Slight rubbing for 10 seconds using one finger and in a smooth circular movement repeated 30 times over a minute period was shown to significantly reduce the keratocyte density in human corneas , and also leads to a greater concentration of inflammatory mediators in the tears Rubbing-related epithelial thinning may include cell flattening, as well as displacement from the rubbed area of some cells, extracellular fluid, mucin, and cytoplasm from any burst cells.
After an experimental fifteen seconds of rubbing in a circular pattern with use of light to moderate force and the finger pad of an index finger, the epithelial thickness of normal human corneas was found to be reduced by Recovery to baseline thickness took 15 to 30 minutes centrally and 30 to 45 minutes mid-peripherally. Patients with atopic dermatitis and mild blepharoconjunctivitis without any keratopathy may have an impaired ocular surface epithelial barrier This may facilitate cellular infiltration from tears or other corneal inflammatory processes 32 Since eye rubbing can induce inflammatory events, 27,33 , any disease or wound healing process with an inflammatory component has the potential to be exacerbated by rubbing trauma.
Cumulative tissue changes caused by repetitious rubbing episodes may also help link chronic rubbing-related trauma to cone formation. Cone deformation commences most often in the paracentral inferonasal cornea, which corresponds to the location where most senile epithelial cells may be more vulnerable to mechanical forces These mechanisms eloquently suggest that even in the absence of any primary ocular disease, keratoconus can be self-induced as a manifestation of compulsive rubbing behavior.
This makes pathological eye rubbing the foundation on which explain the pathophysiology of keratoconus. In order to refute this, it would suffice to demonstrate that corneal deformation could occur without any external force, through the reduction of corneal resistance secondary to a molecular alteration of its collagen fibrils. There is a common assumption that alterations in corneal collagen make the cornea thin and less resistant to the gradient of pressure between the anterior chamber and the atmosphere.
An unknown stromal collagen degeneration may indeed make the cornea less resistant, but the mechanisms by which the corneal deformation could occur progressively remains unclear. Marfan syndrome, a disorder with an identifiable genetic mutation of the fibrillin-1 molecule, represents a perfect counter-example to explain the inconsistency of such theories on the pathogenesis of keratoconus Despite the reduction of collagen strength present in the corneal stroma, no keratoconic pattern is found in the eyes of Marfan syndrome patients.
Although these corneas are thinner, they tend to be flatter rather than steeper This would naturally cause the corneal curvature to decrease , with concomitant progressive thinning. This description better corresponds to what should be truly called an ectatic cornea, since, as for the ectatic aorta, the progressive homogenous stretching and expansion of such a structure leads to an increase in its respective radius of curvature meaning that the curvature logically decreases.
In Marfan syndrome, morphologic abnormalities resulting from fibrillin-1 mutations can produce the displacement of the crystalline lens but fails to produce any corneal changes other than flattening and thinning. However, this strongly suggests that, without an additional factor, altered biomechanics from collagen abnormalities alone are insufficient to account for the steepening and weakening seen in keratoconus.
On the other hand, it may be logically postulated that patients with Marfan syndrome or any other related connective tissue disease would be prone to develop keratoconus if they rub their eyes too frequently, given the technical structural weakness of the corneal wall. In the case of keratoconus, recent studies have demonstrated that the alteration of the corneal curvature and biomechanics are not evenly distributed throughout the corneal wall but are instead c oncentrated within the corneal apical area.
Working with donor corneas, researchers demonstrated using Brillouin measurements that biomechanical alterations in the keratoconic corneas were primarily concentrated within the area of the cone. Outside the cone, the biomechanical properties evaluated with Brillouin measurements were comparable with that in normal corneas 38!
Vos questions / Nos réponses
This focal aspect does not favor the hypothesis of unknown collagen dystrophy, which would affect the stroma globally. Conversely, chronic eye rubbing, which is exerted in the vicinity of the corneal apex where the cascade of tissular changes described previously would predominate is compatible the focal aspect of damage of the corneal stroma.
Some familial cases and genetic research are still in favor of a genetic dimension to keratoconus but as yet, no genetic mutations have been identified for any of the identified keratoconus chromosome loci.
Discordance for keratoconus in two pairs of monozygotic twins has been reported 39 which supports a pathogenetic role for environmental influences such as eye rubbing. Concordance for keratoconus has also been reported between monozygotic twins This concordance may also be due to being in similar environments and confounding variables such as atopy leading to ocular itch and eye rubbing. In essence, it is difficult to explain with genetics the inter-eye variability in the stage of keratoconus and the different ages of onset.
One must then ask — could eye rubbing be the necessary non -genetic variant or epigenetic factor to explain the disease etiology? As alluded to above, genetic components could actually be related to the predisposition of conditions that lead to increased eye rubbing and to variations in corneal thickness and resistance such as Down syndrome, Tourette syndrome, atopy, sleep apnea and sleep disorders, and pregnancy.
A cornea that is genetically weaker or constitutionally thinner may be more vulnerable to any rubbing trauma as previously discussed. The central corneal thickness is one of the most highly heritable human traits. Ethnic-related differences in central corneal thickness may partly account for the increased prevalence of keratoconus in some ethnicities Amongst the identified sixteen new loci associated with central corneal thickness, two were found to confer relatively large risk for keratoconus For the same rubbing pattern, thinner corneas may be at greater risk for keratoconus.
Despite intensive research, no specific gene has been discovered and it is highly probable that none will ever be.
No Rub, no Cone: The Keratoconus Conjecture. - Docteur Damien Gatinel
Rather, efforts conducted in studying molecular genetics to identify people with native thinner or weaker corneas and prone to immune system disorders leading to allergy or atopy should be encouraged. Over the last few decades, acquired risk factors for eye rubbing and corneal weakening have come to the fore. Allergy and atopy may be the most commonly addressed provocative factors for abnormal eye rubbing Many epidemiological surveys, amongst which repeated cross-sectional surveys have most validity, have demonstrated a twofold increase in the prevalence of allergic and asthma during the past two decades 45, Among allergens, house-dust mites have been advocated to be responsible for the increasing trend in the prevalence of allergic diseases While air pollutant s from industrial sources have been drastically reduced in the last decades, air pollutants from vehicle exhausts nitrogen dioxide, diesel exhaust particulates, ozone show some increase in concentration in some urban areas.
Experiments have shown a synergy between air pollutants and allergens The risk of developing sensitization to an allergen is boosted when the exposure to air pollutants has been performed prior to the exposure to the allergen. The tremendous increase in computer usage has led to the development of computer vision syndrome in many individuals. Episodes of rubbing during extended computer use are frequently admitted by patients once properly informed about it. Ocular fatigue and eyestrain are the main components of computer vision syndrome and may elicit pathological eye rubbing Associated evaporative dry eye from reduced blink frequency can also elicit eye rubbing and account in part for the recent increase in the prevalence of keratoconus in the young population.
Recherche / Education
Contact lens wearers often disclose that they periodically rub their eyes after contact lens removal. Post LASIK ectasia could be the consequence of the stromal flap cut and laser photoablation on c orneas already weakened by chronic eye rubbing. Dry eye exacerbation secondary to LASIK may induce rubbing behavior which dramatically increases the risk of corneal ectasia. It is therefore logical that eye rubbing avoidance may reduce the incidence of post-refractive corneal ectasia. The recent increase in prevalence of these acquired risk factors for eye rubbing may account for the increase in the prevalence and annual incidence of keratoconus In the surgical field, the identification of subclinical keratoconus is a primary concern when screening patients for refractive surgery because performing laser-assisted in situ keratomileusis LASIK on undiagnosed keratoconus has been identified as the leading cause of ectasia after refractive surgery.
Several terms have also been used to describe this condition, including subclinical keratoconus , keratoconus suspect , and forme fruste keratoconus. Beyond any semantic debate, what these entities have in common in terms of topography is that they share the faded features of corneas which we diagnose as having keratoconus.
In the light of the conjecture, they correspond to the missing links between corneas that are strictly normal never or rarely rubbed , and corneas very distorted by repeated and pathological rubbing , which correspond to established keratoconus. In our practice, there is indeed remarkable clinical parallelism between these slightly deformed corneas which cause diagnostic problems where the practice of eye rubbing is not very intense or less frequent.
- Desert Heat (Joanna Brady Mysteries).
- Full text of "Dictionary of French and English, English and French"!
- Earthquakes and Engineers: An International History;
- La Burundanga (Angie Porter nº 1) (Spanish Edition).
For example, some women remove their eye make-up every night and rub their eyes daily vigorously on this occasion. This habit may cause moderate corneal deformations which cause the apparition of topographic patterns such as an isolated inferior steepening. Due to the risk of smearing eye cosmetics, these women tend to avoid rubbing their eyes during the day, which prevents the corneal deformation from becoming more severe more rapidly.
In contrast, men are more likely to develop frank keratoconus. The large variations in rubbing intensity, frequency and duration among patients and their effects on corneas of variable native resistance may be reflected in the broad topographic spectrum of warpage and thinning; from minor topographic abnormalities to advanced keratoconus, encompassing all shades of subclinical keratoconus in between. Figure 6 : This 55 yo patient has been referred for refractive surgery evaluation correction of hyperopia.
Minor topographic abnormalities are seen on the right eye topography: a slight inferotemporal steepening A , and a paracentral inferior thinning B. The posterior surface prolateness is increased C. The left eye topography is unremarkable. The right eye topographic features are commonly found in forme fruste keratoconus. When asked about possible chronic rubbing habits, the patient admits that he wipes his right eye often during the day, because this eye feels irritated and watery.
When questioned about his sleeping habits, the patient declares that he constantly sleeps on the stomach, with the head rotated on the left, causing the right orbit to be compressed on the right forearm. In our experience, there is a striking correlation between the side on which patients sleep, and the side where the most pronounced topographic abnormalities are evident. Compression, heating and local contamination may all contribute to ocular irritation at night, leading to itching sensations during the day. The itch in turn triggers repeated eye rubbing leading to various levels of deformation depending on native corneal properties and the duration, frequency, type, and intensity of eye rubbing.
The displacement of the thinnest corneal area may occur early in the pathologic process. However, we also found in another study that there was no inter-eye difference regarding either the thinnest corneal thickness position or the vertical decentration of the thinnest corneal thickness between keratoconic eyes of various stages These findings support the hypothesis that thinnest corneal thickness decentration occurs early in the keratoconic pathologic process.
The downward displacement of the thinnest point may be caused by two synergistic mechanisms. This may preferentially expose the inferior part of the cornea to the rubbing forces, which are exerted on closed eyes.
Recherche / Education
The displacement of the ground substance may be maximal near but inferior to the corneal apex. The second mechanism may be related to the downward direction of the gravity force : one may also hypothesize that this force may induce some asymmetry in the flexure of the weakened corneal wall, which would also incur a more inferiorly pronounced steepening.
Bringing all of these elements together, a new model to explain keratoconus formation emerges. Based on these findings, eye rubbing is detrimental to corneal biomechanical stability through two main pathways, which are synergetic as both reduce the resistance of the cornea Figure 7.
The first pathway outlines the mechanical impact of rubbing on tissue structures such as collagen fibrils. Rubbing-related buckling and flexure of these fibrils may facilitate cone formation, associated with fibrillar slippage in the cone region. The second pathway corresponds to the impact of eye rubbing on cellular structures , which may undergo changes and apoptosis , further compromising corneal structural properties.
- Grundlagen der Kapitalerhaltung im Gesellschaftsrecht (German Edition).
- Engaged!: Outbehave Your Competition to Create Customers for Life.
- Vos questions / Nos réponses.
- No Rub, no Cone: The Keratoconus Conjecture. - Docteur Damien Gatinel.
Without eye rubbing, the absence of increased hydrostatic pressure and shearing forces will not result in significant corneal deformation no keratoconus. Interestingly, inflammatory processes in the cornea usually result in localized topographic flattening. The imbalance between the reduced corneal resistance and abnormal rubbing eventually causes permanent warpage of the cornea. Finding a counterexample to the conjecture would suffice to invalidate it.