Eye as Indicator for Systemic Disease
World Small Animal Veterinary Association World Congress Proceedings, 2013
Eric C. Ledbetter, DVM, DACVO
College of Veterinary Medicine, Cornell University, Ithaca, NY, USA


1.  General concepts

2.  Infectious disease

3.  Immune-mediated disease

4.  Vascular disease

5.  Metabolic/Endocrine disease

6.  Neoplastic disease

7.  Nutritional disease

8.  Systemic toxicities

1) General Concepts

The ocular examination is a valuable diagnostic tool for a wide range of systemic disorders, and it is frequently underused by clinicians for this purpose. Performance of a complete ocular exam requires relatively simple and inexpensive equipment.

Ocular lesions are frequently observed with systemic disease. Examination of the eyes provides a unique opportunity for direct visual examination of the nervous (optic nerve) and vascular (retinal and uveal vessels) systems. Animals with systemic conditions are often first presented for evaluation of their ocular problems, as these lesions may be visually obvious to owners and symptoms of ocular disease are often more readily apparent than subtle systemic abnormalities.

2) Infectious Disease

Many infectious diseases (viral, fungal, bacterial, rickettsial, and parasitic), directly or indirectly, affect the eyes.

Canine distemper virus infects both epithelial and neural tissues and characteristically produces conjunctivitis, lacrimal adenitis (with resultant keratoconjunctivitis sicca), multifocal chorioretinitis, and optic neuritis. Infectious canine hepatitis (either natural infection with canine adenovirus-1 or less commonly from modified-live virus used for vaccination) may be associated with viral infection of the corneal endothelium and uvea with subsequent immune-mediated lesions including corneal edema ("blue eye") and anterior uveitis.

Feline immunodeficiency virus is associated with a variety of ocular lesions (conjunctivitis, anterior uveitis, pars planitis, retinopathy, and uveal lymphoma) that result from direct viral effects and secondary infections. Feline leukemia virus infection may produce retinal dysplasia, retinal hemorrhages, uveal lymphoma, and spastic pupil syndrome. Feline infectious peritonitis is a disseminated pyogranulomatous vasculitis. Ocular lesions are more common with the "dry" form of the disease and may include anterior uveitis, hyphema, chorioretinitis, retinal hemorrhages, retinal detachment, retinal perivascular exudates, and optic neuritis. In addition to upper respiratory tract infection, oral ulceration, and polyarthritis, feline calicivirus is a frequent etiology of ulcerative conjunctivitis in cats. In utero infection with feline panleukopenia virus may result in retinal dysplasia.

The papillomaviruses are group of species-specific viruses that may produce papillomas of the eyelid, conjunctiva, and cornea. These masses are pedunculated with a cauliflower-like surface, may be solitary or multiple, and can be pigmented or unpigmented.

Systemic mycosis includes infection with Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum, Cryptococcus neoformans, and other disseminated opportunistic fungi (Aspergillus, Candida, Sporothrix, etc.). Systemic fungal infections are frequently associated with ocular lesions that may include blepharitis, orbital cellulitis, conjunctivitis, keratitis, anterior uveitis, chorioretinitis, retinal detachments, and optic neuritis. These ocular lesions may occur with or without other systemic clinical abnormalities.

Canine brucellosis results from infection with the gram-negative bacterium Brucella canis. Anterior uveitis, chorioretinitis, and endophthalmitis are observed in dogs with brucellosis. Brucellosis ocular lesions are frequently unilateral and associated with intraocular hemorrhage. Rickettsial infections (e.g., Ehrlichia canis, Anaplasma phagocytophilum, Anaplasma platys, Rickettsia rickettsii) may produce anterior uveitis, hyphema, retinal hemorrhages, chorioretinitis, and optic neuritis. With Rickettsial disease, the ocular lesions result from thrombocytopenia, vasculitis, and hyperviscosity. Borreliosis (Lyme disease) indirectly produces uveal hemorrhages and retinal detachments via glomerulonephritis and systemic hypertension. Borrelia burgdorferi is also speculated to directly cause anterior uveitis, corneal edema, and chorioretinitis by direct ocular infection.

Toxoplasma gondii is a common etiology of ocular disease in cats and a rare cause in dogs. Ocular signs of toxoplasmosis may include anterior uveitis, chorioretinitis, extraocular myositis, scleritis, vitritis, and optic neuritis. Ocular larva migrans (e.g., Toxocara canis) is associated with focal chorioretinal granulomas; intraocular filariasis may occur with Dirofilaria immitis infection; and ophthalmomyiasis interna may produce wandering curvilinear retinal tracts (with retinal edema, hemorrhages, and focal retinal detachments acutely).

As the eyelids are simply modified skin, any parasitic or fungal dermatologic disease can result in blepharitis (e.g., demodectic mange, sarcoptic mange, dermatophytosis). These eyelid infections may present with or without concurrent generalized dermatologic disease.

3) Immune-Mediated Disease

Canine uveodermatologic syndrome (Vogt-Koyanagi-Harada-like syndrome) is an autoimmune disorder of dogs targeting melanocytes. As the name suggests, clinical lesions develop in the eyes and skin. Ocular lesions include varying degrees of anterior and posterior uveitis, uveal depigmentation, retinal detachments, and glaucoma. Dermatologic lesions typically include poliosis (whitening of the hair) and vitiligo (skin depigmentation). Breed predispositions include Akita, Samoyed, Siberian husky, and Shetland sheepdog.

Numerous immune-mediated epidermal diseases, including pemphigus foliaceus, pemphigus erythematosus, pemphigus vulgaris, bullous pemphigoid, drug reactions, atopy, and food allergies, can result in blepharitis.

4) Vascular Disease

With systemic hypertension of any etiology, uveal hemorrhages, hyphema, retinal hemorrhage, vitreal hemorrhage, subretinal fluid, tortuous retinal vessels, and retinal detachments may be observed. Thrombocytopenia and coagulopathies may be associated with periocular or intraocular hemorrhage. With serum hyperviscosity, dilated tortuous conjunctival and retinal vessels, retinal hemorrhages, retinal detachment, and papilledema may develop.

Severe anemia is associated with pale retinal vessels, retinal hemorrhages, and conjunctival pallor. These changes are typically not seen until the hematocrit approaches 5–7%.

5) Metabolic/Endocrine Disease

Diabetes mellitus is a common etiology of cataracts in the dog and a rare etiology in the cat. Diabetic retinopathy (characterized by retinal microaneurysms and hemorrhages) may also develop with chronicity, but is generally not vision threatening. Sustained hypocalcaemia results in focal, punctate to linear lens opacities that begin in the posterior cortex and resemble snowflakes. Hyperlipidemia may result in lipid keratopathy, lipemic uveitis, or lipemia retinalis. The sclera is a classic location for the detection of subtle icterus/jaundice and intraocular structures may also be affected.

6) Neoplastic Disease

Systemic neoplasms may concurrently or secondarily involve the eye, adnexa, or orbit. The uvea is a common site of intraocular metastasis and this may be seen with numerous malignancies (e.g., lymphoma, hemangiosarcoma, osteosarcoma, melanoma, mammary/pancreatic adenocarcinoma, mast cell tumors, squamous cell carcinoma, transitional cell carcinoma). Intraocular metastasis characteristically causes intense and medically refractory uveitis associated with nodular or diffuse uveal infiltrates.

Intracranial neoplasms may produce eyelid dysfunction, pupillary light reflex deficits, reduced vision, and/or blindness. Papilledema or optic nerve extension of the tumor may be evident during ocular examination.

7) Nutritional Disease

In addition to cardiomyopathy, taurine deficiency in cats causes a characteristic retinal lesion called feline central retinal degeneration. The initial lesion is located in the area centralis and slowly progresses to a generalized retinal degeneration and blindness. Correction of the taurine deficiency halts progression of the retinal disease.

8) Systemic Toxicities

Numerous systemic toxins and pharmaceuticals can result in ocular lesions. Examples include:

 Rodenticides causing ocular and periocular hemorrhage

 Etodolac and sulfa antimicrobials are potentially lacrimotoxic

 Ethylene glycol intoxication causes retinal edema, degeneration, and detachment

 Enrofloxacin (and other fluoroquinolones) may produce retinal degeneration in cats

 Ivermectin is potentially retinotoxic


Speaker Information
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Eric C. Ledbetter, DVM, DACVO
College of Veterinary Medicine
Cornell University
Ithaca, NY, USA

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