JPC SYSTEMIC PATHOLOGY

SPECIAL SENSES SYSTEM

April 2024

S-M13

 

Signalment (JPC #1744913): Breed and gender not specified 17-year-old cat  

 

HISTORY: This cat had bilateral retinal hemorrhage and systemic hypertension.

 

HISTOPATHOLOGIC DESCRIPTION: Eye: The retina is diffusely thin with extensive loss of the photoreceptor layer; pseudocyst formation (up to 1 x 0.5mm) in the photoreceptor layer; blending of the inner and outer nuclear layers with loss of the outer plexiform layer; 75% reduction of the inner nuclear layer; loss of ganglion cells; and vacuolation of the nerve fiber and inner plexiform layers (spongiosis or axonal degeneration). Focally, the retinal architecture is completely obscured by hemorrhage and fibrin, few fibroblasts, and scattered macrophages containing phagocytized erythrocytes and a golden-brown granular pigment (hemosiderin). Multifocally, the tunica media of vessels in the retina and choroid is moderately thickened and variably expanded by brightly eosinophilic, hyalinized, homogenous material (hyalinization). Occasionally smaller retinal and choroidal vessels are surrounded by increased clear space (edema). There is rare hypertrophy of the retina pigment epithelium (retinal detachment). The epithelium of the posterior iris forms several knob-like projections that frequently have a clear center (pigmented iridal cysts).

 

MORPHOLOGIC DIAGNOSIS: Eye, retina: Degeneration, diffuse, marked, with retinal detachment, choroidal and retinal vascular hyalinization, focal hemorrhage, and photoreceptor layer pseudocysts, breed unspecified, feline.

 

CONDITION: Hypertensive retinopathy

 

GENERAL DISCUSSION:  

• Most common in cats and less frequently dogs; secondary to systemic hypertension; increasingly frequent cause of retinal and choroidal lesions and blindness in cats over 10 years of age
• Most cases are associated with chronic renal failure
  1. At least 60% of dogs with CRF are hypertensive
• The eye is frequently the first organ to clinically manifest systemic hypertension 
• In cats, evidence does not support association with hyperthyroidism 
• Hypertension in cats is commonly defined as systolic pressure greater than 160 -170 mmHg; cats with hypertensive retinopathy often have systolic blood pressures at or above 200 mmHg

 

PATHOGENESIS:

• Choriocapillaris à supply nutrients to photoreceptors and outer nuclear layer
  1. Retinal detachment à gradual outer retinal ischemic/malnutritional atrophy 
• Diseased nephrons > decreased GFR > increased renin (produced by JGA cells) > converts angiotensinogen (in liver) > angiotensin I > increased angiotensin II via ACE (from macula densa of DCT) > systemic arteriolar vasoconstriction increasing peripheral resistance, increased sodium reabsorption, release of aldosterone from the adrenal cortex, and increased ADH release > distal nephron sodium retention > volume excess and systemic hypertension
• Ocular lesions are the result of sustained & exaggerated autoregulatory vasoconstriction > tunica media hypertrophy > diminished contractile function > fibrous changes > leakage of plasma into arteriolar wall > hyalinization and leiomyocyte necrosis > degeneration > rupture of endothelial & muscle cells > leakage of blood & serum into surrounding retinal tissue > effusive lesions (edema, hemorrhage, retinal detachment)
• Early lesions are most likely only observed experimentally

• Systemic hypertension > sustained autoregulatory vasoconstriction > ↓ blood flow to retina, choroid, or RPE > ischemic necrosis & necrosis of vascular endothelium distal to vasoconstricted precapillary vessels > focal retinal necrosis & plasma +/- RBC exudation 

 

TYPICAL CLINICAL FINDINGS:

• Acute blindness is the most common reason for presentation
• Lesions are bilateral but not necessarily symmetric
• Hyphema and secondary glaucoma
• Retinal vascular tortuosity
• Retinal detachment
• Intravitreal and intra- and subretinal hemorrhages
• Sustained high blood pressure
• In cats with renal dysfunction, the presence or magnitude of hypertension is unrelated to azotemia; persistent lack of urine concentrating ability may be the only indication of chronic renal disease
• Chronic hypertension causes left ventricular hypertrophy, which is often misdiagnosed as hypertrophic cardiomyopathy

 

TYPICAL GROSS FINDINGS:

• Retinal or preretinal hemorrhage
• Retinal edema
• Retinal detachment

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Lesions are primarily in the retinal and choroidal vessels

• Fibrinoid necrosis of the tunica media or medial hypertrophy with adventitial fibrosis
• Early lesions are likely to be seen only under experimental conditions and are the result of exaggerated autoregulatory vasoconstriction in response to systemic hypertension

• Changes secondary to vessel damage:  

• Pre-iridial fibrovascular membrane (PIFM)
• Hyphema and/or secondary glaucoma
  • Localized retinal necrosis
  • Exudative retinal detachment and retinal pigment epithelium (RPE) hypertrophy
  • Photoreceptor atrophy and loss 
  • Retinal hemorrhage, edema, and hemosiderin deposition
    • Ischemic necrosis of RPE > allows for leakage of hypertensive edema fluid from the choroid into the subretinal space

 

ADDITIONAL DIAGNOSTIC TESTS:

 

DIFFERENTIAL DIAGNOSIS:

Causes of retinal degeneration in cats:

• Taurine deficiency: Characteristic central retinal atrophy & myocardial failure
  • Bilateral photoreceptor degeneration; initially affects cone outer segments and eventually affects rods
• Autosomal dominant early-onset rod and cone dysplasia with blindness by a few months of age; Abyssinians

• Single base deletion in the CRX gene
• Degeneration starts in the central retina

• Autosomal recessive late-onset retinal degeneration with blindness by 5-10 years of age; Abyssinians

• Rods more severely affected
• Disorganization of photoreceptor cells and loss of outer nuclear layer (early)
• Complete loss of photoreceptors in the outer segment with thinning of all other retinal layers
• Central retina is less severely affected

• Enrofloxacin: Directly toxic to retina – most often seen in old cats receiving prolonged therapy (due to reduced renal or liver function) or cats given a rapid IV infusion
• Miscellaneous:

• Other causes of ischemic retinal injury: DIC, tumor metastasis, and bacteremia
• Secondary retinal degeneration and detachment due to trauma, glaucoma, infections

 

COMPARATIVE PATHOLOGY:

• Dogs: At least 60% of dogs with chronic renal failure have systemic hypertension; ocular lesions associated with systemic hypertension are similar to the cat; retinal hemorrhage is the most common hypertension-associated ocular lesion (40%)
• Rats: Spontaneously Hypertensive Rats (SHR) are used as human models
• Humans: Chronic diabetes mellitus is a major cause of blindness due to chorioretinal vascular disease leading to retinal degeneration

• Vascular lesion mainly caused by microangiopathy

• Non-human primates: 
  • Diabetic macaques are used as human models for diabetic retinopathy/microvascular disease 
    • Captive western grey kangaroo: Lesions consistent with hypertension in multiple organs; some animals had retinal detachment but no vascular changes observed
      • Etiology unknown

 

References:

1. Higgins D, Rose K, Spratt D. Monotremes and Marsupials. In: Terio KA, McAloose D, St. Leger, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Academic Press; 2018:459-460.
2. Labelle P. The Eye. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1422.
3. Lowenstine LJ, McManamon R, Terio KA. Apes. In: Terio KA, McAloose D, St. Leger, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Academic Press; 2018:378.
4. Wagner JD, Cann JA, et al. Diabetes and obesity research using nonhuman primates. In: Abee CR et al., eds. Nonhuman Primates in Biomedical Research Volume 2: Diseases, 2^nd ed. Waltham, MA: Academic Press; 2012:717-718.
5. Wilcock BP; Njaa BL: Special senses. In: Maxie MG, ed. Jubb Kennedy and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. St. Louis, MO: Elsevier; 2016:470, 472-473.

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