ETIOLOGY, PATHOLOGY AND PATHOGENESIS OF CORNEAL ULCER
Dr . SAMARTH
WHAT IS CORNEAL ULCER???
Corneal ulcer may be defined as discontinuation in normal
epithelial surface of cornea a/w necrosis of the surrounding
Pathologically it is charecterised by oedema & cellular
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
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
4 stages: infiltration,active ulceration,regression,cicatrization.
STAGE OF INFILTRATION
STAGE OF ACTIVE ULCERATION
STAGE OF REGRESSION
STAGE OF CICATRIZATION
Damaged epitheliuminvasion 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
Necrosis may occur.
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
ulcer floor shows grey infiltration & sloughing.
Hyperemia of circumcorneal vessels.
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 laterallydiffuse superficial ulceration.
Ulcer progress deep descemetocele/perforation.
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:
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.
B] PATHOLOGY OF PERFORATED CORNEAL ULCER:
ulceration deepens reaches descemet’s memb.descemetocele.
straining,coughing etc l/t perforation.
After perforationaquaous leaks,IOP falls,iris-lens diaphragm moves
Small perforation,opposite to irispluggs & cicatrization proceeds.
Commonest end resultadherent leucoma.
C] PATHOLOGY OF SLOUGHING CORNEAL ULCER:
d/t highly virulent agent/low resistance.
Whole cornea sloughs,iris becomes inflammedexudates block pupil.
Exudates organize to form PSEUDOCORNEA.
This pseudocornea is weak & thin, so bulges forward along with plastered
iris tissue ectatic cicatrixANTERIOR STAPHYLOMA.
STAPH AUREUS: rapidly progressive.
moderate ant. Chamber reactn with endothelial
round, oval,yellowish-white with dense infiltration & distinct
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
m/c isolated org. from bacterial keratitis.
severe ulcers with dense infiltration may occur if untreated
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”.
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.
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
rapid progression to stromal abscess.
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
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
C) Secondary fungal ulcers: immunocompromised pts.
a)dry looking,greyish white,rolled out margin
b)feathery finger like extension (in stroma underlying intact
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.
fungal ulcer with deep stromal infiltration and sattellite lesions.
The m/c recognized clinical manifestation of infectious epithelial
keratitis are dendritic & geographic ulcer.
small vesicles in epithelium (punctate epithelial keratopathy)
In immunocompromised arrested @ the vesicle stage.
vesicles may coalesce to form a raised dendritic lesion (displaces
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.
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
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 healsabnormal 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
When dendritic ulcer is no longer linear.
A widened dendritic 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.
EPIDEMIOLOGIC STUDY :
wlhemus et al :
geographical ulcer 22% of all cases of infectious epithelial
a/w with use of topical steroids.
geographical ulcer 4% of inf ep keratis cases.
not a/w topical steroids use.
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.
HSV marginal ulcer staph. Marginal infiltrate
Etiology: active HSV immunologic response to staph Ag
Epithelial always absent(if present,late)
Neovascn often never
Progression centrally circumferentially
Blepharitis unrelated usually
Location any meridian typically @2,4,8,10 “o’’clock
4 recognized sequelae:
a) Complete resolution.
b) dentritic epitheliopathy
c) stromal scarring,
“ghost figures” or “footprints” of HSV.
a) subsequent stromal inflammation
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.
Irregularity of corneal surface lack of normal corneal lusture
punctate epithelial erosion persistent epithelial defect stromal
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.
Ulcus rodens: term by Mc kenzie:1854
Idiopathic corneal ulcer.
Severe,inflammatory,painful,peripheral ulcerative keratitis.
Diagnosis of exclusion
A) idiopathic degenerative condition.
B) ischaemic necrosis resulting from vasculitis of limbal vessels.
C) d/t enzyme collagenase & proteoglyconase produced from
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)
Clinical varieties of mooren’s ulcer:
A)BENIGN FORM: -unilateral
-mild to mod. Symptoms
-respond well to t/t
B) VIRULENT FORM: -bilateral
-doesnot respond to t/t
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.
Terrien’s marginal degeneration.(non inflammatory,thinning of
Pellucid marginal degeneration
Senile furrow degeneration.
Staph. Marginal keratitis.
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
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