feline ocular diseases 貓常見眼科疾病的診斷與治療 · 2012-08-26 · gili 8 –genus:...

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貓常見眼科疾病的診斷與治療

林中天林中天

台大獸醫專業學院臨床動物醫學研究所教授

台大附設動物醫院眼科部

Professor in Veterinary OphthalmologySchool of Veterinary Medicine

National Taiwan University

Feline Ocular diseases

• Cats have unique/predisposed diseases in several systems compared to other species.

• It is important to know species difference in ophthalmic diseases:difference in ophthalmic diseases: human, companion animals, large animals, exotic/wild animals etc.

• There are many ocular diseases occurred only in animals, not in humans.

Eye diseases in cats v.s. humans

Factors should be taken into account when diagnose ocular diseases in cats:

• Different ocular structures from human eyes:e.g. animals with NM (Nictitating membrane-third eyelid); retina with tapetum no macula Rods-dominant photoreceptorswith tapetum no macula. Rods dominant photoreceptors.

• Different predisposed diseases from human eyes• Different disease etiology/pathogenesis from human eyes• Different managements of eye diseases from human eyes• Different drug response from human eyes, e.g. glaucoma• Different drug toxicity from human eyes

貓眼角膜結膜疾病貓皰疹病毒性角膜結膜炎貓壞死性角膜炎貓嗜伊紅性角膜結膜炎貓潰瘍性角膜炎

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貓潰瘍性角膜炎

貓葡萄膜疾病貓葡萄膜炎

貓眼角膜結膜疾病的診斷與治療

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Feline Keratitis/Keratoconjunctivitis

• Feline herpesvirus (FHV-1) keratitis• Corneal sequestration• Eosinophilic keratitis

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p• Ulcerative keratitis

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Feline herpesvirus keratoconjunctivits貓皰疹病毒性角膜結膜炎

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Herpesvirus

• Virology– Herpesviridae

• Alpha herpesvirus (Alphaherpesvirinae) G i l i

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– Genus: simplex virus– Feline herpesvirus type 1 (FHV-1)

• Beta herpesviruses • Gamma herpesviruses

Herpesvirus conjunctivitis in cats

• FHV-1 is a common virus in cats (70~ 80% cats carry the virus, most are latent).

• Highly contagious but species-specific

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Highly contagious, but species specific.• Treatable, not curable (viral infection)• Latent & flare up • A key factor inducing clinical diseases is

“STRESS”, similar to “cold sores” in people.

Pathogenesis of FHV-1

• Highly affinity to mucosal epithelial cells of conjunctiva, cornea & nasal, oral cavity.

• Latency of FHV-1

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Latency of FHV 1– Life-long infection– Trigmental ganglion– Shedding virus depends on the stress events

(Nasisse,1992)

Feline herpesvirus type 1 keratitis• Clinical features of virus

– Epidemiology• Seropositive in over 90% of cats

I f ti h i

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– Infection mechanism• Contact, droplets, vertical transmission• Replicate in epithelium and latency within

the trigeminal ganglia• Viral reactivation with clinical disease

– Recrudescent disease

Feline herpesvirus type 1 keratitis• Pathogenesis

Primary infection(cytolytic disease)

Diseased cats Normal cats

Virus clearedminority

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(cytolytic disease)

Latent virus

Recrudescent disease(cytolytic or immunologic disease) Subclinical shedding

Extraneuralpersistence

majority

reactivation

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Feline herpesvirus type 1 keratitis

• Pathogenesis–Cytolytic infection

• Viral replication

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p– Immune-mediated inflammation

• Perssistent stimulation by viral antigens• Low grade or no viral replication

Feline herpesvirus type 1 keratitis• Clinical signs

– Ocular pain with or without respiratory signs • Blepharospasm• Lacrimation

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• Ophthalmic examination– Corneal lesions

• Dendritic or linear ulceration • Edema • Neovascularization

– Conjunctivitis– Symblepharon

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Herpetic dendritic ulceration stained by Rose Bengal

Martin CL. Ophthalmic disease in Veterinary medicine. Mansob publishing, 2005

FELINE HERPESVIRUS–RELATED DISEASES

• Stromal keratitis refers to infection and inflammation of the deeper corneal tissue, and is a less common manifestation of FHV-1 but significantly vision-threatening.

• Stromal FHV-1 keratitis may result from chronic recurrent episodes of keratitis causing stromal collagen

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recurrent episodes of keratitis causing stromal collagen damage and opacification.

• Many ocular diseases are directly caused by or are thought to be related to FHV-1.– KCS– Nasolacrimal obstruction– Symblepharon– Corneal sequestration– Eosinophilic keratitis


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Symblepharon

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• Differential diagnosis– Calicivirus

Chl d hil

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– Chlamydophila

20(Maggs, 2005)

Feline herpesvirus type 1 keratitis• Clinical and laboratory diagnosis

– History– Clinical signs – Ophthalmic examination

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– Cytology• Intranuclear inclusion bodies

– Serology• Can not differentiate immune responses

between vaccination and wild-type viral infection

Nartia B. Brain lesions and experimental equine herpesvirus. Vet Pathol 37:476-479, 2000


• Laboratory diagnosis–Virus detection methods

• Immunofluorescent antibody

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Immunofluorescent antibody• Virus isolation• Polymerase chain reaction

–Nested PCR


• Management– Factors to consider

• Age

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• Age• Immunity• Disease severity

– Corticosteroid contraindicated

Treatment of Feline Herpetic Infection

• Most importantly, do not use topical steroid eyedrop to feline eyes with conjunctivitis unless exceptions

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feline eyes with conjunctivitis unless exceptions. • Topical NSAID may be used for controlling keratitis.• Topical antibiotic if 2nd infection is present.• Topical anti-viral agents may be used, but most are not

commercially available. – Trifluridine, idoxuridine, vidarabine, acyclovir, cidofovir.

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Treatment of Feline Herpetic Infection

• Systemic anti-viral agents: watch for side effects.• INF, e.g. Interferon-alpha 30IU

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, g p(topical, systemic, natural human, recombinant)

• Oral L-lysine is helpful and safe for cats.

L-lysine is helpful in treatment and prevention of clinical diseases

caused by FHV-1 in cats • L-lysine

– A good nutritional supplement for cats

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– As an “adjunctive” therapy of FHV-1 (Not killing or removing the virus away)

– Inhibit FHV-1 replication and activation.– Reduce severity of clinical symptoms.– Prevent recurrence of clinical diseases

from latency.

Why L-lysine is helpful in fighting with FHV-1 infection in cats?

• L-lysine– As a competitor of arginine in FHV-1,

antagonizing the availability of arginine of FHV-1

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1• Arginine, an essential amino acid for viral protein

synthesis of FHV-1.– Anti-stress (prevent recurrence)

– Daily lysine intake “at correct dose” and regular ocular examination are recommended for cats ever with eye problems.

Prognosis of FHV-1 infection

• FHV-1 conjunctivitis and/or keratitis cannot be cured, only controlled.

• Under proper management, the cats can maintain stable ocular condition and good quality of life

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stable ocular condition and good quality of life.• When the cornea is involved, vision may get

worse if the lesion is not controlled. • The disease may causes long-term ocular pain

or/and discomfort without proper treatment.• Most infected cats become latent carriers.

Daily care of chronic FHV-1 cats

• Regular follow-up (examination) for corneal and conjunctival lesions by experienced vets

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experienced vets. • Oral L-lysine.• Prevent stress.

FHV潛伏感染之復發 –緊迫• 原發性病毒感染復原後，有90%的貓會變成慢性潛伏感染，成為無臨床症狀排毒者且隨時可能復發。

易使病毒再度活化復發之緊迫(Stress)情況：

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–旅行–內源性因素造成免疫抑制

(如其他病毒或病原感染)

–外源性因素造成免疫力下降(使用類固醇或化療藥物)

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生病、免疫力不佳

懷孕、泌乳

營養狀況不佳

通風、衛生不佳

生活空間過於擁擠

換至陌生環境、新主人

有新貓或新犬引入

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Eosinophilic Keratitis

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• Eosinophilic keratitis (EK) is also termed proliferative keratoconjunctivitis and it occurs almost exclusively in cats and less commonly in horses.

• A pink-white vascularized mass starting laterally or medially in the peripheral cornea

• Third eyelid or bulbar conjunctiva may also be

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y j yinvolved.

• Lesions are more often unilateral but may be bilateral.• This is a progressive keratopathy and clinical signs of

pain or discharge are variable.• Up to 24% of cats may have accompanying corneal

ulceration.• Young adult mixed breed cats tend to be

overrepresented.

• The etiology and pathogenesis of EK have yet to be determined.– Most likely type I hypersensitivity or a type IV

h iti it ti

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hypersensitivity reaction

• Many scientists strongly suggest that FHV-1 may be related to the pathogenesis of EK.

Eosinophilic keratitis

• Pathogenesis– Unknown Chronic ocular irritation

Immune-mediated

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response to certain allergens

~80 % because of Feline Herpesvirus type 1

(FHV-1) infection


Ultraviolet light


• Ophthalmic examination– Cornea

• White deposits of cheesy consistency

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• Progressive red granulating proliferation• 20% Ulceration

– Blepharospasm

– Conjunctivitis – STT values may be decreased

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Superficial white depositsBarnett. 2006

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White deposits over the corneaBarnett. 2006

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Extensive corneal lesionsBarnett. 2006

Pre‐treat Post‐treat

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Eosinophilic keratitis• Diagnosis• Definitive diagnosis is based on cytological

sampling of the lesion.– A spatula or the handle end of a #15 Bard-Parker

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blade is used to scrape the lesion following topical anesthetic agent and samples are placed on glass slides and air dried.

– Eosinophils, mast cells, lymphocytes, and neutrophils are typically identified on cytologic samples.

mast cellseosinophils

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Angular corneal epithelium cells, eosinophils with red granule, degranulated mast cells. (Wright stain)

Mackey S. Cytologic Diagnosis and Review of Feline Eosinophilic Keratitis. 2005

EOSINOPHILIC KERATITIS

• TreatmentEK generally responds well to topical corticosteroid administration.

1 0% prednisolone acetate

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– 1.0% prednisolone acetate– 0.1% dexamethasone– Starting four times a day and gradually weaning over

the course of several weeks to one to two times daily– Therapy can be discontinued following regression of

lesions, but recurrence is common (>60%) with long-term follow-up.

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• Treatment– Use of corticosteroid should be cautious– Hormonal therapy

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py• Megestrol acetate

– Artificial progesterone• Risks of complications

– If FHV-1 lesion is present• Antiviral agents


• Prognosis– Good if corneal lesion is limited

Lif l t t t if FHV 1 i f ti

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– Life-long treatment if FHV-1 infection is obvious.

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Feline Corneal Sequestration

Corneal sequestrum

• Pathogenesis– unknown

Degenerative necrotic stroma

Brownish-black

plaque on cornea

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80%with FHV-1

keratitis

Chronic cornealirritation and

epithelial defect

on cornea

Corneal sequestrum

• Unique to cats• Breed-related Persian Burmese Himalayan Siamese

• Cause: chronic irritation• FHV-1 keratitis Keratoconjunctivitis sicca Chronic ulcer

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Corneal sequestrum• In one patient survey of cats with corneal

sequestrum in our eye clinic in Taiwan.

• Unilateral (80%) >> bilateral (20%)

• Leading breeds of affected cats:– Persian – Chinchilla– American shorthairs– Mixed/Domestic shorthairs– Himalayan – Others

Corneal sequestrum

Ages of affected cats:Most affects cats are younger than 5 years old at first presentation.

Gender of affected cats:• Persian: more males• Persian: more males • Chinchilla: more females• American shorthairs: even males/females• Mixed/Domestic shorthairs: even males/females• Himalayan: even males/females• Others: males/females

Corneal sequestrum

• Clinical signs and corneal lesions– Brownish-black plaque on cornea

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Brownish black plaque on cornea– Corneal neovascularization/edema– It is often painful, especially if

• Ulceration surrounding sequestrum – Blepharospasm– Lacrimation– Photophobia

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Corneal sequestrum with bullous keratopathy

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Corneal sequestrum with cherry eye/deformed NM cartilage

Corneal sequestrum

• Diagnosis– Clinical signs

O hth l i i ti

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– Ophthalmic examination– Cytology

• Degenerated corneal stroma surrounded by inflammatory cells

The structure of corneal sequestrum

• The cornea contains an amorphous dense substance continuous with epithelial basement membrane and overlaying corneal ulceration.

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• Necrotic keratocytes in spaces of disarranged collagens.

• Keratocyte apoptosis with various degrees of inflammatory cell infiltration.

Cullen et al., 2005

The structure of corneal sequestrum

• Scanning electron microscopy: not iron• Fluorescence spectroscopic analysis: lipid and

protein, the same as normal cornea

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• Ultraviolet-visible light absorbance spectroscopy: 280nm compared to 385nm(normal cornea): melanin particles

• Optical microscopy: melanin

Featherstone et al., 2004

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Optical microphotographFeatherstone et al., 2004

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Corneal sequestrum

• Treatment–Conservative management

• IndicationsC f t bl

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–Comfortable eye–Financial restrain

• Wait for spontaneous sloughing• Medication if corneal ulcer is present.

Corneal sequestrum

–Surgical management• Indications

–Persistent pain–Failure of the plaque to slough

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p q g

• Superficial keratectomy• Conjunctival pedicle flap• Nictitating membrane flap• Corneo-conjunctival transposition

–To promote corneal healing

63superficial keratectomy

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• Granulation develops on defective cornea during corneal wound healing.

• Corneal opacity in the visual axis may i i i i

Corneal condition after surgery

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impair some vision.• Healing cornea progresses

reepithelization.• Eyes become comfortable

after sequestrum removal.

Corneal sequestrum

• Viral cause suspected– Use of corticosteroid should be

cautious

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– Management against FHV-1 if signs of FHV-1 infection are present.

• Prognosis– Disease severity– Good to fair

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Ulcerative Keratitis in cats

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in cats• Definition

– Loss of variable amounts of corneal epithelium or/and stroma

Ulcerative KeratitisUlcerative Keratitis

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epithelium or/and stroma

Ulcerative Keratitis

• Causes of corneal ulcers (in cats)– Trauma– Herpetic keratitis

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Herpetic keratitis

Ulcerative Keratitis• Classification

– Superficial ulceration– Stromal ulceration

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– Descemetocele– Corneal perforation

Special types of corneal ulcers/erosions:

May not be deep, but does not heal well.• Indolent ulcer: loose epithelium, F(+) area

smaller than actual lesion size • Corneal erosion: F(-)• Melting ulcer: F(+) or (-) progress rapidly• Melting ulcer: F(+) or (-), progress rapidly• FHV-1 corneal ulceration: dendritic/linear lesion

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• Pathogenesis– Protease is produced by

• Keratocytes

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• Keratocytes• Leukocytes • Bacteria (e.g. Pseudomonas spp)

– Speed up progression from simple ulcer to deep ulcer or corneal perforation.


• Clinical Signs– Pain and blepharospasm

S id l t

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– Serous, mucoid, or purulent discharge

Ulcerative Keratitis• Diagnosis

– Clinical signs– Ophthalmic examination

• STT

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• Fluorescein• Slit lamp biomicroscopy • Intraocular pressure measurement

– Ancillary diagnostic tests• Bacterial culture• Cytology

Ulcerative Keratitis• Medical Treatment

– Topical• Broad-spectrum antibiotic drop• 1% Atropine

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• 1% Atropine • Artificial tears

– Systemic NSAIDs in severe cases – Do Not use topical corticosteroid.

• Wearing E-Collar


• Surgical Treatment– Debridement

Therapeutic contact lens

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– Therapeutic contact lens– Nictitating membrane flap (NM flap)– Conjunctival flap

Therapeutic bandage lens for animals

• Brands: Germany, USA, Japan.• Rigid or soft.• To prevent disruption of corneal healing

– Prevent disruption by eyelid movementp y y– Drug penetration and drug/tear retention– Pain relief– Protection– Support

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Ulcerative Keratitis • Nictitating membrane flap

– Indicated for• Corneal erosions

S fi i l l l

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• Superficial corneal ulcer– Benefits

• Protect a weakened cornea• Reduce evaporation of tear• Prevent interference of corneal wound healing

by eyelid


• Nictitating membrane flap

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flap

Conjunctival graft (結膜瓣移植角膜修補術)

屬顯微手術，是國際獸醫眼科專科醫師常使用來治療嚴重角膜疾病之方式

角膜清創後，取合適之眼球部結膜瓣 (Bulbar conjunctiva)移至角膜病變區，並縫合至角膜上。使用7-0, 8-0, 或9-0之縫線

角膜手術後之病畜照顧及注意事項 (Post-operative care of corneal surgery)

Wearing Elizabethan collar (戴頭套)Exercise restriction (限制運動)Medication: (藥物控制)( )

Topical and systemic antibiotics (抗生素) Anti-inflammatory agent (消炎劑) Mydriatics-cycloplegics (散瞳劑): to prevent iris

spasm and iris synechiaThird eyelid (NM) flap removal in 4-6 weeks;

Conjunctival graft removal in > 4-8 weeks.


• Prognosis– Healing is rapid in simple corneal

erosion

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erosion.– Healing is delayed in ulceration

deeper than mid stroma or with infection.

– Guarded prognosis if FHV-1 is involved and corneal lesion is severe.

貓葡萄膜疾病之診斷與治療

林中天

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Structure of the eye

• Fibrous:– Outermost layer– cornea and sclera– Support for ocular structure

• Vascular:– Middle layer– uvea (choroid, ciliary body, iris)– Contains major nutritional vessels for

ocular structure• Nervous (neural):

– Innermost layer– Retina– Neural sensory functions

Uveitis in cats

定義

Uveitis: inflammation of uveal tract

‧Anterior uveitis - 虹膜及睫狀體發炎‧Posterior uveitis - 脈絡膜及睫狀體發炎‧Panuveitis 整個葡萄膜發炎‧Panuveitis - 整個葡萄膜發炎

‧A common cause of red eye in dogs and cats‧為貓咪是最常見的眼內疾病‧70%以上的貓有其他同時相伴發生的全身性疾病

Uveitis

• Potentially blinding • Inflammation of uvea• Could be suppurative and non suppurative• Could be suppurative and non-suppurative.• Cause may be complex• Terminology: anterior uveitis/ iridocyclitis,

posterior uveitis/ choroiditis, panuveitis Endophathalmitis, Panophthalmitis.

Terminology related to uveitis• Aqueous flare: Increased opalescence of

aqueous humor (increased level of proteins and cells) due to uveitis.

• Hyphema: Blood or hemorrhage in anterior chamber.

• Keratic precipitates (KP`s): Deposits of inflammaory cells on posterior cornea in uveitis.

• Hypopyon: Pus in anterior chamber. • Iris prolapse: Prolapse of iris through a perforated

cornea or corneo-scleral wound.

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Terminology of uveitis

• Synechia: Adhesions between iris and corneal endothelium (anterior) or iris and anterior lens capsule (posterior).

• Iris bombe: Iris adherent to lens (posteriorsynechia usually caused by uveitis) around whole ofsynechia, usually caused by uveitis) around whole ofpupillary margin, hence non-attached parts bulgeforward due to pressure from behind.

• Chorioretinitis: Inflammation of the choroid and retina.

• Panuveitis: Inflammation of whole uveal tract.

動物臨床症狀

• 畏光(photophobia)• 眼瞼痙攣(blepharospasm)• 流淚(lacrimation)• 流淚(lacrimation)

• 疼痛造成食慾減退及精神沉鬱–睫狀體肌肉(ciliary muscle) 痙攣

臨床症狀

–角膜水腫– Aqueous flare–玻璃體混濁角膜沉澱物(keratic–角膜沉澱物(keratic precipitates)

–前房積膿或積血

臨床症狀

‧縮瞳或瞳孔形狀改變(dyscoria)

‧對散瞳藥(mydriatics)有抗性有抗性

‧黏著(synechiae)

‧iris bombe

‧虹膜腫脹或混濁

‧虹膜色素增加

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臨床症狀

• 視網膜下水腫、出血、滲出液或剝離

• 眼內壓下降• 視力下降• Long term seqeula:

synechia, glaucoma, cataract.

(Maggs 2008)

Uveitis -病因

• Infectious causes• Immune-mediated• Traumatic• Traumatic• Metabolic diseases• Neoplasm• Idiopathic

病因

• 傳染性–細菌：Brucella, Lepto, Lyme disease, TB黴菌：Blastomycosis Cryptococcosis–黴菌：Blastomycosis, Cryptococcosis, Histomycosis, Aspergilosis

–病毒 (cat): FIV, FeLV, FIP, FHV–原虫：Toxoplasmosis

Immune-mediated

• Hypermature cataracts (phacolytic uveitis)• Lens trauma (phacoclastic uveitis)• Immune-mediated thrombocytopenia• Immune-mediated vasculitis

Traumatic

• Penetrating injuries: 2nd bacterial infection• Sharp trauma: uveitis, LIU, intraocular

hemorrhage

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Metabolic diseases

• Diabetes mellitus: lens induced uveitis 2nd to cataract.

• HyperlipidemiaHyperlipidemia• Systemic hypertension

Uveal Neoplasms

• Melanoma• Adenoma• Adenocarcinoma• Lymphosarcoma• TVT

診斷

• 臨床症狀 (painful, red eye, miosis, low IOP)• 詳細眼科學檢查 (for the cause, severity of uveitis, and

2nd complications, esp glaucoma)

• 完整的病史。• 完整身體理學檢查。• 血檢- CBC, 血清生化學• 特定病原之血清學或PCR檢查。﹝如 Blasto, Histo,

Crypto 和 Toxo﹞• 尿檢• 影像學檢查-看胸腔是否有腫瘤或黴菌感染。• 抽眼房液或玻璃體液做培養和細胞檢查。

• 眼科臨床診斷設備• An examination room which can be

darkened• Focal illuminator (eg pen light)• Magnifying device

– direct ophthalmoscope– slit-lamp biomicroscope– surgical loupe

Pen light

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Surgical loupe

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• 眼後房臨床檢查設備• Direct ophthalmoscope• Indirect ophthalmoscope• Pen light plus condensing lens

治療

• 原則：積極控制發炎反應以避免青光眼、黏連及失明等二次性併發症。

• 目標：–找到並針對致病原因治療–控制炎症反應–減輕疼痛

治療

• Anti-microbial agents for infectious cause.• 對症消炎用藥

– Topical corticosteroids ：能減輕炎症反應，次數依嚴重度而定。次數依嚴重度而定。

– Topical NSAID ：能減輕炎症反應，有flurbiprofen, suprofen, diclophenac等。

– Systemic NSAID or steroid: useful in marked anterior uveitis and chorioretinitis

Systemic anti-inflammation

• Control of intraocular inflammation• Different from antibiotics

• Corticosteroid: Prednisolone DexamethasoneCorticosteroid: Prednisolone, Dexamethasone• NSAID (Non-steroids): e.g. Rimadyl (carprofen)

– Effective in controlling uveitis.– When side effects of steroids are concerned.

• Indications and side effects

Mydriatic

Topical atropine 1% ：散瞳以減少不適及黏連。• To relieve ciliary spasm, decrease the risk of

posterior synechiae.• To stablize blood-aqueous barrier.• Side effects: Decrease tear production and

potentially increase IOP.

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預後

• 早期發現並積極治療可改善或痊癒。• 有些致病原因可能使病情持續惡化。• 頑固嚴重者須進行全眼球摘除。

常見後遺症‧虹膜沾黏:向前和角膜沾黏或是向後和水晶體沾黏 (synechia)

‧白內障‧青光眼‧失明

Thank you for your attention!Thank you for your attention!

feline ocular diseases 貓常見眼科疾病的診斷與治療 · 2012-08-26 · gili 8 –genus:...

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