Etiology and Epidemiology of Keratoconus
The cause of keratoconus is unknown. There have been many theories based on its association with other conditions but no theory explains any significant percentage of the keratoconus patients. Microscopic changes appear to occur first in a single cell layer of the epithelium (Teng). It is suggested that enzymes released by this degenerating cell layer cause a breakdown of other layers of the cornea. The degenerating cells become pale and swollen, and the cells become less organized (Leibowitz and Lawless). These cells eventually disappear, leaving one or two superficial epithelial cells (McPherson).
A number of studies have attempted to determine if keratoconus is hereditary. The table below summarizes the findings of some of these studies:
|Study||Number of Keratoconic Patients||Number of Patients (%) with a Blood Relative with Keratoconus|
|Hammerstein||52||10 (19%) in immediate family|
|Macsai||386||(8%) had a relative with keratoconus|
|Tufts||Large Sample||10 (2.6%)|
Thus, in some cases there does appear to be a familial association but it is not an autosomal dominant transmission. ("Autosomal dominant transmission" means that if only one of the parents transmits a gene to a child, the child with have that characteristic.) From the presently available information there is less than one in ten chance that a blood relative of a keratoconic patient will have keratoconus.
There are a number of systemic conditions which apparently have a higher than chance association with keratoconus. Among them are:
- Atopic Disease
A higher percent of keratoconic patients have atopic disease than the general population. Disorders such as hay fever, eczema, asthma, and food allergies are all considered atopic diseases
- Down Syndrome
- Connective Tissue Disorders
Eye rubbing among keratoconic patients has been reported at 66% (Copeman) and 73% (Karseras). This eye rubbing can be very vigorous with patients using excessive force with their knuckles. It has been suggested that corneas already weakened by inflammation can develop thinning and protrusion by this rubbing (Ridley). However, many of the underlying conditions, as previously explained, cause ocular itching as well us underlying tissue changes. At this point, the association of keratoconus and eye rubbing is just a clinical observation and a cause-and-effect relationship has not been established. However, it is certainly worthwhile to discourage eye-rubbing, and to see that an atopic condition is treated properly to minimize rubbing.
Hormonal changes are often hypothesized as possible cause of keratoconus since it often first develops at the time of puberty. Keratoconus also occasionally develops during pregnancy or advances during pregnancy (Copeman). Again, there is no direct evidence of a cause-and-effect relationship.
It has been suggested that the wearing of rigid contact lenses can cause keratoconus in some patients. One study (Hartstein) reported on four patients who had worn corneal contact lenses who developed keratoconus. Three of these patients only developed it in one eye, which is rather unusual.
In a study of 162 keratoconus patients (Gasset) a high number of the patients (26.5%) had been wearing rigid lenses an average of 7.15 years prior to the time of diagnosis. In the same study, only one case of keratoconus was found in a control group of 1248 soft lens wearers.
Mascai et al did a retrospective study of 398 eyes (199 keratoconic patients) whose disease was not attributable to other causes such as allergies, family history, or other syndromes commonly associated with keratoconus. They found that 53 patients (106 eyes) had developed keratoconus after having been fitted with contact lenses.
The average age of diagnosis of keratoconus in the patients wearing contact lenses was 32 years, which was significantly older than those not wearing contact lenses (average 19 years old) prior to the diagnosis of keratoconus. They had worn contact lenses for an average of 12.2 years for 15.3 hours per day prior to the diagnosis. Eighty-nine percent of the patients developing keratoconus after contact lens wear were wearing PMMA lenses, which are an older lens, made of a hard plastic that does not transmit oxygen. This is rather strong evidence that there might be an association between wearing PMMA lenses and keratoconus development. A possible alternative explanation is that most keratoconic patients are myopic (near-sighted) prior to a diagnosis of keratoconus and thus would naturally seek contact lenses. Often the patients with developing keratoconus, before diagnosis, have unsatisfactory spectacle vision and thus might ask for contact lenses in an attempt to find a correction resulting in better vision.