Keratoconus: Symptoms, Causes, Diagnosis, Treatment, Prognosis and Epidemiology

It is an eye disorder that causes progressive thinning of the cornea. This can cause blurred vision, double vision, myopia, astigmatism and sensitivity to light.

Usually, both eyes are affected. In more severe cases, you can see a scar or a circle inside the cornea.

Although the cause is unknown, it is thought to occur due to a combination of genetic, environmental and hormonal factors. About seven percent of those affected have a family history of the disease.

The proposed environmental factors include rubbing eyes and allergies. The underlying mechanism involves changes of the cornea to a cone shape. The diagnosis is by examination with a slit lamp.

Initially, the condition can usually be corrected with glasses or soft contact lenses. As the disease worsens, special contact lenses may be required.

In most people, the disease stabilizes after a few years without serious vision problems. In a small number of people corneal scarring occurs and a cornea transplant is required .

Keratoconus affects approximately 1 in 2000 people. It occurs most commonly in late childhood to early adulthood. Although it occurs in all populations, it may be more frequent in certain ethnic groups, such as the descendants of Asians.

The word is from the Greek kéras meaning cornea and the Latin word cōnus meaning cone.

Signs and symptoms

People with early keratoconus typically notice a slight blurred vision of their vision and go to their doctor who looks for corrective reading or driving glasses.

In early stages, the symptoms of keratoconus may not be different from those of any other refractive defect of the eye. As the disease progresses, vision deteriorates, sometimes rapidly.

Visual acuity deteriorates at all distances, and night vision is often deficient. Some people have vision in one eye that is markedly worse than in the other. The disease is often bilateral, although asymmetric.

Some develop photophobia (sensitivity to bright light), eye strain by squinting to read, or itching in the eye, but there is usually little or no pain sensation.

You can make luminous objects appear as cylindrical tubes with the same intensity at all points.

The classic symptom of keratoconus is the perception of multiple “ghost” images, known as a polypopia monocular. This effect is seen most clearly with a high-contrast field, such as a point of light on a dark background.

Instead of seeing only one point, a person with keratoconus sees many images of the point, distributed in a chaotic pattern. This pattern usually does not change day by day, but over time, it often takes on new forms.

People also commonly notice streaks and distortion of sparkles around light sources. Some even notice that the images move one in relation to the other to the rhythm of their heart. The predominant optical aberration of the eye in keratoconus is coma.

The visual distortion experienced by the person comes from two sources, one is the irregular deformation of the surface of the cornea and the other is the scarring that occurs at the high points exposed.

These factors act to form regions in the cornea that map an image in different places on the retina. The effect may worsen in low light conditions, since the dark-adapted pupil dilates to expose more of the irregular surface of the cornea.

Genetics

It has been found that six genes are associated with the condition. These genes include BANP-ZNF469, COL4A4, FOXO1, FNDC3B, IMMP2L and RXRA-COL5A1. It is likely that other genes are also associated.

Causes

Despite considerable research, the cause of keratoconus remains unclear. Several sources suggest that keratoconus probably arises from several different factors: genetic, environmental or cellular, any of which may be the trigger for the onset of the disease.

Once initiated, the disease usually develops by progressive dissolution of the Bowman’s layer, which lies between the corneal epithelium and the stroma.

As the two come into contact, the cellular and structural changes in the cornea adversely affect their integrity and lead to the bulging and scarring characteristic of the disorder.

Within any individual keratoconic cornea, regions of degenerative thinning may be found that coexist with regions that are healing.

Healing appears to be an aspect of corneal degradation; however, a large, multicenter, recent study suggests that abrasion by contact lenses may increase the likelihood of this finding by a factor greater than two.

Several studies have indicated that keratoconus corneas show signs of increased activity by proteases, a class of enzymes that break some of the collagen cross-links in the stroma, with simultaneous reduced expression of protease inhibitors.

Other studies have suggested that the reduced activity of the enzyme aldehyde dehydrogenase may be responsible for the accumulation of free radicals and oxidant species in the cornea.

Whatever the pathogenetic process, damage caused by activity within the cornea will likely result in a reduction in its thickness and biomechanical strength.

At an ultrastructural level, the weakening of the corneal tissue is associated with an alteration of the regular arrangement of the collagen layers and the orientation of the collagen fibril.

While keratoconus is considered a noninflammatory disorder, one study shows that the use of rigid contact lenses by people leads to the overexpression of proinflammatory cytokines, such as IL-6, TNF-alpha, ICAM-1 and VCAM- 1 in the lacrimal fluid.

A genetic predisposition to keratoconus has been observed, with the disease in certain families and reported incidences of concordance in identical twins.

The frequency of appearance in close relatives is not clearly defined, although it is known that it is considerably higher than that of the general population, and studies have obtained estimates ranging between 6% and 19%.

Two studies involving isolated, largely homogenous communities have mapped putative gene sites to chromosomes 16q and 20q in opposite ways. Most genetic studies agree on an autosomal dominant inheritance model.

A rare autosomal dominant form of severe keratoconus with anterior polar cataract is caused by a mutation in the seed region of mir-184, a microRNA that is highly expressed in the cornea and anterior lens.

Keratoconus is diagnosed more frequently in people with Down syndrome, although the reasons for this link have not yet been determined.

Keratoconus has been associated with atopic diseases, including asthma, allergies and eczema, and it is not uncommon for several or all of these diseases to affect a person. Keratoconus is also associated with Alport syndrome, Down syndrome and Marfan syndrome.

Several studies suggest that vigorous rubbing of the eyes contributes to the progression of keratoconus, and people should be discouraged from the practice. Keratoconus differs from ectasia that is caused by laser assisted eye surgery in Situ Keratomileusis.

Post-LASIK Ectasia has been associated with excessive tissue removal from the stromal bed of the eye during surgery.

Diagnosis

Before any physical examination, the diagnosis of keratoconus often begins with the evaluation of an ophthalmologist or optometrist of the person’s medical history.

Particularly evaluate the main complaint and other visual symptoms, the presence of any history of eye disease or injury that may affect the vision and the presence of any family history of eye disease.

Next, an optometric chart, such as a standard Snellen table of progressively smaller letters, is used to determine the visual acuity of the person.

The ocular examination can proceed to the measurement of the localized curvature of the cornea with a manual keratometer, with detection of irregular astigmatism that suggests a possibility of keratoconus.

Severe cases may exceed the measuring capacity of the instrument. An additional indication may be provided by retinoscopy , in which a beam of light is focused on the person’s retina and the reflex observed when the examiner tilts the light source back and forth.

Keratoconus is among the ophthalmic conditions that exhibit a scissor reflex action of two bands that move back and forth like the blades of a pair of scissors.

If keratoconus is suspected, the ophthalmologist or optometrist will look for other findings characteristic of the disease by a slit lamp examination of the cornea.

An advanced case is usually evident to the examiner and can provide an unambiguous diagnosis before performing more specialized tests.

Under close examination, a yellow-brown to olive-green pigmentation ring known as the Fleischer ring can be seen in about half the eyes with keratoconus.

The Fleischer ring, caused by the deposition of hemosiderin iron oxide within the corneal epithelium, is subtle and may not be easily detectable in all cases, but becomes more evident when viewed under a cobalt blue filter.

Similarly, about 50% of the subjects have Vogt striae, fine tension lines within the cornea caused by stretching and thinning. Stretch marks temporarily disappear while light pressure is applied to the eyeball.

A very pronounced cone can create a V-shaped cleft in the lower eyelid when the person’s gaze is directed downward, which is known as the Munson sign.

Other clinical signs of keratoconus will normally have been present long before the Munson sign becomes apparent, so this finding, although a classic sign of the disease, tends not to be of primary diagnostic importance.

A portable keratoscope, sometimes referred to as a “Placido disk”, can provide a simple non-invasive visualization of the cornea surface by projecting a series of concentric rings of light onto the cornea.

A more definitive diagnosis can be obtained using the corneal topography, in which an automated instrument projects the illuminated pattern on the cornea and determines its topography from the analysis of the digital image.

The topographic map indicates any distortion or scarring of the cornea, with keratoconus revealed by a characteristic curved steepness that is generally below the central line of the eye.

The technique can record a snapshot of the extent and extent of the deformation as a reference point to evaluate its rate of progression. It has a particular value to detect the disorder in its early stages when other signs have not yet been presented.

Phases:

Once keratoconus has been diagnosed, its grade can be classified by several metrics:

  • The inclination of greater curvature of “slight” (<45 D), “advanced” (up to 52 D) or “severe” (> 52 D).
  • The cone morphology: ‘nipple’ (small: 5 mm and almost central), ‘oval’ (larger, below the center and often fallen), or ‘balloon’ (more than 75% of the affected cornea).
  • The corneal thickness is mild (> 506 μm) to advanced (<446 μm).

The increasing use of corneal topography has led to a decrease in the use of these terms.

Level 1:
  • Eccentric inclination Induced myopia and / or astigmatism of ≤ 5.0 D.
  • K-lectura ≤ 48.00 D.
  • The lines of Vogt, typical topography.
Stage 2:
  • Induced myopia and / or astigmatism between 5.00 and 8.00 D.
  • Lectura K ≤ 53.00 D.
  • Paquimetría ≥ 400 μm.
Stage 3:
  • Induced myopia and / or astigmatism between 8.01 and 10.00 D.
  • K-lectura> 53.00 D.
  • Pachymetry 200 to 400 μm.
Stage 4:
  • Refraction not measurable.
  • Lectura K> 55.00 D.
  • Central scars.
  • Paquimetría ≤ 200 μm.

The stage is determined if one of the characteristics is applied.

The corneal thickness is the thinnest measured spot of the cornea.

Treatment

Glasses:

In the early stages of keratoconus, glasses or soft contact lenses may be sufficient to correct mild astigmatism.

As the condition progresses, it may no longer provide the person with a satisfactory degree of visual acuity, and most professionals will move to control the condition with rigid contact lenses, known as rigid gas-permeable lenses ( RGP).

Gas-permeable lenses provide a good level of visual correction, but do not stop the progression of the condition.

In people with keratoconus, rigid contact lenses improve vision by using a tear fluid that fills the gap between the irregular surface of the cornea and the smooth, regular inner surface of the lens, creating the effect of a more cornea soft.

Many specialized types of contact lenses have been developed for keratoconus, and affected people can search for both cornea-specific physicians and contact lens installers who have experience in the management of people with keratoconus.

The irregular cone presents a challenge and the installer will endeavor to produce a lens with optimum contact, stability and inclination. Some trial and error settings may be necessary.

Hybrid lenses:

Traditionally, contact lenses for keratoconus have been the “hard” or gas permeable variety, although manufacturers have also produced specialized “soft” or hydrophilic lenses and, more recently, silicone hydrogel lenses.

A soft lens tends to conform to the conical shape of the cornea, thus decreasing its effect. To counter this, hybrid lenses have been developed that are hard at the center and are surrounded by a soft skirt.

However, soft hybrid or previous generation lenses were not effective for everyone. The lenses of early generation have been discontinued.

The fourth generation of hybrid lens technology has improved, giving more people an option that combines the comfort of a soft lens with the visual acuity of a gas-permeable lens.

Scleral lenses:

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, therefore, can offer improved stability. Easier manipulation may find favor with people with reduced dexterity, such as the elderly.

Piggybacking:

Some people find good vision and comfort correction with a combination of piggyback lenses, in which gas-permeable lenses are worn over soft lenses, both of which provide a degree of vision correction.

A piggyback lens shape uses a soft lens with a central countersunk area to accept the rigid lens. The adjustment of a piggyback lens combination requires experience on the part of the lens adjuster and tolerance on the part of the person with keratoconus.

Surgery:

Corneal transplant:

Corneal transplantation, also known as corneal grafting, is a surgical procedure in which a damaged or diseased cornea is replaced by donated corneal tissue (the graft).

When the whole cornea is replaced it is known as penetrating keratoplasty and when only one part of the cornea is replaced it is known as lamellar keratoplasty. Keratoplasty simply means surgery on the cornea.

The graft is taken from a recently deceased person without known diseases or other factors that may affect the possibility of survival of the donated tissue or the health of the recipient.

The cornea is the transparent front part of the eye that covers the iris, the pupil and the anterior chamber. The surgical procedure is performed by ophthalmologists, doctors who specialize in eyes, and often performed on an outpatient basis.

Donors can be of any age, as shown in the case of Janis Babson, who donated her eyes at age 10. Corneal transplant is done when medications, keratoconus sparing surgery and cross-linking can no longer cure the cornea.

Between 11% and 27% of keratoconus cases will progress to a point where vision correction is no longer possible, the thinning of the cornea will become excessive or the scarring resulting from the use of contact lenses will cause problems of their own, and a corneal transplant or penetrating keratoplasty is required.

Keratoconus is the most common reason for performing penetrating keratoplasty, which generally accounts for about a quarter of these procedures.

The cornea transplant surgeon climbs a lenticule of corneal tissue and then grafts the donor’s cornea into the existing ocular tissue, usually using a combination of individual and running sutures.

The cornea does not have a direct supply of blood, so it is not necessary for the donor tissue to be of the compatible blood type. The eye banks check the donor’s corneas for any cell disease or irregularity.

The acute recovery period can take four to six weeks, and complete stabilization of postoperative vision often takes a year or longer, 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 a healthy eye, its success rate may be 95% or more.

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 cause irritation to the person.

In the USA UU., Corneal transplants (also known as corneal grafts) for keratoconus are usually performed under sedation as outpatient surgery.

In other countries, such as Australia and the United Kingdom, the operation is commonly performed with the person undergoing general anesthesia. All cases require careful follow-up with an eye doctor (ophthalmologist or optometrist) for several years.

Vision often improves a lot after surgery, but even if the actual visual acuity does not improve, because the cornea has a more normal shape once healing is complete, people can wear corrective lenses more easily.

The complications of corneal transplants are mainly related to the vascularization of the corneal tissue and the rejection of the donor’s cornea. The loss of vision is very rare, although a vision difficult to correct is possible.

When the rejection is severe, they often try to repeat the transplants, and are often successful.

Keratoconus will not normally reappear in the transplanted cornea; incidences of this have been observed, but are generally attributed to incomplete excision of the original cornea or inadequate screening of the donor tissue.

The long-term prognosis for corneal transplants performed for keratoconus is usually favorable once the initial healing period is completed and some years go by without problems.

One way to reduce the risk of rejection is to use a technique called deep anterior lamellar keratoplasty.

In a graft, only the outermost epithelium and the main thickness of the cornea, the stroma, are replaced; the endothelium layer is left behind the person and the Descemet membrane, which provides some additional structural integrity to the post-graft cornea.

In addition, it is possible to transplant lyophilized donated tissue. The lyophilization process ensures that this tissue is dead, so there is no possibility of rejection.

Investigation of two trials in Iran provides low to moderate evidence that graft rejection is more likely to occur in penetrating keratoplasty than in deep anterior lamellar keratoplasty, although the likelihood of graft failure was similar with both procedures.

Epiqueratafaquia:

Rarely, a non-penetrating keratoplasty known as epiqueratofaquia (or epicardroplasty) can be performed in cases of keratoconus. The corneal epithelium is removed and a lenticle of donor cornea is grafted on top.

The procedure requires a higher level of skill on the part of the surgeon, and is performed less frequently than a penetrating keratoplasty, since the result is generally less favorable.

However, it can be seen as an option in several cases, especially for young people.

Corneal ring implants:

A segment of the intrastromal corneal ring (also known as intrastromal corneal ring, corneal implant or corneal insertion) is a small device implanted in the eye to correct vision.

The procedure involves an ophthalmologist who makes a small incision in the cornea of ​​the eye and inserts two segments of the ring in a half-moon or semicircular shape between the layers of the corneal stroma, one on each side of the pupil.

The incrustation of the two rings in the cornea aims to flatten the cornea and change the refraction of the light that passes through the cornea to the eye.

A possible surgical alternative to corneal transplantation is the insertion of intrastromal corneal ring segments.

A small incision is made at the periphery of the cornea and two thin arcs of polymethyl methacrylate slide between the layers of the stroma on each side of the pupil before the incision is closed with a suture.

The segments push against the curvature of the cornea, flattening the cone’s peak and returning it to a more natural shape. The procedure offers the benefit of being reversible and even potentially interchangeable since it does not involve the removal of ocular tissue.

Cross-Linking cornea:

Cross-linking of corneal collagen is an ongoing treatment that aims to strengthen the cornea, however, according to a Cochrane survey in 2015, there is insufficient evidence to determine whether it is useful in keratoconus.

In 2016, the Food and Drug Administration of the United States approved the ophthalmic solution of riboflavin and the KXL system for cross-linking based on three 12-month clinical trials.

Radial keratotomy:

Radial keratotomy is a refractive surgery procedure in which the surgeon makes a pattern of radio-shaped incisions in the cornea to modify its shape.

This early surgical option for myopia has largely been replaced by laser-assisted in situ keratomileusis (LASIK) and other similar procedures.

The laser assisted in Situ Keratomileusis is absolutely contraindicated in keratoconus and other conditions of thinning of the cornea, since the removal of the corneal stroma tissue will further damage an already thin and weak cornea.

For similar reasons, radial keratotomy has not generally been used in people with keratoconus.

Forecast

Patients with keratoconus usually present initially with mild astigmatism and myopia, commonly at the onset of puberty, and are diagnosed in late adolescence or early 20 years.

The disease can, however, present itself or progress at any age; In rare cases, keratoconus can occur in children or not until later adulthood.

A diagnosis of the disease at an early age may indicate a greater risk of seriousness in later life.

The patients’ vision seems to fluctuate over a period of months, which leads them to change the lens prescriptions frequently, but as the condition worsens, contact lenses are required in most 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 during a prolonged and otherwise constant course.

Most commonly, keratoconus progresses over a period of 10 to 20 years before the course of the disease usually ceases in the third and fourth decades of life.

Hydrophysia corneal:

Corneal dropsy or corneal rupture is a rare complication seen in people with advanced keratoconus or other corneal ectatic disorders, and is characterized by stromal edema due to the leakage of aqueous humor through a tear in Descemet’s membrane.

Although a dropsy usually causes greater healing of the cornea, it will occasionally benefit a patient by creating a flatter cone, aiding the placement of contact lenses. Corneal transplantation is not usually indicated during corneal dropsy.

In advanced cases, the bulging of the cornea can cause a localized rupture of the Descemet membrane, an inner layer of the cornea. The aqueous humor in the anterior chamber of the eye filters into the cornea before Descemet’s membrane reseals.

The patient experiences pain and a sudden and severe vision opacity, and the cornea acquires a translucent milky white appearance known as corneal dropsy.

Although disconcerting to the patient, the effect is usually temporary and after a period of six to eight weeks, the cornea usually returns to its previous transparency.

Recovery can be assisted non-surgically by bandaging with an osmotic saline solution.

Although a dropsy usually causes greater healing of the cornea, it will occasionally benefit a patient by creating a flatter cone, aiding the placement of contact lenses. Corneal transplantation is not usually indicated during corneal dropsy.

Epidemiology

The National Eye Institute reports that keratoconus is the most common corneal dystrophy in the United States, affecting one in 2,000 Americans, but some reports put the number at one in 500.

The inconsistency may be due to variations in the diagnostic criteria, with some cases of severe astigmatism interpreted as keratoconus, and vice versa. A long-term study found an average incidence rate of 2.0 new cases per 100,000 population per year.

Some studies have suggested a higher prevalence among women, or that people of South Asian ethnicity are 4.4 times more likely to suffer from keratoconus than Caucasians, and they are also more likely to be affected with the previous condition.

Keratoconus is usually bilateral (affects both eyes) although the distortion is usually asymmetric and is rarely completely identical in both corneas.

Unilateral cases tend to be uncommon, and in fact they can be very rare if a very mild condition in the best eye is simply below the limit of clinical detection.

It is common for keratoconus to be diagnosed first in one eye and not later in the other. As the condition progresses in both eyes, the vision in the eye previously diagnosed will often remain worse than that of your neighbor.

History

The German oculist Burchard Mauchart provided an early description in a doctoral dissertation 1748 of a case of keratoconus, which he named diaphanous staphylopathy. However, it was not until 1854 that the British physician John Nottingham (1801-1856) clearly described keratoconus and distinguished it from other ectasies of the cornea.

Nottingham reported cases of “conical cornea” that caught his attention and described several classic features of the disease, including polio, weakness of the cornea and difficulty in matching corrective lenses with the patient’s vision.

In 1859, British surgeon William Bowman used an ophthalmoscope (recently invented by Hermann von Helmholtz ) to diagnose keratoconus, and described how to tilt the instrument’s mirror to better see the conical shape of the cornea.

Bowman also tried to restore vision by pulling the iris with a thin hook inserted through the cornea and stretching the pupil in a vertical slot, like a cat’s.

He reported that he had had some success with the technique, restoring the vision to an 18-year-old woman who previously had not been able to count the fingers at a distance of 20 cm (8 inches).

In 1869, when the Swiss ophthalmologist pioneer Johann Horner wrote a thesis entitled On the treatment of keratoconus, the disorder had acquired its current name.

The treatment at that time, supported by the main German ophthalmologist Albrecht von Graefe , was an attempt to physically reshape the cornea by chemical cauterization with a silver nitrate solution and the application of a causative agent of miosis with a pressure bandage.

In 1888, the treatment of keratoconus became one of the first practical applications of the recently invented contact lens, when the French physician Eugène Kaltmanufactured a scleral glass cover that improved vision by compressing the cornea in a more regular way.

Since the beginning of the 20th century, research on keratoconus has improved the understanding of the disease and has greatly expanded the range of treatment options. The first successful corneal transplant to treat keratoconus was performed in 1936 by Ramón Castroviejo.

Society and Culture

Cost:

According to the findings of the Keratoconus Collaborative Longitudinal Assessment (CLEK), people with keratoconus could be expected to pay more than $ 25,000 during their lifetime after diagnosis, with a standard deviation of $ 19,396.

There is limited evidence on the costs of corneal cross-linking, a cost-effectiveness study calculated the total treatment costs for a person at £ 928 ($ 1,392 US) in the UK National Health Service, but this can be as high as $ 2,500 per eye in other countries.

A 2013 cost-benefit analysis conducted by the Lewin Group for the Eye Bank Association of America estimated an average cost of $ 16,500 for each corneal transplant.

Related disorders

Several other corneal ectatic disorders also cause thinning of the cornea.

Keratoglobus is a very rare condition that causes thinning of the cornea mainly at the margins, which results in a slightly enlarged spherical eye. It may be genetically related to keratoconus.

Pellucid marginal degeneration causes thinning of a narrow band (1-2 mm) of the cornea, usually along the lower corneal margin.

It causes irregular astigmatism that, in the early stages of the disease can be corrected with glasses. The differential diagnosis can be made by slit lamp examination.

Posterior keratoconus, a distinct disorder in spite of its similar name, is a rare abnormality, usually congenital, that causes a non-progressive thinning of the inner surface of the cornea, while the curvature of the anterior surface remains normal. Generally, only one eye is affected.

Post-LASIK ectasia is a complication of laser-assisted eye surgery in Situ Keratomileusis.