Ocular Manifestations of Feline Herpesvirus-1

Louise O’Leary, ISU Ophthalmology Resident 2019

Feline Herpesvirus – 1

• Feline viral rhinotracheitis •Widespread infection – highly contagious • Spread via oronasal/conjunctiva – direct and indirect • Infected as MDA wanes (8-12 weeks) • Vaccines only partially protective

Viral Features• Latency: trigeminal ganglion, +_ cornea +_skin • Recrudesence – immunosuppression: stress, glucocorticoids,

cyclosporine, FeLV, FIV etc. • Rescrudesence vs persistent low level replication • Epitheliotoxic virus – conjunctiva*, cornea, nasal + oral mucous

membranes, dermis – cytolysis of infected cells

Clinical signs

• Sneezing • Nasal/ocular discharge • Blepharospasm • Chemosis/hyperemia • Inappetance • Lethargy

https://en.wikipedia.org/wiki/Feline_viral_rhinotracheitis

Diagnosis• Presumptive • **Co –infections

common** • Pathognomic –

dendritic ulcers • IDEXX Feline Upper

Respiratory Disease PCR Panel – Mycoplasma, Chlamydophila, Bordetella, Herpes? • Other molecular

methods – rarely used

https://veteriankey.com/cornea/

Herpesvirus Specific Treatments• Cidofovir 0.5% ophthalmic solution – BID • Famciclovir 90mg/kg BID PO – plasma and tears – may clear

persistent low level infection • Ganciclovir? • Redundant –trifluridine, idoxuridine, vidarabine etc. • L-lysine? Immune enhancing probiotics? • Reduction of stress

Cidofovir• Inhibits viral replication - effective • Safe, well tolerated • Long acting – BID dosing • Compounding pharmacies • 6 months shelf life • Reasonable priced

Famciclovir• Inhibits viral replication • Tablets (125mg, 250mg, 500mg) • Safe • Well-tolerated – GI side effects,

renal disease? • Easily available • 90mg/kg BID PO – plasma and

tears • May clear persistent infection?

Thomasy et al JAVMA 2016

Conjunctivitis• Most common manifestation • Primary vs recurrent • Uni/bilateral • Hyperemia, chemosis, epiphora,

blepharospasm • +_conjunctival ulcers • Usually self-limiting • Co-infections? • Supportive care - lubricant • Treatment if painful, severe, co-infection

Andrew JFMS 2001

Gould JFMS 2011

Andrew JFMS 2001

Conjunctival Cytology

• Inclusion bodies: - Intranuclear herpes

(rare, need special stain)

- Intracytoplasmic (Mycoplasma, Chlamydia)

• Cellular infiltrate – - Neutrophilic (herpes)

Neutrophilic Conjunctivitis - Herpes

Chlamydophila

Mycoplasma

http://blog.vetbloom.com/ophthalmology/conjunctival-cytology-a-great-diagnostic-tool-youre-probably-not-using/

Treatment of Co-infections• Mycoplasma and Chlamydia - - Doxycycline 10mg/kg PO SID – 4 weeks - Terramycin/Erythyromycin TID

• Calicivirus – RNA virus - Antivirals don’t work, supportive care

Ulcerative Keratitis

• 2nd most common manifestation • Primary infection or recrudescence • Epitheliotoxic virus • Dendritic, geographic ulcer – superficial • Stromal involvement – secondary bacterial

infection • Fluorescein +_ Rose Bengal

https://veteriankey.com/cornea/

https://veteriankey.com/cornea/

FHV-1 Ulcerative Keratitis Treatment• Topical antibiotics +_serum • Atropine • NSAID/gabapentin • Cidofovir 0.5% BID/Famciclovir 90mg/kg BID – 1 week past

resolution of CS • +_E-collar

Non-Healing Corneal Ulcer• Indolent” • Debride loose edges with CTA – repeatable • Diamond burr • **GRID KERATOTOMY CONTRAINDICATED IN

CATS** • Superficial Keratectomy

Loose edges

KCS• Exact pathogenesis

unknown • Clinical signs milder than in

dogs - Conjunctival hyperemia,

lacklustre cornea, recurrent ulcers • Lubricant • Tacrolimus – corneal health • PDT

Andrew JFMS 2001

Symblepharon

• Sequela to primary disease

• Conjunctiva – conjunctiva (bulbar, palpebral, TEL) • Conjunctiva - cornea

• Surgical correction – recurrence frequent, amnion? • Prevention – lubrication/

separation

https://veteriankey.com/conjunctiva/

https://www.visioncareforanimals.com/gallery/eye-diseases

Slatter’s Fundamentals of Veterinary Ophthalmology

Stromal Keratitis

• Uncommon • Steroid use may predispose • Immune-mediated disease –

suspect delayed hypersensitivity to virus in cornea

• Fibrosis, oedema, cellular infiltrate, (stromal) neovascularisation • Non-painful • Vision-threatening

Andrew JFMS 2001

https://www.cliniciansbrief.com/article/conjunctivitis-cats

http://www.abcdcatsvets.org/feline-herpesvirus/

Stromal Keratitis Treatment• Immunosuppression/modulation – topical steroids, cyclosporine • Antiviral

Eosinophilic Keratoconjunctivitis• Role unclear- immune-mediated • Cornea and conjunctiva • White/pink, raised tissue

extending across cornea • Vision-loss/discomfort as

progresses • +_Fluorescein + over tissue

Davidwilliams.uk.

http://mspca.createconquer.com/angell_services/feline-eosinophilic-keratitis/

Diagnosis - Cytology• Single eosinophil!!

Epithelial cells, neutrophils, eosinophils, mast cells Eosinophils

Treatment – Eosinophilic Keraconjunctivitis

• Topical steroid (dex) +_ anti-viral • Optimmune (0.2% CSA) + topical NSAID • 1% CSA • Topical 0.5% megesterol acetate • Systemic anti-inflammatories – triamcinolone, prednisolone • **Slow taper to lowest dose that controls clinical signs** - recurrence common

Corneal Sequestra

• DSH • Predisposing factors – steroids, chronic irritation (ulcer etc) • Pathogenesis unclear • +_pain • +_ulcer around • Can increase in size and depth Andrew JFMS 2001

Treatment – Corneal Sequestra

• Active monitoring — supportive • Treat ulcer if present • Diamond burr removal • Surgical excision +_ grafting procedure • Recurrence

Dermatitis/Blepharitis

• Ulcerative dermatitis: periocular, facial, trunk, distal extremities • Pruritic • Famciclovir 90mg/kg BID

Gould JFMS 2011

https://dermvettacoma.com/feline-herpes-virus-dermatitis/

Canine Herpesvirus– Emerging Pathogen?• First case at ISU • Bilateral, painful, non-resolving conjunctivitis • Dendritic ulcers! • Ganciclovir, Idoxuridine, • Cidofovir?

References• Andrew, S. (2001). Ocular Manifestations of Feline Herpesvirus. Journal of Feline Medicine and Surgery, 3(1), 9–16.  • Gould, D. (2011). Feline Herpesvirus-1: Ocular Manifestations, Diagnosis and Treatment Options. Journal of Feline

Medicine and Surgery, 13(5), 333–346

• Townsend, W. M., Jacobi, S., Tai, S. H., Kiupel, M., Wise, A. G., & Maes, R. K. (2013). Ocular and neural distribution of feline herpesvirus-1 during active and latent experimental infection in cats. BMC veterinary research, 9, 185. doi:10.1186/1746-6148-9-185

• Maggs DJ, Chang E, Nasisse MP, et al. Persistence of herpes simplex virus type 1 DNA in chronic conjunctival and eyelid lesions of mice. J Virol 1998;72:9166–9172

• Maggs DJ, Clarke HE. In vitro efficacy of ganciclovir, cidofovir, penciclovir, foscarnet, idoxuridine, and acyclovir against feline herpesvirus type-1. Am J Vet Res2004;65:399–40

• Lappin, M. R. et al. (2009) ‘Pilot Study to Evaluate the Effect of Oral Supplementation of Enterococcus Faecium SF68 on Cats with Latent Feline Herpesvirus 1’, Journal of Feline Medicine and Surgery, 11(8), pp. 650–654. 

• Nasisse, MP, Glover, TL, Moore, CP, Weigler, BJ (1998) Detection of feline herpesvirus 1 DNA in corneas of cats with eosinophilic keratitis or corneal sequestration. American Journal of Veterinary Research 59, 856–858

• Thomasy SM, Shull O, Outerbridge CA, et al. Oral administration of famciclovir for treatment of spontaneous ocular, respiratory or dermatologic disease attributed to feline herpesvirus type-1: a retrospective review in 59 client-owned cats. J Am Vet Med Assoc 2016

• Sebbag L, Thomasy SM, Woodward AP, et al. Pharmacokinetic modeling of penciclovir and BRL42359 in the plasma and tears of healthy cats to optimize dosage recommendations for oral administration of famciclovir. Am J Vet Res. 2016 Aug;77(8):833-45

References • Ledbetter E, Nicklin A, Spertus et al. Evaluation of topical ophthalmic ganciclovir gel for the treatment of dogs with experimentally induced

ocular canine herpesvirus-1 infection. American Journal of Veterinary Research. Jul 2018, Vol. 79, No. 7, Pages 762-769

• Eric C. Ledbetter, Chloe B. Spertus, Matthew R. Pennington, Gerlinde R. Van de Walle, Bonnie E. Judd, and Hussni O. Mohammed.Journal of Ocular Pharmacology and Therapeutics.Dec 2015.

Questions??