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Keratoconus

Keratoconus Description

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Keratoconus (from Greek: kerato- horn, cornea; and konos cone), is a degenerative disorder of the eye in which structural changes within the cornea cause it to thin and change to a more conical shape than its normal gradual curve.  Keratoconus can cause substantial distortion of vision, with multiple images, streaking and sensitivity to light all often reported by the patient. It is typically diagnosed in the patient's adolescent years and attains its most severe state in the twenties and thirties. If afflicting both eyes, the deterioration in vision can affect the patient's ability to drive a car or read normal print. In most cases, corrective lenses are effective enough to allow the patient to continue to drive legally and likewise function normally. Further progression of the disease may require surgery including intrastromal corneal ring segments, corneal collagen cross-linking, or corneal transplantation. However, despite the disease's unpredictable course, keratoconus can often be successfully managed with little or no impairment to the patient's quality of life.  Keratoconus is the most common dystrophy of the cornea, affecting around one person in a thousand. It seems to occur in populations throughout the world, although it occurs more frequently in certain ethnic groups. The exact cause of keratoconus is uncertain, but has been associated with detrimental enzyme activity within the cornea. A genetic link seems likely, as the incidence rate is greater if a family member has been diagnosed. The progression of keratoconus is rapid in patients having Down syndrome.

Despite considerable research, the etiology of keratoconus remains somewhat of a mystery. A number of sources suggest that keratoconus likely arises from a number of different factors: genetic, environmental or cellular, any of which may form the trigger for the onset of the disease.  A genetic predisposition to keratoconus has been observed, with the disease running in certain families, and incidences reported of concordance in identical twins.The frequency of occurrence in close family members is not clearly defined, though it is known to be considerably higher than that in the general population, and studies have obtained estimates ranging between 6% and 19%. A responsible gene has not been identified: two studies involving isolated, largely homogenetic communities have contrarily mapped putative gene locations to chromosomes 16q and 20q. However, most genetic studies agree on an autosomal dominant model of inheritance.Keratoconus is also diagnosed more often in people with Down syndrome, though the reasons for this link have not yet been determined. Keratoconus has been associated with atopic diseases, which include asthma, allergies, and eczema, and it is not uncommon for several or all of these diseases to affect one person. A number of studies suggest that vigorous eye rubbing contributes to the progression of keratoconus, and that patients should be discouraged from the practice.  Iatrogenic keratoconus has also been observed following LASIK surgery, caused by removal of excessive stromal bed tissue.

Treatments:

A recent surgical alternative to corneal transplant is the insertion of intrastromal corneal ring segments. A small incision is made in the periphery of the cornea and two thin arcs of polymethyl methacrylate are slid between the layers of the stroma on either side of the pupil before the incision is closed. The segments push out against the curvature of the cornea, flattening the peak of the cone and returning it to a more natural shape. The procedure, carried out on an outpatient basis under local anesthesia, offers the benefit of being reversible and even potentially exchangeable as it involves no removal of eye tissue.  The principal intrastromal ring available is known by the trade name of Intacs. Internationally, Ferrara Rings are also available. Intacs are a patented technology and are placed outside the optical zone versus the smaller prismatic Ferrara rings that are placed just inside the 5 mm optical zone. Intacs are the only corneal implants that have gone through the FDA Phase I, II and III clinical trials and were first approved by theFood and Drug Administration (FDA) in the United States in 1999 for myopia; this was extended to the treatment of keratoconus in July 2004..
 
A pair of Intacs after insertion into the corneaClinical studies on the effectiveness of intrastromal rings on keratoconus are in their early stages, and results have so far been generally encouraging, though they have yet to enter into wide acceptance with the refractive surgery community. In common with penetrating keratoplasty, the requirement for some vision correction in the form of spectacles or hydrophilic contact lenses may remain subsequent to the operation. Potential complications of intrastromal rings include accidental penetration through to the anterior chamber when forming the channel, post-operative infection of the cornea, and migration or extrusion of the segments. The rings offer a good chance of vision improvement even in otherwise hard to manage eyes, but results are not guaranteed and in a few cases may worsen.  Early studies on intrastromal corneal rings involved use of two segments to cause global flattening of the cornea. A later study reported that better results could be obtained for those cones located more to the periphery of the cornea by using a single Intacs segment. This leads to preferential flattening of the cone below, but also to steepening the over-flat upper part of the cornea.

Corneal collagen cross linking with riboflavin

Removed corneal epithelium during CCR operation on an eye with post-LASIKcomplication. From Kymionis et al., 2009.A treatment developed at the Technische Universität Dresden, and which has shown early success is Corneal Collagen Cross linking with Riboflavin, also known as CXL, CCR, and CCL. A one-time application of riboflavin solution is administered to the eye and is activated by illumination with UV-A light for approximately 30 minutes. The riboflavin causes new bonds to form across adjacent collagen strands in the stromal layer of the cornea, which recovers and preserves some of the cornea's mechanical strength. The corneal epithelial layer is generally removed in order to increase penetration of the riboflavin into the stroma.  Clinical trials are ongoing, but cross linking is seeing increasing adoption by the ophthalmological community, and has shown success in treating early cases of the disease. The procedure, with epithelium removed, is approved for use throughout Europe, and has recently commenced clinical trials in the USA. Early results are very promising with one study reporting stabilization in all treated eyes, and a slight correction in visual acuity in most patients.  In some cases, crosslinking may also be successfully combined with other treatment methods such as corneal ring segment inserts. Corrective lenses may still be required after this treatment, but it may play an important role in limiting deterioration of vision and reducing the case for corneal transplantation.
 
One way of reducing the risk of rejection is to use a newer technique called a Deep Anterior Lamellar Keratoplasty, referred to as DALK. In a DALK graft, only the outermost epithelium and the main bulk of the cornea, the stroma, are replaced; the patient's rearmost endothelium layer and the Descemet's membrane are left, giving some additional structural integrity to the post-graft cornea. Because a graft rejection usually begins in the endothelium,[citation needed] the chance of a rejection episode is greatly reduced. Furthermore, it is possible to transplant tissue from a donor which has been freeze-dried. The freeze-drying process ensures that this tissue is dead, so there is no chance of a rejection.  Some surgeons prefer to remove the donor epithelium, others leave the donor's cells in place. Removing it can cause a slight improvement in overall vision, but a corresponding increase in visual recovery time.

 

 

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