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The Role of Thyroid Gland Dysfunction in the Development of Keratoconus

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Keratoconus

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Abstract

The number of studies on the development of thyroid gland dysfunction and keratoconus highlights the multifactorial nature of the disease. Many factors seem to be related to keratoconus, such as genetic predisposition, inflammatory markers, environmental conditions, eye rubbing, and metabolic and structural changes, in addition to systemic diseases and hormonal changes. There seems to be evidence that hormonal changes caused by thyroid gland dysfunction are additional factors that, through influencing the corneal structure, could affect keratoconus progression. Thyroid hormones are regulated by the pituitary axis of the thyroid (HPT) and can be imbalanced, besides primary genetic defects, by activating factors that alter homeostasis such as pregnancy, thyroidectomy, or iodine therapy. In this chapter, we emphasize the scientific evidence related to thyroid hormones and the possible correlation to keratoconus.

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References

  1. Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998;42:297–319.

    Article  CAS  PubMed  Google Scholar 

  2. Gatzioufas Z, Thanos S. Acute keratoconus induced by hypothyroxinemia during pregnancy. J Endocrinol Investig. 2008;31:262–6.

    Article  CAS  Google Scholar 

  3. Sugar J, Macsai MS. What causes keratoconus? Cornea. 2012;31(6):716–9.

    Article  PubMed  Google Scholar 

  4. Alhawari HH, Khader YS, Alhawari HH, et al. Autoimmune thyroid disease and keratoconus: is there an association? Int J Endocrinol. 2018;2018:7907512.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Lee R, El-Massry A, El-Massry Y, Randleman JB. Bilateral, asymmetric keratoconus induced by thyrotoxicosis with long-term stability after corneal cross-linking. J Refract Surg. 2018;34(5):354–6.

    Article  PubMed  Google Scholar 

  6. King E. Keratoconus following thyroidectomy. Trans Ophthal Soc U K. 1953;73:31–9.

    Google Scholar 

  7. Howard S, Raine J, Dattani M. Corneal rupture in a child with Down syndrome and hyperthyroidism. BMJ Case Rep. 2009;2009:bcr08.2008.0842.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Koçak Altintas AG, Gül U, Duman S. Bilateral keratoconus associated with Hashimoto’s disease, alopecia areata and atopic keratoconjunctivitis. Eur J Ophthalmol. 1999;9:130–3.

    Article  PubMed  Google Scholar 

  9. Lang GE, Naumann GO. Keratoconus in Alagille syndrome. Klin Monatsbl Augenheilkd. 1991;198:555–7.

    Article  CAS  PubMed  Google Scholar 

  10. Burgi, Konig MP. Endocrine ophthalmopathy. Schweiz Med Wochenschr. 1975;105:1101–10.

    CAS  PubMed  Google Scholar 

  11. Gatzioufas Z, Panos GD, Brugnolli E, Hafezi F. Corneal topographical and biomechanical variations associated with hypothyroidism. J Refract Surg. 2014;30(2):78–9.

    Article  PubMed  Google Scholar 

  12. Thanos S, Oellers P, Meyer Zu Hörste M, et al. Role of thyroxine in the development of keratoconus. Cornea. 2016;35(10):1338–46.

    Article  PubMed  Google Scholar 

  13. Shapiro MB, France TD. The ocular features of Down’s syndrome. Am J Ophthalmol. 1985;99:659–63.

    Article  CAS  PubMed  Google Scholar 

  14. Krachmer JH, Feder RS, Belin MW. Keratoconus and related noninflammatory corneal thinning disorders. Surv Ophthalmol. 1984;28(4):293–322.

    Article  CAS  PubMed  Google Scholar 

  15. Appelbaum A. Keratoconus. Arch Ophthalmol. 1936;15:900–21.

    Article  Google Scholar 

  16. Kahán IL, Varsányi-Nagy M, Tóth M, Nádrai A. The possible role of tear fluid thyroxine in keratoconus development. Exp Eye Res. 1990;50(4):339–43.

    Article  PubMed  Google Scholar 

  17. Bahceci UA, Ozdek S, Pehlivanli Z, Yetkin I, Onol M. Changes in intraocular pressure and corneal and retinal nerve fiber layer thicknesses in hypothyroidism. Eur J Ophthalmol. 2005;15(5):556–61.

    Article  PubMed  Google Scholar 

  18. Coulombre AJ, Coulombre JL. Corneal development. I. Corneal transparency. J Cell Comp Physiol. 1958;51(1):1–11.

    Article  CAS  PubMed  Google Scholar 

  19. Coulombre AJ, Coulombre JL. Corneal development: III. The role of the thyroid in dehydration and the development of transparency. Exp Eye Res. 1964;3(2):105–14.

    Article  CAS  PubMed  Google Scholar 

  20. Conrad AH, Zhang Y, Walker AR, et al. Thyroxine affects expression of KSPG-related genes, the carbonic anhydrase II gene, and KS sulfation in the embryonic chicken cornea. Invest Ophthalmol Vis Sci. 2006;47(1):120–32.

    Article  PubMed  Google Scholar 

  21. Masterson E, Edelhauser HF, Van Horn DL. The role of thyroid hormone in the development of the chick cornea endothelium. Invest Ophthalmol Vis Sci. 1977;16:105–11.

    CAS  PubMed  Google Scholar 

  22. Pereira RC, Jorgetti V, Canalis E. Triiodothyronine induces collagenase-3 and gelatinase B expression in murine osteoblasts. Am J Phys. 1999;277:E496–504.

    CAS  Google Scholar 

  23. Wickham LA, Gao J, Toda I, Rocha EM, Ono M, Sullivan DA. Identification of androgen, estrogen and progesterone receptor mRNAs in the eye. Acta Ophthalmol Scand. 2000;78(2):146–53.

    Article  CAS  PubMed  Google Scholar 

  24. Dias AC, Módulo CM, Jorge AG, et al. Influence of thyroid hormone on thyroid hormone receptor beta-1 expression and lacrimal gland and ocular surface morphology. Invest Ophthalmol Vis Sci. 2007;48(7):3038–42. https://doi.org/10.1167/iovs.06-1309.

    Article  PubMed  Google Scholar 

  25. Chakravarti S, Magnuson T, Lass JH, Jepsen KJ, LaMantia C, Carroll H. Lumican regulates collagen fibril assembly: skin fragility and corneal opacity in the absence of lumican. J Cell Biol. 1998;141:1277–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Swan JS, Hodson SA. Rabbit corneal hydration and the bicarbonate pump. J Membr Biol. 2004;201:33–40.

    Article  CAS  PubMed  Google Scholar 

  27. Bonanno JA. Identity and regulation of ion transport mechanisms in the corneal endothelium. Prog Retin Eye Res. 2003;22:69–94.

    Article  CAS  PubMed  Google Scholar 

  28. Moghimi S, Safizadeh M, Mazloumi M, Hosseini H, Vahedian Z, Rajabi MT. Evaluation of corneal biomechanical properties in patients with thyroid eye disease using Ocular Response Analyzer. J Glaucoma. 2016;25(3):269–73.

    Article  PubMed  Google Scholar 

  29. Lau W, Pye D. A clinical description of Ocular Response Analyzer measurements. Invest Ophthalmol Vis Sci. 2011;52(6):2911–6.

    Article  PubMed  Google Scholar 

  30. Wolffsohn JS, Safeen S, Shah S, et al. Changes of corneal biomechanics with keratoconus. Cornea. 2012;31:849–54.

    Article  PubMed  Google Scholar 

  31. Kamiya K, Shimizu K, Ohmoto F. Effect of aging on corneal biomechanical parameters using the Ocular Response Analyzer. J Refract Surg. 2009;25:888–93.

    Article  PubMed  Google Scholar 

  32. Broman AT, Congdon NG, Bandeen-Roche K, et al. Influence of corneal structure, corneal responsiveness, and other ocular parameters on tonometric measurement of intraocular pressure. J Glaucoma. 2007;16:581–8.

    Article  PubMed  Google Scholar 

  33. Lema I, Durán JA. Inflammatory molecules in the tears of patients with keratoconus. Ophthalmology. 2005;112(4):654–9.

    Article  PubMed  Google Scholar 

  34. Balasubramanian SA, Mohan S, Pye DC, Willcox MD. Proteases, proteolysis and inflammatory molecules in the tears of people with keratoconus. Acta Ophthalmol. 2012;90(4):e303–9.

    Article  PubMed  Google Scholar 

  35. Shetty R, Ghosh A, Lim RR, et al. Elevated expression of matrix metalloproteinase-9 and inflammatory cytokines in keratoconus patients is inhibited by cyclosporine A. Invest Ophthalmol Vis Sci. 2015;56:738–50.

    Article  CAS  PubMed  Google Scholar 

  36. Ihme A, Krieg T, Müller RK, Wollensak J. Biochemical investigation of cells from keratoconus and normal cornea. Exp Eye Res. 1983;36(5):625–63137.

    Article  CAS  PubMed  Google Scholar 

  37. Drózdzm M, Kucharz E, Grucka-Mamczar E. Influence of thyroid hormones on collagen content in tissues of guinea pigs. Endokrinologie. 1979;73(1):105–11.

    PubMed  Google Scholar 

  38. Connors MH, Kollipara S. Peripheral resistance to thyroid hormones. Mayo Clin Proc. 1985;60(5):351.

    Article  CAS  PubMed  Google Scholar 

  39. Goel M, Picciani RG, Lee RK, Bhattacharya SK. Aqueous humor dynamics: a review. Open Ophthalmol J. Netherlands. 2010;4:52–9.

    Article  CAS  Google Scholar 

  40. Stachon T, Stachon A, Hartmann U, Seitz B, Langenbucher A, Szentmáry N. Urea, uric acid, prolactin and fT4 concentrations in aqueous humor of keratoconus patients. Curr Eye Res. 2017;42(6):842–6.

    Article  CAS  PubMed  Google Scholar 

  41. Berardi AC, Oliva F, Berardocco M, la Rovere M, Accorsi P, Maffulli N. Thyroid hormones increase collagen I and cartilage oligomeric matrix protein (COMP) expression in vitro human tenocytes. Muscles Ligaments Tendons J. 2014;4(3):285–91.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Fisher DA, Sack J, Oddie TH, et al. Serum T4, TBG, T3 uptake, T3, reverse T3, and TSH concentrations in children 1 to 15 years of age. J Clin Endocrinol Metab. 1977;45(2):191–8.

    Article  CAS  PubMed  Google Scholar 

  43. El-Massry A, Doheim MF, Iqbal M, et al. Association between keratoconus and thyroid gland dysfunction: a cross-sectional case–control study. J Refract Surg. 2020;36(4):253–7.

    Google Scholar 

  44. Lee R, Hafezi F, Randleman JB. Bilateral keratoconus induced by secondary hypothyroidism after radioactive iodine therapy. J Refract Surg. 2018;34(5):351–3.

    Article  PubMed  Google Scholar 

  45. Tabibian D, de Tejada BM, Gatzioufas Z, et al. Pregnancy-induced changes in corneal biomechanics and topography are thyroid hormone related. Am J Ophthalmol. 2017;184:129–36.

    Article  PubMed  Google Scholar 

  46. Flasko Z, Zemova E, Eppig T, Modis L, Langenbucher A, Wagenpfeil S, Seitz B, Szentmary N. Hypothyroidism is not associated with keratoconus disease: analysis of 626 subjects. J Ophthalmol. 2019;2019:3268595.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Glinoer D. What happens to the normal thyroid during pregnancy? Thyroid. 1999;9:631–5.

    Article  CAS  PubMed  Google Scholar 

  48. Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21(10):1081–125.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Bernardi LA, Scoccia B. The effects of maternal thyroid hormone function on early pregnancy. Curr Opin Obstet Gynecol. 2013;25(4):267–73.

    Article  PubMed  Google Scholar 

  50. De Groot L, Abalovich M, Alexander EK, et al. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline. J Clin Endocrin Metab. 2012;97(8):2543–65.

    Article  Google Scholar 

  51. Ataş M, Duru N, Ulusoy DM, et al. Evaluation of anterior segment parameters during and after pregnancy. Contact Lens Anterior Eye. 2014;37(6):447–50.

    Article  PubMed  Google Scholar 

  52. Bilgihan K, Hondur A, Sul S, Ozturk S. Pregnancy-induced progression of keratoconus. Cornea. 2011;30(9):991–4.

    Article  PubMed  Google Scholar 

  53. Hoogewoud F, Gatzioufas Z, Hafezi F. Transitory topographical variations in keratoconus during pregnancy. J Refract Surg. 2013;29(2):144–6.

    Article  PubMed  Google Scholar 

  54. Hafezi F, Iseli HP. Pregnancy-related exacerbation of iatrogenic keratectasia despite corneal collagen crosslinking. J Cataract Refract Surg. 2008;34(7):1219–21.

    Article  PubMed  Google Scholar 

  55. Padmanabhan P, Radhakrishnan A, Natarajan R. Pregnancy-triggered iatrogenic (post-laser in situ keratomileusis) corneal ectasia—a case report. Cornea. 2010;29(5):569–72.

    Article  PubMed  Google Scholar 

  56. Arya SK, Malik A, Gupta S, Gupta H, Sood S. Spontaneous corneal melting in pregnancy: a case report. J Med Case Rep. 2007;1(1):143.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Oh JY, Kim MK, Park JS, Wee WR. Spontaneous corneal melting during pregnancy: a case report. Cases J. 2009;2(1):7444.

    Article  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Cornea Department, Goiânia Eye Institute, Goiânia, GO, Brazil

    Larissa R. S. Stival

  2. Cornea Department, Federal University of Goiás, Goiânia, GO, Brazil

    Larissa R. S. Stival

  3. Department of Ophthalmology, University of São Paulo, São Paulo, SP, Brazil

    Larissa R. S. Stival

  4. University of São Paulo, São Paulo, SP, Brazil

    Natalia Torres Giacomin

  5. Cornea and Refractive Surgery at Santa Casa, São Paulo, SP, Brazil

    Natalia Torres Giacomin

  6. Cornea and Refractive Surgery Department of Allume, Ophthalmology Institute, São Paulo, SP, Brazil

    Natalia Torres Giacomin

  7. Federal University of Maranhao, São Luís, MA, Brazil

    Natalia Torres Giacomin

  8. Department of Ophthalmology, University of São Paulo, São Paulo, SP, Brazil

    Marcony R. Santhiago

Authors
  1. Larissa R. S. Stival
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  2. Natalia Torres Giacomin
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  3. Marcony R. Santhiago
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Editor information

Editors and Affiliations

  1. Provisão Eye Hospital of Maringá, Maringá, Paraná, Brazil

    Edna Almodin

  2. Federal University of São Paulo, São Paulo, São Paulo, Brazil

    Belquiz Amaral Nassaralla

  3. Nucleo de Medicina Ocular, Goiânia, Goiás, Brazil

    Jordana Sandes

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Stival, L.R.S., Giacomin, N.T., Santhiago, M.R. (2022). The Role of Thyroid Gland Dysfunction in the Development of Keratoconus. In: Almodin, E., Nassaralla, B.A., Sandes, J. (eds) Keratoconus . Springer, Cham. https://doi.org/10.1007/978-3-030-85361-7_4

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  • DOI: https://doi.org/10.1007/978-3-030-85361-7_4

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