Pathology of the uvea

Pathology of the uvea

Carol Naranjo, LV, DACVP, DECVP, PhDIDEXX Laboratories

Uvea

• Anterior:– Iris– Ciliary body

• Posterior:– Choroid

Maggs, Miller, Ofri. Slatter’s fundamentals of Veterinary Ophthalmology, 2013

Normal Histology – Anterior Uvea

Normal histology - Choroid

Tapetal Non-tapetal

Feline tapetum

Uvea

• Congenital disease

• Degenerative, hyperplastic, age related changes

• Uveitis and inflammation w/in the globe

– Non-infectious

– Infectious

CONGENITAL DISEASE

Uvea

Congenital disease

• Iris hypoplasia

• Aniridia

• PPM

Maggs, Miller, Ofri. Slatter’s fundamentals of Veterinary Ophthalmology, 2013

DEGENERATIVE, HYPERPLASTIC,

AGE-RELATED CHANGES

Uvea

Degenerative, hyperplastic, age-related

• Iris atrophy: age-related, trauma, chronic glaucoma

• Cysts of iridociliary epithelium:

– Pars plana cysts: aged cats and horses: NP CB epit

– Sporadic iridal cysts: non-significant

• Except in some breeds (GR, Great Dane, American Bulldog)

Pars plana cysts

IRIS CYSTS

Thin-walled iridociliary cysts in GR

• Pigmentary and cystic glaucoma of GR

– GR uveitis, pigmentary uveitis, cystic uveal dz

• Bilateral, not symmetrical

• No goniodysgenesis

• Clinical and histological differences noted


• Gross:

– Difficult to see cysts

– Pigment:

• Back of the cornea

• Lens capsule

Courtesy of Dr. Dubielzig (COPLOW)


• Histo:

– Sparse to no inflammation

– Cysts in the posterior chamber

• Lens equator or anterior vitreal face

• Single layer of cuboidal to flattened cells

• Pigmented or not

– Free pigment in the ICA

– Heavily pigmented eyes


• Supporting the cysts:– PAS-positive membrane – Collagenous matrix (Masson’s trichrome)

Esson et al., 2009


• IHC:– Vimentin +– NSE +– S100 +– Occ. cytokeratin +

Iridociliary epithelium

Esson et al., 2009


• Glaucoma?

– Physical obstruction by iris

– Pigment dispersion

– PIFMs/PAS

– Posterior synechia/iris bombé

Cysts in other breeds• Great Dane

– Poorly pigmented cysts

Cysts in other breeds• American Bulldog

– Concurrent goniodysgenesis

– Significant inflammation

– PIFMs and pigment dispersion

– Cysts + pigment chronic inflammation and

goniodysgenesis glaucoma

Pumphrey et al., 2013

Canine ocular melanosis

• Pigmentary glaucoma

• Cairn terriers and other breeds

• Bilateral, not symmetrical

• Progressive pigmentation glaucoma

Canine ocular melanosis - Gross

• Thickening and darkening of the uvea

• Pigmented:

– Equatorial and limbal sclera

– Cornea

Cairn terrierYorkshire terrier

Canine ocular melanosis – Histo

• Round, heavily pigmented cells

• Distortion of uveal profile

• Invasion of ICA, sclera, cornea

• Sclera around ON, meninges, choroid, retina

• LP anterior uveitis possible

Canine ocular melanosis - IHC

• Round cells: melanocytes

– HMB45 +

– MITF +

– Melan A –

• Melanophages admixed (CD18 +)

Dawson-Balien et al., 2018

Canine ocular melanosis - EM

Petersen-Jones et al., 2008

Canine ocular melanosis - DDx

• Melanocytoma:

– Double population (round and spindle cells)

– Typically a discrete mass lesion (can be diffuse)

• Melanocytomas or malignant melanomas may

arise w/in ocular melanosis

Melanocytoma

Canine ocular melanosis – other breeds

• Labrador, Boxer, Dachshund, etc.

• Typically unilateral, occ. bilateral

• Similar morphology

• Possibly melanophages? (van de Sandt et al., 2003)

Canine ocular melanosis - prognosis

• Good for general health, bad for eyeball

• Intraorbital spread? (Dees et al., 2013)

UVEITIS

Uvea

Uveitis / Intraocular inflammation

• Difference b/w clinical and histological Dx:

– Aqueous flare

– Hyphema

– Histo:

• Presence of inflammatory cells

• Pathogenesis

– Effect of previous treatment?

• Severity

Systemic hypertension

Intraocular inflammation - terminology

• Uveitis: inflammation of the uvea

• Anterior uveitis/iridocyclitis: iris and CB

• Posterior uveitis/choroiditis: choroid

• Endophthalmitis: uvea and chambers/vitreous

• Panophthalmitis: all the tunics

Uveitis

Hypopyon

Uveitis

Hyphema

Uveitis – Fibrovascular membranes

PIFM

Fibrovascular membranes

PIFM w/ ectropion uvea

PIFM w/ entropion uvea

Post-iridal fibrovascular membrane


PIFM w/ PAS Anterior synechia


Posterior synechia


Cyclitic membranes


Retrocorneal membrane

Pathogenesis

ISCHEMIA

PRO-ANGIOGENIC FACTORS

INFLAMMATION

FIBROVASCULAR MEMBRANES

Hemorrhage Glaucoma

NEOPLASIA

GLAUCOMA

Feline lymphoplasmacytic uveitis

• Very common histo diagnosis

– Histologic pattern

• Cause unknown:

– End-stage?

• Toxoplasma spp., Bartonella spp., FIV, FeLV

– Immune-mediated

Feline LPU – Gross

• Lens luxation/subluxation

• Vitreous liquefied

• Opacity of anterior vitreous

Feline LPU – Histo

• Lymphocytes / Plasma cells

– Anterior uvea

• CB non-pigmented epithelium

– Retina

• Follicle-like structures

• Condensed anterior vitreous

• Hypereosinophilic granular protein

Lymph node

Feline LPU – Glaucoma

• Inflammation in ICA

• PIFM

• Lens lux

• Anterior vitreous prolapse

Equine recurrent uveitis (ERU)

• Typically received after the eye is blind / painful

• Not all uveitis in horses are ERU!

– Important to distinguish the features

– Bilateral (not all cases)

ERU – Gross

• Non-specific:

– Phthisis

– Cataract

– Synechiae

– Pale floccular material over CB processes

ERU – Histo 1. LP in the uvea +/- follicle-like structures

2. Eosinophilic linear inclusions (crystalline protein)

– Non-pigmented CB epithelium

– ONH

3. Eosinophilic homogeneous mb over inner CB

– Red Congo + (like amyloid)

– Green birefringence

IHC, amyloid AA

ERU – Histo (nonspecific)

• PIFM / PAS / retrocorneal membranes

• Cataract

• Retinal detachment

• Inflammation in ON

• Glaucoma

HIK

• Heterochromic iridocyclitis w/ 2ary keratitis• Clinically:

– Corneal edema with pigmented KPs– Iridal depigmentation – Retrocorneal membranes

HIK - Pathology

• LP w/ fewer pigment-laden MO

– MO and MNGC, anterior iris surface

• Iris pigment loss

• Retrocorneal fibrous membranes

– Pigment-laden MO and lymphocytes

• Keratitis

Uveodermatologic syndrome

• VKH-like

• Akitas, Northern breeds, other

• Bilateral and symmetrical

• Dermal dz may not be present

UDS – Gross

• Thickening of the uvea – Variable b/w cases– Symmetrical w/in a case

UDS – Histo

• Granulomatous inflammation

– MO >>> lymphocytes, plasma cells

– MO contain intracytoplasmic melanin granules

• Typically the rest of the globe is quiet

• RD

• Glaucoma

Depigmenting or “quiet” VKH-like

Courtesy Dr. Dubielzig (COPLOW)

Lens-associated uveitis

• Phacolytic uveitis (LIU)

• Phacoclastic uveitis

– Sterile/bland phacophagocytic inflammation

– Asymmetric uveitis:

• Diabetic

• Non-diabetic

• Septic implantation syndrome

Phacolytic uveitis - LIU

• Chronic leakage of lens prot through intact capsule• Gross:

– Mature, hypermature, intumescent cataract • Histologically:

– LP infiltrate in anterior uvea (nonspecific!) – Cataract!!! – Other: glaucoma, PIFM, synechiae, iris bombé,…

• Rule out other diseases!






• Diabetic

• Non-diabetic


Sterile phacoclastic uveitis

• Lens capsule rupture w/o globe penetration

• Grossly:

– Hazy media around lens

• Histo:

– Lens capsule rupture

– Macrophages and MNGC surrounding lens fibers

Asymmetric uveitis – Non-diabetic

• Small breeds (Poodles!)

• Females >> males

• Second eye at risk!

– Immediately to 4 years

• Gross:

– Haziness/opacity of ocular media (endophthalmitis)

– White lining to inner surfaces of the globe

Asymmetric uveitis – Non-diabetic

• Histo:

– Pyogranulomatous inflammation

– Macrophage-rich carpet on inner surfaces

– Penetrating injury

• Corneal/scleral rupture

• Lens capsule rupture

• Sepsis

• FB

Asymmetric uveitis – Diabetic

• Similar pathology to non-diabetic variant

• Miniature Schnauzers overrepresented

• Symmetrical (both eyes at the same time)







• Diabetic

• Non-diabetic


Septic implantation syndrome

• Phacocentric suppurative endophthalmitis

• Response to infectious agents, NOT lens protein

• Male >> female

• Trauma (cat scratch):– 39% of dogs

– 20% of cats

• Duration of clinical signs: 1 week to 1 year prior

Bell et al., 2012

SIS – Gross

• Whitish to tan phacocentric exudate

• Broad posterior synechiae

• Posterior segment uninvolved

SIS – Histo


• Perilenticular and intralenticular inflammation – Suppurative

– Phacitis / abscess

– Cataract

– Bacteria (65% of dogs, 70% of cats), away from inflam• Gram + > Gram – (occ. fungi)

– Corneal / scleral rupture, rarely

Phacoclastic uveitis in rabbits

• Encephalitozoon cuniculi

• Dwarf rabbits

• Vertical transmission

• Cataract and lens capsule rupture

E. cuniculi in rabbits – Gross

E. cuniculi in rabbits – Histo

• Granulomatous to pyogranulomatous inflam

– Anterior and posterior chamber, lens


• Intralenticular inflammation

• Organisms rarely seen

– Gram +, Giemsa, Ziehl-Neelsen

Ziehl Neelsen

Gram’s

Infectious intraocular inflammation

• Not all dz have specific pathological features

– Rickettsiae and Ehrlichiae

– Borrelia spp.

– Bartonella spp.

– Brucella spp.

– Leptospira spp.

• Underdiagnosed

Suppurative endo/panophthalmitis

• Most common consequence of penetrating trauma

• Brachycephalic and large breed

• Gross:

– Tan to yellow exudates throughout globe

– Displaced or ruptured lens

Endophthalmitis

Endophthalmitis + keratitis?


• Histo:

– PMNNs in all structures

– Lens capsule rupture

– Retinal necrosis

– Bacteria (vitreous)

– FB (plant material)


• Site of penetration:

– Cornea: impossible to discern from primary corneal dz

– Sclera:

• Superior: attack, plant

• Inferior:

– Plant or FB from oral cavity

–Dental episode?

Extension into the orbit

Feline infectious peritonitis

• Mutated FeCV/FIPV

• Typically younger than 3 years

• Commonly seen with the “dry” form

– Pyogranulomatous inflammation

• Occ. seen as an neuro-ocular form

FIP – Gross

• Translucent to opaque ocular media

• Solidified aqueous and/or vitreous

– High-protein exudate

FIP – Histo • Mixed inflammation

– Uvea, retina, ON and its meninges

• Regional predominance of:

– Plasma cell-rich inflammation

– Macrophages: atypical (cleaved nuclei, prominent nucleoli)

– Neutrophils

• Vasculitis not always found

Mycotic uveitis

• Geographical restrictions

• Pyogranulomatous chorioretinitis

• PAS or silver stains (GMS, Grocott)

Blastomycosis

• Blastomyces dermatitidis

• Dogs > cats

• Mississippi, Ohio and Missouri River valleys

• Inhalation or inoculation of spores

• Lung > eyes, skin, LN, bone

Blastomycosis – Gross • Tan exudate in the vitreous, retina, choroid

Courtesy of Dr. Dubielzig, COPLOW

Blastomycosis – Histo

• Pyogranulomatous, nodular to diffuse

• Posterior segment

• 10-15 µm diameter, refractile wall

• Broad-based budding

• Splendore-Hoeppli

Blastomycosis – Histo


Splendore Hoeppli

GMS

PAS

Cryptococcosis

• Cryptococcus neoformans

• Cats >>> dogs

• Worldwide

• Inhalation of spores (pigeon droppings)

• Lungs, CNS, LN, skin eyes

Cryptococcosis – Gross • Pyogranulomatous chorioretinitis/endophthalmitis• Gelatinous

Cryptococcosis – Histo

• (Pyo)granulomatous chorioretinitis

• “Soap-bubble”

• Inverse relationship b/w inflam and organisms

• 5-8 µm w/ 1-30 µm-thick capsule – Alcian blue, mucicarmine

• Narrow-based budding

• Pseudohyphae

Cryptococcosis – Histo

Alcian Blue stain

Cryptococcosis –Histo

Narrow-based budding

Pseudohyphae (rare)Courtesy of Dr. Dubielzig, COPLOW

Mucicarmine, Courtesy of Dr. Reilly

Histoplasmosis

• Histoplasma capsulatum

• Cats > dogs (eye)

• Worldwide (Mississippi and Ohio river valleys)

• Spores in soil (bird / bat droppings)

• Lung, intestine, LN, skeleton, skin, eye

Histoplasmosis


Histoplasmosis – Histo • Pyogranulomatous chorioretinitis • 3-5 µm, intrahistiocytic (sparse) • No budding


Histoplasmosis – Histo


GMS

Histoplasmosis

• Presumed Ocular Histoplasmosis (POH)

• Few or no organisms

• Spindle cell membrane internal to the choroid

• Proliferation of RPE

Coccidioidomycosis

• Coccidioides immitis

• Dogs > cats

• SW USA, Central and South America

• Inhalation of spores

• Immunosuppressed and outdor animals

• Lung, bones, eyes

Coccidioidomycosis – Gross


Coccidioidomycossis – Histo

• Pyogranulomatous chorioretinitis / endophthalmitis• Low numbers of organisms• 25-85 µm, thick refractile walls


Aspergillosis

• Aspergillus spp.

• Systemic dz, although eye may be noted first

• German shepherd

• Aberrant immune response

Aspergillosis – Gross

• Pyogranulomatous vitreitis/endophthalmitis

Aspergillosis – Histo

• Pyogranulomatous endophthalmitis

• Centered on vitreous / inner retina

• Intralesional hyphae

– Vitreous

– Lens capsule (ruptured)

Aspergillosis – Histo


Protothecosis• Prototheca zopfii > Prototheca wickerhamii

• Dogs

• World-wide distribution

• GI dz, systemic spread (6/14 systemic signs)

• Ocular involvement: 2/3 of cases

Protothecosis – Gross

• Complete RD, thick tan exudate around retina


Protothecosis – Histo

• (Pyo)granulomatous retinitis – endophthalmitis• Round, 5-10 μm, refractile wall

Protothecosis – EM


Protozoa - Leishmaniosis

• Leishmania spp.

• Dogs >>> cats (immunocompromised)

• Mediterranean, Central and South America

• Spread to other northern areas

• 25-30% of dogs: ocular disease

• Anterior uvea >>>> choroid

Leishmaniosis – Histo

• Granulomatous uveitis, diffuse or nodular

• Intrahistiocytic amastigotes, 1-2 µm

– IHC

• Can see blepharitis, conjunctivitis,

scleritis/episcleritis, keratitis, lacrimal adenitis

Uveal damage after endolaser


Trans-scleral LaserPhotocoagulation

Scleral collagen heat damage

Burn spots


Trans-scleral Laser Photocoagulation

Nerve and Vessel Necrosis


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Pathology of the uvea

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