sys path derm and ocular

what structure produces aqueous humor? where does aqueous humor drain out of the eye?

• aqueous humor is produced by the ciliary body

• drains out of trabecular meshwork

how is corneal optical clarity maintaned?

• avascular

  • nutrition provided by:

    • pre-corneal tear film

    • aqueous humor

• dehydrated

  • maintained by:

    • hydrophobic corneal epithelium

    • corneal endothelial cation pump (Na/K ATPase) — pumps H₂O out

• regular array of collagen lamellae and keratocytes

steps in corneal epithelial wound healing

• initial lag phase — 1 hr

• sliding of epithelial cells at ulcer margin to cover defect

• replication of germinal cells at limbus within 24 hrs

• uncomplicated 2mm ulcer heals in a few days

causes of corneal edema

• epithelial defects (ulcers) — superficial stromal edema

• stromal vascularization — leaky blood vessels

• endothelial defects — deep stromal edema

  • endothelialitis

    • canine adenovirus-1 vaccine reaction (“blue eye”)

    • malignant catarrhal fever

  • endothelial degeneration — age-related

  • endothelial cell damage

clinical appearance of ulcerative keratitis (corneal ulcers)

• corneal edema

• superficial neovascularization

• inflammatory cell infiltrates

which stain can be used to diagnose corneal ulcers?

fluorescein stain — exposed stroma stains green

underlying causes of ulcerative keratitis

• trauma

  • conformational lid defects (ex. entropion)

  • hair irritation

  • foreign body

• exposure

  • lagophthalmos, exophthalmos

  • CN V or VII defects

• keratoconjunctivitis sicca (dry eye)

• primary or secondary infection

causative agent of infectious bovine keratoconjunctivitis

moraxella bovis (gram negative bacillus)

• primary corneal pathogen with cytotoxic effects on neutrophils & corneal epithelial cells

• highly contagious

predisposing factors to infectious bovine keratoconjunctivitis

• summer months

• corneal irritation (fly vectors, UV radiation, long grasses)

• Hereford & Hereford-cross breeds

• younger cattle (higher morbidity)

• cattle housed inside have higher infection rate + longer duration but milder clinical disease

clinical appearance of infectious bovine keratoconjunctivitis

• unilateral (initially) central corneal ulcer

• intense inflammatory cell infiltrates may develop into a stromal abscess

• superficial neovascularization

outcomes of infectious bovine keratoconjunctivitis

• corneal healing with scarring

or

• corneal perforation with iris prolapse (blindness)

clinical appearance of feline herpesvirus-1 keratitis

formation of dendritic ulcers (linear ulcers) — characteristic

pathogenesis of feline herpesvirus-1 keratitis

• virus reactivation and recrudescence

• FHV-1 viral replication in corneal epithelial cells → cell death

• may develop secondary bacterial infections

which stain is used to visualize FHV-1 keratitis?

rose bengal stain — epithelial defect may not extend to basement membrane; necessary to visualize epithelial lesions

causative agents of equine fungal keratitis

• opportunistic pathogens — part of normal conjunctival flora of the horse

  • vary by geographic location

  • aspergillus

  • fusarium

lesions associated with equine fungal keratitis

• ulcerative keratitis, frequently deep stromal

• deep stromal abscesses

• difficult to treat; may progress to corneal perforation & iris prolapse

microscopic findings of equine fungal keratitis

• involvement of posterior 1/3 of cornea

• fungal hyphae found within descemet’s membrane (attracted to carbohydrates) & deep corneal stroma; rarely extend into anterior chamber

• breaks in descemet’s membrane with pyogranulomatous inflammation; occasional multinucleated giant cells

• often very little corneal neovascularization

what are the components & functions of the tear film?

• lipid layer (meibomian glands of the eyelids): forms optically smooth surface & prevents evaporation

• aqueous layer (orbital lacrimal gland & gland of 3rd eyelid): provides nutrients & Ig to the avascular cornea

• mucous layer (goblet cells of the conjunctival epithelium): adsorbs aqueous layer to corneal epithelium

production of what layer of the tear film is decreased with keratoconjunctivitis sicca (dry eye)?

aqueous portion

consequences of corneal desiccation

• acute: corneal epithelium becomes ulcerated

• chronic: corneal epithelium undergoes “epidermalization”

features of corneal “epidermalization”

not specific to KCS — any chronic, end-stage corneal disease

• epithelial thickening with keratinization (↑ opacity)

• rete ridge formation

• pigmentation of the epithelium & superficial stroma

• superficial neovascularization

• superficial inflammation

• goblet cell hyperplasia (conjunctiva)

what is aqueous flare?

• turbid aqueous humor, caused by the presence of:

  • fibrin & other proteins

  • inflammatory cells

• seen with uveitis

hypopion

neutrophils (pus) in anterior chamber

what are consequences of intraocular inflammation?

• corneal edema

  • effects on corneal endothelial cell function

• pre-iridal fibrovascular membranes (PIFM)

• synechia (adhesion)

  • block aqueous drainage

• secondary glaucoma

• retinal detachment

  • protein exudation ± inflammatory cells from choroidal vessels into subretinal space

how do preiridal fibrovascular membranes (PIFM) form?

• angiogenic factors are released into the eye & stimulate iridal blood vessels to proliferate on the anterior surface of the iris

• fragile vessels may bleed spontaneously; leaky!

  • hyphema = blood in anterior chamber

different types of synechia (adhesion)

• anterior: adhesion to the cornea

• posterior: adhesion of the lens

• peripheral anterior: over the iridocorneal angle

how can secondary glaucoma result from intraocular inflammation?

• accumulation of inflammatory cells & fibrin in the iridocorneal angle may obstruct aqueous outflow

• peripheral anterior synechia caused by preiridal fibrovascular membrane can close the angle

• pupillary block: anterior or posterior synechia

where is blastomycosis common? which species does it affect?

• common in wisconsin

• dogs > cats > people (not zoonotic)

pathologic findings of blastomycosis

• pyogranulomatous endophthalmitis & chorioretinitis

• retinal detachment

• thick-walled yeast, broad-based budding

• systemic disease: lungs, skin, bone, eye

where is cryptococcosis common? which species does it affect?

• more widespread than blastomycosis

  • associated with river systems, pigeon droppings

• more common in cats than dogs

pathologic findings of cryptococcosis

• pyogranulomatous chorioretinitis

• also: nasal cavity, cutaneous involvement, brain

• thin-walled yeast, narrow-based budding, thick capsule

where is coccidioidomycosis common?

valley fever (AZ, NM, CA)

pathologic findings of coccidioidomycosis

• pyogranulomatous chorioretinitis

• primarily pulmonary infections

• may disseminate: long bones, heart, CNS, eyes

• round spherules, filled with small endospores

where is histoplasmosis common? what species does it affect?

• widely distributed, esp. Ohio & Mississippi river valleys

  • soil fungus associated with bird & bat droppings

• most common in dogs and cats

pathologic findings of histoplasmosis

• pyogranulomatous chorioretinitis

• primary pulmonary infection with dissemination to GI, liver

• small round yeast, intracytoplasmic in macrophages

which species is affected by lymphoplasmacytic uveitis?

idiopathic disease of cats

clinical signs of lymphoplasmacytic uveitis

• anterior uveitis (bilateral)

  • aqueous flare

  • hypopion (pus in anterior chamber)

  • rubeosis iridis (fibrovascular membrane)

  • anterior & posterior synechia

  • iridal nodules — lymphoid follicles

  • may obliterate ICA → secondary glaucoma

what is the most common cause of blindness in horses?

equine recurrent uveitis — recurrent episodes of anterior & posterior uveitis, typically progressive

equine recurrent uveitis pathogenesis

• multifactorial, complex, controversial

• inciting factors

  • most common: Leptospira infection → antigens cross react with equine cornea and lens antigens

• immune mediated mechanisms result in recurrent bouts, even in the absence of the initiating factor

histopathologic findings of equine recurrent uveitis

• lymphocytic inflammation in the uvea, sometimes follicular

• eosinophilic (hyalinized) membrane coats the ciliary processes — amyloid

• intracytoplasmic inclusions in non-pigmented ciliary body epithelium

causes of impaired aqueous outflow

• fibrovascular membranes

  • synechia — anterior, posterior, peripheral anterior

• pupillary block — iris bombe

• clogging of trabecular meshwork with cells

• obliteration of iridocorneal angle by neoplasia

• goniodysgenesis

what is goniodysgenesis?

• congenital abnormality — malformation of the iridocorneal angle structures

• predisposes animal to development of glaucoma at any age

breed dispositions to goniodysgenesis

cocker spaniel, bassett hound, samoyed, great dane, chow chow, norwegian elkhound

(any breed can be affected)

morphologic features of glaucoma

• retinal atrophy

  • decreased numbers of retinal ganglion cells

  • atrophy & gliosis of the never fiber layer

  • full thickness retinal atrophy (in dogs only)

• cupping of the optic nerve head

• end stage changes

  • buphthalmia (bulging)

  • lens luxation

  • phthisis bulbi (eye shrinks, atrophies)

what is the most common intraocular tumor in the dog?

melanocytoma/malignant melanoma

distribution of melanocytoma/malignant melanoma

• anterior uveal tract — most common

• choroid

• epibulbar/limbar

biologic behavior of melanocytoma/malignant melanoma

• destruction of globe — can fill globe, extend through sclera

• melanocytoma does not metastasize (benign)

• malignant melanoma infrequently metastasizes

• melanocytoma can transform to malignant melanoma

what is the most common intraocular tumor in the cat?

feline diffuse iris melanoma (FDIM)

gross appearance/biologic behavior of feline diffuse iris melanoma (FDIM)

• gross appearance:

  • begins as hyperpigmented foci (freckles) on the iris, over months to years coalesce and form masses involving the iris, ciliary body, choroid

• may invade the iridocorneal angle & cause secondary glaucoma

• distant metastasis may occur infrequently

  • most commonly to liver, lung, kidney, and spleen

characteristics of iridociliary epithelial tumors (origin, species, biologic behavior)

• cell of origin: pigmented or nonpigmented ciliary body epithelium

• common in dogs, less common in cats

• biologic behavior

  • vast majority benign = iridociliary adenomas

  • scleral invasion: iridociliary adenocarcinoma

gross appearance of iridociliary epithelial tumors

• arises in posterior chamber

• may extend through the pupil or invade the iris

• often well vascularized

• typically cream-colored mass; may be partial or completely pigmented

origin/associated risk factors of feline post-traumatic sarcoma

• associated with previous ocular trauma & lens capsule rupture

  • development of tumor may occur months to years following the traumatic event

• cell of origin: lens epithelial cells, released following lens capsule rupture

distribution of feline post-traumatic sarcoma

• lines chambers of the eye, fills globe, extends through sclera, and can invade the optic nerve into the brain

• may reoccur in orbit after enucleation

• distant metastasis possible

which species are most commonly affected by squamous cell carcinoma of eyelids and conjunctiva?

cattle > horses > cats > dogs

how does squamous cell carcinoma develop? what are associated risk factors?

• develops through pre-cancerous stage (plaques > papilloma) before malignant transformation over months or years

• can be associated with viral infections: papilloma, herpes

• associated with UV light exposure

tumors that commonly metastasize to the eye

• lymphoma

• histiocytic sarcoma

• melanoma

• hemangiosarcoma

• mammary adenocarcinoma

• other carcinomas

how are keratinocytes attached to each other?

desmosomal junctions

how are basal keratinocytes attached to the basement membrane?

hemidesmosomal junctions

what are the phases of the hair follicle cycle?

• anagen = growth phase; longest (years)

  • most hairs are in anagen

• catagen = transitional or involuting phase; short

• telogen = resting phase

  • → kenogen

  • → anagen

what can cause telogen hairs to be increased?

conditions such as:

• inflammation

• stress

• alterations in thyroxine, estrogen, and testosterone

• nutritional deficiencies

→ hypotrichosis (thinning hair) / alopecia (no hair)

what is the function of sebaceous glands?

produce sebum that coats the hair:

• maintains normal hydration

• acts as chemical barrier

• gives coat a glossy sheen

• acts as a pheromone

what are the different type of apocrine glands?

• epitrichial — secrete to the primary hair follicles; sweat mixes with sebum to form the protective coating

  • thermoregulation in cattle/horses

• eccrine — secrete directly to skin (paw pads)

anal glands vs anal sac

• anal glands: specialized apocrine glands that open directly onto the anal skin via a duct at the rectoanal junction

  • similar apocrine glands line the anal sacs

• anal sacs: squamous lined cystic cavity containing odiferous secretions

what are hepatoid glands? where are they located?

modified sebaceous glands around the anus, along the tail, prepuce, dorsolumbosacral areas

primary vs. secondary lesions

• primary lesions occur directly

• secondary lesions are often a result of self trauma (scratching or chewing)

papule

• primary lesion

• slightly raised, red, <1 cm

• epidermal & dermal inflammation and edema

• ex. insect bites

macule

• primary lesion

• flat, different color to adjacent skin

• ex. hemorrhage, lentigo (increased pigment), vitiligo (loss of pigment)

plaque

• primary lesion

• raised, flat-topped, semi-firm/firm

• ex. calcium deposits (calcinosis cutis), thickened epidermis with inflammation - e.g. feline eosinophilic granuloma complex

wheals (hives)

• primary lesion

• raised, smooth, semi-firm, well-delineated, and transient

• edema → insect bites or allergy

pustule

• primary lesion

• raised, smooth, soft, pale yellow to green (pus), red periphery

• ex. bacterial infection (very common), pemphigus foliaceus (rare)

vesicle(s) & bulla(e)

• primary lesion

• vesicle <1 cm

• bulla >1cm

• fluid-filled pocket (blisters)

• ex. burns, viral / immune-mediated / bacterial diseases

scale

• secondary lesion

• fragments of keratin on the surface; seen in many diseases

• ↑↑ stratum corneum

collarette

• secondary lesion

• flat to minimally elevated ring of scale that enlarges peripherally

• remnant of an old pustule

• ex. bacterial & fungal infections

crust

• secondary lesion

• desiccated keratin with serum, blood, cellular debris, and inflammatory cells

• seen in many diseases

excoriation

• secondary lesion

• superficial loss of epidermal layers

• secondary to physical trauma (scratching)

erosions & ulcers

• secondary lesions

• clinically look similar

• erosion = partial thickness epidermal defect

• ulcer = full thickness epidermal defect

general causes of hypo- and hyperpigmentation

• secondary lesions

• hyperpigmentation: chronic inflammatory diseases (common), some endocrine diseases (uncommon)

• hypopigmentation: inflammation damaging pigment-containing epidermal cells or melanocytes

lichenification

• secondary lesion

• thickening of the skin, often with hyperpigmentation

• accentuated creases

• associated with chronic inflammation

• rubbing, scratching, irritation

fissure

• secondary lesion

• linear crack

• associated with chronic thickening of the skin

• often seen on/near paw pads

comedo (blackheads)

• secondary lesion

• plugged follicle with keratin & sebum

• ex. endocrine dermatoses (hyperadrenocorticism); pressure points

what is skin scraping best for?

mites — demodex spp.

what are acetate tape preparations/impression smears best for?

bacteria & fungi

what are fine needle aspirates best for?

nodules & tumors

when would a biopsy be appropriate to perform?

• confirm a clinical diagnosis if the chosen treatment has significant side effects

• a nodular lesion, ulcer, or non-healing wound (i.e., possible tumor)

• lesions develop suddenly, are severe, or unusual

• lesions develop during therapy (possible drug reaction)

• multiple clinical differentials and routine exam & ancillary tests do not differentiate

• skin disorder fails to respond to therapy or disorder recurs when therapy is stopped

how do you perform a skin biopsy?

1. collect multiple sites representative of the range of lesions

2. collect some samples at the junction of normal & abnormal

3. include crusts, if present

4. do not surgically prepare the site (including clipping) if lesion is confined to epidermis or superficial dermis

5. use largest punch biopsy possible (6-8mm) or elliptical full thickness biopsies

6. fix in 10% neutral buffered formalin (1:10 ratio of tissue to formalin)

7. consider saving a frozen section or submit for cultures

8. sample before therapy (or with appropriate withdrawal period)

clinical presentation of perivascular dermatitis

• erythema & edema

• most common → all inflammation starts perivascularly

• least diagnostic

what is hyperkeratosis?

• excess of surface layer (stratum corneum) of the epidermis

• primary only in congenital ichthyosis

• common secondary finding in many diseases

• increased rate of keratinocyte proliferation OR delayed shedding of keratin

causes of hyperkeratosis (i.e., scale & crust)

• focal: skin reaction to any inflammation (common)

  • bacteria, fungi, yeasts, ectoparasites

• widespread: underlying metabolic disorders (uncommon/rare)

  • superficial necrolytic dermatitis

  • zinc-responsive dermatosis

clinical presentation/distribution of dermatophilosis (“rain scald”)

• crusts, scale, alopecia

• distribution of lesions: dorsum + lower limbs

dermatophilosis infiltrate & epidermal changes

• distribution of infiltrate: superficial

• neutrophilic infiltrate (bacterial agent)

• epidermal changes: hyperkeratosis

dermatophilosis pathogenesis

trauma to the skin & prolonged wetting → zoospores enter via breaks in the skin surface → invasion with neutrophils → epidermal regeneration → cycle starts again → thick laminar & parakeratotic crusts = characteristic

clinical presentation/distribution of dermatophytosis (“ringworm”)

• crusts, scale, alopecia

• distribution of lesions: face

dermatophytosis infiltrate & epidermal changes

• distribution of infiltrate: superficial

• lymphocytic ± neutrophilic infiltrate (fungal agent)

• epidermal changes: hyperkeratosis

dermatophytosis pathogenesis

• breaks in stratum corneum facilitate invasion by the fungus → adhere to keratinocytes & migrate to follicular orifice

• dermatophytes produce keratinolytic enzymes that hydrolyze keratin and enable them to invade the hair shaft → invade to the keratogenous zone of the hair bulb

  • stop here as cannot survive in viable tissues

• as hair enters telogen, hair is sloughed and fungal growth stops

overall, self-limiting disease

which signalments are affected by zinc-responsive dermatosis?

• syndrome 1: siberian huskies & alaskan malamutes (+ other large breeds) — inherited

• syndrome 2: puppies of any breed with a relative deficiency in Zn — probably secondary to excessively high calcium and/or phytates in diet (compete with zinc)

clinical presentation/distribution of zinc-responsive dermatosis

• crusts, scale, alopecia

• distribution of lesions: face

zinc-responsive dermatosis infiltrate & epidermal changes

• distribution of infiltrate: superficial

• lymphocytic infiltrate

• epidermal changes: hyperkeratosis (parakeratosis)

clinical presentation/distribution of superficial necrolytic dermatitis

• crusts & ulcers

• distribution of lesions: face, feet ± mucocutaneous junctions

superficial necrolytic dermatitis infiltrate & epidermal changes

• distribution of infiltrate: superficial

• lymphocytic ± neutrophilic infiltrate

• epidermal changes: hyperkeratosis (parakeratosis), necrosis, basal hyperplasia

superficial necrolytic dermatitis pathogenesis

• related to hepatic dysfunction & derangement of glucose and amino acid metabolism

  • ↑ glucagon

  • ↓ amino acids → ↓ epidermal proteins → epidermal necrosis

  • abnormal zinc & fatty acid metabolism

• dogs: associated with glucagon-secreting pancreatic tumors, hyperglucagonemia, diabetes mellitus, & liver disease

rare manifestation of liver disease