JPC SYSTEMIC PATHOLOGY

SPECIAL SENSES SYSTEM

April 2024

S-M06

 

Signalment (JPC# 2236716): 5-year-old female mixed breed dog.

 

HISTORY: Five days before presentation to an ophthalmologist, one eye suddenly became cloudy. There was no known history of trauma.

 

HISTOPATHOLOGIC DESCRIPTION: Eye: There are histologic changes in all segments of the globe. The anterior lens capsule is focally discontinuous and large, hyalinized, eosinophilic globules (lens protein) protrude from the lens into the posterior chamber (lens rupture). Lens material is surrounded by numerous viable and degenerate neutrophils, few macrophages, and abundant fibrin, hemorrhage, and proteinaceous fluid which fill the posterior chamber and extend into the anterior chamber. The lens is flattened anteroposteriorly and the lens architecture is effaced by numerous variably sized, brightly eosinophilic, hyalinized, round Morgagnian globules (cataractous change). Aggregates of neutrophils are scattered through the lens and are adhered to the posterior lens capsule. The ciliary body and iris are diffusely expanded by moderate numbers of neutrophils, macrophages, lymphocytes, plasma cells, fibrin, edema, hemorrhage, and congestion, and the drainage angle is narrowed by adhesions of the anterior iris to the cornea (peripheral anterior synechia). The anterior iris surface is expanded up to 60µm by fibrovascular tissue (pre-iridal fibrovascular membrace). In the vitreous body neutrophils and fibrin surround, infiltrate, and efface layers of the detached coiled retina, expand the subretinal space, and mildly infiltrate the choroid. Within the retina, there is diffuse mild to moderate retinal atrophy characterized by: vacuolation and atrophy of the nerve fiber layer; degeneration of ganglion cells (swollen, have clumped Nissl substance, and central chromatolysis) and degeneration and loss of the outer plexiform layer with blending of the inner and outer nuclear layers. The retinal pigment epithelial layer is hypertrophied. The cornea and sclera are expanded by hemorrhage and edema and multifocally infiltrated by low to moderate numbers of similar inflammatory cells as well as reactive fibroblasts. There is moderate corneal vascularization especially at the limbus, and the sclera is diffusely thin. The posterior corneal elastic lamina (Descemet’s membrane) is focally ruptured. The cornea is minimally thickened with irregular clear spaces and loss of clefting within the corneal stroma (edema).

 

MORPHOLOGIC DIAGNOSIS: Eye: Panophthalmitis, fibrinosuppurative, diffuse, severe, with lens rupture, cataractous change, anterior synechia, pre-iridal fibrovascular membrane, retinal detachment and atrophy, scleral thinning, and corneal edema and vascularization, mixed breed, canine.

 

ETIOLOGIC DIAGNOSIS: Phacoclastic uveitis

 

CONDITION: Phacoclastic uveitis; lens-induced uveitis

 

 

GENERAL DISCUSSION: 

• Lens-induced uveitis is divided into two separate and distinct syndromes:
  • Phacolytic uveitis: Mild lymphoplasmacytic anterior uveitis; occurs in response to the leakage of denatured lens protein through lens capsule -> occurs in the course of maturation of cataracts toward liquefaction 
  • Phacoclastic uveitis: Follows rupture of the lens capsule and release of intact lens proteins; more complicated disease histologically
    • Common cause of lens rupture is corneal penetration by foreign objections including thorns, quills, bullets, and cat claws
    • Dogs with rapidly-progressing diabetic cataracts can develop phacoclastic uveitis (with apparently intact lens)
      • More diffuse granulomatous inflammation, often lining the uveal tract 
    • Potential complication of cataract surgery if fragments of lens are left within eye; now uncommon due to improvements in surgical technique
• Seen in all species but most common in dogs
• Septic Implantation Syndrome: Bacterial implantation in lens by penetrating injury; dominated by suppurative inflammation 
  • Phacoclastic uveitis may be contributing factor in pathology

 

PATHOGENESIS: 

• The pathogenesis of lens-induced uveitis is not fully understood
• Lens rupture causes release of large amounts of lens protein; may overwhelm the anterior chamber-associated immune deviation (ACAID)-dependent T-cell tolerance to normal small amounts of lens antigen
• Lymphocytes sensitized to lens-antigen in the spleen return to uvea and instigate pyogranulomatous inflammation and reparative processes
• Inflammation and proliferative healing processing cause further damage and eventually lead to phthisis bulbi and glaucoma
• Rapid surgical removal of lens after perforation is often preventive

 

TYPICAL CLINICAL FINDINGS: 

• Phacolytic uveitis: Usually mild lymphoplasmacytic uveitis, iridocyclitis, and retinitis secondary to chronic release of altered soluble lens proteins from a cataractous lens
• Phacoclastic uveitis: Corneal perforation and mild traumatic uveitis may be managed by conventional therapy; sudden reappearance of severe, intractable uveitis 10-14 days after initial injury with enucleation often necessary due to poor response to therapy and development of phthisis bulbi or glaucoma

 

TYPICAL GROSS FINDINGS: 

• In the bisected globe, vitreous and aqueous are coagulated (typical of uveitis), the lens is flattened, and there may be a visible wedge of opacification extending from the anterior capsule toward the nucleus where the traumatic insult occurred
• Posterior synechia, iris bombe (bulging of iris due to fluid buildup from posterior synechia), and other lesions of severe uveitis are often present  

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Phacolytic uveitis: Mild lymphoplasmacytic anterior uveitis that is similar to what is seen with idiopathic uveitis; cataractous changes within the lens (Morganian globules, etc)
• Phacoclastic uveitis: Varies with duration and amount of lens protein extruded; lesions can be complex and reflect direct effects of trauma (and any implantation of bacteria that occurs), immunologic reaction to lens protein, reparative processes, and often secondary glaucoma that ensues
  1. Lens capsule edges are retracted and coiled outwards at site of perforation, with a wedge of liquified lens material and neutrophils extending from the perforation toward the nucleus
  2. Neutrophilic and histiocytic perilenticular inflammation in anterior and posterior chambers, with lymphocyte-dominated inflammation of uveal stroma
  3. Chronic lesions dominated by proliferative changes
     • Closure or narrowing of irido-corneal angle due to either annular posterior synechiae or obstruction by inflammatory cells with accompanying fibrosis of the trabecular meshwork;
     • Will eventually result in glaucoma with secondary retinal degeneration and atrophy 

 

DIFFERENTIAL DIAGNOSIS:

• Other causes of endophthalmitis include bacterial, fungal (blastomycosis, cryptococcosis, histoplasmosis, aspergillosis, etc.), protozoal (toxoplasmosis or encephalitozoonosis), or parasitic etiologies
• Must be differentiated from lens septic implantation syndrome where penetrating trauma seeds microorganisms (usually bacteria) into the lens
  • Due to the presence of bacteria, inflammation is typically suppurative, while phacoclastic uveitis is usually granulomatous

 

COMPARATIVE PATHOLOGY: 

• Cats: Feline primary intraocular pleomorphic sarcoma may arise secondary to lens-induced uveitis and reparative processes including epithelial metaplasia
• Rabbits: Apparently spontaneous rupture of normal lens with well contained granulomatous reaction 
  1. Similar lesion to phacoanaphylactic uveitis in humans
  2. In rabbits, caused by Encephalitozoon cuniculi infection (often transplacental), which may penetrate and weaken the posterior lens capsule
  3. Syndrome most common in dwarf rabbits, young rabbits
  4. Inflammation characterized by heterophils, foamy macrophages, and multinucleated giant cells
• Birds: Penetrating trauma to the eye can instigate suppurative uveitis
  1. Initial lesion primarily heterophilic; fibrin deposition and necrosis often follow

 

References: 

1. Barthold SW, Griffey SM, Percy DH. Pathology of Laboratory Rodents and Rabbits. 4th ed. Ames, IA: Wiley Blackwell; 2016:294-295.
2. Delaney MA, Treuting PM, Rothenburger JL. Lagomorpha. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:495. 
3. Labelle P. The Eye. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1414-1415.
4. Schmidt R, Reavill DR, Phalen DN. Pathology of Pet and Aviary Birds. 2nd ed. Ames, IA: John Wiley & Sons, Inc.; 2015: 272.
5. Wilcock BP, Njaa BL. Special senses. In: Maxie MG, ed. Jubb Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier; 2016:457-459. 

 

 

Click the slide to view.

---