# Handbook of Genetic Counseling/Keratoconus

Keratoconus

## Assess Knowledge

* What do you already know about Keratoconus?
* What are your concerns today? What issues to you wish to discuss?

## Intake and Family History

* Discuss prepared pedigree to confirm the known cases of keratoconus

## 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 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.

## Incidence and Carrier Frequency

* some cases have a hereditary component and studies indicate that about 8% 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
* has a slight female preponderance
* is more common in contact lens wearers and nearsighted eyes
* some researchers believe allergy may play a role

## Clinical Features

* 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, 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 30
* 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

## Testing

* 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.

## Management and treatment

* eyeglasses or soft contact lenses may be used to correct the mild nearsightedness and astigmatism of early stages
* as the disorder progresses and the cornea continues to thin and change shape, rigid gas permeable contact lenses can be prescribed to correct vision
** contact lenses must be carefully fitted, and frequent checkups and lens changes may be needed to achieve and maintain good vision
** rigid contact lenses aid in flattening the corneal surface and provide optimal visual correction
* in severe cases, a corneal transplant may be needed due to scarring, extreme thinning or contact lens intolerance
** a surgical procedure that replaces the keratoconus cornea with healthy donor tissue
** 20-25% of those with keratoconus ultimately require corneal transplant surgery
*** success rate of greater than 90%
** corneal transplant is warranted when the cornea becomes dangerously thin or when sufficient visual acuity to meet the individual's needs can no longer be achieved by contact lenses due to steepening of the cornea, scaring or lens intolerance
** the more severe the keratoconus is, the more likely it is to see a dramatic improvement immediately after surgery
** the majority of keratoconus patients have their sutures removed 6-12 months after surgery (depends on healing rate)
** a small percentage of transplant patients do obtain uncorrected vision good enough that neither glasses nor contacts are needed after surgery, but in the majority of cases, some form of vision correction is needed after surgery

## Support Groups and Resources

* The National Keratoconus Foundation has a good website with patient resources (www.nkcf.org)
    National Keratoconus Foundation
    Davis Building, Suite 509
    8700 Beverly Boulevard
    Los Angeles, CA 90048
    (310) 855-6455 Office (800) 521-2524 Hotline (310) 652-8411 Fax
    e-mail: nkcf@csmc.edu
* The Center for Keratoconus has an excellent website (www.kcenter.org) with links to support groups, patient information, and research studies.
* The Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study is a multi-center, observational study, the purpose of which is to characterize vision, corneal changes, and patient quality of life findings in keratoconus and to determine the progression of changes occurring with keratoconus over time. The CLEK Study is an eight-year study. Over 1,200 keratoconus patients are enrolled at 15 participating clinics across the United States. To participate in this study, link to the site through the Digital Journal of Ophthalmology's website (www.djo.harvard.edu).
* A keratoconus mailing list is also available for those interested. To subscribe, send "subscribe keratoconus-link YOUR NAME" in the body of a mail message to listproc@ucdavis.edu.

## Notes

The information in this outline was last updated in 2002.