Corneal Ulcers
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Corneal ulcer, often resulting from
keratitis Keratitis is a condition in which the human eye, eye's cornea, the clear dome on the front surface of the eye, becomes inflammation, inflamed. The condition is often marked by moderate to intense pain and usually involves any of the following sy ...
is an inflammatory or, more seriously, infective condition of the
cornea The cornea is the transparency (optics), transparent front part of the eyeball which covers the Iris (anatomy), iris, pupil, and Anterior chamber of eyeball, anterior chamber. Along with the anterior chamber and Lens (anatomy), lens, the cornea ...
involving disruption of its
epithelial Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...
layer with involvement of the corneal stroma. It is a common condition in humans particularly in the tropics and in farming. 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. Vitamin A pla ...
are at high risk for corneal ulcer and may become blind in both eyes persisting throughout life. In
ophthalmology Ophthalmology (, ) is the branch of medicine that deals with the diagnosis, treatment, and surgery of eye diseases and disorders. An ophthalmologist is a physician who undergoes subspecialty training in medical and surgical eye care. Following a ...
, a corneal ulcer usually refers to having an infection, while the term
corneal abrasion Corneal abrasion is a scratch to the surface of the cornea of the eye. Symptoms include pain, redness, light sensitivity, and a feeling like a foreign body is in the eye. Most people recover completely within three days. Most cases are due to m ...
refers more to a scratch injury.


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 lens (optics), lenses placed directly on the surface of the Human eye, eyes. Contact lenses are ocular prosthetic devices used by over 150 million people worldwide, and they can be worn to correct ...
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 Genetics, genetic factors. ...
,
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. ...
,
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 ...
, and keratoconjunctivitis sicca (dry eye). Many micro-organisms cause infective corneal ulcer. Among them are bacteria (including ''Chlamydia trachomatis)'', fungi, viruses, and protozoa: * 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 posi ...
'', ''
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. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...
'', '' Enterococci'', ''
Pseudomonas ''Pseudomonas'' is a genus of Gram-negative bacteria belonging to the family Pseudomonadaceae in the class Gammaproteobacteria. The 348 members of the genus demonstrate a great deal of metabolic diversity and consequently are able to colonize a ...
'', ''
Nocardia ''Nocardia'' is a genus of weakly staining Gram-positive, catalase, catalase-positive, rod-shaped bacteria. It forms partially acid-fast beaded branching filaments (appearing similar to fungi, but being truly bacteria). It contains a total of 8 ...
'', '' N. gonorrhoea'' and ''
Chlamydia trachomatis ''Chlamydia trachomatis'' () is a Gram-negative, Anaerobic organism, anaerobic bacterium responsible for Chlamydia infection, chlamydia and trachoma. ''C. trachomatis'' exists in two forms, an extracellular infectious elementary body (EB) and an ...
'' as well as 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 s ...
'' sp., ''
Candida Candida, or Cándida (Spanish), may refer to: Biology and medicine * ''Candida'' (fungus), a genus of yeasts ** Candidiasis, an infection by ''Candida'' organisms * Malvasia Candida, a variety of grape Places * Candida, Campania, a ''comu ...
'' 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 t ...
'', ''
Mucor ''Mucor'' is a microbial genus of approximately 40 species of molds and dimorphic fungi in the family Mucoraceae. The genus includes both pathogenic and avirulent species, and some members of it can be utilized in biotechnical applications. ...
'', 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
herpes simplex Herpes simplex, often known simply as herpes, is a viral disease, viral infection caused by the herpes simplex virus. Herpes infections are categorized by the area of the body that is infected. The two major types of herpes are Cold sore, ora ...
,
herpes zoster Shingles, also known as herpes zoster or zona, 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. T ...
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 t ...
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 comm ...
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 amoeboid, amoebae that are commonly recovered from soil, fresh water, and other habitat (ecology), habitats. The genus ''Acanthamoeba'' has two stages in its life cycle, the metabolically active trophozoite stage a ...
''
keratitis Keratitis is a condition in which the human eye, eye's cornea, the clear dome on the front surface of the eye, becomes inflammation, inflamed. The condition is often marked by moderate to intense pain and usually involves any of the following sy ...
is characterized by severe pain and is associated with contact lens users swimming in pools. 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 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 facia ...
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 eye containing mainly collagen and some crucial elastic fiber. In the development of t ...
. 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 bacteria belonging to the family Pseudomonadaceae in the class Gammaproteobacteria. The 348 members of the genus demonstrate a great deal of metabolic diversity and consequently are able to colonize a ...
'' infection, but it can be caused by other types of
bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
or
fungi A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...
. These infectious agents produce
protease A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products ...
s 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 ''N''-acetylcysteine, also known as Acetylcysteine and NAC, is a mucolytics that is used to treat paracetamol (acetaminophen) overdose and to loosen thick mucus in individuals with chronic bronchopulmonary disorders, such as pneumonia and ...
. Surgery in the form of corneal transplantation (penetrating keratoplasty) is usually necessary to save the eye.


Signs and symptoms

Corneal ulcers are 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 blood 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 po ...
), 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 making ...
may be responsible for uveitis formation—stimulation of pain receptors in the cornea results in release inflammatory mediators such as
prostaglandin Prostaglandins (PG) are a group of physiology, physiologically active lipid compounds called eicosanoids that have diverse hormone-like effects in animals. Prostaglandins have been found in almost every Tissue (biology), tissue in humans and ot ...
s,
histamine Histamine is an organic nitrogenous compound involved in local immune responses communication, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Discovered in 19 ...
, and
acetylcholine Acetylcholine (ACh) is an organic compound 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. Par ...
. 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 o ...
) 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 eyelid 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, with the ulcer staining green.


Corneal healing

An ulcer of the cornea heals by two methods: migration of surrounding epithelial cells followed by
mitosis Mitosis () is a part of the cell cycle in eukaryote, eukaryotic cells in which replicated chromosomes are separated into two new Cell nucleus, nuclei. Cell division by mitosis is an equational division which gives rise to genetically identic ...
(dividing) of the cells, and introduction of blood vessels from the
conjunctiva In the anatomy of the eye, the conjunctiva (: conjunctivae) 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 gobl ...
. 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 (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...
s and
fibroblast A fibroblast is a type of cell (biology), biological cell typically with a spindle shape that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and ...
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 In ophthalmology and optometry, 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 ...
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 Triarylmethane dye, triarylmethine dyes family. It is available as a dark orange/red powder slightly soluble in water and alcohol. ...
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 human eye, 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 can cause damage to the cornea. A negative (more than 10& ...
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 ta ...
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 give ...
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 paral ...
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, the uvea ( vascular layer). It controls accommodation for vie ...
. 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 Corneal button, donated corneal tissue (the graft). When the entire cornea is replaced it is known as penetrating ...
. 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 invo ...
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 tw ...
—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 mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained hyperglycemia, high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or th ...
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 Disorders of sclera and cornea