Pathology of the Eyelids, Conjunctiva and Orbit

Philippe Labelle, DVM, DACVP Antech Diagnostics 13th Biannual William Magrane Basic Science Course in Veterinary and Comparative Ophthalmology

1 Overview

• Non‐neoplastic diseases of the eyelid skin • Non‐neoplastic diseases of the eyelid margin • Non‐neoplastic diseases of the conjunctiva

2 Eyelid/periocular skin

3 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)

4 Demodicosis

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

5 Demodicosis

6 Demodicosis

7 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

8 Dermatophytosis

Courtesy of Dr. Marlan Fender

9 Dermatophytosis

Courtesy of Dr. Marlan Fender

10 Dermatophytosis

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

11 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

12 Habronemiasis

Courtesy of Dr. Chris Reilly

13 Habronemiasis

Courtesy of Dr. Chris Reilly

14 Eyelid Margin

15 Eyelid Margin

16 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

17 18 Chalazion

19 Chalazion

20 Chalazion

Courtesy of Dr. Chris Reilly

21 Chalazion

Courtesy of Dr. Chris Reilly

22 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)

23 Idiopathic Marginal Blepharitis

24 Idiopathic Marginal Blepharitis

25 Conjunctiva

26 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

27 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

28 Conjunctival Overgrowth

29 Conjunctival Overgrowth

Courtesy of COPLOW

30 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

31 Ligneous Conjunctivitis

Vet Ophthalmol. 2009 12(4):248‐5

32 Ligneous Conjunctivitis

Courtesy of Dr. Chris Reilly

33 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

34 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

35 Solar Elastosis, Fibrosis and Vasculopathy

36 Solar Elastosis, Fibrosis and Vasculopathy

37 Solar Elastosis, Fibrosis and Vasculopathy

38 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

39 Lymphoplasmacytic Conjunctivitis

40 Lymphoplasmacytic Conjunctivitis

41 Lipogranulomatous Conjunctivitis

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

42 Lipogranulomatous Conjunctivitis

43 Lipogranulomatous Conjunctivitis

Courtesy of Dr. Chris Reilly

44 Lipogranulomatous Conjunctivitis

Courtesy of Dr. Chris Reilly

45 Triamcinolone Granuloma

• Macrophages and multinucleated giant cells • Rounded rectangular vacuoles • Rarely biopsied

46 Triamcinolone Granuloma

47 Triamcinolone Granuloma

48 Triamcinolone Granuloma

49 Triamcinolone Granuloma

50 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

51 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)

52 Nodular Granulomatous Episcleritis

Courtesy of Dr. Chris Reilly

53 Nodular Granulomatous Episcleritis

54 Nodular Granulomatous Episcleritis

55 Nodular Granulomatous Episcleritis

56 Nodular Granulomatous Episcleritis

57 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

58 Eosinophilic Conjunctivitis

59 Eosinophilic Conjunctivitis

60 Eosinophilic Conjunctivitis

61 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

62 Feline Herpes Keratoconjunctivitis

Syncytial cell Inclusions

Tongue from a shelter cat Courtesy of Dr. Chris Reilly

63 Feline Herpes Keratoconjunctivitis

Skin from the face of a cat

Inclusions

64 Feline Epitheliotropic Mastocytic Conjunctivitis • 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

65 Feline epitheliotropic mastocytic conjunctivitis

66 Feline epitheliotropic mastocytic conjunctivitis

67 Conjunctival Histoplasmosis

• Histoplasma capsulatum • Cats • Subconjunctival nodules • Pyogranulomatous inflammation • Special stains (GMS) often needed to best visualize the organisms

68 Conjunctival Histoplasmosis

69 Conjunctival Histoplasmosis

70 Conjunctival Histoplasmosis

71 Conjunctival Histoplasmosis

72 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

73 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)

74 Conjunctival/Orbital Onchocerciasis

• Canine • Intraocular k9 • Hodzic A et al. Transbound Emerg Dis 2018 • Komnenou AT et al. VO 2016 • 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 • Feline • Miro G et al. Parasit Vectors 2016 • Tudor et et al Parasitol Res 2016 • Labelle AL et al. VO 2011 • Otranto D et al. Emerg Infect Dis 2015 • Otranto D et al Parasit Vectors 2015 • Otranto D et al. Emerg Infect Dis 2013 • Review • Labelle AL et al. Vet Parasitol, 2013 • Gracio AJ et al. Parasitol Res 2015

75 Conjunctival/Orbital Onchocerciasis

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

76 Conjunctival/Orbital Onchocerciasis

Feline cases

Modified from : Parasit Vectors 2015

77 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

78 Conjunctival/Orbital Onchocerciasis

Courtesy of COPLOW

79 Conjunctival/Orbital Onchocerciasis

Courtesy of Dr. Chris Reilly

80 Conjunctival/Orbital Onchocerciasis

Courtesy of COPLOW

81 Conjunctival/Orbital Onchocerciasis

Feline

82 Conjunctival/Orbital Onchocerciasis

Annular ridges

Striae

Feline

83 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

84 Conjunctival thelaziosis

Papadopoulos E et al. Transbound Emerg Dis 2018.

85 ORBIT

86 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

87 Orbital extraocular polymyositis

Courtesy of COPLOW

88 Orbital lesions

• Abscesses • Cysts • Extension of disease at other sites • Unlikely to be biopsied

89 Orbital lesions

Goblet cells