Keratoconus

Keratoconus (ectatic corneal dystrophy) is an eye condition in which the shape of the cornea bulges and becomes conical (cone-shaped), resulting in thinning and eventual scarring of the central cornea. The disorder affects women more often than men, and occurs more frequently in patients with Down's syndrome, Marfan's syndrome, Addison's disease, neurofibromatosis, allergies, and congenital amaurosis (a rare form of blindness at birth).

Symptoms

Keratoconus is characterized by thinning and protrusion of the central and/or paracentral cornea, resulting in corneal distortion, photophobia, halos around lights, decreased vision, and monocular diplopia (double-vision). Indicative warning signs of early keratoconus include frequent eyeglass prescription changes associated with progressive myopic astigmatism.

The onset of keratoconus occurs predominantly in the late teens. Symptoms usually appear bilaterally, but it is not uncommon to have an asymmetric presentation. During the first 5-7 years of onset, the condition generally worsens with intermittent periods of remission. In many cases, the degenerative process stops as the patient reaches his or her 40s. The first eye affected typically suffers more severe consequences, while the second eye may not show any signs until years later, if at all.

On clinical examination, patients with keratoconus may produce a low intraocular pressure (IOP) reading. This is due to corneal thinning and/or reduced sceral rigidity, either of which can cause a reduction in corneal tension on tonometer applanation.

Causes

Various theories have speculated that biochemical abnormalities may be responsible for the development of keratoconus. Recent studies have shown that abnormalities in proteoglycan metabolism have been associated with keratoconic corneas. Abnormalities in collagen fiber cross-linking have also been documented. There also appears to be some association with certain systemic diseases (see above).

Another theory is that keratoconus represents a degenerative condition attributed to corneal stress factors. Studies that support this theory note that keratoconus develops more often in persons who have a history of recurrent ocular surface irritation secondary to long-term contact lens wear and chronic vernal conjunctivits.

The role of heredity in the development of keratoconus has not been clearly established. Although genetic inheritance of the disorder has been noted, the majority of the cases show no definitive inheritance pattern. In some cases, however, genealogical analysis suggests a sex-linked autosomal dominant mode of inheritance, particularly because of the predominance of familial females with keratoconus

Diagnosis

Early keratoconus usually manifests as a small island of irregular astigmatism in the inferior paracentral cornea. As the cornea bulges outward, the amount of astigmatism increases due to the progressive distortion of the corneal surface. These changes can easily be seen as irregular mires on keratometry readings and on corneal topography, a test used to map the topographical surface area of the cornea.

Munson's sign - On physical examination, Munson's Sign is readily observable without the requirement of sophisticated testing equipment. As the patient gazes inferiorally, the apex of the cone angulates the lower lid outward, forming a 'V-shaped' protrusion. Milder signs of Munson's may be more easily seen when the head is tilted slightly back and upper lids are lifted while the patient gazes downward.

Corneal Hydrops - usually seen in more advanced cases of keratoconus; occurs when Descemet's membrane (a layer within the corneal strata) is stretched beyond its breaking point and ruptures. The influx of fluid from the aqueous results in significant corneal edema and opacification (a whitish-opaque spot appears on the cornea). Hydrops can cause severe pain and significantly reduced vision. Descemet's membrane regeneration is slow. As the membrane layer regenerates, the edema and opacification gradually resolve, but a scar formation will often remain on the cornea. In some cases, hydrops can occur suddenly while rubbing the eye.

KERATOCONUS

Keratoconus has no known cure, and many people do not even know they have it because it begins as nearsightedness and astigmatism. It is a progressive disorder that may progress rapidly or sometimes take years to develop. It can severely affect the way we see the world, including simple tasks such as driving, watching TV, or just reading a book. Some keratoconus patients have described their vision as being “blind with light.”

Keratoconus is a non-inflammatory, self-limiting ectasia of the axial portion of the cornea. It is characterized by progressive thinning and steepening of the central cornea. As the cornea steepens and thins, the patient experiences a decrease in vision which can be mild or severe depending on the amount of corneal tissue affected.

Onset of keratoconus occurs during the teenage years--mean age of onset is age 16 years--but onset has been reported to occur at ages as young as 6 years. Keratoconus rarely develops after age 30 years. Keratoconus shows no gender predilection and is bilateral in over 90% of cases. In general, the disease develops asymmetrically: diagnosis of the disease in the second eye lags about five years after diagnosis in the first. The disease process is active for about five to 10 years, then it may be stable for many years. During the active stage, change may be rapid.

Typically, vision loss can be corrected early by spectacles; later, irregular astigmatism requires optical correction with rigid contact lenses. Contact lenses provide a uniform refracting surface and therefore improve vision. Contact lenses can improve vision, but they can also scar the cornea. Patients should be informed upon diagnosis that they will likely require contact lenses eventually. Although most patients can continue to read and drive, some feel quality of life is adversely affected. Patients need to know that eye examinations will be required annually or more frequently to monitor progression. About 20% of patients will eventually need a corneal transplant.

Etiology

The proposed etiology of keratoconus includes biochemical and physical corneal tissue changes, but no one theory fully explains the clinical findings and associated ocular and non-ocular disorders. It is possible that keratoconus is an end result or final common pathway of many different clinical conditions. It has been found in association with hereditary predisposition, atopic disease, certain systemic disorders, and long-term rigid contact lens wear.

Diagnosis

Identifying moderate or advanced keratoconus is fairly easy. However, diagnosing keratoconus in its early stages is more difficult, requiring a thorough case history, a search for visual and refractive clues and the use of instrumentation. Often, keratoconus patients have had several spectacle prescriptions in a short period, and none has provided satisfactory vision correction. Refractions are often variable and inconsistent. Keratoconus patients often report monocular diplopia or polyopia and complain of distortion rather than blur at both distance and near vision. Some report halos around lights and photophobia.

Many objective signs are present in keratoconus. Retinoscopy shows a scissoring reflex. Direct ophthalmoscopy may show a shadow (Fig. 1). If the pupil is dilated and a +6.00 D lens is in the ophthalmoscopic system, the cone may appear as an oil or honey droplet when the red reflex is observed.

Fig 1.

The keratometer also aids diagnosis. The initial keratometric sign of keratoconus is absence of parallelism and inclination of the mires. These can easily be missed in mild or early cases. As the cornea advances, the mires appear smaller. To extend the range of the keratometer, an ancillary lens is placed on the front of the keratometer . If a +1.25 D lens is used, this extends the range to 60 D. To record a reading, 8 D is added to the drum reading (for example, if the drum reads 45 D, adding 8 D yields an actual reading of 53 D). A +2.25 D lens extends the range to 68 D by adding 16 D to the reading.

The photokeratoscope or topographer placido disc can provide an overview of the cornea and can show the relative steepness of any corneal area. Figure 2 depicts the keratoconic cornea. The even separation of the rings in the spherical and the astigmatic cornea and the uneven spacing of the rings--especially inferiorly--in the keratoconic cornea should be noted. The central rings may show a tear-drop configuration termed "keratokyphosis".

Reduced visual acuity in one eye, due to the disease's asymmetry, may be a clue with the early keratoconus patient. This sign is often associated with oblique astigmatism. In early keratoconus, the patient may become less myopic six months later as the astigmatism increases.

Normal keratoscopy	Early keratoconus

Moderate keratoconus

Keratoconus can result in extremely complex and variable topographical maps, most typically showing areas of inferior steepening. The cone can assume various shapes and sizes, and the apex can be at various locations in relation to the central cornea.

Placido's computerized video topography showing unilateral early keratoconus

SLIT-LAMP DETECTION

The biomicroscope is the only tool which allows a clinician to observe many classical signs of keratoconus: Fleischer's ring, stress lines of Vogt, corneal thinning and scarring, various types of staining with and without lens wear, increased visibility of corneal nerves, and corneal hydrops.

Fleischer's Ring

The Fleischer ring is a yellow-brown to olive-green ring of pigment which may or may not completely surround the base of the cone (Fig. 3). Formed when hemosiderin (iron) pigment is deposited deep in the epithelium , Fleischer's ring often becomes thinner and more discrete with progression. A careful inspection of the keratoconic cornea will reveal a line in approximately 50% of all cases. Locating this ring initially may be made easier by using a cobalt filter and carefully focusing on the superior half of the cornea's epithelium. Once located, the ring should be viewed in white light to assess its extent.

Fig 3.

Lines of Vogt

Lines of Vogt are small and brushlike lines, generally vertical but they can be oblique. These lines can be found in the deep layers of the keratoconic stroma (Fig. 4) and form along the meridian of greatest curvature; the lines disappear when gentle pressure is exerted on the globe through the lid. Lines of Vogt are more easily viewed when they reappear after this pressure is removed. Rigid lens wear sometimes accentuates the lines. In advanced cases of keratoconus, posterior corneal folds may also be present.

Fig 4.

Corneal Thinning

Significant thinning (up to 1/5th cornea thickness) in the advanced stages of the disease (Fig. 5), and a diagnostic criterion based on comparison of central and peripheral corneal thickness has been proposed. Additionally, as the disease progresses, the cone is often displaced inferiorly. The steepest part of the cornea (apex) is generally the thinnest. Apical thinning described is believed to represent an actual reduction in the number of stromal lamellae rather than an overall thinning process.

Fig 5.

Corneal Scarring

Sub-epithelial corneal scarring, not generally seen early, may occur as keratoconus progresses because of ruptures in Bowman's membrane which is then filled with connective tissue (Fig. 6). Deep opacity of the cornea are not uncommon in keratoconus. It has also been reported that flat-fitting contact lenses may produce or accelerate corneal scarring. A raised "callous" is possible but is easily treated by simple debridement or laser ablation. In addition, apical scarring with an overlying epithelial defect and surrounding edema can be confused for ulcerative keratitis in this disease process.

Fig 6.

Swirl Staining

Swirl staining may occur in patients who have never worn contact lenses because basal epithelial cells drop out and the epithelium slides from the periphery as the cornea regenerates. Thus, a hurricane, vortex, or swirl stain may occur (Fig. 7). Swirl staining may be due to rubbing of the eye or can also result from flat- fitting contact lenses. When this is the case, the lens is generally too flat. A steeper lens often diminishes staining.

Fig 7.

Hydrops

Corneal hydrops occurs, generally in advanced cases, when Descemet's membrane ruptures, aqueous flows into the cornea and reseals (Fig. 8). Keratoconus patients who are having an acute episode of corneal hydrops report a sudden loss of vision and a visible white spot on the cornea. Corneal hydrops causes edema and opacification. As Descemet's regenerates, edema and opacification diminish. Occasionally, hydrops can benefit keratoconus patients who have extremely steep corneas. If the cornea scars, a flatter cornea often results, making it easier to fit with a contact lens. An increased incidence of hydrops has also been reported in keratoconus patients with Down's syndrome. Excessive rubbing should be discouraged in this population. Anecdotally, hydrops seemed to be more prevalent when scleral lenses were employed as a treatment option.

Fig 8.

Munson's Sign

Munson's sign is readily observable without using the slit lamp (Fig.9). This sign occurs in advanced keratoconus when the cornea protrudes enough to angulate the lower lid during inferior gaze.

Fig 9.

Ruzutti's Light Reflex

A light reflex projected from the temporal side will be displaced beyond the nasal limbal sulcus when high astigmatism and steep curvatures are present. Although not a pathognomonic sign, Ruzutti's reflex may aid in a diagnosis especially when a biomicroscope or other tools to aid in diagnosis are not available.

Reduced Intraocular Pressure

A low intraocular pressure is generally found. This is a result of a thinner cornea and/ or reduced scleral rigidity. Due to possible artifact and since the reliability of readings are in question caution must be taken in carefully observing nerve fiber layers and the overall health of the optic nerve.

Classification

Keratoconus can be classified by cone shape, central keratometric reading, or progression. The simplest classification systems are based on keratometric reading or shape:

Based on severity of curvature

• Mild <45 D in both meridians

• Moderate 45-52 D in both meridians

• Advanced >52 D in both meridians

• Severe >62 D in both meridians

Based on shape of cone

• Nipple small diameter (5 mm.); round shape; easiest to fit with contact lenses

• Oval large diameter(>5 mm.); often displaced inferiorly; more difficult to fit with lenses, most common by topography

• Globus largest diameter (>6 mm.); 75% of cornea affected; most difficult to fit with lenses

Surgical Treatments

Various types of surgery are available for the patient with keratoconus. Penetrating keratoplasty is the most common. In this procedure, the keratoconic cornea is prepared by removing the central area of the cornea, and a full-thickness corneal button is sutured in its place Usually, trephines between 8.0-8.5 mm are used. Fleischer's ring can be used as the limit of the conical cornea. Generally, the second eye is not grafted until the first eye is successfully rehabilitated. Running sutures, using Merseline, anchored by cardinal sutures provide excellent results (clear, compact grafts). Older patients with a slower healing response and altered tear film generally do better with nylon and interrupted sutures for selective removal. Contact lenses are often required after this procedure for best visual correction.

An alternative is lamellar keratoplasty, a partial corneal transplant. The cornea is removed to the depth of posterior stroma, and the donor button is sutured in place. This technique is technically difficult, and visual acuity is inferior to that obtained after penetrating keratoplasty. As a result, use of lamellar keratoplasty is largely confined to the treatment of large cones or keratoglobus when tectonic support is needed. This technique requires less recovery time, and poses less chance for corneal graft rejection or failure. Its disadvantages include vascularization and haziness of the graft.

· Corneal Transplant

When good vision can no longer be attained with contact lenses or intolerance to the contact lens develops, corneal transplantation (penetrating keratoplasty) is recommended. In this procedure, the central area of the keratoconic cornea is removed, and a full-thickness donor corneal button is sutured in its place. Contact lenses are often required after this procedure for best visual correction.

An alternative is lamellar keratoplasty, a partial corneal transplant. The cornea is removed to the depth of posterior stroma, and the donor button is sutured in place. This technique is technically difficult, and visual acuity is inferior to that obtained after penetrating keratoplasty. As a result, use of lamellar keratoplasty is largely confined to the treatment of large cones or keratoglobus when tectonic support is needed. This technique requires less recovery time, and poses less chance for corneal graft rejection or failure. Its disadvantages include vascularization and haziness of the graft.

For patients with no scarring near the center of the cornea and 20/40 vision or better with contact lenses, another option is surgically grafting a layer of epithelial cells to flatten the cone-shaped cornea. This process is called epikeratophakia. It has comparable results to corneal transplantation and, if unsuccessful, it can be followed with corneal transplantation.

· Corneal Implants

Intrastromal corneal ring segments (INTACS) are currently being studied as an option for the treatment of decreased vision in keratoconus patients. INTACS are implanted into the periphery of the cornea, producing a flattening effect to the central cornea that results in a smoother contour of the corneal surface. The advantage to INTACS is that the ring segments can be removed should any adverse effects arise following the implant procedure, or if improved vision is not successfully obtained.

· Laser

Excimer laser procedures may have some potential merit, having been used recently with some success in removal of nodular "callous" plaques of the central cornea. New developments in excimer corneal modeling may allow lamellar onlay or penetrating grafts to be lathed, thereby eliminating refractive ametropia following various surgical procedures.

THE GENETICS OF KERATOCONUS

In the keratoconic cornea, a possible genetic predisposition to increased sensitivity to apoptotic mediators by keratocytes has also been hypothesized.

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Sources

* Yuksel Totan, Osman Cekic, Erdinc Aydin. Incidence of keratoconus in subjects with vernal keratoconjunctivitis: A videokeratographic study. Ophthalmology 2001; 108:824-827.

* Wilson SE, Lin DTC, Klyce SD. Corneal topography of keratoconus. Cornea 1991; 10: 2-8.