Keratoconus

Keratoconus (Greek: kerato – horn, cornea; and konos – cone) is a degenerative, non-inflammatory disorder of the cornea (the transparent dome at the front of the eye and its main focusing system), characterised by central and para-central thinning and subsequent irregular bulging of the cornea (also known as ectasia). This distortion of the corneal shape, results in irregular astigmatism (abnormality of the curvature of the cornea) with associated reduction in vision. It typically presents in adolescence and progresses in a variable manner. It was first described by the British physician John Nottingham in his text entitled "Practical observations on conical cornea: and on the short sight, and other
defects of vision connected with it
" in 1854.

Slit-lamp picture of an eye with advanced keratoconus showing gross inferior bowing (ectasia) of the cornea with associated thinning (courtesy of Addition Technology Inc).

Epidemiology

It is relatively common, affecting approximately one person in two thousand. It occurs in all ethnic groups world wide with males and females affected equally. It typically is bilateral, but asymmetric with the worse eye continuing to have a poorer prognosis as the condition progresses. Unilateral cases are very rare and it not uncommon for keratoconus to be diagnosed first in one eye and then later in the other.

The occurrence of keratoconus is usually an isolated condition, but has been reported to occur with increased frequency in a number of eye and bodily disorders. Eye associations include allergic eye disease, retinitis pigmentosa and aniridia. Bodily associations include atopy (eczema, hayfever), Magnesium deficiency, Down's syndrome, Turner syndrome and connective tissue disorders, such as Marfans, Ehlers-Danlos, osteogenesis imperfecta and pseuodoxanthoma elasticum. It has been particularly linked to various forms of eye trauma such as hard contact lens wear, allergic eye disease and eye rubbing. An inverse relationship between severity of the condition and diabetes has been reported.

Genetics

A genetic predisposition to keratoconus has been observed with the disease reported with increased incidence in some families. The frequency of occurrence in first and second degree family members of affected individuals is variable although it is known to be considerably higher than that in the general population, and studies have estimated between 6% and 19% of close family members may be affected. Genetic linkage studies have demonstrated multiple loci on different chromosomes, suggesting a number of genes may contribute to keratoconus susceptibility and whilst most genetic studies agree on a dominant autosomal model of inheritance (50% of off-spring affected) other models of inheritence have been suggested and variable penetrance (variable severity in different affected family members) is well documented.

Despite extensive laboratory and clinical research, the causes of keratoconus are poorly understood. It is thought to include biochemical, physical and genetic factors. However, no single proposed theory explains the various clinical features. It is therefore likely that the development of keratoconus is the final common pathway for several different disorders.

Laboratory studies have indicated that keratoconic corneas show signs of increased activity of proteinase enzymes (enzymes that degrade proteins) and a reduced activity in the proteinase enzyme inhibitors. This imbalance between proteinases and their inhibitors can destroy the structural proteins and supporting substrates within the cornea, resulting in thinning and loss of the normal mechanical strength.

As yet, the cause for this increased proteinase enzyme activity in keratoconic corneas is not known. It may be related to a state of increased oxidative stress found within the keratoconic cornea. It is known that the cornea is responsible for absorbing most of the ultraviolet light that enters the eye and it has to process the oxygen free radicals produced by the ultraviolet light. Oxygen free radicals are high energy molecules that can build up causing damage to cells by reacting with proteins, DNA and cell membranes. Normally the cornea eliminates oxygen free radicals by various antioxidant enzymes. It has been shown that keratoconic corneas can be deficient in these antioxidant enzymes, which may cause cell damage and the release of proteinase enzymes.

Another observation has been the evidence of increased apoptosis in keratoconic corneas. Apoptosis is the process of programmed cell death that occurs in tissue development, disease and wound healing. It has been proposed that mechanical trauma to the epithelium (the corneal skin) from rigid contact lenses, vigorous repeated eye rubbing and allergic eye conditions could cause apoptosis to occur in the cornea resulting in cell death and subsequent corneal thinning.

The doctor may notice some things during the examination, or the patient may mention symptoms, that could be caused by keratoconus. These include:

  • Sudden change of vision in just one eye.
  • Double vision when looking with just one eye.
  • Objects both near and far look distorted, but not blurred. In other words, small details of the objects are clear, but the shapes or colors look wrong. Later, distant objects do become blurred.
  • Bright lights look like they have halos around them.

These things might be related to keratoconus, but your doctor must measure the curvature of the cornea to be certain. Several different instruments can be used to measure the curvature of the cornea.

One instrument, called a keratometer, shines a pattern of light onto the cornea. The shape of the reflection of the pattern tells the doctor how the eye is curved. There are also computerized instruments that make three-dimensional "maps" of the cornea, a process called corneal topography.

Individuals with keratoconus typically present to their optician with blurred vision usually in one eye which may be of a fairly rapid onset. Photophobia (difficulty looking at light) and reports of eye-strain are not uncommon. Symptoms of multiple ghost images and flaring around light sources are common. There is often a history of worsening and variable short-sightedness and astigmatism (irregular curvature of the cornea), although the very early stages can be difficult to detect with only one eye being affected initially. More established cases have prescription changes at increasingly frequent intervals with the refractive error being difficult to correct with spectacles or soft contact lenses and the need for rigid (hard) contact lens correction.

Signs

Identifying individuals with moderate or advanced keratoconus is relatively straight forward. However, diagnosing keratoconus in its early stages is often more difficult requiring a thorough history and a careful assessment.

Early signs

  • Astigmatism is irregular i.e. the differences in curvature of the cornea are not perpendicular (at 90 degrees).
  • The red reflex (this is the red eye effect in the pupil often seen when taking photographs) is irregular and not uniform often showing an 'oil droplet' reflex. It can be observed by the Optician or Ophthalmologist (eye doctor) using an Ophthalmoscope (torch-like device used to look at the back of the eye) or a Retinoscope (torch-like device used to assess the strength of short- and long-sightedness and astigmatism)
  • Slit-lamp examination (a microscope device used to examine the eye) shows very fine, vertical, faint stress lines in the cornea (Vogt lines), Fleishers ring, which is a yellow-brown ring of iron pigment seen at the base of the cone beneath the epithelium in approximately 50 per cent of patients and visible corneal nerves.
  • Corneal topography is the most sensitive method for detecting very early keratoconus by identifying subtle, inferior corneal steepening. Corneal topography is a method by which a computer is used to analyze a video picture of the reflection of a series of rings of light projected onto the surface of the eye to make a detailed map of the surface of the cornea based on the position of the rings.

Late signs

  • Progressive corneal thinning (to one-third of the normal thickness) and bulging associated with poor vision from marked irregular astigmatism. The apex of the cone is the thinnest area and is usually displaced inferiorly just below the centre.
  • Corneal protrusion causing bulging of the lower lid on looking down (Munson sign).
  • Scarring of the cornea in severe cases occurs as the disorder progresses with ruptures in Bowman's membrane (the layer of the cornea immediately beneath its skin) which then become filled with scar tissue. 

The treatment of patients with keratoconus depends of the degree of ectasia (corneal bulging) and the resultant irregular astigmatism. Early and mild cases can be treated effectively with astigmatic spectacle correction and soft toric (astigmatism correcting) contact lenses. As the disease progresses rigid (hard) contact lenses become the mainstay of treatment. In the majority of eyes such lenses provide good visual rehabilitation. Unfortunately, they are not the solution in all cases. Discomfort and patient preference may limit the use of rigid contact lens wear and in advanced cases fitting may be problematic. Severe ectasia and central corneal scarring in advanced keratoconus can significantly limit the amount of visual rehabilitation achieved by rigid lenses. In addition, there is a body of evidence to suggest that repeated trauma caused by the wearing of rigid lenses may in some cases be responsible for the acceleration of the condition.

For these reasons, between 10-25% of patients with Keratoconus progress to a point where surgical intervention is required. Surgical options include:

  • Corneal transplantation (or grafting)
    • Penetrating Keratoplasty (full thickness transplantation/grafting)
    • Lamellar keratoplasty (partial thickness transplantation/grafting)
    • Epikeratophakia
  • Intra-corneal ring segment insert
    • Intacs
    • Ferrara Rings
  • Ultraviolet-A/Riboflavin corneal cross linkage (CR3)
  • Lenticular (lens) refractive surgery
    • Refractive lens exchange (cataract extraction) with toric (astigmatism correcting) intraocular lenses
    • Toric phakic intraocular lenses (akin to intraocular contact lenses)
  • Contra indications to surgery in individuals with pre-existing sub-clinical or overt keratoconus
    • Radial keratotomy
    • Refractive Excimer laser surgery