Download Kristina Narfstrom, DVM, PhD, DipECVO

Kristina Narfstrom, DVM, PhD, DipECVO
Professor of Veterinary Ophthalmology
ABNORMAL FUNDUS IN DOGS AND CATS
I. RETINAL INFLAMMATORY DISEASE
DOG
Inflammatory lesions in the ocular fundus are not uncommonly observed in dogs.
However, retinal involvement is usually secondary to disease processes extending
from the choroid or sometimes the vitreous, whereas primary retinal inflammation,
retinitis, is uncommon. The terms chorioretinitis (starting in the choroid) and
retinochoroiditis (initially involving the retina) indicate the primary site and
direction of spread when both the choroid and the retina are involved.
Chorioretinitis
Chorioretinitis may have various causes, and the etiologies include several
infectious diseases, neoplasias, foreign bodies, and trauma. The infectious agents
may be restricted to the eye, but the signs from the ocular fundus may also be a
part of or secondary to a systemic disease. The exact cause of the inflammatory
process is usually hard to establish; the appearance of the lesions in the fundus may
give guidance but is seldom specific, and sampling from the choroid and retina is
difficult and may be associated with undesired complications. However, vitreous
paracentesis to obtain material for cytology and culture can be useful in patients
presenting with severe posterior segment inflammation.
An active inflammation in the retina with or without involvement of the choroid
results in a number of ophthalmoscopic signs that may vary according to both the
severity and the stage of the disease process.
The inflammatory lesions may be unilateral or bilateral and they are usually
irregular in shape. In contrast to the appearance of the inherited retinal dystrophies,
the inflammatory lesions of the fundus are rarely bilaterally symmetrical and
lesions of different stages may be observed within one eye and between the eyes of
one dog. However, certain conditions, for example geographic retinal dysplasia,
may give rise to lesions resembling chorioretinitis.
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The acute stages can be featured ophthalmoscopically by white perivascular
opacities that represent inflammatory cells accumulating around the blood vessels
(cuffing), whereas infiltrates elsewhere are seen as indistinct areas of a grayish or
brownish discoloration in the tapetal fundus and grayish to white lesions in the
nontapetal area. An increase in the severity of the inflammation and the vascular
response causes the retina to become edematous, appearing translucent or even
opaque. Accumulation of exudate between the photoreceptors and the pigment
epithelium may cause a detachment of the neuroretina which leads to visual
impairment or blindness. The detached areas are elevated compared to the
surrounding retina and appear grayish with a distinct border, in contrast to areas
infiltrated by inflammatory cells where the borders are more distinct.
Inflammatory changes affecting the retinal pigment epithelium cause liberation of
pigment. The retinal pigment epithelial layer can become hyperplastic and form
fibrous-like tissue that binds down the retina after the acute phase of inflammation.
The acute changes in the retinal pigment epithelium are often obscured by other
inflammatory signs.
Severe inflammations can be accompanied by hemorrhages. The ophthalmoscopic
appearance depends on the location of the hemorrhage. Discrete, round
hemorrhages are seen if the blood is enclosed within the retinal layers. Bleeding
within the nerve fiber layer is considered to have a flame-shaped appearance,
whereas a subretinal hemorrhage causes an indistinctly bordered, diffuse dull red
area. Bleeding from the superficial retinal vessels can cause a separation of the
vitreous from the retina, which causes the hemorrhage to assume a keelboat shape,
reflecting the force of gravitation. lnflammations involving the retina may also
cause secondary inflammatory changes in the vitreous, manifesting as haze,
nodules of inflammatory cells, and syneresis.
Debris from degenerating neuroretina and pigment from disrupted retinal pigment
epithelial cells are removed by macrophages. Proliferation of connective tissue
elements occurs in the damaged areas and the organization of the scar tissue may
cause retinal folding. Fusion of the outer limiting membrane of the retina to the
choroid is common in chorioretinitis. The retinal pigment epithelium contributes
significantly to the progress of healing; it can become hypertrophic or hyperplastic
or migrate into the lesions. Pigment can also be produced by retinal pigment
epithelium cells that are normally unpigmented, i.e., pigment epithelial cells
overlaying the tapetum lucidum.
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The ophthalmoscopic signs of an inactive chronic inflammatory process are
completely different from the picture of the acute inflammation. Atrophy of the
neural retina in the tapetal fundus is seen as irregular hyperreflective areas with a
distinct border. A well-demarcated zone in the center of the lesions may be heavily
pigmented if the retinal pigment epithelium is affected. Chronic inflammatory
lesions of the retinal pigment epithelium in the non-tapetal fundus show up as
distinctly bordered, depigmented areas. Furthermore, there is always an effect on
the retinal vasculature in the chronic stages of inflammation. The vessels crossing
the inflammatory lesions may be attenuated or sometimes tortuous. Pigment may
also outline the vessels within affected areas.
Viral diseases
Viral diseases can sometimes cause detectable signs in the ocular fundus. A
number of systemic viral diseases can affect the tissues of the eye and the fundus is
considered to be most susceptible to virus preferentially affecting the central
nervous system.
Canine distemper morbillivirus causes posterior segment disease in the dog.
Multiple irregular areas of retinochoroiditis with or without inflammation of the
optic nerve are typical findings, but it has to be remembered that there are no
ophthalmoscopic findings pathognomonic for canine distemper. The signs of
posterior segment disease is not necessarily correlated to the usually more obvious
external ocular signs, e.g., mucopurulent conjunctivitis. Manifest retinal lesions
caused by canine distemper morbillivirus cannot be treated.
In acute stages of the disease, the ophthalmoscopic picture is characterized by
active retinochoroiditis, and the appearance of the multifocal inflammatory lesions
is in correspondence with the previous general description of active inflammation
of the retina and choroid. The non-specific ophthalmoscopic findings are altered
during the transition from acute to chronic retinochoroiditis, as discussed in the
section on chorioretinitis. Visual impairment is usually not detectable in patients
with retinochoroiditis if the optic nerve is not involved. However, in severely
affected eyes, the inflamed areas can coalesce and result in a complete destruction
of the retina, which will cause blindness.
Optic neuritis may accompany the retinochoroiditis. Signs of active inflammation
of the optic nerve head may be visible ophthalmoscopically, and a hyperreflective
peripapillar crescent or, in more severe cases, optic atrophy, can be found in
chronic cases of distemper. Optic neuritis is likely to cause an obvious impairment
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of vision.
The primary retinochoroidal lesions can be subdivided into four types: 1) peracute
generalized retinopathy, 2) chronic generalized retinopathy, 3) dystrophy of the
retinal pigment epithelium with or without damage to the retina, and 4) sporadic
foci of advanced retinal degeneration, focal retinal atrophy and sclerosis. The nontapetal fundus has been considered to be more involved during the acute phase.
Eosinophilic inclusion bodies in glial cells may be found in the acute stages.
Ganglion cells exhibit the most severe degeneration, but the photoreceptors also
degenerate. Depending on the severity of the disease, disorganization of the retinal
layers may occur. Hypertrophy and proliferation of the retinal pigment epithelium
is common in distemper retinochoroiditis.
The presence of virus in the retina may result from primary localization
concurrently with the infection of other organs or follow secondary extension from
the brain. Active retinitis without detectable involvement of the brain or the optic
nerve is seen when the canine distemper virus is primarily located to the retina.
Ganglion cell degeneration in cases with optic neuritis, but in absence of other
inflammatory changes in the retina, suggests a retrograde degenerative process.
Canine herpesvirus
Retinal involvement, including focal edema, neuronal degeneration, gliosis and
infiltration of the ganglion cell layer, and choroiditis may be seen histologically in
canine herpesvirus infection. Chronic signs of inflammatory disease may be
present on ophthalmoscopy in dogs surviving this infection, although the most
characteristic feature is probably retinal dysplasia.
Rickettsial diseases
Tick-borne rickettsial infection may affect the posterior segment of the eye as a
part of the systemic disease. The posterior segment lesions are not pathognomonic,
but hemorrhage is a common feature. The frequency of posterior segment affection
is variable.
Canine Ehrlichiosis
Ehrlichiosis is a tick-borne rickettsial infection which has been reported from
several parts of the New and Old World. Ehrlichia canis is transmitted by the tick
Rhipicephalus sanguineus, but also Ixodes species is a vector of Ehrlichia.
Ehrlichiosis may be complicated by the presence of other diseases transmitted by
the same vector, such as Hemobartonella or Babesia.
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Canine Ehrlischiosis is an acute, febrile disease featured by pancytopenia,
especially thrombocytopenia, which causes serosal and mucosal hemorrhages.
Excessive hemorrhage or secondary bacterial infections may lead to a fatal
outcome. Ophthalmoscopically signs of retinal inflammation, retinal hemorrhage
and hyphema can be observed.
The causative agent can be demonstrated in Giemsa stained smears, where it
appears as blue cytoplasmic inclusions mainly in monocytes and lymphocytes. A
serodiagnostic method (indirect fluorescent antibody technique) is used for
confirmation of infection and detection of chronically infected carriers in which the
Ehrlichia organism rarely can be demonstrated in blood cells. Systemic tetracycline
has been recommended as the treatment of choice.
Rocky Mountain Spotted Fever
This acute infectious disease is caused by Rickettsia rickettsii, which is transmitted
by ticks of the genus Dermacentor. Widespread vasculitis accompanied by
hemorrhage is the result of damage to the vascular endothelium. The ocular lesions
resemble those in canine Ehrlichiosis, although hyphema has been considered to be
less common. However, anterior uveitis, chorioretinitis and sometimes also retinal
hemorrhage is observed.
The diagnosis is confirmed serologically with the indirect fluorescent antibody
technique. Systemic treatment with chloramphenicol, tetracyclines or
enrophloxacin, and symptomatic treatment of the ophthalmic disease, if necessary,
are recommended.
Mycotic diseases
Posterior segment disease may be seen in a number of systemic mycoses in dogs.
The frequency of ocular involvement varies considerably. The infection may
spread hematogenously, directly from the anterior parts of the eye or by infiltration
along the optic nerve and the meninges. Some of these mycotic diseases are:
-Acremoniasis
-Aspergillosis
-Blastomycosis
-Histoplasmosis
-Cryptococcosis
-Coccidioidomycosis
-Geotrichosis
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Cryptococcus neoformans is a saprophytic organism which exists only in a yeast
form and not in a mycelial form unlike other fungi causing mycotic diseases.
Cryptococcus may cause focal or disseminated infections in the dog. The clinical
manifestation is usually featured by signs caused by involvement of the central
nervous system, e.g., ataxia, circling and head tilt. Ocular cryptococcosis has so far
only been reported in cases of disseminated infection and the organism may be
spread by direct extension from granulomatous meningitis and optic neuritis or
hematogenously from more remote locations. Ocular signs without systematic
signs are rare in canine cryptococcosis, but have been reported.
The ocular findings are related to subretinal granulomas, usually grayish-white and
translucent to opaque, which initiate an exudative inflammation.
Ophthalmoscopically, the tapetal fundus appears discolored in areas of retinal
elevation subsequent to accumulation of exudate in the subretinal space, whereas
the corresponding findings in the non-tapetal fundus are gray to tan areas.
Inflammatory changes may be observed in the optic nerve head. In chronic cases
several small pigmented nodules, i.e., cryptococcal granulomas, can be scattered
throughout the tapetal fundus. Intravitreal hemorrhage and exudates may obscure
the ophthalmoscopic view of the fundus in severe cases. Complete retinal
detachment causing blindness has been described.
Vitreous paracentesis for cytology and culture can be diagnostic in ocular
cryptococcosis. New methylene blue, PAS, and hematoxylin-eosin stains can be
used to identify the fungus. Cryptococcus neoformans appears as a round to ovoid
organism, approximately 20 microns in diameter. The cryptococcal elements are
surrounded by a thick polysaccharide capsule.
Histologic changes are usually confined to the posterior segment. In the choroid
and retina, large, multifocal accumulations of macrophages and plasma cells, but
also neutrophils and lymphocytes, and abundant Cryptococcus organisms are
usually seen. The size and location of the inflammatory lesions vary considerably.
Small granulomas containing fungal elements may involve the choroid at several
locations. Other inflammatory foci may involve extensive areas of all retinal
layers, whereas small inflammatory lesions may be distributed within just one or
two layers of the retina. Cryptococcus organisms may be present in the choroid as
well as the proteinaceous subretinal exudates in cases of retinal detachment.
Cryptococcosis is ultimately fatal if not treated. Ketoconazole has been used in the
treatment of cryptococcosis, either alone or in combination with amphotericin B, 56
fluorocytosine. Combination chemotherapy with amphotericin B and either
fluconazole or flucytosine, or both, has also been successful in dogs.
Valley fever or coccidioidomycosis is caused by a dimorphic, saprophytic soil
fungus, Coccidiodes immitis. The disease is endemic in the semi-arid, low altitude
areas of southwestern United States, but cases may occur elsewhere through the
mobility of the canine population. Coccidioidomycosis is mainly caused by
inhalation of spores, whereas transmission from animal to animal is rare,
apparently because the endospores are too fragile. Thus, Coccidiodes immitis
mainly causes respiratory disease characterized by granuloma formation in the
pulmonary and thoracic lymph nodes. It is usually an insidious and chronic
disease. Disseminated coccidioidomycosis occurs most likely in dogs with reduced
capacity to resist infections or develop immunity.
Signs of ocular disease may be the only apparent clinical sign in some patients.
Ocular coccidioidomycosis can affect one or both eyes. Mycotic keratitis is the
most frequent presenting sign. Systemic signs include weight loss, lethargy,
lameness and respiratory disease.
Histologically, the disease is essentially a granulomatous panuveitis with
granulomas appearing most frequently in the ciliary cleft, iris root, ciliary body,
choroid and retina. Various stages of retinal degeneration and exudative retinal
detachment may be present.
Presence of respiratory disease and exposure to the endemic areas should alert the
examiner. The diagnosis should, however, be confirmed by culture or serology.
Aqueous or vitreous paracentesis may yield mononuclear inflammatory cells and
fungal elements. Coccidiodes immitis is a spherical organism 20 to 100 microns in
diameter, containing endospores (2-5 microns in diameter).
Long-term treatment with ketoconazole has been reported to be the therapy of
choice for disseminated coccidiodomycosis. The therapy should be evaluated with
caution, because a recently published study has indicated that long-term
ketoconazole treatment in dogs can cause bilateral, rapidly progressive cataracts.
However, relapses may occur if the treatment is discontinued too early.
Enucleation may be indicated if the eye appears to be the only site of active
infection; otherwise the ocular lesions are treated symptomatically.
Algal disease
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Plant material is rarely associated with posterior segment disease; the most
frequent lesions caused by plant material are seen in the external ocular structures
or in the anterior segment following penetration of the cornea. One alga,
Prototheca, which indeed is a primitive plant, has been reported to cause posterior
segment disease.
The achlorophyllic alga Prototheca is a saprophyte widely spread in the
environment. Two species, Prototheca wickerhamii and Prototheca zopfii, have
been reported to be capable of causing systemic disease in the dog. It is thought
that the organisms are ingested and localized to the colon and then further spread
hematogenously and lymphogenously. The alga usually causes a slowly
disseminating disease affecting the brain, eyes, heart, intestines, kidney and liver.
An acute dissemination has been reported in dogs with colitis.
Prototheca occasionally reaches the eye hematogenously and ocular disease, e.g.,
blindness, may be the presenting sign in some patients. The alga causes anterior
uveitis, chorioretinitis or panuveitis, which may progress to chronic
endophthalmitis. The retina is often detached secondary to the posterior segment
inflammation and blindness is reported to occur in approximately 50% of the cases.
Vitreous paracentesis or sampling of tissue can be used to obtain material so the
organism can be demonstrated and identified by culture. Histologically Prototheca,
which resembles the fungi Cryptococcus, Blastomyces, Candida and
Pneumocystis, is usually found bilaterally in the choroid and subretinal exudates. It
is a unicellular, ovoid organism with a refractile cellulose wall surrounding a
nucleus and granular cytoplasm. Treatment of disseminated protothecosis in dogs
has been unsuccessful thus far.
Protozoan diseases
Posterior segment diseases caused by protozoan are infrequently reported in dogs.
Ocular involvement in Toxoplasmosis and Leishmaniasis have been known for
decades, whereas Neospora caninum has been identified as a potential ocular
pathogen quite recently.
Infections with the protozoon Toxoplasma gondii have been observed in several
avian and mammalian species in most areas of the world. The parasite has an
enteroepithelial cycle occurring only in domestic cats and some other members of
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the family Felidae, resulting in production of oocysts. Toxoplasma has also an
extra-intestinal cycle that occurs in a number of mammals and birds. In the acute
disease, the gastrointestinal tract is involved, which leads to hematogenous and
lymphogenous dissemination to other organs. The lungs and liver are frequently
involved, but also other organs, e.g., lymphnodes and muscles, may show disease.
Subacute or chronic infections may affect the brain, and common signs of
toxoplasmosis in the dog include pneumonia, hepatitis and encephalitis.
Concurrent active infections with canine distemper virus and toxoplasmosis have,
for uncertain reasons, been frequently recorded.
Toxoplasma gondii is also recognized as a cause of ocular disease in several
species. The most common findings are iridocyclitis and retinochoroiditis, but
lesions may occur in most ocular structures. Histologically, there is perivascular
accumulations of cells, hyalinization of vessel walls and infiltration of cells into
the retina. Retinal detachment may be seen in severe cases. Retinal elevations,
without detachment, can be caused by accumulation of exudate within the choroid.
The diagnosis is usually confirmed by high or rising titer of Toxoplasma antibodies
in sera. It has been stated that Toxoplasma retinochoroidits is usually associated
with a stable antibody titer.
Chemotherapy with sulfonamides and pyrimethamine have been used to treat
biologically active and possibly reduplicating Toxoplasma gondii. The aim is to
limit the spread of infection until host immunity is acquired. Sulfadiazine (60
mg/kg per day) is given every 4 to 6 hours and pyrimethamine is administered at a
dosage of 0.5 to 1.0 mg/kg per day. Toxic side effects caused by inhibition of
folate metabolism can be prevented and alleviated with folinic acid (1 mg/kg per
day).
Leishmania donovani is a flagellate protozoan naturally transmitted by sand flies.
It is mainly found in the Mediterranean countries in southern Europe, but
increasing mobility of the canine population has caused cases elsewhere.
Ocular involvement seems to be common in the dog with keratoconjunctivitis as
the most common sign. Other signs of ocular Leishmaniasis are blepharitis and
anterior uveitis. The uveal inflammation progresses to endophthalmitis and the
posterior segment appears to be involved by extension from the anterior parts of
the eye.
Histologically the lesions are characterized by massive infiltration of histiocytes,
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lymphocytes and plasma cells in the affected parts of the eye. The organism may
be present in the cytoplasm of histiocytes. Detection of the organism and serologic
tests can be used to establish the diagnosis.
Parasitic diseases
A hematogenous invasion of the eye by a migrating nematode larva, ocular larva
migrans, is a rare condition in dogs, although the host may be invaded by several
nematode species. However, ocular larva migrans is an important zoonotic disease
and posterior segment disease caused by migrating Toxocara canis which has been
confused with retinoblastoma, a highly malignant condition in children.
Despite that Toxocara canis, an ascarid nematode, is a common and important
intestinal parasite in the dog, cases of intraocular larva migrans are infrequently
reported in this species. However, it has been reported that intraocular findings
associated with Toxocara invasion were present in 39% of working sheepdogs in
New Zealand.
The parasitic granulomas appear as small raised translucent nodules in the tapetal
retina, whereas the corresponding lesions in the non-tapetal fundus have a grayish
color. Multifocal well-delineated areas of subacute to chronic inflammatory lesions
in the fundus, characterized by tapetal hyperreflectivity, depigmented areas in the
non-tapetal fundus and vessel attenuation, may also be found ophthalmoscopically.
Vision may occasionally be severely impaired. These findings are similar to
diffuse unilateral subacute neuroretinitis in humans (which may be bilateral as
well), a condition attributed to toxic damage secondary to nematode migration in
the subretinal space.
Well organized granulomas extending from the choroid to the subretinal space,
eventually with a focally detached retina, are typical histologic findings.
Granulomas may also be found in the optic nerve. Parts of the larvae may be seen
within the granuloma, and numerous eosinophils are present around its periphery.
Because of the focal nature of the granulomas, they can easily be missed by routine
sectioning.
Treatment against the parasite in the retina is normally not indicated, because it is
highly unlikely that vivid larvae are present within the ophthalmoscopically
detectable granulomas. However, the public health and hygiene aspects of
migrating Toxocara canis larvae should be considered.
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Angiostrongylus vasorum is enzootic in parts of Europe and Africa, but may
appear elsewhere, e.g., imported dogs. It is a nematode usually found in the
pulmonary arteries and right side of the heart in dogs and wild carnivores.
However, the parasite can occasionally affect the eyes and the nematode has, in
some spectacular cases, even been free-floating in the anterior chamber (ocular
larva migrans). Angiostrongylus is also capable of causing posterior segment
disease with subsequent impairment of vision.
Ocular signs include granulomatous uveitis or panuveitis, subretinal hemorrhage
and chorioretinitis. Patent angiostrongylosis can be diagnosed by detecting larvae
in feces or in tracheal mucus. The pulmonary nodules associated with the disease
may be seen on thoracic radiographs. One study reports successful treatment
consisting of surgical removal of the organism from the anterior chamber
combined with systemic treatment with levamisole.
Migration of fly larvae from the order Diptera beneath the retina,
ophthalmomyiasis interna posterior, results in subretinal tracks, retinal
hemorrhage, pigmentary disturbances and other signs in humans. A similar
condition has been reported in a dog with a 48-hour history of unilateral
blepharospasm and miosis in which migration of a larva within the tissues of the
posterior segment was monitored. The larva could not be identified but resembled
those of Diptera.
Vascular disease processes
The retinal vasculature is well suited to direct noninvasive examination techniques.
Systemic disease as well as local ocular pathology is capable of causing observable
changes in retinal and choroidal vessels. Specific methods of examination, except
for analysis of blood constituents, blood flow and blood pressure measurements
and coagulation studies, include ophthalmoscopy and fluoresceine angiography.
Furthermore, in the research environment, specific histopathologic studies may be
done as well as studies of the ocular circulation and the sequelae of vascular
disease processes by using radioactively marked microspheres. A short description
of funduscopic lesions associated with systemic hypertension, hyperviscosity and
hyperlipidemia will be given.
Systemic hypertension
Dogs with experimentally-induced hypertension exhibit retinal hemorrhage, retinal
detachment, and arteriolar changes. In spontaneous cases of systemic hypertension,
visual disturbances are often the cause of the initial presentation. The most
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common ocular finding is retinal hemorrhage, but retinal detachment is also
frequently seen.
Hyperviscosity syndromes
In hyperviscosity syndromes, distended and tortuous retinal blood vessels are seen
in conjunction with sacculation of venules, retinal hemorrhage and papilledema.
Hyperlipemia
Hyperlipemia may impart a milky pink coloration to retinal vessels, most easily
observed in the non-tapetal fundus.
Diabetic retinopathy
Diabetic retinopathy occurs in dogs, although the extent and severeness of the
retinal lesions are mild compared to the retinal changes in the human counterpart.
As in man, the ocular lesions include anomalies of the retinal vasculature and
cataract formation. However, whereas in man the vascular changes are of major
importance in the disease and contributing to blindness, in spontaneous-occurring
diabetes in the dog they are much less severe and of minor clinical importance. The
cataract formation, on the other hand, is an early finding in the disease of dogs and
often the reason for a patient with diabetes to be presented for the first time.
In man, the initial retinal vascular changes is the formation of microaneurysms,
resulting from the sacculation of a small area of the capillary wall. Rupture of these
aneurysms results in ophthalmoscopically visible focal hemorrhages, and there
may be accompanying exudation. The vasculature may also form coils and loops.
These are the so called “back-ground” changes in diabetic retinopathy.
“Proliferative” changes may also develop, which include preretinal and vitreal
neovascularization, often with connective tissue formation in the vitreous. The
accompanying severe vitreal hemorrhage and non-rhegmatogenous retinal
detachments that may follow will often cause blindness. In thedog the background
retinopathy occurs in diabetes but not the proliferative changes that develop in the
human. The retinal changes do not occur until late in the course of disease, not
until after 3-5 years, and then generally whether diabetes is treated or not. In both
man and dog the duration of the disease, rather than the severity, appears to
determine the onset of retinal changes.
During the past years, induced canine diabetic retinopathy has provided a useful
model for the study of the human condition. There are several means to induce
diabetes in dogs, but administration of alloxan and experimental galactosemia are
currently used methods.
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Morphological changes in spontaneous and induced diabetic retinopathy of dogs
include thickening of the vascular basement membrane, pericyte loss,
microaneurysm formation, and capillary closure. There is also a loss of smooth
muscle cells in retinal arterioles, most obvious in the central retina, which
accompanies the loss of pericytes. It has also been shown that there are regional
differences in the distribution of vascular lesions within the same retina. Thus,
microaneurysms and acellular capillaries were more prevalent in the superior
temporal retina than in the inferior nasal quadrant, while the distribution of
pericyte ghosts (a pocket in the basement membrane at the site from which a
pericyte has disappeared) in the same eyes were not significantly different between
quadrants.
These findings show that local factors within the eye play an important role in the
response of the retinal microvasculature to the disease process.
Retinopathies with immunologic background
Immune-mediated trombocytopenia is a clinical disease characterized by anemia,
hemorrhage and low platelet counts. The presenting sign is often petechiation and
ecchymosis of the gingiva or conjunctiva. Hyphema and retinal hemorrhage is a
common finding in the disorder. Treatment consists of controlling the hemorrhage.
Blood transfusion may be necessary in severe cases. Systemic corticosteroid
treatment is used (1-2 mg/kg per day) for several weeks and then tapered off to a
low maintenance dose.
Autoimmune hemolytic anemia
Autoimmune hemolytic anemia (AtAH) (AIHA) is an autoimmune disease of both
man and dogs. Presenting clinical signs are acute to chronic anemia and
ophthalmoscopically the retinal vessels are light red and difficult to follow due to
the blood disorder. Treatment is systemic corticosteroids (2-4 mg/kg) for 2 weeks
and then decreasing to maintenance levels. Supportive therapy is often indicated
for the anemia.
Systemic lupus erythematosus
Systemic lupus erythematosus (SLE) is a multisystem disorder with immunologic
abnormalities related to the presence of autoantibodies in the blood and in lesions
of the body. There is a genetic predisposition for the disease and genetic processes
may initiate the systemic problem. Ocular lesions include hemorrhages and serous
retinal detachments. Recommended treatment is as for AIAH (AIHA).
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Secondary retinal degeneration as a sequelae to inflammation
Retinal detachment
Various pathologic conditions of the eye can cause focal, multifocal or total retinal
detachment. The neuroretina is usually separated from the underlying retinal
pigment epithelium, which implies a disruption of the intimate and essential, but
structurally weak, association between the outer segments of the photoreceptors
and the retinal pigment epithelium. The loss of structural integrity is associated
with loss of function and secondary retinal degeneration in the affected area. Thus,
a focal retinal detachment affecting a minor area will usually not result in clinically
detectable visual impairment, whereas detachment of the entire retina is a blinding
condition. Detachments involving large areas of the retina may result in separation
of the peripheral retina from the ora ciliaris retinae. , dialysis . The retina will
only remain attached at the optic nerve head in cases with total retinal detachments
combined with dialysis.
Ophthalmoscopy reveals an anterior displacement of the retinal surface and the
retinal blood vessels. Large volumes of subretinal fluid can cause segments of the
retina to balloon anteriorly, in extreme cases extending to the posterior surface of
the lens. If there is a total detachment with dialysis, the retina will hang in folds,
resembling a grayish colored curtain, from the optic nerve head and the denuded
tapetal fundus will appear hyperreflective when the light is not absorbed by the
retina. Extensive detachments may cause secondary uveitis. Cataracts and other
pathologic changes are likely to develop in severely affected eyes. It is noteworthy
that some vision may be retained in the acute phase of detachments and residual
pupillary light reflexes will then be present.
Retinal detachments, which are not solely associated with developmental defects in
the neuroretina and retinal pigment epithelium, can be subdivided according to the
causative mechanism in rhegmatogenous, traction and exudative detachments. A
rhegmatogenous detachment is caused by a tear in the neuroretina. The tear allows
vitreous and fluid to dissect the neuroretina from the retinal pigment epithelium,
exacerbating the lesion. A force from the vitreous body pulling the neuroretina
anteriorly, e.g., from an organizing hemorrhage in the vitreous body, can result in
traction detachment. Fluid and cell deposition, e.g., in chorioretinitis or
hypertension, in the subretinal space elevates the retina and causes an exudative
detachment.
Rhegmatogenous retinal detachments have been suggested to be the most common
form in dogs, because the majority of the detachments are associated with ocular
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diseases known to induce retinal tears. Many retinal detachments are associated
with lenticular disease. For example, in one study it was shown that 23% of the
detachments occurred after extracapsular cataract extraction. Retinal detachments
secondary to cataract surgery are generally believed to be rhegmatogenous,
although the cause of the neuroretinal tears is difficult to determine. Other causes of
retinal detachment identified in this study include panuveitis, infectious disease
(including bacterial, rickettsial and mycotic infections), systemic hypertension,
trauma and congenital ocular disease. Retinal tears were seen in 26% of the eyes
and traction bands in 5%.
Rhegmatogenous detachments seen in Labrador Retrievers with a syndrome
including skeletal abnormalities and retinal dysplasia have been investigated as a
model for rhegmatogenous retinal detachments in humans. The cause of retinal
tears leading to detachment in this animal model appears to be traction on the
retina from the vitreous. Formation of fibrocellular membranes on the surface of
the totally detached retina, to which the retinal pigment epithelium, non-pigmented
ciliary epithelium, macrophages and glial cells contribute, occurs in a later stage of
the disease. A proliferative vitreoretinopathy of this type is an important cause of
failure in retinal detachment surgery in humans.
Treatment of the retinal detachments depend on the presence of a detectable
underlying disease and the cause and extension of the detached area. Even
extensive detachments may reattach with return of vision, provided that treatment
is commenced early. Failure to reattach leads to degeneration of the retina and loss
of visual capacity in the affected area.
Secondary retinal degeneration may be caused by chorioretinitis or inflammatory
effects on the choriocapillaris with or without involvement of the retinal pigment
epithelium. Neoplastic and proliferative conditions may cause inflammatory
reactions and secondary retinal detachments.
Granulomatous meningoencephalitis (reticulosis)
Granulomatous meningoencephalitis (GME) is an idiopathic non-suppurative
inflammatory disease of the central nervous system (CNS) which can affect the
eye. The disseminated form of GME has previously been described as
inflammatory or granulomatous reticulosis, whereas the focal form was previously
termed neoplastic reticulosis. GME is characterized by proliferation of
reticuloendothelial elements and lymphoplasmic infiltrates of the vessels of the
CNS. The cellular reaction of the intracranial vasculature may apparently be shared
by the blood vessels of the posterior segment of the eye and the anterior uvea.
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Sporadic cases of ocular involvement in dogs have been reported from different
parts of the world.
Perivascular infiltration of mainly histiocytes and mononuclear white blood cells
forming cuffs around blood vessels in the central nervous system, the posterior
segment of the eye and the uveal tract have been described histologically. Silver
stained sections have shown a whorled pattern of reticulin fibrils around the
vessels.
Ocular signs may develop before CNS abnormalities. The disease is usually
bilateral, although the extent of involvement varies. Papillitis and peripapillary
edema has been reported to be the single ophthalmoscopic sign in blind patients.
Various secondary ocular disease processes may be found depending on the
localization of the inflammatory lesions. Infiltration of the uveal tract has been
reported to cause uveitis. Retinal detachment may be found secondary to choroidal
involvement. Secondary glaucoma caused by obstruction of the aqueous humor
flow through the pupil by posterior synechia or exudates process has been reported
as well as glaucoma secondary to obliteration of the aqueous outflow pathways.
Vision may be retrieved temporarily in cases presenting with papillitis by treatment
with corticosteroids, but the prognosis for vision and even long-term survival is
considered to be very poor.
Primary tumors
Primary tumors of the retina, choroid and optic disc may all cause inflammatory
reactions of the posterior structures of the eye. Some examples of primary tumors:
-Astrocytoma
-Medulloepithelioma
-Malignant melanomas
-Secondary tumors
Tumors may involve the posterior segment by extension from a primary focus in
the anterior segment, the optic nerve or the extraocular tissues or by metastasis
from a more remote site.
Metastatic tumors
Metastatic neoplasms in the choroid and retina are often incidental findings. Their
ophthalmoscopic appearance and the clinical course are variable. A number of
tumors and sites of origin have been reported, e.g., mammary gland
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adenocarcinomas, thyroid adenocarcinoma, renal adenocarcinoma, malignant
melanoma, hemangiosarcoma, rhabdomyosarcoma and neurogenic sarcoma.
Lymphomas
Malignant lymphoma, usually affecting both eyes, seems to be the most common
secondary intraocular tumor.
Cat
Several types of infectious diseases affect the cat posterior segment, specifically
the fundus, and give rise to active or passive signs of choroiditis, choroiretinitis,
retinitis or retinochoroiditis. In some types of inflammation optic neuritis and
retinal detachments may also be seen. Such disease are of viral (FIV, FIP, FeLV),
protozoal (toxoplasma gondii), fungal (cryptococcus neoformans, histoplasma
capsulatum, blastomyces dermatitidis, coccidioides immitis, candida albicans),
bacterial (tuberculosis; mucobacterium strains), and parasitic (hypoderma species)
origin.
The lesions observed are usually multifocal, of varying sizes, and can be found
anywhere in the tapetal or non-tapetal fundus. Inactive / chronic inflammatory
lesions in the tapetal fundus are seen as hyperreflective areas, with or without
darkly pigmented demarcations and usually with rather sharp borders. In the nontapetal fundus, inactive lesions appear as depigmented and/or hyperpigmented or
mottled areas. Active inflammatory lesions are seen as hypo-reflective areas,
which are dull blue, green or grey. The borders are usually irregular and fuzzy. In
the non-tapetal fundus, active lesions are hypopigmented, either white or greyish.
Perivascular cuffing may also be seen as white opacities surrounding or running
alongside retinal vessels.
In optic neuritis the optic disc is often fuzzy and indistinct and there may be
neovascularization and haemorrhage in its vicinity. The animal often presents as
acutely blind. Retinal detachment of inflammatory origin is always of the bullous
type, caused by choroidal exudates, which detach the sensory retina from the RPE.
The detachment can be partial or complete, uni- or bilateral. Clinical signs depend
on severity of lesions but cats are usually not presented for examination unless they
go acutely blind, then usually with bilateral complete retinal detachments.
If the fundal lesions are inactive and chronic, there is usually no way of
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determining the underlying cause and no further time need to be spent on the
problem. If the lesion is active, however, attempts should be made to determine the
aetiology. If diagnosis is made, which is often a systemic disease (see above), this
should be treated if possible. In some types of infections and specifically if no
diagnosis is made, anti-inflammatory drugs can be used to modify the
inflammatory reactions, if there are no contraindications for this treatment. In cats,
systemic corticosteroids, 1-2 mg/kg, are usually used. When the clinical signs of
inflammation have subsided, the dosage of corticosteroids can be gradually
reduced. In some animals the inflammation has subsided but some need reduced
levels of corticosteroids on a long-term basis to keep the inflammation under
control. All of these animals should be re-examined periodically to monitor any
side-effects or changes in the disease process. If the retinopathy is accompanied by
anterior uveitis, topical treatment is recommended as well.
Some specific infectious diseases:
Feline infectious peritonitis (FIP) causes a pyogranulomatous inflammation,
especially of blood vessels. Perivascular exudates, retinal haemorrhage, choroidal
exudation, focal retinal detachment and optic neuritis may be seen.
Feline leukaemia virus (FeLV) causes anterior and posterior uveitis and
perivascular cuffing, chorioretinal infiltrates, retinal detachment and optic neuritis
may be seen.
Feline immunodeficiency virus (FIV) causes retinal perivasculitis and white
punctate infiltrates in the vitreous. When located in the periphery this is often
denoted as pars planitis.
Toxoplasma infection causes retinochoroiditis and it is mainly the outer
neuroretinal structures that are affected in the disease. The organism is transmitted
through the ingestion of infected tissues, ingestion of oocytes passed in an infected
cat’s feces, or transplacentally. This severe disease has public health implications.
A strong association between FIV positive status and positive Toxoplasma gondii
titres has been demonstrated in the cat. Topical corticosteroids in combination with
clindamycin (12.5-25 mg/kg orally twice a day for 2 weeks) has been used
successfully to treat the disease. However, animals that are also FIV positive may
respond poorly to treatment. Recurrent inflammatory episodes are frequent and
may subsequently lead to visual impairment or blindness.
Cryptococcus infection is almost always contracted by inhalation of the causative
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organism. The brain and meninges are frequently involved in disseminated disease
and ocular involvement can occur by direct extension from the CNS or by
hematogenous spread. Retinitis, retinochoroiditis and retinal detachments are seen.
Optic neuritis may be present and neovasculatization in the detached retina is not
uncommon. Diagnosis is often difficult but biopsy of affected tissues, including
vitreous paracentesis, is often diagnostic. Treatment consists of chemotherapy and
long-term treatment with itraconazole (50 mg once daily initially, then every other
day treatment for months up to years) has been shown to be effective.
Tuberculosis has public health implications and is potentially zoonotic. The disease
in cats is caused by human, bovine or avian strains of mucobacterium. Ocular signs
include a granulomatous choroiditis which may be accompanied by retinal
detachment. Diagnosis is made by identification of the causative acid-fast bacilli in
affected tissue obtained by biopsy or at post-mortem.
Ophthalmomyiasis interna posterior is caused by the aberrant migration of
parasites to the posterior segment. The lesions are pathognomonic and consist of
curvilinear tracks of uniform width resembling a road map. There may also be
large areas of chorioretinal scarring. Parasites causing the problem are assumed to
be fly larvae of the hypoderma species. Treatment consists of active extraction, if
possible, of the parasite and antiinflammatory treatment.
Diseases affecting retinal circulation in cats
Systemic diseases as well as local ocular pathology are capable of causing
observable changes in retinal and choroidal vessels. Distension, tortuosity,
haemorrhage and trombosis of small retinal vessels frequently occur in these
diseases and also give an inflammatory reaction.
Anaemic retinopathy causes retinal haemorrhage in cats, when blood haemoglobin
levels are low (less than 5 g/dl). Concurrent diseases can include
thrombocytopenia, septicaemia, uraemia, panleukopaenia and lymphosarcoma.
Treatment of the underlying condition is essential.
Hypertension is not an uncommon problem in older cats. Retinal and vitreal
haemorrhages are seen as well as hyphema. There is often bullous retinal
detachment. Feline hypertension is associated with chronic renal disease,
hyperthyroidism, systemic anaemia and hypertrophic cardiomyopathy. Treatment
consists of correction of the underlying condition and specific medical
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antihypertensive therapy and symptomatic treatment of the ophthalmic lesions.
Serum hyperviscosity syndromes are rare phenomena but have been described in
the cat associated with multiple myeloma and Tetralogy of Fallot. Serum
hyperproteinaemia or polycythaemia cause serum hyperviscosity, which can cause
retinal and vitreal haemorrhages and retinal detachment. Clinical signs are
primarily due to sludging of blood and resultant hypoxia. Distended and tortuous
retinal blood vessels are seen, sacculation of venules, retinal haemorrhage and
papilledema. Treatment consists of correcting the underlying disorder and relies on
removal of excess paraproteins.
Hyperlipidemia is an excess of lipid and lipoprotein constituents in the blood. A
primary problem with lipid may exist or the condition may be secondary to other
diseases. The disorder can have a familial component and be influenced by
concurrent disease and diet. Conditions associated with secondary hyperlipidemia
in small animals include diabetes mellitus, hyperadrenocorticism, hepatic
dysfunction, nephrotic syndrome and pancreatitis. A deficiency of lipoprotein
lipase has been suspected in affected cats and it has also been a common ocular
finding in kittens with familial hyperchylomicronemia.
Hyperlipemia may impart a milky pink coloration to retinal vessels. Specific ocular
treatment is not necessary.
Diabetic retinopathy appears to be the sequela to progressive damage to retinal
capillaries with subsequent formation of microaneurysms. Leakage of fluid and
blood from abnormal vessels accounts for retinal and vitreal haemorrhage and
retinal detachments.
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