JPC SYSTEMIC PATHOLOGY

SPECIAL SENSES SYSTEM

April 2024

S-M16

 

Signalment (JPC #2818284): Dog

 

HISTORY: None

 

HISTOPATHOLOGIC DESCRIPTION: Eye: Diffusely adhered to the anterior aspect of the iris is a 0.3 mm thick preiridal fibrovascular membrane (PIFM) composed of granulation tissue (plump fibroblasts with numerous perpendicularly arranged small capillaries) admixed with foci of mature fibrous connective tissue, edema, fibrin, hemorrhage, hemosiderin-laden macrophages, and hematoidin. The iris is advanced rostrally and the PIFM extends across and obscures the iridocorneal angle and trabecular meshwork, causing adhesion between the iris and Descemet’s membrane (peripheral anterior synechia). The iris margin deviates anteriorly through the pupil (ectropion uveae). Extending from the ciliary body and pars plana, covering the posterior lens capsule and to a lesser extent the anterior lens capsule, and adherent to the detached retina at the posterior aspect of the lens, is a variably thick band of fibrin admixed with erythrocytes, rare fibroblasts, lymphocytes, and plasma cells (cyclitic membrane and intravitreal membrane). Multifocally, there is liquification of lenticular fibers with replacement by eosinophilic, globular material (Morgagnian globules) and flocculent debris (cataractous change). There are occasional lens epithelial cells with retained nuclei (bladder cells). Diffusely, there is detachment of the retina, with multifocal traction bands and diffuse atrophy, degeneration, and necrosis affecting all layers of the retina. Rarely, the retinal pigmented epithelium is hypertrophied. There is hemorrhage within posterior and anterior segments (hemophthalmos and hyphema). Multifocally, the corneal epithelium is moderately hyperplastic, there is squamous metaplasia and intercellular edema. The corneal stroma is expanded by numerous small caliber vessels lined by plump endothelium (neovascularization) and fibrosis; infiltrated by aggregates of lymphocytes, plasma calls, and rare macrophages admixed with multifocal areas of hemorrhage; and exhibits irregular clefting of corneal collagen fibers with occasional pale eosinophilic fluid (edema). Periocular musculature is separated and surrounded by abundant hemorrhage.

 

MORPHOLOGIC DIAGNOSIS: 1. Eye: Preiridal, cyclitic, and intravitreal fibrovascular membranes with organizing hemophthalmos, drainage angle occlusion, ectropion uveae, peripheral anterior synechia, cataractous change, and retinal detachment, atrophy, and necrosis, breed not specified, canine.

2. Eye, cornea: Keratitis, chronic, diffuse, mild, with vascularization.

 

CONDITION: Pre-iridal fibrovascular membrane

 

GENERAL DISCUSSION: 

• Preiridal fibrovascular membrane (PIFM) is the most common form of fibrovascular proliferation in the eye
• PIFM is a layer of granulation tissue on the anterior surface of the iris
• PIFM is often associated with chronic retinal detachment, intraocular neoplasms, (ciliary body epithelial tumors), chronic uveitis, chronic glaucoma, and vitreoretinopathy 
• Other fibrovascular membranes: Described by distribution, including retrocorneal, preiridal, posterior iridal, cyclitic, and intravitreal

• Retrocorneal membranes line the posterior aspect of the cornea 
• Intravitreal membranes typically originate from the pars plana ciliary body and may cause vitreal hemorrhage, or be part of the response to chronic intravitreal hemorrhage; may cause traction within the vitreous à retinal detachment
• Cyclitic membranes extend from the ciliary epithelium along the anterior vitreous face, and may extend to carpet the posterior lens capsule and cause neovascular glaucoma
• Fibrovascular proliferation almost never occurs within the uveal stroma itself, only occurring if there is massive injury to the globe

 

PATHOGENESIS:

• PIFM results from budding and migration of capillaries from the iris stroma and recruitment of fibroblasts and myofibroblasts secondary to cytokine production, similar to wound healing in other organs; however, while typically beneficial in other organs, intraocular fibrovascular membranes tend to be detrimental, prone to hemorrhage, and may lead to development of glaucoma
• Many cytokines contribute to fibrovascular proliferation, vascular endothelial growth factor (VEGF) is the most significant
• PIFM myofibroblast retraction may result in iris distortion, most often of the pupillary margin of the iris, resulting in ectropion uveae or entropion uveae
• Neovascular glaucoma may result when:

• PIFM extends to cover and obstruct the pectinate ligament/iridocorneal angle à secondary/neovascular glaucoma
• PIFM extends along the posterior cornea causing a peripheral anterior synechia à secondary glaucoma
• PIFM extends onto the anterior lens surface à posterior synechiae, pupillary block à iris bombe, secondary glaucoma

 

TYPICAL CLINICAL FINDINGS:

• Most often occurs secondary to severe/prolonged anterior uveitis, retinal detachment, ciliary epithelial neoplasms, chronic glaucoma, idiopathic ocular hemorrhage, uveal melanoma, and endophthalmitis
• PIFMs are rarely recognized clinically despite a relatively high frequency in domestic animals with ocular disease

 

TYPICAL GROSS FINDINGS:

• Hyphema (hemorrhage in the anterior chamber)
• Eversion or inversion of the pupillary margin (ectropion/entropion uveae)
• Occlusion of the pupil or filtration angle; buphthalmos (if glaucoma present)

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Membrane composed of varying proportions of newly formed small caliber vessels, spindle cells compatible with fibroblasts and myofibroblasts, and collagenous extracellular matrix; the proportions of each depends on the cause and chronicity
• PIFM may be continuous with retrocorneal membranes or may extend posteriorly into posterior iridal membranes, which may extend to cover the ciliary body (cyclitic membrane)

 

COMPARATIVE PATHOLOGY:

• PIFM in other animals:  

• PIFM occurs with greatest relative frequency in horses, followed by the dog, cat (used as an animal model), and cow; in horses, it is frequently associated with chronic uveitis (periodic ophthalmia, S-M01), non-traumatic keratitis, and/or retinal detachment

 

REFERENCES:

1. Flores MM, Del Piero D, Habecker PL, et. al. A retrospective histologic study of 140 cases of clinically significant equine ocular disorders. J Vet Diag Invest. 2020;32 (3):382-388.
2. Labelle P. The eye.  In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022:1393. 
3. Wilcock BP, Njaa BL. Special senses. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. 6th ed. Vol 1. St. Louis, MO: Elsevier Inc; 2016:447-448. 

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