NORMAL CORNEA HISTOLOGY

1 2 3 1 4 5

5 cells epithelium Stratified Non-keratinising Non-secretory Bowmans-12 microns thick

STROMA keratocytes ARTEFACTUAL CLEFTS

Descemet’s Endothelial cells

CORNEAL REACTION PATTERNS

Atrophy and Oedema

Epithelial hyperplasia

Bullous lifting

Excessive intraepithelial basement membrane

Band keratopathy Dystrophic calcification Epithelial hyperplasia

Breaks in Bowman’s

Stromal thinning

MELT

Neutrophils in stroma. Acute keratitis

Chronic inflammation-chronic keratitis Blood vessels Plasma cells

Foamy macrophages lipid keratopathy

Infective agent-bacteria

protozoa

Dystrophic deposits

Dystrophic deposits

Dystrophic deposits

GUTTAE

Endothelial Cell Loss

Ruptured Descemet’s

Host-donor interface scar

Corneal pathology

Case 1

Fig 6.49 Microbial keratitis

Acute inflammation

Bacterial colonies-Gram + cocci

Diagnosis ?

Bacterial acute keratitis Predisposing factors: adnexal infection, entropion, exposure, dry eyes, contact lens, bullous keratopathy, trauma etc G + cocci-s aureus, S. epidermidis, S pneumoniae, S pyogenes, S viridans G – cocci-N gonorrhoeae, M meningitidis G + bacilli-C Diphtheriae, diphtheroids G- bacilli- Moraxella, Acinebacter, E-coli, K pneumoniae, proteus, psuedomanas G+ filamentous bacteria

Case 2

History Topical steroids after PK. Drop in vision……………….

Fig 6.51 Microbial keratitis

Gram + cocci without inflammation

INFECTIOUS CRYSTALLINE KERATOPATHY Elaboration of biofilm by bacteria-protects them from immune system-therefore no inflammation, but also means poor response to antibiotics. Commonest bugs-strep viridans and staph epidermidis Aso can be caused by fungi and protozoa.

CASE 3

Fig 6.52 Microbial keratitis

Fungal hypha-filamentous branching septate spores Fungal keratitis Penetrate Descemet’s without any problem Fig 6.54 Microbial keratitis

Common causes of fungal keratitis Trauma with organic material Humid warm conditions Exogenous or endogenous(immunocompromised) Aspergillus Candida Fusarium Sabaraud’s or equivalent medium for culturing Immunocompromised, steroids

CASE 4

Fig 6.55 Microbial keratitis

cyst Trophozoite

DIAGNOSIS ?

AMOEBIC KERATITIS Amoebic keratitis-cysts and trophozoites-little inflammation Loss of keratocytes PERIODIC ACID SCHIFF (PAS) + GIEMSA + Can use immunohistochemistry Differential: Acanthamoeba, Hartmannella Vahlkampfia, Naegleria

Amoeba 10-50 microns Replicate by binary fission Exist as trophozoites and cysts Trophozoites are active, infectious and feed by phagocytosing. Cysts from under hostile conditions and have a double layer.

Corneal epithelial trauma predisposes to infection Trophizoites attach to damaged epithelium, multiply and cause cytolysis. Migrate to stroma-elicit inflammation. Trigger keratoneuritis (inflammation follows corneal nerves).

Diagnosis Culture-corneal scrapes, biopsies, keratoplasty specimens. Contact lens, cases and solutions. Non-nutrient agar inoculated and seeded with E-coli-food source for the amoeba. Wet-mount examination of contact lens solution. Can use PAS, calcofluor white, silver stains, immunohistochemistry, EM

CASE 5

Fig 4.14 Herpes simplex

Fig 4.19 Herpes simplex

Stromal thinning

chronic Inflammation With giant cells. Bowman’s loss due to ulceration

Chronic inflammation Scarring vascularisation

Secondary lipid keratopathy Cholesterol clefts=leaky vessels

DIAGNOSIS ?

Herpes simplex chronic DISCIFORM keratitis

HSV DNA VIRUS Type 1 usually, occasionally type 2 Diagnosis-Electron microscopy of affected cells, aspirate from blister, viral cultures, staining paraffin sections with monoclonal antibodies to HSV, PCR on corneal biopsy.

HSV Primary infection-self-limiting periocular vesicles and crusting, follicular and papillary blepharconjunctivitis, punctate epithelial keratopathy. Virus lives in trigeminal ganglion-reactivation Dendritic ulcer

HSV Geographic ulcer Trophic keratitis Stromal infiltrative keratitis Disciform keratitis-type 4 hypersensitivity reaction-immune response to parasitized corneal stromal keratocytes-sets up vicious circle of inflammation-scarring-inflammation.

Complications Uveitis Glaucoma Episcleritis Scleritis Secondary bacteria infection Perforation Recurrence in corneal graft.

CASE 6

Fig 6.32 Corneal ectasia

Fig 6.33 Corneal ectasia

Angulated Bowman’s breaks

Perl’s stain shows intraepithelial iron deposits-Fleischer’s ring

DIAGNOSIS ?

KERATOCONUS Associations: Atopy Down’s syndrome Turner’s syndrome Marfan’s syndrome Ehlors-Danlos syndrome Aniridia Retinitis pigmentosa Ectopia Lentis Microcornea Non-specific systemic collagen abnormalities Chronic eye rubbing. Cause of prominent corneal nerves.

Fig 6.35 Corneal ectasia

Ruptured Descemet’s-KC Hydrops-PAS stain

CASE 7

Fig 6.22 Stromal dystrophies

Masson’s trichrome stain-deep pink, non-birefringent hyaline bodies in anterior stroma

DIAGNOSIS ?

GRANULAR DYSTROPHY Masson’s trichrome positive hyaline deposits. Mutations in BIG H3 /TGF-B1 gene-encodes keratoepithelin protein. Exclude Avellino dystrophy (combined Lattice and Granular dystrophy)-by doing a Congo Red. Can recur in corneal graft-due to migration of host keratocytes into donor stroma, with elaboration of abnormal keratoepithelin

CASE 8

Fig 6.20 Stromal dystrophies

3

DIAGNOSIS ?

LATTICE DYSTROPHY Multiple, discrete, spindle shaped amyloid deposits in superficial, mid and deep stroma. Apple green birefringence of Congo red positive amyloid deposits when cross polarised Type 1,2 and 3 Mutations in BIG H3 / TGF-B1 gene Exclude Avellino by doing Masson’s trichrome stain Other amyloid stains: Thioflavine T, Immunohistochemisty using antibodies to amyloid, Sirius Red. Recurs in graft because of migration of host keratocytes into donor stroma-elaboration of amyloid in donor graft.

CASE 9

Fig 6.24 Stromal dystrophies

DIAGNOSIS?

MACULAR DYSTROPHY Alcian blue positive, deposits. Present in all layers except epithelium. Deposits in keratocytes and between collagen lamellae Material is mucopolysaccharide. Can recur in graft

Summary of corneal stains Lattice dystrophy-amyloid-use Congo Red / Sirius red and view under cross polarised light-apple green birefringence Granular dystrophy-hyaline material-use Masson’s trichrome Avellino dystrophy-use both Congo Red and Masson’s trichrome Macular dystrophy-mucopolysaccharide-use Alcian Blue or Hale’s colloidal iron stains or PAS Iron-use Perl’s / Prussian Blue stain- BLUE colour Calcium in band keratopathy- Alizarin Red- Red colour Basemant membranes, Descemet’s, Fungi- PAS stain- great for guttata. Bugs-Gram (bacteria), PAS (Fungi and Amoeba), Grocott silver stains for fungi.

CASE 10

Epithelial bullous lifting. Thinned epithelium over bulla Epithelium loses polarity

Excessive intraepithelial basement membrane-indication of chronic corneal oedema

Endothelial cell loss Thickened Descemet’s-implies chronic endothelial cell loss No obvious guttata

Patient had a cataract operation 1 year ago

DIAGNOSIS ?

Pseudoaphakic Bullous Keratopathy

CASE 11

HISTORY 65 YEAR OLD MALE Recent cataract operation Early corneal decompensation. No better PK

Fuch’s Endothelial Dystrophy Axial diffuse guttae or excrescences Endothelial cell loss Thickened-multilayered Descemet’s Burried guttata Can get non-guttate forms, with just very thickened Descemet’s. With chronicity, fibrous degenerative pannus formation under epithelium.

CASE 12

Multilayered cells-retrocorneal surface No previous surgery or trauma

Cytokeratin positive Multilayered cells

DIAGNOSIS ?

POSTERIOR POLYMORPHOUS DYSTROPHY Autosomal dominant, but can be recessive Circumscribed or total opacities in childhood Cells assume epithelial characteristics (stain for cytokeratin 7) Histological differential diagnosis-epithelial downgrowth, ICE syndrome, CHED (these conditions express cytokeratins)

Table 6.1 Inheritance of corneal dystrophies

CASE 13

Fig 6.65 Corneal thinning and melting disorders

Shelved / sloping stroma Pauciinflammatory perforation Ruptured and recoiled Descemet’s Shelved / sloping stroma Pauciinflammatory perforation

DIAGNOSIS ?

Rheumatoid Corneal melt Rheumatoid arthritis Systemic lupus erythematosis Scleroderma Churg-Strauss. Wegener’s granulomatosis Polyarteritis nodosa Giant cell arteritis Relapsing polychondritis Rosacea Dysentery Leukaemias Above are associated with peripheral corneal ulcers and melt Other causes of peripheral corneal ulceration: Marginal, Mooren’s Terrien’s. Imbalance between matrix metalloproteinases and tissue inhibitors of metalloproteinases Enzymes released by keratocytes and epithelial cells to cause dissolution of stromal collagen.