pressure in these animals is usually
warranted. If systemic blood pressure measurement is consistently
greater than 170-180 mm Hg systolic and signs of end-organ
damage such as hyphema or retinal hemorrhage are present,
antihypertensive therapy is warranted.1,4,29

Ophthalmic Examination

A complete ophthalmic examination should be performed in


every animal presenting for hyphema. The examination should
include assessment of menace response and maze test to evaluate
vision in both eyes.36 Dazzle reflex and consensual pupillary light Fig. 9. Petechiae in a patient that presented for heat stroke. (Image courtesy of
reflex from the affected to unaffected eye are especially useful Andrew Mackin.)
102 M.R. Telle, C. Betbeze / Topics in Companion An Med 30 (2015) 97–106

Additional Laboratory Tests

Because finding an underlying cause for hyphema is essential


to determining appropriate treatment for the patient, additional
laboratory tests that are not included in the initial physical and
ophthalmic examination are almost always indicated.
A “minimum database” including serum chemistry, complete
blood count (CBC), and urinalysis should be performed in every
patient presenting with hyphema. A serum chemistry may help
identify irregularities in liver and renal values, as well as other
electrolytes and organ systems. The serum chemistry may also
show recognizable patterns for some endocrine diseases such as
hyperadrenocorticism in dogs or hyperthyroidism in cats. If these
or other endocrine diseases are suspected, further blood tests
including thyroid tests and adrenocorticotropic hormone stimula-
tion or low-dose dexamethasone suppression tests may be indi-
cated. A CBC allows evaluation of different cell lines and may
Fig. 10. Hyphema present in a 1-year-old indoor or outdoor cat with penetrating
corneal trauma. Note the anterior synechiae and dyscoric pupil. This clotted blood
indicate involvement or one or more cell lines. If all cell lines
likely resulted from sharp iris trauma and completely resolved with empirical appear affected, bone marrow disease may be suspected and a
medical therapy. core biopsy of the bone marrow may be recommended.36,39
A blood smear and manual platelet count should be performed
in all of these animals, as some blood analyzers may show
Evaluation of the anterior chamber as well as fundoscopic abnormal platelet numbers because of clumps or megaplatelets.
examination in both eyes are essential ophthalmic tests. Additionally, blood smears should be used to look for blood
Because systemic diseases causing hyphema can manifest in parasites or abnormal red cell morphology or color that may
many different ways and cause varying degrees of blood-ocular indicate other systemic disease (i.e., spherocytes may be seen with
barrier breakdown, examination of the anterior chamber may immune-mediated hemolytic anemia or schistocytes may suggest
reveal hyphema, hypopyon, or aqueous flare. 1,36 Although hemangiosarcoma or disseminated intravascular coagulation). A
examining the intraocular structures is vitally important, blood smear also allows for a manual platelet count to be
investigation of these structures may be nearly impossible in performed. In patients with anemia, a reticulocyte count should
animals experiencing complete or total hyphema. Complete be performed to assess regeneration of the red blood cells.7 Lastly,
hyphema results from the entire anterior chamber being filled a urinalysis and urine specific gravity determination should be
with blood and is usually seen with acute hemorrhage.36 performed to investigate for indications of renal insufficiency,
Hyphema may appear differently depending on the underlying hematuria, infection, proteinuria, or any other abnormalities that
cause. When evaluating the blood, it is important to note may assist in the diagnosis of a systemic disease.
whether the blood is clotted in the anterior chamber or if it Additional tests such as titers (tick and viral) and a coagulation
remains unclotted. If the blood is clotted, a traumatic or panel (prothrombin time, partial prothromboplastin time) may be
infectious cause is more likely, whereas if the blood is not indicated based on the patient's history and risk factors for certain
clotted, a bleeding abnormality should be moved higher on the diseases. A coagulation panel should be recommended for patients
differential list. Bleeds resulting from detached retinas, neo- of all ages, as systemic (primary or acquired) bleeding disorders
plasia, or congenital ocular abnormalities may appear clotted or may be present in young or old animals. In cats, feline leukemia
unclotted depending on the severity and duration of the bleed.1 virus (FeLV), feline infectious peritonitis (FIP), feline immunodefi-
When the blood obscures evaluation of the intraocular struc- ciency virus (FIV), and toxoplasmosis (Toxoplasma gondii) should
tures, ocular ultrasonography should be used to evaluate these always be considered in susceptible populations. Snap tests for
structures (see the Diagnostic Imaging section).2 FeLV and FIV may be performed, but PCR tests also exist for these
conditions in animals whose test results are negative but show
significant clinical signs. Uveitis or chorioretinitis is commonly
seen in cats with the dry form of FIP, but FIP is extremely difficult
to diagnose.40 Routine laboratory findings on CBC and chemistry
such as mature neutrophilia and hyperglobulinemia may suggest
FIP, but are not definitive. Fluid analysis, imaging, cytologic and
histologic examination, antibody testing, PCR testing, and immu-
nohistochemistry may also be used to diagnose the condition, but
postmortem findings are unfortunately the most useful indicators
of FIP.40 Serological testing may be helpful in diagnosing toxo-
plasmosis, FIV, FIP, or FeLV, but the seroprevalence of each of these
diseases combined was 90% in a study. The seroprevalence of FIV
was 22.9%, FeLV was 5.95%, feline coronaviruses was 27%, and
T. gondii was 78.5%, showing that the results may not be as helpful
as those of other tests.36,41

Diagnostic Imaging

Fig. 11. A complete physical and ophthalmic examination is necessary in all cases
When investigating systemic diseases, thoracic and abdominal
of hyphema. Serial tonometry is especially important to monitor for glaucoma imaging can be extremely useful. Because neoplasia, infectious
development. diseases, and fungal diseases (as discussed previously) are
M.R. Telle, C. Betbeze / Topics in Companion An Med 30 (2015) 97–106 103

Table 1
Etiologies of Hyphema

Trauma
Blunt force trauma
Penetrating eye wounds
Vehicular trauma and animal fights
Proptosis
Gunshot wounds

Coagulopathies
Acquired (i.e., rodenticide intoxication, thrombocytopenia,
immune-mediated, DIC, drug toxicity, and infection)
Inherited or congenital

Bleeding disorders
Thrombocytopenia
Anemia
Drug induced
Infectious agents (i.e., ehrlichiosis, FeLV, and FIV)
Neoplasia

Neoplasia
Fig. 12. B-mode ocular ultrasound with a 12-MHz probe. Note the hyphema in Primary (i.e., ocular melanoma and adenoma)
anterior chamber and classical seagull sign of retinal detachment in this 4-year-old Secondary (i.e., lymphoma, hemangiosarcoma, multiple myeloma,
boxer with lymphoma. and transmissible venereal tumor)

Infectious diseases
Tick borne (i.e., Rocky Mountain spotted fever and ehrlichiosis)
common causes of hyphema, abdominal ultrasound and thoracic Bacterial (i.e., brucellosis and leptospirosis)
radiographs are recommended in any patient without an obvious Fungal (i.e., aspergillosis)
cause of hyphema. Thoracic radiographs may reveal primary or Other (i.e., protothecosis)
metastatic disease, evidence of pulmonary, pericardial, or pleural Systemic hypertension
hemorrhage and can change the therapy and possibly worsen the Renal failure
prognosis for the patient. Abdominal ultrasound may reveal fluid or Protein-losing nephropathy
blood in the abdomen or abnormalities in the abdominal organs. Hyperthyroidism
Hyperadrenocorticism
Perhaps one of the most useful diagnostic imaging tools for Pheochromocytoma
patients with hyphema is the use of B-mode real-time ocular Diabetes mellitus
ultrasonography.2 This imaging can assist in diagnosing intra-
Congenital anomalies
ocular masses, intraocular hemorrhage, and retinal detachments, Collie eye anomaly
especially when visualization of the intraocular structures is Persistent hyaloid artery
compromised by injury or hyphema in the eye2,5 (Fig 12). This Vitreoretinal dysplasia
practice can assist in giving a more accurate prognosis for vision Retinal detachment
and comfort in the affected eye. Most of the time, ocular ultra- Primary
sonography is performed by a board-certified ophthalmologist or Secondary (i.e., trauma, infectious diseases, inflammation,
neoplasia, systemic hypertension, and congenital anomalies)
radiologist and a topical anesthetic should be applied to the
affected cornea before performing the ultrasound.5 Anterior uveitis
Neoplasia
Further diagnostic imaging including computed tomography
Immune-mediated
with or without contrast or magnetic resonance imaging may be Infectious disease
warranted when more serious involvement of structures of the
Chronic glaucoma
head, neck, or central nervous system are suspected; however,
these imaging modalities usually require a referral institution and DIC, disseminated intravascular coagulation.
a significant monetary commitment and should be thoroughly
discussed with the owner.1 Skull radiographs may be helpful in
identifying orbital fractures or other abnormalities in the skull1 segment.1 Careful attention should be paid to the integrity of the
(Table 1). cornea before using these medications because corticosteroids
may be contraindicated when corneal abrasions, penetrating
wounds, or corneal ulcers are present.1 It is common to have
Treatment some hyphema associated with penetrating trauma to the cornea
and the clinician must weigh the need for anti-inflammatory
Therapy for hyphema in the small animal patient should medication against the severity of the corneal injury because
always include treatment of the underlying disease and associated corticosteroids may delay healing. Systemic corticosteroids such
conditions. For treatment of the eye with hyphema, however, as prednisone may also be used to prevent reoccurrence of
empirical treatments with topical corticosteroids and mydriatics hemorrhage if they are not contraindicated in a patient.1,2,5,43
are usually instituted immediately. If the blood or fibrin is clotted, Although nonsteroidal anti-inflammatory drugs are commonly
intracameral injection of tissue-plasminogen activator (TPA) or used to treat uveitis to decrease inflammation, nonsteroidal anti-
systemic aminocaproic acid could be instituted.1,2,5,36,42 inflammatory drugs are generally avoided when treating hyphema
Topical corticosteroids are used to prevent bleeding from because they interfere with platelet function and may actually
reoccurring by inhibiting fibrinolysis and reestablishing the cause more bleeding to occur.1,5,36,43
blood-ocular barrier.42,43 The most commonly used topical corti- Topical parasympatholytics (i.e., 1% atropine) are used to
costeroids are dexamethasone sodium phosphate and predniso- prevent formation of posterior synechiae and iris bombe, to
lone acetate, as both of these medications have the ability to stabilize the blood-aqueous barrier, and decrease ciliary body
penetrate the intact cornea and act directly on the anterior spasm.1,2,5,36,42 Topical administration of atropine 2-3 times a
104 M.R. Telle, C. Betbeze / Topics in Companion An Med 30 (2015) 97–106

Fig. 13. (A) Hyphema and fibrin 5 days after initial medical therapy for uveitis was instituted. (B) Intracameral injection of tissue-plasminogen activator (TPA) (250 mg/mL)
into the anterior chamber. At this time, there was no active bleeding into the eye and the blood clot was still present. The hyphema completely resolved 12 hours after
injection.

day is recommended for initial therapy, but once dilation of the structures has occurred during the process. In general, animals
pupil has occurred, the frequency of administration should be with retinal disease including retinal detachment or vitreal,
reduced to avoid increased IOP and potential development of choroidal, or retinal hemorrhages have a grave to poor prognosis
glaucoma.1,5,36 It is important to serially check IOP during the for vision.1,2,36 In cases of uncomplicated hyphema with small
management of hyphema.1 If increased IOP is noted, atropine volumes of blood, the condition may take up to 1 week to
should be discontinued and glaucoma treatment should be started disappear; however, if the hyphema persists or recurs, further
immediately.1,36,43 diagnostics should be performed to investigate another possible
Parasympathomimetics such as pilocarpine have been used for underlying diagnosis. Enucleation should be performed in animals
treatment of hyphema36 in the past because of their ability to when neoplasia is of primary concern; however, further diagnos-
assist with blood removal through the trabecular meshwork and tics such as thoracic and abdominal radiographs should be
enhance fibinolysin activity.1 However, the use of this drug class in performed to look for metastasis. When metastasis is noted, the
the treatment of hyphema has become increasingly more con- prognosis is worse, although enucleation may still provide some
troversial because it is a miotic, which may increase the chance of comfort and palliative treatment for the patient.1,2,36 Animals with
posterior synechiae formation and iris bombe. This medication chronic hyphema usually suffer from secondary complications
also induces anterior uveitis, which is commonly already present such as glaucoma, and the prognosis for vision is usually poor.1
in cases of hyphema.1,18,36,43 In patients with smaller amounts of hyphema that do not have
In acute cases presenting within 72 hours of clot formation, an significantly increased IOP, treatment should be implemented and
injection of TPA can lead to quick resolution of the clot1,44 (Fig 13). prognosis should be reassessed when the hyphema has resolved
TPA is a synthetic fibrinolytic agent that is known to promote and an accurate assessment of the integrity of the intraocular
fibrinolysis in the anterior chamber of human and animal eyes.44 structures can be made.1,36 These patients have the best prognosis
Although the use of TPA in the treatment of hyphema is some- for vision.
times viewed as controversial, a 1992 study revealed substantial
fibrinolysis when TPA was injected intracamerally.44 TPA is most
effective within 72 hours of clot formation, but has been noted to Conclusion
be effective for up to a week after clot formation. It is indicated
only if recurrence of bleeding is unlikely.1,5,36,45 Topical and Hyphema is a common ocular abnormality seen in small
systemic fibrinolytics are commonly used in humans experiencing animal practice, especially in emergency cases. Several underlying
hyphema because they are known to prevent recurrent bleed- diseases are commonly associated with intraocular hemorrhage,
ing.1,5,46 E-aminocaproic acid, another fibrinolytic agent, is known including trauma, neoplasia, infectious disease, bleeding abnor-
to interfere with the conversion of plasminogen to plasmin.47 A malities, congenital abnormalities, retinal detachment, systemic
1974 study demonstrated that hyphema disappeared in the dog hypertension, and anterior uveitis. Because these etiologies are
eyes injected with E-aminocaproic acid46; however, this therapy is complex and very different, obtaining a detailed history and
not regularly used in veterinary medicine mostly because of cost, performing a thorough physical and ocular examination are
difficult administration schedule, and significant side effects.5 essential to determine the most likely cause of the hyphema.
As previously discussed, significant sequelae such as secondary Additional diagnostic testings including CBC, serum chemistry,
glaucoma and cataracts can develop from hyphema. If these urinalysis, coagulation panel, radiography, and ultrasonography
conditions develop, the prognosis for vision and healing is poor are helpful in determining an underlying cause and giving an
and enucleation may be considered as a final treatment option36 accurate prognosis for vision and comfort. A full ophthalmic
(Table 2). examination including tonometry and fluorescein staining should
be performed before starting the therapy. The most common
empirical therapy includes topical or systemic corticosteroids
Prognosis and mydriatics. Additional treatments with TPA and aminocaproic
acid have also been described in particular cases. Protecting the
Prognosis for hyphema greatly depends on the underlying eye from sequelae, specifically glaucoma or chronic uveitis, is a
cause of the bleeding and how much damage to the intraocular vital part of treatment to decrease discomfort and preserve vision.
M.R. Telle, C. Betbeze / Topics in Companion An Med 30 (2015) 97–106 105

Table 2
Treatment of Hyphema

Drug class and names Disorder and use Dose and frequency

Topical corticosteroids Uveitis or inflammation 1 Drop in affected eye(s) 4-6 times daily
Prednisolone acetate
suspension 1%
Dexamethasone
solution 0.1%

Topical parasympatholytics Uveitis or inflammation 1 Drop in affected eye(s) 2-3 times daily
Atropine 1% Used for the prevention of posterior synechiae  Frequency should be reduced once dilation of pupil has occurred to prevent
and iris bombe development of glaucoma
Stabilize blood-aqueous barrier
Decreased ciliary body spasms

Topical NSAIDs Uveitis or inflammation 1 Drop in affected eye(s) 3-4 times daily
(controversial)
Flurbiprofen 0.03%  Use of topical and systemic NSAIDs is controversial because they may interfere
Diclofenac 0.1% with platelet function

Systemic corticosteroids Uveitis or inflammation 1 mg/kg/day


Prednisone  Check for contraindications in patients
 Rule out disease processes such as lymphoma before prescribing
Systemic NSAIDs Uveitis or inflammation Carprofen:
(controversial) Dogs: 2 mg/kg PO every 12 hours
Carprofen
Deracoxib Deracoxib:
Aspirin Dogs: 1-2 mg/kg PO every 24 hours
Robenacoxib (cats)

Aspirin:
Dogs: 10-15 mg/kg PO every 8-12 hours
Cats: 10 mg/kg PO every 48-72 hours

Robenacoxib:
Cats: 1 mg/kg PO once daily for 3 days

Fibrinolytics Blood, fibrin, or clot dissolution TPA:


Tissue-plasminogen 25-75 mg intracamerally
activator (TPA)
E-aminocaproic EACA:
acid (EACA) Not regularly recommended

NSAID, nonsteroidal anti-inflammatory drugs; PO, orally.

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