Introduction

 
Keratoconus (kehr-uh-toh-KOH-nus) is the most common corneal dystrophy that leads to severe visual impairment, with a prevalence of 1 to 430/2000. It is not a common known eye disorder, but it's by no means rare, and it is becoming more common due to the use of modern diagnostic equipment. Corneal transplant is the most commonly performed transplant surgery. Keratoconus is the most common degenerative condition of the front window of the eye which leads to corneal transplantation in the Western world.

Until recently, KC was managed by fitting a rigid gas-permeable contact lens, and penetrating keratoplasty when contact lenses could not be tolerated any more. With one in five needing a penetrating keratoplasty (the traditional corneal transplant), our mission was to reduce the numbers having this invasive surgery, which is now happening. 

Etiology

• The underlying reason for its development remains obscure; currently the topic of much research

• Usually an inherited corneal disorder, often in an autosomal recessive fashion 
  

• Family members may have it, but it also can be random with no other family members affected (sporadic)

• Most likely that the cause is due to more than one factor

The path that leads to the thinning of the cornea may start with a "trigger", followed by a cascade of events in the eye tissues

The primary trigger is not known

Possible options include hormonal changes in the patient, genetic predisposition to altered cytokines and/or their receptors in the patient's cornea, or a pattern of eye-rubbing or poor fitting RGP lenses that could release factors

Abnormal levels of degradative protease activity may then lead to a slow, progressive dissolution of Bowman's layer and the epithelial basement membrane

The epithelium then comes into contact with the stroma, cytokines/growth factors are released, and as a result, the cells begin to produce scar tissue and proteases

• A disorder with local micro-environmental changes rather than a situation where the entire cornea is involved

Within a single keratoconus cornea there are areas of increased protease activity (thinning) and other areas of ongoing wound healing (scar tissue buildup)

• Recent advances in molecular techniques make it possible to examine the molecular components in wounded or diseased corneas
  

CD45 (leukocyte common antigen or T200), a transmembrane phosphotyrosine phosphatase (normally found associated with blood cells), has been found to be present in more cells within keratoconus corneas than normal

These cells may represent the source of some of the proteolytic enzymes reported to be associated with keratoconus

A gene product referred to as glucose regulated protein (GRP78) has been found in greater quantity in normal corneas

A protein that aids or "chaperones" the folding and secretion of other proteins produced in cells.The reduction in GRP78 could affect the secretion and folding of the major structural proteins of the cornea which are reduced in the keratoconus cornea.

The cause of Keratoconus is not fully known
 

 

Incidence and Carrier Frequency 

• Some cases have a hereditary component and studies indicate that about 10% of patients have affected relatives
  
• Most cases appear to be sporadic
  

• The actual incidence is uncertain, large studies estimate 50 to 230 per 100,000
  
• According to one study, the estimated prevalence in first-degree relatives is 3.34%, which is 15 to 67 times higher than that in the general population (0.23-0.05%). (Am J Med Genet 2000 Aug 28;93(5):403-9 )
  
• Occurs in all ethnic groups, with certain ethnic groups effected more.
  

• Has a slight female preponderance
  

• Is more common in contact lens wearers and nearsighted eyes
  

• Some researchers believe allergy may play a role

 

Shown above is the contour of a Keratoconus cornea

 

 

• Non-inflammatory eye condition in which the normally round dome-shaped cornea progressively thins causing a cone-like bulge to develop
  

Results in significant visual impairment

• A degenerative condition where the cornea thins in affected areas and scar tissue develops
  

Can lead to astigmatism - often regular at first but becoming increasingly irregular as the disease progresses

• Surface thinning can create several optical zones that individually focus the same image to different areas of the retina, thus creating multiple perceived images
  

• Has been associated with other medical disorders including atopic disease, Down's syndrome, Ehlers-Danlos syndrome, Marfan's syndrome, craniofacial dysostosis and osteogenesis imperfecta
  

• Not a blinding disorder in the classical sense, but does result in increasing near-sightedness (things far away are out of focus) and irregular astigmatism (things look tilted)
  

• Is almost always bilateral (90% of cases)

Natural History 

• In the earliest stages, slight blurring, distortion of vision, and increased sensitivity to glare and light occur
  

Symptoms usually first appear in the late teens and early twenties

Mean age of onset is 16; onset as young as 6 yrs has been  recorded

Rarely develops after age 40

• May progress for 10-20 years and then slow in its progression
  

May halt at any stage from mild to severe

• Each eye may be affected differently
  

Disease develops asymmetrically: diagnosis of the disease in the second eye generally occurs about five years after diagnosis in the first

• Patients may endure discomfort and reduced vision over a long period of time.

 

• Can usually be diagnosed with slit lamp examination of the cornea
  

• Early cases may require corneal topography, a test that makes a stereo image which gives a topographic map of the corneal curvature
  

• When advanced, the cornea will be thinner in areas and this can be measured by pachymetry
  

• The biomicroscope is the only tool which allows a clinician to observe many classical signs of keratoconus: Fleischer's ring, stress lines of Vogt, corneal thinning and scarring, various types of staining with and without lens wear, increased visibility of corneal nerves, and corneal hydrops

 Ghosting

 

As Keratoconus progress’s the abnormalities of the cornea severely affect the way we see the world, making simple tasks like driving, watching TV or reading a book, difficult. This distortion has been compared to viewing a street sign through your car windshield during a driving rainstorm.

• Decreased visual acuity due to irregular astigmatism and/or corneal scarring (frequently changing prescriptions with glasses or contact lenses)
• Distorted and blurred vision.
  
• Glare and light sensitivity
• An acute corneal hydrops may induce pain

Signs

• Bilateral, progressive thinning of the corneal stroma, most often paracentral temporal inferior
• Distortion of the corneal contour with keratometry and computerized corneal topography, retinoscopy, and keratoscopy
• Vertical Vogt's striae may be evident in Descemet membrane at the apex of the cone
• Munson's sign: indentation of the lower lid by the conic cornea in downgaze
• Fleischer's ring: ring shaped iron deposition at the level of the epithelial basement membrane
• Descemet membrane rupture may result in acute hydrops with stromal edema and subepithelial central scarring

 Corneal curvature
Mild keratoconus    < 45D
Moderate keratoconus    45 - 52D
Advanced keratoconus    52 - 65D
Severe keratoconus    > 62D
 

Corneal thickness in microns
Normal cornea     543 Microns
Early keratoconus    506 Microns
Moderate keratoconus    473 Microns
Advanced keratoconus    446 Microns

Management 

• Glasses can be prescribed to correct the induced astigmatism in early keratoconus. Once the cylindrical power increases beyond 4.0 diopters visual intolerance may occur at which time prescribed contact lenses are needed
• UV-Crosslinking (to halt the progression of KC)
• Fitting of high performance soft toric lenses, piggyback lens systems, soft perm, and rigid gas-permeable Prescribed Contact Lenses.
• Scleral Lens Prosthetic Device

Selective cases (and by selecting your surgeon carefully) may be suitable for the following surgical operations: 

• Intacs
• Ferrara Rings
• Implantable Contact Lenses (Phakic / Toric)
• Deep anterior lamellar keratoplasty (DALK)

Selective cases in the near future may be eligible for (made possible due to UV - Crosslinking) limited customized topography guided surface ablation. An ALTK is another option which is on the horizon. A Penetrating Keratoplasty is considered as an absolute last option.