Incorrect sleeping position and eye rubbing in patients with unilateral or highly asymmetric keratoconus: a case-control study

Keratoconus (KC) is a corneal ectatic disorder that has been classically defined as a progressive, asymmetric, and often bilateral, non-inflammatory condition occurring in adolescence or early adulthood that produces a thinning and steepening of the cornea and causes irregular astigmatism, myopia, and poor visual acuity [1]. The estimated prevalence of KC is approximately 50 to 230/100,000.¹ People are usually affected bilaterally although it is often asymmetric [2]. The reported prevalence of eye rubbing ranges from 66 to 73% in patients with KC, which is concerning as approximately 15% of the worldwide population appears to be suffering from ocular allergies, even more so in industrialized countries [3]. Some studies support that KC is associated with parental consanguinity [4] or other genetic systemic disorders [5], which may render some population genetically more susceptible to the disease than others. Keratoconus could then be triggered by an environmental factor such as repeated biochemical stress on a genetically fragile cornea. However, even if there is a genetic support [6], no causative gene(s) has yet been found and most of keratoconus cases are sporadic. This multifactorial disease with underlying genetic, biomechanical, and environmental processes has remained poorly understood for more than 150 years. A high percentage of KC patients have an atopic disease or allergy, and as a consequence, they frequently rub their eyes [7]. Rabinowitz [8] and Naderan et al. [9] performed case-control studies which found that keratoconus patients rubbed their eyes more often than normal controls (80 and 83% vs. 58 and 52%, respectively).

Eye rubbing is of great concern to eye care practitioners in symptomatic patients, such as patients with ocular allergy, and they usually question patients about the frequency of these symptoms during their routine clinical practice [10]. Repetitive mechanical trauma can cause corneal weakening, by increasing apoptosis and oxidative damage, due to cyclic shear stress on corneal microstructures [11]. McMonnies and Boneham [12] proved a significant relationship between severe eye rubbing and keratoconus on the side of hand dominance. However, there are also examples in the literature [13] of keratoconus after chronic eye rubbing by the nondominant hand. The reported frequency of unilateral KC, as a subset of KC patients, varies depending on the methods used for diagnosis [14]. The reported frequency of unilateral KC using computerized videokeratography techniques ranges between 0.5 and 4% [2]. Different studies [15‐19] have shown that KC patients display a higher prevalence of obstructive sleep apnea compared with the general population. Another study has shown an association between floppy eyelid syndrome and KC [20]; it seems to be a cause of corneal collagen crosslinking failure [21]. In our clinical practice, we have noticed that patients with unilateral keratoconus often sleep on their stomach or on their side, with a direct contact of the eye on the pillow (“pillow hugging”).

To our knowledge, there is no study in the literature that evaluates the possible influence of the patient’s sleep position on the development of keratoconus. Therefore, the aim of this case-control study was to assess eye rubbing and sleeping position in French patients with unilateral or highly asymmetric keratoconus (UHAKC).

This French case-control study aimed to identify new risk factors associated with UHAKC. The results showed a significant association between UHAKC and the following factors: eye rubbing, either during the day or in the morning and especially when it was done on the ipsilateral side; an incorrect sleeping position, i.e., sleeping on sides with the eye compressed against the pillow (“pillow hugging”) or on their stomach. Also, eye rubbing and sleeping on the side of the worse eye were significantly higher than the better eye side in UHAKC patients. This study was the first methodical analysis of an incorrect sleeping position and eye rubbing habits in unilateral or highly asymmetric KC. The results of this study regarding an association between eye rubbing and UHAKC were unequivocal. Our data also showed an association between an incorrect sleeping position and UHAKC, a finding that has never been described before in the literature, even if it had previously been suspected in patients with floppy eyelid syndrome [20, 31].

Eye rubbing has been shown to be associated with KC, and this was confirmed in our multivariate analysis. Although atopy and eye rubbing have been previously investigated [10, 32, 33], how eye rubbing is done and the sleeping position are new, especially in unilateral or highly asymmetrical KC, and are related to the focal nature. However, the cause of keratoconus is still unknown [34], but rubbing the eye is a well-known risk factor [34, 35]. This supports the hypothesis of mechanical fatigue of the cornea after repeated shear stress on its surface, and it could be a possible mechanism for initiating and/or inducing progression of KC, especially when the trauma is strong and prolonged. Korb et al. [36] have found that normal patients rubbed their eyes using their finger pads, generated a force < 0.45 kg/2.54 cm², whereas KC patients used their knuckles, rubbing longer and more often, and generated a force > 4.5 kg/2.54 cm². We agree that it is the more potent environmental factor for the development of KC [37]. In our study, all UHAKC patients were aware of the possible role of eye rubbing as a contributing factor in the development of KC, and after receiving this information, they controlled the impulse to rub their eyes. Some studies have already shown the important role of eye rubbing [26, 27, 34‐36, 38‐41], especially during adolescence.

For example, Coyle and al. [38] have reported the occurrence of unilateral KC in a boy who used digital massage of the affected eye to control episodes of paroxysmal atrial tachycardia. Additionally, Lindsay et al. [39] have reported the case of a patient with unilateral punctal agenesis and epiphora who developed unilateral KC due to regular eye rubbing and tear wiping.

Regarding the sleeping position, we were the first to identify it as a risk factor for KC. Interestingly, the most affected eye did not correlate with the dominant hand, but rather with the preferential side on which patients were used to sleeping. In our study, UHAKC patients were used to sleeping more often on the side of the worse eye than on the side of the better eye. Keratoconus appears to be more common in patients who sleep on their stomach or on one side, which results in a compression of the globe and could be related to increased heat generated locally during sleep. There are several mechanisms [40, 41] by which eye rubbing and the sleeping position could be involved in KC development. It could be assumed that the release of interleukin-1 by a damaged corneal epithelium could result in keratocyte apoptosis and tissue remodeling [42]. A mechanical trauma and increased intraocular pressure could also contribute to the pathogenesis. According to us, the association of all these environmental factors, including eye rubbing, allergy, and an incorrect sleeping position (ocular compression and increased temperature), could lead to the known biochemical changes in KC, i.e., increased activity of inflammatory mediators, induced keratocyte apoptosis, increased fibroblast activity, increased enzyme activities stretching the cornea (proteolytic enzymes) [43, 44], decreased proteinase inhibitor levels [45], and decreased stromal collagen. Thus, a vicious cycle could be induced because a biomechanical stress leads to biochemical changes and contributes to stromal thinning. Considering these arguments, we hypothesize that this focal biomechanical impairment could be primarily caused by eye rubbing, but probably with a stronger and prolonged impact of sleeping position in UHAKC eyes.

In our study, only one KC patient did not report any eye rubbing and no family history of KC, which is related to the fact that most KC cases are sporadic. Furthermore, compared with other studies, the higher percentage of eye rubbing in our study could be explained by the repetition of the question during each consultation, sometimes with the help of a relative. In some cases, patients initially denied rubbing their eyes because they were not aware that they do it automatically, and the testimony of relatives helped patients to realize that they do in fact rub their eyes.

Though not specified in our results, our study also conclude that there is no significant association between smoking and KC.

In addition to these considerations, patients with repeated episodes of allergy or dry eye could be at higher risk of keratoconus, again, due to excessive eye rubbing. Allergy has been found to be more prevalent in KC patients than in controls, as in the present study. The relationship between allergy and KC is less marked in our study than in other studies conducted in Israel [46], Lebanon [47], and Saudi Arabia [48]. This discrepancy may be due to the environmental influence of warm and sunny countries, which prevail in the abovementioned countries. This could explain the higher prevalence of KC reported in Middle East with an increased frequency of eye rubbing. We could consider the possibility that the direct and prolonged contact of the eyelids against the bed linen could increase the contamination of the ocular surface with irritants and allergens such as dust mites. This could contribute to increased local pruritus and subsequently to increased eye rubbing of the affected side, which could partly explain the asymmetry.

In our study, allergy was significantly associated with KC in the univariate analysis but not in the multivariate analysis. This could be due to the high prevalence of allergy in the control group (51.6%), which could be in turn due to the small sample size in this cohort.

In addition, we decided to study whether stress at work and working in front of a computer screen had any effect. We assumed that these factors could be responsible for eye rubbing and therefore could have participated in the asymmetric nature of KC. In our study, these items were not significantly associated with KC; again, this could be due to the small sample size and the high rates found in the control group. Thus, further studies are needed to confirm our findings.

Fortunately, not all eye rubbers or persons sleeping in an incorrect position will develop KC. Indeed, KC may well not develop before sustained and strong rubbing episodes after an extended period during which the cornea buckles permanently and induces irregular astigmatism and increased myopia via central or paracentral steepening. As already mentioned, we assumed that genetic factors for KC [49] could make the cornea more fragile and likely to develop KC, but in the absence of repeated and vigorous corneal trauma, KC does not tend to manifest. Patients with diseases that reduce corneal resistance could also be more likely to experience progressive and permanent corneal deformation whilst applying a similar eye rubbing trauma.

This study has some limitations. Most data were self-reported by patients so that they might be subjected to a recall bias or omission, but since both KC and control patients were asked the same questions, the relative difference should prevail. However, the questions were very similar to those used in the questionnaire validated in other studies [26, 29]. Another limitation is the controversial definition of unilateral or highly asymmetrical KC. In 2015, the Global Consensus on Keratoconus and Ectatic Diseases brought together 4 multinational corneal societies (Cornea Society, Asia Cornea Society, PanCornea and EuCornea) to establish consensus statements and recommendations for the diagnostic and managements of keratoconus. One of the conclusions of the consensus was that “true unilateral keratoconus does not exist” but, “secondary unilateral induced ectasia may be caused by a pure mechanical process” [14]. Tomography [29, 50] is currently recognized as the best and most widely used test to diagnose early or subclinical KC, and the use of quantitative videokeratography-derived indices [51, 52] could be more reproducible for quantifying unilateral or highly asymmetrical KC. Repetitive mechanical trauma [53] applied on the cornea results in a permanent thinning and deformation which also explains very well the frequent inter-eye asymmetry, as a large proportion of patients tend to rub one eye more than the other. We also evaluated the frequency of eye rubbing in the questionnaire, but we could not establish statistics on this item due to the variable and unreliable reports from patients. However, the importance of the frequency of eye rubbing is an important element in the development of keratoconus and tends to be associated with the severity and laterality of this disease. In some patients who rub only one eye, a strictly unilateral KC can be observed, and no clinically detectable topographic or biomechanical alteration can be found in the other unrubbed eye [54‐56]. It should be noted that we monitored all patients of the UHAKC group for a minimum of 1 year, and none developed KC in the contralateral eye.

Furthermore, our relatively small sample size due to the low prevalence of unilateral KC and selective criteria used to define it limit the ability to discriminate with better precision, the risk among groups. A selection bias may have occurred in UHAKC patients because they were not aware that we compared them with non-UHAKC patients; the risk of systematic self-selection other than voluntary compliance is very limited. Therefore, cases and controls were individually matched only for age and sex, because it’s known that KC is more prevalent in men than women, and appears in the second and third decade of life. We decided to select candidates for refractive surgery as controls because most of them were young, healthy, with sufficient myopia, and/or astigmatism to perform refractive surgery, allowing groups to be compared after matching on age and sex. Finally, it is noteworthy that the obtained results were only based on a single dataset, which need to be confirmed by other studies. Nevertheless, our data on the prevalence of the known risk factors were very similar to published data.

In summary, our data provide strong evidence of an association between eye rubbing, incorrect sleeping position, and UHAKC, emphasizing the need for public health awareness of the deleterious consequences of vigorous eye rubbing and incorrect sleeping position. Medical colleagues need to improve the management of eye rubbing and to detect an incorrect sleeping position in diagnosed KC or patients at risk. Further studies are needed to evaluate the long-term stability of KC after eye rubbing cessation and adopting a new correct sleeping position.