Corneal Ulcer

Corneal ulcer may be defined as discontinuation in
normal epithelial surface of cornea associated with
necrosis of the surrounding corneal tissue.
Pathologically it is characterised by oedema and
cellular infiltration. Common types of corneal ulcers
are described below.
INFECTIVE KERATITIS
BACTERIAL CORNEAL ULCER
Being the most anterior part of eyeball, the cornea is
exposed to atmosphere and hence prone to get
infected easily. At the same time cornea is protected
from the day-to-day minor infections by the normal
defence mechanisms present in tears in the form of
lysozyme, betalysin, and other protective proteins.
Therefore, infective corneal ulcer may develop when:
either the local ocular defence mechanism is
jeopardised, or
there is some local ocular predisposing disease,
or host's immunity is compromised, or
the causative organism is very virulent.
Etiology
There are two main factors in the production of
purulent corneal ulcer:
Damage to corneal epithelium; and
Infection of the eroded area.
However, following three pathogens can invade
the intact corneal epithelium and produce ulceration:
Neisseria gonorrhoeae, Corynebacterium
diphtheriae and Neisseria meningitidis.
1. Corneal epithelial damage. It is a prerequisite for
most of the infecting organisms to produce corneal
ulceration. It may occur in following conditions:
i. Corneal abrasion due to small foreign body,
misdirected cilia, concretions and trivial trauma
in contact lens wearers or otherwise.
ii. Epithelial drying as in xerosis and exposure
keratitis.
iii. Necrosis of epithelium as in keratomalacia.
iv. Desquamation of epithelial cells as a result of
corneal oedema as in bullous keratopathy.
v. Epithelial damage due to trophic changes as
in neuroparalytic keratitis.
2. Source of infection include:
i. Exogenous infection. Most of the times corneal
infection arises from exogenous source like
conjunctival sac, lacrimal sac (dacryocystitis),
infected foreign bodies, infected vegetative
material and water-borne or air-borne infections.
ii. From the ocular tissue. Owing to direct

anatomical continuity, diseases of the
conjunctiva readily spread to corneal epithelium,
those of sclera to stroma, and of the uveal tract
to the endothelium of cornea.
iii. Endogenous infection. Owing to avascular
nature of the cornea, endogenous infections
are of rare occurrence.
3. Causative organisms. Common bacteria associated
with corneal ulceration are: Staphylococcus aureus,
Pseudomonas pyocyanea, Streptococcus
pneumoniae, E. coli, Proteus, Klebsiella, N.
gonorrhoea, N. meningitidis and C. diphtheriae.
Pathogenesis and pathology of corneal ulcer
Once the damaged corneal epithelium is invaded by
the offending agents the sequence of pathological
changes which occur during development of corneal
ulcer can be described under four stages, viz.,
infiltration, active ulceration, regression and
cicatrization. The terminal course of corneal ulcer
depends upon the virulence of infecting agent, host
defence mechanism and the treatment received.
Depending upon the prevalent circumstances the
course of corneal ulcer may take one of the three
forms:
(A) Ulcer may become localised and heal;
(B) Penetrate deep leading to corneal perforation;
or
(C) Spread fast in the whole cornea as sloughing
corneal ulcer.
The salient pathological features of these are as
under:
[A] Pathology of localised corneal ulcer
1. Stage of progressive infiltration (Fig. 5.2A). It is
characterised by the infiltration of polymorphonuclear
and/or lymphocytes into the epithelium
from the peripheral circulation supplemented by
similar cells from the underlying stroma if this tissue
is also affected. Subsequently necrosis of the
involved tissue may occur, depending upon the
virulence of offending agent and the strength of host
defence mechanism.
2. Stage of active ulceration (Fig. 5.2B). Active
ulceration results from necrosis and sloughing of the
epithelium, Bowman's membrane and the involved
stroma. The walls of the active ulcer project owing to
swelling of the lamellae by the imbibition of fluid and
the packing of masses of leucocytes between them.
This zone of infiltration may extend to a considerable
distance both around and beneath the ulcer. At this
stage, sides and floor of the ulcer may show grey
infiltration and sloughing.
During this stage of active ulceration, there occurs
hyperaemia of circumcorneal network of vessels which
results into accumulation of purulent exudates on the
cornea. There also occurs vascular congestion of the
iris and ciliary body and some degree of iritis due to
absorption of toxins from the ulcer. Exudation into
the anterior chamber from the vessels of iris and ciliary
body may lead to formation of hypopyon.

Ulceration may further progress by lateral extension
resulting in diffuse superficial ulceration or it may
progress by deeper penetration of the infection
leading to Descemetocele formation and possible
corneal perforation. When the offending organism is
highly virulent and/or host defence mechanism is
jeopardised there occurs deeper penetration during
stage of active ulceration.
3. Stage of regression (Fig. 5.2C). Regression is
induced by the natural host defence mechanisms
(humoral antibody production and cellular immune
defences) and the treatment which augments the
normal host response. A line of demarcation develops
around the ulcer, which consists of leucocytes that
neutralize and eventually phagocytose the offending
organisms and necrotic cellular debris. The digestion
of necrotic material may result in initial enlargement
of the ulcer. This process may be accompanied by
superficial vascularization that increases the humoral
and cellular immune response. The ulcer now begins
to heal and epithelium starts growing over the edges.
4. Stage of cicatrization (Fig. 5.2D). In this stage
healing continues by progressive epithelization which
forms a permanent covering. Beneath the epithelium,
fibrous tissue is laid down partly by the corneal
fibroblasts and partly by the endothelial cells of the
new vessels. The stroma thus thickens and fills in
under the epithelium, pushing the epithelial surface
anteriorly.
The degree of scarring from healing varies. If the
ulcer is very superficial and involves the epithelium
only, it heals without leaving any opacity behind.
When ulcer involves Bowman's membrane and few
superficial stromal lamellae, the resultant scar is called
a 'nebula'. Macula and leucoma result after healing of
ulcers involving up to one-third and more than that
of corneal stroma, respectively.
[B] Pathology of perforated corneal ulcer
Perforation of corneal ulcer occurs when the ulcerative
process deepens and reaches up to Descemet's
membrane. This membrane is tough and bulges out
as Descemetocele (Fig. 5.3). At this stage, any
exertion on the part of patient, such as coughing,
sneezing, straining for stool etc. will perforate the
corneal ulcer. Immediately after perforation, the
aqueous escapes, intraocular pressure falls and the

iris-lens diaphragm moves forward. The effects of
perforation depend upon the position and size of
perforation. When the perforation is small and
opposite to iris tissue, it is usually plugged and healing
by cicatrization proceeds rapidly (Fig. 5.4). Adherent
leucoma is the commonest end result after such a
catastrophe.
[C] Pathology of sloughing corneal ulcer and
formation of anterior staphyloma
When the infecting agent is highly virulent and/or
body resistance is very low, the whole cornea sloughs
with the exception of a narrow rim at the margin and
total prolapse of iris occurs. The iris becomes inflamed

and exudates block the pupil and cover the iris
surface; thus a false cornea is formed. Ultimately
these exudates organize and form a thin fibrous layer
over which the conjunctival or corneal epithelium
rapidly grows and thus a pseudocornea is formed.
Since the pseudocornea is thin and cannot withstand
the intraocular pressure, so it usually bulges forward
along with the plastered iris tissue. This ectatic cicatrix
is called anterior staphyloma which, depending upon
its extent, may be either partial or total. The bands of
scar tissue on the staphyloma vary in breadth and
thickness, producing a lobulated surface often
blackened with iris tissue which resembles a bunch
of black grapes (hence the name staphyloma).
Clinical picture
In bacterial infections the outcome depends upon
the virulence of organism, its toxins and enzymes,
and the response of host tissue.
Broadly bacterial corneal ulcers may manifest as:
i. Purulent corneal ulcer without hypopyon; or
ii. Hypopyon corneal ulcer.
In general, following symptoms and signs may be
present :
Symptoms
1. Pain and foreign body sensation occurs due to
mechanical effects of lids and chemical effects of
toxins on the exposed nerve endings.
2. Watering from the eye occurs due to reflex
hyperlacrimation.
3. Photophobia, i.e., intolerance to light results from
stimulation of nerve endings.
4. Blurred vision results from corneal haze.
5. Redness of eyes occurs due to congestion of
circumcorneal vessels.
Signs
1. Lids are swollen.
2. Marked blepharospasm may be there.
3. Conjunctiva is chemosed and shows conjunctival
hyperaemia and ciliary congestion.
4. Corneal ulcer usually starts as an epithelial defect
associated with greyish-white circumscribed
infiltrate (seen in early stage). Soon the epithelial
defect and infiltrate enlarges and stromal oedema
develops. A well established bacterial ulcer is
characterized by (Fig. 5.5):
Yellowish-white area of ulcer which may be oval
or irregular in shape.

Margins of the ulcer are swollen and over hanging.
Floor of the ulcer is covered by necrotic material.
Stromal oedema is present surrounding the ulcer
area.
Characteristic features produced by some of the
causative bacteria are as follows:
Staphylococal aureus and streptococcus
pneumoniae usually produce an oval, yellowish
white densely opaque ulcer which is surrounded
by relatively clear cornea.
Pseudomonas species usually produce an irregular
sharp ulcer with thick greenish mucopurulent
exudate, diffuse liquefactive necrosis and
semiopaque (ground glass) surrounding cornea.
Such ulcers spread very rapidly and may even
perforate within 48 to 72 hours.
Enterobacteriae (E. coli, Proteus sp., and Klebsiella
sp.) usually produce a shallow ulcer with
greyish white pleomorphic suppuration and
diffuse stromal opalescence. The endotoxins
produced by these Gram –ve bacilli may produce
ring-shaped corneal infilterate.
5. Anterior chamber may or may not show pus
(hypopyon). In bacterial corneal ulcers the
hypopyon remains sterile so long as the
Descemet's membrane is intact.
6. Iris may be slightly muddy in colour.
7. Pupil may be small due to associated toxin–
induced iritis.
8. Intraocular pressure may some times be raised
(inflammatory glaucoma).

Complications of corneal ulcer
1. Toxic iridocyclitis. It is usually associated with
cases of purulent corneal ulcer due to absorption of
toxins in the anterior chamber.
2. Secondary glaucoma. It occurs due to fibrinous
exudates blocking the angle of anterior chamber
(inflammatory glaucoma).
3. Descemetocele. Some ulcers caused by virulent
organisms extend rapidly up to Descemet's membrane,
which gives a great resistance, but due to the effect
of intraocular pressure it herniates as a transparent
vesicle called the descemetocele or keratocele
(Fig.5.3). This is a sign of impending perforation and
is usually associated with severe pain.
4. Perforation of corneal ulcer. Sudden strain due
to cough, sneeze or spasm of orbicularis muscle may
convert impending perforation into actual perforation
(Fig. 5.4). Following perforation, immediately pain is
decreased and the patient feels some hot fluid
(aqueous) coming out of eyes.
Sequelae of corneal perforation include :
i. Prolapse of iris. It occurs immediately following
perforation in a bid to plug it.
ii. Subluxation or anterior dislocation of lens
may occur due to sudden stretching and rupture
of zonules.
iii. Anterior capsular cataract. It is formed when
the lens comes in contact with the ulcer following
a perforation in the pupillary area.
iv. Corneal fistula. It is formed when the perforation
in the pupillary area is not plugged by iris and
is lined by epithelium which gives way
repeatedly. There occurs continuous leak of
aqueous through the fistula.
v. Purulent uveitis, endophthalmitis or even
panophthalmitis may develop due to spread of
intraocular infection.
vi. Intraocular haemorrhage in the form of either
vitreous haemorrhage or expulsive choroidal
haemorrhage may occur in some patients due to
sudden lowering of intraocular pressure.
5. Corneal scarring. It is the usual end result of
healed corneal ulcer. Corneal scarring leads to
permanent visual impairment ranging from slight
blurring to total blindness. Depending upon the
clinical course of ulcer, corneal scar noted may be
nebula, macula, leucoma, ectatic cicatrix or kerectasia,
adherent leucoma or anterior staphyloma (for details
see pages 122).
Management of a case of corneal ulcer
[A] Clinical evaluation
Each case with corneal ulcer should be subjected to:
1. Thorough history taking to elicit mode of onset,
duration of disease and severity of symptoms.

2. General physical examination, especially for
built, nourishment, anaemia and any immunocompromising
disease.
3. Ocular examination should include:
i. Diffuse light examination for gross lesions of
the lids, conjunctiva and cornea including
testing for sensations.
ii. Regurgitation test and syringing to rule out
lacrimal sac infection.
iii. Biomicroscopic examination after staining of
corneal ulcer with 2 per cent freshlyprepared
aqueous solution of fluorescein dye or sterilised
fluorescein impregnated filter paper strip to note
site, size, shape, depth, margin, floor and
vascularization of corneal ulcer. On
biomicroscopy also note presence of keratic
precipitates at the back of cornea, depth and
contents of anterior chamber, colour and pattern
of iris and condition of crystalline lens.
[B] Laboratory investigations
(a) Routine laboratory investigations such as
haemoglobin, TLC, DLC, ESR, blood sugar, complete
urine and stool examination should be carried out in
each case.
(b) Microbiological investigations. These studies
are essential to identify causative organism, confirm
the diagnosis and guide the treatment to be instituted.
Material for such investigations is obtained by
scraping the base and margins of the corneal ulcer
(under local anaesthesia, using 2 percent xylocaine)
with the help of a modified Kimura spatula or by
simply using the bent tip of a 20 gauge hypodermic
needle. The material obtained is used for the following
investigations:
i. Gram and Giemsa stained smears for possible
identification of infecting organisms.
ii. 10 per cent KOH wet preparation for
identification of fungal hyphae.
iii. Calcofluor white (CFW) stain preparation is
viewed under fluorescence microscope for
fungal filaments, the walls of which appear
bright apple green.
iv. Culture on blood agar medium for aerobic
organisms.
v. Culture on Sabouraud's dextrose agar medium
for fungi.
[C] Treatment
I. Treatment of uncomplicated corneal ulcer
Bacterial corneal ulcer is a vision threatening
condition and demands urgent treatment by
identification and eradication of causative bacteria.
Treatment of corneal ulcer can be discussed under
three headings:
1. Specific treatment for the cause.
2. Non-specific supportive therapy.
3. Physical and general measures.
1. The specific treatment
(a) Topical antibiotics. Initial therapy (before
results of culture and sensitivity are available)
should be with combination therapy to cover
both gram-negative and gram-positive
organisms.
It is preferable to start fortified gentamycin (14
mg/ml) or fortified tobramycin (14mg/ml)
eyedrops along with fortified cephazoline (50mg/
ml), every ½ to one hour for first few days and
then reduced to 2 hourly. Once the favourable
response is obtained, the fortified drops can be
substituted by more diluted commercially
available eye-drops, e.g. :
Ciprofloxacin (0.3%) eye drops, or
Ofloxacin (0.3%) eye drops, or
Gatifloxacin (0.3%) eye drops.
(b) Systemic antibiotics are usually not required.
However, a cephalosporine and an aminoglycoside
or oral ciprofloxacin (750 mg twice daily)
may be given in fulminating cases with
perforation and when sclera is also involved.
2. Non-specific treatment
(a) Cycloplegic drugs. Preferably 1 percent atropine
eye ointment or drops should be used to reduce
pain from ciliary spasm and to prevent the
formation of posterior synechiae from secondary
iridocyclitis. Atropine also increases the blood
supply to anterior uvea by relieving pressure
on the anterior ciliary arteries and so brings
more antibodies in the aqueous humour. It also
reduces exudation by decreasing hyperaemia
and vascular permeability. Other cycloplegic
which can be used is 2 per cent homatropine
eye drops.

(b) Systemic analgesics and anti-inflammatory
drugs such as paracetamol and ibuprofen relieve
the pain and decrease oedema.
(c) Vitamins (A, B-complex and C) help in early
healing of ulcer.
3. Physical and general measures
(a) Hot fomentation. Local application of heat
(preferably dry) gives comfort, reduces pain
and causes vasodilatation.
(b) Dark goggles may be used to prevent
photophobia.
(c) Rest, good diet and fresh air may have a
soothing effect.
II. Treatment of non-healing corneal ulcer
If the ulcer progresses despite the above therapy the
following additional measures should be taken:
1. Removal of any known cause of non-healing
ulcer. A thorough search for any already missed
cause not allowing healing should be made and
when found, such factors should be eliminated.
Common causes of non-healing ulcers are as
under:
i. Local causes. Associated raised intraocular
pressure, concretions, misdirected cilia,
impacted foreign body, dacryocystitis,
inadequate therapy, wrong diagnosis,
lagophthalmos and excessive vascularization
of ulcer.
ii. Systemic causes: Diabetes mellitus, severe
anaemia, malnutrition, chronic debilitating
diseases and patients on systemic steroids.
2. Mechanical debridement of ulcer to remove
necrosed material by scraping floor of the ulcer
with a spatula under local anaesthesia may hasten
the healing.
3. Cauterisation of the ulcer may also be considered
in non-responding cases. Cauterisation may be
performed with pure carbolic acid or 10-20 per
cent trichloracetic acid.
4. Bandage soft contact lens may also help in
healing.
5. Peritomy, i.e., severing of perilimbal conjunctival
vessels may be performed when excessive corneal
vascularization is hindering healing.
III. Treatment of impending perforation
When ulcer progresses and perforation seems
imminent, the following additional measures may help
to prevent perforation and its complications:
1. No strain. The patient should be advised to
avoid sneezing, coughing and straining during
stool etc. He should be advised strict bed rest.
2. Pressure bandage should be applied to give
some external support.
3. Lowering of intraocular pressure by
simultaneous use of acetazolamide 250 mg QID
orally, intravenous mannitol (20%) drip stat, oral
glycerol twice a day, 0.5% timolol eyedrops twice
a day, and even paracentesis with slow evacuation
of aqueous from the anterior chamber may be
performed if required.
4. Tissue adhesive glue such as cynoacrylate is
helpful in preventing perforation.
5. Conjunctival flap. The cornea may be covered
completely or partly by a conjunctival flap to
give support to the weak tissue.
6. Bandage soft contact lens may also be used.
7. Penetrating therapeutic keratoplasty (tectonic
graft) may be undertaken in suitable cases, when
available.
IV. Treatment of perforated corneal ulcer
Best is to prevent perforation. However, if perforation
has occurred, immediate measures should be taken
to restore the integrity of perforated cornea.
Depending upon the size of perforation and
availability, measures like use of tissue adhesive glues,
covering with conjunctival flap, use of bandage soft
contact lens or therapeutic keratoplasty should be
undertaken. Best is an urgent therapeutic
keratoplasty.