Understanding Keratoconus

Introduction

Keratoconus, also called conical cornea, results in the cornea changing from domeshaped to cone-shaped through the progressive thinning of the cornea. Because the cornea is the part of the eye that refracts most of the light entering, the change of its shape prevents incoming light from being focused properly, ultimately distorting vision. In addition, vision may be impaired as a result of swelling and scarring of tissue. Keratoconus is a slow-developing disorder that almost always affects both eyes, though each eye may be affected differently. It is also almost fortuitous that usually one eye is much more affected than the other. This allows many patients to carry on with their normal activities. However, it is also responsible for delayed diagnosis in many cases.

Keratoconus is a condition of obscure etiology that is characterized by the thinning and steepening of the central and/or para-central cornea. The condition usually occurs in the second or third decade of life resulting in a moderate to marked decrease in visual acuity secondary to irregular astigmatism and corneal scarring.

Keratoconus most often occurs bilaterally, however there is often asymmetry with one eye affected more than the other and generally the first eye to develop the condition has a more marked progression.

This differential rate of progression may be an important consideration when counseling patients on the progression of the condition. Cases of unilateral keratoconus are rare but can occasionally be seen in clinical practice.The clinical management of keratoconus varies depending on the severity of the condition and can range from non-surgical options such as glasses and contact lenses to surgical interventions including Intacs, partial grafts, and penetrating keratoplasty once Keratoconus progress’s to an advanced state. This is why an early cross-linking treatment is advised as early
as possible.

Keratoconus History

Early reference to keratoconus was made by Mauchart in 1748 and by Taylor in 1766, but the condition was first adequately described and distinguished from other corneal ectasia by Nottingham
in 1854.

As mentioned by Nottingham in his classical treatise on keratoconus written in 1854 (yes, that is how long we have known about keratoconus) “… a candle, when looked at, appears like a number of lights, confusedly running into one another”

At that time, the treatment of keratoconus consisted of cauterizing the conical area with silver nitrate and the instillation of miotics accompanied by a pressure dressing.

In the early months of 1888, a French ophthalmologist, Eugene Kalt, began work on a crude glass shell designed to “compress the steep conical apex thereby correcting the condition.” This was the first known application of a contact lens for the correction of keratoconus.

Prevalence of Keratoconus in the Population

Keratoconus occurs with approximately equal gender distribution in every region and every ethnicity throughout the world. Many studies have been conducted to estimate the incidence and prevalence of the condition, and, although the incidence varies somewhat from to country to country, a 1986 population-based study in the US indicated that approximately 5 in 10,000 people have keratoconus. Studies from various other areas of the world have reported prevalence from a high of 1 in 250 to 1 in 2000 population. This Prevalence figure will increase because of the use of modern diagnostic equipment which is becoming more readily available and cheaper these days. It is anecdotally felt by some, that the prevalence in India would vary from 1 in 2000 to 1 in 4000 population.

An early onset and increased severity of keratoconus was found in recent studies in ethnic (Asian) groups. This may be related to a combination of genetic and / or environmental factors. However it also indicates that in non-western countries the prevalence of Keratoconus could be much (4.4 times) higher than what it’s thought to be.

If all the prevalence of corneal thinning disorders closely related to Keratoconus was all added together then this figure would be high from the outset. Keratoconus is routinely mis-diagnosed (it’s confused as “normal” Astigmatism regularly) and under diagnosed. Here are some of the categories where figures are lost.

Corneal Ectasia (keratoglobus, pellucid marginal corneal degeneration, Terrien’s marginal degeneration, Posterior Ectasia, forme fruste keratoconus)

Corneal Dystrophies (epithelial basement membrane dystrophy and stromal dystrophies such as granular, lattice, or macular dystrophy)

Corneal Warpage secondary to rigid contact lens wear or irregular astigmatism. Many people in the general population wear glasses without knowing it is due to them having keratoconus or even the optician who prescribed them the glasses knowing this. Mild forms of Keratoconus are common, and it is only in the advanced stages of the disorder a referral to an eye hospital is made for diagnoses.

Therefore, only advanced stages of Keratoconus are noted for statistical purposes generally. This is when it is too late and the Keratoconus has become problematic. We at Clear Vision Eye Center, Mumbai, India strongly feel that the improved early detection of Keratoconus is vital, because with the advent of the cross-linking treatment milder forms of Keratoconus can be treated before they get advanced and problematic. Milder keratoconus patients are the ones who can be helped the most, to stay out of the medical loop, and therefore an earlier intervention with the
Crosslinking treatment is warranted as it’s been proved to be a preventative measure.

Primary Corneal Ectasia

This is a new term being used to describe Keratoconus and all the other forms of corneal thinning disorders of the cornea. Keratoconus is the most common out of all of them. The thinning characteristic of all the corneal thinning disorders is the common feature between them, and it’s the thinning aspect which needs to be addressed by using this term to describe it.

Secondary Corneal Ectasia

(Also called Keratectasia or Iatrogenic Keratectasia) This is when excessive thinning of the eye wall can cause the shape and focusing power of the eye to become unstable after Laser eye treatment as an uncommon complication arising out it. Careful screening to detect pre-existing corneal abnormalities (Keratoconus), conservative limits on treatment (not removing too much corneal tissue), and pre-operative measurement of corneal thickness all combine to limit this risk.

However, to date there is no foolproof method to detect potential cases prior to the Laser Surgery.

Every thing which has been discussed above about the prevalence of Keratoconus shows that the prevalence of Keratoconus is much more common than previously thought, and with the increasing use of modern diagnostic equipment it is even higher. The first thing an eye care specialist looks at is the front surface of the eye of a patient, which needs to be checked with the latest modern diagnostic testing equipment these days. Many of the Primary Corneal Ectasia can be picked up sooner and treated earlier, which would not have been picked-up other-wise.

In most circumstances most practices don’t even have access to a corneal topography machine, which should be a standard feature of any modern practice. The front surface of the eye is very important, because the cornea is responsible for most of the eye’s total focusing power; and also it’s where most medical intervention are done to the eye to treat and correct the visual errors that a patients has. Therefore it is imperative, that a practice modernizes to have the latest corneal diagnostic test equipment to-hand.

Etiology of Keratoconus

There has always been speculation as to the cause of keratoconus, but during the past 10 years our scientific knowledge of the condition has steadily increased.

Although we now have a much better understanding of the cellular and molecular changes that occur in this condition, keratoconus remains a condition of unknown etiology. Recent research conducted by Steven Wilson, MD, at the University of Washington suggests that keratoconus somehow accelerates the process of keratocyte apoptosis, which is the programmed death of corneal cells that occurs following injury. Minor external traumas, such as eye rubbing, poorly fitted contact lenses, and ocular allergies can release cytokines from the epithelium that stimulate keratocyte apoptosis (the earliest observable stromal response to an epithelial injury).

Although keratocyte apoptosis is virtually never detectable in the absence of epithelial injury in normal patients, a high percentage of keratoconus patients show evidence of such cell death. This typically takes place first in the anterior stroma and is manifested by breaks in Bowman’s layer and later as stromal thinning. Wilson has also suggested that genetics may play a role in the etiology of keratoconus, in that some patients may have a genetic predisposition to chronic keratocyte apoptosis.

It has been suggested that keratoconus corneas may have increased enzyme activities and decreased levels of enzyme inhibitors. This combination results in the production of toxic by-products that bring about a cascade of events throughout the cornea, resulting in corneal thinning and scarring.

Two chief mechanisms for the development of keratoconus have been put forward. One proposes that ectasia is closely associated with tissue degradation or reduced maintenance, whereas the other suggests that it is due to slippage between collagen fibrils, with no overall tissue loss.

Genetics in Keratoconus

One of the strongest arguments for a genetic component in keratoconus etiology is that the condition can run in families. Although most patients diagnosed with keratoconus report no positive family history, the likelihood that keratoconus will be found in one or more member of the immediate family is 3.4%, which is 15 to 70 times higher than the general population rate. In addition, keratoconus has been reported in identical twins and in two or more generations of many families. The advent of computerized corneal mapping techniques has made earlier detection of sub-clinical, and/or slowly progressive forms of the condition more precise. Therefore, it is suspected that familial prevalence rates will most likely increase. Using corneal topographical findings, in 1990 Rabinowitz and his colleagues from UCLA, California, showed that 50% of randomly selected family members of keratoconus patients displayed subtle topographical abnormalities somewhat suspect of keratoconus.

Studies to identify the association of keratoconus with various chromosomes have been performed. Reports on a small number of families with keratoconus show a connection between keratoconus and defects on chromosomes 21, 17, and 13. However, at this time it is unknown exactly what specific parts of these chromosomes are defective or how the defects might cause keratoconus.

Future investigations will most likely conclude that more than one gene is associated with the diverse clinical presentations seen in keratoconus. This is based on the fact that there is considerable variation among individuals with keratoconus and so multiple genes are most likely involved. For example, keratoconus manifests in many forms and degrees of severity:

  • It can be unilateral or bilateral,
  • It can affect the central or midperipheral cornea,
  • It can be mild or severe,
  • It can start in childhood or later in life, and
  • It can occur in more than one family member or in one individual only.

The Environment and Keratoconus

Although it is generally believed that keratoconus has a genetic component, there are increasing data that suggest the environment might also play a role in the development of the condition.

Research has discovered that corneas with keratoconus have been exposed to a number of factors that can produce reactive oxygen species (i.e., free radicals). These include ultraviolet light, atopy, mechanical eye rubbing, and poorly fitted contact lenses. They propose that susceptible corneas exhibit an inability to process reactive oxygen species because they lack the necessary protective enzymes (e.g., ALDH3 and superoxide dismutase). The reactive oxygen species result in an accumulation of toxic byproducts such as MDA and peroxynitrites that can damage corneal proteins and trigger a cascade of events that disrupt the cornea’s cellular structure and function. This can result in corneal thinning, scarring, and apoptosis.

If this theory is valid, it might be prudent for keratoconus patients to minimize the factors that can cause reactive oxygen species to be formed. It might be helpful for patients to do the following:

  • Reduce exposure to ultraviolet (UV) light by wearing UV protecting sunglasses outdoors.
  • Avoid excessive mechanical trauma such as vigorous eye rubbing and
    poorly fitting contact lenses.
  • Manage atopy/allergies through environmental and/or pharmacologic intervention.
  • Use preservative-free artificial tears and lens care products that are efficacious compatible with the patient’s ocular surface.

Although the environmental damage theory is interesting, at this time there is no conclusive evidence to support the fact that changes in diet, environment, or emotional state can influence the eventual course of the disease. This is supported by the fact that keratoconus occurs throughout the world in a wide range of geographic, social, and dietary conditions.

Associated Conditions

Keratoconus has been associated with a number of systemic conditions including Down’s syndrome (trisomy of chromosome 21). A number of authors have reported that the incidence of keratoconus in Down’s syndrome is between 5.5% and 15%, which is considerably higher that the incidence of approximately 5 per 10,000 (0.05%) cited for the general population. Occasionally, keratoconus is also seen in individuals with connective tissue disorders such as Osteogenesis Imperfecta, Ehlers-Danlos Syndrome, and joint hypermobility.

Hallmarks of Keratoconus

Although the etiology of keratoconus remains somewhat obscure, its clinical manifestations have been well documented. Some on the major hallmarks of keratoconus include:

  • A decline in visual acuity (usually greater in one eye than the other).
  • A distorted retinoscopy reflex in which there is rapid movement of the light in
    the periphery and slow movement in the center of the pupil. The reflex appears to spin or swirl around a point corresponding to the apex of the cone.
  • Distortion of or an inability to superimpose the bottom right keratometry mire.
  • Frequent changes in spectacle cylinder power and axis.
  • Increased myopia.
  • Squeezing of the eyelids to create a pinhole effect.
  • The appearance of halos or starbursts
    around light during nighttime viewing.
  • Associated atopic disease.