Selected Feline Diseases

Transcription

1 Selected Feline Diseases Are Cats from Mars?! A Discussion of Selected Feline Ocular Diseases Feline Herpes Virus Feline Sequestrum Feline UveiRs Feline Glaucoma Kimberly Hsu, DVM, MSc, DACVO Eye Care For Animals St. Charles, IL Feline Herpes Virus-1 Pathogenesis Clinical ManifestaRons Diagnosis Therapy Pathogenesis of FHV-1 Mucosal infecron Nasal, conjuncrval Epithelial replicaron Axonal spread (Hematogenous spread?) Latency: trigeminal ganglia Lifelong latency with stress-induced reacrvaron Axonal spread CytolyRc or immunopathologic disease 1

2 FHV-1 Spread Herpes viruses are highly species specific! Macrodroplets with sneezing can travel up to 1.3m (space your rescue kennels) Fomites ie. humans! Stages of FHV-1 InfecRon Primary our focus today Latent Recrudescent Where is it on the spectrum? FHV-1 Primary InfecRon Cytopathic FHV-1 (acute ulcera2ve) Immunogenic Immunosuppressive Chronic (Stromal) Kera22s LP Conjunc2vi2s Eosinophilic Conjunc2vi2s & Kera22s Oncogenic Sneezing and nasal discharge Oeen OU ConjuncRviRs (conjuncrval hyperemia +/- chemosis) DendriRc/superficial corneal ulcers (not always dendrirc but these are pathognomonic) Oeen 2-3 weeks, may be self-limirng Direct viral cytolysis May result in symblepharon Typically recur even when adhesions are resected 2

3 Latent and Recrudescent Stages When in doubt: blame it on herpes?! Latent Stage No clinical disease Latency established in the trigeminal ganglia Recrudescent Stage Recrudescence with increased corrsol (stress) or exogenous steroid administraron Uni or OU Oeen no respiratory signs and usually no symblepharon formaron May not be self-limirng Cytopathic or immunologic (spectrum) Treat herpes but may also need to treat: LymphocyRc plasmacyrc conjuncrvirs Stromal kerarrs Eosinophilic kerarrs Non-healing ulcers, ETC.!!! Immune-mediated conjuncrvirs and kerarrs Sequestrum + conformaronal factors in brachycephalic cats Idiopathic uveirs? FHV-1 is hard to diagnose! Cytology: non-specific, oeen neutrophilic inflammaron Serology (ELISA and SN) Does not differenrate between vaccine or infecron induced response Titers with SN may be low with recrudescent infecron Immunofluorescence Assay (IFA) Limited sensirvity Lack of difference between diseased and normal animals SubjecRve nature of determining fluorescence Viral IsolaRon (VI) Difficult transport and processing Only + in 11% of normal cats and 18% of cats with clinical disease No significant difference between diseased cats vs. normal cats using VI, IFA, SN or ELISA so diagnoscc tescng may be of limited diagnoscc value FHV-1 never detected by both VI and IFA in clinically normal cats If both VI and IFA are negarve, cat most likely does not have FHV Is PCR the be all and end all?! Sadly, probably not! Variable detecron rates between labs High detecron rates in clinically normal cats Also, what does detecron mean? DetecRon may be Coincidental ConsequenRal Causal CLINICAL SIGNS AND RESPONSE TO THERAPY! 3

4 Therapy SupporRve Care AnRbioRc therapy Mycoplasma/Chlamydophlia-associated conjuncrvirs Superficial corneal ulcers LubricaRon AnR-viral Therapy Immunomodulatory Therapy Client EducaRon Managing expectarons is important Recurrence is common and frustrarng No cure Therapy oeen feels like an art-form For chronic disease, oeen balancing need to decrease viral load AND decreasing overacrvity of the immune system Oeen takes Rme to find out what works for each individual cat; what works can change over Rme Therapy and office visits may cause stress and make FHV-1 worse Chlamydophila & Mycoplasma Clinical signs ConjuncRval hyperemia & chemosis CHlamydophila causes CHemosis! Serous ocular discharge Treatment Oxytetracycline (ie. Terramycin TID) Rarely PO Doxycycline Erythromycin TID (parrcularly if tetracycline is causing irritaron) FHV-1 destroys conjuncrval goblet cells! (causes qualitarve KCS) QualitaRve tear film deficiency and instability plays large role in FHV conjuncrvirs Goblet cell recovery can take months ConjuncRviRs can persist long aeer viral acrvity clears Loss of mucous component of tear film can lead to: ConjuncRviRs UlceraRve kerarrs Corneal scarring 4

5 Lubricate using a mucinomimerc! Products that are designed to mimic the mucous component of tear film Typically have an added linear polymer or viscoelasrc substance in addiron to an aqueous vehicle Can have one or more of the following ingredients: Sodium hyaluronate, ChondroiRn sulfate 1-2% methylcellulose Glycerin, Dextran Lubricant will also help reduce irritaron associated with mild spasrc entropion ConsideraRons in AnR-Viral Therapy PotenRal host toxicity All are virostarc - NO virucidal drugs Acyclovir (bone marrow suppression) Valacyclovir (renal toxicity) Extralabel use Frequent applicaron needed for topical No cure or treatment for latent virus Topical MedicaRons Cidofovir 0.5% = Top Pick! Compounded Dosed BID due to reservoir effect (minimizes stress!) Excellent in vitro efficacy Nasolacrimal cicatrizaron in rabbits not seen in cats Dose dependent renal toxicity in humans Trifluridine 1% (ViropCc or compounded) May srng Dosed 4-6x daily Idoxuridine 0.1% solucon or 0.5% ointment Compounded Dosed 4-6x daily Oral Famciclovir Variable metabolism and absorpron Most recent recommendaron: 90mg/kg BID Previous: 40 mg/kg oral Famciclovir TID Current studies ongoing lower dose 15-40mg/kg TID may be effecrve Considered very safe (no systemic adverse effects) Possible variable efficacy with compounded formularons?! Single dose on admission to shelter did not decrease shedding or help clinical signs 5

6 Where do you start? Sample protocol Cidofovir 0.5% BID x ~3 weeks (or 2 weeks past resoluron of signs) Non-responsive cases Famciclovir 90mg/kg PO BID or 40mg/ kg PO TID Remend or OpRxcare BID-TID x 4-6 weeks +/- Terramycin or Erythromycin x ~3 weeks if chemosis or superficial ulcer are present +/- Tobramycin if ulcers are deeper or drop needed How about Lysine? 250mg-500mg PO BID Antagonizes arginine, essenral viral amino acid Earlier studies suggest decreased viral shedding and severity of clinical signs BUT Recent studies: Lysine supplemented cats had higher disease scores, shed more virus and had reduced food intake Various L-lysine concentrarons did not inhibit in vitro replicaron of FHV-1 at L-arginine concentrarons sufficient to maintain cell growth Worth a try but no real indicaron. Other therapies Up and Coming? Voodoo??? Lactoferrin (iron binding glycoprotein) Interferons INFα etc. (anr-viral cytokines) Further studies are needed! General Strategies Minimize stress Feliway? Minimize crowding GeneRcs?? AnR-inflammatories The Art of TreaRng Herpes Can provide symptomarc relief of conjuncrvirs for primary FHV-1 Timing of therapy? Safest to start with anrviral first and add in if mild conjuncrvirs remains NSAIDs Diclofenac or flurbiprofen CorRcosteroid? May weaken local immune system you re playing with fire! Usually necessary for eosinophilic kerarrs or immune-mediated conjuncrvirs/kerarrs Dexamethasone or Prednisolone Gentocin Durafilm (gentamicin, betamethasone), can dilute AddiRonal Immunomodulatory therapy Tacrolimus and Cyclosporine for Eosinophilic KeratoconjuncRviRs 6

7 Corneal Sequestrum Amber to black, flat, oeen axial, area of dessicated cornea Variable pain and corneal vascularizaron Unknown erology pigment remains undefined (not melanin or porphyrins) FHV-1 More likely to be playing a role in mesocephalic cats Eyelid abnormalires ie. entropion or macropalpebral fissure Persians, Himalayans, and Burmese are predisposed Trauma Note: Do not perform a grid keratotomy in a cat as you may cause corneal sequestrum! Corneal Sequestrum Typical progression Increase in both diameter and depth May slough, but oeen not unrl the resultant corneal ulcer is very deep (risk of deep ulceraron!) Can take months to years to slough! Recommended treatment: referral for surgical excision Superficial keratectomy +/- grae May have recurrence &/or develop bilaterally Treat underlying cause if idenrfied ie. entropion, FHV-1 If surgery is not an opron Topical anrbiorc BID-TID (prophylaxis) Lubricant BID-TID (decrease fricron) UveiRs in Cats Breakdown of blood aqueous barrier Aqueous flare KeraRc precipitates Fibrin Hyphema Male predisposiron, 7-10 y 38-70% of cats have a concurrent systemic disease! But oeen immune-mediated The internal medicine work-up of ophtho due to InfecRous NeoplasRc Many possible systemic causes! Viral FIP, FeLV, FIV, FHV Bacterial Bartonella, Mycobacterium sp., Ehrlichia sp., Borrelia burgdoreri Fungal/algal Cryptococcus, Histoplasma, Blastomycosis, Candida, Cocidiodes, Aspergillus ParasiRc Cuterebra Protozoal Toxoplasma gondii, Leishmania sp. 7

8 How likely is it due to systemic disease? Immune-mediated Acute Anterior uveirs, relarvely mild with flare only No systemic signs Unilateral Systemic Disease Chronic PanuveiRs or choriorernirs Systemic signs Bilateral KeraRc precipitates, cells or fibrin in anterior chamber DIAGNOSTIC TESTING INDICATED! Example of UveiRs DiagnosRc Work-up Ocular exam Physical exam CBC/Chem +/-UA InfecRous disease tesrng ** RESPONSE TO THERAPY** Thoracic radiographs Abdominal US Feline UveiRs Treatment Treat underlying cause, if idenrfied SymptomaRc anr-inflammatory therapy Prednisolone Acetate 1% BID-6x daily Diclofenac 0.1% BID-6x daily CauRous use with oral anr-inflammatories (diagnosrc tesrng first) SubconjuncRval steroid injecrons Taper slowly! Oeen transiron from combinaron therapy to NSAID only Recurrences may need repeat therapy or chronic low dose meds Be caurous with corrcosteroids, parrcularly in cats with a history of FHV-1 Atropine to reduce ciliary spasm, prevent synechiae Ointment is oeen preferable to soluron due to bixer taste Q24h-TID Feline Glaucoma Glaucoma in cats more oeen insidious, gradually progressive disease; oeen few overt clinical signs Some vision may be preserved in even buphthalmic globes, relarve preservaron of the rerna Mild corneal changes Primary glaucoma is rare Glaucoma secondary to uveirs >90% of the cases Other: Diffuse feline melanoma the major neoplasrc cause Raised hyperpigmentaron, thickened iris; decreased PLR Typically progressive glaucoma Feline Aqueous MisdirecRon Syndrome Shallow anterior chamber Typically responsive to Dorzolamide +/- surgery 8

9 Therapy of Feline Glaucoma Treat any underlying uveirs Dorzolamide BID-TID treatment of choice Brinzolamide less effecrve? Timolol 0.25% BID-TID No Latanoprost! Cats lack FP receptors Transient effect? May make uveirs worse References FHV-1 Dx and Tx Maggs, D. J., et al. "EvaluaRon of serologic and viral detecron methods for diagnosing feline herpesvirus-1 infecron in cats with acute respiratory tract or chronic ocular disease." Journal of the American Veterinary Medical Associa2on (1999): Maggs, David J. "Update on pathogenesis, diagnosis, and treatment of feline herpesvirus type 1." Clinical techniques in small animal prac1ce 20.2 (2005): Slack JM, SRles J, Leutenegger CM, Moore GE, Pogranichniy RM. Effects of topical ocular administraron of high doses of human recombinant interferon alpha-2b and feline recombinant interferon omega on naturally occurring viral keratoconjuncrvirs in cats. Am J Vet Res [Internet]. Am Vet Med Assoc; 2013;74(2): Maggs, David J., et al. "Effects of dietary lysine supplementaron in cats with enzoorc upper respiratory disease." Journal of Feline Medicine & Surgery 9.2 (2007): Drazenovich, Tracy L., et al. "Effects of dietary lysine supplementaron on upper respiratory and ocular disease and detecron of infecrous organisms in cats within an animal shelter." American journal of veterinary research (2009): Cave NJ, Dennis K, Gopakumar G, Dunowska M. Effects of physiologic concentrarons of l-lysine on in vitro replicaron of feline herpesvirus 1. Am J Vet Res Jun;75(6): References Famciclovir Lim CC, Reilly CM, Thomasy SM, Kass PH, Maggs DJ. Effects of feline herpesvirus type 1 on tear film break-up Rme, Schirmer tear test results, and conjuncrval goblet cell density in experimentally infected cats. Am J Vet Res Mar;70(3): Thomasy SM, Maggs DJ, Moulin NK, et al. PharmacokineRcs and safety of penciclovir following oral administraron of famci- clovir to cats. Am J Vet Res 2007;68: Thomasy SM, Lim CC, Reilly CM, et al. EvaluaRon of orally administered famciclovir in cats experimentally infected with feline herpesvirus type-1. Am J Vet Res 2011;72: Thomasy SM, Whixem T, Bales JL, Ferrone M, Stanley SD, Maggs DJ. PharmacokineRcs of penciclovir in healthy cats following oral administraron of famciclovir or intravenous infusion of penciclovir. Am J Vet Res Jul;73(7): Thomasy, Sara M., et al. "Oral administraron of famciclovir for treatment of spontaneous ocular, respiratory, or dermatologic disease axributed to feline herpesvirus type 1: 59 cases ( )." Journal of the American Veterinary Medical Associa2on (2016): References Sequestrum, UveiRs and Glaucoma Nasisse, M. P., et al. "DetecRon of feline herpesvirus 1 DNA in corneas of cats with eosinophilic kerarrs or corneal sequestraron." American journal of veterinary research 59.7 (1998): Maggs DJ. Feline uveics. An 'intraocular lymphadenopathy'. J Feline Med Surg Mar;11(3): Maggs D. J., M. R. Lappin, and M. P. Nasisse. "DetecRon of feline herpesvirus-specific anrbodies and DNA in aqueous humor from cats with or without uveirs." American journal of veterinary research 60.8 (1999): McLellan GJ, Miller PE. Feline glaucoma a comprehensive review. Vet Ophthalmol [Internet]. Blackwell Publishing Ltd; 2011;14(Supplement 1):