Keratopathies - Ophtnotes

Summary

Keratopathy is defined as disease of the cornea. There are many different types of keratopathy; some have local causes, whereas others have systemic causes. Here, we provide a summary of some of the important types of keratopathy to learn about for the Duke-Elder exam.

Neurotrophic keratopathy

Neurotrophic keratopathy (NK) is caused by loss of trigeminal innervation to the cornea, resulting in anaesthesia (partial or complete) and ulceration of the cornea. Loss of innervation results in intracellular oedema, exfoliation, loss of goblet cells and breakdown of the epithelium, causing persistent ulceration.

Causes

NK may be caused by any condition that damages the trigeminal nerve.

Stroke

Tumour

Surgical ablation of the trigeminal ganglia (for trigeminal neuralgia)

Peripheral neuropathy (e.g. due to diabetes)

Infection – herpes simplex and herpes zoster keratitis

Clinical features

Loss of sensation to the cornea (painless)

Persistent epithelial defect (i.e. ulceration) which can lead to stromal oedema and stromal “melting” (where the cornea becomes very soft due to enzymatic degradation and breakdown of corneal collagen)

Management

Discontinue any potentially toxic drugs

Topical lubricants – for associated dry eye/corneal exposure

Topical/systemic anticollagenase agents e.g. tetracyclines

Cenegermin – a topical recombinant human nerve growth factor, has been reported to be of benefit in moderate/severe ulcers (but the long-term effects are not yet known)

Protection of the ocular surface e.g. taping the eyelids (especially at night), botulinum toxin-induced ptosis, partial/complete tarsorrhaphy (joining of the upper and lower eyelids, temporarily or permanently), therapeutic silicone contact lenses

An epithelial erosion and defect in the central cornea with conjunctival hyperaemia, secondary to lateral medullary syndrome (Wallenberg syndrome). Image courtesy of Wu et al.

Exposure keratopathy

Inability to close the eyelids (lagophthalmos) causes the cornea to be exposed to the external environment for a prolonged period. This can result in drying of the ocular surface, despite normal tear production, causing a dry and eventually ulcerated eye. Exposure keratopathy can also lead to microbial keratitis, and permanent visual loss due to scarring

Causes

Exposure keratopathy can be caused by any condition that impairs the ability of the eye to protect the cornea: by inability to completely close the eyelid, an inadequate blink rate or blink reflex, or decreased protective lubrication of the cornea.

Neuroparalysis e.g. facial nerve palsy

Reduced muscle tone in Parkinson’s disease

Mechanical e.g. lid scarring, eczematous skin tightening, post-blepharoplasty

Proptosis

Medication effets – especially sedatives or neuromuscular blockers

Clinical features

Symptoms of dry eye syndrome – burning, stinging, tearing, itching, gritty feeling, foreign body sensation, redness, light sensitivity, frequent blinding, eye pain/headache

Punctate epithelial changes involving the inferior 1/3 of the cornea (especially with nocturnal lagophthalmos)

Epithelial breakdown, stromal melting, occasionally resulting in perforation

Inferior fibrovascular change

Secondary infection

Management

Depends on whether the lagophthalmos is expected to recover, and the severity of exposure.

Reversible exposure: artificial tears and ointment, taping the lid at night, bandage contact lenses, temporary tarsorrhaphy

Permanent exposure: permanent tarsorrhaphy, gold weight upper lid insertion (for facial nerve palsy)

Metabolic keratopathy

Metabolic keratopathy is caused by various diseases involving characteristic deposits in the cornea. The causes of metabolic keratopathy are summarised below.

Wilson’s disease

See our ‘Genetic disorders with ocular manifestations’ notes for more detail on Wilson’s disease.

Wilson’s disease is a rare autosomal recessive disorder characterised by copper deposition around the body. It is caused by a deficiency of caeruloplasmin, a copper-carrying protein

The typical presentation is neuropsychiatric or hepatic symptoms in a young person

A fine copper dusting in Descemet’s membrane causes a brownish-yellow ring, called a Kayser-Fleischer ring

Some patients have anterior capsular ‘sunflower’ cataracts

Treatment is with the chelating agent penicillamine, which can reverse the Kayser-Fleischer rings

Fabry disease

Fairy disease is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme alpha-galactosidase A. This results in abnormal tissue accumulation of a glycolipid

All males and some heterozygous females with the gene are affected

Systemic features

Episodic burning in the extremities (acroparaesthesia) and GI tract

Angiokeratomas (benign cutaneous capillary lesions)

Cardiomyopathy

Renal disease

Ocular manifestations

Golden vortex keratopathy (occurs in 75%), also known as whorl keratopathy or cornea verticillata – white to golden-brown corneal opacities in a vortex pattern. This is often the first feature of Fabry disease

Wedge- or spoke-shaped posterior cataract – known as ‘Fabry cataract’

‘Corkscrew vessels’ (conjunctival vascular tortuosity) and aneurysm formation

Retinal vascular tortuosity

Ocular changes seen in patients with Fabry disease: (A) vortex keratopathy, (B) increased tortuosity of conjunctival vessels, and (C) increased tortuosity of retinal vessels. Image courtesy of Pitz et al. (D) Vortex keratopathy (cornea verticillata) in a patient with Fabry disease. Image courtesy of Burlina et al.

Cystinosis

A rare autosomal recessive lysosomal storage disorder caused by a mutation in the CTNS gene

Characterised by widespread deposition of cystine crystals —> renal failure in childhood and other systemic problems

Keratopathy can occur in the first year of life: cystine crystals are deposited in the cornea and conjunctiva —> photophobia, epithelial erosions and visual impairment

Management is with cysteamine

Mucopolysaccharidoses (MPS)

A group of lysosomal storage disorders (mainly autosomal recessive) involving defective breakdown of glycosaminoglycans. Altered metabolites accumulate intracellular

Systemic features: coarse facial features, heart disease, skeletal abnormalities, learning difficult

Keratopathy: diffuse stromal haze and punctate corneal opacification (occurring in all MPS apart from Hunter and Sanfilippo MPS)

Lecithin-cholesterol-acyltransferase (LCAT) deficiency

Autosomal recessive disorder of lipoprotein metabolism, caused by a mutation in the LCAT gene

Two forms of the disease are found: Norum disease (complete disease, with systemic manifestations) and fisheye disease (partial disease, causing only corneal opacification)

The keratopathy involves numerous small greyish dots throughout the cornea, often concentrated in the periphery

Immunoprotein deposition

Several systemic diseases (e.g. multiple myeloma, Waldenström macroglobulinaemia, some lymphoproliferative disorders and leukaemia) result in immunoprotein deposition.

When the cornea is involved, bands of punctate flake-like opacities are seen, largely in the posterior stroma.

Management:

Treat the underlying disease

Corneal transplantation for severe corneal involvement

Tyrosinaemia type 2

Very rare autosomal recessive disease caused by a mutation in the TAT gene —> elevated plasma tyrosine levels

Systemic features: painful palmar and plantar hyperkeratotic lesions, CNS involvement

Ocular features: bilateral pseudodendritic keratitis with crystalline edges —> photophobia, watering, redness

Calcific Band Keratopathy

Calcific Band Keratopathy (also known as Band Keratopathy) is a corneal degeneration that involves the age-related deposition of calcium salts in the Bowman layer, epithelial basement membrane and anterior stroma.

Aetiology:

Age-related

Ocular disease: glaucoma, anterior uveitis (especially in children after juvenile idiopathic arthritis), intraocular surgery

Metabolic: secondary to hypercalcaemia

Hereditary

Idiopathic

Signs:

A band-shaped horizontal opacity that grows from peripheral cornea towards the central cornea

The initial deposits are grey, but the colour develops into chalky-white, and with dots in the areas of corneal nerves

Advanced lesions can become nodular and elevated