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Page 1: Pathology of the Eyelids, Conjunctiva and Orbit · 6/5/2018  · Nodular Granulomatous Episcleritis •Episclerokeratitis, episcleritis, NGE •Smooth nodules to diffuse thickening

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Pathology of the Eyelids, Conjunctiva and Orbit

Philippe Labelle, DVM, DACVPAntech Diagnostics

13th Biannual William Magrane Basic Science Course in Veterinary and Comparative Ophthalmology

Page 2: Pathology of the Eyelids, Conjunctiva and Orbit · 6/5/2018  · Nodular Granulomatous Episcleritis •Episclerokeratitis, episcleritis, NGE •Smooth nodules to diffuse thickening

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Overview

• Non‐neoplastic diseases of the eyelid skin

• Non‐neoplastic diseases of the eyelid margin

• Non‐neoplastic diseases of the conjunctiva

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Eyelid/periocular skin

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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)

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Demodicosis

• Demodex sp.

• Juvenile and adult forms

• Localized and generalized

• Perivascular inflammation, periadnexalinflammation, folliculitis and furunculosis

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Demodicosis

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Demodicosis

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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

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Dermatophytosis

Courtesy of Dr. Marlan Fender

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Dermatophytosis

Courtesy of Dr. Marlan Fender

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Dermatophytosis

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

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Habronemiasis

• Draschia megastoma, Habronemamicrostoma/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

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Habronemiasis

Courtesy of Dr. Chris Reilly

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Habronemiasis

Courtesy of Dr. Chris Reilly

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Eyelid Margin

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Eyelid Margin

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Chalazion

• Meibomian adenitis

• Lipogranulomatous inflammation

• Secondary to leakage of meibomiansecretions, most often from neoplasia

• Macrophages and multinucleated giant cells

• Acicular cytoplasmic clefts on HE, refractile/birefringent material

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Chalazion

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Chalazion

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Chalazion

Courtesy of Dr. Chris Reilly

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Chalazion

Courtesy of Dr. Chris Reilly

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Idiopathic Marginal Blepharitis

• Dogs

• Sterile granuloma syndrome

• Granulomatous to pyogranulomatousinflammation

• Typically forms a mass effect, but can be poorly circumscribed or diffuse

• Can be bilateral. 

• Unknown etiology

• No microorganisms (HE or special stains)

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Idiopathic Marginal Blepharitis

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Idiopathic Marginal Blepharitis

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Conjunctiva

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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

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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

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Conjunctival Overgrowth

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Conjunctival Overgrowth

Courtesy of  COPLOW

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Ligneous Conjunctivitis

• Doberman Pinscher, Yorkshire terrier,  Golden Retriever, Scottish terrier

• Conjunctivitis, hard consistency, pseudomembranous exudate

• Subepithelial deposition of  mostly acellular hyalinizedeosinophilic 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

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Vet Ophthalmol. 2009 12(4):248‐5

Ligneous Conjunctivitis

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Ligneous Conjunctivitis

Courtesy of Dr. Chris Reilly

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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

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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

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Solar Elastosis, Fibrosis and Vasculopathy

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Solar Elastosis, Fibrosis and Vasculopathy

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Solar Elastosis, Fibrosis and Vasculopathy

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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

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Lymphoplasmacytic Conjunctivitis

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Lymphoplasmacytic Conjunctivitis

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Lipogranulomatous Conjunctivitis

• Cats

• Nodular inflammation

• Macrophages with lipid lakes, multinucleated giant cells may be present

• Can be associated with neoplasia

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Lipogranulomatous Conjunctivitis

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Lipogranulomatous Conjunctivitis

Courtesy of Dr. Chris Reilly

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Lipogranulomatous Conjunctivitis

Courtesy of Dr. Chris Reilly

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Triamcinolone Granuloma

• Macrophages and multinucleated giant cells

• Rounded rectangular vacuoles

• Rarely biopsied

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Triamcinolone Granuloma

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Triamcinolone Granuloma

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Triamcinolone Granuloma

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Triamcinolone Granuloma

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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

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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)

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Nodular Granulomatous Episcleritis

Courtesy of Dr. Chris Reilly

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Nodular Granulomatous Episcleritis

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Nodular Granulomatous Episcleritis

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Nodular Granulomatous Episcleritis

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Nodular Granulomatous Episcleritis

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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) Herpesvirusinfection in cats

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Eosinophilic Conjunctivitis

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Eosinophilic Conjunctivitis

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Eosinophilic Conjunctivitis

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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

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Feline Herpes Keratoconjunctivitis

Courtesy of Dr. Chris ReillyTongue from a shelter cat

Inclusions

Syncytial cell

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Feline Herpes Keratoconjunctivitis

Skin from the face of a cat

Inclusions

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Feline Epitheliotropic MastocyticConjunctivitis

• Mast cells are numerous 

• Mast cells infiltrate the surface epithelium

• Edema and papillary epithelial hyperplasia

• May be allergic

• Association with eosinophilic conjunctivitis?

• FHV‐1 is not a likely cause/factor

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Published in: B. Beckwith-Cohen; R. R. Dubielzig; D. J. Maggs; L. B. C. Teixeira; Vet Pathol 54, 141-146.DOI: 10.1177/0300985816653793 Copyright © 2016 American College of Veterinary Pathologists

Feline epitheliotropic mastocyticconjunctivitis

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Published in: B. Beckwith-Cohen; R. R. Dubielzig; D. J. Maggs; L. B. C. Teixeira; Vet Pathol 54, 141-146.DOI: 10.1177/0300985816653793Copyright © 2016 American College of Veterinary Pathologists

Feline epitheliotropic mastocyticconjunctivitis

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Conjunctival Histoplasmosis

• Histoplasma capsulatum

• Cats

• Subconjunctival nodules

• Pyogranulomatous inflammation

• Special stains (GMS) often needed to best visualize the organisms

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Conjunctival Histoplasmosis

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Conjunctival Histoplasmosis

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Conjunctival Histoplasmosis

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Conjunctival Histoplasmosis

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Conjunctival/Orbital Onchocerciasis

• Onchocerca lupi• Dogs and cats• Europe, Tunisia, Turkey, Iran, USA, Canada (USA)

• Subconjunctival or periscleral/orbital nodules• Granulomatous inflammation• Eosinophils may be present in large numbers, there may be fibrosis

• Parasites may not elicit severe inflammation

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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• One report of aberrant location (larynx)

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Conjunctival/Orbital Onchocerciasis

• Canine• Hodzic A et al. Transbound Emerg Dis 

2018• Colella V et al. PLoS Negl trop Dis 2018• McLean NJ et al. VO 2017• Verocai GG et al. Emerg Infect Dis 2016• Alho AM et al. Parasitol Int 2016• Miro G et al. Parasit Vectors 2016• Tudor et et al Parasitol Res 2016• Otranto D et al. Emerg Infect Dis 2015• Otranto D et al Parasit Vectors 2015• Otranto D et al. Emerg Infect Dis 2013• Labelle AL et al. Vet Parasitol, 2013

• Intraocular k9• Komnenou AT et al. VO 2016

• Feline• Labelle AL  et al. VO 2011

• Review• Gracio AJ et al. Parasitol Res 2015

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Conjunctival/Orbital Onchocerciasis

Modified from : Am J Trop Med Hyg. 2013 Mar;88(3):601‐5

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Conjunctival/Orbital Onchocerciasis

Modified from : Parasit Vectors 2015

Feline cases

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Conjunctival/Orbital Onchocerciasis

Vet Ophthalmol. 

2002 5(4):119‐26

Vet Ophthalmol. 2016 May;19(3):245‐249Emerg Infect Dis. 2015 21(5):868‐871

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Conjunctival/Orbital Onchocerciasis

Courtesy of COPLOW

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Conjunctival/Orbital Onchocerciasis

Courtesy of Dr. Chris Reilly

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Conjunctival/Orbital Onchocerciasis

Courtesy of COPLOW

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Conjunctival/Orbital Onchocerciasis

Feline

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Conjunctival/Orbital Onchocerciasis

Feline

Annular ridges

Striae

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Parasitic Conjunctivitis

• Histolopathologic findings are non‐specific• Unlikely to be biopsied

• Thelaziosis (Thelazia callipaeda)– Dogs, cats, rare (Europe)– Subclinical to severe, also keratitis– Papadopoulos E et al. Transbound Emerg Dis 2018– Seixas F et al. Vet Parasitol 2018

• Dirofilariasis (Dirofilaria repens)– Dogs, rare (Europe, UK)– Agapito D et a. J Small Anim Pract 2018– Graham‐Brown J et al. Vet Rec 2016

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Conjunctival thelaziosis

Papadopoulos E et al. Transbound EmergDis 2018.

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ORBIT

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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

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Orbital extraocular polymyositis

Courtesy of COPLOW

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Orbital lesions

• Abscesses

• Cysts

• Extension of disease at other sites

• Unlikely to be biopsied

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Orbital lesions

Goblet cells