Feline Ocular diseases. Eye diseases in cats v.s. humans. Feline Keratitis/Keratoconjunctivitis

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1 Professor in Veterinary Ophthalmology School 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: 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 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 4 Feline Keratitis/Keratoconjunctivitis Feline herpesvirus (FHV-1) keratitis Corneal sequestration Eosinophilic keratitis Ulcerative keratitis 5 6 1

2 Herpesvirus Feline herpesvirus keratoconjunctivits Virology Herpesviridae Alpha herpesvirus (Alphaherpesvirinae) Genus: simplex virus Feline herpesvirus type 1 (FHV-1) Beta herpesviruses Gamma herpesviruses 7 8 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 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 Life-long infection Trigmental ganglion Shedding virus depends on the stress events (Nasisse,1992) 9 10 Feline herpesvirus type 1 keratitis Clinical features of virus Epidemiology Seropositive in over 90% of cats 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 Extraneural persistence Diseased cats Primary infection (cytolytic disease) Recrudescent disease (cytolytic or immunologic disease) minority majority reactivation Normal cats Virus cleared Latent virus Subclinical shedding

3 Feline herpesvirus type 1 keratitis Feline herpesvirus type 1 keratitis Pathogenesis Cytolytic infection Viral replication Immune-mediated inflammation Perssistent stimulation by viral antigens Low grade or no viral replication 13 Clinical signs Ocular pain with or without respiratory signs Blepharospasm Lacrimation Ophthalmic examination Corneal lesions Dendritic or linear ulceration Edema Neovascularization Conjunctivitis Symblepharon 14 Herpetic dendritic ulceration stained by Rose Bengal 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 visionthreatening. Stromal FHV-1 keratitis may result from chronic 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 Martin CL. Ophthalmic disease in Veterinary medicine. Mansob publishing, Feline herpesvirus type 1 keratitis Symblepharon

4 Feline herpesvirus type 1 keratitis Differential diagnosis Calicivirus Chlamydophila hil 19 (Maggs, 2005) 20 Feline herpesvirus type 1 keratitis Clinical and laboratory diagnosis History Clinical signs Ophthalmic examination Cytology Intranuclear inclusion bodies Nartia B. Brain lesions and experimental equine herpesvirus. Vet Pathol 37: , 2000 Serology Can not differentiate immune responses between vaccination and wild-type viral infection 21 Feline herpesvirus type 1 keratitis Laboratory diagnosis Virus detection methods Immunofluorescent antibody Virus isolation Polymerase chain reaction Nested PCR 22 Feline herpesvirus type 1 keratitis Management Factors to consider 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. Topical NSAID may be used for controlling keratitis. Topical antibiotic if 2 nd infection is present. Topical anti-viral agents may be used, but most are not commercially available. Trifluridine, idoxuridine, vidarabine, acyclovir, cidofovir

5 Treatment of Feline Herpetic Infection Systemic anti-viral agents: watch for side effects. INF, e.g. Interferon-alpha 30IU (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 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 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. 27 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. 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. 28 Daily care of chronic FHV-1 cats Regular follow-up (examination) for corneal and conjunctival lesions by experienced vets. Oral L-lysine. Prevent stress. 29 FHV 復 90% 臨 狀 復 易 度 復 (Stress) 力不 泌 狀 不 不 旅行 ( ) 力 降 ( 類 療 )

6 Eosinophilic Keratitis 31 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 involved. 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. 32 The etiology and pathogenesis of EK have yet to be determined. Most likely type I hypersensitivity or a type IV hypersensitivity reaction Many scientists strongly suggest that FHV-1 may be related to the pathogenesis of EK. 33 Eosinophilic keratitis Pathogenesis Unknown Chronic ocular irritation Immune-mediated response to certain allergens ~80 % because of Feline Herpesvirus type 1 (FHV-1) infection Eosinophilic keratitis Ultraviolet light 34 Eosinophilic keratitis Ophthalmic examination Cornea White deposits of cheesy consistency Progressive red granulating proliferation 20% Ulceration Blepharospasm Conjunctivitis STT values may be decreased Superficial white deposits 35 Barnett

7 White deposits over the cornea Extensive corneal lesions Barnett Barnett Pre treat Post treat Diagnosis Eosinophilic keratitis Definitive diagnosis is based on cytological sampling of the lesion. A spatula or the handle end of a #15 Bard-Parker 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 eosinophils mast cells EOSINOPHILIC KERATITIS Angular corneal epithelium cells, eosinophils with red granule, degranulated mast cells. (Wright stain) Treatment EK generally responds well to topical corticosteroid administration. 1.0% 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 longterm follow-up. Mackey S. Cytologic Diagnosis and Review of Feline Eosinophilic Keratitis

8 Eosinophilic keratitis Treatment Use of corticosteroid should be cautious Hormonal therapy Megestrol acetate Artificial progesterone Risks of complications If FHV-1 lesion is present Antiviral agents Eosinophilic keratitis Prognosis Good if corneal lesion is limited Life-long treatment t t if FHV-1 1infection is obvious. Feline Corneal Sequestration Pathogenesis unknown 80% with FHV-1 keratitis Corneal sequestrum Chronic corneal irritation and epithelial defect Degenerative necrotic stroma Brownishblack plaque on cornea Corneal sequestrum Unique to cats Breed-related Persian Burmese Himalayan Siamese Cause: chronic irritation FHV-1 keratitis Keratoconjunctivitis sicca Chronic ulcer 47 8

9 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 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 Corneal neovascularization/edema It is often painful, especially if Ulceration surrounding sequestrum Blepharospasm Lacrimation Photophobia

10 Corneal sequestrum with bullous keratopathy Corneal sequestrum with cherry eye/deformed NM cartilage Corneal sequestrum Diagnosis Clinical signs 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. Necrotic keratocytes in spaces of disarranged collagens. Keratocyte apoptosis with various degrees of inflammatory cell infiltration. 57 Cullen et al., The structure of corneal sequestrum Scanning electron microscopy: not iron Fluorescence spectroscopic analysis: lipid and protein, the same as normal cornea Ultraviolet-visible light absorbance spectroscopy: 280nm compared to 385nm(normal cornea): melanin particles Optical microscopy: melanin Featherstone et al., Optical microphotograph Featherstone et al.,

11 Corneal sequestrum Corneal sequestrum Treatment Conservative management Indications Comfortable eye Financial restrain Wait for spontaneous sloughing Medication if corneal ulcer is present. 61 Surgical management Indications Persistent pain Failure of the plaque to slough Superficial keratectomy Conjunctival pedicle flap Nictitating membrane flap Corneo-conjunctival transposition To promote corneal healing 62 superficial keratectomy Corneal condition after surgery Corneal sequestrum Granulation develops on defective cornea during corneal wound healing. Corneal opacity in the visual axis may impair i some vision. i Healing cornea progresses reepithelization. Eyes become comfortable after sequestrum removal. 65 Viral cause suspected Use of corticosteroid should be cautious Management against FHV-1 if signs of FHV-1 infection are present. Prognosis Disease severity Good to fair 66 11

12 in cats Definition Loss of variable amounts of corneal epithelium or/and stroma Causes of corneal ulcers (in cats) Trauma Herpetic keratitis Classification Superficial ulceration Stromal ulceration 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 12

13 Pathogenesis Protease is produced by Keratocytes Leukocytes Bacteria (e.g. Pseudomonas spp) Speed up progression from simple ulcer to deep ulcer or corneal perforation. Clinical Signs Pain and blepharospasm Serous, mucoid, or purulent discharge Diagnosis Clinical signs Ophthalmic examination STT Fluorescein Slit lamp biomicroscopy Intraocular pressure measurement Ancillary diagnostic tests Bacterial culture Cytology 75 Medical Treatment Topical Broad-spectrum antibiotic drop 1% Atropine Artificial tears Systemic NSAIDs in severe cases Do Not use topical corticosteroid. Wearing E-Collar 76 Therapeutic bandage lens for animals Surgical Treatment Debridement Therapeutic contact lens Nictitating membrane flap (NM flap) Conjunctival flap Brands: Germany, USA, Japan. Rigid or soft. To prevent disruption of corneal healing Prevent disruption by eyelid movement Drug penetration and drug/tear retention Pain relief Protection Support 77 13

14 Nictitating membrane flap Indicated for Corneal erosions Superficial i corneal ulcer Benefits Protect a weakened cornea Reduce evaporation of tear Prevent interference of corneal wound healing by eyelid 79 Ulcerative Keratitis Nictitating membrane flap 80 Conjunctival graft ( ) (Bulbar conjunctiva) 7-0, 8-0, 9-0 (Postoperative care of corneal surgery) Wearing Elizabethan collar ( ) Exercise restriction ( ) Medication: ( ) Topical and systemic antibiotics ( ) Anti-inflammatory agent ( ) Mydriatics-cycloplegics ( ): to prevent iris spasm and iris synechia Third eyelid (NM) flap removal in 4-6 weeks; Conjunctival graft removal in > 4-8 weeks. Prognosis Healing is rapid in simple corneal 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

15 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: inflammation of uveal tract Uveitis in cats Uveitis Potentially blinding Inflammation of uvea 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. 15

16 Terminology of uveitis Synechia: Adhesions between iris and corneal endothelium (anterior) or iris and anterior lens capsule (posterior). Iris bombe: Iris adherent to lens (posterior synechia, usually caused by uveitis) around whole of pupillary margin, hence non-attached parts bulge forward due to pressure from behind. Chorioretinitis: Inflammation of the choroid and retina. Panuveitis: Inflammation of whole uveal tract. (photophobia) (blepharospasm) (lacrimation) (ciliary muscle) Aqueous flare (keratic precipitates) 16

17 Long term seqeula: synechia, glaucoma, cataract. (Maggs 2008) Uveitis - Infectious causes Immune-mediated Traumatic Metabolic diseases Neoplasm Idiopathic Brucella, Lepto, Lyme disease, TB Blastomycosis, Cryptococcosis, Histomycosis, Aspergilosis (cat): FIV, FeLV, FIP, FHV 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 17

18 Metabolic diseases Diabetes mellitus: lens induced uveitis 2nd to cataract. Hyperlipidemia Systemic hypertension Uveal Neoplasms Melanoma Adenoma Adenocarcinoma Lymphosarcoma TVT (painful, red eye, miosis, low IOP) (for the cause, severity of uveitis, and 2nd complications, esp glaucoma) - CBC, PCR Blasto, Histo, Crypto Toxo - An examination room which can be darkened Focal illuminator (eg pen light) Magnifying device direct ophthalmoscope slit-lamp biomicroscope surgical loupe Pen light 18

19 Surgical loupe 19

20 Direct ophthalmoscope Indirect ophthalmoscope Pen light plus condensing lens Anti-microbial agents for infectious cause. Topical corticosteroids Topical NSAID flurbiprofen, suprofen, diclophenac Systemic NSAID or steroid: useful in marked anterior uveitis and chorioretinitis Systemic anti-inflammation Control of intraocular inflammation Different from antibiotics Corticosteroid: Prednisolone, Dexamethasone NSAID (Non-steroids): e.g. Rimadyl (carprofen) Effective in controlling uveitis. When side effects of steroids are concerned. Mydriatic Topical atropine 1% To relieve ciliary spasm, decrease the risk of posterior synechiae. To stablize blood-aqueous barrier. Side effects: Decrease tear production and potentially increase IOP. Indications and side effects 20

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