Eye rubbing has long been acknowledged as a risk factor for keratoconus (KC), but its role in the pathogenesis of KC may not have been accorded sufficient prominence. This article puts forth the conjecture that KC is not a dystrophy of unknown genetics and biomolecular substratum, but rather a syndrome caused by eye rubbing, i.e., what has been called “keratoconus” is the direct consequence of mechanical trauma to the cornea by chronic and incessant eye rubbing, resulting in the progressive deformation and thinning of the corneal wall, the hallmarks of the disease. The conjecture is challenged in this article to investigate its compatibility with what is currently known about KC. The conjecture does not contradict previous clinical or experimental findings about KC, all of which can be interpreted in light of this proposed mechanism. Rather, it is a synthetic approach that incorporates the results of previous genetic and biochemical perspectives for understanding the pathophysiology of KC. In fact, this mechanical disease proposition would appear more compatible with explaining the variability of KC expression between patients, between eyes, and the predominance of sporadic cases. As such, eye rubbing may not be solely a risk factor as often coined in medical literature, but the direct cause of the syndrome labeled “keratoconus.” In conclusion, this mechanical theory provides a better explanatory framework for what is currently known about KC and confirms the validity of the “no rub, no cone” conjecture.
Gatinel D. Eye rubbing; a sine qua non for keratoconus? Int J Kerat Ect Cor Dis 2016;5(1):6-12.
For Medical Dictionary for the Health Professions and Nursing. Medical dictionary for the health professions and nursing. S.v. “ectatic.” [cited 2017 Sep 3]. Available from: http://medical-dictionary.thefreedictionary.com/ectatic.
Smolek MK, Klyce SD. Is keratoconus a true ectasia? An evaluation of corneal surface area. Arch Ophthalmol 2000 Sep;118(9):1179-1186.
Gatinel D, Malet J, Hoang-Xuan T, Azar DT. Corneal elevation topography: best fit sphere, elevation distance, asphericity, toricity, and clinical implications. Cornea 2011 May;30(5): 508-515.
Gordon-Shaag A, Millodot M, Kaiserman I, Sela T, Barnett Itzhaki G, Zerbib Y, Matityahu E, Shkedi S, Miroshnichenko S, Shneor E. Risk factors for keratoconus in Israel: a case-control study. Ophthalmic Physiol Opt 2015 Nov;35(6):673-681.
Naderan M, Shoar S, Rezagholizadeh F, Zolfaghari M, Naderan M. Characteristics and associations of keratoconus patients. Cont Lens Anterior Eye 2015 Jun;38(3):199-205.
Sugar J, Macsai MS. What causes keratoconus? Cornea 2012 Jun;31(6):716-719.
Georgiou T, Funnell CL, Cassels-Brown A, O'Conor R. Influence of ethnic origin on the incidence of keratoconus and associated atopic disease in Asians and white patients. Eye (Lond) 2004 Apr;18(4):379-383.
Woodward MA, Blachley TS, Stein JD. The association between sociodemographic factors, common systemic diseases, and keratoconus: an analysis of a nationwide heath care claims database. Ophthalmology 2016 Mar;123(3):457-465.
McMonnies CW. The evidentiary significance of case reports: eye rubbing and keratoconus. Optom Vis Sci 2008 Apr;85(4): 262-269.
Ioannidis AS, Speedwell L, Nischal KK. Unilateral keratoconus in a child with chronic and persistent eye rubbing. Am J Ophthalmol 2005 Feb;139(2):356-357.
Lindsay RG, Bruce AS, Gutteridge IF. Keratoconus associated with continual eye rubbing due to punctal agenesis. Cornea 2000 Jul;19(4):567-569.
Bral N, Termote K. Unilateral keratoconus after chronic eye rubbing by the nondominant hand. Case Rep Ophthalmol 2017 Dec;8(3):558-561.
Panahi-Bazaz MR, Sharifipour F, Moghaddasi A. Bilateral keratoconus and corneal hydrops associated with eye rubbing in a 7-year-old girl. J Ophthalmic Vis Res 2014 Jan;9(1):101-105.
Yusuf IH, Salmon JF. Iridoschisis and keratoconus in a patient with severe allergic eye disease and compulsive eye rubbing: a case report. J Med Case Rep 2016 May;10(1):134.
McMonnies CW. Eye rubbing type and prevalence including contact lens ‘removal-relief’ rubbing. Clin Exp Optom 2016 Jul;99(4):366-372.
McMonnies CW. The possible significance of the baropathic nature of keratectasias. Clin Exp Optom 2013 Mar;96(2):197-200.
McMonnies CW, Boneham GC. Corneal responses to intraocular pressure elevations in keratoconus. Cornea 2010 Jul;29(7):764-770.
Korb DR, Leahy CD, Greiner JV. Prevalence and characteristics of eye rubbing for keratoconic and non-keratoconic subjects. Invest Ophthalmol Vis Sci 1991;32(Suppl):884.
Muller LJ, Pels E, Vrensen GF. The specific architecture of the anterior stroma accounts for maintenance of corneal curvature. Br J Ophthalmol 2001 Apr;85(4):437-443.
Bron, AJ.; Tripathi, RC.; Wolff, E.; Tripathi, BJ. The cornea and sclera. In: Bron AJ, Tripathi RC, Tripathi BJ, editors. Wolff's anatomy of the eye and orbit. 8th ed. London: Chapman & Hall Medical; 1997. pp. 233-267.
McMonnies CW. Mechanisms of rubbing-related corneal trauma in keratoconus. Cornea 2009 Jul;28(6):607-615.
Dupps WJ Jr. Biomechanical modeling of corneal ectasia. J Refract Surg 2005 Mar-Apr;21(2):186-190.
Perone JM, Conart JB, Bertaux PJ, Sujet-Perone N, Ouamara N, Sot M, Henry JJ. Mechanical modeling of a keratoconic cornea. Cornea 2017 Oct;36(10):1263-1266.
Tan JC, Kalapesi FB, Coroneo MT. Mechanosensitivity and the eye: cells coping with pressure. Br J Ophthalmol 2006 Mar;90(3):383-388.
Balasubramanian SA, Pye DC, Willcox MD. Effects of eye rubbing on the levels of protease, protease activity and cytokines in tears: relevance in keratoconus. Clin Exp Optom 2013 Mar;96(2):214-218.
Balasubramanian SA, Pye DC, Willcox MD. Are proteinases the reason for keratoconus? Curr Eye Res 2010 Mar;35(3): 185-191.
Kallinikos P, Efron N. On the etiology of keratocyte loss during contact lens wear. Invest Ophthalmol Vis Sci 2004 Sep;45(9):3011-3020.
McMonnies CW, Alharbi A, Boneham GC. Epithelial responses to rubbing-related mechanical forces. Cornea 2009 Nov;29(11):1223-1231.
Yokoi K, Yokoi N, Kinoshita S. Impairment of ocular surface epithelium barrier function in patients with atopic dermatitis. Br J Ophthalmol 1998 Jul;82(7):797-800.
Blackie CA, McMonnies CW, Korb DR. Warm compresses and the risks of elevated corneal temperature with massage. Cornea 2013 Jul;32(7):e146-e149.
Greiner JV, Peace DG, Baird RS, Allansmith MR. Effects of eye rubbing on the conjunctiva as a model of ocular inflammation. Am J Ophthalmol 1985 Jul;100(1):45-50.
Baum J. On the location of the cone and the etiology of keratoconus. Cornea 1995 Mar;14(2):142-143.
Bron AJ. Keratoconus. Cornea 1988 Sep;7(3):163-169.
Maumenee IH. The eye in the Marfan syndrome. Trans Am Ophthalmol Soc 1981 Feb;79(6):684-733.
Sultan G, Baudouin C, Auzerie O, De Saint Jean M, Goldschild M, Pisella PJ; Marfan Study Group. Cornea in Marfan disease: orbscan and in vivo confocal microscopy analysis. Invest Ophthalmol Vis Sci 2002 Jun;43(6):1757-1764.
Scarcelli G, Pineda R, Yun SH. Brillouin optical microscopy for corneal biomechanics. Invest Ophthalmol Vis Sci 2012 Jan;53(1):185-190.
Scarcelli G, Yun SH. In vivo Brillouin optical microscopy of the human eye. Opt Express 2012 Apr;20(8):9197-9202.
Scarcelli G, Besner S, Pineda R, Yun SH. Biomechanical characterization of keratoconus corneas ex vivo with Brillouin microscopy. Invest Ophthalmol Vis Sci 2014 Jun;55(7): 4490-4495.
Burdon KP, Vincent AL. Insights into keratoconus from a genetic perspective. Clin Exp Optom 2013 Mar;96(2): 146-154.
McMahon TT, Shin JA, Newlin A, Edrington TB, Sugar J, Zadnik K. Discordance for keratoconus in two pairs of monozygotic twins. Cornea 1999 Jul;18(4):444-451.
Nowak DM, Gajecka M. The genetics of keratoconus. Middle East Afr J Ophthalmol 2011 Jan;18(1):2-6.
Abu-Amero KK, Hellani AM, Alansouri SM, Kalantan H, Al-Muammar AM. High-resolution analysis of DNA copy number alterations in patients with isolated sporadic keratoconus. Mol Vis 2011 Mar;17:822-826.
Dimasi DP, Burdon KP, Craig JE. The genetics of central corneal thickness. Br J Ophthalmol 2009 Aug;94(8):971-976.
Chowers I, Anteby I, Ever-Hadani P, Frucht-Pery J. Traumatic wound dehiscence after cataract extraction. J Cataract Refract Surg 2001 Aug;27(8):1238-1242.
Harrison RJ, Klouda PT, Easty DL, Manku M, Charles J, Stewart CM. Association between keratoconus and atopy. Br J Ophthalmol 1989 Oct;73(10):816-822.
Charpin D, Raherison C, Dutau H, Taytard A. Epidémiologie des maladies allergiques respiratoires: données actuelles. Rev Mal Resp 2000;17(1):139-158.
Woolcock, AJ.; Peat, JK. Evidence for the increase in asthma worldwide. In: Chadwick DJ, Cardew G, editors. The rising trends in asthma (Ciba Foundation Symposium 206). Chichester: Wiley; 1997. pp. 122-139.
Custovic A, Smith A, Woodcock A. Indoor allergen are a primary cause of asthma. Eur Respir Rev 1998;53:155-158.
Totan Y, Hepsen IF, Cekic O, Gündüz A, Aydin E. Incidence of keratoconus in subjects with vernal keratoconjunctivitis: a videokeratographic study. Ophthalmology 2001 Apr;108(4): 824-827.
Boutin-Forzano S, Hammou Y, Gouitaa M, Charpin D. Air pollution and atopy. Eur Ann Allergy Clin Immunol 2005 Jan;37(1):11-16.
Munshi S, Varghese A, Dhar-Munshi S. Computer vision syndrome—a common cause of unexplained visual symptoms in the modern era. Int J Clin Pract 2017 Jul;71(7):12962.
Godefrooij DA, de Wit GA, Uiterwaal CS, Imhof SM, Wisse RP. Age-specific incidence and prevalence of keratoconus: a nationwide registration study. Am J Ophthalmol 2017 Mar;175:169-172.
Saad A, Gatinel D. Topographic and tomographic properties of forme fruste keratoconus corneas. Invest Ophthalmol Vis Sci 2010 Nov;51(11):5546-5555.
Saad A, Guilbert E, Gatinel D. Corneal enantiomorphism in normal and keratoconic eyes. J Refract Surg 2014 Aug;30(8): 542-547.
Francis IC, Loughhead JA. Bell's phenomenon. A study of 508 patients. Aust J Ophthalmol 1984 Feb;12(1):15-21.
Karseras AG, Ruben M. Aetiology of keratoconus. Br J Ophthalmol 1976 Jul;60(7):522-525.
Tretter TM, Rabinowitz YS, Yang H, Rotter JI. Etiological factors in keratoconus. Ophthalmology1995;102(Suppl):156.
Zadnik K, Barr JT, Edrington TB, Everett DF, Jameson M, McMahon TT, Shin JA, Sterling JL, Wagner H, Gordon MO. Baseline findings in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) study. Invest Ophthalmol Vis Sci 1998 Dec;39(13):2537-2546.
Carlson AN. Expanding our understanding of eye rubbing and keratoconus. Cornea 2010 Feb;29(2):245.