Ophthalmic Clues to Systemic Disease

Mary B. Glaze, DVM, MS, DACVO Gulf Coast Animal Eye Clinic Houston, Texas Categories of Disease: DAMNIT

 Degenerative  Autoimmune  Metabolic  Neoplastic/Nutritional  Infectious/Inflammatory/Immunologic  Toxic/Traumatic IMMUNE-MEDIATED DISEASE Immune-mediated Thrombocytopenia

 Subconjunctival hemorrhage  Hyphema  Retinal hemorrhage Uveodermatologic Syndrome (VKH-like Syndrome)

 Destruction of dermal and uveal melanocytes  Young, male dogs, esp Akita, Samoyed, Siberian husky  Bilateral panuveitis  Vitiligo, poliosis Uveodermatologic Syndrome Uveodermatologic Syndrome Uveodermatologic Syndrome METABOLIC DISEASE Incidence of Diabetic Cataracts

 Approx. 21% of diabetic dogs already have cataracts at the time of initial diagnosis

 41% develop cataracts within the first 100 days & 75% develop cataracts within 1 year

 Over 100,000 cataract surgeries are performed per year, many on diabetic dogs. Why do diabetic dogs develop cataracts? Diabetic Cataracts Gizzo, a 7-yr-old Maltese

4/10/07 5/9/07

6/16/07 7/13/07 Why don’t cats develop diabetic cataracts? Diabetes mellitus

 Hyperlipidemia  Lipid-laden aqueous  Lipemia retinalis

 Low risk of significant diabetic retinopathy Hypothyroidism

 Corneal lipidosis  Supplementation halts progression

 Lipid-laden aqueous

 Lipemia retinalis Hypoparathyroidism

 Hypocalcemia impacts cell membrane permeability within lens  Non-progressive multifocal lens opacities Hyperadrenocorticism Hypertensive Retinopathy

 Geriatric cats and dogs  Mean systolic BP >180 mm Hg  Vascular ischemia  Transudation  Hemorrhage  Detachment Hypertensive Retinopathy Early Disease

 Vision “normal”  Coincidental finding  Retinal pathology  Multifocal edema  Multifocal hemorrhages  Localized separation Hypertensive Retinopathy Advanced Disease

 Acute vision loss  Systemic illness?  Ocular signs  Dilated pupils  Detachment  Hemorrhage Hypertensive Retinopathy Advanced Disease Hypertensive Retinopathy Complicated

 Hyphema  Secondary glaucoma Hypertensive Retinopathy Therapy

 Calcium channel blocker: amlodipine besylate (Norvasc®) 0.625mg daily PO Hypertensive Retinopathy Prognosis

 If treated early: vision may return  If treated late: retina may reattach but secondary degeneration precludes vision Canine Hypertension NEOPLASIA Lymphosarcoma

 Most common metastatic ocular tumor in dogs and cats  Hemorrhage Lymphosarcoma Lymphosarcoma Lymphosarcoma NUTRITIONAL DISORDERS Taurine Deficiency

 Feline disorder  Initially recognized in cats fed dog food  Commercial diets once inadequate Taurine Deficiency INFECTIOUS DISEASE Causes of Uveitis in Dogs

 102 dogs with uveitis (NCSU 1989-2000)  17.6% infectious  7/18 Ehrlichiosis  5/18 Blastomycosis  2/18 Protothecosis  1/18 Rocky Mt Spotted Fever  2/18 Others  24.5% neoplastic  58% idiopathic/immune-mediated

Massa et al, Vet Ophthalmol (2002) 5:93-98. Causes of Feline Uveitis

 Clinical Retrospective Study  Etiology determined in only 30% of 53 cats with uveitis  Davidson et al. JAAHA 1991, 22:77-83.  Histopathologic Retrospective Study  Etiology determined in only 67% of cats with uveitis  Peiffer, Wilcock. JAVMA 1991, 198:135-138. Causes of Feline Uveitis

 Retrospective study of 120 cats  Total with definitive diagnosis: 30.8%  Neoplasia n=5  FeLV n=3  FIV n=8  FIP n=19  Cryptococcosis n=1  Positive toxo or bartonella titers: 29.2%  Idiopathic: 40.8%  Jinks et al. Vet Ophthalmology 2016, 19:30-37. BACTERIAL DISEASES Brucellosis

 Relapsing uveitis  Hypopyon common  Progression to panophthalmitis Brucellosis

 Response to therapy limited  Potential zoonotic Bartonellosis  Gram-negative intra-erythrocytic bacteria  B.henselae: Etiologic agent of cat scratch disease

Time Magazine, February 23, 2004 Bartonellosis

 Transmission  Fleas: Ctenocephalides felis  Ticks: Rhipicephalus sanguineous  Species differences  Feline: B. henselae  Canine: B. vinsonii (berkhoffii)  Epidemiology  12-67% of US cats are seropositive  1-4% of US dogs are seropositive Bartonellosis: Clinical Signs

 Feline  Canine  Fever  Endocarditis  Lymphadenopathy  Cutaneous vasculitis  Gingivitis  Hepatitis  Neurologic disorders  Polyarthritis  Endocarditis  Meningoencephalitis  Hyperglobulinemia  IMHA  Osteomyelitis  Uveitis  Uveitis Bartonellosis

 In 2000, Lappin identified DNA of B.henselae in aqueous of cats with uveitis Bartonella: Anterior Uveitis

5-mo-old Siamese, Anterior uveitis, Response to azithromycin alone Canine Bartonellosis

 2 yr old F/S spaniel mix  Febrile  Anterior uveitis  Choroiditis  B.vinsonii titer 1:512  Resolution of clinical signs with treatment

Michau et al. Vet Ophthalmol 2003,6:299-304. Canine Bartonellosis

 Retrospective study of 24 dogs  Bilateral ocular lesions in 4/24  Anterior uveitis and polyarthritis  Multifocal chorioretinitis  Hyphema and oral petechiae  Retinal detachment and hypertension

Breitschwerdt et al. JAAHA 2004,40:92-101. Diagnosis of Bartonellosis

 What constitutes active infection?  +3 or +4 Western blot?  + PCR?  Lappin: PCR or culture, plus serology  Are we treating the disease or the test?? Borreliosis (Lyme Disease)

 Borrelia burgdorferi  Endemic in northeastern and upper midwestern states  Tick vector: Ixodes  Classic rash: erythema migrans  Arthritis, nephritis, endocarditis, meningitis Borreliosis (Lyme Disease)

 Ocular involvement considered rare  In humans, clinical signs occur in late- stage disease:  Uveitis  Episcleritis  Keratitis  Optic neuritis Borreliosis

 B. burgdorferi isolated from pony eye with uveitis  In study of 132 seropositive dogs:  5 had primary ocular symptoms  Conjunctivitis, uveitis, retinal petechiae/detachment, chorioretinitis  Study failed to eliminate role of ehrlichiosis: 24 dogs were seropositive for E.canis Borreliosis

 Uveitis reported in 10-year-old Siberian Husky from north Texas  Spirochetes noted in blood smear  Marginal pancytopenia  B. burgdorferi negative, B. turicatae positive

Whitney et al. Vet Clin Pathol 2007, 36:212-216. RICKETTSIAL DISEASES E.canis-associated Ocular Disease

 17 of 56 dogs (30.5%) with E.canis presented with bilateral ocular disease  Panuveitis with retinal detachment (11/17)  Exudative anterior uveitis (5/17)  Hyphema/retinal hemorrhage (5/17)  Optic neuritis (1/17)

 11 of these 17 patients (65%) : Ocular signs only

Leiva et al, Veterinary Ophthalmology (2005) 8: 387-393. E.canis-associated Ocular Disease

 Posterior ocular signs  ELISA titers ≥ 1:320  Poorer therapeutic response (15%)  Generalized retinal atrophy (3/5)  Phthisis bulbi (2/5)  Anterior uveitis  Lower titers  Good therapeutic response (85%)

Leiva et al: Veterinary Ophthalmology (2005) Pathogenesis of Ocular Signs

 Monocytic disruption of uveal and retinal vascular endothelia  uveitis and retinal perivascular infiltrates  Thrombocytopenia and coagulopathy  hyphema and retinal hemorrhages  Hyperviscosity syndrome  retinal vessel tortuosity and hemorrhage Clinical Ehrlichiosis: Anterior Uveitis

 Breakdown in blood- aqueous barrier Aqueous flare, keratic precipitates  Corneal endothelial disruption  edema  Diminished ciliary body function  decreased IOP Clinical Ehrlichiosis: Anterior Uveitis

 2-yr-old M Chow  Urban origin  4-6 wk hx of cloudy eyes OU  Physical exam WNL Clinical Ehrlichiosis: Anterior Uveitis

 Thrombocytopenia  E.canis < 1:40  A. platys morulae Clinical Ehrlichiosis: Hyphema Clinical Ehrlichiosis: Intraocular hemorrhage Clinical Ehrlichiosis: Periocular Hemorrhage Clinical Ehrlichiosis: Chorioretinitis Clinical Ehrlichiosis: Necrotizing Scleritis Rocky Mountain Spotted Fever

 Etiologic agent: Rickettsia rickettsii  Clinical signs resemble ehrlichiosis  Fever  Mucous membrane petechiae / ecchymoses  Limb edema  Multiple organ pathology  Shorter disease course, occurring seasonally (March thru October) Pathogenesis of RMSF

 Transmitted by Dermacentor spp  Organism replicates in vascular endothelium  Necrotizing vasculitis  Increased permeability, multisystemic edema  Coagulation activation, decreased perfusion Rocky Mountain Spotted Fever Protozoal diseases Toxoplasmosis

Reactivation of tissue cysts? Immunopathology due to auto-antigen, molecular mimicry, loss of immune tolerance? Toxoplasmosis

 Serum titers  IgM rises and falls over 2-4 months with new infection or reactivation of dormant bradyzoites  IgG rises after IgM and stays positive for years  Many cats are IgG positive  Healthy, ill, with or without uveitis Toxoplasmosis Canine Toxoplasmosis Leishmaniasis

 Endemic to Mediterranean region and South America (10-70% seroprevalence)  L.chagasi, L.donovani in the Americas  L.mexicana in Texas  Fox Hound uniquely susceptible in USA Human Leishmaniasis

 Cutaneous ulcers  Disseminated and chronic skin lesions resembling lepromatous leprosy  Mucocutaneous destruction  Visceral form, with hepatomegaly, splenomegaly, anemia (100% fatality rate in 2 years if untreated) Leishmaniasis Clinical signs of Canine Leishmaniosis

 Exfoliative dermatitis affecting face, pinna and limbs (56-90%)  Lymphadenopathy  Splenomegaly  Weight loss  Epistaxis Leishmaniosis

 24% of infected dogs have ocular disease  52% blepharitis  34% keratoconjunctivitis  42% anterior uveitis

Pena et al. Vet Ophthalmol 2000; 3:35-41. Leishmaniosis - Blepharitis

Images courtesy of Dr. Marta Leiva Leishmaniosis – Anterior Uveitis

Images courtesy of Dr. Marta Leiva Leishmaniosis - Panuveitis

Images courtesy of Dr. Marta Leiva Feline Leishmaniosis Leishmaniasis: Diagnosis

 Cytology of lymph nodes, spleen, bone marrow  IFA  ELISA  PCR  Culture of aspirates Leishmaniasis: Public Health

 Dog ownership a significant risk factor for child seropositivity Mazloumi et al. Am J Trop Med Hyg (2002) 67:511-515.  Treated dogs pose risk of transmission to people and pets in community VIRAL DISEASE Canine Distemper Infectious Canine Hepatitis (Adenovirus)

 Ocular signs 1-3 weeks following illness or vaccine  Anterior uveitis/ corneal edema  Sight hounds susceptible to complications Feline Leukemia

 Considered a predisposing factor  Primary effects limited to LSA and neurologic signs Feline Leukemia

 Spastic pupil syndrome Feline Infectious Peritonitis

 Vasculitis results in exudative panuveitis Feline Infectious Peritonitis (FIP) Feline Infectious Peritonitis (FIP) Feline Immunodeficiency Virus (FIV)

 Chronic mild uveitis  Anterior vitreous cellular infiltrate Feline Immunodeficiency Virus (FIV) FUNGAL DISEASE Blastomycosis

 Initial chorioretinitis, progressing to panophthalmitis Blastomycosis Blastomycosis Other Mycoses

 Cryptococcosis

 Histoplasmosis Histoplasmosis Aspergillosis PARASITIC DISEASES Dirofilariasis Aberrant migration of fourth-stage larvae from subconjunctival space into eye Myiasis Ophthalmomyiasis Ocular Onchocerciasis

 Transmitted by Simulium black flies or Culicoides gnats/midges  Europe (esp Greece), Western USA  Acute form: conjunctivitis, periorbital swelling  Chronic form: granulomatous nodules containing parasite  Biopsy demonstrates parasite in tissues U.S. Distribution

Map courtesy of Dr. Richard Dubielzig Ocular Onchocerciasis

Images courtesy of Dr. Anastasia Komnenou Ocular Onchocerciasis

Images courtesy of Dr. Anastasia Komnenou TOXICITIES Enrofloxacin Toxicity

 Dose-related idiosyncratic rxn  Irreversible photoreceptor damage  Dosage should not exceed 5mg/kg/day Ivermectin Toxicity

 Profound overdose with large animal preparations  Dilated pupils, retinal and disc edema  Vision usually returns in 2-10 days