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Meteoukki W, Fodil M, Adda Negaz N, Rahmoun N, Lardjam Hetraf S, Ouhaibi Djellouli H, Djelti Messal A, Abdi M, Samia Aberkane M, Chiali A, Derdour A, Idder A, Zemani-Fodil F. Association of IL4 rs2070874, FoxP3 rs3761548 Polymorphisms with Keratoconus in Algeria. JOVR [Internet]. 2021Oct.25 [cited 2024Apr.26];16(4):558–565. Available from: https://knepublishing.com/index.php/JOVR/article/view/9745
https://doi.org/10.18502/jovr.v16i4.9745
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Wafaa Meteoukki
Wafaa Meteoukki
Laboratoire de Génétique Moléculaire et Cellulaire (LGMC), Université des Sciences et de la Technologie d’Oran Mohamed BOUDIAF- USTO-MB, BP 1505, El M’naouer, 31000 Oran, Algérie
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Mostefa Fodil
Mostefa Fodil
Agence Thématique de Recherche en Sciences de la Santé (ATRSS)– Oran, Algérie
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Nawel Adda Negaz
Nawel Adda Negaz
Agence Thématique de Recherche en Sciences de la Santé (ATRSS)– Oran, Algérie
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Nesrine Rahmoun
Nesrine Rahmoun
Laboratoire de Génétique Moléculaire et Cellulaire (LGMC), Université des Sciences et de la Technologie d’Oran Mohamed BOUDIAF- USTO-MB, BP 1505, El M’naouer, 31000 Oran, Algérie
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Sarah Lardjam Hetraf
Sarah Lardjam Hetraf
Laboratoire de Génétique Moléculaire et Cellulaire (LGMC), Université des Sciences et de la Technologie d’Oran Mohamed BOUDIAF- USTO-MB, BP 1505, El M’naouer, 31000 Oran, Algérie
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Hadjira Ouhaibi Djellouli
Hadjira Ouhaibi Djellouli
Laboratoire de Génétique Moléculaire et Cellulaire (LGMC), Université des Sciences et de la Technologie d’Oran Mohamed BOUDIAF- USTO-MB, BP 1505, El M’naouer, 31000 Oran, Algérie
-
Ahlem Djelti Messal
Ahlem Djelti Messal
Laboratoire de Génétique Moléculaire et Cellulaire (LGMC), Université des Sciences et de la Technologie d’Oran Mohamed BOUDIAF- USTO-MB, BP 1505, El M’naouer, 31000 Oran, Algérie
-
Meriem Abdi
Meriem Abdi
Laboratoire de Génétique Moléculaire et Cellulaire (LGMC), Université des Sciences et de la Technologie d’Oran Mohamed BOUDIAF- USTO-MB, BP 1505, El M’naouer, 31000 Oran, Algérie
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Meriem Samia Aberkane
Meriem Samia Aberkane
Laboratoire de Génétique Moléculaire et Cellulaire (LGMC), Université des Sciences et de la Technologie d’Oran Mohamed BOUDIAF- USTO-MB, BP 1505, El M’naouer, 31000 Oran, Algérie
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Abdelillah Chiali
Abdelillah Chiali
Clinique Chiali, Oran, Algérie
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Amine Derdour
Amine Derdour
Laboratoire de Génétique Médicale Appliquée à l’Ophtalmologie, Clinique Hammou Boutlélis Oran, Algérie
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Aicha Idder
Aicha Idder
Agence Thématique de Recherche en Sciences de la Santé (ATRSS)– Oran, Algérie
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Faouzia Zemani-Fodil
Faouzia Zemani-Fodil
Laboratoire de Génétique Moléculaire et Cellulaire (LGMC), Université des Sciences et de la Technologie d’Oran Mohamed BOUDIAF- USTO-MB, BP 1505, El M’naouer, 31000 Oran, Algérie
Published Date
- Oct 25, 2021
Association of IL4 rs2070874, FoxP3 rs3761548 Polymorphisms with Keratoconus in Algeria
Abstract
Purpose: The aim of this case–control study was to determine the impact of environmental factors on the predisposition to develop keratoconus in a sample of Western Algerian population. Subsequently, we were interested in the implication of two single nucleotide polymorphisms (SNPs) IL4 rs2070874 and FOXP3 rs3761548, previously described as contributing to the occurrence of allergy, in the development of keratoconus.
Methods: The study included 70 unrelated KC cases and 70 controls originating from Western Algeria. DNA genotyping was done using predesigned probe-based allelic discrimination TaqMan® assays. Allele and genotype frequencies were compared between the cases and controls by Chi-square test and odds ratios with 95% confidence intervals.
Results: A significant association between risk factors such as family history, atopy, eye rubbing, and the development of keratoconus was found in our sample. Smoking would provide a protective effect against the pathology. No statistically significant differences were found in the allele and genotype frequencies between cases and controls neither for IL4 rs2070874 nor for FOXP3 rs3761548.
Conclusion: Our study provides, for the first time, a clear demonstration of the absence of association of the allergy-associated IL4 and FOXP3 polymorphisms with KC in a sample from Western Algerian population.
Keywords:
Case–Control Study, FOXP3 Gene, IL4 Gene, Keratoconus, Polymorphisms, Western Algeria
References
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2. Lema I, Sobrino T, Durán JA, Brea D, Díez-Feijoo E. Subclinical keratoconus and inflammatory molecules from tears. Br J Ophthalmol 2009;93:820–824.
3. Jun AS, Cope L, Speck C, Feng X, Lee S, Meng H, et al. Subnormal cytokine profile in the tear fluid of keratoconus patients. PLoS ONE 2011;6:e16437.
4. Davidson AE, Hayes S, Hardcastle AJ, Tuft SJ. The pathogenesis of keratoconus. Eye Lond Engl 2014;28:189–195.
5. Harrison RJ, Klouda PT, Easty DL, Manku M, Charles J, Stewart CM. Association between keratoconus and atopy. Br J Ophthalmol 1989;73:816–822.
6. McMonnies CW, Boneham GC. Keratoconus, allergy, itch, eye-rubbing and hand-dominance. Clin Exp Optom 2003;86:376–384.
7. Nemet AY, Vinker S, Bahar I, Kaiserman I. The association of keratoconus with immune disorders. Cornea 2010;29:1261–1264.
8. Bijlsma FJ, van Kuik J, van Hoffen E, de Jonge N, Tilanus MGJ, Gmelig-Meyling FHJ, et al. Acute cardiac transplant rejection is associated with low frequencies of interleukin-4 producing helper T-Lymphocytes rather than with interleukin-4 promoter or splice variants. Hum Immunol 2002;63:317–323.
9. Vijayanand P, Seumois G, Simpson LJ, Abdul-Wajid S, Baumjohann D, Panduro M, et al. Interleukin-4 production by follicular helper T cells requires the conserved Il4 enhancer hypersensitivity site V. Immunity 2012;36:175–187.
10. Harada Y, Tanaka S, Motomura Y, Harada Y, Ohno S, Ohno S, et al. The 3′ enhancer CNS2 is a critical regulator of interleukin-4-mediated humoral immunity in follicular helper T cells. Immunity 2012;36:188–200.
11. Movahedi M, Amirzargar AA, Nasiri R, Hirbod-Mobarakeh A, Farhadi E, Tavakol M, et al. Gene polymorphisms of interleukin-4 in allergic rhinitis and its association with clinical phenotypes. Am J Otolaryngol 2013;34:676–681.
12. Gervaziev YV, Kaznacheev VA, Gervazieva VB. Allelic polymorphisms in the interleukin-4 promoter regions and their association with bronchial asthma among the Russian population. Int Arch Allergy Immunol 2006;141:257–264.
13. Suzuki I, Hidaka N, Yamaguchi E, Kawakami Y. Association between a C+33T polymorphism in the IL-4 promoter region and total serum IgE levels. Clin Htmlent Glyphamp Asciiamp Exp Allergy 2000;30:1746–1749.
14. Yang H-J. Association between the interleukin-4 gene C- 589T and C+33T polymorphisms and asthma risk: a metaanalysis. Arch Med Res 2013;44:127–135.
15. Denyer MP, Pinheiro DY, Garden OA, Shepherd AJ. Missed, not missing: phylogenomic evidence for the existence of avian FOXP3. Pappalardo F, éditeur. PLoS ONE 2016;11:e0150988.
16. Maruyama T, Konkel JE, Zamarron BF, Chen W. The molecular mechanisms of FOXP3 gene regulation. Semin Immunol 2011;23:418–423.
17. Zhang L, Zhang Y, Desrosiers M, Wang C, Zhao Y, Han D. Genetic association study of FOXP3 polymorphisms in allergic rhinitis in a Chinese population. Hum Immunol 2009;70:930–934.
18. Fodor E, Garaczi E, Polyánka H, Koreck A, Kemény L, Széll M. The rs3761548 polymorphism of FOXP3 is a protective genetic factor against allergic rhinitis in the Hungarian female population. Hum Immunol 2011;72:926–929.
19. World Medical Association. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA 2013;310:2191–2194.
20. Hollingsworth JG, Efron N. Observations of banding patterns (Vogt Striae) in keratoconus: a confocal microscopy study. Cornea 2005;24:162–166.
21. Brożek JL, Bousquet J, Agache I, Agarwal A, Bachert C, Bosnic-Anticevich S, et al. Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines – 2016 revision. J Allergy Clin Immunol 2017;140:950–958.
22. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.
23. Kennedy RH, Bourne WM, Dyer JA. A 48-year clinical and epidemiologic study of keratoconus. Am J Ophthalmol 1986;101:267–273.
24. Li X, Rabinowitz YS, Rasheed K, Yang H. Longitudinal study of the normal eyes in unilateral keratoconus patients. Ophthalmology 2004;111:440–446.
25. Rabinowitz YS. Keratoconus. Surv Ophthalmol 1998;42:297–319.
26. Cozma I, Atherley C, James NJ. Influence of ethnic origin on the incidence of keratoconus and associated atopic disease in Asian and White patients. Eye 2005;19:924– 925.
27. Moussa S, Grabner G, Ruckhofer J, Dietrich M, Reitsamer H. Genetics in keratoconus – what is new? Open Ophthalmol J 2017;11:201–210.
28. Gordon-Shaag A, Millodot M, Shneor E, Liu Y. The genetic and environmental factors for keratoconus. BioMed Res Int 2015;2015:795738.
29. Barbara R, Gordon-Shaag A, Millodot M, Shneor E, Essa M, Anton M. Prevalence of keratoconus among young Arab students in Israel. Int J Keratoconus Ectatic Corneal Dis 2014;3:9–14.
30. Gordon-Shaag A, Millodot M, Essa M, Garth J, Ghara M, Shneor E. Is consanguinity a risk factor for keratoconus? Optom Vis Sci 2013;90:448–454.
31. 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 2004;18:379–383.
32. Galvis V, Sherwin T, Tello A, Merayo J, Barrera R, Acera A. Keratoconus: an inflammatory disorder? Eye 2015;29:843–859.
33. Boumendjel A, Tridon A, Ughetto S, Messarah M, Salah Boulakoud M. Environnement allergénique d’une population d’enfants asthmatiques à Annaba (Algérie). Ann Biol Clin (Paris) 2010;68:317–324.
34. Bawazeer AM, Hodge WG, Lorimer B. Atopy and keratoconus: a multivariate analysis. Br J Ophthalmol 2000;84:834–836.
35. Balasubramanian SA, Pye DC, Willcox MD. Effects of eye rubbing on the levels of protease, protease activity and cytokines in tears: relevance in keratoconus: eye rubbing in keratoconus. Clin Exp Optom 2013;96:214–218.
36. Chan E, Snibson GR. Current status of corneal collagen cross-linking for keratoconus: a review: cross-linking and keratoconus. Clin Exp Optom 2013;96:155–164.
37. Spoerl E, Raiskup-Wolf F, Kuhlisch E, Pillunat LE. Cigarette smoking is negatively associated with keratoconus. J Refract Surg 2008;24:S737–S740.
38. Rahmoun N, El Mecherfi KE, Bouchetara A, Lardjem Hetraf S, Dahmani Amira C, Adda Neggaz L, et al. Association of REL polymorphism with cow’s milk proteins allergy in pediatric Algerian population. Fetal Pediatr Pathol 2018;37:74–83.
39. Vargiolu M, Silvestri T, Bonora E, Dolzani P, Pulsatelli L, Addimanda O, et al. Interleukin-4/interleukin-4 receptor gene polymorphisms in hand osteoarthritis. Osteoarthr Cartil 2010;18:810–816.
40. FitzGerald LM, Zhao S, Leonardson A, Geybels MS, Kolb S, Lin DW, et al. Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: an analysis of 12,082 prostate cancer cases. Prostate Cancer Prostatic Dis 2018;21:228–237.
41. Battle NC, Choudhry S, Tsai H-J, Eng C, Kumar G, Beckman KB, et al. Ethnicity-specific gene–gene interaction between IL-13 and IL-4Rα among African Americans with asthma. Am J Respir Crit Care Med 2007;175:881–887.
42. Majumder P, Panda SK, Ghosh S, Dey SK. Interleukin gene polymorphisms in chronic periodontitis: a case– control study in the Indian population. Arch Oral Biol 2019;101:156–164.
43. Elsohafy M, Elghzaly A, Abdelsalam H, Gaballah M. Assessment of the possible role of FOXP3 gene (rs3761548) polymorphism in psoriasis vulgaris susceptibility and pathogenesis: Egyptian study. Indian Dermatol Online J2019;10:401.
44. Cekin N, Pinarbasi E, Bildirici AE, Donmez G, Oztemur Z, Bulut O, et al. FOXP3 rs3761548 polymorphism is associated with knee osteoarthritis in a Turkish population. Int J Rheum Dis 2018;21:1779–1786.
45. Jahan P, Ramachander VRV, Maruthi G, Nalini S, Latha KP, Murthy TSR. FOXP3 promoter polymorphism (rs3761548) in breast cancer progression: a study from India. Tumor Biol 2014;35:3785–3791.
46. Zadnik K, Steger-May K, Fink BA, Joslin CE, Nichols JJ, Rosenstiel CE, et al. Between-eye asymmetry in keratoconus. Cornea 2002;21:671–679.
47. Terrence Coyle J. Keratoconus and eye rubbing. Am J Ophthalmol 1984;97:527–528.
48. Gritz DC, McDonnell PJ. Keratoconus and ocular massage. Am J Ophthalmol 1988;106:757–758.
49. Jafri B, Lichter H, Stulting RD. Asymmetric keratoconus attributed to eye rubbing. Cornea 2004;23:560–564.
50. Koenig SB. Bilateral recurrent self-induced keratoconus. Eye Contact Lens Sci Clin Pract 2008;34:343–344.
51. Rehany U, Lahav M, Shoshan S. Collagenolytic activity in keratoconus. Ann Ophthalmol 1982;14:751–754.
52. McMonnies CW. Inflammation and keratoconus. Optom Vis Sci Off Publ Am Acad Optom 2015;92:e35–e41.
2. Lema I, Sobrino T, Durán JA, Brea D, Díez-Feijoo E. Subclinical keratoconus and inflammatory molecules from tears. Br J Ophthalmol 2009;93:820–824.
3. Jun AS, Cope L, Speck C, Feng X, Lee S, Meng H, et al. Subnormal cytokine profile in the tear fluid of keratoconus patients. PLoS ONE 2011;6:e16437.
4. Davidson AE, Hayes S, Hardcastle AJ, Tuft SJ. The pathogenesis of keratoconus. Eye Lond Engl 2014;28:189–195.
5. Harrison RJ, Klouda PT, Easty DL, Manku M, Charles J, Stewart CM. Association between keratoconus and atopy. Br J Ophthalmol 1989;73:816–822.
6. McMonnies CW, Boneham GC. Keratoconus, allergy, itch, eye-rubbing and hand-dominance. Clin Exp Optom 2003;86:376–384.
7. Nemet AY, Vinker S, Bahar I, Kaiserman I. The association of keratoconus with immune disorders. Cornea 2010;29:1261–1264.
8. Bijlsma FJ, van Kuik J, van Hoffen E, de Jonge N, Tilanus MGJ, Gmelig-Meyling FHJ, et al. Acute cardiac transplant rejection is associated with low frequencies of interleukin-4 producing helper T-Lymphocytes rather than with interleukin-4 promoter or splice variants. Hum Immunol 2002;63:317–323.
9. Vijayanand P, Seumois G, Simpson LJ, Abdul-Wajid S, Baumjohann D, Panduro M, et al. Interleukin-4 production by follicular helper T cells requires the conserved Il4 enhancer hypersensitivity site V. Immunity 2012;36:175–187.
10. Harada Y, Tanaka S, Motomura Y, Harada Y, Ohno S, Ohno S, et al. The 3′ enhancer CNS2 is a critical regulator of interleukin-4-mediated humoral immunity in follicular helper T cells. Immunity 2012;36:188–200.
11. Movahedi M, Amirzargar AA, Nasiri R, Hirbod-Mobarakeh A, Farhadi E, Tavakol M, et al. Gene polymorphisms of interleukin-4 in allergic rhinitis and its association with clinical phenotypes. Am J Otolaryngol 2013;34:676–681.
12. Gervaziev YV, Kaznacheev VA, Gervazieva VB. Allelic polymorphisms in the interleukin-4 promoter regions and their association with bronchial asthma among the Russian population. Int Arch Allergy Immunol 2006;141:257–264.
13. Suzuki I, Hidaka N, Yamaguchi E, Kawakami Y. Association between a C+33T polymorphism in the IL-4 promoter region and total serum IgE levels. Clin Htmlent Glyphamp Asciiamp Exp Allergy 2000;30:1746–1749.
14. Yang H-J. Association between the interleukin-4 gene C- 589T and C+33T polymorphisms and asthma risk: a metaanalysis. Arch Med Res 2013;44:127–135.
15. Denyer MP, Pinheiro DY, Garden OA, Shepherd AJ. Missed, not missing: phylogenomic evidence for the existence of avian FOXP3. Pappalardo F, éditeur. PLoS ONE 2016;11:e0150988.
16. Maruyama T, Konkel JE, Zamarron BF, Chen W. The molecular mechanisms of FOXP3 gene regulation. Semin Immunol 2011;23:418–423.
17. Zhang L, Zhang Y, Desrosiers M, Wang C, Zhao Y, Han D. Genetic association study of FOXP3 polymorphisms in allergic rhinitis in a Chinese population. Hum Immunol 2009;70:930–934.
18. Fodor E, Garaczi E, Polyánka H, Koreck A, Kemény L, Széll M. The rs3761548 polymorphism of FOXP3 is a protective genetic factor against allergic rhinitis in the Hungarian female population. Hum Immunol 2011;72:926–929.
19. World Medical Association. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA 2013;310:2191–2194.
20. Hollingsworth JG, Efron N. Observations of banding patterns (Vogt Striae) in keratoconus: a confocal microscopy study. Cornea 2005;24:162–166.
21. Brożek JL, Bousquet J, Agache I, Agarwal A, Bachert C, Bosnic-Anticevich S, et al. Allergic Rhinitis and Its Impact on Asthma (ARIA) guidelines – 2016 revision. J Allergy Clin Immunol 2017;140:950–958.
22. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988;16:1215.
23. Kennedy RH, Bourne WM, Dyer JA. A 48-year clinical and epidemiologic study of keratoconus. Am J Ophthalmol 1986;101:267–273.
24. Li X, Rabinowitz YS, Rasheed K, Yang H. Longitudinal study of the normal eyes in unilateral keratoconus patients. Ophthalmology 2004;111:440–446.
25. Rabinowitz YS. Keratoconus. Surv Ophthalmol 1998;42:297–319.
26. Cozma I, Atherley C, James NJ. Influence of ethnic origin on the incidence of keratoconus and associated atopic disease in Asian and White patients. Eye 2005;19:924– 925.
27. Moussa S, Grabner G, Ruckhofer J, Dietrich M, Reitsamer H. Genetics in keratoconus – what is new? Open Ophthalmol J 2017;11:201–210.
28. Gordon-Shaag A, Millodot M, Shneor E, Liu Y. The genetic and environmental factors for keratoconus. BioMed Res Int 2015;2015:795738.
29. Barbara R, Gordon-Shaag A, Millodot M, Shneor E, Essa M, Anton M. Prevalence of keratoconus among young Arab students in Israel. Int J Keratoconus Ectatic Corneal Dis 2014;3:9–14.
30. Gordon-Shaag A, Millodot M, Essa M, Garth J, Ghara M, Shneor E. Is consanguinity a risk factor for keratoconus? Optom Vis Sci 2013;90:448–454.
31. 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 2004;18:379–383.
32. Galvis V, Sherwin T, Tello A, Merayo J, Barrera R, Acera A. Keratoconus: an inflammatory disorder? Eye 2015;29:843–859.
33. Boumendjel A, Tridon A, Ughetto S, Messarah M, Salah Boulakoud M. Environnement allergénique d’une population d’enfants asthmatiques à Annaba (Algérie). Ann Biol Clin (Paris) 2010;68:317–324.
34. Bawazeer AM, Hodge WG, Lorimer B. Atopy and keratoconus: a multivariate analysis. Br J Ophthalmol 2000;84:834–836.
35. Balasubramanian SA, Pye DC, Willcox MD. Effects of eye rubbing on the levels of protease, protease activity and cytokines in tears: relevance in keratoconus: eye rubbing in keratoconus. Clin Exp Optom 2013;96:214–218.
36. Chan E, Snibson GR. Current status of corneal collagen cross-linking for keratoconus: a review: cross-linking and keratoconus. Clin Exp Optom 2013;96:155–164.
37. Spoerl E, Raiskup-Wolf F, Kuhlisch E, Pillunat LE. Cigarette smoking is negatively associated with keratoconus. J Refract Surg 2008;24:S737–S740.
38. Rahmoun N, El Mecherfi KE, Bouchetara A, Lardjem Hetraf S, Dahmani Amira C, Adda Neggaz L, et al. Association of REL polymorphism with cow’s milk proteins allergy in pediatric Algerian population. Fetal Pediatr Pathol 2018;37:74–83.
39. Vargiolu M, Silvestri T, Bonora E, Dolzani P, Pulsatelli L, Addimanda O, et al. Interleukin-4/interleukin-4 receptor gene polymorphisms in hand osteoarthritis. Osteoarthr Cartil 2010;18:810–816.
40. FitzGerald LM, Zhao S, Leonardson A, Geybels MS, Kolb S, Lin DW, et al. Germline variants in IL4, MGMT and AKT1 are associated with prostate cancer-specific mortality: an analysis of 12,082 prostate cancer cases. Prostate Cancer Prostatic Dis 2018;21:228–237.
41. Battle NC, Choudhry S, Tsai H-J, Eng C, Kumar G, Beckman KB, et al. Ethnicity-specific gene–gene interaction between IL-13 and IL-4Rα among African Americans with asthma. Am J Respir Crit Care Med 2007;175:881–887.
42. Majumder P, Panda SK, Ghosh S, Dey SK. Interleukin gene polymorphisms in chronic periodontitis: a case– control study in the Indian population. Arch Oral Biol 2019;101:156–164.
43. Elsohafy M, Elghzaly A, Abdelsalam H, Gaballah M. Assessment of the possible role of FOXP3 gene (rs3761548) polymorphism in psoriasis vulgaris susceptibility and pathogenesis: Egyptian study. Indian Dermatol Online J2019;10:401.
44. Cekin N, Pinarbasi E, Bildirici AE, Donmez G, Oztemur Z, Bulut O, et al. FOXP3 rs3761548 polymorphism is associated with knee osteoarthritis in a Turkish population. Int J Rheum Dis 2018;21:1779–1786.
45. Jahan P, Ramachander VRV, Maruthi G, Nalini S, Latha KP, Murthy TSR. FOXP3 promoter polymorphism (rs3761548) in breast cancer progression: a study from India. Tumor Biol 2014;35:3785–3791.
46. Zadnik K, Steger-May K, Fink BA, Joslin CE, Nichols JJ, Rosenstiel CE, et al. Between-eye asymmetry in keratoconus. Cornea 2002;21:671–679.
47. Terrence Coyle J. Keratoconus and eye rubbing. Am J Ophthalmol 1984;97:527–528.
48. Gritz DC, McDonnell PJ. Keratoconus and ocular massage. Am J Ophthalmol 1988;106:757–758.
49. Jafri B, Lichter H, Stulting RD. Asymmetric keratoconus attributed to eye rubbing. Cornea 2004;23:560–564.
50. Koenig SB. Bilateral recurrent self-induced keratoconus. Eye Contact Lens Sci Clin Pract 2008;34:343–344.
51. Rehany U, Lahav M, Shoshan S. Collagenolytic activity in keratoconus. Ann Ophthalmol 1982;14:751–754.
52. McMonnies CW. Inflammation and keratoconus. Optom Vis Sci Off Publ Am Acad Optom 2015;92:e35–e41.