Corneal Problems - Non Acute

The cornea is the avascular convex, slightly elliptical shaped anterior transparent part of the globe. It is the main site 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 inflammatory conditions can all potentially extend from one to the other.

This record provides an overview of long-standing or recurring corneal problems. Most of these patients will be under ongoing ophthalmologist supervision and will be familiar with their condition. For more acute problems, see our record on Corneal Problems - Acute. Other related records include:

Recurrent Corneal Erosion Syndrome
Dry Eye (Keratoconjunctivitis Sicca)
Corneal Microcysts
Contact Lenses (types and care)
Contact Lens Problems
Eye Trauma
Foreign Body in the Eye

You may also find our record on Examination of the Eye helpful.

When these patients present to you, your role is to decide whether this is part of an ongoing chronic problem (ongoing progression or an acute exacerbation) or whether this is a new problem. This will dictate the urgency of the referral. The symptoms associated with an acute problem and corneal assessment in primary care are discussed more fully in the record on acute corneal problems (see link above). In summary, complaints suggesting more acute pathology include:

• Pain
• Photophobia
• Sudden drop in visual acuity
• Red eye
• Systemic symptoms (e.g. headaches, nausea, general malaise)

It may be difficult to gauge the degree of additional pathology in a previously diseased cornea but it is worth checking the following:

• 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.
• 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 adnexae. If the symptoms warrant it, do a full systemic examination (see Disorders below).

Don't forget to discuss your findings with the patient. "Your left eye is seeing much less than your right; would you say that's about normal for you?" They can be very good at judging what is about right and what isn't for them.

The care of these patients is generally best left to ophthalmologists unless there is a clear written management plan suggesting otherwise. Your main role is to decide the urgency of referral. Be guided by the symptoms and don't hesitate to have a chat over the phone to your local team.

• 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's 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 below) and may be associated with Ehlers-Danlos type IV.⁴
• 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

Marginal keratitis

• 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 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. It is more common in middle-aged, fair-skinned females.⁴
• Presentation - non-specific irritation, burning and redness associated with inferior punctate epithelial defects and peripheral neovascularisation. There may be lid and conjunctival involvement too.
• Management⁴ - refer for topical steroids and a course of systemic antibiotics (e.g. doxycycline 100 mg od for 12 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 disease⁴

• 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 PUK (peripheral ulcerative keratitis).
• Presentation - this recurrent condition presents with acute uni/bilateral exacerbations characterised by decreased visual acuity, variable pain and redness (may be none).
• Management - treatment will involve systemic immunosuppression, topical immunosuppression, ocular lubricants and globe protection (such as an eye shield). Both the ophthalmologists and rheumatologists will be involved in patient care.

Other disorders

• Mooren ulcer - where PUK-associated ulceration occurs and is idiopathic, it is referred to as Mooren's ulcer.⁵ This is a (usually unilateral) ulcerative condition 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; 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 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 diseases tissue (results are limited).

Age-related degenerations

• 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).⁴ 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 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 keratopathy⁴

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.

Band keratopathy

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, e.g. prolonged glaucoma, long-standing corneal oedema and corneal dystrophies.⁵ It can also arise in the context of systemic disease such as hypercalcaemia, hyperuricaemia and in chronic renal failure.⁴ 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 shargreen - 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 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.

Keratoconus

• Nature - a progressive conical distortion of the cornea, starting in puberty, characterises this condition which is bilateral. It is the commonest primary corneal ectasia.⁵ The aetiology is not clear but repeated trauma (e.g. eye rubbing) and perhaps connective tissue disorders may contribute.⁴
• Presentation - 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.

Keratoglobus

See description above; it may also be acquired (probably as an end stage keratoconus).⁴ 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.

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 shiny 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: 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 is usually enough.

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. Vortex keratopathy has also been seen associated with indomethacin, tamoxifen use and clofazimine toxicity. Drug induced keratopathy has been described in the use of certain oriental herbal medicines.⁶

Thygeson's superficial punctate keratopathy

This is a rare, idiopathic condition that usually arises in the younger population (infant to 24 years).⁴ 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.⁵ 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.

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, 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 and Sanfilippo syndromes) 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 (e.g. brown, ruby red, bright green or yellow).