Keratoconus is a non-inflammatory eye (ocular) condition characterized by progressive changes of the shape of the cornea. The cornea is the thin-walled, "dome-shaped" transparent region forming the front of the eyeball; it serves as a protective covering and helps to focus or bend (refract) light waves onto the retina at the back of the eye. In those with Keratoconus, slowly progressive thinning of the cornea causes it to protrude forward in a conical shape, leading to blurry vision and other vision problems. Keratoconus often begins at puberty. Although the specific underlying cause of the condition is unknown, investigators indicate that genetic factors may play some role. In addition, in some cases, Keratoconus may occur in association with a variety of other disorders.
As noted above, Keratoconus is characterized by slowly progressive thinning and conical projection of the cornea. Both corneas are usually affected (bilateral), although the progression and severity of the condition in each eye may differ. The abnormal conical shape leads to changes in the ability of the cornea to help focus visual images appropriately on the retina (i.e., refractive abnormalities). (The retina, the innermost membrane at the back of the eye, contains light-responding nerve cells [rods, cones] that convert visual images into nerve impulses, which are conveyed via the optic nerve to the brain.) Keratoconus may initially cause slight blurring of vision and abnormally increased sensitivity to glare. With progressive corneal changes, affected individuals develop increasing nearsightedness (myopia) and progressive distortion of vision (astigmatism). Visual abnormalities associated with Keratoconus often become apparent during adolescence or young adulthood.
The specific underlying mechanism(s) responsible for Keratoconus remain unknown. The condition may occur as an isolated abnormality or be associated with certain underlying disorders (see below).
In some cases, Keratoconus appears to occur randomly for unknown reasons (sporadically) without an apparent family history. In other instances, the condition has affected more than one family member, suggesting that genetic factors may play some role. According to some investigators, certain familial cases may suggest autosomal dominant or autosomal recessive transmission or may represent multifactorial inheritance. Human traits, including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother.
In autosomal dominant disorders, a single copy of the disease gene (received from either the mother or father) may be expressed “dominating” the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.
In autosomal recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.
In disorders with multifactorial inheritance, the condition may arise due to the interaction of several genes, possibly in association with certain non-genetic (e.g., environmental) factors.
As noted above, Keratoconus may also sometimes occur in association with certain underlying disorders, such as Leber’s Congenital Amaurosis, Down Syndrome, Ehlers-Danlos Syndrome, or Marfan Syndrome. (For additional information on these disorders, please choose the appropriate name as your search term in the Rare Disease Database or see the “Related Disorders” section of this report below.)
Keratoconus tends to occur more often among adolescents than adults. One long-term study in the United States indicated a prevalence rate of 54.5 diagnosed cases of Keratoconus per 100,000 population. Involvement was limited to one eye in forty one percent of patients at the time of diagnosis, and both eyes were affected in 59 percent.
Keratoconus may be diagnosed based upon a complete patient and family history and thorough eye examination. Such examination may include evaluation of the external appearance of the eyes, visual acuity, eye movements, and visual fields; the use of an illuminated microscope to view internal structures of the front of the eyes (slit-lamp examination); and/or additional diagnostic assessments.
In some individuals with Keratoconus, vision may be improved with the use of appropriate eyeglasses or contact lenses. However, progressive changes in vision often necessitate frequent prescription changes.
Evidence suggests that appropriate contact lenses may often provide more effective visual correction and thus should be considered when eyeglasses are not sufficient. However, some affected individuals may not be able to wear contact lenses due to progressively severe corneal thinning, corneal scarring, and/or contact intolerance. In cases of severe visual deterioration in which contact lenses cannot sufficiently correct vision or are not tolerated, corneal transplantation may be required. A corneal transplant is a surgical procedure in which abnormal corneal tissue is removed and replaced with healthy donor corneal tissue.
Genetic counseling may be of benefit for individuals with Keratoconus and their families. Other treatment for the condition is symptomatic and supportive.
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Beers MH, et al., eds. The Merck Manual. 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:722.
Zadnik K, et al. Corneal scarring and vision in keratoconus: a baseline report from the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. Cornea. 2000;19:804-12.
Wang Y, et al. Genetic epidemiological study of keratoconus: evidence for major gene determination. Am J Med Genet. 2000;93:403-09.
Olson RJ, et al. Penetrating keratoplasty for keratoconus: a long-term review of results and complications. J Cataract Refract Surg. 2000;26:987-91.
Schmitt-Bernard C, et al. Keratographic analysis of a family with keratoconus in identical twins. J Cataract Refract Surg. 2000;26:1830-32.
Rabinowitz YS, et al. Molecular genetic analysis in autosomal dominant keratoconus. Cornea. 1992;11:302-08.
McDonnell PJ, et al. Electrosurgical keratoplasty. Clinicopathologic correlation. Arch Ophthalmol. 1988;106:235-38.
Ihalainen A. Clinical and epidemiological features of keratoconus: genetic and external factors in the pathogenesis of the disease. Acta Ophthal Suppl. 1986;178:1-66.
Kennedy RH, et al. A 48-year clinical and epidemiologic study of keratoconus. Am J Ophthalmol. 1986;101:267-73.
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Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 148300; 8/29/00. Available at: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?148300.
Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 244500; 2/19/94. Available at: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?244500.