CORNEAL ULCER

Def: A corneal ulcer, or ulcerative keratitis, or eyesore is an inflammatory or more seriously, infective
condition of the cornea involving disruption of its epithelial layer with involvement of the corneal
stroma.

It is a common condition in humans particularly in the tropics and the agrarian societies. In developing
countries, Children afflicted by Vitamin A deficiency are at high risk for corneal ulcer and may become
blind in both eyes, which may persist lifelong.

Corneal anatomy of the human

The cornea is a transparent structure that is part of the outer layer of the eye. It refracts light and
protects the contents of the eye. The corneal thickness ranges from 450 to 610 micrometres and on an
average 550 µm thick in caucasian eyes. In Indian eyes, the average thickness is slightly less at 510 µm.
The trigeminal nerve supplies the cornea via the long ciliary nerves. There are pain receptors in the
outer layers and pressure receptors are deeper.

Transparency is achieved through a lack of blood vessels, pigmentation, and keratin, and through tight
layered organization of the collagen fibers. The collagen fibers cross the full diameter of the cornea in a
strictly parallel fashion and allow 99 percent of the light to pass through without scattering.

There are five layers in the human cornea, from outer to inner:

 Epithelium
 Bowman's layer
 Stroma
 Descemet's membrane
 Endothelium

The outer layer is the epithelium, which is 25 to 40 µm and five to seven cell layers thick. The epithelium
holds the tear film in place and also prevents water from invading the cornea and disrupting the
collagen fibers. This prevents corneal edema, which gives it a cloudy appearance. It is also a barrier to
infectious agents. The epithelium sticks to the basement membrane, which also separates the
epithelium from the stroma. The corneal stroma comprises 90 percent of the thickness of the cornea. It
contains the collagen fibers organized into lamellae. The lamellae are in sheets which separate easily.
Posterior to the stroma is Descemet's membrane, which is a basement membrane for the corneal
endothelium. The endothelium is a single cell layer that separates the cornea from the aqueous humor.
Corneal healing

An ulcer of the cornea heals by two methods:

1) migration of surrounding epithelial cells followed by mitosis (dividing) of the cells, and
introduction of blood vessels from the conjunctiva. Superficial small ulcers heal rapidly by the
first method.
2) However, larger or deeper ulcers often require the presence of blood vessels to supply
inflammatory cells. White blood cells and fibroblasts produce granulation tissue and then scar
tissue, effectively healing the cornea. The ulcer heals by the fourth day

1. Superficial and deep corneal ulcers

Corneal ulcers are a common human eye disease. They are caused by

 Trauma, particularly with vegetable matter, as also

 Chemical injury,
 Contact lenses and
 Infections.

Other eye conditions can cause corneal ulcers, such as

i. entropion,
ii. distichiae,
iii. corneal dystrophy, and
iv. keratoconjunctivitis sicca (dry eye).

Many micro-organisms cause infective corneal ulcer. Among them are

 bacteria,
 fungi,
 viruses,
 protozoa, and
 chlamydia.

Bacterial keratitis is caused by

1) Staphylococcus aureus,
2) Streptococcus viridans,
3) Escherichia coli,
4) Enterococci,
5) Pseudomonas,
6) Nocardia

and many other bacteria.

Fungal keratitis causes deep and severe corneal ulcer. It is caused by

1) Aspergillus sp.,
2) Fusarium sp.,
3) Candida sp., as also
4) Rhizopus,
5) Mucor, and other fungi.

The typical feature of fungal keratitis is slow onset and gradual progression, where signs are much more
than the symptoms. Small satellite lesions around the ulcer are a common feature of fungal keratitis and
hypopyon is usually seen.

Viral keratitis causes corneal ulceration. It is caused most commonly by

1) Herpes simplex,
2) Herpes Zoster
3) Adenoviruses.
4) coronaviruses & many other viruses.

Herpes virus cause a dendritic ulcer, which can recur and relapse over the lifetime of an individual.

Protozoa infection like Acanthamoeba keratitis is characterized by severe pain and is associated with
contact lens users swimming in pools. Chlamydia trachomatis can also contribute to development of
corneal ulcer.

Superficial ulcers involve a loss of part of the epithelium.

Deep ulcers extend into or through the stroma and can result in severe scarring and corneal perforation.

Descemetoceles occur when the ulcer extends through the stroma. This type of ulcer is especially
dangerous and can rapidly result in corneal perforation, if not treated in time.

The location of the ulcer depends somewhat on the cause. Central ulcers are typically caused by

1) trauma,
2) dry eye, or
3) exposure from facial nerve paralysis or exophthalmos.

 Entropion,
 severe dry eye and
 trichiasis (inturning of eye lashes)

may cause ulceration of the peripheral cornea.

Immune-mediated eye disease can cause ulcers at the border of the cornea and sclera. These include

 Rheumatoid arthritis,
 rosacea,
 systemic sclerosis which lead to a special type of corneal ulcer called Mooren's ulcer. It has a
circumferential crater like depression of the cornea, just inside the limbus, usually with an
overhanging edge.

Symptoms

Corneal ulcers are extremely painful due to nerve exposure, and can cause

 tearing,
 squinting, and
 vision loss of the eye.

There may also be signs of anterior uveitis, such as

 miosis (small pupil),

 aqueous flare (protein in the aqueous humour), and
 redness of the eye.

An axon reflex may be responsible for uveitis formation — stimulation of pain receptors in the cornea
results in release inflammatory mediators such as

 prostaglandins,
 histamine, and
 acetylcholine.

Diagnosis/investigations

1) Diagnosis is done by direct observation under magnified view of slit lamp revealing the ulcer on the
cornea.
2) The use of fluorescein stain, which is taken up by exposed corneal stroma and appears green, helps
in defining the margins of the corneal ulcer, and can reveal additional details of the surrounding
epithelium. Herpes simplex ulcers show a typical dendritic pattern of staining.
3) Rose-Bengal dye is also used for supra-vital staining purposes, but it may be very irritating to the
eyes. In descemetoceles, the Descemet's membrane will bulge forward and after staining will appear
as a dark circle with a green boundary, because it does not absorb the stain.
4) Doing a corneal scraping and examining under the microscope with stains like Gram's and KOH
preparation may reveal the bacteria and fungi respectively.
5) Microbiological culture tests may be necessary to isolate the causative organisms for some cases.
6) Other tests that may be necessary include a

 Schirmer's test for keratoconjunctivitis sicca and

 an analysis of facial nerve function for facial nerve paralysis.
Treatment

 Proper diagnosis is essential for optimal treatment. Bacterial corneal ulcer require intensive
fortified antibiotic therapy to treat the infection.
 Fungal corneal ulcers require intensive application of topical anti-fungal agents.
 Viral corneal ulceration caused by herpes virus may respond to antivirals like topical acyclovir
ointment instilled at least five times a day.
 Alongside, supportive therapy like pain medications are given, including topical cycloplegics like

 atropine or
 homatropine

To dilate the pupil and thereby stop spasms of the ciliary muscle.

Superficial ulcers may heal in less than a week.

Deep ulcers and descemetoceles may require

 conjunctival grafts or conjunctival flaps,

 soft contact lenses, or corneal transplant.

 Proper nutrition, including protein intake and Vitamin C are usually advised. In cases of
Keratomalacia, where the corneal ulceration is due to a deficiency of Vitamin A, supplementation of
the Vitamin A by oral or intramuscular route is given.
 Drugs that are usually contraindicated in corneal ulcer are topical

 corticosteroids and
 anesthetics

- These should not be used on any type of corneal ulcer because they prevent healing, may lead to
superinfection with fungi and other bacteria and will often make the condition much worse.
 2. Refractory corneal ulcers

Refractory corneal ulcers are superficial ulcers that heal poorly and tend to recur. They are also known
as indolent ulcers or Boxer ulcers. They are believed to be caused by a defect in the basement
membrane and a lack of hemidesmosomal attachments. They are recognized by undermined epithelium
that surrounds the ulcer and easily peels back. Refractory corneal ulcers are most commonly seen in
diabetics and often occur in the other eye later. They are similar to Cogan's cystic dystrophy.

Treatment

Topical fortified antibiotics are used at hourly intervals to treat infectious corneal ulcers. Cycloplegic eye
drops are applied to give rest to the eye. Pain medications are given as needed. Loose epithelium and
ulcer base can be scraped off and sent for culture sensitivity studies to find out the pathogenic
organism. This helps in choosing appropriate antibiotics. Complete healing takes anywhere from about a
few weeks to several months.

Refractory corneal ulcers can take a long time to heal, sometimes months. In case of progressive or non-
healing ulcers, surgical intervention by an ophthalmologist with corneal transplantation may be required
to save the eye. In all corneal ulcers it is important to rule out predisposing factors like diabetes mellitus
and immunodeficiency.

3. Melting ulcers

Melting ulcers are a type of corneal ulcer involving progressive loss of stroma in a dissolving fashion. This
is most commonly seen in Pseudomonas infection, but it can be caused by other types of bacteria or
fungi. These infectious agents produce proteases and collagenases which break down the corneal
stroma. Complete loss of the stroma can occur within 24 hours. Treatment includes antibiotics and
collagenase inhibitors such as acetylcysteine. Surgery in the form of corneal transplantation (penetrating
keratoplasty) is usually necessary to save the eye.