Keratoconus Classification and external resources
The "conical cornea" that is characteristic of keratoconus
ICD-10	H18.6
ICD-9	371.6
OMIM	148300
DiseasesDB	7158
MedlinePlus	001013
eMedicine	oph/104

Keratoconus (from Greek: kerato- horn, cornea; and konos cone), 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 gradual curve. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Greek (el ελληνική γλώσσα or simply el ελληνικά — "Hellenic" is an Indo-European language, spoken today by 15-22 million people mainly Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens Eyes are organs that detect Light, and send signals along the Optic nerve to the visual areas of the brain The cornea is the transparent front part of the Eye that covers the iris, Pupil, and Anterior chamber. A cone is a three-dimensional Geometric shape that tapers smoothly from a flat round base to a point called the apex or vertex In Mathematics, the concept of a curve tries to capture the intuitive idea of a geometrical one-dimensional and continuous object Keratoconus can cause substantial distortion of vision, with multiple images, streaking and sensitivity to light all often reported by the patient. In Psychology, visual perception is the ability to interpret information from Visible light reaching the Eyes The resulting Perception is also Photophobia is a Symptom of excessive sensitivity to Light and the aversion to Sunlight or well-lit places Keratoconus is the most common dystrophy of the cornea, affecting around one person in a thousand, and it seems to occur in populations throughout the world, although some ethnic groups experience a greater prevalence than others. Corneal dystrophy is a group of disorders characterised by a noninflammatory inherited bilateral opacity of the transparent front part of the Eye called the Cornea 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 its progression following diagnosis is unpredictable. Diagnosis is the identification by Process of elimination, of the nature of anything 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. A corrective lens is a lens worn in front of the Eye, mainly used to treat Myopia, Hyperopia, astigmatism, and adjustable focus Further progression of the disease may require surgery including transplantation of the cornea. Surgery (from the χειρουργική cheirourgikē, via chirurgiae meaning "hand work" is a medical specialty that uses operative manual and instrumental Despite its uncertainties, keratoconus can be successfully managed with a variety of clinical and surgical techniques, and often with little or no impairment to the patient's quality of life.

History

Practical observations on conical cornea, Nottingham's ground-breaking text on keratoconus, 1854

In a 1748 doctoral dissertation, the German oculist Burchard Mauchart provided an early description of a case of keratoconus,^[1] which he called staphyloma diaphanum. Ophthalmology is the branch of Medicine which deals with the diseases and surgery of the visual pathways including the Eye, Brain Burchard David Mauchart (1696-1751 was professor of Anatomy and Surgery at the University of Tübingen, Germany, and a pioneer in the field However, it was not until 1854 that British physician John Nottingham clearly described keratoconus and distinguished it from other ectasias of the cornea. An aneurysm (or aneurism) is a localized blood-filled dilation (balloon-like bulge of a blood vessel caused by disease or weakening of the vessel wall ^[1] 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. Diplopia, commonly known as double vision, is the simultaneous Perception of two images of a single object ^[2] 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. Sir William Bowman 1st Baronet ( July 20, 1816 - March 29, 1892) was an English surgeon, Histologist & The ophthalmoscope (or funduscope) is an instrument used to examine the Eye. ^[3] 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 slit, like that of a cat. The iris consists of Pigmented Fibrovascular tissue known as a stroma. The pupil is the hole that is located in the center of the iris of the eye and that controls the amount of light that enters the Eye. 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,^[4] the disorder had acquired its current name. Johann Friedrich Horner ( 27 March, 1831 - 20 December, 1886) was an ophthalmologist based at the University of Zurich, 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. Friedrich Wilhelm Ernst Albrecht von Graefe (or Gräfe; May 22, 1828 &ndash July 20, 1870) was a pioneering German Silver nitrate also known as lunar caustic is a soluble Chemical compound with Chemical formula Ag[[Nitrogen N]] O 3 Miosis is Constriction of the Pupil of the Eye. This is a normal response to an increase in light but can also be associated with certain Pathological ^[1] 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 which improved vision by compressing the cornea into a more regular shape. A contact lens (also known simply as a contact) is a corrective, cosmetic, or therapeutic lens usually placed on the Cornea Eugène Kalt (1861-1941 was a French Ophthalmologist who developed the first known application of a Contact lens for the correction of Keratoconus. ^[5] 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.

Features

Symptoms

A simulation of the multiple images seen by a person with keratoconus. Diplopia, commonly known as double vision, is the simultaneous Perception of two images of a single object
". . . a candle, when looked at, appears like a number of lights, confusedly running into one another" — Nottingham^[2]

People with early keratoconus typically notice a minor blurring of their vision and come to their clinician seeking corrective lenses for reading or driving. ^[6][7] At early stages, the symptoms of keratoconus may be no different from those of any other refractive defect of the eye. A symptom' (from Greek σύμπτωμα, "accident misfortune that which befalls" from συμπίπτω, "I befall" from A refractive error, or refraction error, is an error in the focusing of Light by the Eye and a frequent reason for reduced Visual acuity As the disease progresses, vision deteriorates, sometimes rapidly. Visual acuity becomes impaired at all distances, and night vision is often quite poor. Eye examination Visual acuity (VA is acuteness or clearness of vision, especially form vision which is dependent on the sharpness of the retinal focus within the Night vision is the ability to see in a dark environment Whether by biological or technological means night vision is made possible by a combination of two approaches sufficient 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. Photophobia is a Symptom of excessive sensitivity to Light and the aversion to Sunlight or well-lit places Asthenopia (aesthenopia or eye strain is an ophthalmological condition that manifests itself through nonspecific Symptoms such as fatigue red eyes eye strain pain Itch ( Latin: pruritus) is an unpleasant Sensation that evokes the desire or Reflex to scratch ^[6] There is however normally little or no sensation of pain. Pain, in the sense of physical pain, is a typical sensory experience that may be described as the unpleasant awareness of a noxious stimulus or bodily harm

The classic symptom of keratoconus is the perception of multiple 'ghost' images, known as monocular polyopia. Diplopia, commonly known as double vision, is the simultaneous Perception of two images of a single object This effect is most clearly seen with a high contrast field, such as a point of light on a dark background. Contrast is the difference in visual properties that makes an object (or its representation in an image distinguishable from other objects and the 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. Lens flare is the light scattered in lens systems through generally unwanted image formation mechanisms such as internal reflection and Scattering from Some even notice the images moving relative to one another in time with their heart beat.

Signs and diagnosis

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. Physical examination or clinical examination is the process by which a Health care provider investigates the body of a Patient for signs Diagnosis is the identification by Process of elimination, of the nature of anything Ophthalmology is the branch of Medicine which deals with the diseases and surgery of the visual pathways including the Eye, Brain Optometry is a health care profession concerned with Eyes and related structures as well as vision, Visual systems and vision information The medical history or Anamnesis of a Patient is information gained by a Physician or other healthcare professional by asking specific questions The Chief Complaint (CC or termed Presenting Complaint (PC in the UK is a concise statement describing the Symptom, problem Condition, Diagnosis An eye chart, such as a standard Snellen chart of progressively smaller letters, is then used to determine the patient's visual acuity. An eye chart is a chart used to measure Visual acuity. Types of eye charts include the Snellen chart, Landolt C, and the Lea test. A Snellen chart is an Eye chart used by Eye care professionals and others to measure Visual acuity. An optotype is a standardized symbol for testing vision. Optotypes can be specially shaped letters numbers or geometric symbols Eye examination Visual acuity (VA is acuteness or clearness of vision, especially form vision which is dependent on the sharpness of the retinal focus within the The eye examination may proceed to measurement of the localised curvature of the cornea with a manual keratometer,^[8] with detection of irregular astigmatism suggesting a possibility of keratoconus. An eye examination is a battery of tests performed by an Optometrist or Ophthalmologist assessing vision and ability to focus on and discern A keratometer, also known as a ophthalmometer, is a diagnostic instrument for measuring the curvature of the anterior surface of the Cornea, particularly for Astigmatism is an optical defect whereby vision is blurred due to the inability of the optics of the eye to focus a point object into a sharp focused image on the retina Severe cases can exceed the instrument's measuring ability. ^[7] 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. Retinoscopy is a technique to obtain an objective measurement of the refractive condition of a patient's Eyes. The vertebrate retina is a light sensitive part inside the inner layer of the Eye. 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. Scissors are hand operated cutting instruments consisting of a pair of Metal Blades connected in such a way that the blades meet and cut materials placed ^[9][7]

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. Ophthalmology is the branch of Medicine which deals with the diseases and surgery of the visual pathways including the Eye, Brain Optometry is a health care profession concerned with Eyes and related structures as well as vision, Visual systems and vision information The slit lamp is an instrument consisting of a high-intensity Light source that can be focused to shine as a slit ^[10] 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. Fleischer rings are pigmented rings in the peripheral Cornea, resulting from Iron deposition in basal epithelial cells ^[11] 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. Hemosiderin or haemosiderin is an abnormal Microscopic Pigment found in the Human body Cobalt blue is a cool slightly desaturated blue Color, historically made using Cobalt salts ^[7] Similarly, around 50% of subjects exhibit Vogt's striae, fine stress lines within the cornea caused by stretching and thinning. " Striae " is also a general term referring to thin narrow grooves or channels or a thin line or band especially if several of them are parallel or close together ^[11] The striae temporarily disappear while slight pressure is applied to the eyeball. ^[7] 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. An eyelid is a thin fold of skin that covers and protects an Eye. Munson's sign is a Medical sign of a V-shaped indentation in the Lower eyelid when the patient's gaze is directed downwards ^[6] Other clinical signs of keratoconus will normally have presented themselves long before Munson's sign becomes apparent,^[12] and so this finding, though a classic sign of the disease, tends not to be of primary diagnostic importance. A Sign is an indication of some fact or quality and a medical sign is an objective indication of some medical fact or quality that is detected by a Physician

Corneal topogram of a keratoconic eye

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 keratoscope, sometimes known as Placido's disk, is an ophthalmic instrument for assessing the shape of the anterior surface of the Cornea. The term non-invasive in Medicine has two meanings A Medical procedure which does not penetrate mechanically, nor break the Skin 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. Corneal topography, also known as photokeratoscopy or videokeratography, is a non-invasive Medical imaging technique for mapping the surface 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. ^[1] 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. ^[13]

Once keratoconus has been diagnosed, its degree may be classified by several metrics:^[14]

• 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). A dioptre, or diopter, is a Unit of measurement of the Optical power of a lens or curved Mirror, which is equal to the reciprocal A dioptre, or diopter, is a Unit of measurement of the Optical power of a lens or curved Mirror, which is equal to the reciprocal A dioptre, or diopter, is a Unit of measurement of the Optical power of a lens or curved Mirror, which is equal to the reciprocal

Increasing use of corneal topography has led to a decline in use of these terms. ^[14]

Epidemiology

The National Eye Institute reports that keratoconus is the most common corneal dystrophy in the United States, affecting approximately 1 in 2,000 Americans,^[15][16] but some reports place the figure as high as 1 in 500. The National Eye Institute (NEI is one of the US National Institutes of Health that was established in 1968. Corneal dystrophy is a group of disorders characterised by a noninflammatory inherited bilateral opacity of the transparent front part of the Eye called the Cornea ^[17] The inconsistency may be due to variations in diagnostic criteria,^[7] with some cases of severe astigmatism interpreted as those of keratoconus, and vice versa. ^[12] A long-term study found a mean incidence rate of 2. 0 new cases per 100,000 population per year. ^[16] It is suggested that males and females, and all ethnicities appear equally susceptible, though some recent studies have cast doubt upon this,^[18] suggesting a higher prevalence amongst females; the literature however varying as to its extent. Also, a study carried out in the UK^[19] suggests that people of an 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^[16] (affecting both eyes) although the distortion is usually asymmetric and is rarely completely identical in both corneas. ^[7] 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. ^[12] 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.

Prognosis

Patients 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. Astigmatism is an optical defect whereby vision is blurred due to the inability of the optics of the eye to focus a point object into a sharp focused image on the retina In rare cases keratoconus can occur in children or not present until later adulthood. ^[7] A diagnosis of the disease at an early age may indicate a greater risk of severity in later life. ^[1][20] 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. A contact lens (also known simply as a contact) is a corrective, cosmetic, or therapeutic lens usually placed on the Cornea 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^[12] before the course of the disease generally ceases.

Corneal hydrops

In advanced cases, bulging of the cornea can result in a localized rupture of Descemet's membrane, an inner layer of the cornea. Descemet's membrane is the Basement membrane that lies between the corneal proper substance also called stroma and the endothelial layer of the Cornea Aqueous humor from the eye's anterior chamber seeps into the cornea before Descemet's membrane reseals. The aqueous humor is a thick watery substance that is between the lens and the cornea The anterior chamber is the fluid-filled space inside the Eye between the iris and the Cornea 's innermost surface the Endothelium. 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. ^[21] 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. Osmosis is the Diffusion of a solvent (frequently water through a semi-permeable membrane, from a solution of low solute concentration (high water potential In Medicine, saline (also saline solution) is a general term referring to a sterile solution of Sodium chloride (table Salt) in water 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. ^[21] 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. Corneal transplantation, also known as corneal grafting or penetrating keratoplasty, is a Surgical procedure where a damaged or diseased Cornea ^[21]

Pathophysiology and cause

Despite considerable research, the etiology of keratoconus remains somewhat of a mystery. Etiology (alternatively aetiology, aitiology) is the study of causation. ^[1] 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. ^[22][23] Once initiated, the disease normally develops by progressive dissolution of Bowman's layer,^[7] which lies between the corneal epithelium and stroma. The Bowman's membrane ( Bowman's layer, anterior limiting lamina, anterior elastic lamina) is a smooth layer in the Eye. In biology and medicine epithelium is a tissue composed of cells that line the cavities and surfaces of structures throughout the body The substantia propria (or stroma of Cornea) is fibrous tough unyielding and perfectly transparent 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 vertebrate retina is a light sensitive part inside the inner layer of the Eye. Diplopia, commonly known as double vision, is the simultaneous Perception of two images of a single object The effect can worsen in low light conditions as the dark-adapted pupil dilates to expose more of the irregular surface of the cornea. The pupil is the hole that is located in the center of the iris of the eye and that controls the amount of light that enters the Eye. 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. ^[24]

A number of studies have indicated that keratoconic corneas show signs of increased activity by proteases,^[22] a class of enzymes that break some of the collagen cross-linkages in the stroma, with a simultaneous reduced expression of protease inhibitors. A protease is any Enzyme that conducts Proteolysis, that is begins protein Catabolism by Hydrolysis of the Peptide bonds that link Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Collagen is the main Protein of Connective tissue in Animals and the most abundant protein in Mammals making up about 50% of the whole-body protein Gene expression is the process by which inheritable information from a Gene, such as the DNA sequence, is made into a functional Gene product, such Enzyme inhibitors are Molecules that bind to Enzymes and decrease their activity. ^[25] 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. Aldehyde dehydrogenases, EC 1213, are a group of Enzymes that Catalyse the Oxidation (dehydrogenation of Aldehydes Mitochrondrial In Chemistry, radicals (often referred to as free radicals) are atoms molecules or ions with Unpaired electrons on an otherwise Open shell ^[26] 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. The term pathogenesis means step by step development of a disease due to a series of changes in the structure and /or function of a cell/tissue/organ being caused by a microbial, chemical or physical

A genetic predisposition to keratoconus has been observed,^[27] with the disease running in certain families,^[28] and incidences reported of concordance in identical twins. For other uses see Concordance. Concordance as used in Genetics usually means the presence of the same trait in both ^[10] 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,^[1] and studies have obtained estimates ranging between 6% and 19%. ^[29] 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. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance A chromosome is an organized structure of DNA and Protein that is found in cells. ^[29] However, most genetic studies agree on an autosomal dominant model of inheritance. An autosome is a non-sex Chromosome. It is an ordinarily paired type of chromosome that is the same in both Sexes of a species. ^[6] Keratoconus is also diagnosed more often in people with Down syndrome, though the reasons for this link have not yet been determined. Down syndrome, Down's syndrome, or trisomy 21 is a Chromosomal disorder caused by the presence of all or part of an extra 21st chromosome. ^[30] 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. Atopy (/ˈætəpi/ Greek ἀτοπία - placelessness or atopic syndrome is an allergic Hypersensitivity affecting parts of the body Asthma is a chronic Condition involving the Respiratory system in which the airways occasionally constrict become inflamed, and are Allergy is a disorder of the Immune system often also referred to as Atopy. Eczema (from Greek έκζεμα) is a form of Dermatitis, or Inflammation of the Epidermis. 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. ^{[31][32][33][34][35]}

Treatment

Contact lenses

Main article: Contact lens

In early stages of keratoconus, spectacles or soft contact lenses can suffice to correct for the mild astigmatism. A contact lens (also known simply as a contact) is a corrective, cosmetic, or therapeutic lens usually placed on the Cornea Glasses, also called eyeglasses or spectacles, are frames bearing lenses worn in front of the Eyes normally for vision correction, As the condition progresses, spectacles may no longer provide the patient with a satisfactory degree of visual acuity, and most clinical practitioners will move to managing the condition with rigid contact lenses (or RGPs).

Rigid gas permeable lens for keratoconus

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. Tears are the liquid product of a process of lacrimation to clean and lubricate the Eyes The word lacrimation may also be used in a medical or literary sense 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^[22] and the fitter will endeavour to produce a lens with the optimal contact, stability and steepness. Some trial-and-error fitting may prove necessary. ^[12]

Traditionally, contact lenses for keratoconus have been the 'hard' or rigid gas-permeable variety, although manufacturers have also produced specialized 'soft' or hydrophilic lenses and, most recently, silicone hydrogel lenses. Hydrophile, from the Greek (hydros "water" and φιλια (philia "friendship" refers to a physical property of a Molecule 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. Soft or hybrid lenses do not however prove effective for every patient. ^[36]

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. ^[37] 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. A scleral lens is a large type of Contact lens that rests on the Sclera and creates a tear -filled vault over the Cornea. ^[38] The larger size of the lenses may make them unappealing or uncomfortable to some, however their easier handling can find favour with patients with reduced dexterity, such as the elderly.

Surgical options

Corneal transplant

Main article: Cornea transplant

Corneal transplant for keratoconus, approximately 1 week after surgery. Corneal transplantation, also known as corneal grafting or penetrating keratoplasty, is a Surgical procedure where a damaged or diseased Cornea Multiple light reflections indicate folds in the cornea which later resolved.

Between 10% and 25% of cases of keratoconus^[23][39][40] 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. ^[41] 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. A trephine (/ˌtɹɪˈfiːn/ is a Surgical instrument with a cylindrical Blade. In Medicine, grafting is a Surgical procedure to transplant tissue without a blood supply. Organ donation is the removal of the tissues of the Human body from a person who has recently Died, or from a living donor for the purpose of transplanting The cornea does not have a direct blood supply, and so donor tissue is not required to be blood type matched. A blood type (also called a blood group) is a classification of Blood based on the presence or absence of inherited Antigenic substances on the Eye banks check the donor corneas for any disease or cellular irregularities. Eye banks retrieve and store Eyes for Cornea transplants and research

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. ^[40] 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. ^[23] 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. A patient is any person who receives medical attention care or treatment. In other countries, such as Australia and the UK, the operation is commonly performed with the patient undergoing a general anaesthetic. All cases a require careful follow-up with an eye surgeon (ophthalmologist) 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. Transplant rejection occurs when a transplanted organ or tissue fails to be accepted by the body of the transplant recipient Vision loss is very rare, though difficult-to-correct vision is possible. Vision loss or visual loss is the absence of vision where it existed before which can happen either acutely (i When rejection is severe, repeat transplants are often attempted, and are frequently successful. ^[42] 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. ^[43] 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.

DALK transplants

One way of reducing the risk of rejection is to use a newer technique called a Deep Anterior Lamellar Keratoplasty, referred to as DALK. In a DALK graft, only the outermost epithelium and the main bulk of the cornea, the stroma, are replaced; the patient's rearmost endothelium layer is retained, giving some additional structural integrity to the post-graft cornea. The corneal endothelium is a monolayer of specialized flattened mitochondria-rich cells that lines the posterior surface of the Cornea and faces the Anterior ^[44] Because a graft rejection usually begins in the endothelium, the chance of a rejection episode is greatly reduced. Furthermore, it is possible to transplant tissue from a donor which has been freeze-dried. Freeze drying (also known as lyophilization or cryodesiccation) is a Dehydration process typically used to preserve a perishable material The freeze-drying process ensures that this tissue is dead, so there is no chance of a rejection. ^[44]

Some surgeons prefer to remove the donor epithelium, others leave the donor's cells in place. Removing it can cause a slight improvement in overall vision, but a corresponding increase in visual recovery time.

Epikeratophakia

Rarely, 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. ^[22] 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. ^[45]

Corneal ring segment inserts

Main article: Intrastromal corneal ring segments

A pair of Intacs inserts

A recent surgical alternative to corneal transplant is the insertion of intrastromal corneal ring segments. Intrastromal corneal rings (or intracorneal rings) are small devices implanted in the Eye to correct vision. 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. Poly(methyl methacrylate ( PMMA) or poly(methyl 2-methylpropenoate is a Thermoplastic and transparent Plastic. The pupil is the hole that is located in the center of the iris of the eye and that controls the amount of light that enters the Eye. ^[46] 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. Local anesthesia is any technique to render part of the body insensitive to pain without affecting consciousness ^[46]

The two principal 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 Food and Drug Administration (FDA) in the United States in 1999 for myopia; this was extended to the treatment of keratoconus in July 2004. Myopia (from Greek: μυωπία myopia "near-sightedness" also called near- or short-sightedness, is a refractive defect ^[47] 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. ^[48]

Clinical studies on the effectiveness of intrastromal rings on keratoconus are in their early stages, and results have so far been generally encouraging,^[49][50] though they have yet to enter into wide acceptance with the refractive surgery community. In common with penetrating keratoplasty, the requirement for some vision correction in the form of spectacles or hydrophilic contact lenses may remain subsequent to the operation. Potential complications of intrastromal rings include accidental penetration through to the anterior chamber when forming the channel, post-operative infection of the cornea, and migration or extrusion of the segments. An infection is the detrimental Colonization of a host Organism by a foreign Species. ^[50] The rings offer a good chance of vision improvement even in otherwise hard to manage eyes, but results are not guaranteed and in a few cases may worsen.

Early studies on intrastromal corneal rings involved use of two segments to cause global flattening of the cornea. ^[51] A later study reported that better results could be obtained for those cones located more to the periphery of the cornea by using a single Intacs segment. This leads to preferential flattening of the cone below, but also to steepening the over-flat upper part of the cornea. ^[52]

Radial keratotomy

Main article: Radial keratotomy

Radial keratotomy is a refractive surgery procedure where the surgeon makes a spoke-like pattern of incisions into the cornea to modify its shape. Radial keratotomy (RK is a refractive surgical procedure to correct Myopia. Refractive eye surgery is any Eye surgery used to improve the refractive state of the Eye and decrease or eliminate dependency on Glasses or Contact This early surgical option for myopia has been largely superseded by LASIK and other similar procedures. Myopia (from Greek: μυωπία myopia "near-sightedness" also called near- or short-sightedness, is a refractive defect LASIK or Lasik ( Laser -assisted In situ Keratomileusis) is a type LASIK itself 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. ^[53]

For similar reasons, radial keratotomy has also generally not been used for keratoconic patients. ^[54][55] However, an Italian clinic has reported some success with a modified asymmetric radial keratotomy procedure,^[56] 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. A pachymeter is a Medical device used to measure the thickness of the Eye 's Cornea. The patient may initially experience photophobia and fluctuation of vision, in common with other forms of refractive surgery ^[56]. Photophobia is a Symptom of excessive sensitivity to Light and the aversion to Sunlight or well-lit places However, it must be emphasized, that the asymmetric radial keratotomy technique has not yet gone through the official experimentation and follow-up period, which is generally required by the Italian National Health Service to accept a new surgery technique before it can be proposed to patients.

Corneal Collagen Crosslinking with Riboflavin

A recent treatment, developed at the Technische Universität Dresden, and which has shown early success is Corneal Collagen Crosslinking with Riboflavin, variously known as CXL, CCL, and C3-R. The Technische Universität Dresden (usually translated from German as Dresden University of Technology and abbreviated TU Dresden or TUD A one-time application of riboflavin solution is administered to the eye and is activated by illumination with UV-A light for approximately 30 minutes. Riboflavin ( E101) also known as vitamin B2, is an easily absorbed Micronutrient with a key role in maintaining Health Ultraviolet ( UV) light is Electromagnetic radiation with a Wavelength shorter than that of Visible light, but longer than X-rays ^[25][57] The riboflavin causes new cross-linking bonds to form across adjacent collagen strands in the stroma, and so recovers some of the cornea's mechanical strength. ^[58] The corneal epithelium is usually surgically abraded beforehand in order to increase penetration of the riboflavin into the stroma,^[58] but an unproven alternative is to leave the epithelium intact with the intent of reducing the impact upon the patient. ^[59]

Collagen crosslinking with riboflavin has been shown to reduce and arrest the progression of keratoconus, and also in some cases even reverse it, particularly when applied in combination with intracorneal ring segments. ^[60] A recent study showed that when collagen crosslinking with riboflavin was combined with Intacs, twice as much improvement occurred compared to Intacs alone. Intrastromal corneal rings (or intracorneal rings) are small devices implanted in the Eye to correct vision. ^[61] Clinical trials are continuing, but the treatment is seeing increasing adoption by the ophthalmological community, and has shown success in treating early cases of the disease. In health care clinical trials are conducted to allow safety and Efficacy data to be collected for new drugs or devices ^[62] The procedure is approved for use in Europe, and has recently commenced clinical trials in the USA. ^[63] Corrective lenses may still be required after the treatment if they were needed before but it is hoped that it could limit further deterioration in the patient's vision and reduce the case for keratoplasty. ^[64]

Related disorders

Several other non-inflammatory eye disorders, generally rarer than keratoconus, also cause thinning of the cornea:^[12]

Keratoglobus

Keratoglobus is a very rare condition that causes corneal thinning primarily at the margins, resulting in a spherical, slightly enlarged eye. Keratoglobus (from Greek: kerato- horn cornea and globus round is a degenerative non- inflammatory disorder of the Eye in which It may be genetically related to keratoconus. ^[22]

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 irregular astigmatism that can often be corrected by spectacles. Differential diagnosis may be made by slit-lamp examination. ^[10]

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, while the curvature of the anterior surface remains normal. Normally only a single eye is affected. ^[22]

See also

• List of eye diseases and disorders
• Ophthalmology

References

External links

Keratoconus associations:

• Keratoconus Australia
• National Keratoconus Foundation (US)
• Information from Keratoconus Self Help and Support Group (UK)
• Information from KC Global, The Global Keratoconus Foundation
• Information from KC Support, for Families
• European meeting on keratoconus Euro kératocône 2007/2009

Web articles on keratoconus:

• C3-R - A New Treatment to Strengthen the Cornea for Keratoectasia and Keratoconus.
• Helping the Keratoconus Patient Cope by Bezalel Schendowich
• Asymmetric Radial Keratotomy for the Correction of Keratoconus
• Case Studies

Other:

• Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study
• Vision Simulations See what people with keratoconus see
• Facts About the Cornea and Corneal Disease The National Eye Institute (NEI)