JPC SYSTEMIC PATHOLOGY
Signalment (JPC Accession # 2045612): Mixed breed dog, age and gender unspecified
HISTORY: This dog developed bilateral cataracts and was euthanized when vision impairment was almost total
HISTOPATHOLOGIC DESCRIPTION: Eye: Multifocally, separating rostral corneal stromal fibers and mildly elevating the corneal epithelium are numerous extracellular clear to foamy vacuoles and acicular clefts (lipid vacuoles and cholesterol clefts) that are up to 150 um long and are surrounded by many macrophages with swollen pale vacuolated cytoplasm and an eccentrically displaced nucleus (lipid-laden macrophages) and fewer multinucleated giant cells. In the most severely affected areas, the cornea is thickened up to 1.7 mm. Multifocally, within the corneal stroma, there are few to many lymphocytes and fibroblasts and few small caliber blood vessels (vascularization). The overlying rostral corneal epithelium is variably hyperplastic, up to 2.5 times normal thickness, with acanthosis and prominent rete ridges.
MORPHOLOGIC DIAGNOSIS: Eye, cornea: Lipidosis and histiocytosis, chronic, multifocal, moderate, with vascularization, mixed breed, canine
ETIOLOGIC DIAGNOSIS: Corneal lipid dystrophy
CONDITION: Corneal lipidosis; corneal lipoidosis; spontaneous crystalline corneal opacities
- Corneal dystrophies are bilateral, inherited (but not necessarily congenital) defects in structure or function of one or more corneal components; subclassified as epithelial, stromal, or endothelial; the most common in the dog are the lipid and mineral stromal dystrophies
- Corneal lipid dystrophy is characterized by the deposition of cholesterol, phospholipids, and neutral fats within the corneal stroma and is unassociated with a previous keratitis or serum lipid abnormality
- Many breeds are predisposed including Beagles, Airedale terriers, German shepherd dogs, Collies, Cavalier King Charles spaniels, Shetland sheepdogs, and Siberian huskies
- Corneal dystrophies occur most frequently in the dog and are rarely reported in the cat
- Not completely understood
- Lipid deposition can occur secondary to inborn errors of metabolism (corneal dystrophy) or can be acquired (lipid keratopathy)
- Corneal lipid dystrophies are inherited and arise spontaneously
TYPICAL CLINICAL FINDINGS:
- Bilateral, symmetric, oval or circular, well-demarcated, gray-white or silver, crystalline or metallic opacities in the central or paracentral cornea
TYPICAL GROSS FINDINGS:
- Same as clinical findings
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Cholesterol crystals and clefts with lipid vacuoles in the anterior stroma (keratocytes), which are sometimes surrounded by lipid-laden macrophages (cholesterol granuloma) and variable numbers of leukocytes (generally there is a limited inflammatory response and limited vascular ingrowth)
- +/- vascularization
ADDITIONAL DIAGNOSTIC TESTS:
- Diagnosis based on clinical signs and histopathology
- Acquired lipid deposition may arise secondary to severe keratitis, hyperlipoproteinemia, hyperlipemia, hypercholesterolemia, thyroid atrophy, lymphocytic thyroiditis, or thyroid carcinoma
- Corneal hypermelanosis is associated with chronic corneal irritation; results from progressive ingrowth of new germinal cells that have retained pigment from the bulbar conjunctiva; corneal epithelium is hyperplastic with rete ridge formation, keratinization, and a thick basement membrane
- Mineral deposition is a deposition of calcium salts primarily in the anterior stroma and epithelial basement membrane; predisposing corneal changes include desiccation, anesthesia, edema, or inflammation; hypercalcemia exacerbates the mineralization
- Diets high in cholesterol result in lipid deposition within the corneal stroma, iris, and uveal tract
- Animal model for a corneal lipid dystrophy in man known as “corneal arcus”
- Lipid keratopathy of Watanabe rabbits
- Dutch Belted rabbits have a distinct form of anterior corneal dystrophy
- Many different corneal lipid dystrophies with different causes
- Crystalline opacities in Siberian huskies resemble the central crystalline dystrophy of Schnyder in humans (Schnyder’s stromal dystrophy)
- Lipid keratopathy occurs commonly in female anurans; the cause is unknown but it may be associated with oogenesis
- In an experimental study, corneal lipid deposition in Cuban (captive) tree frogs was significantly higher on diets with high-cholesterol (association between serum lipids and corneal lipid deposition)
- Bilateral lipid keratopathy has been reported in an alpaca in association with hypercholesterolemia
- Dubielzig RR, Ketring KL, McLellan GJ, Albert DM. Diseases of the cornea and sclera. In: Veterinary Ocular Pathology: A Comparative Review. Louis, MO: Elsevier Limited; 2010:206-208.
- Garibaldi BA, Pequet Goad ME. Lipid keratopathy in the Watanabe (WHHL) Rabbit. Vet Pathol. 1998; 25:173-4.
- Labelle P. The eye. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby Elsevier; 2016:1298-1299.
- Ledbetter EC, Gilger BC. Diseases and surgery of the canine cornea and sclera: In: Gelatt KN, Veterinary Ophthalmology. 5th ed. Ames, IA: Blackwell Publishing; 2013:1015-1020.
- Richter M, Grest P, Spiess B. Bilateral lipid keratopathy and atherosclerosis in an alpaca (Lama pacos) due to hypercholesterolemia. J Vet Intern Med. 2006;20:1503-1507.
- Shilton CM, Smith DA, Crawshaw GJ, Valdes E, et al. Corneal lipid deposition in Cuban tree frogs (Osteopilus septentrionalis) and its relationship to serum lipids: an experimental study. J Zoo Wildl Med. 2001;32(3):305-319.
- Walton KW, Dunkerley DJ. Studies on the pathogenesis of corneal arcus formation II. Immunofluorescent studies on lipid deposition in the eye of the lipid-fed rabbit. J Pathol. 1974;114:217-229.
- Wilcock BP, Njaa BL. Special senses: In: Maxie MG, ed. Jubb, Kennedy , and Palmer’s Pathology of Domestic Animals. 6th ed. Vol 1. Philadelphia, PA: Saunders Elsevier;2016:433.
- Williams DL, Whitaker R. The amphibian eye—a clinical review. J Zoo Wildl Med. 1994;25:18–28.