The cornea is the avascular convex, slightly elliptical-shaped anterior transparent part of the globe. It is one of the sites of refraction of light entering the eye and provides a clear medium through which the light can travel. It is limited at its periphery by the corneal limbus, where the transparent cornea stops and the opaque sclera starts. It is intimately related to the conjunctiva via its epithelium which is continuous (if slightly different in nature) between the cornea and the conjunctiva. Thus infections, inflammatory conditions and trauma can all potentially extend from one to the other.
Other related separate articles include: Recurrent Corneal Erosion Syndrome, Dry Eyes (keratoconjunctivitis sicca), Corneal Foreign Bodies, Injuries and Abrasions, Eye Trauma, Contact Lenses (Types and Care) and Contact Lens Problems.
Always remember that babies with suspected corneal abnormalities should be referred urgently, even if they appear to be otherwise well and, if there is likely to be a wait before the patient can see the ophthalmologist, you can do little harm by giving them some preservative-free ocular lubricants or artificial tears which are a good first step in helping to relieve initial discomfort for many conditions. Pain can be addressed with oral analgesics; avoid topical anaesthetics as these are toxic to the corneal epithelium if used repeatedly.
Symptoms in corneal problems
- Pain - this occurs with infective, inflammatory and several other corneal problems unless there is gross neuropathy, in which case severe disease may cause minimal discomfort. Beware of the patient who complains of severe pain with only a very small apparent defect which you suspect to be of infective origin: this is a characteristic presentation in patients who have acquired the potentially devastating acanthamoebic keratitis.
- Photophobia - this frequently accompanies pain.
- Reduced visual acuity - any lesion affecting the central visual axis (ie occurring over the pupil area) or condition distorting the shape of the cornea will affect the visual acuity. Excess lacrimation (epiphora) due to pain can also temporarily affect the vision.
- Red eye - this frequently accompanies the above symptoms.
- Systemic symptoms - it is not unusual for patients with acute corneal disease to complain of headaches, feeling slightly nauseated and feeling generally run down.
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Assessment of the cornea
The cornea in primary care
See separate article Examination of the Eye for more detail about how to perform these assessments.
- Test the visual acuity of both eyes.
- Observe the cornea in plain light. Are there any areas of gross opacification?
- Check for sensation: twist a clean tissue or cotton ball to a tip and lightly touch the centre of the cornea: this should elicit a brisk and immediate response from the patient.
- Apply fluorescein stain to look for defects (if you suspect corneal perforation, perform a Seidel's test).
- If you have access to a slit lamp, assess the cornea from the anterior (epithelial) surface, through the stroma and to the posterior (endothelial) surface by gently moving the focus backwards by a few millimetres. Look for defects (fluorescein uptake), oedema (area of haziness) and infiltrates (a well-demarcated white lesion within the stroma). Vascularisation may occur over the surface or through the stroma, indicating more long-standing disease.
- Examine the rest of the globe and its adnexae. If the symptoms warrant it, do a full systemic examination.
Further assessment of the cornea in a specialist unit
- Pachymetry - this is the measurement of corneal thickness. It is a painless investigation involving placing a measuring probe lightly on the surface of the anaesthetised cornea.
- Specular microscopy - this is a photographic investigation that enables the corneal endothelial cells to be accurately assessed.
- Corneal topography - this is another painless investigation which maps the surface of the cornea rather like an ordnance survey map, showing the gradient at each spot and therefore highlighting asymmetries, such as are found in the dystrophic conditions, for example.
- Microbiological investigations - a corneal scrape (clinic) or biopsy (theatre) may need to be done.
Acute corneal problems
- Nature - infection of one or more layers of the cornea. Most bacteria can only produce keratitis once the integrity of epithelium is compromised, such as following a corneal abrasion or prolonged contact lens wear. Neisseria gonorrhoeae and Haemophilus influenzae are the exception, being able to cross intact epithelium. Risk factors include:
- Extrinsic factors, eg contact lens wear (especially prolonged or associated with poor hygiene), corneal trauma (accidental or surgical) and drug-related (such as contaminated medication, prolonged steroid therapy and some glaucoma medication).
- Ocular surface disease, eg poor tear film.
- Corneal epithelial abnormalities, eg neurotrophic keratopathy, viral keratitis.
- Systemic disease, eg diabetes, debilitating disease and hypovitaminosis A.
- Presentation - redness, pain, photophobia, foreign body sensation and reduced visual acuity. There will usually be an epithelial defect ± the presence of white cell infiltrate ± oedema.
- Management - refer:
- These patients will need intensive topical antibiotic treatment (often after microbiology cultures) ± cycloplegics.
- Topical steroids may be added during the healing stage. A balance has to be struck between reducing corneal scarring through inflammatory suppression and the possible adverse effects (including prolonging the infection, raising the intraocular pressure and inhibiting collagen synthesis). For this reason, steroids should only be given under specialist supervision.
- Patients with severe infection or in whom treatment compliance may be poor are admitted. A few others (eg this is their only functioning eye) may also be admitted.
- When explaining your plan to the patient, tell them to discontinue any contact lens wear and to bring all their contact lens equipment (lenses, storage box and cleaning solution) with them - these will be sent off to microbiology; they will be destroyed in the culturing process.
- Nature - the most common culprits are the herpes simplex virus (HSV), causing herpes simplex eye infections, and the varicella zoster virus (VZV), causing herpes zoster ophthalmicus. These can cause damage at all layers of the cornea and the surrounding structures, either through direct viral invasion or as a result of secondary inflammation.
- HSV: primary infection is very mild and usually occurs in early childhood, characterised by a viral-type upper respiratory tract infection and slight rash. Secondary infection varies from superficial dendritic ulcers to deep stromal involvement. The patient presents with typical features of corneal problems (see 'Symptoms in corneal problems', above). There is often decreased corneal sensation. Triggers for viral reactivation include ultraviolet (UV) light, trauma, cold, menstruation and psychological stress.
- VZV: years to decades after the primary varicella infection (chickenpox), there is the development of an influenza-type illness, neuralgia, and macular-papular rash over the distribution of the ophthalmic branch of the trigeminal nerve (occasionally crosses this barrier). Keratitis develops in about 65% of these patients (Hutchinson's sign: cutaneous involvement of the tip of the nose suggests an increased likelihood of ocular complications). Precipitating factors include physical trauma, surgery, immunosuppression and systemic illness.
- Management - refer in both cases, as the degree of corneal involvement needs to be carefully assessed to determine the need for (usually) topical antivirals ± cycloplegia (HSV), systemic antivirals (VZV), topical steroids (in some cases of deep HSV) and to monitor for complications (such as necrosis, ulceration/perforation, scarring). Immunosuppressive drugs such as ciclosporin A are new alternatives to corticosteroid use in select HSV patients. Most patients also benefit from lubricants. Whilst it is best practice to refer the patient with suspected HSV, in the case of a well-established case of recurrent infections in an individual living in a rural area, treatment may exceptionally be started in the community, where there is an agreed written plan with the local specialist.
Fungal keratitis (keratomycosis)
- Nature - a rare but potentially devastating infection most commonly caused by Aspergillus and Fusarium species and typically seen in agricultural settings or where an injury has occurred involving organic matter such as wood or plants. Candidal keratitis is seen in AIDS patients. Other susceptible patients are debilitated individuals and those with pre-existing corneal disease.
- Presentation - similar symptoms to bacterial keratitis but onset is very gradual and less severe. It may be diagnosed following non-response to treatment of 'bacterial' keratitis.
- Management - refer. The cornea is scraped and topical antimycotic therapy initiated (although doubt has been cast as to the effectiveness of current available therapies). The treatment may last many weeks and unresponsive cases may require systemic treatment or even a therapeutic penetrating keratoplasty (corneal transplant).
- Nature - the most feared is the Acanthamoeba species - a ubiquitous free-living protozoan found in air, water (fresh, salty, tap, swimming pools and hot tubs) as well as dust, soil or sewage. It largely survives in freezing to boiling temperatures and the chlorination of swimming pools. Contact lens wearers are at risk (although anybody can be infected). It can cause a devastating, sight-threatening infection.
- Presentation - this ranges from asymptomatic to a foreign body sensation, reduced visual acuity and extreme pain (disproportionate to mild clinical findings). Punctate or dendritiform defects may be present with small, white satellite lesions.
- Management - refer. Topical amoebicides will be used in association with topical steroids. In severe cases, a therapeutic penetrating keratoplasty may be needed to preserve the globe.
Other infectious keratitis
- Luetic interstitial keratitis - stromal inflammation associated with, amongst others, syphilis infection.
- Microsporidial keratitis - bilateral diffuse keratitis or unilateral deep keratitis seen in the immunocompromised.
- Infectious crystalline keratopathy - a rare indolent infection associated with HSV, acanthamoebic keratitis, Streptococcus viridans and long-term topical steroid therapy.
- Nature - corneal grafting (keratoplasty) is the most common and most successful of all procedures. It can be performed as an elective procedure to improve vision, or as an emergency in the case of corneal perforation. Early postoperative complications include:
- Wound leak.
- Raised intraocular pressure.
- Persistent epithelial defect (>2 weeks).
- Graft failure.
- Graft rejection.
- Urrets-Zavalia syndrome (iris ischaemia).
- Presentation - patients who have undergone a keratoplasty and present with any of the symptoms outlined above should be assumed to have one of the above complications until assumed otherwise. Each has a slightly different presentation: these patients will be under close ophthalmological review in the first year at least. It is worth noting that corneal graft rejection most often occurs within the first two years following the procedure.
- Management - refer. Ideally, the operating surgeon should see the patient but, if they are not available (eg out of hours), refer to the on-call ophthalmologist who will initiate the management and liaise with the team.
Non-acute corneal problems
- Abnormalities of size:
- Megalocornea - the cornea is too large - this is an uncommon, bilateral and non-progressive condition which is usually X-linked recessive. It is associated with myopia, astigmatism, cataracts and, later on in life, lens dislocation and glaucoma. It may be associated with Marfan's syndrome, Apert's syndrome, Ehlers-Danlos syndrome, Down's syndrome and osteogenesis imperfecta.
- Microcornea - may be unilateral or bilateral and the rest of the eye may be normal (although there are reports of associations with optic nerve hypoplasia, scleroderma, cataract formation, iris abnormalities and secondary angle-closure glaucoma). It may be associated with fetal alcohol syndrome, Turner syndrome, Ehlers-Danlos syndrome, Weill-Marchesani syndrome, Waardenburg's syndrome, Nance-Horan syndrome and Cornelia de Lange's syndrome.
- Abnormalities of shape:
- Cornea plana - is a flat cornea: it is a rare bilateral condition which shows autosomal dominant and recessive patterns of inheritance and which is associated with peripheral sclerocornea, severe refractive errors, cataracts and colobomata.
- Keratoglobus - is the condition where there is an abnormally steeped, thin, round cornea. It is one of the corneal ectasias (see 'Corneal ectasias', below) and may be associated with Ehlers-Danlos syndrome type IV.
- Corneal opacities - the cornea may be cloudy at birth for a number of reasons and these babies should always be referred for urgent ophthalmological opinion. The opacity may be one of the following:
- Diffuse - caused by congenital glaucoma, birth trauma, fetal alcohol syndrome and, rarely, other causes (small print).
- Focal and central - caused by birth trauma, Peter's anomaly (a corneal dysgenesis) or neonatal keratitis.
- Focal and peripheral - caused by scleroderma (opacification and vascularisation of the cornea), presence of a limbal dermoid or neonatal keratitis.
Disorders of the periphery of the cornea
- Nature - a disorder caused by hypersensitivity to staphylococcal toxins, more commonly occurring in patients suffering from chronic staphylococcal keratitis or blepharitis. It is characterised by peripheral infiltrates and multiple epithelial defects which eventually coalesce. It is a recurring condition.
- Presentation - typically, the patient is all too familiar with their symptoms of mild irritation and discomfort associated with a red, watery eye. Occasionally, discomfort is severe.
- Management - refer for confirmation of diagnosis and a short course of topical steroids.
- Nature - occurs in patients suffering from acne rosacea but the severity of the ocular condition does not correlate with that of the skin condition. It is more common in middle-aged, fair-skinned females.
- Presentation - nonspecific irritation, burning and redness associated with inferior punctate epithelial defects and peripheral neovascularisation. There may be lid and conjunctival involvement too.
- Management - refer for topical steroids and a course of systemic antibiotics (eg doxycycline 100 mg od for twelve weeks). Concurrent blepharitis also needs addressing. In very severe cases where there is the threat of corneal perforation, systemic immunosuppression is used.
Ulcerative keratitis in systemic disease
- Nature - this is particularly associated with rheumatoid arthritis where there is severe, progressive corneal thinning (perforation may occur). Ulcerative keratitis also occurs in other conditions such as Wegener's granulomatosis, systemic lupus erythematosus, relapsing polychondritis and polyarteritis nodosa. It may be referred to as 'peripheral ulcerative keratitis' (PUK).
- Presentation - this recurrent condition presents with acute unilateral/bilateral exacerbations characterised by decreased visual acuity, variable pain and redness (there may be none).
- Management - treatment will involve systemic immunosuppression, topical immunosuppression, ocular lubricants and globe protection (such as an eye shield). Both ophthalmologists and rheumatologists will be involved in patient care.
- Mooren's ulcer - where PUK-associated ulceration occurs and is idiopathic, it is referred to as Mooren's ulcer. This is an ulcerative condition (usually unilateral) which arises as a result of an autoimmune response to corneal antigens. It is rare but serious, particularly in young Africans in whom the more aggressive form of the disease is seen, and treatment depends on subtype (ranges from topical steroids/antibiotics to aggressive systemic steroid treatment).
- Dellen - localised saucer-shaped thinning of the cornea caused by localised tear film instability. Managed with lubricants; it is a transient condition.
- Phlyctenulosis - small pinkish-white nodule develops with an associated red eye. It occurs as a result of a nonspecific delayed hypersensitivity reaction to bacterial and viral antigens. These lesions may resolve spontaneously or be treated with a short course of antibiotics or topical steroids.
- Terrien's marginal degeneration - uncommon, idiopathic bilateral thinning of the cornea, usually occurring in the third to fourth decade of life, more often in males. There may be pain, there is decrease in visual acuity and, eventually, surgery may be needed to excise the diseased tissue (results are limited).
- Arcus senilis (sometimes referred to as corneal annulus or anterior embryotoxon) - this is the most common peripheral corneal opacity, which may occur alone or in association with hyperlipidaemia (especially if present in younger individuals). It is caused by lipid droplets in the corneal stroma. Rarely, it is unilateral, in which case it is associated with carotid disease or ocular hypotony.
- Vogt's limbal girdle - a common, innocuous age-related finding characterised by peripheral chalky-white crescents at the 3 o'clock and 9 o'clock positions.
- Cornea guttata - an innocuous change in endothelial cells that is mainly significant in that it can be a precursor of early Fuchs' endothelial dystrophy (see 'Dystrophic conditions', below).
This involves deposits of lipid within the cornea, which may be idiopathic or associated with previous keratitis or disordered lipid metabolism. There are two types, one of which is associated with corneal vascularisation if left untreated. It looks like a bright white, well-defined patch on the cornea, sometimes associated with a 'feeding' vessel. It requires laser or surgical removal.
This common sign is the deposition of calcium salts within the cornea, most commonly found in chronic uveitis but also associated with a number of other causes, eg prolonged glaucoma, long-standing corneal oedema and corneal dystrophies. It can also arise in the context of systemic disease such as hypercalcaemia, hyperuricaemia and in chronic renal failure. It looks like a grey band of opacity going horizontally across the cornea. Chelation is the treatment of choice: sodium edetate is applied until all the calcium is removed. Ultimately, the underlying condition needs to be addressed.
Other degenerative conditions
- Spheroidal degeneration - a bilateral condition (with many eponyms!) of unknown cause, mostly occurring in men working outdoors. Small golden-brown lesions accumulate in the cornea, associated with generalised haziness. UV protection helps but, ultimately, these patients may need surgical removal of the lesions.
- Salzmann's nodular degeneration - discrete grey opacities arise in the cornea, secondary to chronic keratitis (especially trachoma). They may be associated with a red eye, irritation and blurred vision. The treatment is as for spheroidal degeneration.
- Crocodile shagreen - this describes a faint network of stromal opacities resembling crocodile skin. It is innocuous.
These are a group of progressive, usually bilateral, conditions which affect one of the various layers of the cornea - epithelium, Bowman layer, stroma or endothelium. One of the more commonly encountered ones is Fuchs' endothelial dystrophy. This autosomal dominant inherited condition is more commonly seen in women and is significant in that it is associated with an increase in prevalence of primary open angle glaucoma. Symptoms include reduced visual acuity (due to corneal oedema) and pain (due to progressively exposed nerve endings). It is treated with hypotonic eye drops but may go on to need a bandage contact lens or even surgery.
- Nature - a progressive conical distortion of the cornea, starting in puberty, characterises this condition which is bilateral. It is the most common primary corneal ectasia. The aetiology is not clear but repeated trauma (eg eye rubbing) and perhaps connective tissue disorders may contribute.
- Presentation - it can occur in the second to third decade of life with progressive visual impairment requiring frequent spectacle changes and occasional sudden transient corneal oedema (acute hydrops) as the weakened Descemet's membrane of the cornea cracks. The chronic changes are nearly always bilateral.
- Management - it is treated with spectacles initially, then contact lenses. Ultimately, these patients benefit from keratoplasty (corneal transplant). Acute hydrops is managed with topical hypertonic sodium chloride and topical homatropine; it may take weeks to months to resolve.
Pellucid marginal degeneration
This condition is similar to keratoconus but occurs later in life (second to fourth decade) and slit-lamp findings differ slightly. Treatment is the same.
See description under 'Abnormalities of shape', above; it may also be acquired (probably as an end-stage keratoconus). It arises as a result of thinning of the stromal (middle) layer of the cornea. Treatment may include protection from trauma, specialised contact lens wear or surgery.
- Nature - damage to the cornea as a result of improper tear cover/wetting of its surface. The tear film may be reduced or it may be normal but the blink rate is reduced (facial nerve palsy, severe proptosis, eyelid scarring).
- Presentation - a progressively painful red eye if left untreated in the presence of reduced tear film. Look for loss of shiny reflection from the corneal surface.
- Management - if recovery of the underlying problem is anticipated, aggressive lubrication will do. Otherwise, lid surgery will be considered (tarsorrhaphy- where the lids are partially sutured together).
- Nature - this occurs when there is loss of sensation in the cornea (eg acoustic neuroma, diabetes, herpes simplex virus (HSV) affecting fifth cranial nerve) and a secondary intracellular oedema (the pathogenesis is unknown).
- Presentation - variable: a painless red eye with mild visual impairment secondary to corneal oedema through to epithelial defects leading to corneal ulceration. A decrease in corneal sensation is the key factor.
- Management - this depends on the severity but lubrication ± protection overnight will usually be enough.
This is when the shape is slightly rugby ball-shaped rather than truly spherical, so causing a refractive error. This is most commonly treated with corrective spectacles and contact lenses (in some cases, the latter may be the best way of improving sight). Surgery is also an option in the private sector.
The cornea can be affected by a number of systemically administered drugs, including gold (causing chrysiasis - deposition of gold deposits), and antimalarials and amiodarone - both of which give rise to vortex keratopathy characterised by whorl-like corneal deposits. Vortex keratopathy has also been seen associated with indometacin, tamoxifen use and clofazimine toxicity. Drug-induced keratopathy has been described in the use of certain oriental herbal medicines.
Thygeson's superficial punctate keratopathy
This is a rare, idiopathic condition that usually arises in the younger population (from infant to age 24 years). It is characterised by recurrent episodes of pain and foreign body sensation (± blurred vision, red eye, photophobia and tearing) and crumb-like, non-staining white opacities scattered over the corneal surface. It is usually bilateral but asymmetrical. It is managed with courses of topical steroids. Although the visual prognosis is good, patients have to be monitored for complications of treatment and, unfortunately, frequently return.
- Cystinosis - ocular features include progressive deposition of cystine crystals causing photophobia, blepharospasm, epithelial erosions and reduced visual acuity. Later on, the iris, lens and retina are also involved.
- Immunoprotein deposits - eg multiple myeloma, Waldenström's macroglobulinaemia, monoclonal gammopathy. Uncommonly, these cause bilateral corneal deposits which, when severe, may require penetrating keratoplasty.
- Mucopolysaccharidoses - corneal deposits typically occur in most of these (except Hunter's syndrome and Sanfilippo syndrome) and tend to be most severe in Hurler's syndrome. The retina and optic nerve may also be affected in these patients.
- Wilson's disease - the Kayser-Fleischer ring is described in these patients: copper is deposited around the periphery of the cornea. It may only be visible by gonioscopy (a mirrored contact lens used to look at the angle between the iris and cornea) where it may be found to be variable in colour (eg brown, ruby red, bright green or yellow).
Further reading & references
- Khan FH et al, Emergency Care of Corneal Abrasion, Medscape, Jun 2011
- Bashour M, Corneal Foreign Body, Medscape, Apr 2010
- Kanski J. Clinical Ophthalmology, A Systematic Approach, 5th ed. Butterworth Heinemann (2003)
- Murillo-Lopez FH, Bacterial Keratitis, Medscape Nov 2011
- Preferred practice patterns: Bacterial keratitis, American Academy of Ophthalmology (October 2011)
- Jackson TL; Moorfields Manual of Ophthalmology, Mosby (2008)
- Denniston AKO, Murray PI. Oxford Handbook of Ophthalmology (OUP), 2009.
- Wilhelmus KR; Therapeutic interventions for herpes simplex virus epithelial keratitis. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD002898. DOI: 10.1002/14651858.CD002898.pub3.
- Knickelbein JE, Hendricks RL, Charukamnoetkanok P; Management of Herpes Simplex Virus Stromal Keratitis: An Evidence-based Review. Surv Ophthalmol. 2009 Mar-Apr;54(2):226-34.
- FlorCruz NV, Peczon IV; Medical interventions for fungal keratitis. Cochrane Database of Systematic Reviews 2008, Issue 1. Art. No.: CD004241. DOI: 10.1002/14651858.CD004241.pub2.
- Willshaw H et al; A Handbook of Paediatric Ophthalmology, 2000
- Akatsu T, Santo RM, Nakayasu K, et al; Oriental herbal medicine induced epithelial keratopathy. Br J Ophthalmol. 2000 Aug;84(8):934.
|Original Author: Dr Olivia Scott||Current Version: Dr Gurvinder Rull||Peer Reviewer: Dr John Cox|
|Last Checked: 16/05/2012||Document ID: 933 Version: 23||© EMIS|
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