Pathology of the Eyelids, Conjunctiva and Orbit

Philippe Labelle, DVM, DACVP Antech Diagnostics 12th Biannual William Magrane Basic Science Course in Veterinary and Comparative Ophthalmology Overview

• Non-neoplastic diseases of the eyelid skin • Non-neoplastic diseases of the eyelid margin • Non-neoplastic diseases of the conjunctiva Eyelid/periocular skin General Considerations

• Any skin disease can affect the eyelid skin (allergic/hypersensitivity disease, zinc-responsive dermatosis, pemphigus foliaceus, demodicosis, dermatophytosis, habronemiasis, etc) • Eyelid skin reacts similarly to skin elsewhere • Eyelids may be the first or the most severely affected site • Veterinary Ocular Pathology (Dubielzig et al.), Veterinary Dermatopathology (Gross, Ihrke, Walder) Demodicosis

• Demodex sp. • Juvenile and adult forms • Localized and generalized • Perivascular inflammation, periadnexal inflammation, folliculitis and furunculosis Demodicosis Demodicosis Dermatophytosis

• Microsporum sp., Trichophyton sp. • Fungal hyphae and spores colonize hairs • Folliculitis and furunculosis • Lesions may be more subtle in cats and pustular disease may predominate Dermatophytosis

Courtesy of Dr. Marlan Fender Dermatophytosis

Fungal hyphae invade the hair shaft. Spores surround the hair. Hamster Habronemiasis

• Draschia megastoma, Habronema microstoma/majus, Habronema muscae • Eosinophilic and granulomatous inflammation • Larvae may be few in numbers • May be diagnosed as “Equine eosinophilic granuloma” if no larvae are present Habronemiasis

Courtesy of Dr. Chris Reilly Habronemiasis

Courtesy of Dr. Chris Reilly Eyelid Margin Eyelid Margin Chalazion

• Meibomian adenitis • Lipogranulomatous inflammation • Secondary to leakage of meibomian secretions, most often from neoplasia • Macrophages and multinucleated giant cells • Acicular cytoplasmic clefts on HE, refractile/birefringent material

Chalazion Chalazion Chalazion

Courtesy of Dr. Chris Reilly Chalazion

Courtesy of Dr. Chris Reilly Idiopathic Marginal Blepharitis

• Dogs • Sterile granuloma syndrome • Granulomatous to pyogranulomatous inflammation • Typically forms a mass effect, but can be poorly circumscribed or diffuse • Can be bilateral. • Unknown etiology • No microorganisms (HE or special stains) Idiopathic Marginal Blepharitis Idiopathic Marginal Blepharitis Conjunctiva General Considerations

• The conjunctiva has limited ways in which it responds to injury • Conjunctival biopsies rarely identify a specific cause for the conjunctivitis • Only a few specific entities • Biopsies are taken late in the disease process, often after treatment Conjunctival Overgrowth

• Rabbits • Pseudopterigium • Unknown cause • Hyperplastic conjunctival tissue • Normal tissue organization • Extends to cover the cornea • Does not invade and is not adhered to the cornea

• Note: true pterygium should have solar/actinic changes (ie solar elastosis +/- actinic keratosis) and will invade the cornea following dissolution of Bowman’s membrane Conjunctival Overgrowth Conjunctival Overgrowth

Courtesy of COPLOW Ligneous Conjunctivitis

• Doberman Pinscher, Yorkshire terrier, Golden Retriever, Scottish terrier • Conjunctivitis, hard consistency, pseudomembranous exudate • Subepithelial deposition of mostly acellular hyalinized eosinophilic matrix • PTAH positive, Congo red negative • Fibrin deposition in the conjunctiva, oral cavity, esophagus and +/- glomeruli and other sites • Plasminogen deficiency in humans and some dogs – Plasmin is fibrinolytic – PTAH positive (compatible with fibrin)

• Mason et al, JSAP, 2016; Mason et al, JSAP, 2012; Torres et al, VO 2009; McLean et al JAVMA, 2008; Ramsey et al, JAAHA , 1996 Ligneous Conjunctivitis

Vet Ophthalmol. 2009 12(4):248-5 Ligneous Conjunctivitis

Courtesy of Dr. Chris Reilly Solar Elastosis, Fibrosis and Vasculopathy • Conjunctiva, not cornea • “Solar conjunctivitis” • Overlaps with solar induced neoplasia • Solar elastosis – Altered fibers within the superficial substantia propria – New production +/- degradation of collagen and elastin • Can form plaques in horses • Often seen with conjunctival squamous cell carcinoma, hemangioma or hemangiosarcoma Solar Elastosis, Fibrosis and Vasculopathy • Solar “fibrosis” – Altered collagen, pale, hypocellular (sclerotic) – Forms a band underlying the epithelium – Not true fibrosis • Solar vasculopathy – Rare, more common in skin – Thickened hyalin vessel walls – May be endothelial swelling Solar Elastosis, Fibrosis and Vasculopathy Solar Elastosis, Fibrosis and Vasculopathy Solar Elastosis, Fibrosis and Vasculopathy Lymphoplasmacytic conjunctivitis

• Most common inflammatory response • Does not suggest a specific etiology • Infectious and non-infectious causes • Perivascular to diffuse • Non-ulcerative • Can be severe enough to warrant concern for neoplasia Lymphoplasmacytic Conjunctivitis Lymphoplasmacytic Conjunctivitis Lipogranulomatous Conjunctivitis

• Cats • Nodular inflammation • Macrophages with lipid lakes, multinucleated giant cells may be present • Can be associated with neoplasia Lipogranulomatous Conjunctivitis Lipogranulomatous Conjunctivitis

Courtesy of Dr. Chris Reilly Lipogranulomatous Conjunctivitis

Courtesy of Dr. Chris Reilly Triamcinolone Granuloma

• Macrophages and multinucleated giant cells • Rounded rectangular vacuoles • Rarely biopsied Triamcinolone Granuloma Triamcinolone Granuloma Triamcinolone Granuloma Triamcinolone Granuloma Nodular Granulomatous Episcleritis

• Episclerokeratitis, episcleritis, NGE • Smooth nodules to diffuse thickening • Most often in the limbal conjunctiva • Also occurs in other conjunctival sites, orbit • Unknown cause • Epithelioid and spindle macrophages admixed with lymphocytes and plasma cells • Some spindle cells are myofibroblasts Nodular Granulomatous Episcleritis

• The relative proportion of inflammatory cell types is highly variable • The macrophages do not form distinct granulomas • Some cases may include multinucleated giant cells or eosinophils • Cases with a predominance of spindle cells have been called nodular fasciitis • Special stains for infectious organisms are always negative (and must be) • The proportion of T-cells and B-cells has been said to be predictive of response to treatment (B-cell predominant were more refractory).

• Breaux et al. VO, 2007 (T vs B); Barnes et al, VO 2010 (orbit) Nodular Granulomatous Episcleritis

Courtesy of Dr. Chris Reilly Nodular Granulomatous Episcleritis Nodular Granulomatous Episcleritis Nodular Granulomatous Episcleritis Nodular Granulomatous Episcleritis Eosinophilic conjunctivitis

• Eosinophils are a component of the inflammation • Eosinophils may not be the predominant cell type (lymphoplasmacytic) • Perivascular to diffuse • Allergic/ hypersensitivity disease • Cannot exclude (or confirm) Herpesvirus infection in cats Eosinophilic Conjunctivitis Eosinophilic Conjunctivitis Eosinophilic Conjunctivitis Herpes Keratoconjunctivitis

• Cats, primarily kittens • Unlikely to be biopsied • Window for inclusions is narrow • May include eosinophils

• Role of Herpervirus in adult cats is controversial • Clinical lesions suspected to be, diagnosed as, and treated for herpesviral infection lack any histologic evidence to specifically support a viral cause • The presence of eosinophils is not a helpful feature as many hypersensitivity disease has eosinophils as a hallmark of the lesion Feline Herpes Keratoconjunctivitis

Syncytial cell Inclusions

Tongue from a shelter cat Courtesy of Dr. Chris Reilly Feline Herpes Keratoconjunctivitis

Skin from the face of a cat

Inclusions Conjunctival Histoplasmosis

• Histoplasma capsulatum • Cats • Subconjunctival nodules • Pyogranulomatous inflammation • Special stains (GMS) often needed to best visualize the organisms Conjunctival Histoplasmosis Conjunctival Histoplasmosis Conjunctival Histoplasmosis Conjunctival Histoplasmosis ORBIT Conjunctival/Orbital Onchocerciasis

• Onchocerca lupi • Dogs and cats • 205 canine, 2 feline and 18 human infections in Europe, Tunisia, Turkey, Iran and the USA (2015). • Subconjunctival or periscleral/orbital nodules • Granulomatous inflammation • Eosinophils may be present in large numbers, there may be fibrosis • Parasites may not elicit severe inflammation Conjunctival/Orbital Onchocerciasis

• Must be differentiated from other nematodes with microfilariae • Annular/circumferential ridges distinguish from Dirofilaria immitis • Association with onchocerciasis and glaucoma in humans, unclear in dogs and cats • Endosymbiotic bacteria Wolbachia • Larval development in blackflies Conjunctival/Orbital Onchocerciasis

• Canine • Intraocular k9 • Tudor et et al Parasitol Res 2016 • Komnenou AT et al. VO 2016 • Otranto D et al. Emerg Infect Dis 2015 • Otranto D et al Parasit Vectors 2015 • Otranto D et al. Emerg Infect Dis • Feline 2013 • Labelle AL et al. VO 2011 • Labelle AL et al. Vet Parasitol, 2013 • Fascia P et al VO 2010 • Zarfoss et al. Vet Pathol 2007 • Review • Komnenou A et al. VO 2002 • Gracio AJ et al. Parasitol Res 2015 • Egyed Z et al. Vet Parasitol, 2001 Conjunctival/Orbital Onchocerciasis

Modified from : Am J Trop Med Hyg. 2013 Mar;88(3):601-5 Conjunctival/Orbital Onchocerciasis

Feline cases

Modified from : Parasit Vectors 2015 Conjunctival/Orbital Onchocerciasis

Vet Ophthalmol. 2002 5(4):119-26

Emerg Infect Dis. 2015 21(5):868-871 Vet Ophthalmol. 2016 May;19(3):245-249 Conjunctival/Orbital Onchocerciasis

Courtesy of COPLOW Conjunctival/Orbital Onchocerciasis

Courtesy of Dr. Chris Reilly Conjunctival/Orbital Onchocerciasis

Courtesy of COPLOW Conjunctival/Orbital Onchocerciasis

Feline Conjunctival/Orbital Onchocerciasis

Annular ridges

Striae

Feline Orbital extraocular polymyositis

• Affects all the extraocular muscles except the retractor bulbi muscle • Rare disease, typically young dogs • Bilateral and variably symmetric exophthalmos, retraction of the upper eyelid, and mild chemosis • Chronic: enophthalmos and strabismus • CD3+ predominant lymphocytic myositis with myonecrosis • Attempts at regeneration with muscle atrophy and fibrosis • Immune-mediated attack directed specifically against the extraocular muscles is suspected • Unlikely to be biopsied Orbital extraocular polymyositis

Courtesy of COPLOW