539
Views
15
CrossRef citations to date
0
Altmetric
Cornea, Limbus & Ocular Surface

The Effect of Age, Gender and Body Mass Index on Tear Film Neuromediators and Corneal Nerves

, , , , , , & ORCID Icon show all
Pages 411-418 | Received 23 Jul 2019, Accepted 07 Sep 2019, Published online: 18 Sep 2019

References

  • Rózsa AJ, Beuerman RW. Density and organization of free nerve endings in the corneal epithelium of the rabbit. Pain. 1982;14(2):105–20. doi:10.1016/0304-3959(82)90092-6.
  • Zander E, Weddell G. Observations on the innervation of the cornea. J Anat. 1951;85:68–99.
  • MacIver MB, Tanelian DL. Structural and functional specialization of A delta and C fiber free nerve endings innervating rabbit corneal epithelium. J Neurosci. 1993;13(10):4511–24. doi:10.1523/JNEUROSCI.13-10-04511.1993.
  • Al-Aqaba MA, Fares U, Suleman H, Lowe J, Dua HS. Architecture and distribution of human corneal nerves. Br J Ophthalmol. 2010;94(6):784–89. doi:10.1136/bjo.2009.173799.
  • Tervo K, Tervo T, Eranko L, Vannas A, Cuello AC, Eränkö O. Substance P-immunoreactive nerves in the human cornea and iris. Invest Ophthalmol Vis Sci. 1982;23:671–74.
  • Uusitalo H, Krootila K, Palkama A. Calcitonin gene-related peptide (CGRP) immunoreactive sensory nerves in the human and guinea pig uvea and cornea. Exp Eye Res. 1989;48(4):467–75. doi:10.1016/0014-4835(89)90030-4.
  • Garcia-Hirschfeld J, Lopez-Briones LG, Belmonte C. Neurotrophic influences on corneal epithelial cells. Exp Eye Res. 1994;59(5):597–605. doi:10.1006/exer.1994.1145.
  • Yang L, Di G, Qi X, Qu M, Wang Y, Duan H, Danielson P, Xie L, Zhou Q. Substance P promotes diabetic corneal epithelial wound healing through molecular mechanisms mediated via the neurokinin-1 receptor. Diabetes. 2014;63(12):4262–74. doi:10.2337/db14-0163.
  • Kovács I, Ludány A, Kőszegi T, Fehér J, Kovács B, Szolcsányi J, Pintér E, Koszegi T, Fehér J, Kovács B, et al. Substance P released from sensory nerve endings influences tear secretion and goblet cell function in the rat. Neuropeptides. 2005;39(4):395–402. doi:10.1016/j.npep.2005.04.003.
  • Markoulli M, You J, Kim J, Duong CL, Tolentino JB, Karras J, Lum E. Corneal nerve morphology and tear film substance P in diabetes. Optom Vis Sci. 2017;94(7):726–31. doi:10.1097/OPX.0000000000001096.
  • Nakamura M. Restoration of corneal epithelial barrier function and wound healing by substance P and IGF-1 in rats with capsaicin-induced neurotrophic keratopathy. Invest Ophthalmol Vis Sci. 2003;44(7):2937–40. doi:10.1167/iovs.02-0868.
  • Mikulec AA, Tanelian DL. CGRP increases the rate of corneal re-epithelialization in an in vitro whole mount preparation. J Ocul Pharmacol Ther. 1996;12(4):417–23. doi:10.1089/jop.1996.12.417.
  • Quattrini C, Tavakoli M, Jeziorska M, Kallinikos P, Tesfaye S, Finnigan J, Marshall A, Boulton AJ, Efron N, Malik RA. Surrogate markers of small fiber damage in human diabetic neuropathy. Diabetes. 2007;56(8):2148–54. doi:10.2337/db07-0285.
  • Edwards K, Pritchard N, Vagenas D, Russell A, Malik RA, Efron N. Utility of corneal confocal microscopy for assessing mild diabetic neuropathy: baseline findings of the LANDMark study. Clin Exp Optom. 2012;95(3):348–54. doi:10.1111/j.1444-0938.2012.00740.x.
  • Kass-Iliyya L, Javed S, Gosal D, Kobylecki C, Marshall A, Petropoulos IN, Ponirakis G, Tavakoli M, Ferdousi M, Chaudhuri KR, et al. Small fiber neuropathy in Parkinson’s disease: a clinical, pathological and corneal confocal microscopy study. Park Relat Disord. 2015;21(12):1454–60. doi:10.1016/j.parkreldis.2015.10.019.
  • Misra SL, Kersten HM, Roxburgh RH, Danesh-Meyer HV, McGhee CNJ. Corneal nerve microstructure in Parkinson’s disease. J Clin Neurosci. 2017;39:53–58. doi:10.1016/j.jocn.2017.02.033.
  • Ferrari G, Grisan E, Scarpa F, Fazio R, Comola M, Quattrini A, Comi G, Rama P, Riva N. Corneal confocal microscopy reveals trigeminal small sensory fiber neuropathy in amyotrophic lateral sclerosis. Front Aging Neurosci. 2014;6:278. doi:10.3389/fnagi.2014.00278.
  • Ponirakis G, Al Hamad H, Sankaranarayanan A, Khan A, Chandran M, Ramadan M, Tosino R, Gawhale PV, Alobaidi M, AlSulaiti E, et al. Association of corneal nerve fiber measures with cognitive function in dementia. Ann Clin Transl Neurol. 2019;6(4):689–97. doi:10.1002/acn3.746.
  • Mikolajczak J, Zimmermann H, Kheirkhah A, Kadas EM, Oberwahrenbrock T, Muller R, Ren A, Kuchling J, Dietze H, Prüss H, et al. Patients with multiple sclerosis demonstrate reduced subbasal corneal nerve fibre density. Mult Scler. 2017;23(14):1847–53. doi:10.1177/1352458516677590.
  • Yamada M, Ogata M, Kawai M, Mashima Y. Decreased substance P concentrations in tears from patients with corneal hypesthesia. Am J Ophthalmol. 2000;129(5):671–72. doi:10.1016/S0002-9394(00)00415-3.
  • Lambiase A, Micera A, Sacchetti M, Cortes M, Mantelli F, Bonini S. Alterations of tear neuromediators in dry eye disease. Arch Ophthalmol. 2011;129(8):981–86. doi:10.1001/archophthalmol.2011.200.
  • Tavakoli M, Ferdousi M, Petropoulos IN, Morris J, Pritchard N, Zhivov A, Ziegler D, Pacaud D, Romanchuk K, Perkins BA, et al. Normative values for corneal nerve morphology assessed using corneal confocal microscopy: a multinational normative data set. Diabetes Care. 2015;38(5):838–43. doi:10.2337/dc14-1100.
  • Niederer RL, Perumal D, Sherwin T, McGhee CNJ. Age-related differences in the normal human cornea: a laser scanning in vivo confocal microscopy study. Br J Ophthalmol. 2007;91(9):1165–69. doi:10.1136/bjo.2006.112656.
  • Grupcheva CN, Wong T, Riley AF, McGhee CNJ. Assessing the sub-basal nerve plexus of the living healthy human cornea by in vivo confocal microscopy. Clin Exp Ophthalmol. 2002;30(3):187–90. doi:10.1046/j.1442-9071.2002.00507.x.
  • Wu T, Ahmed A, Bril V, Orszag A, Ng E, Nwe P, Perkins BA. Variables associated with corneal confocal microscopy parameters in healthy volunteers: implications for diabetic neuropathy screening. Diabet Med. 2012;29(9):e297–303. doi:10.1111/j.1464-5491.2012.03678.x.
  • Erie JC, McLaren JW, Hodge DO, Bourne WM. The effect of age on the corneal subbasal nerve plexus. Cornea. 2005;24(6):705–09. doi:10.1097/01.ico.0000154387.51355.39.
  • Micera A, Di Zazzo A, Esposito G, Longo R, Foulsham W, Sacco R, Sgrulletta R, Bonini S. Age-related changes to human tear composition. Invest Ophthalmol Vis Sci. 2018;59(5):2024–31. doi:10.1167/iovs.17-23358.
  • Nättinen J, Jylhä A, Aapola U, Mäkinen P, Beuerman R, Pietilä J, Vaajanen A, Uusitalo H. Age-associated changes in human tear proteome. Clin Proteomics. 2019;16(1):11. doi:10.1186/s12014-019-9233-5.
  • Marco B, Alessandro R, Philippe F, Fabio B, Paolo R, Giulio F. The effect of aging on nerve morphology and substance P expression in mouse and human corneas. Invest Ophthalmol Vis Sci. 2018;59(13):5329–35. doi:10.1167/iovs.18-24707.
  • Sullivan DA, Rocha EM, Aragona P, Clayton JA, Ding J, Golebiowski B, Hampel U, McDermott AM, Schaumberg DA, Srinivasan S, et al. TFOS DEWS II sex, gender, and hormones report. Ocul Surf. 2017;15(3):284–333. doi:10.1016/j.jtos.2017.04.001.
  • Stapleton F, Alves M, Bunya VY, Jalbert I, Lekhanont K, Malet F, Na KS, Schaumberg D, Uchino M, Vehof J, et al. TFOS DEWS II epidemiology report. Ocul Surf. 2017;15(3):334–65. doi:10.1016/j.jtos.2017.05.003.
  • Acosta MC, Alfaro ML, Borrás F, Belmonte C, Gallar J. Influence of age, gender and iris color on mechanical and chemical sensitivity of the cornea and conjunctiva. Exp Eye Res. 2006;83(4):932–38. doi:10.1016/j.exer.2006.04.018.
  • Golebiowski B, Papas EB, Stapleton F. Factors affecting corneal and conjunctival sensitivity measurement. Optom Vis Sci. 2008;85(4):241–46. doi:10.1097/OPX.0b013e3181694f96.
  • Callaghan BC, Gao LL, Li Y, Zhou X, Reynolds E, Banerjee M, Pop-Busui R, Feldman EL, Ji L. Diabetes and obesity are the main metabolic drivers of peripheral neuropathy. Ann Clin Transl Neurol. 2018;5(4):397–405. doi:10.1002/acn3.531.
  • Yadav RL, Sharma D, Yadav PK, Shah DK, Agrawal K, Khadka R, Islam MN. Somatic neural alterations in non-diabetic obesity: a cross-sectional study. BMC Obes. 2016;3(1):50. doi:10.1186/s40608-016-0131-3.
  • Sharma S, Tobin V, Vas PRJ, Malik RA, Rayman G. The influence of age, anthropometric and metabolic variables on LDIFLARE and corneal confocal microscopy in healthy individuals. Bhattacharya S, editor. PLoS One. 2018;13(3):e0193452. doi:10.1371/journal.pone.0193452.
  • Schiano Lomoriello D, Abicca I, Parravano M, Giannini D, Russo B, Frontoni S, Picconi F. Early alterations of corneal subbasal plexus in uncomplicated type 1 diabetes patients. J Ophthalmol. 2019;2019:1–8. doi:10.1155/2019/9818217.
  • Cornblath DR, Chaudhry V, Carter K, Lee D, Seysedadr M, Miernicki M, Joh T. Total neuropathy score: validation and reliability study. Neurology. 1999;53(8):1660–64. doi:10.1212/WNL.53.8.1660.
  • Kwai NCG, Arnold R, Wickremaarachchi C, Lin CSY, Poynten AM, Kiernan MC, Krishnan AV. Effects of axonal ion channel dysfunction on quality of life in type 2 diabetes. Diabetes Care. 2013;36(5):1272–77. doi:10.2337/dc12-1310.
  • Sung JY, Park SB, Liu YT, Kwai N, Arnold R, Krishnan AV, Lin CSY. Progressive axonal dysfunction precedes development of neuropathy in type 2 diabetes. Diabetes. 2012;61(6):1592–98. doi:10.2337/db11-1509.
  • Markoulli M, Gokhale M, You J. Substance P in flush tears and schirmer strips of healthy participants. Optom Vis Sci. 2017;94(4):527–33. doi:10.1097/OPX.0000000000001040.
  • Sack RA, Tan KO, Tan A. Diurnal tear cycle: evidence for a nocturnal inflammatory constitutive tear fluid. Invest Ophthalmol Vis Sci. 1992;33(3):626–40. doi:10.1083/jcb.34.1.327.
  • Petropoulos IN, Ferdousi M, Marshall A, Alam U, Ponirakis G, Azmi S, Fadavi H, Efron N, Tavakoli M, Malik RA. The inferior whorl for detecting diabetic peripheral neuropathy using corneal confocal microscopy. Invest Ophthalmol Vis Sci. 2015;56(4):2498–504. doi:10.1167/iovs.14-15919.
  • Petropoulos IN, Alam U, Fadavi H, Asghar O, Green P, Ponirakis G, Marshall A, Boulton AJMM, Tavakoli M, Malik RA. Corneal nerve loss detected with corneal confocal microscopy is symmetrical and related to the severity of diabetic polyneuropathy. Diabetes Care. 2013;36(11):3646–51. doi:10.2337/dc13-0193.
  • Vagenas D, Pritchard N, Edwards K, Shahidi AM, Sampson GP, Russell AW, Malik RA, Efron N. Optimal image sample size for corneal nerve morphometry. Optom Vis Sci. 2012;89(5):812–17. doi:10.1097/OPX.0b013e318264cc62.
  • Kalteniece A, Ferdousi M, Petropoulos I, Azmi S, Adam S, Fadavi H, Marshall A, Boulton AJM, Efron N, Faber CG, et al. Greater corneal nerve loss at the inferior whorl is related to the presence of diabetic neuropathy and painful diabetic neuropathy. Sci Rep. 2018;8(1):3283. doi:10.1038/s41598-018-21643-z.
  • Dabbah MA, Graham J, Petropoulos IN, Tavakoli M, Malik RA. Automatic analysis of diabetic peripheral neuropathy using multi-scale quantitative morphology of nerve fibres in corneal confocal microscopy imaging. Med Image Anal. 2011;15(5):738–47. doi:10.1016/j.media.2011.05.016.
  • Chen X, Graham J, Dabbah MA, Petropoulos IN, Tavakoli M, Malik RA. An automatic tool for quantification of nerve fibers in corneal confocal microscopy images. IEEE Trans Biomed Eng. 2017;64(4):786–94. doi:10.1109/TBME.2016.2573642.
  • Malik RA, Kallinikos P, Abbott CA, Van Schie CHM, Morgan P, Efron N, Boulton AJM. Corneal confocal microscopy: a non-invasive surrogate of nerve fibre damage and repair in diabetic patients. Diabetologia. 2003;46(5):683–88. doi:10.1007/s00125-003-1086-8.
  • Petropoulos IN, Manzoor T, Morgan P, Fadavi H, Asghar O, Alam U, Ponirakis G, Dabbah MA, Chen X, Graham J, et al. Repeatability of in vivo corneal confocal microscopy to quantify corneal nerve morphology. Cornea. 2013;32(5):1–7. doi:10.1097/ICO.0b013e3182749419.
  • Petropoulos IN, Alam U, Fadavi H, Marshall A, Asghar O, Dabbah MA, Chen X, Graham J, Ponirakis G, Boulton AJM, et al. Rapid automated diagnosis of diabetic peripheral neuropathy with in vivo corneal confocal microscopy. Invest Ophthalmol Vis Sci. 2014;55(4):2062–70. doi:10.1167/iovs.13-13787.
  • Chen X, Graham J, Petropoulos IN, Ponirakis G, Asghar O, Alam U, Marshall A, Ferdousi M, Azmi S, Efron N, et al. Corneal nerve fractal dimension: a novel corneal nerve metric for the diagnosis of diabetic sensorimotor polyneuropathy. Invest Ophthalmol Vis Sci. 2018;59(2):1113–18. doi:10.1167/iovs.17-23342.
  • Marfurt CF, Cox J, Deek S, Dvorscak L. Anatomy of the human corneal innervation. Exp Eye Res. 2010;90(4):478–92. doi:10.1016/j.exer.2009.12.010.
  • Golebiowski B, Chao C, Stapleton F, Jalbert I. Corneal nerve morphology, sensitivity, and tear neuropeptides in contact lens wear. Optom Vis Sci. 2017;94(4):534–42. doi:10.1097/OPX.0000000000001063.
  • Faragher RGA, Mulholland B, Tuft SJ, Sandeman S, Khaw PT. Aging and the cornea. Br J Ophthalmol. 1997;81(10):814–17. doi:10.1136/bjo.81.10.814.
  • Gipson IK. Age-related changes and diseases of the ocular surface and cornea. Invest Ophthalmol Vis Sci. 2013;54(14):ORSF48–53. doi:10.1167/iovs.13-12840.
  • Markoulli M, Flanagan J, Tummanapalli SS, Wu J, Willcox M. The impact of diabetes on corneal nerve morphology and ocular surface integrity. Ocul Surf. 2018;16(1):45–57. doi:10.1016/j.jtos.2017.10.006.
  • Lutty GA. Effects of diabetes on the eye. Invest Ophthalmol Vis Sci. 2013;54(14):ORSF81–7. doi:10.1167/iovs.13-12979.
  • Didenko TN, Smoliakova GP, Sorokin EL, Egorov VV. Clinical and pathogenetic features of neurotrophic corneal disorders in diabetes. Vestn Oftalmol. 1999;115:7–11.
  • Sacchetti M, Lambiase A. Neurotrophic factors and corneal nerve regeneration. Neural Regener Res. 2017;12(8):1220–24. doi:10.4103/1673-5374.213534.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.