The "conical cornea" that is characteristic of keratoconus
|Classification and external resources|
Keratoconus (KC, KTCN) (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 the more 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. 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 fitted by a specialist are effective enough to allow the patient to continue to drive legally and likewise function normally. Further progression of the disease may require surgery, for which several options are available, including intrastromal corneal ring segments, corneal collagen cross-linking, mini asymmetric radial keratotomy and, in 25% of cases, corneal transplantation.
Estimates of the prevalence for keratoconus range from 1 in 500 to 1 in 2000 people, but difficulties with differential diagnosis cause uncertainty as to its prevalence. It seems to occur in populations throughout the world, although it is observed more frequently in certain ethnic groups, such as South Asians. Environmental and genetic factors are considered possible causes, but the exact cause is uncertain. It has been associated with detrimental enzyme activity within the cornea.
- 1 Signs and symptoms
- 2 Diagnosis
- 3 Pathophysiology
- 4 Treatment
- 4.1 Contact lenses, scleral lenses and prosthetic devices
- 4.2 Surgical options
- 5 Prognosis
- 6 Epidemiology
- 7 History
- 8 Related disorders
- 9 References
- 10 External links
Signs and symptoms
People with early keratoconus typically notice a minor blurring of their vision and come to their clinician seeking corrective lenses for reading or driving. At early stages, the symptoms of keratoconus may be no different from those of any other refractive defect of the eye. As the disease progresses, vision deteriorates, sometimes rapidly. Visual acuity becomes impaired at all distances, and night vision is often poor. Some individuals have vision in one eye that is markedly worse than that in the other. The disease is often bilateral, though asymmetrical. Some develop photophobia (sensitivity to bright light), eye strain from squinting in order to read, or itching in the eye, but there is normally little or no sensation of pain. It may cause luminous objects to appear as cylindrical pipes with the same intensity at all points.
The classic symptom of keratoconus is the perception of multiple "ghost" images, known as monocular polyopia. This effect is most clearly seen with a high contrast field, such as a point of light on a dark background. Instead of seeing just one point, a person with keratoconus sees many images of the point, spread out in a chaotic pattern. This pattern does not typically change from day to day, but over time, it often takes on new forms. Patients also commonly notice streaking and flaring distortion around light sources. Some even notice the images moving relative to one another in time with their heart beat. The predominant optical aberration of the eye in keratoconus is the so-called coma. The visual distortion experienced by the patient comes from two sources, one being the irregular deformation of the surface of the cornea, and the other being scarring that occurs on its exposed highpoints. These factors act to form regions on the cornea that map an image to different locations on the retina. The effect can worsen in low light conditions, as the dark-adapted pupil dilates to expose more of the irregular surface of the cornea.
Prior to any physical examination, the diagnosis of keratoconus frequently begins with an ophthalmologist's or optometrist's assessment of the patient's medical history, particularly the chief complaint and other visual symptoms, the presence of any history of ocular disease or injury which might affect vision, and the presence of any family history of ocular disease. An eye chart, such as a standard Snellen chart of progressively smaller letters, is then used to determine the patient's visual acuity. The eye examination may proceed to measurement of the localized curvature of the cornea with a manual keratometer, with detection of irregular astigmatism suggesting a possibility of keratoconus. Severe cases can exceed the instrument's measuring ability. A further indication can be provided by retinoscopy, in which a light beam is focused on the patient's retina and the reflection, or reflex, observed as the examiner tilts the light source back and forth. Keratoconus is amongst the ophthalmic conditions that exhibit a scissor reflex action of two bands moving toward and away from each other like the blades of a pair of scissors.
If keratoconus is suspected, the ophthalmologist or optometrist will search for other characteristic findings of the disease by means of slit lamp examination of the cornea. An advanced case is usually readily apparent to the examiner, and can provide for an unambiguous diagnosis prior to more specialized testing. Under close examination, a ring of yellow-brown to olive-green pigmentation known as a Fleischer ring can be observed in around half of keratoconic eyes. The Fleischer ring, caused by deposition of the iron oxide hemosiderin within the corneal epithelium, is subtle and may not be readily detectable in all cases, but becomes more evident when viewed under a cobalt blue filter. Similarly, around 50% of subjects exhibit Vogt's striae, fine stress lines within the cornea caused by stretching and thinning. The striae temporarily disappear while slight pressure is applied to the eyeball. A highly pronounced cone can create a V-shaped indentation in the lower eyelid when the patient's gaze is directed downwards, known as Munson's sign. Other clinical signs of keratoconus will normally have presented themselves long before Munson's sign becomes apparent, and so this finding, though a classic sign of the disease, tends not to be of primary diagnostic importance.
A handheld keratoscope, sometimes known as "Placido's disk", can provide a simple noninvasive visualization of the surface of the cornea by projecting a series of concentric rings of light onto the cornea. A more definitive diagnosis can be obtained using corneal topography, in which an automated instrument projects the illuminated pattern onto the cornea and determines its topology from analysis of the digital image. The topographical map indicates any distortions or scarring in the cornea, with keratoconus revealed by a characteristic steepening of curvature which is usually below the centreline of the eye. The technique can record a snapshot of the degree and extent of the deformation as a benchmark for assessing its rate of progression. It is of particular value in detecting the disorder in its early stages when other signs have not yet presented.
Once keratoconus has been diagnosed, its degree may be classified by several metrics:
- The steepness of greatest curvature from 'mild' (< 45 D), 'advanced' (up to 52 D) or 'severe' (> 52 D);
- The morphology of the cone: 'nipple' (small: 5 mm and near-central), 'oval' (larger, below-center and often sagging), or 'globus' (more than 75% of cornea affected);
- The corneal thickness from mild (> 506 μm) to advanced (< 446 μm).
Increasing use of corneal topography has led to a decline in use of these terms.
Clinical classification of Keratoconus in stages by Krumeich
|Stage is determined if one of the characteristics applies.
Corneal thickness is the thinnest measured spot of the cornea.
Despite considerable research, the etiology of keratoconus remains unclear. Several 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. Once initiated, the disease normally develops by progressive dissolution of Bowman's layer, which lies between the corneal epithelium and stroma. As the two come into contact, cellular and structural changes in the cornea adversely affect its integrity and lead to the bulging and scarring characteristic of the disorder. Within any individual keratoconic cornea, regions of degenerative thinning coexisting with regions undergoing wound healing may be found. Scarring appears to be an aspect of the corneal degradation; however, a recent, large, multicenter study suggests abrasion by contact lenses may increase the likelihood of this finding by a factor over two.
A number of studies have indicated keratoconic corneas show signs of increased activity by proteases, a class of enzymes that break some of the collagen cross-linkages in the stroma, with a simultaneous reduced expression of protease inhibitors. Other studies have suggested that reduced activity by the enzyme aldehyde dehydrogenase may be responsible for a build-up of free radicals and oxidising species in the cornea. Whatever the pathogenetical process, the damage caused by activity within the cornea likely results in a reduction in its thickness and biomechanical strength. While keratoconus is considered a noninflammatory disorder, one study shows wearing rigid contact lenses by patients leads to overexpression of proinflammatory cytokines, such as IL-6, TNF-alpha, ICAM-1, and VCAM-1 in the tear fluid.
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%. Two studies involving isolated, largely homogenetic communities have contrarily mapped putative gene locations to chromosomes 16q and 20q. Most genetic studies agree on an autosomal dominant model of inheritance. A rare, autosomal dominant form of severe keratoconus with anterior polar cataract is caused by a mutation in the seed region of mir-184, a microRNA that is highly expressed in the cornea and anterior lens. Keratoconus is diagnosed more often in people with Down's 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. Keratoconus is also associated with Alport syndrome, Down syndrome and Marfan syndrome. A number of studies suggest vigorous eye rubbing contributes to the progression of keratoconus, and patients should be discouraged from the practice. Keratoconus differs from Ectasia which is caused by LASIK eye surgery. Post-LASIK Ectasia has been associated with the excessive removal of the eye's stromal bed tissue during surgery.
Contact lenses, scleral lenses and prosthetic devices
In early stages of keratoconus, spectacles or soft contact lenses can suffice to correct for the mild astigmatism. As the condition progresses, these may no longer provide the patient with a satisfactory degree of visual acuity, and most clinical practitioners will move to manage the condition with rigid contact lenses, known as rigid, gas-permeable, (RGP) lenses. RGP lenses provide a good level of visual correction, but do not arrest progression of the condition.
In keratoconic patients, rigid contact lenses improve vision by means of tear fluid filling the gap between the irregular corneal surface and the smooth regular inner surface of the lens, thereby creating the effect of a smoother cornea. Many specialized types of contact lenses have been developed for keratoconus, and affected people may seek out both doctors specialized in conditions of the cornea, and contact lens fitters who have experience managing patients with keratoconus. The irregular cone presents a challenge and the fitter will endeavor to produce a lens with the optimal contact, stability and steepness. Some trial-and-error fitting may prove necessary.
Traditionally, contact lenses for keratoconus have been the 'hard' or RGP variety, although manufacturers have also produced specialized 'soft' or hydrophilic lenses and, most recently, silicone hydrogel lenses. A soft lens has a tendency to conform to the conical shape of the cornea, thus diminishing its effect. To counter this, hybrid lenses have been developed which are hard in the centre and encompassed by a soft skirt. However, soft or earlier generation hybrid lenses did not prove effective for every patient. Early generation lenses like SoftPerm have been discontinued. The fourth generation of hybrid lens technology has improved significantly, giving more patients an option that combines the comfort of a soft lens with the visual acuity of an RGP lens. The new generation of technology fixes the issues prevalent in earlier generations and allows contact lenses to be fitted for the majority of patients. This technology of hybrid concepts as taken a new leg with the combined efforts of certain manfucatures, namely CooperVision, SyngerEyes, and Eyetrust vision.
Some patients also find good vision correction and comfort with a "piggyback" lens combination, in which RGP lenses are worn over soft lenses, both providing a degree of vision correction. One form of piggyback lens makes use of a soft lens with a countersunk central area to accept the rigid lens. Fitting a piggyback lens combination requires experience on the part of the lens fitter, and tolerance on the part of the keratoconic patient.
Scleral lenses are sometimes prescribed for cases of advanced or very irregular keratoconus; these lenses cover a greater proportion of the surface of the eye and hence can offer improved stability. The larger size of the lenses may make them unappealing or uncomfortable to some; however, their easier handling can find favor with patients with reduced dexterity, such as the elderly.
Mini sclerals have been available for a few years are a hybrid between a conventional RGP lens and a full scleral and just vault over the cornea into the limbus region. Light in weight, high in oxygen permeability and easy maintenance makes this an option for cases where a patient's condition has advanced beyond specialized soft lens. An example is Esclera or SoClear.
PROSE (prosthetic replacement of the ocular surface ecosystem) treatment can improve vision and alleviate symptoms in patients with diseases that cause corneal ectasia, including keratoconus. PROSE uses custom fabricated prosthetic devices to improve vision by masking irregularities on the cornea’s surface and transmitting a sharp image to the back of the eye.
Corneal collagen crosslinking with riboflavin, (also known as CXL, C3-R, CCL and KXL ), involves a one-time application of riboflavin solution to the eye that 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 to increase penetration of the riboflavin into the stroma.
Clinical trials began in Germany in 1998 and Italy in 2004, and cross-linking has shown success in retarding or stopping progression of the disease. Results from an Australian study published in 2008 showed stabilization in all treated eyes, and a slight correction in visual acuity in most patients. The procedure without removing epithelium was first performed in 2004 in Beverly Hills. The procedure, with epithelium removed, is approved for use throughout Europe, and commenced clinical trials in the USA in 2008. By 2010, over 300 patients were treated in the United States in those trials, which are composed of two randomized, controlled, multisite clinical trials for the treatment of progressive keratoconus and post LASIK ectasia.
In some cases, collagen cross-linking may also be combined with other treatments to improve corneal asymmetry, optical refraction or corneal strength. Successful treatment methods include Mini Asymmetric Radial Keratotomy (M.A.R.K.), corneal ring segment inserts (Intacs, Ferrara or Keraring rings),  Topography Guided Laser, Keraflex, or CISIS (MyoRing Treatment). In the latter case Riboflavin is injected into a corneal pocket to bypass the epithelium, which is not required to be removed and, therefore, this treatment method is painless. Corrective lenses are normally required after these treatments, but with smaller, more normalized prescriptions. Increased corneal symmetry allows for more comfortable contact lens wear, often of daily disposable lenses. These newer methods may have an important role in limiting deterioration of vision, increasing unaided and uncorrected vision, and reducing the case for corneal transplantation. 
Corneal ring implants
Intrastromal corneal ring segments (ICRS)
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 by a suture. 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 anaesthesia, offers the benefit of being reversible and even potentially exchangeable as it involves no removal of eye tissue.
The principal intrastromal ring segment available is known by the trade name Intacs and Keraring (Mediphacos). Ferrara rings are also available. Intacs are a patented technology and are placed outside the optical zone, whereas the smaller prismatic Kerarings and Ferrara rings are placed just inside the 5 mm optical zone. Intacs are the only corneal implants to have gone through the FDA Phase I, II and III clinical trials and were first approved by the Food and Drug Administration (FDA) in the United States in 1999 for myopia; this was extended to the treatment of keratoconus in July 2004.
Clinical studies on the effectiveness of intrastromal ring segments 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, postoperative infection of the cornea, and migration or extrusion of the segments including corneal melting. 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 ring segments involved use of two segments to cause global flattening of the cornea. A later study reported 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.
MyoRing (Dioptex) is a complete continous ring for implantation into a corneal pocket for the treatment of low, moderate and high myopia  and all grades of Keratoconus. MyoRing is an internationally patented device. It is approved for treatment as a medical device in the European Union since 2006 and many other countries outside EU. MyoRing insertion into the cornea (CISIS) can replace keratoplasty in most cases of keratoconus, CISIS stands for Corneal Improvement and Safe Imaging Solution. It cannot be used anymore if the corneal thickness is less than 350 microns.
Keraflex (Microwave Thermoplasty)
Keraflex (Avedro, Inc.) is a new microwave thermokeratoplasty procedure used for the treatment of keratoconus. Keraflex transforms and flatten the corneal shape by the means of microwave energy transmitted by a circular electrode, which automatically delivers the treatment to the desired specification. Microwaves cause collagen fibers to shrink, hence producing a corneal flattening. After the actual corneal flattening with microwave energy, riboflavin drops are administered over the treatment area and ultraviolet light is administered to crosslink the corneal collagen to lock-in the corneal flattening.
To date, there is no concrete evidence on how long the cornea remains stable after the combined treatments of Keraflex and focal CXL. The first cohort of patients was treated in late November 2009, and stability data are not yet available. A larger cohort was treated in January 2010.
Radial keratotomy is a refractive surgery procedure developed by Russian ophtalmologist Svyatoslav Fyodorov in 1974, where the surgeon makes a spoke-like pattern of incisions into the cornea to modify its shape. This early surgical option for myopia has been largely superseded by LASIK and other similar procedures. LASIK is absolutely contraindicated in keratoconus and other corneal thinning conditions as removal of corneal stromal tissue will further damage an already thin and weak cornea.
Mini asymmetric radial keratotomy
The mini asymmetric radial keratotomy is a surgical technique developed by Italian ophthalmologist Marco Abbondanza in 1993 and improved in 2005. It consists of a series of micro-incisions, always made with a diamond knife, designed to cause a controlled scarring of the cornea, which changes its thickness and shape. This procedure, if done properly, is able to correct astigmatism and allows at least temporal correction of the first and second stage of keratoconus, postponing the need for a cornea transplant. The Mini Asymmetric Radial Keratotomy can also be used in combination with the cross-linking (also known as CXL, CCR, CCL and KXL), parasurgical treatment for keratoconus.
Between 11% and 27% of cases of keratoconus will progress to a point where vision correction is no longer possible, thinning of the cornea becomes excessive, or scarring as a result of contact lens wear causes problems of its own, and a corneal transplantation or penetrating keratoplasty becomes required. Keratoconus is the most common grounds for conducting a penetrating keratoplasty, generally accounting for around a quarter of such procedures. The corneal transplant surgeon trephines a lenticule of corneal tissue and then grafts the donor cornea to the existing eye tissue, usually using a combination of running and individual sutures. The cornea does not have a direct blood supply, so the donor tissue is not required to be blood type matched. Eye banks check the donor corneas for any disease or cellular irregularities.
The acute recovery period can take four to six weeks, and full postoperative vision stabilization often takes a year or more, but most transplants are very stable in the long term. The National Keratoconus Foundation reports that penetrating keratoplasty has the most successful outcome of all transplant procedures, and when performed for keratoconus in an otherwise healthy eye, its success rate can be 95% or greater. The sutures used usually dissolve over a period of three to five years, but individual sutures can be removed during the healing process if they are causing irritation to the patient.
In the USA, corneal transplants (also known as corneal grafts) for keratoconus are usually performed under sedation as outpatient surgery. In other countries, such as Australia and the UK, the operation is commonly performed with the patient undergoing a general anaesthetic. All cases require a careful follow-up with an eye doctor (ophthalmologist or optometrist) for a number of years. Frequently, vision is greatly improved after the surgery, but even if the actual visual acuity does not improve, because the cornea is a more normal shape after the healing is completed, patients can more easily be fitted with corrective lenses. Complications of corneal transplants are mostly related to vascularization of the corneal tissue and rejection of the donor cornea. Vision loss is very rare, though difficult-to-correct vision is possible. When rejection is severe, repeat transplants are often attempted, and are frequently successful. Keratoconus will not normally reoccur in the transplanted cornea; incidences of this have been observed, but are usually attributed to incomplete excision of the original cornea or inadequate screening of the donor tissue. The long-term outlook for corneal transplants performed for keratoconus is usually favorable once the initial healing period is completed and a few years have elapsed without problems.
One way of reducing the risk of rejection is to use a technique called deep anterior lamellar keratoplasty (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 postgraft cornea. Furthermore, it is possible to transplant freeze-dried donor tissue. The freeze-drying process ensures this tissue is dead, so there is no chance of rejection.
Some surgeons prefer to remove the donor epithelium; others leave it in place. Removing it can cause a slight improvement in overall vision, but a corresponding increase in visual recovery time.
Rarely, a nonpenetrating keratoplasty known as an epikeratophakia (or epikeratoplasty) may be performed in cases of keratoconus. The corneal epithelium is removed and a lenticule of donor cornea is grafted on top of it. The procedure requires a greater level of skill on the part of the surgeon, and is less frequently performed than a penetrating keratoplasty, as the outcome is generally less favorable. However, it may be seen as an option in a number of cases, particularly for young patients.
Patients with keratoconus typically present initially with mild astigmatism and myopia, commonly at the onset of puberty, and are diagnosed by the late teenage years or early 20s. The disease can, however, present or progress at any age; in rare cases, keratoconus can present in children or not until later adulthood. A diagnosis of the disease at an early age may indicate a greater risk of severity in later life. Patients' vision will seem to fluctuate over a period of months, driving them to change lens prescriptions frequently, but as the condition worsens, contact lenses are required in the majority of cases. The course of the disorder can be quite variable, with some patients remaining stable for years or indefinitely, while others progress rapidly or experience occasional exacerbations over a long and otherwise steady course. Most commonly, keratoconus progresses for a period of 10 to 20 years before the course of the disease generally ceases in the third and fourth decades of life.
In advanced cases, bulging of the cornea can result in a localized rupture of Descemet's membrane, an inner layer of the cornea. Aqueous humor from the eye's anterior chamber seeps into the cornea before Descemet's membrane reseals. The patient experiences pain and a sudden severe clouding of vision, with the cornea taking on a translucent milky-white appearance known as a corneal hydrops. Although disconcerting to the patient, the effect is normally temporary and after a period of six to eight weeks, the cornea usually returns to its former transparency. The recovery can be aided nonsurgically by bandaging with an osmotic saline solution. Although a hydrops usually causes increased scarring of the cornea, occasionally it will benefit a patient by creating a flatter cone, aiding the fitting of contact lenses. corneal transplantation is not usually indicated during corneal hydrops.
The National Eye Institute reports keratoconus is the most common corneal dystrophy in the United States, affecting about one in 2,000 Americans, but some reports place the figure as high as one in 500. The inconsistency may be due to variations in diagnostic criteria, with some cases of severe astigmatism interpreted as those of keratoconus, and vice versa. A long-term study found a mean incidence rate of 2.0 new cases per 100,000 population per year. Some studies have suggested a higher prevalence amongst females, or that people of South Asian ethnicity are 4.4 times as likely to suffer from keratoconus as Caucasians, and are also more likely to be affected with the condition earlier.
Keratoconus is normally bilateral (affecting both eyes) although the distortion is usually asymmetric and is rarely completely identical in both corneas. Unilateral cases tend to be uncommon, and may in fact be very rare if a very mild condition in the better eye is simply below the limit of clinical detection. It is common for keratoconus to be diagnosed first in one eye and not until later in the other. As the condition then progresses in both eyes, the vision in the earlier-diagnosed eye will often remain poorer than that in its fellow.
The German oculist Burchard Mauchart provided an early description in a 1748 doctoral dissertation of a case of keratoconus, which he called staphyloma diaphanum. However, it was not until 1854 that British physician John Nottingham (1801 – 1856) clearly described keratoconus and distinguished it from other ectasias of the cornea. Nottingham reported the cases of "conical cornea" that had come to his attention, and described several classic features of the disease, including polyopia, weakness of the cornea, and difficulty matching corrective lenses to the patient's vision. In 1859, British surgeon William Bowman used an ophthalmoscope (recently invented by Hermann von Helmholtz) to diagnose keratoconus, and described how to angle the instrument's mirror so as to best see the conical shape of the cornea. Bowman also attempted to restore vision by pulling on the iris with a fine hook inserted through the cornea and stretching the pupil into a vertical slit, like that of a cat. He reported that he had had a measure of success with the technique, restoring vision to an 18-year old woman who had previously been unable to count fingers at a distance of 8 inches (20 cm). By 1869, when the pioneering Swiss ophthalmologist Johann Horner wrote a thesis entitled On the treatment of keratoconus, the disorder had acquired its current name. The treatment at that time, endorsed by the leading German ophthalmologist Albrecht von Graefe, was an attempt to physically reshape the cornea by chemical cauterization with a silver nitrate solution and application of a miosis-causing agent with a pressure dressing. In 1888, the treatment of keratoconus became one of the first practical applications of the then newly invented contact lens, when the French physician Eugène Kalt manufactured a glass scleral shell that improved vision by compressing the cornea into a more regular shape. Since the start of the 20th century, research on keratoconus has both improved understanding of the disease and greatly expanded the range of treatment options. The first successful corneal transplantation to treat keratoconus was done in 1936 by Ramon Castroviejo.
- Keratoglobus is a very rare condition that causes corneal thinning primarily at the margins, resulting in a spherical, slightly enlarged eye. It may be genetically related to keratoconus.
- Pellucid marginal degeneration causes thinning of a narrow (1–2 mm) band of the cornea, usually along the inferior corneal margin. It causes irregular astigmatism that, in the early stages of the disease can be corrected by spectacles. Differential diagnosis may be made by slit-lamp examination.
- Posterior keratoconus, a distinct disorder despite its similar name, is a rare abnormality, usually congenital, which causes a nonprogressive thinning of the inner surface of the cornea, while the curvature of the anterior surface remains normal. Usually only a single eye is affected.
- Post-LASIK ectasia is a complication of LASIK eye surgery.
- Weissman, Barry A; Yeung, Karen K. "Keratoconus". Medscape.
- "About Keratoconus Eye Disease". National Keratoconus Foundation.
- Czugala, Marta; Karolak, Justyna A; Nowak, Dorota M; Polakowski, Piotr; Pitarque, Jose; Molinari, Andrea; Rydzanicz, Malgorzata; Bejjani, Bassem A; Yue, Beatrice Y J T; Szaflik, Jacek P; Gajecka, Marzena (2 November 2011). "Novel mutation and three other sequence variants segregating with phenotype at keratoconus 13q32 susceptibility locus". European Journal of Human Genetics 20 (4): 389–397. doi:10.1038/ejhg.2011.203.
- Gajecka, Marzena; Nowak, DorotaM (2011). "The genetics of keratoconus". Middle East African Journal of Ophthalmology 18 (1): 2. doi:10.4103/0974-9233.75876.
- Nottingham J. Practical observations on conical cornea: and on the short sight, and other defects of vision connected with it. London: J. Churchill, 1854.
- Feder R, Kshettry P (2005). "Non-inflammatory Ectactic Disorders, Chapter 78". In Krachmer J. Cornea. Mosby. ISBN 0-323-02315-0.
- Epstein A (2000). "Keratoconus and related disorders" (PDF). North Shore Contact Lens. Retrieved 8 September 2007.
- Pantanelli S, MacRae S, Jeong TM, Yoon G (November 2007). "Characterizing the wave aberration in eyes with keratoconus or penetrating keratoplasty using a high-dynamic range wavefront sensor". Ophthalmology 114 (11): 2013–21. doi:10.1016/j.ophtha.2007.01.008. PMID 17553566.
- Nakagawa T; Maeda N; Kosaki R et al. (June 2009). "Higher-order aberrations due to the posterior corneal surface in patients with keratoconus". Investigative Ophthalmology & Visual Science 50 (6): 2660–5. doi:10.1167/iovs.08-2754. PMID 19029032.
- Nordan LT (1997). "Keratoconus: diagnosis and treatment". International Ophthalmology Clinics 37 (1): 51–63. doi:10.1097/00004397-199703710-00005. PMID 9101345.
- Zadnik K (1997). The ocular examination : measurements and findings. Philadelphia: W.B. Saunders. ISBN 0-7216-5209-3.
- Rabonitz Y (2004). "Ectatic Disorders of the Cornea". In Foster C et al. The Cornea (4th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 889–911. ISBN 0-7817-4206-4.
- Edrington TB, Zadnik K, Barr JT (1995). "Keratoconus". Optometry Clinics 4 (3): 65–73. PMID 7767020.
- Krachmer JH, Feder RS, Belin MW (1984). "Keratoconus and related noninflammatory corneal thinning disorders". Survey of Ophthalmology 28 (4): 293–322. doi:10.1016/0039-6257(84)90094-8. PMID 6230745.
- Caroline P, Andre M, Kinoshita B, and Choo, J. "Etiology, Diagnosis, and Management of Keratoconus: New Thoughts and New Understandings". Pacific University College of Optometry. Retrieved 15 December 2008.
- Maguire LJ, Bourne WM (August 1989). "Corneal topography of early keratoconus". American Journal of Ophthalmology 108 (2): 107–12. PMID 2757091.
- Gupta D. "Keratoconus: A clinical update" (PDF). Archived from the original on 15 May 2006. Retrieved 26 March 2006.
- J Refract Surg. 2009 Apr;25(4):357-65.
- Klin Monbl Augenheilkd. 1997 Aug;211(2):94-100.
- Arffa R (1997). Grayson's Diseases of the Cornea. Chap. 17. Mosby. pp. 452–454. ISBN 0-8151-3654-4.
- Brown D. National Keratoconus Foundation: Research Overview. http://www.nkcf.org. Accessed 12 February 2006.
- Barr JT; Wilson BS; Gordon MO et al. (January 2006). "Estimation of the incidence and factors predictive of corneal scarring in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study". Cornea 25 (1): 16–25. doi:10.1097/01.ico.0000164831.87593.08. PMID 16331035.
- "The Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study Archive".
- Spoerl E, Wollensak G, Seiler T (July 2004). "Increased resistance of crosslinked cornea against enzymatic digestion". Current Eye Research 29 (1): 35–40. doi:10.1080/02713680490513182. PMID 15370365.
- Gondhowiardjo TD; van Haeringen NJ; Völker-Dieben HJ et al. (March 1993). "Analysis of corneal aldehyde dehydrogenase patterns in pathologic corneas". Cornea 12 (2): 146–54. doi:10.1097/00003226-199303000-00010. PMID 8500322.
- Lema I, Durán JA, Ruiz C, Díez-Feijoo E, Acera A, Merayo J (August 2008). "Inflammatory response to contact lenses in patients with keratoconus compared with myopic subjects". Cornea 27 (7): 758–63. doi:10.1097/ICO.0b013e31816a3591. PMID 18650659.
- Edwards M, McGhee CN, Dean S (December 2001). "The genetics of keratoconus". Clinical & Experimental Ophthalmology 29 (6): 345–51. doi:10.1046/j.1442-9071.2001.d01-16.x. PMID 11778802.
- Zadnik K; Barr JT; Edrington TB et al. (December 1998). "Baseline findings in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study". Investigative Ophthalmology & Visual Science 39 (13): 2537–46. PMID 9856763.
- Merin S (2005). Inherited Eye Disorders: Diagnosis and Management. Boca Raton: Taylor & Francis. ISBN 1-57444-839-0.
- Hughes AE, Bradley DT, Campbell M, Lechner J, Dash DP, Simpson DA, Willoughby CE (2011). "Mutation Altering the miR-184 Seed Region Causes Familial Keratoconus with Cataract". The American Journal of Human Genetics 32 (8): 691–7. doi:10.1016/j.ajhg.2011.09.014. PMC 3213395. PMID 21996275. Retrieved 14 October 2011.
- Rabinowitz YS (1998). "Keratoconus". Survey of Ophthalmology 42 (4): 297–319. doi:10.1016/S0039-6257(97)00119-7. PMID 9493273.
- Kumar, Vinay (2007). "Eye: Cornea, Degenerations and Dystrophies". Robbins Basic Pathology (8th ed.). Philadelphia: Saunders/Elsevier. ISBN 978-1416029731.
- Koenig SB (November 2008). "Bilateral recurrent self-induced keratoconus". Eye & Contact Lens 34 (6): 343–4. doi:10.1097/ICL.0b013e31818c25eb. PMID 18997547.
- McMonnies CW, Boneham GC (November 2003). "Keratoconus, allergy, itch, eye-rubbing and hand-dominance". Clinical & Experimental Optometry 86 (6): 376–84. doi:10.1111/j.1444-0938.2003.tb03082.x. PMID 14632614.
- Bawazeer AM, Hodge WG, Lorimer B (August 2000). "Atopy and keratoconus: a multivariate analysis". The British Journal of Ophthalmology 84 (8): 834–6. doi:10.1136/bjo.84.8.834. PMC 1723585. PMID 10906086.
- Jafri B, Lichter H, Stulting RD (August 2004). "Asymmetric keratoconus attributed to eye rubbing". Cornea 23 (6): 560–4. doi:10.1097/01.ico.0000121711.58571.8d. PMID 15256993.
- Ioannidis AS, Speedwell L, Nischal KK (February 2005). "Unilateral keratoconus in a child with chronic and persistent eye rubbing". American Journal of Ophthalmology 139 (2): 356–7. doi:10.1016/j.ajo.2004.07.044. PMID 15734005.
- Lindsay RG, Bruce AS, Gutteridge IF (July 2000). "Keratoconus associated with continual eye rubbing due to punctal agenesis". Cornea 19 (4): 567–9. doi:10.1097/00003226-200007000-00034. PMID 10928781.
- "Corneal Dystrophies (including Keratoconus)". Eye Info. RNIB. Retrieved 20 January 2009.
- Rubinstein MP, Sud S (1999). "The use of hybrid lenses in management of the irregular cornea". Contact Lens & Anterior Eye 22 (3): 87–90. doi:10.1016/S1367-0484(99)80044-7. PMID 16303411.
- "SoftPerm Hybrid Contact Lenses Discountinued=".
- Davis Robert, Eiden Barry. Hybrid Contact Lens Management. Contact Lens Spectrum: .
- Davis Robert. Recent Hybrid Lens Technology. TreatKerataconus: .
- "Duette and K-Lens Contact Lenses". Kerataconus: .
- Yeung K, Eghbali F, Weissman BA (September 1995). "Clinical experience with piggyback contact lens systems on keratoconic eyes". Journal of the American Optometric Association 66 (9): 539–43. PMID 7490414.
- Pullum KW, Buckley RJ (November 1997). "A study of 530 patients referred for rigid gas permeable scleral contact lens assessment". Cornea 16 (6): 612–22. doi:10.1097/00003226-199711000-00003. PMID 9395869.
- "Mediphacos, Ltda". ASCRS.
- Baran I, Bradley JA, Alipour F, Rosenthal P, Le HG, Jacobs DS (October 2012). "PROSE treatment of corneal ectasia". Contact Lens & Anterior Eye 35 (5): 222–7. doi:10.1016/j.clae.2012.04.003. PMID 22633003.
- DeLoss KS, Fatteh NH, Hood CT (November 2014). "Prosthetic Replacement of the Ocular Surface Ecosystem (PROSE) Scleral Device Compared to Keratoplasty for the Treatment of Corneal Ectasia". American Journal of Ophthalmology 158 (5): 974–982.e2. doi:10.1016/j.ajo.2014.07.016. PMID 25058902.
- Lee JC, Chiu GB, Bach D, Bababeygy SR, Irvine J, Heur M (December 2013). "Functional and visual improvement with prosthetic replacement of the ocular surface ecosystem scleral lenses for irregular corneas". Cornea 32 (12): 1540–3. doi:10.1097/ICO.0b013e3182a73802. PMID 24145631.
- Renesto Ada, C; Sartori, M; Campos, M (Jan–Feb 2011). "[Cross-linking and intrastromal corneal ring segment].". Arquivos brasileiros de oftalmologia 74 (1): 67–74. doi:10.1590/s0004-27492011000100017. PMID 21670914.
- Kymionis GD, Diakonis VF, Coskunseven E, Jankov M, Yoo SH, Pallikaris IG (2009). "Customized pachymetric guided epithelial debridement for corneal collagen cross linking". BMC Ophthalmology 9: 10. doi:10.1186/1471-2415-9-10. PMC 2744909. PMID 19715585.
- "Holcomb C3-R®- Proprietary, Non-Surgical Corneal Crosslinking". Brian Boxer Wachler.
- Romppainen, T.; Bachmann, L. M.; Kaufmann, C.; Kniestedt, C.; Mrochen, M.; Thiel, M. A. (1 December 2007). "Effect of Riboflavin-UVA Induced Collagen Cross-linking on Intraocular Pressure Measurement". Investigative Ophthalmology & Visual Science. pp. 5494–5498. doi:10.1167/iovs.06-1479.
- "KXL, Accelerated Crosslinking". Avedro.
- Spoerl E, Wollensak G, Dittert DD, Seiler T (2004). "Thermomechanical behavior of collagen-cross-linked porcine cornea". Ophthalmologica 218 (2): 136–40. doi:10.1159/000076150. PMID 15004504.
- Kanellopolous, A (September 2009). "Comparison of Sequential vs Same-day Simultaneous Collagen Cross-linking and Topography-guided PRK for Treatment of Keratoconus" 25 (9). Journal of Refractive Surgery. pp. S812–S818. doi:10.3928/1081597X-20090813-10.
- Wittig-Silva C, Whiting M, Lamoureux E, Lindsay RG, Sullivan LJ, Snibson GR (September 2008). "A randomized controlled trial of corneal collagen cross-linking in progressive keratoconus: preliminary results". Journal of Refractive Surgery 24 (7): S720–5. PMID 18811118.
- Boxer Wachler, Brian (January 2005). "Corneal crosslinking with riboflavin, A new treatment to strengthen the cornea for keratoectasia and keratoconus". Cataract and Refractive Surgery Today.
- Hasson, Matt (25 January 2008). "FDA backs launch of collagen cross-linking clinical trials". Ocular Surgery News. Retrieved 26 February 2008.
- "Avedro to acquire Corneal Collagen Crosslinking Phase III study rights from Peschke Meditrade". News-medical.net. Retrieved 13 November 2012.
- "CRSTodayEurope.com > August 2009 > Refractive Changes Following CXL". Bmctoday.net. Retrieved 4 July 2013.
- Chan CC, Sharma M, Wachler BS (January 2007). "Effect of inferior-segment Intacs with and without C3-R on keratoconus". Journal of Cataract and Refractive Surgery 33 (1): 75–80. doi:10.1016/j.jcrs.2006.09.012. PMID 17189797.
- Maria Clara Arbelaez, MD (April 2013). "ICRS Implantation Plus LASEK and Accelerated CXL". Cataract & Refractive Surgery Today.
- "Thermo-biomechanical system gets CE mark | OphthalmologyTimes". Modernmedicine.com. 7 May 2010. Retrieved 4 July 2013.
- Daxer A, Mahmoud H and Venkateswaran RS. Corneal Crosslinking and Visual Rehabilitation in Keratoconus in One Session without epithelial debridement: New Technique. Cornea 2010;29:1176-1179.
- Studeny P, Krizova D, Stranak Z. Clinical outcomes after Complete Intracorneal Ring Implantation and Corneal Crosslinking in an Intrastromal Pocket in One Session for Keratoconus. Journal of Ophthalmology 2014, S1 doi:10.1155/2014/568128.
- Tan, D.; Por, Y-M. (July 2007). "Current treatment options for corneal ectasia". Current Opinion in Ophthalmology 18 (4): 279–283. doi:10.1097/ICU.0b013e3281a7ecaa. PMID 17568202.
- Hersh, Peter S. "Keratoconus approach is promising - Ophthalmology Times Europe". Oteurope.com. Retrieved 7 December 2012.
- Yanoff M, Duker J (2004). Ophthalmology (2nd ed.). Mosby. ISBN 0-323-01634-0.
- New Humanitarian Device Approval INTACS Prescription Inserts for Keratoconus - H040002
- Jorge Alio (July 2013). "Keratoconus treatment". Ophthalmology Times Europe 9 (6).
- US FDA, New Humanitarian Device Approval INTACS Prescription Inserts for Keratoconus - H040002
- Ruckhofer J (August 2002). "[Clinical and histological studies on the intrastromal corneal ring segments (ICRS(R), Intacs(R))]". Klinische Monatsblätter für Augenheilkunde (in German) 219 (8): 557–74. doi:10.1055/s-2002-34421. PMID 12353173.
- Miranda D, Sartori M, Francesconi C, Allemann N, Ferrara P, Campos M (2003). "Ferrara intrastromal corneal ring segments for severe keratoconus". Journal of Refractive Surgery 19 (6): 645–53. PMID 14640429.
- Boxer Wachler, BS; Christie, JP; Chandra, NS; Chou, B; Korn, T; Nepomuceno, R (2003). "Intacs for keratoconus". Ophthalmology 110 (5): 1031–40. doi:10.1016/S0161-6420(03)00094-0. PMID 12750109.
- Sharma M, Boxer Wachler BS (May 2006). "Comparison of single-segment and double-segment Intacs for keratoconus and post-LASIK ectasia". American Journal of Ophthalmology 141 (5): 891–5. doi:10.1016/j.ajo.2005.12.027. PMID 16546107.
- Hosny, Mohamed; Mayah, Israa; Sidky, M Karim; Anis, Mohamed (January 2015). "Femtosecond laser-assisted implantation of complete versus incomplete rings for keratoconus treatment". Clinical Ophthalmology: 121. doi:10.2147/OPTH.S73855.
- Studeny, Pavel; Krizova, Deli; Stranak, Zbynek (2014). "Clinical Outcomes after Complete Intracorneal Ring Implantation and Corneal Collagen Cross-Linking in an Intrastromal Pocket in One Session for Keratoconus". Journal of Ophthalmology 2014: 1–5. doi:10.1155/2014/568128.
- Daxer A. (2008). "Corneal intrastromal implantation surgery for the treatment of moderate and high myopia.". J Cataract Refract Surg 34: 194–8.
- Daxer A, Mahmoud H, Venkatesvaran RS. (2010). "Intracorneal continous ring implantation for keratoconus: one year follow-up.". J Cataract Refract Surg 36: 1296–1302.
- "CISIS, MyoRing Treatment". DIOPTEX.
- "Keraflex Clinical Trial Starts in the US". National Keratoconus Foundation. August 2012.
- Vega-Estrada, A; Alió, JL; Plaza Puche, AB; Marshall, J (November 2012). "Outcomes of a new microwave procedure followed by accelerated cross-linking for the treatment of keratoconus: a pilot study.". Journal of Refractive Surgery 28 (11): 787–93. doi:10.3928/1081597X-20121011-07. PMID 23347373.
- "Keraflex treatment for keratoconus". ILMO > About us About us Company profile Our Team Departments, Units and Services ILMO Istituto Laser Microchirurgia Oculare.
- Laura Straub (March 2010). "Thermo-Biomechanics for Treating Keratoconus and Refractive Errors". Cataract & Refractive Surgery Today Europe.
- Jabbur NS, Stark WJ, Green WR (November 2001). "Corneal ectasia after laser-assisted in situ keratomileusis". Archives of Ophthalmology 119 (11): 1714–6. doi:10.1001/archopht.119.11.1714. PMID 11709027.
- Colin J, Velou S (February 2003). "Current surgical options for keratoconus". Journal of Cataract and Refractive Surgery 29 (2): 379–86. doi:10.1016/S0886-3350(02)01968-5. PMID 12648653.
- Bergmanson JP, Farmer EJ (1999). "A return to primitive practice? Radial keratotomy revisited". Contact Lens & Anterior Eye 22 (1): 2–10. doi:10.1016/S1367-0484(99)80024-1. PMID 16303397.
- Lombardi, M.; Abbondanza, M. (1997). "Asymmetric radial keratotomy for the correction of keratoconus". Journal of Refractive Surgery 13 (3): 302–307. PMID 9183763.
- Felicita Donalisio - Sab, 24 May 2008 - 02:05 (24 May 2008). "La curva pericolosa della cornea" (in Italian). IlGiornale.it. Retrieved 13 November 2012.
- Kohlhaas, M.; Draeger, J.; Böhm, A.; Lombardi, M.; Abbondanza, M.; Zuppardo, M.; Görne, M. (2008). "Zur Aesthesiometrie der Hornhaut nach refraktiver Hornhautchirurgie" [Aesthesiometry of the cornea after refractive corneal surgery]. Klinische Monatsblätter für Augenheilkunde (in German) 201 (10): 221–223. doi:10.1055/s-2008-1045898. PMID 1453657.
- Da bmctoday.net
- Da tv.mediaset.it
- Schirmbeck T, Paula JS, Martin LF, Crósio Filho H, Romão E (2005). "[Efficacy and low cost in keratoconus treatment with rigid gas-permeable contact lens]". Arquivos Brasileiros De Oftalmologia (in Portuguese) 68 (2): 219–22. PMID 15905944.
- Javadi MA; Motlagh BF; Jafarinasab MR et al. (November 2005). "Outcomes of penetrating keratoplasty in keratoconus". Cornea 24 (8): 941–6. doi:10.1097/01.ico.0000159730.45177.cd. PMID 16227837.
- Mamalis N, Anderson CW, Kreisler KR, Lundergan MK, Olson RJ (October 1992). "Changing trends in the indications for penetrating keratoplasty". Archives of Ophthalmology 110 (10): 1409–11. doi:10.1001/archopht.1992.01080220071023. PMID 1417539.
- Al-Mezaine H, Wagoner MD (March 2006). "Repeat penetrating keratoplasty: indications, graft survival, and visual outcome". The British Journal of Ophthalmology 90 (3): 324–7. doi:10.1136/bjo.2005.079624. PMC 1856933. PMID 16488955.
- Rubinfeld RS, Traboulsi EI, Arentsen JJ, Eagle RC (June 1990). "Keratoconus after penetrating keratoplasty". Ophthalmic Surgery 21 (6): 420–2. PMID 2381677.
- Sugita, Juntaru (1997). "Advances in Corneal Research: Selected Transactions of the World Congress on the Cornea" IV. pp. 163–166.
- Wagoner MD, Smith SD, Rademaker WJ, Mahmood MA (2001). "Penetrating keratoplasty vs. epikeratoplasty for the surgical treatment of keratoconus". Journal of Refractive Surgery 17 (2): 138–46. PMID 11310764.
- Davis, L (1997). "Keratoconus: Current understanding of diagnosis and management". Clinical Eye and Vision Care 9: 13. doi:10.1016/S0953-4431(96)00201-9.
- Grewal S, Laibson PR, Cohen EJ, Rapuano CJ (1999). "Acute hydrops in the corneal ectasias: associated factors and outcomes". Transactions of the American Ophthalmological Society 97: 187–98; discussion 198–203. PMC 1298260. PMID 10703124.
- US National Eye Institute, Facts About The Cornea and Corneal Disease Keratoconus. Accessed 12 February 2006.
- Kennedy RH, Bourne WM, Dyer JA (March 1986). "A 48-year clinical and epidemiologic study of keratoconus". American Journal of Ophthalmology 101 (3): 267–73. PMID 3513592.
- Weissman BA, Yeung KK. Keratoconus. eMedicine: Keratoconus. Accessed 24 December 2011.
- Fink BA; Wagner H; Steger-May K et al. (September 2005). "Differences in keratoconus as a function of gender". American Journal of Ophthalmology 140 (3): 459–68. doi:10.1016/j.ajo.2005.03.078. PMID 16083843.
- Pearson AR, Soneji B, Sarvananthan N, Sandford-Smith JH (August 2000). "Does ethnic origin influence the incidence or severity of keratoconus?". Eye 14 (4): 625–8. doi:10.1038/eye.2000.154. PMID 11040911.
- Bowman W, On conical cornea and its treatment by operation. Ophthalmic Hosp Rep and J R Lond Ophthalmic Hosp. 1859;9:157.
- Horner JF, Zur Behandlung des Keratoconus. Klinische Monatsblätter für Augenheilkunde. 1869.
- Pearson RM (September 1989). "Kalt, keratoconus, and the contact lens". Optometry and Vision Science 66 (9): 643–6. doi:10.1097/00006324-198909000-00011. PMID 2677884.
- Castroviejo R (1948). "Keratoplasty for the Treatment of Keratoconus". Transactions of the American Ophthalmological Society 46: 127–53. PMC 1312756. PMID 16693468.
- Castroviejo, R.: International Abstract of Surgery, 65:5, December 1937.
- Jinabhai, Amit; Radhakrishnan, Hema; O'Donnell, Clare (23 December 2010). "Pellucid corneal marginal degeneration: A review". Contact Lens & Anterior Eye 34 (2): 56–63. doi:10.1016/j.clae.2010.11.007. PMID 21185225. Retrieved 9 July 2012.
|Wikimedia Commons has media related to Keratoconus.|
|Wikimedia Commons has media related to corneal collagen crosslinking.|
- National Keratoconus Foundation (US)
- Keratoconus Support and Awareness
- Keratoconus Freedom forum
- UK Keratoconus Self Help and Support Group
- Simulation of Keratoconus Patient Vision
- Scleral Lens Education Society
- Keratoconus Australia Association
- Group blog by keratoconus patients