Keratoconus is a degenerative non-inflammatory 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 even curve. Keratoconus can cause substantial distortion of the vision, with multiple images, streaking and sensitivity to light all often reported by the patient. Though frequently thought of as a rare condition, keratoconus is the most common distrophy of the cornea, affecting around one person in a thousand, and seems to occur equally in all ethnic groups worldwide. It is typically diagnosed in the patient's adolescent years and attains its most severe state in the twenties and thirties.
Keratoconus is a little-understood disease with an uncertain cause, and the course of its progression following diagnosis is unpredictable. The associated deterioration in vision, if in both eyes, can affect the person's ability, for example, to drive a car legally. It does not, however, lead to blindness, and in most cases, corrective lenses are effective enough to allow the patient to continue to drive and likewise function normally. Further progression of the disease may lead to a need for surgery. Keratoconus continues to be somewhat of a mysterious disease, but it can be successfully managed with a variety of clinical and surgical techniques often with little or no impairment to the patient's quality of life.
HistoryIn a 1748 doctoral dissertation, a German oculist named Burchard Mauchart provided an early description of a case of keratoconus, which he called staphyloma diaphanum. However, it was not until 1854 that British physician John Nottingham 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 German physician and physicist 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 the vision by pulling on the iris with a fine hook inserted through the cornea and stretching the pupil into a vertical stenopeic 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 Gräfe, 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 Eugene Kalt manufactured a glass scleral shell which improved vision by compressing the cornea into a more regular shape.Since the start of the twentieth century, research on keratoconus has both improved understanding of the disease and greatly expanded the range of treatment options.
FeaturesSymptomsPeople 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 quite poor. Some individuals have vision in one eye that is markedly worse than that in the other eye. Some develop photophobia (sensitivity to bright light), eye strain from squinting in order to read, or itching in the eye. Otherwise, there is little or no sensation of pain.
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.
Signs and diagnosisPrior 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 localised 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 specialised 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, and is caused by deposition of the iron oxide hemosiderin within the corneal epithelium. The Fleischer ring 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 the examiner with a simple non-invasive visualization of the surface of the cornea by projecting a series of concentric rings of light onto the cornea. A more definitive diagnosis of keratoconus 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 present in the cornea, with keratoconus revealed by a characteristic steepening of curvature which is usually inferior to (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 providing a detection of the disorder in its early stages when other signs have not yet presented.
Once the presence of keratoconus has been established, its degree may be classified by a number of means helpful to the examiner:
* 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 the use of these terms by some practitioners.
EpidemiologyThe National Eye Institute reports that keratoconus is the most common corneal dystrophy in the United States, affecting approximately 1 in every 2,000 Americans, but some reports place the figure as high as 1 in every 500. The inconsistency may be due to variations in diagnostic criteria, with some cases of high astigmatism intepreted 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. Males and females, and all ethnicities appear equally susceptible, though some recent studies have cast doubt upon this, suggesting a higher prevalence amongst females; the literature however varying as to its extent. 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 eye will often persist to be poorer than that in its fellow.
PrognosisPatients with keratoconus typically present initially with mild astigmatism, commonly at the onset of puberty, and are diagnosed as having the disease by the late teenage years or early 20s. In rare cases keratoconus can occur in children or not present 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 become 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 ten to twenty years before the course of the disease generally ceases.
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 non-surgically 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. Very occasionally, in extreme cases, the cornea thins to the point that a partial rupture occurs, resulting in a small, bead-like swelling on the cornea that has been filled with fluid. When this occurs, a corneal transplant can become urgently necessary to avoid complete rupture and resulting loss of the eye.
Pathophysiology and causeDespite considerable research, the etiology of keratoconus remains somewhat of a mystery. According to the United States National Keratoconus Foundation, it is likely that keratoconus can arise 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, the membrane lying 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 that are characteristic of the disorder. Within any individual keratoconic cornea, there may be found regions of degenerative thinning coexisting with regions undergoing wound healing.
The visual distortion experienced by the patient comes from two sources, one being the irregular deformation of the surface of the cornea; 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 and give rise to the symptom of monocular polyopia. The effect can worsen in low light conditions as the dark-adapted pupil dilates to expose more of the irregular surface of the cornea. Scarring appears to be an aspect of the corneal degradation; however, a recent, large, multi-center study suggests that abrasion by contact lenses may increase the likelihood of this finding by a factor of over two.
A number of studies have indicated that keratoconic corneas show signs of increased activity by proteases, a class of enzymes that break some of the collagen cross-linkages in the corneal 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. It seems likely that, whatever the pathogenetical process, the damage caused by activity within the cornea results in a reduction in its thickness and biomechanical strength.
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 expressly 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 a dominant autosomal model of inheritence. 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 may contribute to the progression of keratoconus, and that patients should be discouraged from the practice.
TreatmentContact lensesIn early stages of keratoconus, spectacles can suffice to correct for the mild astigmatism. As the condition progresses, spectacles may fail to provide the patient with a satisfactory degree of visual acuity, and most clinical practitioners will move to managing the condition with contact lenses.
In keratoconic patients, 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 endeavour to produce a lens with the optimal contact, stability and steepness. Some trial-and-error fitting may prove necessary.
Traditionally, lenses for keratoconus have been the "hard" or rigid gas-permeable contact lens variety, although manufacturers have also produced specialized "soft" or hydrophilic lenses. A soft lens has a tendency to conform to the conical shape of the cornea, thus nulling its effect. To counter this, hybrid lenses have been recently developed which are hard in the centre and encompassed by a soft skirt. Soft or hybrid lenses do not however prove effective for every patient.
Some patients also find good vision correction and comfort with a "piggyback" lens combination, in which gas permeable rigid 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.
Surgical optionsCorneal transplantBetween 10% to 25% 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, 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, and so 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 post-operative 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.
Cornea transplants for keratoconus are usually performed under sedation as outpatient surgery, and require careful follow-up with an eye surgeon 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.
EpikeratophakiaRarely, a non-penetrating 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 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. It may however be seen as an option in a number of cases, particularly for young patients.
Corneal ring segment insertsA 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 slid between the layers of the corneal stroma either side of the pupil, the incision then being 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 anaesthesia, offers the benefit of being reversible and even potentially exchangeable as it involves no removal of eye tissue.
The two principle types of intrastromal rings available are known by the trade names of Intacs and Ferrara rings. Intacs are flatter and less centrally placed than the prismatic Ferrara rings. Intacs were first approved by the FDA in the United States in 1999 for myopia; this was extended to the treatment of keratoconus in July 2004. Ferrara rings await FDA approval for keratoconus. A development on the concept involves the injection of a transparent synthetic gel into a channel bored through the stroma. As the gel polymerises, it stiffens and takes on similar properties to the pre-formed rings.
Clinical 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 all refractive surgeons. In common with a penetrating keratoplasty, the requirement for some vision correction in the form of hydrophilic (soft) contact lenses or spectacles 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 it is not guaranteed and in a few cases may worsen.
Radial keratotomyRadial keratotomy is a refractive surgery procedure 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. Unfortunately, LASIK cannot be used for people with keratoconus because removal of corneal tissue can further damage their already weakened corneas. In Germany, for example, performing laser treatment on kerataconus patients is illegal.
For similar reasons, radial keratotomy has also generally not been used for keratoconic patients. However, an Italian clinic has reported some success with a modified asymmetric radial keratotomy procedure, in which the incisions are confined to one sector of the eye. The corneal thickness is first measured using a pachymeter, then the surgeon makes cuts to a depth of 70-80% of the measured thickness. The patient may initially experience photophobia and fluctuation of vision after radial keratotomy, just as with other forms of refractive surgery.
RiboflavinA new treatment which has shown success but which has not yet been approved in all countries involves a one-time application of riboflavin eye drops to the eye. The riboflavin, when activated by approximately 30 minutes illumination with UV-A light, augments the collagen cross-links within the stroma and so recovers some of the cornea's mechanical strength. The treatment, developed at the Dresden University of Technology, has been shown to slow or arrest the progression of keratoconus, and in some cases even reverse it, particularly when applied in combination with intracorneal ring segments. Clinical trials are continuing, and to date relatively few procedures have been performed but the technique is showing promise in treating early cases of the disease. Corrective lenses may still be required after the treatment but it is hoped that it could limit further deterioration in the patient's vision and reduce the case for keratoplasty.
Related disordersSeveral other non-inflammatory eye disorders, generally rarer than keratoconus, also cause thinning of the cornea:
Keratoglobus Keratoglobus is a very rare condition that may be genetically related to keratoconus. It causes corneal thinning, primarily at the margins, resulting in a spherical, slightly enlarged eye.
Pellucid marginal degeneration Pellucid marginal degeneration causes thinning of a narrow (1-2 mm) band of the cornea, usually along the inferior corneal margin. It causes an irregular astigmatism that can often be corrected by spectacles.
Posterior keratoconus Keratoconus and posterior keratoconus are distinct disorders, despite their similar names. Posterior keratoconus is a rare abnormality, usually congenital, which causes a non-progressive thinning of the inner surface of the cornea. Posterior keratoconus generally affects only a single eye.
