JPC SYSTEMIC PATHOLOGY
SPECIAL SENSES SYSTEM
Signalment (JPC #2818284): Dog
HISTOPATHOLOGIC DESCRIPTION: Eye: Diffusely adhered to the anterior aspect of the iris is a 0.3 mm thick preiridal fibrovascular membrane composed of granulation tissue (plump fibroblasts with numerous small capillaries) admixed with foci of mature fibrous connective tissue, edema, fibrin and hemorrhage. The iris is advanced rostrally and the preiridal fibrovascular membrane extends across the iridocorneal angle, obscuring the pectinate ligament and trabecular meshwork, causing adhesion between the iris and Descmet’s membrane (anterior synechia) and resulting in obstruction of the ciliary cleft. The membrane in this region multifocally contains hemosiderin-laden macrophages, hemorrhage, fibrin, edema, and hematoidin crystals. The iris margin deviates anteriorly through the pupil (ectropion uveae). Extending from the ciliary body, covering the posterior lens capsule and to a lesser extent the anterior lens capsule, and adherent at the posterior aspect of the lens to the detached retina, is a variably thick band of fibrin admixed with erythrocytes, rare fibroblasts, lymphocytes, and plasma cells (cyclitic membrane). Multifocally, there is disruption of lenticular fibers with replacement by eosinophilic, globular material (Morgagnian globules) and flocculent debris (cataractous change). Diffusely, there is detachment of the retina, with multifocal traction bands and diffuse atrophy, degeneration and necrosis affecting all layers of the retina. Multifocally, the retinal pigmented epithelium is hypertrophied. There is hemorrhage within posterior and anterior segments (hemophthalmos and hyphema) and the optic nerve. Multifocally, the corneal epithelium is moderately hyperplastic. The corneal stroma is expanded by numerous small caliber vessels lined by plump endothelium (neovascularization); infiltrated by aggregates of lymphocytes, plasma calls, and rare macrophages admixed with multifocal areas of hemorrhage; and corneal collagen fibers are diffusely mildly separated by clear space (edema). Periocular musculature is separated and surrounded by abundant hemorrhage.
- Eye: Preiridal and cyclitic fibrovascular membranes with organizing hemophthalmos, drainage angle occlusion, ectropion uveae, peripheral anterior synechia, cataractous change, and focally extensive retinal detachment and necrosis, breed not specified, canine.
- Eye, cornea: Keratitis, chronic, diffuse, mild, with vascularization.
CONDITION: Pre-iridal fibrovascular membrane
- 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 most often associated with chronic retinal detachment, intraocular neoplasms, (ciliary body epithelial tumors), chronic uveitis, and chronic glaucoma, and has been reported in conjunction with vitreoretinopathy in Shih Tzu dogs (34/50 globes studied)
- Other fibrovascular membranes: described by distribution, including retrocorneal, preiridal, posterior iridal, cyclitic, and intravitreal
- Intravitreal membranes typically originate from the pars plana ciliary body and may be the cause of vitreal hemorrhage, but may also 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
- 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
- Of the many cytokines that 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 compativle 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)
- 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) and/or retinal detachment
- PIFM has been induced in rodents on high protein diets, in rabbits by ligation of the long ciliary arteries, and in monkeys as a long-term sequela to irradiation of aphacic eyes
- Dubielzig RR, Ketring KL, McLellan GJ, Albert DM. Veterinary Ocular Pathology: a comparative review. Louis, MO: Saunders Elsevier; 2010:429, 436.
- Labelle P. The eye. In: Zachary JF, Pathologic basis of Veterinary Disease. 6th ed. St. Louis, MO: Mosby Inc; 2016:1279-1280.
- Papaioannou NG, Dubielzig RR. Histopathological and immunohistochemical features of vitreoretinopathy in Shih Tzu dogs. Comp. Pathol. 2013;148(2-3):230-235.
- 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.