Corneal Problems

The cornea is the avascular convex, slightly elliptical shaped anterior transparent part of the globe. It is the main structure responsible for the refraction of light entering the eye and provides a clear media 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.

• Pain - this occurs with any 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 Acanthamoeba keratitis.
• Photophobia - this frequently accompanies pain
• Reduced visual acuity - any lesion affecting the central visual axis (i.e. occurring over the pupil area) or condition distorting the shape of the cornea will affect the visual acuity. Excess lacrimation 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 nauseous and feeling generally run down.

The cornea in primary care

• Test visual acuity
• 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. 10% fluorescein (the dark orange concentrated strips) should be applied first if you are suspecting a laceration ± perforation. Dilute fluorescein pre-mixed with a topical anaesthetic will otherwise do to asess the corneal surface for any defects.
  

  Seidel's Test This is a test designed to assess for the presence of anterior chamber leakage (and hence globe perforation). Apply a strip of 10% fluorescein to the affected area and look at it with a cobalt blue filter. The fluorescein appears as a dark orange colour. Any leaking aqueous will dilute it, giving it a bright luminescence (Seidel's positive). This indicates a perforation. Put a hard shield over the eye, make the patient nil by mouth until ophthalmology review and refer urgently.

• 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 millimeters. 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 adnexiae. If the symptoms warrant it, do a full systemic examination (see disorders below).

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 anesthetized 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 ordinance 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.

Infections

Bacterial keratitis ³

• Nature - infection of one or more layers of the cornea. Most bacteria can only produce keratitis once the integrity of epithelium is compromised; N.gonorrhoeae and H.influenzae are the exception, being able to cross intact epithelium. Risk factors include contact lens wear (prone to P. aeruginosa infection), pre-existing corneal disease, conditions pre-disposing to dry eye, topical steroid therapy, hypovitaminosis A and blepharoconjunctivitis.
• 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. There is controversy over the use of topical steroids which have both positive and negative effects.

Viral keratitis

• Nature - the most common culprits are the herpes simplex virus - HSV (causing herpes simplex eye infections) and the varicella zoster virus - VSV (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.
• Presentation -
  • 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 above).
  • VSV: influenza-type illness, neuralgia, macular-papular rash over the distribution of the ophthalmic branch of the trigeminal nerve (occasionally crosses this barrier).
• Management - refer in both cases as degree of corneal involvement needs to be carefully assessed to determine the need for topical antivirals (HSV), systemic antivirals (VSV), topical steroids (in some cases of deep HSV) and to monitor for complications (necrosis, ulceration / perforation, scarring).

Fungal keratitis (keratomycosis) ⁴

• Nature - rare but potentially devastating infection most commonly caused by Aspergillus and Fusarium species and typically seen in agricultural settings or where an injury occurred involving organic matter such as wood or plants. Candida keratitis is seen in AIDS patients.
• Presentation - similar symptoms to bacterial keratitis but onset very gradual and less severe. May be diagnosed following non-response to treatment of 'bacterial' keratitis.
• Management - refer. The cornea should be scraped and topical antimycotic therapy initiated. The treatment may last many weeks and unresponsive cases may require systemic treatment or even a therapeutic penetrating keratoplasty (corneal transplant).

Protozoal keratitis

• Nature - the most feared is the Acanthamoeba species - a ubiquitous free-living protozoan found in air, soil and fresh water. It survives 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 - pain disproportionate to clinical signs: 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 the herpes simplex virus, acanthamoeba keratitis, Strep. viridans and long-term topical steroid therapy.

Trauma ⁵

Minor mechanical injury

• Nature - this is relatively common as fingernails, paper, foreign bodies and an assortment of other objects can cause abrasions (and less commonly, lacerations)
• Management - a full assessment as above should be performed. Abrasions - even very large ones - heal very well and the patient should be reassured. A 5-7 day course of topical chloramphenicol ointment (provides better lubrication, and therefore comfort, than drops) and advice to take simple oral analgesia as required should do. Review if the abrasion was large ± refer if concerned. Lacerations should be referred as they can easily mask a penetrating injury. Cover the eye with a rigid shield and make a same day referral.

Major mechanical injury

• Nature -this may range from contusion (closed injury although there may be associated corneal epithelial abrasion) to a full thickness open injury
• Management - if the history suggests a major injury, refer for further assessment, even if there is little to be seen on examination. An apparent simple corneal abrasion may overlie iris or retinal damage.

Chemical injury ⁶

Nature - this may range from trivial to sight threatening. The severity of the injury is proportional to the properties of the chemical, the amount of ocular surface affected and the duration of exposure (including retention of particles in the conjunctival fornices). Alkalis (particularly ammonium and sodium hydroxide) tend to penetrate deeper than do acids and cause particularly severe damage.
• Management:
  • IRRIGATE - do not waste time taking a history - this can be done once irrigation is underway or after. Irrigate copiously (several litres may be required for up to 30 minutes) and test pH frequently - even after normality (about 7) has been achieved as retained particles can lower the pH again.
  • After irrigation, take history and baseline examination - don't forget visual acuities as this may be the only point of reference if they deteriorate
  • Refer. A white eye does not preclude referral: limbal ischaemia blanches the vessels immediately around the cornea.

Thermal injury ⁶

• Nature - these may be thermal or ultraviolet (UV), the latter occurring in wielders not wearing protection and when bright light is reflected off concrete and snow. The damage is usually superficial.
• Management - most can be treated as corneal abrasions (see above). Analgesia is important, particularly in the case of UV burns which are notoriously painful. (Do not give topical analgesia to take home as this impedes epithelial healing).

Corneal foreign bodies

These most commonly occur in the context of DIY work, in manual labourers and car mechanics. They can usually simply be removed with a cotton bud under topical anaesthetic. A slit lamp and a steady hand enable removal of more deeply embedded FBs. Metallic FBs often leave a residual rust ring which should be removed then or subsequently (it should work its way more superficially after about a week). The patient should be warned that it will be more painful when the anaesthetic wears off but that the acute pain should not last more than a day. Centrally placed FBs may result in slightly altered visual acuity for a few weeks.

Contact lens problems

Contact lenses are now worn by millions of people, and the problems associated with wearing them are well recognised. The wearing of contact lenses causes changes in the cornea in terms of structure, turnover, tear production and oxygen and carbon dioxide levels. These changes in themselves can produce problems and may also exacerbate pre-existing conditions. Contact lens related problems may also be associated with the type of lens used, the frequency with which the lenses are changed, the cleaning systems used for the lenses as well as wearer related factors. The range of problems which may occur include minor problems from inadequate rinsing to loss of vision as a result of microbial keratitis. These problems are fully outlined in our dedicated article.

Recurrent corneal erosion syndrome (RCES)

RCES is a relatively common condition characterised by recurrent breakdown of the epithelium due to a defective adhesion to the underlying basement membrane. The initial insult is usually minor trauma such as a scratch but it may also occur in certain corneal dystrophies. There is a cycle of tearing of the epithelium (typically on waking as the lids open) which gradually resolves over hours but reoccurs the following day. The mainstay of treatment is regular lubricants until the defective basement membrane has fully healed. Occasionally, debridement is required to manage epithelial flaps. Other management options include prophylactic lubricants, bandage contact lens wear and epithelial keratectomy (the entire epithelium is removed in order to allow regrowth of fresh cells over the membrane and to stop the cycle of small epithelial flaps being torn into big ones on waking). Systemic tetracycline has also been found to be helpful although the reason why is not clear.

Congenital problems ⁷

• Abnormalities of size - megalocornea (where the cornea is too large) 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 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 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 syndrome, Nance-Horan syndrome and Cornelia de Lange syndrome.
• Abnormalities of shape - a flat cornea is known as cornea plana: 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. On the other hand, keratoglobus is the condition where there is an abnormally steeped, thin, round cornea.
• Corneal opacities - the corneal 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

Marginal keratitis

• Nature - a disorder caused by hypersensitivity to staphylococcal toxins, more commonly occurring in patients suffering from chronic staphylococcal keratitis. 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 short course of topical steroids.

Rosacea keratitis

• Nature - occurs in patients suffering from acne rosacea but the severity of the ocular condition does not correlate with that of the skin condition.
• Presentation - non-specific irritation, burning and redness associated with inferior punctate epithelial defects and peripheral neovascularization. There may be lid and conjunctival involvement too.
• Management - refer for topical steroids and a course of systemic antibiotics (e.g. doxycycline 100mg od for 6 weeks).

Other disorders

• Dellen - localised saucer-shaped thinning of the cornea caused by localised tear film instability. Managed with lubricants; transient condition.
• Phlyctenulosis - small pinkish-white nodule develops with an associated red eye. It occurs as a result as a result of a non-specific delayed hypersensitivity reaction to bacterial antigens. It is treated with a short course of antibiotics.
• Mooren ulcer - this uni / bilateral ulcerative condition arises as a result of an autoimmune response to corneal antigens. It is rare but serious and treatment depends on subtype (ranges from dietary to aggressive systemic steroid treatment).
• Terrien marginal degeneration - uncommon, idiopathic bilateral thinning of the cornea usually occurring in males after the fourth decade of life. There may be pain, there is decrease in visual acuity and eventually, surgery may be needed to excise the diseases tissue (results are limited).
• Ulcerative keratitis in systemic disease - this is particularly associated with rheumatoid arthritis where there is severe, progressive corneal thinning (perforation may occur) which is treated with topical steroids ± cyclosporin and systemic steroids. Ulcerative keratitis also occurs in the vasculitic conditions.

Degenerative conditions

Age-related degenerations

• Arcus senilis - this is the most common peripheral corneal opacity which may occur alone or in association with hyperlipidaemia. Rarely, it is unilateral in which case it is associated with carotid disease or ocular hypotony.
• Vogt limbal girdle - 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 below).

Lipid keratopathy

This involves deposits of lipid within the cornea which is associated with corneal vascularisation if left untreated. It requires laser or surgical removal.

Band keratopathy

This common condition is characterised by the deposition of calcium salts within the cornea, most commonly due to chronic uveitis but also associated with a number of other causes. Chelation is the treatment of choice: sodium edetate is applied until all the calcium is removed.

Other degenerative conditions

• Spheroidal degeneration - a bilateral condition (with many eponyms!) of unkown 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 nodular degeneration - discrete grey opacities arise in the cornea secondary to chronic keratitis (especially trachoma). The treatment is as for spheroidal degeneration.

Dystrophic conditions

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 AD 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.

Corneal ectasias

Keratoconus

• Nature - a progressive cone-like distortion of the cornea, starting in puberty, characterises this condition which is bilateral.
• Presentation - this results in progressive visual impairment requiring frequent spectacle changes and occasional sudden transient corneal oedema (acute hydrops) as the weakened Descemet membrane of the cornea cracks.
• Management - it is treated with spectacles initially, then contact lenses. Ultimately, these patients benefit from keratoplasty (corneal transplant).

Pellucid marginal degeneration

This condition is similar to keratoconus but occurs later in life and slit-lamp findings differ slightly. Treatment is the same.

Neurokeratopathies

Exposure keratopathy

• 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 - progressively painful red eye if left untreated in the presence of reduced tear film. Look for loss of shiney reflection from corneal surface.
• Management - if recovery of underlying problem is anticipated, aggressive lubrication will do. Otherwise, lid surgery will be considered (tarsorrhaphy- where the lids are partially sutured together).

Neurotrophic keratopathy

• Nature - this occurs when there is loss of sensation in the cornea (e.g. acoustic neuroma, diabetes, herpes simplex affecting fifth cranial nerve) and a secondary intracellular oedema (the pathogenesis is unknown).
• Presentation - variable from mild visual impairment secondary to corneal oedema through to epithelial defects leading to corneal ulceration.
• Management - lubrication ± patching.

Miscellaneous conditions

Astigmatism

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.

Drug-induced keratopathies

The cornea can be affected by a number of systemically administered drugs including gold (causing chryiasis - deposition of gold deposits), antimalarials and amiodarone (both of which give rise to vortex keratopathy characterised by whorl-like corneal deposits). It has also been described in the use of certain oriental herbal medicines. ⁸

Metabolic keratopathies:

• 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 - e.g. multiple myeloma, Waldenstrom 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 and Sanfilppo syndromes) and tend to be most severe in Hurler's syndrome. The retina and optic nerve may also be affected in these patients.
• Wilson disease - the Kayser-Fleischer ring is described in these patients: copper is deposited around the periphery of the cornea.