JPC SYSTEMIC PATHOLOGY

SPECIAL SENSES SYSTEM

April 2024

S-M08 (NP)

 

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 moderate numbers of extracellular clear to foamy vacuoles (lipid) and acicular cholesterol clefts that are up to 150 µm 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 are few to many lymphocytes and fibroblasts and few small caliber blood vessels (vascularization). The overlying anterior 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 and epithelial hyperplasia, mixed breed, canine.

 

ETIOLOGIC DIAGNOSIS: Corneal lipid dystrophy

 

CAUSE: Unknown

 

CONDITION: Corneal lipidosis; corneal lipoidosis; spontaneous crystalline corneal opacities

 

GENERAL DISCUSSION:

• 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

 

PATHOGENESIS:

• Not completely understood
• Lipid deposition can occur secondary to inborn errors of metabolism (corneal dystrophy) or can be acquired (lipid keratopathy)
• Corneal lipid accumulation may be seen with long-term corticosteroid therapy (Maggs, Slatter's Veterinary Ophthalmology, 2008)
• Some corneal lipid dystrophies are inherited and arise spontaneously

 

TYPICAL CLINICAL FINDINGS:

 

TYPICAL GROSS 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:

 

DIFFERENTIAL DIAGNOSIS:

• 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

 

COMPARATIVE PATHOLOGY:

• Rabbits:
  • Genetic corneal dystrophy in New Zealand White rabbits
  • 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
  • White rabbits used as model for drug-induced phospholipidosis (PLD), an accumulation of intracellular phospholipids in the cornea caused by ophthalmic drugs or chemicals (Yamagiwa, Toxicol Pathol. 2019)
• Mice and rats
  • Lysosomal accumulation of lipid, glycosaminoglycans, mucopolysaccharides, and other substances within the cytoplasm of epithelial cells, endothelial cells, or keratocytes
  • Also known as corneal phospholipidosis
  • TEM: Lamellar and crystalline inclusions
• Amphibians:
  • 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)
  • Some affected animals, concurrent xanthomas have been observed in the brain, pituitary gland, stomach, lung, ovary, nerves, arteries, and periarticular soft tissues

 

REFERENCES:

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley Blackwell; 2016: 318.
2. Labelle P. The Eye. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1413.
3. Ledbetter EC, Gilger BC. Diseases and surgery of the canine cornea and sclera: In: Gelatt KN, ed. Veterinary Ophthalmology. 5th ed. Ames, IA: Blackwell Publishing; 2013:1015-1020.
4. Maggs DJ. Cornea and Sclera. In: Slatter's Veterinary Ophthalmology, 4^th Ed. St. Louis, MO:Sauders Elsevier. 2018:181.
5. Pessier AP. Amphibia. In: Terio KA, McAloose D, St. Leger J, eds, Pathology of Wildlife and Zoo Animals. San Diego, CA:2018:928.
6. 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.
7. Yamagiwa Y, Takei Y, Koizumi H, Nemoto S, Kurata M, Satoh H. Pathological Features of Corneal Phospholipidosis in Juvenile White Rabbits Induced by Ocular Instillation of Chloroquine or Amiodarone. Toxicol Pathol. 2019;47(1):26-34.

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