ETIOLOGY, PATHOLOGY AND PATHOGENESIS OF CORNEAL ULCER

1. By
Dr . SAMARTH
MISHRA

2. WHAT IS CORNEAL ULCER???
Corneal ulcer may be defined as discontinuation in normal
epithelial surface of cornea a/w necrosis of the surrounding
corneal tissue.
Pathologically it is charecterised by oedema & cellular
infiltration.

4. CORNEAL ULCER (ULCERATIVE KERATITIS):
 DEPENDING ON LOCATION :
a)central corneal ulcer
b) peripheral corneal ulcer
 DEPENDING ON PURULENCE
a)purulent corneal ulcer or suppurative corneal ulcer (most bacterial &
fungal Corneal ulcer )
b)non-purulent corneal ulcers( viral, chlamydial & allergic Corneal ulcer)
 DEPENDING UPON ASSOCIATION WITH HYPOPYON:
a simple Corneal ulcer (without hypopyon)
b) hypopyon corneal ulcer

5. DEPENDING UPON DEPTH OF ULCER:
a)superficial Corneal ulcer
b)deep Corneal ulcer
c)corneal ulcer with impending perforation
d)perforated corneal ulcer
DEPENDING UPON SLOUGH FORMATION :
a)non-sloughing corneal ulcer
b)sloughing corneal ulcer

6. Staphylococcus aureus
Pseudomonas pyocyanea
Streptococcus pneumoniae
E.coli
Proteus
Klebsiella
N.gonorrhoea
N.meningitidis (can invade intact corneal epithelium)
C.diphtheriae

7. 4 stages: infiltration,active ulceration,regression,cicatrization.
 STAGE OF INFILTRATION
 STAGE OF ACTIVE ULCERATION
 STAGE OF REGRESSION
 STAGE OF CICATRIZATION

8. Damaged epitheliuminvasion by offending agents
Terminal course depends on virulence of agent,host defence mechanism
and treatment received.
Course of ulcer maybe:
a)become localized and heal
b)penetrate deep l/t perforation.
c)spread fast as sloughing corneal ulcer.
A]PATHOLOGY OF LOC ALIZED CORNEAL ULCER:
1. Stage of infiltration: PMN/lymphocytes into epithelium from peripheral
circulation.
Necrosis may occur.

9. 2.Stage of active ulceration: results from sloughing of epithelium and
bowmen’s memb. & necrosis
Ulcer wall project s(swelling of lamellae by imbibition of fluid & packing
by leucocytes).
ulcer floor shows grey infiltration & sloughing.
Hyperemia of circumcorneal vessels.
purulent exudates.
vascular congestion of iris ‘& ciliary body.
Iritis d/t absorption of toxins from ulcer.
Exudation into anterior chamber from vessels of iris & cilary body may
lead to formation of HYPOPYON(sterile,fluid)
Ulcer progress laterallydiffuse superficial ulceration.
Ulcer progress deep descemetocele/perforation.

10. 3.Stage of regression:
host defense mechanism (humoral /cellular & appropriate t/t )
Line of demarcation devp.( leucocytes neutralize & phagocytose the
offending org. ,debris)
Ulcer begins to heal & epithelium starts growing over the edges.
4.stage of cicatrization:
Healing continues.
Fibrous tissue laid down( corneal fibroblasts & endothelial cells)
Stroma thickens & pushes the epithelial surface anteriorly.
inolves epithelium only no scarring
 bowman’s memb.scar forms( nebula)
Macula & leucoma results after >1/3rd of corneal stroma.

14. B] PATHOLOGY OF PERFORATED CORNEAL ULCER:
ulceration deepens reaches descemet’s memb.descemetocele.
 straining,coughing etc l/t perforation.
After perforationaquaous leaks,IOP falls,iris-lens diaphragm moves
forward.
Small perforation,opposite to irispluggs & cicatrization proceeds.
Commonest end resultadherent leucoma.
C] PATHOLOGY OF SLOUGHING CORNEAL ULCER:
d/t highly virulent agent/low resistance.
Whole cornea sloughs,iris becomes inflammedexudates block pupil.
Exudates organize to form PSEUDOCORNEA.
This pseudocornea is weak & thin, so bulges forward along with plastered
iris tissue ectatic cicatrixANTERIOR STAPHYLOMA.

15. Perforated corneal ulcer

16. STAPH AUREUS: rapidly progressive.
moderate ant. Chamber reactn with endothelial
plaques/hypopyon.
round, oval,yellowish-white with dense infiltration & distinct
border.
stromal microabscess with an ill defined border may develop.
 NON-AUREUS STAPH. :cause oppertunistic infectn.
•  >85% of eyelid cultures from normal population are +ve for
non-aureus staph.
m/c isolated org. from bacterial keratitis.
severe ulcers with dense infiltration may occur if untreated

19. STREP. PNEUMONIAE/ PNEUMOCOCCUS:
after corneal trauma,dacryocystitis etc
acute,purulent,rapidly progressive with a deep stromal abscess.
ant. Chamber reactn is severe with marked hypopyon.
”hypopyon corneal ulcer” by pneumococcus.
”corneal ulcer with hypopyon”hypopyon d/t any other cause.
charecteristic feature of hypopyon corneal ulcer caused by
pneumococcus is called “ULCER SERPENS”.
NOCARDIA ASTEROIDES:
gram +ve,acid fast bacillus with branching filaments.
produces indolent ulcers after minor trauma particularly in
exposure to contaminated soil.
nocardia can survive in neutrophils & macrophages a/w production
of superoxide dismutase.

20. Pseudomonas: m/c gram –ve org isolated from severe keratitis.
a/w soft contact lens.
rapid progression,dense sromal infiltration.
marked suppuration,liquefactive necrosis & descemetocele
formation or corneal perforation are charecteristic.
Neisseria: invade intact epithelium.
l/t rapid perforation.
B.cereus: chr. By distinct stromal ring infiltrate remote from the site of
injury.
rapid progression to stromal abscess.
corneal perforation.

21.  Incidence has increased d/t injudicious use of antibiotics & steroids.
Antibiotics: Disturb the symbiosis b/w bacteria & fungi.
Steroids: make fungi facultative pathogens(actually symbiotic
saprophytes).
ETIOLOGY:
Filamentous fungi: Aspergillus(m/c), Fusarium, Alternaria,
Cephalosporium, Curvularia, Penicillium
YEASTS: Candida albicans, Cryptococcus
 MODE OF INFECTION:
A)Injury by vegetative material. E.g: leaf,thorn,crop etc.
(field workers affected )
B)Injury by animal tail

22. C) Secondary fungal ulcers: immunocompromised pts.
CHARECTERISTIC FEATURES:
a)dry looking,greyish white,rolled out margin
b)feathery finger like extension (in stroma underlying intact
epithelium).
c)sterile immune ring( of wesseley) i.e a yellow line of demarcation
seen d/t fungal Ag- host Ab reaction.
d) multiple,small,sattellite lesion seen.
e)non-sterile ,thick ,immobile,big hypopyon seen d/t fungal hyphae
invasion in contrast to bacterial hypopyon( sterile, mobile).
f)symptoms milder than the clinical signs.

23. fungal ulcer with deep stromal infiltration and sattellite lesions.

24. close up view of stromal infiltrations

25. Stromal infiltrations and sattellite lesions.

26. affect conjunctiva & cornea,so typical lesionkeratoconjunctivitis.
Etiological agents: HSV,HZV,Adenovirus etc
CLASSIFICATION OF HSV KERATITIS :
1)Infectious epithelial keratitis:
a) cornea vesicles
b) dendritic ulcer
c) geographical ulcer
d) marginal ulcer
2) neurotrophic keratopathy/ trophic ulcer/ metaherpetic
ulcer/indolent ulcer
3) stromal keratitis:
a)necrotizing stromal keratitis
b)immune stromal keratitis

27. 4) endothelitis:
a)disciform
b)diffuse
c)linear
The m/c recognized clinical manifestation of infectious epithelial
keratitis are dendritic & geographic ulcer.
small vesicles in epithelium (punctate epithelial keratopathy)
vesicles coalesce
dendritic ulcer
geographic ulcer

28. In immunocompromised arrested @ the vesicle stage.
vesicles may coalesce to form a raised dendritic lesion (displaces
fluorescin(-ve stain))
This raised lesion, which is clinically the precursor of dendritic ulcer in
immunocompetent host, may not progress to a dendritic ulcer in the
immunocompromised host & therefore may not be recognized as
infectious epithelial keratitis.
So, all pts with HSV corneal vesicles
should be recognized as having infectious keratitis & treated promptly.
 Hsv  two types. Hsv 1 (above waist), hsv 2 (below waist)
Hsv are epitheliotrophic,but may become neurotrophic.

30. Typical lesion of recurrent epithelial keratitis.
Irregular,branching,linear lesions with terminal bulbs & swollen
epithelial borders which contain live virus.
TRUE ULCER, as it extends through basement membrane.
Stains +ve for fluorescin along the length of lesion

32. swollen borders  actually raised (stain –ve with fluorescin).
Rose bengal stain which stains devitalised cells ,is typically taken up by
swollen epithelial cells at ulcer border.
After ulcer healsabnormal appearing epithelium (for several weeks)
HSV DENDRITIC EPITHELIOPATHY( dendritic in shape but not ulcerated,
represents ulcer healing epithelium)
D/D : a) varicella zoster pseudodendrites
b) recently healed epithelial defects
Diff. from HSV because,these are raised rather than ulcerated & do not
stain fluorescin.

33. When dendritic ulcer is no longer linear.
A widened dendritic ulcer.
TRUE ULCER
Has swollen border that contains live virus.
The scalloped or geographic borders are imp. to recognise to diff this
lesion from healing abrasions & neurotrophic keratopathy, which tend to
have smooth border.

35. EPIDEMIOLOGIC STUDY :
 wlhemus et al :
geographical ulcer 22% of all cases of infectious epithelial
keratitis.
 a/w with use of topical steroids.
Liesegang:
geographical ulcer 4% of inf ep keratis cases.
not a/w topical steroids use.

36. Another manifestation of hsv inf epi. keratitis.
Proximity to limbus a/w unique features.
Infiltrated quickly by WBCs from nearby blood vessels.
Typical presentation: anterior stromal infiltrate underlying the ulcer &
adjacent limbal injection.
Patient more symptomatic d/t intense inflammation.
D/D : staphylococcal marginal(catarrhal) disease.

37. HSV marginal ulcer staph. Marginal infiltrate
Etiology:  active HSV  immunologic response to staph Ag
Epithelial always absent(if present,late)
defect
Neovascn often never
Progression centrally circumferentially
Blepharitis unrelated usually
Location any meridian typically @2,4,8,10 “o’’clock
position

38. 4 recognized sequelae:
a) Complete resolution.
b) dentritic epitheliopathy
c) stromal scarring,
“ghost figures” or “footprints” of HSV.
a) subsequent stromal inflammation
(in 25%)

39. who have had infec.epi.keratitis  at risk.
Arises from impaired corneal innervation in combination with
decreased tear secretion.
Oval,smooth border ( in contrast to geograph. ulcer)
Stroma at ulcer bed develops typically a grayish white opacification.
Complications:
stromal scarring,neovascularisation,necrosis,perforation,secondary
bacterial infection.
Irregularity of corneal surface  lack of normal corneal lusture
punctate epithelial erosion persistent epithelial defect stromal
ulceration.

41. d/t reactivation of latent virus.
A)MICRODENDRITIC EPITHELIAL ULCER: peripheral & stellate rather
than dendritic in shape.
in contrast to HSV dendritis,these have tapered ends which lacks bulbs.
B)NEUROPARALYTIC ULCER: occur as a sequelae of acute infection &
gasserion ganglion destruction.

42. Ulcus rodens: term by Mc kenzie:1854
Idiopathic corneal ulcer.
Severe,inflammatory,painful,peripheral ulcerative keratitis.
Diagnosis of exclusion
ETIOLOGY:
A) idiopathic degenerative condition.
B) ischaemic necrosis resulting from vasculitis of limbal vessels.
C) d/t enzyme collagenase & proteoglyconase produced from
conjunctiva.
D) autoimmune d/s: Ab against corneal epithelium present in serum.
E) a/w HCV,helminthiasis ( molecular mimicry to cross reacting
epitopes of cornea, Ag-Ab reactn to helminth @ peripheral cornea
provokes inflammation & ulceration)

45. Clinical varieties of mooren’s ulcer:
A)BENIGN FORM: -unilateral
-slow progress
-elderly
-mild to mod. Symptoms
-respond well to t/t
B) VIRULENT FORM: -bilateral
-rapidly progressive
-younger pt
-scleral inolvement(high)
-a/w pain
-doesnot respond to t/t

46. FEATURES:
 starts @ corneal margin as gray infiltrates.
 coalesce to form shallow furrow over whole cornea.
 peripheral central progression
 ulcer undermines epithelium & superficial stromal lamellae & forms
whitish overlying edge
 base--> becomes vascularised
RARELY perforates,sclera uninvolved.
D/D:
Terrien’s marginal degeneration.(non inflammatory,thinning of
cornea’epithelium intact)
Pellucid marginal degeneration
Senile furrow degeneration.
Staph. Marginal keratitis.

47. a) Tiny tears: may also cause ulcers. Can form from direct
trauma,scratches,or particles such as sand,glass,metal. Such injury
make it easier for bacteria to invade & cause a serious ulcer.
b) DRY EYES :( SICCA) e.g sjogren’s syndrome
c) CHEMICAL BURNS: alkali /acidic burn
d) THERMAL /RADIATION BURNS
e) D/T EXPOSURE KERATITIS: lagophthalmos,lid abnormalities,facial
palsy,proptosis,thyroid d/s.
f) ATOPIC: d/t follicles / pappila
g) VITAMIN –A DEFICIENCY: dietary deprivation,secondary d/s that
affect fat absorption & storage like celiac d/s and cystic fibrosis.
h) BASEMENT MEMBRANE ABNORMALITIES: microcysts,evidence of
map-dot-finger or anterior stromal dystrophies
i) IMMUNE RELATED D/S:wegener’s granulomatosis,RA,other collagen
vascular d/s.