Keratoconus | Understanding and definition of the Keratoconus

Keratoconus 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 affects around one person in a thousand. It seems to occur in populations throughout the world, although it occurs more frequently in certain ethnic groups such as South Asians. The exact cause of keratoconus is uncertain, but has been associated with detrimental enzyme activity within the cornea. Environmental and genetic factors are considered possible causes, but the findings are still yet inconclusive. The progression of keratoconus is rapid in patients having Down syndrome.

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 quite poor. Some individuals have vision in one eye that is markedly worse than that in the other eye. The disease is often bilateral, though asymmetrical in many patients. 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.

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 as an optical system in keratoconus is the so-called coma.

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 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. 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 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 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.

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.

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 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 patients complain of chronic eye rubbing and also think it as a possible cause to the disease but it is not so; however, it has been observed that keratoconus progresses faster due to eye-rubbing.

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 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. While keratoconus is considered a non-inflammatory disorder, one study shows that wearing rigid contact lenses by patients leads to overexpression of pro-inflammatory cytokines, such as IL-6, TNF-alpha, ICAM-1, and VCAM-1 in the tear fluid.

Patients with keratoconus typically present initially with mild astigmatism, 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. It tends to progress more rapidly in patients when the first presentation is in second decade of life. Most commonly, keratoconus progresses for a period of ten to twenty 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 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. 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.

The National Eye Institute reports that keratoconus is the most common corneal dystrophy in the United States, affecting approximately 1 in 2,000 Americans, but some reports place the figure as high as 1 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. It is suggested that 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. Also, a study carried out in the UK suggests that people of a South Asian heritage 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 persist to be poorer than that in its fellow.