1. NORMAL CORNEA HISTOLOGY

2. 1 2 3 1 4 5

3. 5 cells epithelium Stratified Non-keratinising Non-secretory
Bowmans microns thick

4. STROMA
keratocytes
ARTEFACTUAL CLEFTS

5. Descemet’s
Endothelial cells

6. CORNEAL REACTION PATTERNS

7. Atrophy and
Oedema

8. Epithelial hyperplasia

9. Bullous lifting

10. Excessive intraepithelial basement membrane

11. Band keratopathy
Dystrophic calcification
Epithelial
hyperplasia

12. Breaks in Bowman’s

13. Stromal thinning

14. MELT

16. Neutrophils in stroma.
Acute keratitis

17. Chronic inflammation-chronic keratitis
Blood vessels
Plasma cells

18. Foamy macrophages
lipid keratopathy

19. Infective agent-bacteria

20. protozoa

21. Dystrophic deposits

22. Dystrophic deposits

23. Dystrophic deposits

24. GUTTAE

25. Endothelial
Cell
Loss

26. Ruptured Descemet’s

27. Host-donor interface
scar

28. Corneal pathology

29. Case 1

30. Fig 6.49 Microbial keratitis

31. Acute
inflammation

33. Bacterial colonies-Gram + cocci

34. Diagnosis ?

35. 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

36. Case 2

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

38. Fig 6.51 Microbial keratitis

41. Gram + cocci without inflammation

42. 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.

43. CASE 3

44. Fig 6.52 Microbial keratitis

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

46. 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

47. CASE 4

48. Fig 6.55 Microbial keratitis

49. cyst
Trophozoite

50. DIAGNOSIS ?

51. 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

52. 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.

53. 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).

54. 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

55. CASE 5

56. Fig 4.14 Herpes simplex

57. Fig 4.19 Herpes simplex

59. Stromal thinning

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

61. Chronic inflammation
Scarring
vascularisation

62. Secondary lipid keratopathy
Cholesterol clefts=leaky vessels

63. DIAGNOSIS ?

64. Herpes simplex chronic DISCIFORM keratitis

65. 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.

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

67. 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.

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

69. CASE 6

70. Fig 6.32 Corneal ectasia

71. Fig 6.33 Corneal ectasia

72. Angulated Bowman’s breaks

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

75. DIAGNOSIS ?

76. 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.

77. Fig 6.35 Corneal ectasia

78. Ruptured Descemet’s-KC Hydrops-PAS stain

79. CASE 7

80. Fig 6.22 Stromal dystrophies

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

84. DIAGNOSIS ?

85. 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

86. CASE 8

87. Fig 6.20 Stromal dystrophies

88. 3

90. DIAGNOSIS ?

91. 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.

92. CASE 9

93. Fig 6.24 Stromal dystrophies

96. DIAGNOSIS?

97. 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

98. 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.

99. CASE 10

101. Epithelial bullous lifting.
Thinned epithelium over bulla
Epithelium loses polarity

102. Excessive intraepithelial basement membrane-indication of chronic corneal oedema

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

104. Patient had a cataract operation 1 year ago

105. DIAGNOSIS ?

106. Pseudoaphakic Bullous Keratopathy

107. CASE 11

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

111. 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.

112. CASE 12

113. Multilayered cells-retrocorneal surface
No previous surgery or trauma

114. Cytokeratin positive
Multilayered cells

115. DIAGNOSIS ?

116. 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)

117. Table 6.1 Inheritance of corneal dystrophies

118. CASE 13

119. Fig 6.65 Corneal thinning and melting disorders

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

122. DIAGNOSIS ?

123. 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.