The pathogenesis of KERATOCONUS

Abstract

The editor, I appreciate the opportunity to respond to Dr Gatinel’s comments as they address some key issues in relation to the pathogenesis of keratoconus (KC). In regard to links between KC and primary open angle glaucoma, Hashemi and coauthors reviewed the associations between KC and posterior segment structures and reported extensive evidence of morphological and functional changes in the retina, optic nerve head and choroid being found in KC patients [1]. These changes included significantly larger disc and cup areas and deeper cup depth in KC patients than in non-KC individuals [1]. It is possible that exposure to rubbing-related or other mechanisms for episodes of elevated intraocular pressure (IOP) might be involved in the development of posterior segment changes observed in KC patients [2]. For instance, increased tissue hydrostatic pressure and ubiquitination processes that could occur during episodes of IOP elevation may help explain both retinal and corneal cellular changes seen in KC patients [2]. Accordingly, increased hydrostatic pressure in corneal stroma may damage keratocytes and reduce their collagen maintenance functions. Poorly maintained collagen may increase the possibility of thinning and reduced resistance to IOP distending forces with associated increased susceptibility for bulging responses during episodes of IOP elevation [2]. In regard to the notion of bulging corneal responses due to IOP forces and an expected increase in corneal surface area: in the earlier stages of KC development, it appears that stromal fibrils/lamellae may not significantly stretch in response to IOP distending forces. That the corneal surface area is conserved can be explained by the concepts of biomechanical coupling [3] or curvature transfer [4]. These explanations involve steepening/bulging/protrusion of a central/para-central/pre-cone corneal area that is less resistant to IOP, which is compensated for by a flattening of curvature in a diametrically opposed area. The lamellae length required to form the bulge is provided by reduced curvature in the flattened zone. Thus, at least in the earlier stages of KC development, corneal surface area is not significantly changed despite a localized steepened area of bulge response. Colour topographical maps of early KC will sometimes very clearly show the compensating flatter peripheral area diametrically opposed to a steeper/bulging/pre-cone central or para-central area. Correction with rigid contact lenses appears to alter corneal topography such that this observation is not often apparent subsequently. KC corneas assume a conical shape in the most advanced cases [5]. and stretching/elongation of stromal fibrils and lamellae may be part of cone formation as well as an increase in corneal surface area. As far as rubbing being the sine qua non mechanism for KC pathogenesis, there is the need to consider patients who don’t have abnormal rubbing habits. For these patients KC development/progression may sometimes be explained by a finding of ocular hypertension especially if combined with having genetically thinner or otherwise weaker corneas which are more susceptible to bulge responses. For any activity which elevates IOP [2], ocular hypertensive patients are exposed to much higher increases in distending IOP forces than those with normal range IOP. Similarly however, for patients with normal range IOP, potentially significant episodic IOP elevations can also be associated with a wide range of common activities [2], Rubbing may be the most important, especially when it occurs as a chronic habit and involves severe forces and associated frequent/longer episodes of very high IOP. But apart from rubbing, much longer duration episodes of lower degrees of IOP elevation may be significant. For example, during extended periods involving prone positions (sleep, sunbathing, back massage or spinal surgery) episodes of elevation up to 40 mmHg have been recorded [6] which could contribute to KC development. Prone sleeping IOP elevation may be exacerbated by contact between an eye and bedding which has been found to elevate IOP by a mean of 22 ± 5 mmHg (peak 40 ± 11 mmHg) [7]. Eye contact with a hand or arm would also exacerbate prone sleep IOP elevations. Of 100 normal control patients presenting for the correction of refractive error, 32% reported daily prone sleeping and 10% indicated sleeping prone as their favorite position [2]. If there is a sine qua non factor in the multifactorial pathogenesis of KC, then rather than just rubbing, it might be a localized steepening/bulging response to elevated IOP distending forces in a thinner/weaker pre-cone corneal area.