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University of Pennsylvania University of Pennsylvania
ScholarlyCommons ScholarlyCommons
Departmental Papers (Vet) School of Veterinary Medicine
11-1-1999
Hyphema Part I Pathophysiologic Considerations Hyphema Part I Pathophysiologic Considerations
Andraacutes M Komaacuteromy
David T Ramsey
Dennis E Brooks
Cynthia C Ramsey
Maria E Kallberg
See next page for additional authors
Follow this and additional works at httpsrepositoryupenneduvet_papers
Part of the Ophthalmology Commons and the Veterinary Medicine Commons
Recommended Citation Recommended Citation Komaacuteromy A M Ramsey D T Brooks D E Ramsey C C Kallberg M E amp Andrew S E (1999) Hyphema Part I Pathophysiologic Considerations Compendium on Continuing Education for the Practicing Veterinarian 21 (11) 1064-1069 Retrieved from httpsrepositoryupenneduvet_papers51
Dr Komaacuteromy was affiliated with the University of Pennsylvania from 2003-2012 Part II can be found at httprepositoryupenneduvet_papers52
This paper is posted at ScholarlyCommons httpsrepositoryupenneduvet_papers51 For more information please contact repositorypoboxupennedu
Hyphema Part I Pathophysiologic Considerations Hyphema Part I Pathophysiologic Considerations
Abstract Abstract Hemorrhage in the anterior chamber of the eye or hyphema results from a breakdown of the blood-ocular barrier (BOB) and is frequently associated with inflammation of the iris ciliary body or retina Hyphema can also occur by retrograde blood flow into the anterior chamber via the aqueous humor drainage pathways without BOB breakdown Hyphema attributable to blunt or perforating ocular trauma is more common than that resulting from endogenous causes When trauma has been eliminated as a possible cause it is prudent to assume that every animal with hyphema has a serious systemic disease until proven otherwise
Disciplines Disciplines Medicine and Health Sciences | Ophthalmology | Veterinary Medicine
Comments Comments Dr Komaacuteromy was affiliated with the University of Pennsylvania from 2003-2012
Part II can be found at httprepositoryupenneduvet_papers52
Author(s) Author(s) Andraacutes M Komaacuteromy David T Ramsey Dennis E Brooks Cynthia C Ramsey Maria E Kallberg and Stacy E Andrew
This journal article is available at ScholarlyCommons httpsrepositoryupenneduvet_papers51
1064 20TH ANNIVERSARY Vol 21 No 11 November 1999
CE Article 5 (15 contact hours) Helereed Peer Review
FOCAL POINT
Hyphema is frequently associated with iridocyclitis and generally indicates severe intraocular or systemic disease
KEY FACTS
Athorough diagnostic evaluation should be initiated when hyphema is present p 1064
Hyphema generally results from a breakdown of the blood-ocular barrier p 1064
The diagnostic differentials for hyphema do not differ substantially from those for hemorrhage into other areas of the body p 1065
When trauma has been eliminated as source of hyphema the diagnostic and therapeutic approach is directed by results of the physical and ophthalmic examinations p 1065
and e with of pel of the frequ rna blood Iy calHyphema Part 1 and ( but iPathophysiologic Considerations hyph(
University of florida
Andras M Komaromy DLmedvet
Dennis E Brooks DVM PhD
Maria E Kallberg DVM Stacy E Andrew DVM
capsu do nl
Michigan State University move David T Ramsey DVM anteri
ous a Cynthia C Ramsey DVM MS Be(
highe age F blooe lower
ABSTRACT Hemorrhage in the anterior chamber of the eye or hyphema results from a breakmiddot predi down of the blood-ocular barrier (BOB) and is frequently associated with inflammation of the the al iris ciliary body or retina Hyphema can also occur by retrograde blood flow into the anterior chamber via the aqueous humor drainage pathways without BOB breakdown Hyphema atmiddot PAntributable to blunt or perforating ocular trauma is more common than that resulting from enmiddot
Widogenous causes When trauma has been eliminated as a possible cause it is prudent to asshyagnossume that every animal with hyphema has aserious systemic disease until proven otherwise tially
H body
)Phema is defined as hemorrhage within the anterior chamber of the eye diagn (Figure 1) In contrast the accumulation of leukocytes in the nterior hyphl chamber is termed h)P0pyon The etiopathogenesis of hyphema is mulshy dison
tifactorial but ultimately the final common pathway is breakdown of the soum blood-ocular barrier (BOB) and subsequent inrraocular hemorrhage that is ofshy so thl ten associated with inflammation Many of the mechanisms that cause intraocushy ation lar hemorrhage may also result in hemorrhage in other parts of the body This I1Ism~
article foclIses on hyphema as a red flag for sight-threatening ocular or lifeshythreatening systemic hemorrhagic disease Irido
When hyphema is present a thorough diagrwstic evaluation similar ro that inshy lri( dicated for any third-compartment hemorrhage (eg hemoabdomen hemothoshy ocula rax) should be initiated Attentive clinicians will recognize the importance of a aque( thorough diagnostic workup before or during the initial treatment of hyphema ner I Death attributable to systemic or vital organ hemorrhage may occur if the diagshy terns) nostic workup is incomplete Part I of this two-parr presentation focuses on the rncltJ many pathophysiologic mechanisms that most frequenrly result in hyphema the f each of which is considered as a separate entity in this article However concurshy discu rent involvement of more than one mechanism is common Part II will cover dishy ble c agnosis and treatment of hyphema left L
cyclil BLOOD-OCULAR BARRIER ceils
The BOB which consists of the blood-aqueous and blood-retinal barriers preshyvents erythrocytes and leukocytes and inhibits tissue fluids and proteins from entershy Trau ing nonvascular ocular tissues and compartments The BOB consists of endothelial H~
- ------ - - -- - - - - - -- - - ---
Compendium November 1999 20TH ANNIVERSARY Small AnimalExotics 1065
and epithelial tight junctions with variations in their degree of permeability l Dysfunction of the blood-aqueous barrier frequently results in hypheshyrna breakdown of the blood-r-tinal barrier generalshyly causes retinal subretinal and choroidal hemorrhage but infrequently results in hyphema The posterior lens capsule and zonules limit but do not com pletely preven t movement of blood from the anterior chamber to the vitreshyous and vice versa
Figure 1-Hyphema in a dog
Because the intraocular pressure (lOP) is normally higher than the pressure in the aqueous humor drainshyage pathways (the scleral venous plexus) retrograde blood flow into the anterior chamber is prevented lOP lower than the pressure in the scleral venous plexus may predispose to hyphema via retrograde blood flow into the anterior chamber
PATHOPHYSIOLOGIC APPROACH With the exception of severe intraocular disease the dishy
agnostic differentials for hyphema do not differ substanshytially from those for hemorrhage in other areas of the body (eg hemothorax hemoabdomen) therefore the diagnostic approach to determine the underlying cause of hyphema is similar In addition to systemic causes ocular disorders should be considered Clinicians must develop a sound understanding of the potential causes of hyphema so they are able to construct a list of differential considershyations for each mechanism The most common mechashynisms of hemorrhage that may result in hyphema follow
Iridocyclitis Iridocyclitis (anterior uveitis) is the most common
ocular disease associated with a breakdown of the bloodshyaqueous barrier Disruption of the blood-aqueous barshyrier may lead to aqueous flare (predominantly proshyteins) hypopyon andor hyphema depending on the inciting stimulus and duration of the disease Most of the pathophysiologic mechanisms of BOB breakdown discussed in the remainder of this article are also possishyble causes for iridocyclitis Regardless of the caLIse if left untreated hyphema will eventually result in iridoshycyclitis when chemotactic triggers recruit inflammatory cells for cleanup
Trauma Hyphema attributable to exogenous causes (blunt or
perforating trauma) is probshyably more common than that resulting from endogenous causes (see Causes of Hypheshyrna) Blunt trauma to the head seldom resuhs in hypheshyrna because the eyeball is proshytected by anterior portions of the bony orbit and orbital soft tissues However severe blunt trauma to the anterior orbital rim or periorbital soft tissues and eyeball may reshy
suit in hyphema In this case -- - - - - -- - -- - -- - -- -- - - - - examination and palpation
of the periorbital area usualshyIy reveals clinical signs of trauma such as swelling and bruising of the eyelids and conjunctiva fracture of the bony orbit or orbital hemorrhage and resultant orbital mass effect Bilateral hyphema is seldom caused by mild trauma When blunt ocular trauma occurs the sudden rise in lOP associated with ocular indentation causes anterior chamber angle distortion and may result in rupture of iris stromal or ciliary body vessels and subsequent hyphema4
Perforating trauma (eg cat scratch BB pellets) to the eye baH (cornea sclera) with direct damage to inshytraocular vasculature is more likely to result in traushymatic hyphema than is blunt trauma Traumatic hyshyphema can also be associated with proptosis of the globe and may be accompanied by structural damage to the eye including lens subluxation and dislocation vitreous hemorrhage or retinal detachment Head rashydiographs help to reveal fractures of the orbit or skull in trauma cases When exogenous sources of hyphema have been eliminated the diagnostic approach is furshyther directed by results of physical and ophthalmic exshyamll1atIons
Thrombocytopenia Lack of an adequate number of circulating platelets
can result in hyphema and hemorrhage secondary to ongoing capiuary microtrauma induced by normal acshytiviry or exogenous insult6 Thrombocytopenia is typishyfied clinically by petechial hemorrhage of mucosal and cutaneous surfaces Hyphema and concurrent petechial hemorrhages should prompt clinicians to consider thrombocytopenia as a likely mechanism of disease Thrombocywpenia may be induced by immune-medishyated destruction of platelets infectious agents (eg Ehrlichia canis platys or risticii Leptojpira species Rickettsia rickettsil) sepsis splenomegaly neoplasia or disseminated intravascular coagulation
ANTERIOR UVEITIS bull PERFORATING TRAUMA PETECHIAL HEMORRHAGE
middot
1066 Small An imalExotics 20TH ANNIVERSARY Compendium November 1999
Causes of Hyphema
Trauma2-5
bull Blunt bull Penetrating (with or without foreign body)
Thrombocytopenia6-10
bull Decreased platelet production in the bone marrow -Drug or chemical toxicity-induced bone marrow
hypoplasia (eg estrogens antiinflammatory agents antibiotics tranquilizing agents diuretic agents dapsone myelosuppressive chemotherapy)
-Toxic doses of irradiation -Chronic infections (e g feline leukemia virus
[FeLV] Ehrlichia canis Ehrlichia platys canine distemper parvovirus heartworm disease)
-Myeloproliferative disorders (eg FeLV feline immunodeficiency virus [FIV]) lymphoma tumor metastasis
-Estrogen-secreting tumors (eg Sertoli cell tumor) -Myelofibrosis -Immune-mediated megakaryocytic hypoplasia or
aplasia -Chronic renal disease
bull Reduced circulating platelet life span -Sequestration (eg splenomegaly) -Immune-mediated platelet destruction -Nonimmunologic platelet destruction
bull Microangiopathic thrombocytopenia (eg disseminated intravascular coagulation [DIG] tumor microvasculature [hemangiosarcoma hepatic tumors])
bull Microangiopathic hemolytic anemia bull Severe vascular injury and vasculitis (see
Vasculitis and uveitis) bull Drug-induced (eg heparin) bull Platelet loss via hemorrhage (usually mild
thrombocytopenia) bull Infectious agents (eg E canis Rickettsia
rickettsii Dirofilaria)
Thrombocytopathy (defects in platelet adhesion aggregation or release reactions)o
bull Inherited von Willebrands disease and other
hereditary thrombopathias including breed-specific thrombopathias
bull SystemiC illness Uremia collagen deficiency disease hepatic disease pancreatitis ehrlichiosis (E canis pound platys) FeLV dysproteinemia gammopathies myeloproliferativemyelodysplastic disorders DIG Iymphoproliferative disorders multiple myeloma
bull Drug-induced NSAIDs corticosteroids diuretic agents tranquilizers synthetic colloid solutions (eg dextran) 0- and ~-blockers and stimulators hormonal agents (eg prostacyclin estrogen) vinca alkaloids antibiotics and antiparasitic agents heparin
bull Antibody-mediated platelet dysfunction Immuneshymediated thrombocytopathy systemic lupus erythematosus
Coagulopathy 81012-14
bull Inherited bull Acquired
Vasculitis and uveitisl 5-21
bull Infectious Rocky Mountain spotted fever ehrlichiosis leptospirosis brucellosis piroplasmosis leishmaniasis ophthalmomyiasis interna ocular filariasis (Dirofilaria immitis) tuberculosis geotrichosis protothecosis toxoplasmosis (Toxoplasma gondii) FIV FeLV feline infectious peritonitis (FIP) canine adenovirus 1 cryptococcosis blastomycosis coccidioidomycosis candidiasis
bull Immune-mediated (eg uveodermatologic syndrome) bull Neoplasia (eg lymphosarcoma ocular sarcoma
metastatic tumors)
bull Lens-induced uveitis bull Episcleritis bull SystemiC inflammatory response syndrome SepSiS
endotoxemia (eg pyometra) bull Secondary to keratitis or trauma
bull Idiopathic
Noninflammatory vascular disorders22
bull Hyperadrenocorticism bull Ehlers-Danlos syndrome
Hypel
bull M(
an eh
bull Se po
Syste
Neov
bull Re
Throm Defe
can res fen s m be ind qui red rain dr rhy she renden counr
Coagu Abnc
parhwa abnorrr rna C rhird-cc body c be inhe rhages neous I coagulc
bocYlOl able de signs 0 1
owners
Compendium November 1999 20TH ANNIVERSARY Small AnimalExotics 1067
Causes of Hyphema (continued)
Hyperviscosity syndrome923-27
bull Mono- or polyclonal gammopathies Multiple myeloma lymphoma leukemia chronic inflammation antigenic stimulation (eg dirofilariasis) FIV FIP ehrlichiosis (E canis E platys)
bull Severe erythrocytosis Hemorrhagic gastroenteritis polycythemia vera erythropoietin-secreting neoplasms
Systemic hypertension 28-30
Neovascularization of uveal and retinal tissues bull Retinal detachment61831-JJ
-Primary -Secondary Lenticular disease infectious diseases
(see Vasculitis and uveitis) nonseptic inflammation (see Vasculitis and uveitis) trauma (see Trauma) intraocular neoplasia (see Neoplasia) systemic neoplasia (eg multiple myeloma) systemic hypertension (ie hypertensive retinopathy see
Thrombocytopathy Defects in platelet adhesion aggregation or release
can result in ineffectual platelet function II These deshyfects may be inherited (eg von Willebrands disease) be induced by systemic disorders or as in most acshyquired cases occur as an idiosyncratic reaction to cershytain drugs (see Causes of Hyphema) Thrombocytopashythy should be suspected in patients with hemorrhagic tendency prolonged bleeding time appropriate platelet count and normal tests of secondary hemorrhage
Coagulopathy Abnormalities of the intrinsic extrinsic or common
pathways of the clotting cascade may result in clotting abnormalities and subsequent hemorrhage and hypheshymao Coagulopathies are typified clinically by large third-compartment or major organ hemorrhages (eg body cavity pulmonary musdedeep tissue) and may be inherited or acquired Although ecchymotic hemorshyrhages are classically described in coagulopathies cutashyneous hemorrhages are less common in animals with coagulopathies than are thrombocyropenias and thromshybocytopathies Clinical presentation is extremely varishyable depending on the site of hemorrhage Secondary signs of anemia (weakness pallor) are often noted by owners of animals with a coagulopathy
Systemic Hypertension section in text) congenital abnormalities (eg retinal dysplasia) senile degenerative changes
bull Chronic glaucoma6
bull Intraocular neoplasia34
-Primary Lymphosarcoma adenoma and adenocarcinoma melanoma posttraumatic ocular sarcoma in cats
-Secondary Adenocarcinoma transitional cell carcinoma lymphoma multiple myeloma
Congenital anomalies 3135
bull Collie eye anomaly bull Vitreoretinal dysplasia (eg in Bedlington terriers
Sealyham terriers Labrador retrievers) bull Persistent hyaloid artery (eg with persistent
hyperplastic primary vitreous in Doberman pinschers)
Anemia
Vasculitis Vascular endothelial cell abnormalities may result in
transmural extravasation of blood from vascular chanshynels in the iris and ciliary body resulting in breakdown of the blood-aqueous barrier and hyphema Vasculitis may result from primary or secondary immune-mediatshyed destruction of endothelial cells (eg immune-medishyated vasculitis toxoplasmosis) infectious diseases (eg leptospirosis Rocky Mountain spotted fever feline inshyfectious peritonitis) neoplasia or systemic inflammatoshyry response syndrome (eg sepsis) Noninflammatory vascular disorders including hyperadrenocorticism and Ehler-Danlos syndrome can also result in hemorrhage
Hyperviscosity Syndrome Diseases that produce excessive globulins or other plasshy
ma proteins may result in hyphema because of (1) vascushylar endothelial cell compromise caused by intravascular sludging of blood with vessel wall necrosis (2) infiltrashytion of proteins into the vessel wall (3) inhibition of hemostasis secondary to reduction in clotting factors andor (4) coating of platelets by abnormal paraproteins resul ring in abnormal platelet aggregation 23 Funduscopic examination of the contralateral eye may reveal engorged retinal vasculature and retinal hemorrhages Common causes of hyperviscosity include plasma cell myeloma
ECCHYMOTIC HEMORRHAGE bull NONINFLAMMATORY VASCULAR DISORDERS bull PLASMA PROTEINS
I
1068 Small AnimalExotics 20TH ANNIVERSARY Compendium November 1999
lymphoma ehrlichiosis and chronic inflammatory disshy cell and fibroblast proliferation and subsequent ftbrovasshy often ease Serum total solids will generally be excessively eleshy cular membrane formation l6 The most frequent site of intrao vated because of hyperglobulinemia Hyperviscosity synshy fibrovascular membrane formation in eyes with chronic older drome can also be induced by severe erythrocytosis such retinal detachment is overlying the anterior iris surface glOsar as hemorrhagic gastroenteritis polycythemia vera and (pre-iridal ftbrovascular membrane) 16 Acute hyp hema montlshyerythropoietin~secreting neoplasms may occur if the retinal vasculature tears when the neushy unilatc
rosensory retina detaches from the underlying retinal traoCI SystemiC Hypertension pigment epithelial cells Clinicians must derermine the intrao
Hyphema arrributable to systemic hyperrension is cause of the retinal detachshy ondaI most common in old cats and dogs and is often caused ment because life-threarenshy oma) by chronic renal insufftciency Systemic hypertension ing systemic disease may be suit in affects only the arterial vascular system Chronic high the underlying abnormality arterial pressure may result in arteriosclerosis and aushy (see Causes of Hyphema) in Cong toregulatory arteriolar vasospasm Arteriolar disease our experience sponraneshy H)
causes ischemia and capillary permeability changes ous (idiopathic) retinal deshy to cor (with leakage of plasma proteins) and eventually hemshy tachment is rare in dogs and cawse
The more commoll causes oforrhage In our experience most cases of hyphema cats and an underlying cause is cha illtraocular hemorrhage werefrom vasoular hypertension are attribu table to retinall is usually present tribU[
detachment (see Neovascularization of Uveal and Retishy severekllown 20 years ago Since then
nal Tissues section) and most likely occur in response Chronic Glaucoma new infictiom causes of rerrler to choroidal vascular hypertension Hyphema may be Pre-iridal fibrovascular hypema such as felille er spa less commonly caused by tearing of retinal vasculature membranes are also frequentshy immunodeficiency virus have plere that occurs during retinal detachment Otber common ly detected in eyes with been detected Research Oller the subselt causes of vascular hypertension include hyperthyroidism chronic (end-stage) glaucoshy and vpast 20 years has demollstrated hyperadrenocorticism hyperaldosteronism and pheoshy ma G It is likely that hypheshy curs smarty mediators of chromocytoma ma attributable to chronic fetal rneollasclilarizatiort and
glaucoma occurs secondary tent hintraocular inflammation TheNeovascularization of Uveal and Retinal Tissues to tearing and leakage of the body
methodologies for diAgnosticAlthough the presence of blood vessels is necessary in fragile pre-iridal mlcrovascushyworkup hmle improved with themost tissues neovascularization or angiogenesis of tissues lature f Anen
advent ofB-modecan cause severe disease The surfaces of the retina and Acc iris are vulnerable to symptomatic neovasCldarizationl6 Intraocular Neoplasia ultrasonography computed severe Possible causes for neovascularization are ischemia (inshy Growth of a neoplasm largshy l tomography and magnetic can cc cluding long-standing retinal detachment) intraocular er than 2 to 3 mm-l requires resonallce imaging Howeller low 5 neoplasia and inflammation 6 Vascular proliferation on development of a microvasshy the primar) management issues dothe the anterior iris surhce (rubeosis iridis) leads to the forshy cular network to facilitate vesselofhyphema halle remained mation of a pre-iridal ftbrovascular membrane which delivery of nutrients and unchartged A few new can involve the peripheral iris and iridocorneal drainage oxygen and removal of treatment OptiOIlS have been angle and result in obstruction of aqueous humor outshy catabolites 38 Primary and added such as tissue flow Angiogenesis a complex process that incllldes metastatic intraocular neoshy I B(
plasminogm actillator and mdegradation of extracellular matrix and endothelial cell plasms of the anterior uveal topical carbonic anhydrllSe thproliferation is stringently regulated by numerous tissues are highly vascular
2 l(shyinhibitors UnfortulUltely theproangiogenic and antiangiogenic factors Examples of These neoplasms secrete mprognosis for main fair-ling lIisiollgrowth factors that stimulate endothelial cell proliferashy vascular growth factors (eg 3 l(shy
tion include fibroblast growth factors insulinlike growth VEGF TGF-~) that stimushy in an eye with hyphema has Ai factors transforming growth factor-~ (TGF-~) and vasshy late formation and rapid generally remained the Sfme 4 G cular endothelial growth factor (VEGF)lG The newly growth of vessels to support oller the past 20 years H
grown vessels are exceedingly fragile leal( readily and can and sustain rumor growthY 5 G pIpotentially result in hemorrhage and hyphema17 Newly developed capillaries 2(
of neoplasms are prone to 6 MRetinal Detachment hemorrhage because they p
Long-standing retinal detachment stimulates producshy have incomplete basement tion of growth factors that induce vascular endothelial membranes are leaky and 7 Jo
ARTERIOLAR DISEASE PRE-IRIDAL FIBROVASCULAR MEMBRANE GROWTH FACTORS
15
I
Compendium November 1999 20TH ANNIVERSARY S~nia AnimalExotics 1069
often fracture J6 lS Animals with hyphema attributable to
intraocular neoplasia are usually in late middle age or older however we have diagnosed ciliary body hemanshygiosarcoma and iris melanoma in dogs as young as 7 months of age Most primary inrraocular neoplasms are unilateral and thus hyphema attributable to primary inshytraocular neoplasia is unilateral Bilateral primary intraocular neoplasms are reponed infrequenrlyj~ Secshyondary or metastatic intraocular neoplasia (eg lymphshyoma) may affect one or both eyes and may -therefore reshysult in unilateral or bilateral hyphema
Congenital Ocular Anomalies Hyphema in young animals should prompt clinicians
to consider congenital ocular malformation as a ilikely cause Collie eye anomaly which is recessively inherited is characterized by defects of the choroid and sclera atshytributable to abnormal mesodermal differentiation5J In severe cases of vitreoretinal dysplasia (eg in Bedlington terriers Sealyham terriers Labrador retrievers or springshyer spaniels) retinal folding is sufficient to permit comshyplete retinal detachmenr 3 135 Retinal detachment and subsequent hyphema may occur w~h collie eye anomaly and vitreoretinal dysplasia Persistent hyaloid artery ocshycurs sporadically in dogs and is caused by failure of the fetal hyaloid vasculature to regress l5 Rupture of a persisshytent hyaloid artery leads to hemorrhage into the vitreolls body with blood passing into the anterior chamber l5
Anemia According to our experience and a previous report 40
severe acute anemia (eg severe tick or flea infestation) can cause hyphema when hemoglobin rapidly drops beshylow 5 mgdl Insufficient oxygen supply may cause enshydothelial cells to die which leads to leaking of blood vessels
REFERENCES I Belhorn R An overview of the blood-ocular barriers Seyshy
mour R Roberts Memorial Lecture Prog Vet Comp Ophshythalmoll(3)205- 2171991
2 Wilson FM Traumatic hyphema Pathogenes is and manageshyment Ophthalmology 87(9)910- 919 1980
3 Winston SM Ocular emergencies Vet Clin North Am Small Anim Pract II (1 )59-76 1981
4 Gottsch JD H yphema Diagnosis and mallJgemenr Retina 10(Suppll)S65-S71 1990
5 Gilger Be Hamilton HL Wilkie DA et a1 Traumatic oculat proptosis in dogs and cats 84 cases (1980-1993) jAVMA 206(8)1186-11901995
6 Mackin A Cani ne immune-mediated thrombocytopcniashyParr I Compend Contin Educ lract Vet 17(3) 353-364 1995
7 Jordan HL Grindem CB Breitschwerdt EB Thrombocyshy
topenia in cats A retrospective study of 41 cases j Vet Intern Med7(5)261-265 1993
8 Peterso n JL Co uto CG Wellman ML H emosta tic disorshyder in cats A retrospective study and review of the literashyture j Vet Illtem Med ) (5 )298-302 1995
9 Shelton G H Linenberger ML Hematologic abnormalities associated with retroviral in fectio ns in the car Semi Vet Med Surg Small Anim 10(4)220-233 1 )95
10 Boudreaux MK Platelets and coagulation Vet Clin North Am Small Anim hart 26(5) I 065-1087 1996
I Ruiz de Gopegui R Feldman BF Acquired and inherited platelet dysfunction in small animals Compelle Conlill Edltc Pract Vet 20(9) 1039- 1052 1998
12 Fogh JM f ogh IT Inherited coagulation disorders Vet Clin NorthAm Small Anim Pmct 18(1 )231-243 1988
13 Hart SW Noire I Hemostatic disorders in feline immunoshydeficiency virus-seropositive cats j Vet [ntem Med 8(5)355shy362 1994
14 Lisciandro Sc H ohenhaus A Brooks M Coagulation abshynormalities in 22 cats with naturally occurring liver disease j Vet [ntem Med 12(2) 71-75 1998
15 Davidson MG Breitschwerdt EB Nas isse MP Roberts SM Ocular manifestations of Rocky Mountain sported fever in dogsjAVMA 194(6)777-78 1 1989
16 Peiffer J I RL Wilcock BP Yin H The padlOgencs is and sigshynificance of pre-iridal fibrovascular membrane in domes tic animals Vet Pat hoI 27(I)4 1-45 1990
17 Collins BK Moore CPo Diseases and surgery of the canine anterior uvea in Gdatt KN (ed) Veteril1UJ Ophthalmology ed 3 Baltimore Lippincott Williams amp Wilkins 1999 pp 755-795
18 Glaze MB Gelatt KN Feline ophthalmology in Gelart KN (ed) VeterinalJ Ophthalmology ed 3 Baltimore Lippincott Williams amp Wilkins 1999 pp 997-1052
19 Peiffer J r RL Wilcock BP Histopathologic study of uveitis in cats 139 caSes (1978- 1988) jAVMA 198(1) 135- 138 1991
20 Chavki n MJ Lappin MR Powell Cc et al Seroepidemioshylogic and clinical observations of 93 cases of uveitis in (1[1
Prog Vet Comp OphthalmoI2(1)29-36 1992 2 Bisrner S Allergic- and immunologic-mediared diseases of
the eye and adncxae Vet Clin North Am Small Anim Prtlct 24 (4)7 11-734 1994
22 Freeman LJ Hegreberg GA Robinette JD Ehlers-Danlos syndrome in dogs and cats Semin Vet IIled Surg Sma Al1im 2(3)221 - 227 1987
23 Lane IF RobertS SM Lappin MR Ocular manifestations of vascular disease Hypertension hyperv iscos ity and hypershylipidemia jAAHA 29( 1)28-36 1993
24 Hendrix DVH Celatt KN Smith PJ et al Ophthalmic dis shyease as the presenting complaim in five dogs with multiple myelomajAAHA34(2)121 - 1281998
25 Foster ES Lothrop Jr CD Pol)c)themia vera in a cat wirh cardiac hypertrophy jAVMA 192( (2) 1736-1738 1988
26 Hammer AS Couto CG Complications of multiple myeloshyma jAAHA 30(1)9-14 1994
27 Forresror SD G reco DS Relford RL Serum hyperviscos it) syndrome associated with multiple myeloma in rwo cats jAVMA 200(1)79-82 1992
28 Dimski DS Hawkins EC Canine sys temic hypertension Compend Con tin Educ Pract Vet 10(10) 1152- 1158 1988
29 Stiles J Polzin DJ Bisrner SI The prevalence of retinoparhy in cats with systemic hypertension and chronic renal failure Ot hyperthyroidism jAAHA 30(6) 564-572 1994
(alltilues 011 page 1091)
COLLIE EYE ANOMALY VITREORETINAL OYSPLASIA bull PERSISTENT HYALOIO ARTERY
Hyphema Part I Pathophysiologic Considerations Hyphema Part I Pathophysiologic Considerations
Abstract Abstract Hemorrhage in the anterior chamber of the eye or hyphema results from a breakdown of the blood-ocular barrier (BOB) and is frequently associated with inflammation of the iris ciliary body or retina Hyphema can also occur by retrograde blood flow into the anterior chamber via the aqueous humor drainage pathways without BOB breakdown Hyphema attributable to blunt or perforating ocular trauma is more common than that resulting from endogenous causes When trauma has been eliminated as a possible cause it is prudent to assume that every animal with hyphema has a serious systemic disease until proven otherwise
Disciplines Disciplines Medicine and Health Sciences | Ophthalmology | Veterinary Medicine
Comments Comments Dr Komaacuteromy was affiliated with the University of Pennsylvania from 2003-2012
Part II can be found at httprepositoryupenneduvet_papers52
Author(s) Author(s) Andraacutes M Komaacuteromy David T Ramsey Dennis E Brooks Cynthia C Ramsey Maria E Kallberg and Stacy E Andrew
This journal article is available at ScholarlyCommons httpsrepositoryupenneduvet_papers51
1064 20TH ANNIVERSARY Vol 21 No 11 November 1999
CE Article 5 (15 contact hours) Helereed Peer Review
FOCAL POINT
Hyphema is frequently associated with iridocyclitis and generally indicates severe intraocular or systemic disease
KEY FACTS
Athorough diagnostic evaluation should be initiated when hyphema is present p 1064
Hyphema generally results from a breakdown of the blood-ocular barrier p 1064
The diagnostic differentials for hyphema do not differ substantially from those for hemorrhage into other areas of the body p 1065
When trauma has been eliminated as source of hyphema the diagnostic and therapeutic approach is directed by results of the physical and ophthalmic examinations p 1065
and e with of pel of the frequ rna blood Iy calHyphema Part 1 and ( but iPathophysiologic Considerations hyph(
University of florida
Andras M Komaromy DLmedvet
Dennis E Brooks DVM PhD
Maria E Kallberg DVM Stacy E Andrew DVM
capsu do nl
Michigan State University move David T Ramsey DVM anteri
ous a Cynthia C Ramsey DVM MS Be(
highe age F blooe lower
ABSTRACT Hemorrhage in the anterior chamber of the eye or hyphema results from a breakmiddot predi down of the blood-ocular barrier (BOB) and is frequently associated with inflammation of the the al iris ciliary body or retina Hyphema can also occur by retrograde blood flow into the anterior chamber via the aqueous humor drainage pathways without BOB breakdown Hyphema atmiddot PAntributable to blunt or perforating ocular trauma is more common than that resulting from enmiddot
Widogenous causes When trauma has been eliminated as a possible cause it is prudent to asshyagnossume that every animal with hyphema has aserious systemic disease until proven otherwise tially
H body
)Phema is defined as hemorrhage within the anterior chamber of the eye diagn (Figure 1) In contrast the accumulation of leukocytes in the nterior hyphl chamber is termed h)P0pyon The etiopathogenesis of hyphema is mulshy dison
tifactorial but ultimately the final common pathway is breakdown of the soum blood-ocular barrier (BOB) and subsequent inrraocular hemorrhage that is ofshy so thl ten associated with inflammation Many of the mechanisms that cause intraocushy ation lar hemorrhage may also result in hemorrhage in other parts of the body This I1Ism~
article foclIses on hyphema as a red flag for sight-threatening ocular or lifeshythreatening systemic hemorrhagic disease Irido
When hyphema is present a thorough diagrwstic evaluation similar ro that inshy lri( dicated for any third-compartment hemorrhage (eg hemoabdomen hemothoshy ocula rax) should be initiated Attentive clinicians will recognize the importance of a aque( thorough diagnostic workup before or during the initial treatment of hyphema ner I Death attributable to systemic or vital organ hemorrhage may occur if the diagshy terns) nostic workup is incomplete Part I of this two-parr presentation focuses on the rncltJ many pathophysiologic mechanisms that most frequenrly result in hyphema the f each of which is considered as a separate entity in this article However concurshy discu rent involvement of more than one mechanism is common Part II will cover dishy ble c agnosis and treatment of hyphema left L
cyclil BLOOD-OCULAR BARRIER ceils
The BOB which consists of the blood-aqueous and blood-retinal barriers preshyvents erythrocytes and leukocytes and inhibits tissue fluids and proteins from entershy Trau ing nonvascular ocular tissues and compartments The BOB consists of endothelial H~
- ------ - - -- - - - - - -- - - ---
Compendium November 1999 20TH ANNIVERSARY Small AnimalExotics 1065
and epithelial tight junctions with variations in their degree of permeability l Dysfunction of the blood-aqueous barrier frequently results in hypheshyrna breakdown of the blood-r-tinal barrier generalshyly causes retinal subretinal and choroidal hemorrhage but infrequently results in hyphema The posterior lens capsule and zonules limit but do not com pletely preven t movement of blood from the anterior chamber to the vitreshyous and vice versa
Figure 1-Hyphema in a dog
Because the intraocular pressure (lOP) is normally higher than the pressure in the aqueous humor drainshyage pathways (the scleral venous plexus) retrograde blood flow into the anterior chamber is prevented lOP lower than the pressure in the scleral venous plexus may predispose to hyphema via retrograde blood flow into the anterior chamber
PATHOPHYSIOLOGIC APPROACH With the exception of severe intraocular disease the dishy
agnostic differentials for hyphema do not differ substanshytially from those for hemorrhage in other areas of the body (eg hemothorax hemoabdomen) therefore the diagnostic approach to determine the underlying cause of hyphema is similar In addition to systemic causes ocular disorders should be considered Clinicians must develop a sound understanding of the potential causes of hyphema so they are able to construct a list of differential considershyations for each mechanism The most common mechashynisms of hemorrhage that may result in hyphema follow
Iridocyclitis Iridocyclitis (anterior uveitis) is the most common
ocular disease associated with a breakdown of the bloodshyaqueous barrier Disruption of the blood-aqueous barshyrier may lead to aqueous flare (predominantly proshyteins) hypopyon andor hyphema depending on the inciting stimulus and duration of the disease Most of the pathophysiologic mechanisms of BOB breakdown discussed in the remainder of this article are also possishyble causes for iridocyclitis Regardless of the caLIse if left untreated hyphema will eventually result in iridoshycyclitis when chemotactic triggers recruit inflammatory cells for cleanup
Trauma Hyphema attributable to exogenous causes (blunt or
perforating trauma) is probshyably more common than that resulting from endogenous causes (see Causes of Hypheshyrna) Blunt trauma to the head seldom resuhs in hypheshyrna because the eyeball is proshytected by anterior portions of the bony orbit and orbital soft tissues However severe blunt trauma to the anterior orbital rim or periorbital soft tissues and eyeball may reshy
suit in hyphema In this case -- - - - - -- - -- - -- - -- -- - - - - examination and palpation
of the periorbital area usualshyIy reveals clinical signs of trauma such as swelling and bruising of the eyelids and conjunctiva fracture of the bony orbit or orbital hemorrhage and resultant orbital mass effect Bilateral hyphema is seldom caused by mild trauma When blunt ocular trauma occurs the sudden rise in lOP associated with ocular indentation causes anterior chamber angle distortion and may result in rupture of iris stromal or ciliary body vessels and subsequent hyphema4
Perforating trauma (eg cat scratch BB pellets) to the eye baH (cornea sclera) with direct damage to inshytraocular vasculature is more likely to result in traushymatic hyphema than is blunt trauma Traumatic hyshyphema can also be associated with proptosis of the globe and may be accompanied by structural damage to the eye including lens subluxation and dislocation vitreous hemorrhage or retinal detachment Head rashydiographs help to reveal fractures of the orbit or skull in trauma cases When exogenous sources of hyphema have been eliminated the diagnostic approach is furshyther directed by results of physical and ophthalmic exshyamll1atIons
Thrombocytopenia Lack of an adequate number of circulating platelets
can result in hyphema and hemorrhage secondary to ongoing capiuary microtrauma induced by normal acshytiviry or exogenous insult6 Thrombocytopenia is typishyfied clinically by petechial hemorrhage of mucosal and cutaneous surfaces Hyphema and concurrent petechial hemorrhages should prompt clinicians to consider thrombocytopenia as a likely mechanism of disease Thrombocywpenia may be induced by immune-medishyated destruction of platelets infectious agents (eg Ehrlichia canis platys or risticii Leptojpira species Rickettsia rickettsil) sepsis splenomegaly neoplasia or disseminated intravascular coagulation
ANTERIOR UVEITIS bull PERFORATING TRAUMA PETECHIAL HEMORRHAGE
middot
1066 Small An imalExotics 20TH ANNIVERSARY Compendium November 1999
Causes of Hyphema
Trauma2-5
bull Blunt bull Penetrating (with or without foreign body)
Thrombocytopenia6-10
bull Decreased platelet production in the bone marrow -Drug or chemical toxicity-induced bone marrow
hypoplasia (eg estrogens antiinflammatory agents antibiotics tranquilizing agents diuretic agents dapsone myelosuppressive chemotherapy)
-Toxic doses of irradiation -Chronic infections (e g feline leukemia virus
[FeLV] Ehrlichia canis Ehrlichia platys canine distemper parvovirus heartworm disease)
-Myeloproliferative disorders (eg FeLV feline immunodeficiency virus [FIV]) lymphoma tumor metastasis
-Estrogen-secreting tumors (eg Sertoli cell tumor) -Myelofibrosis -Immune-mediated megakaryocytic hypoplasia or
aplasia -Chronic renal disease
bull Reduced circulating platelet life span -Sequestration (eg splenomegaly) -Immune-mediated platelet destruction -Nonimmunologic platelet destruction
bull Microangiopathic thrombocytopenia (eg disseminated intravascular coagulation [DIG] tumor microvasculature [hemangiosarcoma hepatic tumors])
bull Microangiopathic hemolytic anemia bull Severe vascular injury and vasculitis (see
Vasculitis and uveitis) bull Drug-induced (eg heparin) bull Platelet loss via hemorrhage (usually mild
thrombocytopenia) bull Infectious agents (eg E canis Rickettsia
rickettsii Dirofilaria)
Thrombocytopathy (defects in platelet adhesion aggregation or release reactions)o
bull Inherited von Willebrands disease and other
hereditary thrombopathias including breed-specific thrombopathias
bull SystemiC illness Uremia collagen deficiency disease hepatic disease pancreatitis ehrlichiosis (E canis pound platys) FeLV dysproteinemia gammopathies myeloproliferativemyelodysplastic disorders DIG Iymphoproliferative disorders multiple myeloma
bull Drug-induced NSAIDs corticosteroids diuretic agents tranquilizers synthetic colloid solutions (eg dextran) 0- and ~-blockers and stimulators hormonal agents (eg prostacyclin estrogen) vinca alkaloids antibiotics and antiparasitic agents heparin
bull Antibody-mediated platelet dysfunction Immuneshymediated thrombocytopathy systemic lupus erythematosus
Coagulopathy 81012-14
bull Inherited bull Acquired
Vasculitis and uveitisl 5-21
bull Infectious Rocky Mountain spotted fever ehrlichiosis leptospirosis brucellosis piroplasmosis leishmaniasis ophthalmomyiasis interna ocular filariasis (Dirofilaria immitis) tuberculosis geotrichosis protothecosis toxoplasmosis (Toxoplasma gondii) FIV FeLV feline infectious peritonitis (FIP) canine adenovirus 1 cryptococcosis blastomycosis coccidioidomycosis candidiasis
bull Immune-mediated (eg uveodermatologic syndrome) bull Neoplasia (eg lymphosarcoma ocular sarcoma
metastatic tumors)
bull Lens-induced uveitis bull Episcleritis bull SystemiC inflammatory response syndrome SepSiS
endotoxemia (eg pyometra) bull Secondary to keratitis or trauma
bull Idiopathic
Noninflammatory vascular disorders22
bull Hyperadrenocorticism bull Ehlers-Danlos syndrome
Hypel
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can res fen s m be ind qui red rain dr rhy she renden counr
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Compendium November 1999 20TH ANNIVERSARY Small AnimalExotics 1067
Causes of Hyphema (continued)
Hyperviscosity syndrome923-27
bull Mono- or polyclonal gammopathies Multiple myeloma lymphoma leukemia chronic inflammation antigenic stimulation (eg dirofilariasis) FIV FIP ehrlichiosis (E canis E platys)
bull Severe erythrocytosis Hemorrhagic gastroenteritis polycythemia vera erythropoietin-secreting neoplasms
Systemic hypertension 28-30
Neovascularization of uveal and retinal tissues bull Retinal detachment61831-JJ
-Primary -Secondary Lenticular disease infectious diseases
(see Vasculitis and uveitis) nonseptic inflammation (see Vasculitis and uveitis) trauma (see Trauma) intraocular neoplasia (see Neoplasia) systemic neoplasia (eg multiple myeloma) systemic hypertension (ie hypertensive retinopathy see
Thrombocytopathy Defects in platelet adhesion aggregation or release
can result in ineffectual platelet function II These deshyfects may be inherited (eg von Willebrands disease) be induced by systemic disorders or as in most acshyquired cases occur as an idiosyncratic reaction to cershytain drugs (see Causes of Hyphema) Thrombocytopashythy should be suspected in patients with hemorrhagic tendency prolonged bleeding time appropriate platelet count and normal tests of secondary hemorrhage
Coagulopathy Abnormalities of the intrinsic extrinsic or common
pathways of the clotting cascade may result in clotting abnormalities and subsequent hemorrhage and hypheshymao Coagulopathies are typified clinically by large third-compartment or major organ hemorrhages (eg body cavity pulmonary musdedeep tissue) and may be inherited or acquired Although ecchymotic hemorshyrhages are classically described in coagulopathies cutashyneous hemorrhages are less common in animals with coagulopathies than are thrombocyropenias and thromshybocytopathies Clinical presentation is extremely varishyable depending on the site of hemorrhage Secondary signs of anemia (weakness pallor) are often noted by owners of animals with a coagulopathy
Systemic Hypertension section in text) congenital abnormalities (eg retinal dysplasia) senile degenerative changes
bull Chronic glaucoma6
bull Intraocular neoplasia34
-Primary Lymphosarcoma adenoma and adenocarcinoma melanoma posttraumatic ocular sarcoma in cats
-Secondary Adenocarcinoma transitional cell carcinoma lymphoma multiple myeloma
Congenital anomalies 3135
bull Collie eye anomaly bull Vitreoretinal dysplasia (eg in Bedlington terriers
Sealyham terriers Labrador retrievers) bull Persistent hyaloid artery (eg with persistent
hyperplastic primary vitreous in Doberman pinschers)
Anemia
Vasculitis Vascular endothelial cell abnormalities may result in
transmural extravasation of blood from vascular chanshynels in the iris and ciliary body resulting in breakdown of the blood-aqueous barrier and hyphema Vasculitis may result from primary or secondary immune-mediatshyed destruction of endothelial cells (eg immune-medishyated vasculitis toxoplasmosis) infectious diseases (eg leptospirosis Rocky Mountain spotted fever feline inshyfectious peritonitis) neoplasia or systemic inflammatoshyry response syndrome (eg sepsis) Noninflammatory vascular disorders including hyperadrenocorticism and Ehler-Danlos syndrome can also result in hemorrhage
Hyperviscosity Syndrome Diseases that produce excessive globulins or other plasshy
ma proteins may result in hyphema because of (1) vascushylar endothelial cell compromise caused by intravascular sludging of blood with vessel wall necrosis (2) infiltrashytion of proteins into the vessel wall (3) inhibition of hemostasis secondary to reduction in clotting factors andor (4) coating of platelets by abnormal paraproteins resul ring in abnormal platelet aggregation 23 Funduscopic examination of the contralateral eye may reveal engorged retinal vasculature and retinal hemorrhages Common causes of hyperviscosity include plasma cell myeloma
ECCHYMOTIC HEMORRHAGE bull NONINFLAMMATORY VASCULAR DISORDERS bull PLASMA PROTEINS
I
1068 Small AnimalExotics 20TH ANNIVERSARY Compendium November 1999
lymphoma ehrlichiosis and chronic inflammatory disshy cell and fibroblast proliferation and subsequent ftbrovasshy often ease Serum total solids will generally be excessively eleshy cular membrane formation l6 The most frequent site of intrao vated because of hyperglobulinemia Hyperviscosity synshy fibrovascular membrane formation in eyes with chronic older drome can also be induced by severe erythrocytosis such retinal detachment is overlying the anterior iris surface glOsar as hemorrhagic gastroenteritis polycythemia vera and (pre-iridal ftbrovascular membrane) 16 Acute hyp hema montlshyerythropoietin~secreting neoplasms may occur if the retinal vasculature tears when the neushy unilatc
rosensory retina detaches from the underlying retinal traoCI SystemiC Hypertension pigment epithelial cells Clinicians must derermine the intrao
Hyphema arrributable to systemic hyperrension is cause of the retinal detachshy ondaI most common in old cats and dogs and is often caused ment because life-threarenshy oma) by chronic renal insufftciency Systemic hypertension ing systemic disease may be suit in affects only the arterial vascular system Chronic high the underlying abnormality arterial pressure may result in arteriosclerosis and aushy (see Causes of Hyphema) in Cong toregulatory arteriolar vasospasm Arteriolar disease our experience sponraneshy H)
causes ischemia and capillary permeability changes ous (idiopathic) retinal deshy to cor (with leakage of plasma proteins) and eventually hemshy tachment is rare in dogs and cawse
The more commoll causes oforrhage In our experience most cases of hyphema cats and an underlying cause is cha illtraocular hemorrhage werefrom vasoular hypertension are attribu table to retinall is usually present tribU[
detachment (see Neovascularization of Uveal and Retishy severekllown 20 years ago Since then
nal Tissues section) and most likely occur in response Chronic Glaucoma new infictiom causes of rerrler to choroidal vascular hypertension Hyphema may be Pre-iridal fibrovascular hypema such as felille er spa less commonly caused by tearing of retinal vasculature membranes are also frequentshy immunodeficiency virus have plere that occurs during retinal detachment Otber common ly detected in eyes with been detected Research Oller the subselt causes of vascular hypertension include hyperthyroidism chronic (end-stage) glaucoshy and vpast 20 years has demollstrated hyperadrenocorticism hyperaldosteronism and pheoshy ma G It is likely that hypheshy curs smarty mediators of chromocytoma ma attributable to chronic fetal rneollasclilarizatiort and
glaucoma occurs secondary tent hintraocular inflammation TheNeovascularization of Uveal and Retinal Tissues to tearing and leakage of the body
methodologies for diAgnosticAlthough the presence of blood vessels is necessary in fragile pre-iridal mlcrovascushyworkup hmle improved with themost tissues neovascularization or angiogenesis of tissues lature f Anen
advent ofB-modecan cause severe disease The surfaces of the retina and Acc iris are vulnerable to symptomatic neovasCldarizationl6 Intraocular Neoplasia ultrasonography computed severe Possible causes for neovascularization are ischemia (inshy Growth of a neoplasm largshy l tomography and magnetic can cc cluding long-standing retinal detachment) intraocular er than 2 to 3 mm-l requires resonallce imaging Howeller low 5 neoplasia and inflammation 6 Vascular proliferation on development of a microvasshy the primar) management issues dothe the anterior iris surhce (rubeosis iridis) leads to the forshy cular network to facilitate vesselofhyphema halle remained mation of a pre-iridal ftbrovascular membrane which delivery of nutrients and unchartged A few new can involve the peripheral iris and iridocorneal drainage oxygen and removal of treatment OptiOIlS have been angle and result in obstruction of aqueous humor outshy catabolites 38 Primary and added such as tissue flow Angiogenesis a complex process that incllldes metastatic intraocular neoshy I B(
plasminogm actillator and mdegradation of extracellular matrix and endothelial cell plasms of the anterior uveal topical carbonic anhydrllSe thproliferation is stringently regulated by numerous tissues are highly vascular
2 l(shyinhibitors UnfortulUltely theproangiogenic and antiangiogenic factors Examples of These neoplasms secrete mprognosis for main fair-ling lIisiollgrowth factors that stimulate endothelial cell proliferashy vascular growth factors (eg 3 l(shy
tion include fibroblast growth factors insulinlike growth VEGF TGF-~) that stimushy in an eye with hyphema has Ai factors transforming growth factor-~ (TGF-~) and vasshy late formation and rapid generally remained the Sfme 4 G cular endothelial growth factor (VEGF)lG The newly growth of vessels to support oller the past 20 years H
grown vessels are exceedingly fragile leal( readily and can and sustain rumor growthY 5 G pIpotentially result in hemorrhage and hyphema17 Newly developed capillaries 2(
of neoplasms are prone to 6 MRetinal Detachment hemorrhage because they p
Long-standing retinal detachment stimulates producshy have incomplete basement tion of growth factors that induce vascular endothelial membranes are leaky and 7 Jo
ARTERIOLAR DISEASE PRE-IRIDAL FIBROVASCULAR MEMBRANE GROWTH FACTORS
15
I
Compendium November 1999 20TH ANNIVERSARY S~nia AnimalExotics 1069
often fracture J6 lS Animals with hyphema attributable to
intraocular neoplasia are usually in late middle age or older however we have diagnosed ciliary body hemanshygiosarcoma and iris melanoma in dogs as young as 7 months of age Most primary inrraocular neoplasms are unilateral and thus hyphema attributable to primary inshytraocular neoplasia is unilateral Bilateral primary intraocular neoplasms are reponed infrequenrlyj~ Secshyondary or metastatic intraocular neoplasia (eg lymphshyoma) may affect one or both eyes and may -therefore reshysult in unilateral or bilateral hyphema
Congenital Ocular Anomalies Hyphema in young animals should prompt clinicians
to consider congenital ocular malformation as a ilikely cause Collie eye anomaly which is recessively inherited is characterized by defects of the choroid and sclera atshytributable to abnormal mesodermal differentiation5J In severe cases of vitreoretinal dysplasia (eg in Bedlington terriers Sealyham terriers Labrador retrievers or springshyer spaniels) retinal folding is sufficient to permit comshyplete retinal detachmenr 3 135 Retinal detachment and subsequent hyphema may occur w~h collie eye anomaly and vitreoretinal dysplasia Persistent hyaloid artery ocshycurs sporadically in dogs and is caused by failure of the fetal hyaloid vasculature to regress l5 Rupture of a persisshytent hyaloid artery leads to hemorrhage into the vitreolls body with blood passing into the anterior chamber l5
Anemia According to our experience and a previous report 40
severe acute anemia (eg severe tick or flea infestation) can cause hyphema when hemoglobin rapidly drops beshylow 5 mgdl Insufficient oxygen supply may cause enshydothelial cells to die which leads to leaking of blood vessels
REFERENCES I Belhorn R An overview of the blood-ocular barriers Seyshy
mour R Roberts Memorial Lecture Prog Vet Comp Ophshythalmoll(3)205- 2171991
2 Wilson FM Traumatic hyphema Pathogenes is and manageshyment Ophthalmology 87(9)910- 919 1980
3 Winston SM Ocular emergencies Vet Clin North Am Small Anim Pract II (1 )59-76 1981
4 Gottsch JD H yphema Diagnosis and mallJgemenr Retina 10(Suppll)S65-S71 1990
5 Gilger Be Hamilton HL Wilkie DA et a1 Traumatic oculat proptosis in dogs and cats 84 cases (1980-1993) jAVMA 206(8)1186-11901995
6 Mackin A Cani ne immune-mediated thrombocytopcniashyParr I Compend Contin Educ lract Vet 17(3) 353-364 1995
7 Jordan HL Grindem CB Breitschwerdt EB Thrombocyshy
topenia in cats A retrospective study of 41 cases j Vet Intern Med7(5)261-265 1993
8 Peterso n JL Co uto CG Wellman ML H emosta tic disorshyder in cats A retrospective study and review of the literashyture j Vet Illtem Med ) (5 )298-302 1995
9 Shelton G H Linenberger ML Hematologic abnormalities associated with retroviral in fectio ns in the car Semi Vet Med Surg Small Anim 10(4)220-233 1 )95
10 Boudreaux MK Platelets and coagulation Vet Clin North Am Small Anim hart 26(5) I 065-1087 1996
I Ruiz de Gopegui R Feldman BF Acquired and inherited platelet dysfunction in small animals Compelle Conlill Edltc Pract Vet 20(9) 1039- 1052 1998
12 Fogh JM f ogh IT Inherited coagulation disorders Vet Clin NorthAm Small Anim Pmct 18(1 )231-243 1988
13 Hart SW Noire I Hemostatic disorders in feline immunoshydeficiency virus-seropositive cats j Vet [ntem Med 8(5)355shy362 1994
14 Lisciandro Sc H ohenhaus A Brooks M Coagulation abshynormalities in 22 cats with naturally occurring liver disease j Vet [ntem Med 12(2) 71-75 1998
15 Davidson MG Breitschwerdt EB Nas isse MP Roberts SM Ocular manifestations of Rocky Mountain sported fever in dogsjAVMA 194(6)777-78 1 1989
16 Peiffer J I RL Wilcock BP Yin H The padlOgencs is and sigshynificance of pre-iridal fibrovascular membrane in domes tic animals Vet Pat hoI 27(I)4 1-45 1990
17 Collins BK Moore CPo Diseases and surgery of the canine anterior uvea in Gdatt KN (ed) Veteril1UJ Ophthalmology ed 3 Baltimore Lippincott Williams amp Wilkins 1999 pp 755-795
18 Glaze MB Gelatt KN Feline ophthalmology in Gelart KN (ed) VeterinalJ Ophthalmology ed 3 Baltimore Lippincott Williams amp Wilkins 1999 pp 997-1052
19 Peiffer J r RL Wilcock BP Histopathologic study of uveitis in cats 139 caSes (1978- 1988) jAVMA 198(1) 135- 138 1991
20 Chavki n MJ Lappin MR Powell Cc et al Seroepidemioshylogic and clinical observations of 93 cases of uveitis in (1[1
Prog Vet Comp OphthalmoI2(1)29-36 1992 2 Bisrner S Allergic- and immunologic-mediared diseases of
the eye and adncxae Vet Clin North Am Small Anim Prtlct 24 (4)7 11-734 1994
22 Freeman LJ Hegreberg GA Robinette JD Ehlers-Danlos syndrome in dogs and cats Semin Vet IIled Surg Sma Al1im 2(3)221 - 227 1987
23 Lane IF RobertS SM Lappin MR Ocular manifestations of vascular disease Hypertension hyperv iscos ity and hypershylipidemia jAAHA 29( 1)28-36 1993
24 Hendrix DVH Celatt KN Smith PJ et al Ophthalmic dis shyease as the presenting complaim in five dogs with multiple myelomajAAHA34(2)121 - 1281998
25 Foster ES Lothrop Jr CD Pol)c)themia vera in a cat wirh cardiac hypertrophy jAVMA 192( (2) 1736-1738 1988
26 Hammer AS Couto CG Complications of multiple myeloshyma jAAHA 30(1)9-14 1994
27 Forresror SD G reco DS Relford RL Serum hyperviscos it) syndrome associated with multiple myeloma in rwo cats jAVMA 200(1)79-82 1992
28 Dimski DS Hawkins EC Canine sys temic hypertension Compend Con tin Educ Pract Vet 10(10) 1152- 1158 1988
29 Stiles J Polzin DJ Bisrner SI The prevalence of retinoparhy in cats with systemic hypertension and chronic renal failure Ot hyperthyroidism jAAHA 30(6) 564-572 1994
(alltilues 011 page 1091)
COLLIE EYE ANOMALY VITREORETINAL OYSPLASIA bull PERSISTENT HYALOIO ARTERY
1064 20TH ANNIVERSARY Vol 21 No 11 November 1999
CE Article 5 (15 contact hours) Helereed Peer Review
FOCAL POINT
Hyphema is frequently associated with iridocyclitis and generally indicates severe intraocular or systemic disease
KEY FACTS
Athorough diagnostic evaluation should be initiated when hyphema is present p 1064
Hyphema generally results from a breakdown of the blood-ocular barrier p 1064
The diagnostic differentials for hyphema do not differ substantially from those for hemorrhage into other areas of the body p 1065
When trauma has been eliminated as source of hyphema the diagnostic and therapeutic approach is directed by results of the physical and ophthalmic examinations p 1065
and e with of pel of the frequ rna blood Iy calHyphema Part 1 and ( but iPathophysiologic Considerations hyph(
University of florida
Andras M Komaromy DLmedvet
Dennis E Brooks DVM PhD
Maria E Kallberg DVM Stacy E Andrew DVM
capsu do nl
Michigan State University move David T Ramsey DVM anteri
ous a Cynthia C Ramsey DVM MS Be(
highe age F blooe lower
ABSTRACT Hemorrhage in the anterior chamber of the eye or hyphema results from a breakmiddot predi down of the blood-ocular barrier (BOB) and is frequently associated with inflammation of the the al iris ciliary body or retina Hyphema can also occur by retrograde blood flow into the anterior chamber via the aqueous humor drainage pathways without BOB breakdown Hyphema atmiddot PAntributable to blunt or perforating ocular trauma is more common than that resulting from enmiddot
Widogenous causes When trauma has been eliminated as a possible cause it is prudent to asshyagnossume that every animal with hyphema has aserious systemic disease until proven otherwise tially
H body
)Phema is defined as hemorrhage within the anterior chamber of the eye diagn (Figure 1) In contrast the accumulation of leukocytes in the nterior hyphl chamber is termed h)P0pyon The etiopathogenesis of hyphema is mulshy dison
tifactorial but ultimately the final common pathway is breakdown of the soum blood-ocular barrier (BOB) and subsequent inrraocular hemorrhage that is ofshy so thl ten associated with inflammation Many of the mechanisms that cause intraocushy ation lar hemorrhage may also result in hemorrhage in other parts of the body This I1Ism~
article foclIses on hyphema as a red flag for sight-threatening ocular or lifeshythreatening systemic hemorrhagic disease Irido
When hyphema is present a thorough diagrwstic evaluation similar ro that inshy lri( dicated for any third-compartment hemorrhage (eg hemoabdomen hemothoshy ocula rax) should be initiated Attentive clinicians will recognize the importance of a aque( thorough diagnostic workup before or during the initial treatment of hyphema ner I Death attributable to systemic or vital organ hemorrhage may occur if the diagshy terns) nostic workup is incomplete Part I of this two-parr presentation focuses on the rncltJ many pathophysiologic mechanisms that most frequenrly result in hyphema the f each of which is considered as a separate entity in this article However concurshy discu rent involvement of more than one mechanism is common Part II will cover dishy ble c agnosis and treatment of hyphema left L
cyclil BLOOD-OCULAR BARRIER ceils
The BOB which consists of the blood-aqueous and blood-retinal barriers preshyvents erythrocytes and leukocytes and inhibits tissue fluids and proteins from entershy Trau ing nonvascular ocular tissues and compartments The BOB consists of endothelial H~
- ------ - - -- - - - - - -- - - ---
Compendium November 1999 20TH ANNIVERSARY Small AnimalExotics 1065
and epithelial tight junctions with variations in their degree of permeability l Dysfunction of the blood-aqueous barrier frequently results in hypheshyrna breakdown of the blood-r-tinal barrier generalshyly causes retinal subretinal and choroidal hemorrhage but infrequently results in hyphema The posterior lens capsule and zonules limit but do not com pletely preven t movement of blood from the anterior chamber to the vitreshyous and vice versa
Figure 1-Hyphema in a dog
Because the intraocular pressure (lOP) is normally higher than the pressure in the aqueous humor drainshyage pathways (the scleral venous plexus) retrograde blood flow into the anterior chamber is prevented lOP lower than the pressure in the scleral venous plexus may predispose to hyphema via retrograde blood flow into the anterior chamber
PATHOPHYSIOLOGIC APPROACH With the exception of severe intraocular disease the dishy
agnostic differentials for hyphema do not differ substanshytially from those for hemorrhage in other areas of the body (eg hemothorax hemoabdomen) therefore the diagnostic approach to determine the underlying cause of hyphema is similar In addition to systemic causes ocular disorders should be considered Clinicians must develop a sound understanding of the potential causes of hyphema so they are able to construct a list of differential considershyations for each mechanism The most common mechashynisms of hemorrhage that may result in hyphema follow
Iridocyclitis Iridocyclitis (anterior uveitis) is the most common
ocular disease associated with a breakdown of the bloodshyaqueous barrier Disruption of the blood-aqueous barshyrier may lead to aqueous flare (predominantly proshyteins) hypopyon andor hyphema depending on the inciting stimulus and duration of the disease Most of the pathophysiologic mechanisms of BOB breakdown discussed in the remainder of this article are also possishyble causes for iridocyclitis Regardless of the caLIse if left untreated hyphema will eventually result in iridoshycyclitis when chemotactic triggers recruit inflammatory cells for cleanup
Trauma Hyphema attributable to exogenous causes (blunt or
perforating trauma) is probshyably more common than that resulting from endogenous causes (see Causes of Hypheshyrna) Blunt trauma to the head seldom resuhs in hypheshyrna because the eyeball is proshytected by anterior portions of the bony orbit and orbital soft tissues However severe blunt trauma to the anterior orbital rim or periorbital soft tissues and eyeball may reshy
suit in hyphema In this case -- - - - - -- - -- - -- - -- -- - - - - examination and palpation
of the periorbital area usualshyIy reveals clinical signs of trauma such as swelling and bruising of the eyelids and conjunctiva fracture of the bony orbit or orbital hemorrhage and resultant orbital mass effect Bilateral hyphema is seldom caused by mild trauma When blunt ocular trauma occurs the sudden rise in lOP associated with ocular indentation causes anterior chamber angle distortion and may result in rupture of iris stromal or ciliary body vessels and subsequent hyphema4
Perforating trauma (eg cat scratch BB pellets) to the eye baH (cornea sclera) with direct damage to inshytraocular vasculature is more likely to result in traushymatic hyphema than is blunt trauma Traumatic hyshyphema can also be associated with proptosis of the globe and may be accompanied by structural damage to the eye including lens subluxation and dislocation vitreous hemorrhage or retinal detachment Head rashydiographs help to reveal fractures of the orbit or skull in trauma cases When exogenous sources of hyphema have been eliminated the diagnostic approach is furshyther directed by results of physical and ophthalmic exshyamll1atIons
Thrombocytopenia Lack of an adequate number of circulating platelets
can result in hyphema and hemorrhage secondary to ongoing capiuary microtrauma induced by normal acshytiviry or exogenous insult6 Thrombocytopenia is typishyfied clinically by petechial hemorrhage of mucosal and cutaneous surfaces Hyphema and concurrent petechial hemorrhages should prompt clinicians to consider thrombocytopenia as a likely mechanism of disease Thrombocywpenia may be induced by immune-medishyated destruction of platelets infectious agents (eg Ehrlichia canis platys or risticii Leptojpira species Rickettsia rickettsil) sepsis splenomegaly neoplasia or disseminated intravascular coagulation
ANTERIOR UVEITIS bull PERFORATING TRAUMA PETECHIAL HEMORRHAGE
middot
1066 Small An imalExotics 20TH ANNIVERSARY Compendium November 1999
Causes of Hyphema
Trauma2-5
bull Blunt bull Penetrating (with or without foreign body)
Thrombocytopenia6-10
bull Decreased platelet production in the bone marrow -Drug or chemical toxicity-induced bone marrow
hypoplasia (eg estrogens antiinflammatory agents antibiotics tranquilizing agents diuretic agents dapsone myelosuppressive chemotherapy)
-Toxic doses of irradiation -Chronic infections (e g feline leukemia virus
[FeLV] Ehrlichia canis Ehrlichia platys canine distemper parvovirus heartworm disease)
-Myeloproliferative disorders (eg FeLV feline immunodeficiency virus [FIV]) lymphoma tumor metastasis
-Estrogen-secreting tumors (eg Sertoli cell tumor) -Myelofibrosis -Immune-mediated megakaryocytic hypoplasia or
aplasia -Chronic renal disease
bull Reduced circulating platelet life span -Sequestration (eg splenomegaly) -Immune-mediated platelet destruction -Nonimmunologic platelet destruction
bull Microangiopathic thrombocytopenia (eg disseminated intravascular coagulation [DIG] tumor microvasculature [hemangiosarcoma hepatic tumors])
bull Microangiopathic hemolytic anemia bull Severe vascular injury and vasculitis (see
Vasculitis and uveitis) bull Drug-induced (eg heparin) bull Platelet loss via hemorrhage (usually mild
thrombocytopenia) bull Infectious agents (eg E canis Rickettsia
rickettsii Dirofilaria)
Thrombocytopathy (defects in platelet adhesion aggregation or release reactions)o
bull Inherited von Willebrands disease and other
hereditary thrombopathias including breed-specific thrombopathias
bull SystemiC illness Uremia collagen deficiency disease hepatic disease pancreatitis ehrlichiosis (E canis pound platys) FeLV dysproteinemia gammopathies myeloproliferativemyelodysplastic disorders DIG Iymphoproliferative disorders multiple myeloma
bull Drug-induced NSAIDs corticosteroids diuretic agents tranquilizers synthetic colloid solutions (eg dextran) 0- and ~-blockers and stimulators hormonal agents (eg prostacyclin estrogen) vinca alkaloids antibiotics and antiparasitic agents heparin
bull Antibody-mediated platelet dysfunction Immuneshymediated thrombocytopathy systemic lupus erythematosus
Coagulopathy 81012-14
bull Inherited bull Acquired
Vasculitis and uveitisl 5-21
bull Infectious Rocky Mountain spotted fever ehrlichiosis leptospirosis brucellosis piroplasmosis leishmaniasis ophthalmomyiasis interna ocular filariasis (Dirofilaria immitis) tuberculosis geotrichosis protothecosis toxoplasmosis (Toxoplasma gondii) FIV FeLV feline infectious peritonitis (FIP) canine adenovirus 1 cryptococcosis blastomycosis coccidioidomycosis candidiasis
bull Immune-mediated (eg uveodermatologic syndrome) bull Neoplasia (eg lymphosarcoma ocular sarcoma
metastatic tumors)
bull Lens-induced uveitis bull Episcleritis bull SystemiC inflammatory response syndrome SepSiS
endotoxemia (eg pyometra) bull Secondary to keratitis or trauma
bull Idiopathic
Noninflammatory vascular disorders22
bull Hyperadrenocorticism bull Ehlers-Danlos syndrome
Hypel
bull M(
an eh
bull Se po
Syste
Neov
bull Re
Throm Defe
can res fen s m be ind qui red rain dr rhy she renden counr
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parhwa abnorrr rna C rhird-cc body c be inhe rhages neous I coagulc
bocYlOl able de signs 0 1
owners
Compendium November 1999 20TH ANNIVERSARY Small AnimalExotics 1067
Causes of Hyphema (continued)
Hyperviscosity syndrome923-27
bull Mono- or polyclonal gammopathies Multiple myeloma lymphoma leukemia chronic inflammation antigenic stimulation (eg dirofilariasis) FIV FIP ehrlichiosis (E canis E platys)
bull Severe erythrocytosis Hemorrhagic gastroenteritis polycythemia vera erythropoietin-secreting neoplasms
Systemic hypertension 28-30
Neovascularization of uveal and retinal tissues bull Retinal detachment61831-JJ
-Primary -Secondary Lenticular disease infectious diseases
(see Vasculitis and uveitis) nonseptic inflammation (see Vasculitis and uveitis) trauma (see Trauma) intraocular neoplasia (see Neoplasia) systemic neoplasia (eg multiple myeloma) systemic hypertension (ie hypertensive retinopathy see
Thrombocytopathy Defects in platelet adhesion aggregation or release
can result in ineffectual platelet function II These deshyfects may be inherited (eg von Willebrands disease) be induced by systemic disorders or as in most acshyquired cases occur as an idiosyncratic reaction to cershytain drugs (see Causes of Hyphema) Thrombocytopashythy should be suspected in patients with hemorrhagic tendency prolonged bleeding time appropriate platelet count and normal tests of secondary hemorrhage
Coagulopathy Abnormalities of the intrinsic extrinsic or common
pathways of the clotting cascade may result in clotting abnormalities and subsequent hemorrhage and hypheshymao Coagulopathies are typified clinically by large third-compartment or major organ hemorrhages (eg body cavity pulmonary musdedeep tissue) and may be inherited or acquired Although ecchymotic hemorshyrhages are classically described in coagulopathies cutashyneous hemorrhages are less common in animals with coagulopathies than are thrombocyropenias and thromshybocytopathies Clinical presentation is extremely varishyable depending on the site of hemorrhage Secondary signs of anemia (weakness pallor) are often noted by owners of animals with a coagulopathy
Systemic Hypertension section in text) congenital abnormalities (eg retinal dysplasia) senile degenerative changes
bull Chronic glaucoma6
bull Intraocular neoplasia34
-Primary Lymphosarcoma adenoma and adenocarcinoma melanoma posttraumatic ocular sarcoma in cats
-Secondary Adenocarcinoma transitional cell carcinoma lymphoma multiple myeloma
Congenital anomalies 3135
bull Collie eye anomaly bull Vitreoretinal dysplasia (eg in Bedlington terriers
Sealyham terriers Labrador retrievers) bull Persistent hyaloid artery (eg with persistent
hyperplastic primary vitreous in Doberman pinschers)
Anemia
Vasculitis Vascular endothelial cell abnormalities may result in
transmural extravasation of blood from vascular chanshynels in the iris and ciliary body resulting in breakdown of the blood-aqueous barrier and hyphema Vasculitis may result from primary or secondary immune-mediatshyed destruction of endothelial cells (eg immune-medishyated vasculitis toxoplasmosis) infectious diseases (eg leptospirosis Rocky Mountain spotted fever feline inshyfectious peritonitis) neoplasia or systemic inflammatoshyry response syndrome (eg sepsis) Noninflammatory vascular disorders including hyperadrenocorticism and Ehler-Danlos syndrome can also result in hemorrhage
Hyperviscosity Syndrome Diseases that produce excessive globulins or other plasshy
ma proteins may result in hyphema because of (1) vascushylar endothelial cell compromise caused by intravascular sludging of blood with vessel wall necrosis (2) infiltrashytion of proteins into the vessel wall (3) inhibition of hemostasis secondary to reduction in clotting factors andor (4) coating of platelets by abnormal paraproteins resul ring in abnormal platelet aggregation 23 Funduscopic examination of the contralateral eye may reveal engorged retinal vasculature and retinal hemorrhages Common causes of hyperviscosity include plasma cell myeloma
ECCHYMOTIC HEMORRHAGE bull NONINFLAMMATORY VASCULAR DISORDERS bull PLASMA PROTEINS
I
1068 Small AnimalExotics 20TH ANNIVERSARY Compendium November 1999
lymphoma ehrlichiosis and chronic inflammatory disshy cell and fibroblast proliferation and subsequent ftbrovasshy often ease Serum total solids will generally be excessively eleshy cular membrane formation l6 The most frequent site of intrao vated because of hyperglobulinemia Hyperviscosity synshy fibrovascular membrane formation in eyes with chronic older drome can also be induced by severe erythrocytosis such retinal detachment is overlying the anterior iris surface glOsar as hemorrhagic gastroenteritis polycythemia vera and (pre-iridal ftbrovascular membrane) 16 Acute hyp hema montlshyerythropoietin~secreting neoplasms may occur if the retinal vasculature tears when the neushy unilatc
rosensory retina detaches from the underlying retinal traoCI SystemiC Hypertension pigment epithelial cells Clinicians must derermine the intrao
Hyphema arrributable to systemic hyperrension is cause of the retinal detachshy ondaI most common in old cats and dogs and is often caused ment because life-threarenshy oma) by chronic renal insufftciency Systemic hypertension ing systemic disease may be suit in affects only the arterial vascular system Chronic high the underlying abnormality arterial pressure may result in arteriosclerosis and aushy (see Causes of Hyphema) in Cong toregulatory arteriolar vasospasm Arteriolar disease our experience sponraneshy H)
causes ischemia and capillary permeability changes ous (idiopathic) retinal deshy to cor (with leakage of plasma proteins) and eventually hemshy tachment is rare in dogs and cawse
The more commoll causes oforrhage In our experience most cases of hyphema cats and an underlying cause is cha illtraocular hemorrhage werefrom vasoular hypertension are attribu table to retinall is usually present tribU[
detachment (see Neovascularization of Uveal and Retishy severekllown 20 years ago Since then
nal Tissues section) and most likely occur in response Chronic Glaucoma new infictiom causes of rerrler to choroidal vascular hypertension Hyphema may be Pre-iridal fibrovascular hypema such as felille er spa less commonly caused by tearing of retinal vasculature membranes are also frequentshy immunodeficiency virus have plere that occurs during retinal detachment Otber common ly detected in eyes with been detected Research Oller the subselt causes of vascular hypertension include hyperthyroidism chronic (end-stage) glaucoshy and vpast 20 years has demollstrated hyperadrenocorticism hyperaldosteronism and pheoshy ma G It is likely that hypheshy curs smarty mediators of chromocytoma ma attributable to chronic fetal rneollasclilarizatiort and
glaucoma occurs secondary tent hintraocular inflammation TheNeovascularization of Uveal and Retinal Tissues to tearing and leakage of the body
methodologies for diAgnosticAlthough the presence of blood vessels is necessary in fragile pre-iridal mlcrovascushyworkup hmle improved with themost tissues neovascularization or angiogenesis of tissues lature f Anen
advent ofB-modecan cause severe disease The surfaces of the retina and Acc iris are vulnerable to symptomatic neovasCldarizationl6 Intraocular Neoplasia ultrasonography computed severe Possible causes for neovascularization are ischemia (inshy Growth of a neoplasm largshy l tomography and magnetic can cc cluding long-standing retinal detachment) intraocular er than 2 to 3 mm-l requires resonallce imaging Howeller low 5 neoplasia and inflammation 6 Vascular proliferation on development of a microvasshy the primar) management issues dothe the anterior iris surhce (rubeosis iridis) leads to the forshy cular network to facilitate vesselofhyphema halle remained mation of a pre-iridal ftbrovascular membrane which delivery of nutrients and unchartged A few new can involve the peripheral iris and iridocorneal drainage oxygen and removal of treatment OptiOIlS have been angle and result in obstruction of aqueous humor outshy catabolites 38 Primary and added such as tissue flow Angiogenesis a complex process that incllldes metastatic intraocular neoshy I B(
plasminogm actillator and mdegradation of extracellular matrix and endothelial cell plasms of the anterior uveal topical carbonic anhydrllSe thproliferation is stringently regulated by numerous tissues are highly vascular
2 l(shyinhibitors UnfortulUltely theproangiogenic and antiangiogenic factors Examples of These neoplasms secrete mprognosis for main fair-ling lIisiollgrowth factors that stimulate endothelial cell proliferashy vascular growth factors (eg 3 l(shy
tion include fibroblast growth factors insulinlike growth VEGF TGF-~) that stimushy in an eye with hyphema has Ai factors transforming growth factor-~ (TGF-~) and vasshy late formation and rapid generally remained the Sfme 4 G cular endothelial growth factor (VEGF)lG The newly growth of vessels to support oller the past 20 years H
grown vessels are exceedingly fragile leal( readily and can and sustain rumor growthY 5 G pIpotentially result in hemorrhage and hyphema17 Newly developed capillaries 2(
of neoplasms are prone to 6 MRetinal Detachment hemorrhage because they p
Long-standing retinal detachment stimulates producshy have incomplete basement tion of growth factors that induce vascular endothelial membranes are leaky and 7 Jo
ARTERIOLAR DISEASE PRE-IRIDAL FIBROVASCULAR MEMBRANE GROWTH FACTORS
15
I
Compendium November 1999 20TH ANNIVERSARY S~nia AnimalExotics 1069
often fracture J6 lS Animals with hyphema attributable to
intraocular neoplasia are usually in late middle age or older however we have diagnosed ciliary body hemanshygiosarcoma and iris melanoma in dogs as young as 7 months of age Most primary inrraocular neoplasms are unilateral and thus hyphema attributable to primary inshytraocular neoplasia is unilateral Bilateral primary intraocular neoplasms are reponed infrequenrlyj~ Secshyondary or metastatic intraocular neoplasia (eg lymphshyoma) may affect one or both eyes and may -therefore reshysult in unilateral or bilateral hyphema
Congenital Ocular Anomalies Hyphema in young animals should prompt clinicians
to consider congenital ocular malformation as a ilikely cause Collie eye anomaly which is recessively inherited is characterized by defects of the choroid and sclera atshytributable to abnormal mesodermal differentiation5J In severe cases of vitreoretinal dysplasia (eg in Bedlington terriers Sealyham terriers Labrador retrievers or springshyer spaniels) retinal folding is sufficient to permit comshyplete retinal detachmenr 3 135 Retinal detachment and subsequent hyphema may occur w~h collie eye anomaly and vitreoretinal dysplasia Persistent hyaloid artery ocshycurs sporadically in dogs and is caused by failure of the fetal hyaloid vasculature to regress l5 Rupture of a persisshytent hyaloid artery leads to hemorrhage into the vitreolls body with blood passing into the anterior chamber l5
Anemia According to our experience and a previous report 40
severe acute anemia (eg severe tick or flea infestation) can cause hyphema when hemoglobin rapidly drops beshylow 5 mgdl Insufficient oxygen supply may cause enshydothelial cells to die which leads to leaking of blood vessels
REFERENCES I Belhorn R An overview of the blood-ocular barriers Seyshy
mour R Roberts Memorial Lecture Prog Vet Comp Ophshythalmoll(3)205- 2171991
2 Wilson FM Traumatic hyphema Pathogenes is and manageshyment Ophthalmology 87(9)910- 919 1980
3 Winston SM Ocular emergencies Vet Clin North Am Small Anim Pract II (1 )59-76 1981
4 Gottsch JD H yphema Diagnosis and mallJgemenr Retina 10(Suppll)S65-S71 1990
5 Gilger Be Hamilton HL Wilkie DA et a1 Traumatic oculat proptosis in dogs and cats 84 cases (1980-1993) jAVMA 206(8)1186-11901995
6 Mackin A Cani ne immune-mediated thrombocytopcniashyParr I Compend Contin Educ lract Vet 17(3) 353-364 1995
7 Jordan HL Grindem CB Breitschwerdt EB Thrombocyshy
topenia in cats A retrospective study of 41 cases j Vet Intern Med7(5)261-265 1993
8 Peterso n JL Co uto CG Wellman ML H emosta tic disorshyder in cats A retrospective study and review of the literashyture j Vet Illtem Med ) (5 )298-302 1995
9 Shelton G H Linenberger ML Hematologic abnormalities associated with retroviral in fectio ns in the car Semi Vet Med Surg Small Anim 10(4)220-233 1 )95
10 Boudreaux MK Platelets and coagulation Vet Clin North Am Small Anim hart 26(5) I 065-1087 1996
I Ruiz de Gopegui R Feldman BF Acquired and inherited platelet dysfunction in small animals Compelle Conlill Edltc Pract Vet 20(9) 1039- 1052 1998
12 Fogh JM f ogh IT Inherited coagulation disorders Vet Clin NorthAm Small Anim Pmct 18(1 )231-243 1988
13 Hart SW Noire I Hemostatic disorders in feline immunoshydeficiency virus-seropositive cats j Vet [ntem Med 8(5)355shy362 1994
14 Lisciandro Sc H ohenhaus A Brooks M Coagulation abshynormalities in 22 cats with naturally occurring liver disease j Vet [ntem Med 12(2) 71-75 1998
15 Davidson MG Breitschwerdt EB Nas isse MP Roberts SM Ocular manifestations of Rocky Mountain sported fever in dogsjAVMA 194(6)777-78 1 1989
16 Peiffer J I RL Wilcock BP Yin H The padlOgencs is and sigshynificance of pre-iridal fibrovascular membrane in domes tic animals Vet Pat hoI 27(I)4 1-45 1990
17 Collins BK Moore CPo Diseases and surgery of the canine anterior uvea in Gdatt KN (ed) Veteril1UJ Ophthalmology ed 3 Baltimore Lippincott Williams amp Wilkins 1999 pp 755-795
18 Glaze MB Gelatt KN Feline ophthalmology in Gelart KN (ed) VeterinalJ Ophthalmology ed 3 Baltimore Lippincott Williams amp Wilkins 1999 pp 997-1052
19 Peiffer J r RL Wilcock BP Histopathologic study of uveitis in cats 139 caSes (1978- 1988) jAVMA 198(1) 135- 138 1991
20 Chavki n MJ Lappin MR Powell Cc et al Seroepidemioshylogic and clinical observations of 93 cases of uveitis in (1[1
Prog Vet Comp OphthalmoI2(1)29-36 1992 2 Bisrner S Allergic- and immunologic-mediared diseases of
the eye and adncxae Vet Clin North Am Small Anim Prtlct 24 (4)7 11-734 1994
22 Freeman LJ Hegreberg GA Robinette JD Ehlers-Danlos syndrome in dogs and cats Semin Vet IIled Surg Sma Al1im 2(3)221 - 227 1987
23 Lane IF RobertS SM Lappin MR Ocular manifestations of vascular disease Hypertension hyperv iscos ity and hypershylipidemia jAAHA 29( 1)28-36 1993
24 Hendrix DVH Celatt KN Smith PJ et al Ophthalmic dis shyease as the presenting complaim in five dogs with multiple myelomajAAHA34(2)121 - 1281998
25 Foster ES Lothrop Jr CD Pol)c)themia vera in a cat wirh cardiac hypertrophy jAVMA 192( (2) 1736-1738 1988
26 Hammer AS Couto CG Complications of multiple myeloshyma jAAHA 30(1)9-14 1994
27 Forresror SD G reco DS Relford RL Serum hyperviscos it) syndrome associated with multiple myeloma in rwo cats jAVMA 200(1)79-82 1992
28 Dimski DS Hawkins EC Canine sys temic hypertension Compend Con tin Educ Pract Vet 10(10) 1152- 1158 1988
29 Stiles J Polzin DJ Bisrner SI The prevalence of retinoparhy in cats with systemic hypertension and chronic renal failure Ot hyperthyroidism jAAHA 30(6) 564-572 1994
(alltilues 011 page 1091)
COLLIE EYE ANOMALY VITREORETINAL OYSPLASIA bull PERSISTENT HYALOIO ARTERY
- ------ - - -- - - - - - -- - - ---
Compendium November 1999 20TH ANNIVERSARY Small AnimalExotics 1065
and epithelial tight junctions with variations in their degree of permeability l Dysfunction of the blood-aqueous barrier frequently results in hypheshyrna breakdown of the blood-r-tinal barrier generalshyly causes retinal subretinal and choroidal hemorrhage but infrequently results in hyphema The posterior lens capsule and zonules limit but do not com pletely preven t movement of blood from the anterior chamber to the vitreshyous and vice versa
Figure 1-Hyphema in a dog
Because the intraocular pressure (lOP) is normally higher than the pressure in the aqueous humor drainshyage pathways (the scleral venous plexus) retrograde blood flow into the anterior chamber is prevented lOP lower than the pressure in the scleral venous plexus may predispose to hyphema via retrograde blood flow into the anterior chamber
PATHOPHYSIOLOGIC APPROACH With the exception of severe intraocular disease the dishy
agnostic differentials for hyphema do not differ substanshytially from those for hemorrhage in other areas of the body (eg hemothorax hemoabdomen) therefore the diagnostic approach to determine the underlying cause of hyphema is similar In addition to systemic causes ocular disorders should be considered Clinicians must develop a sound understanding of the potential causes of hyphema so they are able to construct a list of differential considershyations for each mechanism The most common mechashynisms of hemorrhage that may result in hyphema follow
Iridocyclitis Iridocyclitis (anterior uveitis) is the most common
ocular disease associated with a breakdown of the bloodshyaqueous barrier Disruption of the blood-aqueous barshyrier may lead to aqueous flare (predominantly proshyteins) hypopyon andor hyphema depending on the inciting stimulus and duration of the disease Most of the pathophysiologic mechanisms of BOB breakdown discussed in the remainder of this article are also possishyble causes for iridocyclitis Regardless of the caLIse if left untreated hyphema will eventually result in iridoshycyclitis when chemotactic triggers recruit inflammatory cells for cleanup
Trauma Hyphema attributable to exogenous causes (blunt or
perforating trauma) is probshyably more common than that resulting from endogenous causes (see Causes of Hypheshyrna) Blunt trauma to the head seldom resuhs in hypheshyrna because the eyeball is proshytected by anterior portions of the bony orbit and orbital soft tissues However severe blunt trauma to the anterior orbital rim or periorbital soft tissues and eyeball may reshy
suit in hyphema In this case -- - - - - -- - -- - -- - -- -- - - - - examination and palpation
of the periorbital area usualshyIy reveals clinical signs of trauma such as swelling and bruising of the eyelids and conjunctiva fracture of the bony orbit or orbital hemorrhage and resultant orbital mass effect Bilateral hyphema is seldom caused by mild trauma When blunt ocular trauma occurs the sudden rise in lOP associated with ocular indentation causes anterior chamber angle distortion and may result in rupture of iris stromal or ciliary body vessels and subsequent hyphema4
Perforating trauma (eg cat scratch BB pellets) to the eye baH (cornea sclera) with direct damage to inshytraocular vasculature is more likely to result in traushymatic hyphema than is blunt trauma Traumatic hyshyphema can also be associated with proptosis of the globe and may be accompanied by structural damage to the eye including lens subluxation and dislocation vitreous hemorrhage or retinal detachment Head rashydiographs help to reveal fractures of the orbit or skull in trauma cases When exogenous sources of hyphema have been eliminated the diagnostic approach is furshyther directed by results of physical and ophthalmic exshyamll1atIons
Thrombocytopenia Lack of an adequate number of circulating platelets
can result in hyphema and hemorrhage secondary to ongoing capiuary microtrauma induced by normal acshytiviry or exogenous insult6 Thrombocytopenia is typishyfied clinically by petechial hemorrhage of mucosal and cutaneous surfaces Hyphema and concurrent petechial hemorrhages should prompt clinicians to consider thrombocytopenia as a likely mechanism of disease Thrombocywpenia may be induced by immune-medishyated destruction of platelets infectious agents (eg Ehrlichia canis platys or risticii Leptojpira species Rickettsia rickettsil) sepsis splenomegaly neoplasia or disseminated intravascular coagulation
ANTERIOR UVEITIS bull PERFORATING TRAUMA PETECHIAL HEMORRHAGE
middot
1066 Small An imalExotics 20TH ANNIVERSARY Compendium November 1999
Causes of Hyphema
Trauma2-5
bull Blunt bull Penetrating (with or without foreign body)
Thrombocytopenia6-10
bull Decreased platelet production in the bone marrow -Drug or chemical toxicity-induced bone marrow
hypoplasia (eg estrogens antiinflammatory agents antibiotics tranquilizing agents diuretic agents dapsone myelosuppressive chemotherapy)
-Toxic doses of irradiation -Chronic infections (e g feline leukemia virus
[FeLV] Ehrlichia canis Ehrlichia platys canine distemper parvovirus heartworm disease)
-Myeloproliferative disorders (eg FeLV feline immunodeficiency virus [FIV]) lymphoma tumor metastasis
-Estrogen-secreting tumors (eg Sertoli cell tumor) -Myelofibrosis -Immune-mediated megakaryocytic hypoplasia or
aplasia -Chronic renal disease
bull Reduced circulating platelet life span -Sequestration (eg splenomegaly) -Immune-mediated platelet destruction -Nonimmunologic platelet destruction
bull Microangiopathic thrombocytopenia (eg disseminated intravascular coagulation [DIG] tumor microvasculature [hemangiosarcoma hepatic tumors])
bull Microangiopathic hemolytic anemia bull Severe vascular injury and vasculitis (see
Vasculitis and uveitis) bull Drug-induced (eg heparin) bull Platelet loss via hemorrhage (usually mild
thrombocytopenia) bull Infectious agents (eg E canis Rickettsia
rickettsii Dirofilaria)
Thrombocytopathy (defects in platelet adhesion aggregation or release reactions)o
bull Inherited von Willebrands disease and other
hereditary thrombopathias including breed-specific thrombopathias
bull SystemiC illness Uremia collagen deficiency disease hepatic disease pancreatitis ehrlichiosis (E canis pound platys) FeLV dysproteinemia gammopathies myeloproliferativemyelodysplastic disorders DIG Iymphoproliferative disorders multiple myeloma
bull Drug-induced NSAIDs corticosteroids diuretic agents tranquilizers synthetic colloid solutions (eg dextran) 0- and ~-blockers and stimulators hormonal agents (eg prostacyclin estrogen) vinca alkaloids antibiotics and antiparasitic agents heparin
bull Antibody-mediated platelet dysfunction Immuneshymediated thrombocytopathy systemic lupus erythematosus
Coagulopathy 81012-14
bull Inherited bull Acquired
Vasculitis and uveitisl 5-21
bull Infectious Rocky Mountain spotted fever ehrlichiosis leptospirosis brucellosis piroplasmosis leishmaniasis ophthalmomyiasis interna ocular filariasis (Dirofilaria immitis) tuberculosis geotrichosis protothecosis toxoplasmosis (Toxoplasma gondii) FIV FeLV feline infectious peritonitis (FIP) canine adenovirus 1 cryptococcosis blastomycosis coccidioidomycosis candidiasis
bull Immune-mediated (eg uveodermatologic syndrome) bull Neoplasia (eg lymphosarcoma ocular sarcoma
metastatic tumors)
bull Lens-induced uveitis bull Episcleritis bull SystemiC inflammatory response syndrome SepSiS
endotoxemia (eg pyometra) bull Secondary to keratitis or trauma
bull Idiopathic
Noninflammatory vascular disorders22
bull Hyperadrenocorticism bull Ehlers-Danlos syndrome
Hypel
bull M(
an eh
bull Se po
Syste
Neov
bull Re
Throm Defe
can res fen s m be ind qui red rain dr rhy she renden counr
Coagu Abnc
parhwa abnorrr rna C rhird-cc body c be inhe rhages neous I coagulc
bocYlOl able de signs 0 1
owners
Compendium November 1999 20TH ANNIVERSARY Small AnimalExotics 1067
Causes of Hyphema (continued)
Hyperviscosity syndrome923-27
bull Mono- or polyclonal gammopathies Multiple myeloma lymphoma leukemia chronic inflammation antigenic stimulation (eg dirofilariasis) FIV FIP ehrlichiosis (E canis E platys)
bull Severe erythrocytosis Hemorrhagic gastroenteritis polycythemia vera erythropoietin-secreting neoplasms
Systemic hypertension 28-30
Neovascularization of uveal and retinal tissues bull Retinal detachment61831-JJ
-Primary -Secondary Lenticular disease infectious diseases
(see Vasculitis and uveitis) nonseptic inflammation (see Vasculitis and uveitis) trauma (see Trauma) intraocular neoplasia (see Neoplasia) systemic neoplasia (eg multiple myeloma) systemic hypertension (ie hypertensive retinopathy see
Thrombocytopathy Defects in platelet adhesion aggregation or release
can result in ineffectual platelet function II These deshyfects may be inherited (eg von Willebrands disease) be induced by systemic disorders or as in most acshyquired cases occur as an idiosyncratic reaction to cershytain drugs (see Causes of Hyphema) Thrombocytopashythy should be suspected in patients with hemorrhagic tendency prolonged bleeding time appropriate platelet count and normal tests of secondary hemorrhage
Coagulopathy Abnormalities of the intrinsic extrinsic or common
pathways of the clotting cascade may result in clotting abnormalities and subsequent hemorrhage and hypheshymao Coagulopathies are typified clinically by large third-compartment or major organ hemorrhages (eg body cavity pulmonary musdedeep tissue) and may be inherited or acquired Although ecchymotic hemorshyrhages are classically described in coagulopathies cutashyneous hemorrhages are less common in animals with coagulopathies than are thrombocyropenias and thromshybocytopathies Clinical presentation is extremely varishyable depending on the site of hemorrhage Secondary signs of anemia (weakness pallor) are often noted by owners of animals with a coagulopathy
Systemic Hypertension section in text) congenital abnormalities (eg retinal dysplasia) senile degenerative changes
bull Chronic glaucoma6
bull Intraocular neoplasia34
-Primary Lymphosarcoma adenoma and adenocarcinoma melanoma posttraumatic ocular sarcoma in cats
-Secondary Adenocarcinoma transitional cell carcinoma lymphoma multiple myeloma
Congenital anomalies 3135
bull Collie eye anomaly bull Vitreoretinal dysplasia (eg in Bedlington terriers
Sealyham terriers Labrador retrievers) bull Persistent hyaloid artery (eg with persistent
hyperplastic primary vitreous in Doberman pinschers)
Anemia
Vasculitis Vascular endothelial cell abnormalities may result in
transmural extravasation of blood from vascular chanshynels in the iris and ciliary body resulting in breakdown of the blood-aqueous barrier and hyphema Vasculitis may result from primary or secondary immune-mediatshyed destruction of endothelial cells (eg immune-medishyated vasculitis toxoplasmosis) infectious diseases (eg leptospirosis Rocky Mountain spotted fever feline inshyfectious peritonitis) neoplasia or systemic inflammatoshyry response syndrome (eg sepsis) Noninflammatory vascular disorders including hyperadrenocorticism and Ehler-Danlos syndrome can also result in hemorrhage
Hyperviscosity Syndrome Diseases that produce excessive globulins or other plasshy
ma proteins may result in hyphema because of (1) vascushylar endothelial cell compromise caused by intravascular sludging of blood with vessel wall necrosis (2) infiltrashytion of proteins into the vessel wall (3) inhibition of hemostasis secondary to reduction in clotting factors andor (4) coating of platelets by abnormal paraproteins resul ring in abnormal platelet aggregation 23 Funduscopic examination of the contralateral eye may reveal engorged retinal vasculature and retinal hemorrhages Common causes of hyperviscosity include plasma cell myeloma
ECCHYMOTIC HEMORRHAGE bull NONINFLAMMATORY VASCULAR DISORDERS bull PLASMA PROTEINS
I
1068 Small AnimalExotics 20TH ANNIVERSARY Compendium November 1999
lymphoma ehrlichiosis and chronic inflammatory disshy cell and fibroblast proliferation and subsequent ftbrovasshy often ease Serum total solids will generally be excessively eleshy cular membrane formation l6 The most frequent site of intrao vated because of hyperglobulinemia Hyperviscosity synshy fibrovascular membrane formation in eyes with chronic older drome can also be induced by severe erythrocytosis such retinal detachment is overlying the anterior iris surface glOsar as hemorrhagic gastroenteritis polycythemia vera and (pre-iridal ftbrovascular membrane) 16 Acute hyp hema montlshyerythropoietin~secreting neoplasms may occur if the retinal vasculature tears when the neushy unilatc
rosensory retina detaches from the underlying retinal traoCI SystemiC Hypertension pigment epithelial cells Clinicians must derermine the intrao
Hyphema arrributable to systemic hyperrension is cause of the retinal detachshy ondaI most common in old cats and dogs and is often caused ment because life-threarenshy oma) by chronic renal insufftciency Systemic hypertension ing systemic disease may be suit in affects only the arterial vascular system Chronic high the underlying abnormality arterial pressure may result in arteriosclerosis and aushy (see Causes of Hyphema) in Cong toregulatory arteriolar vasospasm Arteriolar disease our experience sponraneshy H)
causes ischemia and capillary permeability changes ous (idiopathic) retinal deshy to cor (with leakage of plasma proteins) and eventually hemshy tachment is rare in dogs and cawse
The more commoll causes oforrhage In our experience most cases of hyphema cats and an underlying cause is cha illtraocular hemorrhage werefrom vasoular hypertension are attribu table to retinall is usually present tribU[
detachment (see Neovascularization of Uveal and Retishy severekllown 20 years ago Since then
nal Tissues section) and most likely occur in response Chronic Glaucoma new infictiom causes of rerrler to choroidal vascular hypertension Hyphema may be Pre-iridal fibrovascular hypema such as felille er spa less commonly caused by tearing of retinal vasculature membranes are also frequentshy immunodeficiency virus have plere that occurs during retinal detachment Otber common ly detected in eyes with been detected Research Oller the subselt causes of vascular hypertension include hyperthyroidism chronic (end-stage) glaucoshy and vpast 20 years has demollstrated hyperadrenocorticism hyperaldosteronism and pheoshy ma G It is likely that hypheshy curs smarty mediators of chromocytoma ma attributable to chronic fetal rneollasclilarizatiort and
glaucoma occurs secondary tent hintraocular inflammation TheNeovascularization of Uveal and Retinal Tissues to tearing and leakage of the body
methodologies for diAgnosticAlthough the presence of blood vessels is necessary in fragile pre-iridal mlcrovascushyworkup hmle improved with themost tissues neovascularization or angiogenesis of tissues lature f Anen
advent ofB-modecan cause severe disease The surfaces of the retina and Acc iris are vulnerable to symptomatic neovasCldarizationl6 Intraocular Neoplasia ultrasonography computed severe Possible causes for neovascularization are ischemia (inshy Growth of a neoplasm largshy l tomography and magnetic can cc cluding long-standing retinal detachment) intraocular er than 2 to 3 mm-l requires resonallce imaging Howeller low 5 neoplasia and inflammation 6 Vascular proliferation on development of a microvasshy the primar) management issues dothe the anterior iris surhce (rubeosis iridis) leads to the forshy cular network to facilitate vesselofhyphema halle remained mation of a pre-iridal ftbrovascular membrane which delivery of nutrients and unchartged A few new can involve the peripheral iris and iridocorneal drainage oxygen and removal of treatment OptiOIlS have been angle and result in obstruction of aqueous humor outshy catabolites 38 Primary and added such as tissue flow Angiogenesis a complex process that incllldes metastatic intraocular neoshy I B(
plasminogm actillator and mdegradation of extracellular matrix and endothelial cell plasms of the anterior uveal topical carbonic anhydrllSe thproliferation is stringently regulated by numerous tissues are highly vascular
2 l(shyinhibitors UnfortulUltely theproangiogenic and antiangiogenic factors Examples of These neoplasms secrete mprognosis for main fair-ling lIisiollgrowth factors that stimulate endothelial cell proliferashy vascular growth factors (eg 3 l(shy
tion include fibroblast growth factors insulinlike growth VEGF TGF-~) that stimushy in an eye with hyphema has Ai factors transforming growth factor-~ (TGF-~) and vasshy late formation and rapid generally remained the Sfme 4 G cular endothelial growth factor (VEGF)lG The newly growth of vessels to support oller the past 20 years H
grown vessels are exceedingly fragile leal( readily and can and sustain rumor growthY 5 G pIpotentially result in hemorrhage and hyphema17 Newly developed capillaries 2(
of neoplasms are prone to 6 MRetinal Detachment hemorrhage because they p
Long-standing retinal detachment stimulates producshy have incomplete basement tion of growth factors that induce vascular endothelial membranes are leaky and 7 Jo
ARTERIOLAR DISEASE PRE-IRIDAL FIBROVASCULAR MEMBRANE GROWTH FACTORS
15
I
Compendium November 1999 20TH ANNIVERSARY S~nia AnimalExotics 1069
often fracture J6 lS Animals with hyphema attributable to
intraocular neoplasia are usually in late middle age or older however we have diagnosed ciliary body hemanshygiosarcoma and iris melanoma in dogs as young as 7 months of age Most primary inrraocular neoplasms are unilateral and thus hyphema attributable to primary inshytraocular neoplasia is unilateral Bilateral primary intraocular neoplasms are reponed infrequenrlyj~ Secshyondary or metastatic intraocular neoplasia (eg lymphshyoma) may affect one or both eyes and may -therefore reshysult in unilateral or bilateral hyphema
Congenital Ocular Anomalies Hyphema in young animals should prompt clinicians
to consider congenital ocular malformation as a ilikely cause Collie eye anomaly which is recessively inherited is characterized by defects of the choroid and sclera atshytributable to abnormal mesodermal differentiation5J In severe cases of vitreoretinal dysplasia (eg in Bedlington terriers Sealyham terriers Labrador retrievers or springshyer spaniels) retinal folding is sufficient to permit comshyplete retinal detachmenr 3 135 Retinal detachment and subsequent hyphema may occur w~h collie eye anomaly and vitreoretinal dysplasia Persistent hyaloid artery ocshycurs sporadically in dogs and is caused by failure of the fetal hyaloid vasculature to regress l5 Rupture of a persisshytent hyaloid artery leads to hemorrhage into the vitreolls body with blood passing into the anterior chamber l5
Anemia According to our experience and a previous report 40
severe acute anemia (eg severe tick or flea infestation) can cause hyphema when hemoglobin rapidly drops beshylow 5 mgdl Insufficient oxygen supply may cause enshydothelial cells to die which leads to leaking of blood vessels
REFERENCES I Belhorn R An overview of the blood-ocular barriers Seyshy
mour R Roberts Memorial Lecture Prog Vet Comp Ophshythalmoll(3)205- 2171991
2 Wilson FM Traumatic hyphema Pathogenes is and manageshyment Ophthalmology 87(9)910- 919 1980
3 Winston SM Ocular emergencies Vet Clin North Am Small Anim Pract II (1 )59-76 1981
4 Gottsch JD H yphema Diagnosis and mallJgemenr Retina 10(Suppll)S65-S71 1990
5 Gilger Be Hamilton HL Wilkie DA et a1 Traumatic oculat proptosis in dogs and cats 84 cases (1980-1993) jAVMA 206(8)1186-11901995
6 Mackin A Cani ne immune-mediated thrombocytopcniashyParr I Compend Contin Educ lract Vet 17(3) 353-364 1995
7 Jordan HL Grindem CB Breitschwerdt EB Thrombocyshy
topenia in cats A retrospective study of 41 cases j Vet Intern Med7(5)261-265 1993
8 Peterso n JL Co uto CG Wellman ML H emosta tic disorshyder in cats A retrospective study and review of the literashyture j Vet Illtem Med ) (5 )298-302 1995
9 Shelton G H Linenberger ML Hematologic abnormalities associated with retroviral in fectio ns in the car Semi Vet Med Surg Small Anim 10(4)220-233 1 )95
10 Boudreaux MK Platelets and coagulation Vet Clin North Am Small Anim hart 26(5) I 065-1087 1996
I Ruiz de Gopegui R Feldman BF Acquired and inherited platelet dysfunction in small animals Compelle Conlill Edltc Pract Vet 20(9) 1039- 1052 1998
12 Fogh JM f ogh IT Inherited coagulation disorders Vet Clin NorthAm Small Anim Pmct 18(1 )231-243 1988
13 Hart SW Noire I Hemostatic disorders in feline immunoshydeficiency virus-seropositive cats j Vet [ntem Med 8(5)355shy362 1994
14 Lisciandro Sc H ohenhaus A Brooks M Coagulation abshynormalities in 22 cats with naturally occurring liver disease j Vet [ntem Med 12(2) 71-75 1998
15 Davidson MG Breitschwerdt EB Nas isse MP Roberts SM Ocular manifestations of Rocky Mountain sported fever in dogsjAVMA 194(6)777-78 1 1989
16 Peiffer J I RL Wilcock BP Yin H The padlOgencs is and sigshynificance of pre-iridal fibrovascular membrane in domes tic animals Vet Pat hoI 27(I)4 1-45 1990
17 Collins BK Moore CPo Diseases and surgery of the canine anterior uvea in Gdatt KN (ed) Veteril1UJ Ophthalmology ed 3 Baltimore Lippincott Williams amp Wilkins 1999 pp 755-795
18 Glaze MB Gelatt KN Feline ophthalmology in Gelart KN (ed) VeterinalJ Ophthalmology ed 3 Baltimore Lippincott Williams amp Wilkins 1999 pp 997-1052
19 Peiffer J r RL Wilcock BP Histopathologic study of uveitis in cats 139 caSes (1978- 1988) jAVMA 198(1) 135- 138 1991
20 Chavki n MJ Lappin MR Powell Cc et al Seroepidemioshylogic and clinical observations of 93 cases of uveitis in (1[1
Prog Vet Comp OphthalmoI2(1)29-36 1992 2 Bisrner S Allergic- and immunologic-mediared diseases of
the eye and adncxae Vet Clin North Am Small Anim Prtlct 24 (4)7 11-734 1994
22 Freeman LJ Hegreberg GA Robinette JD Ehlers-Danlos syndrome in dogs and cats Semin Vet IIled Surg Sma Al1im 2(3)221 - 227 1987
23 Lane IF RobertS SM Lappin MR Ocular manifestations of vascular disease Hypertension hyperv iscos ity and hypershylipidemia jAAHA 29( 1)28-36 1993
24 Hendrix DVH Celatt KN Smith PJ et al Ophthalmic dis shyease as the presenting complaim in five dogs with multiple myelomajAAHA34(2)121 - 1281998
25 Foster ES Lothrop Jr CD Pol)c)themia vera in a cat wirh cardiac hypertrophy jAVMA 192( (2) 1736-1738 1988
26 Hammer AS Couto CG Complications of multiple myeloshyma jAAHA 30(1)9-14 1994
27 Forresror SD G reco DS Relford RL Serum hyperviscos it) syndrome associated with multiple myeloma in rwo cats jAVMA 200(1)79-82 1992
28 Dimski DS Hawkins EC Canine sys temic hypertension Compend Con tin Educ Pract Vet 10(10) 1152- 1158 1988
29 Stiles J Polzin DJ Bisrner SI The prevalence of retinoparhy in cats with systemic hypertension and chronic renal failure Ot hyperthyroidism jAAHA 30(6) 564-572 1994
(alltilues 011 page 1091)
COLLIE EYE ANOMALY VITREORETINAL OYSPLASIA bull PERSISTENT HYALOIO ARTERY
middot
1066 Small An imalExotics 20TH ANNIVERSARY Compendium November 1999
Causes of Hyphema
Trauma2-5
bull Blunt bull Penetrating (with or without foreign body)
Thrombocytopenia6-10
bull Decreased platelet production in the bone marrow -Drug or chemical toxicity-induced bone marrow
hypoplasia (eg estrogens antiinflammatory agents antibiotics tranquilizing agents diuretic agents dapsone myelosuppressive chemotherapy)
-Toxic doses of irradiation -Chronic infections (e g feline leukemia virus
[FeLV] Ehrlichia canis Ehrlichia platys canine distemper parvovirus heartworm disease)
-Myeloproliferative disorders (eg FeLV feline immunodeficiency virus [FIV]) lymphoma tumor metastasis
-Estrogen-secreting tumors (eg Sertoli cell tumor) -Myelofibrosis -Immune-mediated megakaryocytic hypoplasia or
aplasia -Chronic renal disease
bull Reduced circulating platelet life span -Sequestration (eg splenomegaly) -Immune-mediated platelet destruction -Nonimmunologic platelet destruction
bull Microangiopathic thrombocytopenia (eg disseminated intravascular coagulation [DIG] tumor microvasculature [hemangiosarcoma hepatic tumors])
bull Microangiopathic hemolytic anemia bull Severe vascular injury and vasculitis (see
Vasculitis and uveitis) bull Drug-induced (eg heparin) bull Platelet loss via hemorrhage (usually mild
thrombocytopenia) bull Infectious agents (eg E canis Rickettsia
rickettsii Dirofilaria)
Thrombocytopathy (defects in platelet adhesion aggregation or release reactions)o
bull Inherited von Willebrands disease and other
hereditary thrombopathias including breed-specific thrombopathias
bull SystemiC illness Uremia collagen deficiency disease hepatic disease pancreatitis ehrlichiosis (E canis pound platys) FeLV dysproteinemia gammopathies myeloproliferativemyelodysplastic disorders DIG Iymphoproliferative disorders multiple myeloma
bull Drug-induced NSAIDs corticosteroids diuretic agents tranquilizers synthetic colloid solutions (eg dextran) 0- and ~-blockers and stimulators hormonal agents (eg prostacyclin estrogen) vinca alkaloids antibiotics and antiparasitic agents heparin
bull Antibody-mediated platelet dysfunction Immuneshymediated thrombocytopathy systemic lupus erythematosus
Coagulopathy 81012-14
bull Inherited bull Acquired
Vasculitis and uveitisl 5-21
bull Infectious Rocky Mountain spotted fever ehrlichiosis leptospirosis brucellosis piroplasmosis leishmaniasis ophthalmomyiasis interna ocular filariasis (Dirofilaria immitis) tuberculosis geotrichosis protothecosis toxoplasmosis (Toxoplasma gondii) FIV FeLV feline infectious peritonitis (FIP) canine adenovirus 1 cryptococcosis blastomycosis coccidioidomycosis candidiasis
bull Immune-mediated (eg uveodermatologic syndrome) bull Neoplasia (eg lymphosarcoma ocular sarcoma
metastatic tumors)
bull Lens-induced uveitis bull Episcleritis bull SystemiC inflammatory response syndrome SepSiS
endotoxemia (eg pyometra) bull Secondary to keratitis or trauma
bull Idiopathic
Noninflammatory vascular disorders22
bull Hyperadrenocorticism bull Ehlers-Danlos syndrome
Hypel
bull M(
an eh
bull Se po
Syste
Neov
bull Re
Throm Defe
can res fen s m be ind qui red rain dr rhy she renden counr
Coagu Abnc
parhwa abnorrr rna C rhird-cc body c be inhe rhages neous I coagulc
bocYlOl able de signs 0 1
owners
Compendium November 1999 20TH ANNIVERSARY Small AnimalExotics 1067
Causes of Hyphema (continued)
Hyperviscosity syndrome923-27
bull Mono- or polyclonal gammopathies Multiple myeloma lymphoma leukemia chronic inflammation antigenic stimulation (eg dirofilariasis) FIV FIP ehrlichiosis (E canis E platys)
bull Severe erythrocytosis Hemorrhagic gastroenteritis polycythemia vera erythropoietin-secreting neoplasms
Systemic hypertension 28-30
Neovascularization of uveal and retinal tissues bull Retinal detachment61831-JJ
-Primary -Secondary Lenticular disease infectious diseases
(see Vasculitis and uveitis) nonseptic inflammation (see Vasculitis and uveitis) trauma (see Trauma) intraocular neoplasia (see Neoplasia) systemic neoplasia (eg multiple myeloma) systemic hypertension (ie hypertensive retinopathy see
Thrombocytopathy Defects in platelet adhesion aggregation or release
can result in ineffectual platelet function II These deshyfects may be inherited (eg von Willebrands disease) be induced by systemic disorders or as in most acshyquired cases occur as an idiosyncratic reaction to cershytain drugs (see Causes of Hyphema) Thrombocytopashythy should be suspected in patients with hemorrhagic tendency prolonged bleeding time appropriate platelet count and normal tests of secondary hemorrhage
Coagulopathy Abnormalities of the intrinsic extrinsic or common
pathways of the clotting cascade may result in clotting abnormalities and subsequent hemorrhage and hypheshymao Coagulopathies are typified clinically by large third-compartment or major organ hemorrhages (eg body cavity pulmonary musdedeep tissue) and may be inherited or acquired Although ecchymotic hemorshyrhages are classically described in coagulopathies cutashyneous hemorrhages are less common in animals with coagulopathies than are thrombocyropenias and thromshybocytopathies Clinical presentation is extremely varishyable depending on the site of hemorrhage Secondary signs of anemia (weakness pallor) are often noted by owners of animals with a coagulopathy
Systemic Hypertension section in text) congenital abnormalities (eg retinal dysplasia) senile degenerative changes
bull Chronic glaucoma6
bull Intraocular neoplasia34
-Primary Lymphosarcoma adenoma and adenocarcinoma melanoma posttraumatic ocular sarcoma in cats
-Secondary Adenocarcinoma transitional cell carcinoma lymphoma multiple myeloma
Congenital anomalies 3135
bull Collie eye anomaly bull Vitreoretinal dysplasia (eg in Bedlington terriers
Sealyham terriers Labrador retrievers) bull Persistent hyaloid artery (eg with persistent
hyperplastic primary vitreous in Doberman pinschers)
Anemia
Vasculitis Vascular endothelial cell abnormalities may result in
transmural extravasation of blood from vascular chanshynels in the iris and ciliary body resulting in breakdown of the blood-aqueous barrier and hyphema Vasculitis may result from primary or secondary immune-mediatshyed destruction of endothelial cells (eg immune-medishyated vasculitis toxoplasmosis) infectious diseases (eg leptospirosis Rocky Mountain spotted fever feline inshyfectious peritonitis) neoplasia or systemic inflammatoshyry response syndrome (eg sepsis) Noninflammatory vascular disorders including hyperadrenocorticism and Ehler-Danlos syndrome can also result in hemorrhage
Hyperviscosity Syndrome Diseases that produce excessive globulins or other plasshy
ma proteins may result in hyphema because of (1) vascushylar endothelial cell compromise caused by intravascular sludging of blood with vessel wall necrosis (2) infiltrashytion of proteins into the vessel wall (3) inhibition of hemostasis secondary to reduction in clotting factors andor (4) coating of platelets by abnormal paraproteins resul ring in abnormal platelet aggregation 23 Funduscopic examination of the contralateral eye may reveal engorged retinal vasculature and retinal hemorrhages Common causes of hyperviscosity include plasma cell myeloma
ECCHYMOTIC HEMORRHAGE bull NONINFLAMMATORY VASCULAR DISORDERS bull PLASMA PROTEINS
I
1068 Small AnimalExotics 20TH ANNIVERSARY Compendium November 1999
lymphoma ehrlichiosis and chronic inflammatory disshy cell and fibroblast proliferation and subsequent ftbrovasshy often ease Serum total solids will generally be excessively eleshy cular membrane formation l6 The most frequent site of intrao vated because of hyperglobulinemia Hyperviscosity synshy fibrovascular membrane formation in eyes with chronic older drome can also be induced by severe erythrocytosis such retinal detachment is overlying the anterior iris surface glOsar as hemorrhagic gastroenteritis polycythemia vera and (pre-iridal ftbrovascular membrane) 16 Acute hyp hema montlshyerythropoietin~secreting neoplasms may occur if the retinal vasculature tears when the neushy unilatc
rosensory retina detaches from the underlying retinal traoCI SystemiC Hypertension pigment epithelial cells Clinicians must derermine the intrao
Hyphema arrributable to systemic hyperrension is cause of the retinal detachshy ondaI most common in old cats and dogs and is often caused ment because life-threarenshy oma) by chronic renal insufftciency Systemic hypertension ing systemic disease may be suit in affects only the arterial vascular system Chronic high the underlying abnormality arterial pressure may result in arteriosclerosis and aushy (see Causes of Hyphema) in Cong toregulatory arteriolar vasospasm Arteriolar disease our experience sponraneshy H)
causes ischemia and capillary permeability changes ous (idiopathic) retinal deshy to cor (with leakage of plasma proteins) and eventually hemshy tachment is rare in dogs and cawse
The more commoll causes oforrhage In our experience most cases of hyphema cats and an underlying cause is cha illtraocular hemorrhage werefrom vasoular hypertension are attribu table to retinall is usually present tribU[
detachment (see Neovascularization of Uveal and Retishy severekllown 20 years ago Since then
nal Tissues section) and most likely occur in response Chronic Glaucoma new infictiom causes of rerrler to choroidal vascular hypertension Hyphema may be Pre-iridal fibrovascular hypema such as felille er spa less commonly caused by tearing of retinal vasculature membranes are also frequentshy immunodeficiency virus have plere that occurs during retinal detachment Otber common ly detected in eyes with been detected Research Oller the subselt causes of vascular hypertension include hyperthyroidism chronic (end-stage) glaucoshy and vpast 20 years has demollstrated hyperadrenocorticism hyperaldosteronism and pheoshy ma G It is likely that hypheshy curs smarty mediators of chromocytoma ma attributable to chronic fetal rneollasclilarizatiort and
glaucoma occurs secondary tent hintraocular inflammation TheNeovascularization of Uveal and Retinal Tissues to tearing and leakage of the body
methodologies for diAgnosticAlthough the presence of blood vessels is necessary in fragile pre-iridal mlcrovascushyworkup hmle improved with themost tissues neovascularization or angiogenesis of tissues lature f Anen
advent ofB-modecan cause severe disease The surfaces of the retina and Acc iris are vulnerable to symptomatic neovasCldarizationl6 Intraocular Neoplasia ultrasonography computed severe Possible causes for neovascularization are ischemia (inshy Growth of a neoplasm largshy l tomography and magnetic can cc cluding long-standing retinal detachment) intraocular er than 2 to 3 mm-l requires resonallce imaging Howeller low 5 neoplasia and inflammation 6 Vascular proliferation on development of a microvasshy the primar) management issues dothe the anterior iris surhce (rubeosis iridis) leads to the forshy cular network to facilitate vesselofhyphema halle remained mation of a pre-iridal ftbrovascular membrane which delivery of nutrients and unchartged A few new can involve the peripheral iris and iridocorneal drainage oxygen and removal of treatment OptiOIlS have been angle and result in obstruction of aqueous humor outshy catabolites 38 Primary and added such as tissue flow Angiogenesis a complex process that incllldes metastatic intraocular neoshy I B(
plasminogm actillator and mdegradation of extracellular matrix and endothelial cell plasms of the anterior uveal topical carbonic anhydrllSe thproliferation is stringently regulated by numerous tissues are highly vascular
2 l(shyinhibitors UnfortulUltely theproangiogenic and antiangiogenic factors Examples of These neoplasms secrete mprognosis for main fair-ling lIisiollgrowth factors that stimulate endothelial cell proliferashy vascular growth factors (eg 3 l(shy
tion include fibroblast growth factors insulinlike growth VEGF TGF-~) that stimushy in an eye with hyphema has Ai factors transforming growth factor-~ (TGF-~) and vasshy late formation and rapid generally remained the Sfme 4 G cular endothelial growth factor (VEGF)lG The newly growth of vessels to support oller the past 20 years H
grown vessels are exceedingly fragile leal( readily and can and sustain rumor growthY 5 G pIpotentially result in hemorrhage and hyphema17 Newly developed capillaries 2(
of neoplasms are prone to 6 MRetinal Detachment hemorrhage because they p
Long-standing retinal detachment stimulates producshy have incomplete basement tion of growth factors that induce vascular endothelial membranes are leaky and 7 Jo
ARTERIOLAR DISEASE PRE-IRIDAL FIBROVASCULAR MEMBRANE GROWTH FACTORS
15
I
Compendium November 1999 20TH ANNIVERSARY S~nia AnimalExotics 1069
often fracture J6 lS Animals with hyphema attributable to
intraocular neoplasia are usually in late middle age or older however we have diagnosed ciliary body hemanshygiosarcoma and iris melanoma in dogs as young as 7 months of age Most primary inrraocular neoplasms are unilateral and thus hyphema attributable to primary inshytraocular neoplasia is unilateral Bilateral primary intraocular neoplasms are reponed infrequenrlyj~ Secshyondary or metastatic intraocular neoplasia (eg lymphshyoma) may affect one or both eyes and may -therefore reshysult in unilateral or bilateral hyphema
Congenital Ocular Anomalies Hyphema in young animals should prompt clinicians
to consider congenital ocular malformation as a ilikely cause Collie eye anomaly which is recessively inherited is characterized by defects of the choroid and sclera atshytributable to abnormal mesodermal differentiation5J In severe cases of vitreoretinal dysplasia (eg in Bedlington terriers Sealyham terriers Labrador retrievers or springshyer spaniels) retinal folding is sufficient to permit comshyplete retinal detachmenr 3 135 Retinal detachment and subsequent hyphema may occur w~h collie eye anomaly and vitreoretinal dysplasia Persistent hyaloid artery ocshycurs sporadically in dogs and is caused by failure of the fetal hyaloid vasculature to regress l5 Rupture of a persisshytent hyaloid artery leads to hemorrhage into the vitreolls body with blood passing into the anterior chamber l5
Anemia According to our experience and a previous report 40
severe acute anemia (eg severe tick or flea infestation) can cause hyphema when hemoglobin rapidly drops beshylow 5 mgdl Insufficient oxygen supply may cause enshydothelial cells to die which leads to leaking of blood vessels
REFERENCES I Belhorn R An overview of the blood-ocular barriers Seyshy
mour R Roberts Memorial Lecture Prog Vet Comp Ophshythalmoll(3)205- 2171991
2 Wilson FM Traumatic hyphema Pathogenes is and manageshyment Ophthalmology 87(9)910- 919 1980
3 Winston SM Ocular emergencies Vet Clin North Am Small Anim Pract II (1 )59-76 1981
4 Gottsch JD H yphema Diagnosis and mallJgemenr Retina 10(Suppll)S65-S71 1990
5 Gilger Be Hamilton HL Wilkie DA et a1 Traumatic oculat proptosis in dogs and cats 84 cases (1980-1993) jAVMA 206(8)1186-11901995
6 Mackin A Cani ne immune-mediated thrombocytopcniashyParr I Compend Contin Educ lract Vet 17(3) 353-364 1995
7 Jordan HL Grindem CB Breitschwerdt EB Thrombocyshy
topenia in cats A retrospective study of 41 cases j Vet Intern Med7(5)261-265 1993
8 Peterso n JL Co uto CG Wellman ML H emosta tic disorshyder in cats A retrospective study and review of the literashyture j Vet Illtem Med ) (5 )298-302 1995
9 Shelton G H Linenberger ML Hematologic abnormalities associated with retroviral in fectio ns in the car Semi Vet Med Surg Small Anim 10(4)220-233 1 )95
10 Boudreaux MK Platelets and coagulation Vet Clin North Am Small Anim hart 26(5) I 065-1087 1996
I Ruiz de Gopegui R Feldman BF Acquired and inherited platelet dysfunction in small animals Compelle Conlill Edltc Pract Vet 20(9) 1039- 1052 1998
12 Fogh JM f ogh IT Inherited coagulation disorders Vet Clin NorthAm Small Anim Pmct 18(1 )231-243 1988
13 Hart SW Noire I Hemostatic disorders in feline immunoshydeficiency virus-seropositive cats j Vet [ntem Med 8(5)355shy362 1994
14 Lisciandro Sc H ohenhaus A Brooks M Coagulation abshynormalities in 22 cats with naturally occurring liver disease j Vet [ntem Med 12(2) 71-75 1998
15 Davidson MG Breitschwerdt EB Nas isse MP Roberts SM Ocular manifestations of Rocky Mountain sported fever in dogsjAVMA 194(6)777-78 1 1989
16 Peiffer J I RL Wilcock BP Yin H The padlOgencs is and sigshynificance of pre-iridal fibrovascular membrane in domes tic animals Vet Pat hoI 27(I)4 1-45 1990
17 Collins BK Moore CPo Diseases and surgery of the canine anterior uvea in Gdatt KN (ed) Veteril1UJ Ophthalmology ed 3 Baltimore Lippincott Williams amp Wilkins 1999 pp 755-795
18 Glaze MB Gelatt KN Feline ophthalmology in Gelart KN (ed) VeterinalJ Ophthalmology ed 3 Baltimore Lippincott Williams amp Wilkins 1999 pp 997-1052
19 Peiffer J r RL Wilcock BP Histopathologic study of uveitis in cats 139 caSes (1978- 1988) jAVMA 198(1) 135- 138 1991
20 Chavki n MJ Lappin MR Powell Cc et al Seroepidemioshylogic and clinical observations of 93 cases of uveitis in (1[1
Prog Vet Comp OphthalmoI2(1)29-36 1992 2 Bisrner S Allergic- and immunologic-mediared diseases of
the eye and adncxae Vet Clin North Am Small Anim Prtlct 24 (4)7 11-734 1994
22 Freeman LJ Hegreberg GA Robinette JD Ehlers-Danlos syndrome in dogs and cats Semin Vet IIled Surg Sma Al1im 2(3)221 - 227 1987
23 Lane IF RobertS SM Lappin MR Ocular manifestations of vascular disease Hypertension hyperv iscos ity and hypershylipidemia jAAHA 29( 1)28-36 1993
24 Hendrix DVH Celatt KN Smith PJ et al Ophthalmic dis shyease as the presenting complaim in five dogs with multiple myelomajAAHA34(2)121 - 1281998
25 Foster ES Lothrop Jr CD Pol)c)themia vera in a cat wirh cardiac hypertrophy jAVMA 192( (2) 1736-1738 1988
26 Hammer AS Couto CG Complications of multiple myeloshyma jAAHA 30(1)9-14 1994
27 Forresror SD G reco DS Relford RL Serum hyperviscos it) syndrome associated with multiple myeloma in rwo cats jAVMA 200(1)79-82 1992
28 Dimski DS Hawkins EC Canine sys temic hypertension Compend Con tin Educ Pract Vet 10(10) 1152- 1158 1988
29 Stiles J Polzin DJ Bisrner SI The prevalence of retinoparhy in cats with systemic hypertension and chronic renal failure Ot hyperthyroidism jAAHA 30(6) 564-572 1994
(alltilues 011 page 1091)
COLLIE EYE ANOMALY VITREORETINAL OYSPLASIA bull PERSISTENT HYALOIO ARTERY
Compendium November 1999 20TH ANNIVERSARY Small AnimalExotics 1067
Causes of Hyphema (continued)
Hyperviscosity syndrome923-27
bull Mono- or polyclonal gammopathies Multiple myeloma lymphoma leukemia chronic inflammation antigenic stimulation (eg dirofilariasis) FIV FIP ehrlichiosis (E canis E platys)
bull Severe erythrocytosis Hemorrhagic gastroenteritis polycythemia vera erythropoietin-secreting neoplasms
Systemic hypertension 28-30
Neovascularization of uveal and retinal tissues bull Retinal detachment61831-JJ
-Primary -Secondary Lenticular disease infectious diseases
(see Vasculitis and uveitis) nonseptic inflammation (see Vasculitis and uveitis) trauma (see Trauma) intraocular neoplasia (see Neoplasia) systemic neoplasia (eg multiple myeloma) systemic hypertension (ie hypertensive retinopathy see
Thrombocytopathy Defects in platelet adhesion aggregation or release
can result in ineffectual platelet function II These deshyfects may be inherited (eg von Willebrands disease) be induced by systemic disorders or as in most acshyquired cases occur as an idiosyncratic reaction to cershytain drugs (see Causes of Hyphema) Thrombocytopashythy should be suspected in patients with hemorrhagic tendency prolonged bleeding time appropriate platelet count and normal tests of secondary hemorrhage
Coagulopathy Abnormalities of the intrinsic extrinsic or common
pathways of the clotting cascade may result in clotting abnormalities and subsequent hemorrhage and hypheshymao Coagulopathies are typified clinically by large third-compartment or major organ hemorrhages (eg body cavity pulmonary musdedeep tissue) and may be inherited or acquired Although ecchymotic hemorshyrhages are classically described in coagulopathies cutashyneous hemorrhages are less common in animals with coagulopathies than are thrombocyropenias and thromshybocytopathies Clinical presentation is extremely varishyable depending on the site of hemorrhage Secondary signs of anemia (weakness pallor) are often noted by owners of animals with a coagulopathy
Systemic Hypertension section in text) congenital abnormalities (eg retinal dysplasia) senile degenerative changes
bull Chronic glaucoma6
bull Intraocular neoplasia34
-Primary Lymphosarcoma adenoma and adenocarcinoma melanoma posttraumatic ocular sarcoma in cats
-Secondary Adenocarcinoma transitional cell carcinoma lymphoma multiple myeloma
Congenital anomalies 3135
bull Collie eye anomaly bull Vitreoretinal dysplasia (eg in Bedlington terriers
Sealyham terriers Labrador retrievers) bull Persistent hyaloid artery (eg with persistent
hyperplastic primary vitreous in Doberman pinschers)
Anemia
Vasculitis Vascular endothelial cell abnormalities may result in
transmural extravasation of blood from vascular chanshynels in the iris and ciliary body resulting in breakdown of the blood-aqueous barrier and hyphema Vasculitis may result from primary or secondary immune-mediatshyed destruction of endothelial cells (eg immune-medishyated vasculitis toxoplasmosis) infectious diseases (eg leptospirosis Rocky Mountain spotted fever feline inshyfectious peritonitis) neoplasia or systemic inflammatoshyry response syndrome (eg sepsis) Noninflammatory vascular disorders including hyperadrenocorticism and Ehler-Danlos syndrome can also result in hemorrhage
Hyperviscosity Syndrome Diseases that produce excessive globulins or other plasshy
ma proteins may result in hyphema because of (1) vascushylar endothelial cell compromise caused by intravascular sludging of blood with vessel wall necrosis (2) infiltrashytion of proteins into the vessel wall (3) inhibition of hemostasis secondary to reduction in clotting factors andor (4) coating of platelets by abnormal paraproteins resul ring in abnormal platelet aggregation 23 Funduscopic examination of the contralateral eye may reveal engorged retinal vasculature and retinal hemorrhages Common causes of hyperviscosity include plasma cell myeloma
ECCHYMOTIC HEMORRHAGE bull NONINFLAMMATORY VASCULAR DISORDERS bull PLASMA PROTEINS
I
1068 Small AnimalExotics 20TH ANNIVERSARY Compendium November 1999
lymphoma ehrlichiosis and chronic inflammatory disshy cell and fibroblast proliferation and subsequent ftbrovasshy often ease Serum total solids will generally be excessively eleshy cular membrane formation l6 The most frequent site of intrao vated because of hyperglobulinemia Hyperviscosity synshy fibrovascular membrane formation in eyes with chronic older drome can also be induced by severe erythrocytosis such retinal detachment is overlying the anterior iris surface glOsar as hemorrhagic gastroenteritis polycythemia vera and (pre-iridal ftbrovascular membrane) 16 Acute hyp hema montlshyerythropoietin~secreting neoplasms may occur if the retinal vasculature tears when the neushy unilatc
rosensory retina detaches from the underlying retinal traoCI SystemiC Hypertension pigment epithelial cells Clinicians must derermine the intrao
Hyphema arrributable to systemic hyperrension is cause of the retinal detachshy ondaI most common in old cats and dogs and is often caused ment because life-threarenshy oma) by chronic renal insufftciency Systemic hypertension ing systemic disease may be suit in affects only the arterial vascular system Chronic high the underlying abnormality arterial pressure may result in arteriosclerosis and aushy (see Causes of Hyphema) in Cong toregulatory arteriolar vasospasm Arteriolar disease our experience sponraneshy H)
causes ischemia and capillary permeability changes ous (idiopathic) retinal deshy to cor (with leakage of plasma proteins) and eventually hemshy tachment is rare in dogs and cawse
The more commoll causes oforrhage In our experience most cases of hyphema cats and an underlying cause is cha illtraocular hemorrhage werefrom vasoular hypertension are attribu table to retinall is usually present tribU[
detachment (see Neovascularization of Uveal and Retishy severekllown 20 years ago Since then
nal Tissues section) and most likely occur in response Chronic Glaucoma new infictiom causes of rerrler to choroidal vascular hypertension Hyphema may be Pre-iridal fibrovascular hypema such as felille er spa less commonly caused by tearing of retinal vasculature membranes are also frequentshy immunodeficiency virus have plere that occurs during retinal detachment Otber common ly detected in eyes with been detected Research Oller the subselt causes of vascular hypertension include hyperthyroidism chronic (end-stage) glaucoshy and vpast 20 years has demollstrated hyperadrenocorticism hyperaldosteronism and pheoshy ma G It is likely that hypheshy curs smarty mediators of chromocytoma ma attributable to chronic fetal rneollasclilarizatiort and
glaucoma occurs secondary tent hintraocular inflammation TheNeovascularization of Uveal and Retinal Tissues to tearing and leakage of the body
methodologies for diAgnosticAlthough the presence of blood vessels is necessary in fragile pre-iridal mlcrovascushyworkup hmle improved with themost tissues neovascularization or angiogenesis of tissues lature f Anen
advent ofB-modecan cause severe disease The surfaces of the retina and Acc iris are vulnerable to symptomatic neovasCldarizationl6 Intraocular Neoplasia ultrasonography computed severe Possible causes for neovascularization are ischemia (inshy Growth of a neoplasm largshy l tomography and magnetic can cc cluding long-standing retinal detachment) intraocular er than 2 to 3 mm-l requires resonallce imaging Howeller low 5 neoplasia and inflammation 6 Vascular proliferation on development of a microvasshy the primar) management issues dothe the anterior iris surhce (rubeosis iridis) leads to the forshy cular network to facilitate vesselofhyphema halle remained mation of a pre-iridal ftbrovascular membrane which delivery of nutrients and unchartged A few new can involve the peripheral iris and iridocorneal drainage oxygen and removal of treatment OptiOIlS have been angle and result in obstruction of aqueous humor outshy catabolites 38 Primary and added such as tissue flow Angiogenesis a complex process that incllldes metastatic intraocular neoshy I B(
plasminogm actillator and mdegradation of extracellular matrix and endothelial cell plasms of the anterior uveal topical carbonic anhydrllSe thproliferation is stringently regulated by numerous tissues are highly vascular
2 l(shyinhibitors UnfortulUltely theproangiogenic and antiangiogenic factors Examples of These neoplasms secrete mprognosis for main fair-ling lIisiollgrowth factors that stimulate endothelial cell proliferashy vascular growth factors (eg 3 l(shy
tion include fibroblast growth factors insulinlike growth VEGF TGF-~) that stimushy in an eye with hyphema has Ai factors transforming growth factor-~ (TGF-~) and vasshy late formation and rapid generally remained the Sfme 4 G cular endothelial growth factor (VEGF)lG The newly growth of vessels to support oller the past 20 years H
grown vessels are exceedingly fragile leal( readily and can and sustain rumor growthY 5 G pIpotentially result in hemorrhage and hyphema17 Newly developed capillaries 2(
of neoplasms are prone to 6 MRetinal Detachment hemorrhage because they p
Long-standing retinal detachment stimulates producshy have incomplete basement tion of growth factors that induce vascular endothelial membranes are leaky and 7 Jo
ARTERIOLAR DISEASE PRE-IRIDAL FIBROVASCULAR MEMBRANE GROWTH FACTORS
15
I
Compendium November 1999 20TH ANNIVERSARY S~nia AnimalExotics 1069
often fracture J6 lS Animals with hyphema attributable to
intraocular neoplasia are usually in late middle age or older however we have diagnosed ciliary body hemanshygiosarcoma and iris melanoma in dogs as young as 7 months of age Most primary inrraocular neoplasms are unilateral and thus hyphema attributable to primary inshytraocular neoplasia is unilateral Bilateral primary intraocular neoplasms are reponed infrequenrlyj~ Secshyondary or metastatic intraocular neoplasia (eg lymphshyoma) may affect one or both eyes and may -therefore reshysult in unilateral or bilateral hyphema
Congenital Ocular Anomalies Hyphema in young animals should prompt clinicians
to consider congenital ocular malformation as a ilikely cause Collie eye anomaly which is recessively inherited is characterized by defects of the choroid and sclera atshytributable to abnormal mesodermal differentiation5J In severe cases of vitreoretinal dysplasia (eg in Bedlington terriers Sealyham terriers Labrador retrievers or springshyer spaniels) retinal folding is sufficient to permit comshyplete retinal detachmenr 3 135 Retinal detachment and subsequent hyphema may occur w~h collie eye anomaly and vitreoretinal dysplasia Persistent hyaloid artery ocshycurs sporadically in dogs and is caused by failure of the fetal hyaloid vasculature to regress l5 Rupture of a persisshytent hyaloid artery leads to hemorrhage into the vitreolls body with blood passing into the anterior chamber l5
Anemia According to our experience and a previous report 40
severe acute anemia (eg severe tick or flea infestation) can cause hyphema when hemoglobin rapidly drops beshylow 5 mgdl Insufficient oxygen supply may cause enshydothelial cells to die which leads to leaking of blood vessels
REFERENCES I Belhorn R An overview of the blood-ocular barriers Seyshy
mour R Roberts Memorial Lecture Prog Vet Comp Ophshythalmoll(3)205- 2171991
2 Wilson FM Traumatic hyphema Pathogenes is and manageshyment Ophthalmology 87(9)910- 919 1980
3 Winston SM Ocular emergencies Vet Clin North Am Small Anim Pract II (1 )59-76 1981
4 Gottsch JD H yphema Diagnosis and mallJgemenr Retina 10(Suppll)S65-S71 1990
5 Gilger Be Hamilton HL Wilkie DA et a1 Traumatic oculat proptosis in dogs and cats 84 cases (1980-1993) jAVMA 206(8)1186-11901995
6 Mackin A Cani ne immune-mediated thrombocytopcniashyParr I Compend Contin Educ lract Vet 17(3) 353-364 1995
7 Jordan HL Grindem CB Breitschwerdt EB Thrombocyshy
topenia in cats A retrospective study of 41 cases j Vet Intern Med7(5)261-265 1993
8 Peterso n JL Co uto CG Wellman ML H emosta tic disorshyder in cats A retrospective study and review of the literashyture j Vet Illtem Med ) (5 )298-302 1995
9 Shelton G H Linenberger ML Hematologic abnormalities associated with retroviral in fectio ns in the car Semi Vet Med Surg Small Anim 10(4)220-233 1 )95
10 Boudreaux MK Platelets and coagulation Vet Clin North Am Small Anim hart 26(5) I 065-1087 1996
I Ruiz de Gopegui R Feldman BF Acquired and inherited platelet dysfunction in small animals Compelle Conlill Edltc Pract Vet 20(9) 1039- 1052 1998
12 Fogh JM f ogh IT Inherited coagulation disorders Vet Clin NorthAm Small Anim Pmct 18(1 )231-243 1988
13 Hart SW Noire I Hemostatic disorders in feline immunoshydeficiency virus-seropositive cats j Vet [ntem Med 8(5)355shy362 1994
14 Lisciandro Sc H ohenhaus A Brooks M Coagulation abshynormalities in 22 cats with naturally occurring liver disease j Vet [ntem Med 12(2) 71-75 1998
15 Davidson MG Breitschwerdt EB Nas isse MP Roberts SM Ocular manifestations of Rocky Mountain sported fever in dogsjAVMA 194(6)777-78 1 1989
16 Peiffer J I RL Wilcock BP Yin H The padlOgencs is and sigshynificance of pre-iridal fibrovascular membrane in domes tic animals Vet Pat hoI 27(I)4 1-45 1990
17 Collins BK Moore CPo Diseases and surgery of the canine anterior uvea in Gdatt KN (ed) Veteril1UJ Ophthalmology ed 3 Baltimore Lippincott Williams amp Wilkins 1999 pp 755-795
18 Glaze MB Gelatt KN Feline ophthalmology in Gelart KN (ed) VeterinalJ Ophthalmology ed 3 Baltimore Lippincott Williams amp Wilkins 1999 pp 997-1052
19 Peiffer J r RL Wilcock BP Histopathologic study of uveitis in cats 139 caSes (1978- 1988) jAVMA 198(1) 135- 138 1991
20 Chavki n MJ Lappin MR Powell Cc et al Seroepidemioshylogic and clinical observations of 93 cases of uveitis in (1[1
Prog Vet Comp OphthalmoI2(1)29-36 1992 2 Bisrner S Allergic- and immunologic-mediared diseases of
the eye and adncxae Vet Clin North Am Small Anim Prtlct 24 (4)7 11-734 1994
22 Freeman LJ Hegreberg GA Robinette JD Ehlers-Danlos syndrome in dogs and cats Semin Vet IIled Surg Sma Al1im 2(3)221 - 227 1987
23 Lane IF RobertS SM Lappin MR Ocular manifestations of vascular disease Hypertension hyperv iscos ity and hypershylipidemia jAAHA 29( 1)28-36 1993
24 Hendrix DVH Celatt KN Smith PJ et al Ophthalmic dis shyease as the presenting complaim in five dogs with multiple myelomajAAHA34(2)121 - 1281998
25 Foster ES Lothrop Jr CD Pol)c)themia vera in a cat wirh cardiac hypertrophy jAVMA 192( (2) 1736-1738 1988
26 Hammer AS Couto CG Complications of multiple myeloshyma jAAHA 30(1)9-14 1994
27 Forresror SD G reco DS Relford RL Serum hyperviscos it) syndrome associated with multiple myeloma in rwo cats jAVMA 200(1)79-82 1992
28 Dimski DS Hawkins EC Canine sys temic hypertension Compend Con tin Educ Pract Vet 10(10) 1152- 1158 1988
29 Stiles J Polzin DJ Bisrner SI The prevalence of retinoparhy in cats with systemic hypertension and chronic renal failure Ot hyperthyroidism jAAHA 30(6) 564-572 1994
(alltilues 011 page 1091)
COLLIE EYE ANOMALY VITREORETINAL OYSPLASIA bull PERSISTENT HYALOIO ARTERY
I
1068 Small AnimalExotics 20TH ANNIVERSARY Compendium November 1999
lymphoma ehrlichiosis and chronic inflammatory disshy cell and fibroblast proliferation and subsequent ftbrovasshy often ease Serum total solids will generally be excessively eleshy cular membrane formation l6 The most frequent site of intrao vated because of hyperglobulinemia Hyperviscosity synshy fibrovascular membrane formation in eyes with chronic older drome can also be induced by severe erythrocytosis such retinal detachment is overlying the anterior iris surface glOsar as hemorrhagic gastroenteritis polycythemia vera and (pre-iridal ftbrovascular membrane) 16 Acute hyp hema montlshyerythropoietin~secreting neoplasms may occur if the retinal vasculature tears when the neushy unilatc
rosensory retina detaches from the underlying retinal traoCI SystemiC Hypertension pigment epithelial cells Clinicians must derermine the intrao
Hyphema arrributable to systemic hyperrension is cause of the retinal detachshy ondaI most common in old cats and dogs and is often caused ment because life-threarenshy oma) by chronic renal insufftciency Systemic hypertension ing systemic disease may be suit in affects only the arterial vascular system Chronic high the underlying abnormality arterial pressure may result in arteriosclerosis and aushy (see Causes of Hyphema) in Cong toregulatory arteriolar vasospasm Arteriolar disease our experience sponraneshy H)
causes ischemia and capillary permeability changes ous (idiopathic) retinal deshy to cor (with leakage of plasma proteins) and eventually hemshy tachment is rare in dogs and cawse
The more commoll causes oforrhage In our experience most cases of hyphema cats and an underlying cause is cha illtraocular hemorrhage werefrom vasoular hypertension are attribu table to retinall is usually present tribU[
detachment (see Neovascularization of Uveal and Retishy severekllown 20 years ago Since then
nal Tissues section) and most likely occur in response Chronic Glaucoma new infictiom causes of rerrler to choroidal vascular hypertension Hyphema may be Pre-iridal fibrovascular hypema such as felille er spa less commonly caused by tearing of retinal vasculature membranes are also frequentshy immunodeficiency virus have plere that occurs during retinal detachment Otber common ly detected in eyes with been detected Research Oller the subselt causes of vascular hypertension include hyperthyroidism chronic (end-stage) glaucoshy and vpast 20 years has demollstrated hyperadrenocorticism hyperaldosteronism and pheoshy ma G It is likely that hypheshy curs smarty mediators of chromocytoma ma attributable to chronic fetal rneollasclilarizatiort and
glaucoma occurs secondary tent hintraocular inflammation TheNeovascularization of Uveal and Retinal Tissues to tearing and leakage of the body
methodologies for diAgnosticAlthough the presence of blood vessels is necessary in fragile pre-iridal mlcrovascushyworkup hmle improved with themost tissues neovascularization or angiogenesis of tissues lature f Anen
advent ofB-modecan cause severe disease The surfaces of the retina and Acc iris are vulnerable to symptomatic neovasCldarizationl6 Intraocular Neoplasia ultrasonography computed severe Possible causes for neovascularization are ischemia (inshy Growth of a neoplasm largshy l tomography and magnetic can cc cluding long-standing retinal detachment) intraocular er than 2 to 3 mm-l requires resonallce imaging Howeller low 5 neoplasia and inflammation 6 Vascular proliferation on development of a microvasshy the primar) management issues dothe the anterior iris surhce (rubeosis iridis) leads to the forshy cular network to facilitate vesselofhyphema halle remained mation of a pre-iridal ftbrovascular membrane which delivery of nutrients and unchartged A few new can involve the peripheral iris and iridocorneal drainage oxygen and removal of treatment OptiOIlS have been angle and result in obstruction of aqueous humor outshy catabolites 38 Primary and added such as tissue flow Angiogenesis a complex process that incllldes metastatic intraocular neoshy I B(
plasminogm actillator and mdegradation of extracellular matrix and endothelial cell plasms of the anterior uveal topical carbonic anhydrllSe thproliferation is stringently regulated by numerous tissues are highly vascular
2 l(shyinhibitors UnfortulUltely theproangiogenic and antiangiogenic factors Examples of These neoplasms secrete mprognosis for main fair-ling lIisiollgrowth factors that stimulate endothelial cell proliferashy vascular growth factors (eg 3 l(shy
tion include fibroblast growth factors insulinlike growth VEGF TGF-~) that stimushy in an eye with hyphema has Ai factors transforming growth factor-~ (TGF-~) and vasshy late formation and rapid generally remained the Sfme 4 G cular endothelial growth factor (VEGF)lG The newly growth of vessels to support oller the past 20 years H
grown vessels are exceedingly fragile leal( readily and can and sustain rumor growthY 5 G pIpotentially result in hemorrhage and hyphema17 Newly developed capillaries 2(
of neoplasms are prone to 6 MRetinal Detachment hemorrhage because they p
Long-standing retinal detachment stimulates producshy have incomplete basement tion of growth factors that induce vascular endothelial membranes are leaky and 7 Jo
ARTERIOLAR DISEASE PRE-IRIDAL FIBROVASCULAR MEMBRANE GROWTH FACTORS
15
I
Compendium November 1999 20TH ANNIVERSARY S~nia AnimalExotics 1069
often fracture J6 lS Animals with hyphema attributable to
intraocular neoplasia are usually in late middle age or older however we have diagnosed ciliary body hemanshygiosarcoma and iris melanoma in dogs as young as 7 months of age Most primary inrraocular neoplasms are unilateral and thus hyphema attributable to primary inshytraocular neoplasia is unilateral Bilateral primary intraocular neoplasms are reponed infrequenrlyj~ Secshyondary or metastatic intraocular neoplasia (eg lymphshyoma) may affect one or both eyes and may -therefore reshysult in unilateral or bilateral hyphema
Congenital Ocular Anomalies Hyphema in young animals should prompt clinicians
to consider congenital ocular malformation as a ilikely cause Collie eye anomaly which is recessively inherited is characterized by defects of the choroid and sclera atshytributable to abnormal mesodermal differentiation5J In severe cases of vitreoretinal dysplasia (eg in Bedlington terriers Sealyham terriers Labrador retrievers or springshyer spaniels) retinal folding is sufficient to permit comshyplete retinal detachmenr 3 135 Retinal detachment and subsequent hyphema may occur w~h collie eye anomaly and vitreoretinal dysplasia Persistent hyaloid artery ocshycurs sporadically in dogs and is caused by failure of the fetal hyaloid vasculature to regress l5 Rupture of a persisshytent hyaloid artery leads to hemorrhage into the vitreolls body with blood passing into the anterior chamber l5
Anemia According to our experience and a previous report 40
severe acute anemia (eg severe tick or flea infestation) can cause hyphema when hemoglobin rapidly drops beshylow 5 mgdl Insufficient oxygen supply may cause enshydothelial cells to die which leads to leaking of blood vessels
REFERENCES I Belhorn R An overview of the blood-ocular barriers Seyshy
mour R Roberts Memorial Lecture Prog Vet Comp Ophshythalmoll(3)205- 2171991
2 Wilson FM Traumatic hyphema Pathogenes is and manageshyment Ophthalmology 87(9)910- 919 1980
3 Winston SM Ocular emergencies Vet Clin North Am Small Anim Pract II (1 )59-76 1981
4 Gottsch JD H yphema Diagnosis and mallJgemenr Retina 10(Suppll)S65-S71 1990
5 Gilger Be Hamilton HL Wilkie DA et a1 Traumatic oculat proptosis in dogs and cats 84 cases (1980-1993) jAVMA 206(8)1186-11901995
6 Mackin A Cani ne immune-mediated thrombocytopcniashyParr I Compend Contin Educ lract Vet 17(3) 353-364 1995
7 Jordan HL Grindem CB Breitschwerdt EB Thrombocyshy
topenia in cats A retrospective study of 41 cases j Vet Intern Med7(5)261-265 1993
8 Peterso n JL Co uto CG Wellman ML H emosta tic disorshyder in cats A retrospective study and review of the literashyture j Vet Illtem Med ) (5 )298-302 1995
9 Shelton G H Linenberger ML Hematologic abnormalities associated with retroviral in fectio ns in the car Semi Vet Med Surg Small Anim 10(4)220-233 1 )95
10 Boudreaux MK Platelets and coagulation Vet Clin North Am Small Anim hart 26(5) I 065-1087 1996
I Ruiz de Gopegui R Feldman BF Acquired and inherited platelet dysfunction in small animals Compelle Conlill Edltc Pract Vet 20(9) 1039- 1052 1998
12 Fogh JM f ogh IT Inherited coagulation disorders Vet Clin NorthAm Small Anim Pmct 18(1 )231-243 1988
13 Hart SW Noire I Hemostatic disorders in feline immunoshydeficiency virus-seropositive cats j Vet [ntem Med 8(5)355shy362 1994
14 Lisciandro Sc H ohenhaus A Brooks M Coagulation abshynormalities in 22 cats with naturally occurring liver disease j Vet [ntem Med 12(2) 71-75 1998
15 Davidson MG Breitschwerdt EB Nas isse MP Roberts SM Ocular manifestations of Rocky Mountain sported fever in dogsjAVMA 194(6)777-78 1 1989
16 Peiffer J I RL Wilcock BP Yin H The padlOgencs is and sigshynificance of pre-iridal fibrovascular membrane in domes tic animals Vet Pat hoI 27(I)4 1-45 1990
17 Collins BK Moore CPo Diseases and surgery of the canine anterior uvea in Gdatt KN (ed) Veteril1UJ Ophthalmology ed 3 Baltimore Lippincott Williams amp Wilkins 1999 pp 755-795
18 Glaze MB Gelatt KN Feline ophthalmology in Gelart KN (ed) VeterinalJ Ophthalmology ed 3 Baltimore Lippincott Williams amp Wilkins 1999 pp 997-1052
19 Peiffer J r RL Wilcock BP Histopathologic study of uveitis in cats 139 caSes (1978- 1988) jAVMA 198(1) 135- 138 1991
20 Chavki n MJ Lappin MR Powell Cc et al Seroepidemioshylogic and clinical observations of 93 cases of uveitis in (1[1
Prog Vet Comp OphthalmoI2(1)29-36 1992 2 Bisrner S Allergic- and immunologic-mediared diseases of
the eye and adncxae Vet Clin North Am Small Anim Prtlct 24 (4)7 11-734 1994
22 Freeman LJ Hegreberg GA Robinette JD Ehlers-Danlos syndrome in dogs and cats Semin Vet IIled Surg Sma Al1im 2(3)221 - 227 1987
23 Lane IF RobertS SM Lappin MR Ocular manifestations of vascular disease Hypertension hyperv iscos ity and hypershylipidemia jAAHA 29( 1)28-36 1993
24 Hendrix DVH Celatt KN Smith PJ et al Ophthalmic dis shyease as the presenting complaim in five dogs with multiple myelomajAAHA34(2)121 - 1281998
25 Foster ES Lothrop Jr CD Pol)c)themia vera in a cat wirh cardiac hypertrophy jAVMA 192( (2) 1736-1738 1988
26 Hammer AS Couto CG Complications of multiple myeloshyma jAAHA 30(1)9-14 1994
27 Forresror SD G reco DS Relford RL Serum hyperviscos it) syndrome associated with multiple myeloma in rwo cats jAVMA 200(1)79-82 1992
28 Dimski DS Hawkins EC Canine sys temic hypertension Compend Con tin Educ Pract Vet 10(10) 1152- 1158 1988
29 Stiles J Polzin DJ Bisrner SI The prevalence of retinoparhy in cats with systemic hypertension and chronic renal failure Ot hyperthyroidism jAAHA 30(6) 564-572 1994
(alltilues 011 page 1091)
COLLIE EYE ANOMALY VITREORETINAL OYSPLASIA bull PERSISTENT HYALOIO ARTERY
I
Compendium November 1999 20TH ANNIVERSARY S~nia AnimalExotics 1069
often fracture J6 lS Animals with hyphema attributable to
intraocular neoplasia are usually in late middle age or older however we have diagnosed ciliary body hemanshygiosarcoma and iris melanoma in dogs as young as 7 months of age Most primary inrraocular neoplasms are unilateral and thus hyphema attributable to primary inshytraocular neoplasia is unilateral Bilateral primary intraocular neoplasms are reponed infrequenrlyj~ Secshyondary or metastatic intraocular neoplasia (eg lymphshyoma) may affect one or both eyes and may -therefore reshysult in unilateral or bilateral hyphema
Congenital Ocular Anomalies Hyphema in young animals should prompt clinicians
to consider congenital ocular malformation as a ilikely cause Collie eye anomaly which is recessively inherited is characterized by defects of the choroid and sclera atshytributable to abnormal mesodermal differentiation5J In severe cases of vitreoretinal dysplasia (eg in Bedlington terriers Sealyham terriers Labrador retrievers or springshyer spaniels) retinal folding is sufficient to permit comshyplete retinal detachmenr 3 135 Retinal detachment and subsequent hyphema may occur w~h collie eye anomaly and vitreoretinal dysplasia Persistent hyaloid artery ocshycurs sporadically in dogs and is caused by failure of the fetal hyaloid vasculature to regress l5 Rupture of a persisshytent hyaloid artery leads to hemorrhage into the vitreolls body with blood passing into the anterior chamber l5
Anemia According to our experience and a previous report 40
severe acute anemia (eg severe tick or flea infestation) can cause hyphema when hemoglobin rapidly drops beshylow 5 mgdl Insufficient oxygen supply may cause enshydothelial cells to die which leads to leaking of blood vessels
REFERENCES I Belhorn R An overview of the blood-ocular barriers Seyshy
mour R Roberts Memorial Lecture Prog Vet Comp Ophshythalmoll(3)205- 2171991
2 Wilson FM Traumatic hyphema Pathogenes is and manageshyment Ophthalmology 87(9)910- 919 1980
3 Winston SM Ocular emergencies Vet Clin North Am Small Anim Pract II (1 )59-76 1981
4 Gottsch JD H yphema Diagnosis and mallJgemenr Retina 10(Suppll)S65-S71 1990
5 Gilger Be Hamilton HL Wilkie DA et a1 Traumatic oculat proptosis in dogs and cats 84 cases (1980-1993) jAVMA 206(8)1186-11901995
6 Mackin A Cani ne immune-mediated thrombocytopcniashyParr I Compend Contin Educ lract Vet 17(3) 353-364 1995
7 Jordan HL Grindem CB Breitschwerdt EB Thrombocyshy
topenia in cats A retrospective study of 41 cases j Vet Intern Med7(5)261-265 1993
8 Peterso n JL Co uto CG Wellman ML H emosta tic disorshyder in cats A retrospective study and review of the literashyture j Vet Illtem Med ) (5 )298-302 1995
9 Shelton G H Linenberger ML Hematologic abnormalities associated with retroviral in fectio ns in the car Semi Vet Med Surg Small Anim 10(4)220-233 1 )95
10 Boudreaux MK Platelets and coagulation Vet Clin North Am Small Anim hart 26(5) I 065-1087 1996
I Ruiz de Gopegui R Feldman BF Acquired and inherited platelet dysfunction in small animals Compelle Conlill Edltc Pract Vet 20(9) 1039- 1052 1998
12 Fogh JM f ogh IT Inherited coagulation disorders Vet Clin NorthAm Small Anim Pmct 18(1 )231-243 1988
13 Hart SW Noire I Hemostatic disorders in feline immunoshydeficiency virus-seropositive cats j Vet [ntem Med 8(5)355shy362 1994
14 Lisciandro Sc H ohenhaus A Brooks M Coagulation abshynormalities in 22 cats with naturally occurring liver disease j Vet [ntem Med 12(2) 71-75 1998
15 Davidson MG Breitschwerdt EB Nas isse MP Roberts SM Ocular manifestations of Rocky Mountain sported fever in dogsjAVMA 194(6)777-78 1 1989
16 Peiffer J I RL Wilcock BP Yin H The padlOgencs is and sigshynificance of pre-iridal fibrovascular membrane in domes tic animals Vet Pat hoI 27(I)4 1-45 1990
17 Collins BK Moore CPo Diseases and surgery of the canine anterior uvea in Gdatt KN (ed) Veteril1UJ Ophthalmology ed 3 Baltimore Lippincott Williams amp Wilkins 1999 pp 755-795
18 Glaze MB Gelatt KN Feline ophthalmology in Gelart KN (ed) VeterinalJ Ophthalmology ed 3 Baltimore Lippincott Williams amp Wilkins 1999 pp 997-1052
19 Peiffer J r RL Wilcock BP Histopathologic study of uveitis in cats 139 caSes (1978- 1988) jAVMA 198(1) 135- 138 1991
20 Chavki n MJ Lappin MR Powell Cc et al Seroepidemioshylogic and clinical observations of 93 cases of uveitis in (1[1
Prog Vet Comp OphthalmoI2(1)29-36 1992 2 Bisrner S Allergic- and immunologic-mediared diseases of
the eye and adncxae Vet Clin North Am Small Anim Prtlct 24 (4)7 11-734 1994
22 Freeman LJ Hegreberg GA Robinette JD Ehlers-Danlos syndrome in dogs and cats Semin Vet IIled Surg Sma Al1im 2(3)221 - 227 1987
23 Lane IF RobertS SM Lappin MR Ocular manifestations of vascular disease Hypertension hyperv iscos ity and hypershylipidemia jAAHA 29( 1)28-36 1993
24 Hendrix DVH Celatt KN Smith PJ et al Ophthalmic dis shyease as the presenting complaim in five dogs with multiple myelomajAAHA34(2)121 - 1281998
25 Foster ES Lothrop Jr CD Pol)c)themia vera in a cat wirh cardiac hypertrophy jAVMA 192( (2) 1736-1738 1988
26 Hammer AS Couto CG Complications of multiple myeloshyma jAAHA 30(1)9-14 1994
27 Forresror SD G reco DS Relford RL Serum hyperviscos it) syndrome associated with multiple myeloma in rwo cats jAVMA 200(1)79-82 1992
28 Dimski DS Hawkins EC Canine sys temic hypertension Compend Con tin Educ Pract Vet 10(10) 1152- 1158 1988
29 Stiles J Polzin DJ Bisrner SI The prevalence of retinoparhy in cats with systemic hypertension and chronic renal failure Ot hyperthyroidism jAAHA 30(6) 564-572 1994
(alltilues 011 page 1091)
COLLIE EYE ANOMALY VITREORETINAL OYSPLASIA bull PERSISTENT HYALOIO ARTERY
Recommended