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Corneal ulcer is an inflammatory or, more seriously, infective condition of the
cornea The cornea is the transparent front part of the eye that covers the iris, pupil, and anterior chamber. Along with the anterior chamber and lens, the cornea refracts light, accounting for approximately two-thirds of the eye's total optical power ...
involving disruption of its
epithelial Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellula ...
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 Vitamin A deficiency (VAD) or hypovitaminosis A is a lack of vitamin A in blood and tissues. It is common in poorer countries, especially among children and women of reproductive age, but is rarely seen in more developed countries. Nyctalopia (ni ...
are at high risk for corneal ulcer and may become blind in both eyes, which may persist lifelong. In ophthalmology, a corneal ulcer usually refers to having an infectious cause while the term corneal abrasion refers more to physical abrasions.


Types


Superficial and deep corneal ulcers

Corneal ulcers are a common human eye disease. They are caused by trauma, particularly with vegetable matter, as well as chemical injury,
contact lenses Contact lenses, or simply contacts, are thin lenses placed directly on the surface of the eyes. Contact lenses are ocular prosthetic devices used by over 150 million people worldwide, and they can be worn to correct vision or for cosmetic ...
and infections. Other eye conditions can cause corneal ulcers, such as
entropion Entropion is a medical condition in which the eyelid (usually the lower lid) folds inward. It is very uncomfortable, as the eyelashes continuously rub against the cornea causing irritation. Entropion is usually caused by genetic factors. This is d ...
,
distichiasis A distichia is an eyelash that arises from an abnormal part of the eyelid. This abnormality, attributed to a genetic mutation, is known to affect dogs and humans. Distichiae usually exit from the duct of the meibomian gland at the eyelid margin. T ...
,
corneal dystrophy Corneal dystrophy is a group of rare hereditary disorders characterised by bilateral abnormal deposition of substances in the transparent front part of the eye called the cornea. Signs and symptoms Corneal dystrophy may not significantly affect v ...
, and
keratoconjunctivitis sicca Dry eye syndrome (DES), also known as keratoconjunctivitis sicca (KCS), is the condition of having dry eyes. Other associated symptoms include irritation, redness, discharge, and easily fatigued eyes. Blurred vision may also occur. Symptoms range ...
(dry eye). Many micro-organisms cause infective corneal ulcer. Among them are bacteria, fungi, viruses, protozoa, and chlamydia: * Bacterial keratitis is caused by ''
Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often positive ...
'', ''
Streptococcus viridans The viridans streptococci are a large group of commensal streptococcal Gram-positive bacteria species that are α-hemolytic, producing a green coloration on blood agar plates (hence the name "viridans", from Latin "vĭrĭdis", green), although ...
'', ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'', ''
Enterococci ''Enterococcus'' is a large genus of lactic acid bacteria of the phylum Bacillota. Enterococci are gram-positive cocci that often occur in pairs (diplococci) or short chains, and are difficult to distinguish from streptococci on physical charac ...
'', ''
Pseudomonas ''Pseudomonas'' is a genus of Gram-negative, Gammaproteobacteria, belonging to the family Pseudomonadaceae and containing 191 described species. The members of the genus demonstrate a great deal of metabolic diversity and consequently are able ...
'', '' Nocardia'', '' N. gonorrhoea'' and many other bacteria. * Fungal keratitis causes deep and severe corneal ulcer. It is caused by ''
Aspergillus ' () is a genus consisting of several hundred mold species found in various climates worldwide. ''Aspergillus'' was first catalogued in 1729 by the Italian priest and biologist Pier Antonio Micheli. Viewing the fungi under a microscope, Miche ...
'' sp., ''
Fusarium ''Fusarium'' is a large genus of filamentous fungi, part of a group often referred to as hyphomycetes, widely distributed in soil and associated with plants. Most species are harmless saprobes, and are relatively abundant members of the soil mi ...
'' sp., '' Candida'' sp., as also ''
Rhizopus ''Rhizopus'' is a genus of common saprophytic fungi on plants and specialized parasites on animals. They are found in a wide variety of organic substances, including "mature fruits and vegetables", jellies, syrups, leather, bread, peanuts, and ...
'', ''
Mucor ''Mucor'' is a microbial genus of approximately 40 species of molds in the family Mucoraceae. Species are commonly found in soil, digestive systems, plant surfaces, some cheeses like Tomme de Savoie, rotten vegetable matter and iron oxide re ...
'', 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 Hypopyon is a medical condition involving inflammatory cells in the anterior chamber of the eye. It is an exudate rich in white blood cells, seen in the anterior chamber, usually accompanied by redness of the conjunctiva and the underlying epis ...
is usually seen. * Viral keratitis causes corneal ulceration. It is caused most commonly by
herpes simplex Herpes simplex is a viral infection caused by the herpes simplex virus. Infections are categorized based on the part of the body infected. Oral herpes involves the face or mouth. It may result in small blisters in groups often called cold ...
,
herpes zoster Shingles, also known as zoster or herpes zoster, is a viral disease characterized by a painful skin rash with blisters in a localized area. Typically the rash occurs in a single, wide mark either on the left or right side of the body or face. ...
and
adenovirus Adenoviruses (members of the family ''Adenoviridae'') are medium-sized (90–100 nm), nonenveloped (without an outer lipid bilayer) viruses with an icosahedral nucleocapsid containing a double-stranded DNA genome. Their name derives from the ...
es. It can also be caused by
coronavirus Coronaviruses are a group of related RNA viruses that cause diseases in mammals and birds. In humans and birds, they cause respiratory tract infections that can range from mild to lethal. Mild illnesses in humans include some cases of the com ...
es and many other viruses. Herpes virus cause a dendritic ulcer, which can recur and relapse over the lifetime of an individual. * Protozoa infection like ''
Acanthamoeba ''Acanthamoeba'' is a genus of amoebae that are commonly recovered from soil, fresh water, and other habitats. ''Acanthamoeba'' has two evolutive forms, the metabolically active trophozoite and a dormant, stress-resistant cyst. Trophozoites are ...
''
keratitis Keratitis is a condition in which the eye's cornea, the clear dome on the front surface of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves any of the following symptoms: pain, impaired e ...
is characterized by severe pain and is associated with contact lens users swimming in pools. * ''
Chlamydia trachomatis ''Chlamydia trachomatis'' (), commonly known as chlamydia, is a bacterium that causes chlamydia, which can manifest in various ways, including: trachoma, lymphogranuloma venereum, nongonococcal urethritis, cervicitis, salpingitis, pelvic inflamma ...
'' 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 Corneal perforation is an anomaly in the cornea resulting from damage to the corneal surface. A corneal perforation means that the cornea has been penetrated, thus leaving the cornea damaged. The cornea is a clear part of the eye which controls an ...
, if not treated in time. The location of the ulcer depends somewhat on the cause. Central ulcers are typically caused by trauma, dry eye, or exposure from
facial nerve paralysis Facial nerve paralysis is a common problem that involves the paralysis of any structures innervated by the facial nerve. The pathway of the facial nerve is long and relatively convoluted, so there are a number of causes that may result in facial ...
or
exophthalmos Exophthalmos (also called exophthalmus, exophthalmia, proptosis, or exorbitism) is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral (as is often seen in Graves' disease) or unilateral (as is often seen in ...
. Entropion, severe dry eye and trichiasis (inturning of eyelashes) may cause ulceration of the peripheral cornea. Immune-mediated eye disease can cause ulcers at the border of the cornea and
sclera The sclera, also known as the white of the eye or, in older literature, as the tunica albuginea oculi, is the opaque, fibrous, protective, outer layer of the human eye containing mainly collagen and some crucial elastic fiber. In humans, and som ...
. 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.


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.


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 ''Pseudomonas'' is a genus of Gram-negative, Gammaproteobacteria, belonging to the family Pseudomonadaceae and containing 191 described species. The members of the genus demonstrate a great deal of metabolic diversity and consequently are able ...
'' infection, but it can be caused by other types of
bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
or
fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...
. These infectious agents produce
protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes (increases reaction rate or "speeds up") proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the ...
s and
collagenase Collagenases are enzymes that break the peptide bonds in collagen. They assist in destroying extracellular structures in the pathogenesis of bacteria such as ''Clostridium''. They are considered a virulence factor, facilitating the spread of ...
s 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 Acetylcysteine, also known as ''N''-acetylcysteine (NAC), is a medication that is used to treat paracetamol overdose and to loosen thick mucus in individuals with chronic bronchopulmonary disorders like pneumonia and bronchitis. It has been used ...
. Surgery in the form of corneal transplantation (penetrating keratoplasty) is usually necessary to save the eye.


Signs and 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 Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and ...
, such as
miosis Miosis, or myosis (), is excessive constriction of the pupil.Farlex medical dictionary
citing: ...
(small pupil), aqueous flare (protein in the
aqueous humour The aqueous humour is a transparent water-like fluid similar to plasma, but containing low protein concentrations. It is secreted from the ciliary body, a structure supporting the lens of the eyeball. It fills both the anterior and the posterio ...
), and redness of the eye. An
axon reflex The axon reflex (or the flare response) is the response stimulated by peripheral nerves of the body that travels away from the nerve cell body and branches to stimulate target organs. Reflexes are single reactions that respond to a stimulus makin ...
may be responsible for uveitis formation—stimulation of pain receptors in the cornea results in release inflammatory mediators such as
prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...
s,
histamine Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered in ...
, and
acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...
. Sensitivity to light (
photophobia Photophobia is a medical symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of ...
) is also a common symptom of corneal ulcer. Redness of the affected eye is common. Brow ache and head ache may be present. Drooping of eye lid may be present. Slit lamp examination shows loss of epithelium. The site of the ulcer is studied and marked in case sheet. The edge of the ulcer is studied. Whether satellite lesion is present or not is seen. Next, the cornea is stained with 1% fluorescein. The ulcer is stained green.


Corneal healing

An ulcer of the cornea heals by two methods: migration of surrounding epithelial cells followed by
mitosis In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
(dividing) of the cells, and introduction of blood vessels from the
conjunctiva The conjunctiva is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the eye). It is composed of non-keratinized, stratified squamous epithelium with goblet cells, stratified columnar epithelium ...
. Superficial small ulcers heal rapidly by the first method. However, larger or deeper ulcers often require the presence of blood vessels to supply inflammatory cells.
White blood cell White blood cells, also called leukocytes or leucocytes, are the cell (biology), cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and de ...
s and
fibroblast A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...
s produce
granulation tissue Granulation tissue is new connective tissue and microscopic blood vessels that form on the surfaces of a wound during the healing process. Granulation tissue typically grows from the base of a wound and is able to fill wounds of almost any size ...
and then scar tissue, effectively healing the cornea.


Diagnosis

Diagnosis is done by direct observation under magnified view of
slit lamp A slit lamp is an instrument consisting of a high-intensity light source that can be focused to shine a thin sheet of light into the eye. It is used in conjunction with a biomicroscope. The lamp facilitates an examination of the anterior segm ...
revealing the ulcer on the cornea. The use of
fluorescein Fluorescein is an organic compound and dye based on the xanthene tricyclic structural motif, formally belonging to triarylmethine dyes family. It is available as a dark orange/red powder slightly soluble in water and alcohol. It is widely used ...
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. 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. Doing a corneal scraping and examining under the microscope with stains like Gram's and KOH preparation may reveal the bacteria and fungi respectively. Microbiological culture tests may be necessary to isolate the causative organisms for some cases. Other tests that may be necessary include a
Schirmer's test Schirmer's test determines whether the eye produces enough tears to keep it moist. This test is used when a person experiences very dry eyes or excessive watering of the eyes. It poses no risk to the subject. A negative (more than 10 mm of mo ...
for keratoconjunctivitis sicca and an analysis of
facial nerve The facial nerve, also known as the seventh cranial nerve, cranial nerve VII, or simply CN VII, is a cranial nerve that emerges from the pons of the brainstem, controls the muscles of facial expression, and functions in the conveyance of tas ...
function for facial nerve paralysis.


Treatment

Proper diagnosis is essential for optimal treatment. The cause of the ulcer is to be decided. Whether infective or non-infective. 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 Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically given i ...
or
homatropine Homatropine (Equipin, Isopto Homatropine) is an anticholinergic medication that is an antagonist at muscarinic acetylcholine receptors and thus the parasympathetic nervous system. It is used in eye drops as a cycloplegic (to temporarily paraly ...
to dilate the pupil and thereby stop spasms of the
ciliary muscle The ciliary muscle is an intrinsic muscle of the eye formed as a ring of smooth muscleSchachar, Ronald A. (2012). "Anatomy and Physiology." (Chapter 4) . in the eye's middle layer, uvea ( vascular layer). It controls accommodation for viewing ...
. Superficial ulcers may heal in less than a week. Deep ulcers and descemetoceles may require conjunctival grafts or conjunctival flaps, soft
contact lens Contact lenses, or simply contacts, are thin lenses placed directly on the surface of the eyes. Contact lenses are ocular prosthetic devices used by over 150 million people worldwide, and they can be worn to correct vision or for cosmetic ...
es, or
corneal transplant Corneal transplantation, also known as corneal grafting, is a surgical procedure where a damaged or diseased cornea is replaced by donated corneal tissue (the graft). When the entire cornea is replaced it is known as penetrating keratoplasty ...
. 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
corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involv ...
s and
anesthetics An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two ...
—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.


Refractory ulcers

Topical 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 Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
and immunodeficiency. Conjunctival flap may be drawn over the ulcer as an alternative.


See also


Seasonal corneal ulcer

* Christmas Eye, a seasonal epidemic of corneal ulceration which predominantly occurs only within a particular region of Australia * Vernal keratoconjunctivitis, a recurrent, bilateral, and self-limiting inflammation of conjunctiva, having a periodic seasonal incidence: Grade 3


References


External links

* https://www.aao.org/eye-health/diseases/corneal-ulcer * https://www.merckmanuals.com/home/eye-disorders/corneal-disorders/corneal-ulcer {{DEFAULTSORT:Corneal ulcer LASIK Disorders of sclera and cornea