The Cornea in Diabetes Mellitus

  • S. Akbar Hasan


Although the cornea may appear disease free in the diabetic, marked biochemical and ultrastructural abnormalities are present altering form and function. Awareness of these manifestations of corneal disease in diabetes can lead to steps that prevent more overt complications.


Diabetic Retinopathy Ocular Surface Aldose Reductase Proliferative Diabetic Retinopathy Corneal Endothelium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Henkind P, Wise GN. Descemet’s wrinkles in diabetes. Am J Ophthamol. 1961;52:371.Google Scholar
  2. 2.
    Armaly MF, Baloglou PJ. Diabetes mellitus and the eye: I. Changes in the anterior segment. Arch Opthalmol. 1967;77:485–492.Google Scholar
  3. 3.
    Schwartz DE. Corneal sensitivity in diabetics. Arch Ophthalmol. 1974;91:174–178.PubMedGoogle Scholar
  4. 4.
    Marano CW. Matschinsky FM. Biochemical manifestations of diabetes mellitus in microscopic layers of the cornea and retina. Diabetes Metabol Rev. 1989;5:1–15.CrossRefGoogle Scholar
  5. 5.
    Narayanan S. Aldose reductase and its inhibition in the control of diabetic complications. Ann Clin Lab Sci. 1993;23:148–158.PubMedGoogle Scholar
  6. 6.
    Jacot JL, Hosotani H, Glover JP, Lois N, Robison WG Jr. Diabetic-like corneal sensitivity loss in galactose-fed rats ameliorated with aldose reductase inhibitors. J Ocul Pharmacol Ther. 1998;14:169–180.CrossRefPubMedGoogle Scholar
  7. 7.
    Kern TS, Engerman RL. Distribution of aldose reductase in ocular tissues. Exp Eye Res. 1981;33:175–181.CrossRefPubMedGoogle Scholar
  8. 8.
    Friend J, Kiorpes TC, Thoft RA. Diabetes mellitus and the rabbit corneal epithelium. Invest Ophthalmol Vis Sci. 1987;21:317–321.Google Scholar
  9. 9.
    Ludvigson MJ, Sorenson RL. Immunohistochemical localization on aldolase reductase. II. Rat eye and kidney. Diabetes. 1980;29:450–459.CrossRefPubMedGoogle Scholar
  10. 10.
    Cobo LM, Hatchell DL. Treatment of severe diabetic keratopathy with a topical aldose reductase inhibitor: clinical response and electron microscopy (ARVO Abstract). Invest Ophthalmol Vis Sci. 1980;26(suppl):176.Google Scholar
  11. 11.
    Fukushi S, Merola LO, Tanaka M. Reepithelialization of denuded corneas in diabetic rats. Exp Eye Res. 1980;31:611–621.CrossRefPubMedGoogle Scholar
  12. 12.
    Matsuda M, et al. The effects of aldose reductase inhibitor on the corneal endothelial morphology in diabetic rats. Curr Eye Res. 1987;6:391–397.CrossRefPubMedGoogle Scholar
  13. 13.
    Meyer LA, Ubels JL, Edelhauser HF. Corneal endothelial morphology in the rat. Effects of aging, diabetes, and topical aldose reductase inhibitor treatment. Invest Ophthalmol Vis Sci. 1988;29:940–948.PubMedGoogle Scholar
  14. 14.
    Ramamurthi S, Rahman MQ, Dutton GN, Ramaesh K. Pathogenesis, clinical features and management of recurrent corneal erosions. Eye. 2006;20:635–644.CrossRefPubMedGoogle Scholar
  15. 15.
    Woessner JF, Jr. Matrix metalloproteinases and their inhibitors in connective tissue remodeling. Faseb J. 1991;5:2145–2154.PubMedGoogle Scholar
  16. 16.
    Takahashi H, Akiba K, Noguchi T, Ohmura T, Takahashi R, Ezure Y, Ohara K, Zieske JD. Matrix metalloproteinase activity is enhanced during corneal wound repair in high glucose condition. Curr Eye Res. 2000;21:608–615.PubMedGoogle Scholar
  17. 17.
    Murata T, Nagai R, Ishibashi T, Inomata H, Ikeda K, Horiuchi S. The relationship between accumulation of advanced glycation end products and expression of vascular endothelial growth factor in human diabetic retinas. Diabetologia. 1997;40:764–769.CrossRefPubMedGoogle Scholar
  18. 18.
    Dunn JA, Patrick JS, Thorpe SR, Baynes JW. Oxidation of glycated proteins: age-dependent accumulation of Ne-(carboxymethyl) lysine in lens proteins. Biochemistry. 1989;28:9464–9468.CrossRefPubMedGoogle Scholar
  19. 19.
    Araki N, Ueno N, Chakrabarti B, Morino Y, Horiuchi S. Immunochemical evidence for the presence of advanced glycation end products and its positive correlation with aging. J Biol Chem. 1992;267:10211–10214.PubMedGoogle Scholar
  20. 20.
    Horiuchi S, Araki N, Morino Y. Immunochemical approach to characterize advanced glycation end products of the Maillard reaction: evidence for the presence of a common structure. J Biol Chem. 1991;266:7329–7332.PubMedGoogle Scholar
  21. 21.
    Yuichi K, Tomohiko U, Tetsuro O, et al. Advanced glycation end products in diabetic corneas. Invest Ophthalmol Vis Sci. 2000;41:362–368.Google Scholar
  22. 22.
    Nishida, T. Cornea. Cornea. 2nd ed. Vol. 1. Chapter 1. Philadelphia: Elsevier Mosby; 2005.Google Scholar
  23. 23.
    Yu L. Chen X. Qin G. Xie H. Lv P. Tear film function in type 2 diabetic patients with retinopathy. Ophthalmologica. 2008;222:284–291.CrossRefPubMedGoogle Scholar
  24. 24.
    Yoon KC, Im SK, Seo MS. Changes of tear film and ocular surface in diabetes mellitus. Korean J Ophthalmol. 2004;18:168–174.CrossRefPubMedGoogle Scholar
  25. 25.
    Inoue K, Kato S, Ohara C, Numaga J, Amano S, Oshika T. Ocular and systemic factors relevant to diabetic keratoepitheliopathy. Cornea. 2001;20:798–801.CrossRefPubMedGoogle Scholar
  26. 26.
    Quadrado MJ, Popper M, Morgado AM, Murta JN, Van Best JA. Diabetes and corneal cell densities in humans by in vivo confocal microscopy. Cornea. 2006;25:761–768.CrossRefPubMedGoogle Scholar
  27. 27.
    Hosotani H, Ohashi Y, Yamada M, et al. Reversal of abnormal corneal epithelial cell morphological characteristics and reduced corneal sensitivity in diabetic patients by aldose reductase inhibitor, CT-112. Am J Ophthalmol. 1995;119:288–294.PubMedGoogle Scholar
  28. 28.
    Azar DT, Spurr-Michaud SJ, Tisdale AS, et al. Altered epithelial-basement membrane interactions in diabetic corneas. Arch Ophthalmol. 1992;110:537–540.PubMedGoogle Scholar
  29. 29.
    Tabatabay CA, Bumbacher M, Baumgartner B, et al. Reduced number of hemidesmosomes in the corneal epithelium of diabetics with proliferative vitreoretinopathy. Graefes Arch Clin Exp Ophthalmol. 1988;226:389–392.CrossRefPubMedGoogle Scholar
  30. 30.
    Ljubimov AV, Huang ZS, Huang GH, et al. Human corneal epithelial basement membrane and integrin alterations in diabetes and diabetic retinopathy. J Histochem Cytochem. 1998;46:1033–1041.PubMedGoogle Scholar
  31. 31.
    Kabosova A, Kramerov AA, Aoki AM, et al. Human diabetic corneas preserve wound healing, basement membrane, integrin and MMP-10 differences from normal corneas in organ culture. Exp Eye Res. 2003;77:211–217.CrossRefPubMedGoogle Scholar
  32. 32.
    Saghizadeh M, Brown DJ, Castellon R, et al. Overexpression of matrix metalloproteinase-10 and matrix metalloproteinase-3 in human diabetic corneas: a possible mechanism of basement membrane and integrin alterations. Am J Pathol. 2001;158:723–734.PubMedGoogle Scholar
  33. 33.
    Ishii Y, Lahav M, Mukai Y. Corneal changes in diabetic patients and streptozotocin diabetic rats: an ultrastructural correlation. Invest Ophthmol Vis Sci. 1981;20(suppl):154.Google Scholar
  34. 34.
    Bierhaus A, Hofmann MA, Ziegler R, Nawroth PP. AGEs and their interaction with AGE-receptors in vascular disease and diabetes mellitus. I. The AGE concept. Cardiovasc Res. 1998;37:586–600.CrossRefPubMedGoogle Scholar
  35. 35.
    Midena E, Brugin E, Ghirlando A, Sommavilla M, Avogaro A. Corneal diabetic neuropathy: a confocal microscopy study. J Refract Surg. 2006;22(9 Suppl):S1047–S1052.PubMedGoogle Scholar
  36. 36.
    Waite JH, Beetham WP. The visual mechanism in diabetes mellitus (a comparative study of 2002 diabetics, and 457 non-diabetics for control). N Engl J Med. 1935;212:367–443.CrossRefGoogle Scholar
  37. 37.
    Chang PY, Carrel H, Huang JS, et al. Decreased density of corneal basal epithelium and subbasal corneal nerve bundle changes in patients with diabetic retinopathy. Am J Ophthalmol. 2006;142(3):488–490.CrossRefPubMedGoogle Scholar
  38. 38.
    Inoue K, Kato S, Inoue Y, Amano S, Oshika T. The corneal endothelium and thickness in type II diabetes mellitus. Jpn J Ophthalmol. 2002;46:65–69.CrossRefPubMedGoogle Scholar
  39. 39.
    Keoleian JM, et al. Structural and functional studies of the corneal endothelium and diabetes mellitus. Am J Ophthalmol. 1992;113:64–70.PubMedGoogle Scholar
  40. 40.
    Schultz RO, Matsuda M, et al. Corneal endothelial changes in type I, type II diabetes mellitus. Am J Ophthalmol. 1984;98:401–410.CrossRefPubMedGoogle Scholar
  41. 41.
    Schultz RO, Peters MA, Sobocinski K, et al. Diabetic corneal neuropathy. Trans Am Opthalmol Soc. 1983;81:107–124.Google Scholar
  42. 42.
    Pardos JG, Krachmer JH. Comparison of endothelial cell density in diabetics and a control population. Am J Ophthalmol. 1980;90:172–174.PubMedGoogle Scholar
  43. 43.
    Lass JH, et al. A morphological and fluorophotometric analysis of the corneal endothelium in type I diabetes mellitus and cystic fibrosis. Am J Ophthalmol. 1985;100:783–788.PubMedGoogle Scholar
  44. 44.
    Busted N, Olsen T, Schmitz O. Clinical observations on the corneal thickness and the corneal endothelium in diabetes mellitus. Br J Ophthalmol. 1981;65:687–690.CrossRefPubMedGoogle Scholar
  45. 45.
    Matsuda M, et al. Relationship of corneal endothelial morphology to diabetic retinopathy, duration of diabetes, and glycemic control. Jpn J Opthalmol. 1990;34:53–56.Google Scholar
  46. 46.
    Buettner H, Bourne WM. Effect of trans pars plana surgery on the corneal endothelium. Dev Ophthalmol. 1981;2:28–34.PubMedGoogle Scholar
  47. 47.
    Itoi M, et al. Specular microscopic studies of the corneal endothelia of Japanese diabetics. Cornea. 1989;8:2–6.CrossRefPubMedGoogle Scholar
  48. 48.
    Olsen T, Busted N. Corneal thickness in eyes with diabetic and nondiabetic neovascularisation. Br J Ophthalmol. 1981;65:691–693.CrossRefPubMedGoogle Scholar
  49. 49.
    Hoshino M, Hoshino T. Schirmer test in diabetic patients. Jpn J Clin Ophthalmol. 1989;43:1917–1920.Google Scholar
  50. 50.
    Binder A, Maddison PJ, Skinner P, Kurtz A, Isenberger DA. Sjogren's syndrome: association with type-1 diabetes mellitus. Br J Rheumatol. 1989;28:516–520.Google Scholar
  51. 51.
    Barrera R, Cinta-Mane-M, Rodriguez-JF, Jimenez A. Keratoconjunctivitis sicca and diabetes mellitus in a dog. J Am Vet Med Assoc. 1992;200:1967–1968.PubMedGoogle Scholar
  52. 52.
    Sreebny LM, Yu A, Green A, Valdini A. Xerostomia in diabetes mellitus. Diabetes Care.199215:900–904.Google Scholar
  53. 53.
    Stolwijk TR, Kuizenga A, van-Haeringen NJ, Kijlstra A, Oosterhuis JA, van Best JA. Analysis of tear fluid proteins in insulin dependent diabetes mellitus. Acta Ophthalmol Copenh. 1994;72:357–362.CrossRefPubMedGoogle Scholar
  54. 54.
    Ramos RC, Suarez AM, Russell AS. Low tear production in patients with diabetes mellitus. Clin Exp Rheum. 1994;12:375–380.Google Scholar
  55. 55.
    Stolwijk TR, van Best JA, Lemkes HH, de-Keizer RJ, Oosterhuis JA. Determination of basal tear turnover in insulin dependent diabetes mellitus patients by fluorophotometry. Int Ophthalmol. 1991;15:377–382.CrossRefPubMedGoogle Scholar
  56. 56.
    Sullivan DA, Edwards JA, Wickham LA, et al. Identification and endocrine control of sex steroid binding sites in the lacrimal gland. Curr Eye Res. 1996;15:279–291.CrossRefPubMedGoogle Scholar
  57. 57.
    Takeuchi K, Hori Y, Hayakawa T, et al. A case of an old woman with Sjogren's syndrome associated with insulin dependent diabetes mellitus. Ryumachi. 1996;36:769–774.PubMedGoogle Scholar
  58. 58.
    Ekgardt VF, Tarasova LN, Teplova SN, Alekhina TV. Systemic and local immunity in patients with diabetic retinopathy. Vestn Oftalmol. 1998;114:46–48.PubMedGoogle Scholar
  59. 59.
    Robinson CP, Yamachika S, Bounous DI, et al. A novel NOD-derived murine model of primary Sjogren's syndrome. Arthritis Rheum. 1998;41:150–156.CrossRefPubMedGoogle Scholar
  60. 60.
    Grus FH, Augustin AJ, Evangelou NG, Toth-Sagi K. Analysis of tear protein pattern as a diagnostic tool for the detection of dry eyes. Eur J Ophthalmol. 1998;18:90–97.Google Scholar
  61. 61.
    Rogell JD. Corneal hypesthesia and retinopathy in diabetes mellitus. Ophthalmology. 1980;87:229–233.PubMedGoogle Scholar
  62. 62.
    Nielsen NV. Corneal sensitivity and vibratory perception in diabetes mellitus, Acta Ophthalmol. 1978;56:406–411.Google Scholar
  63. 63.
    Riss B, Binder S. Corneal sensitivity after photocoagulation for diabetic retinopathy. Graefes Arch Klin Exp Ophthalmol. 1981;217:143–147.CrossRefGoogle Scholar
  64. 64.
    Schultz R, Van Horn D, Peters M, et al. Diabetic keratopathy. Trans Am Ophthalmol Soc. 1982;79:180–199.Google Scholar
  65. 65.
    Nepp J, et al. Is there a correlation between the severity of diabetic retinopathy and keratoconjunctivitis sicca? Cornea. 2000;19(14):487–491.CrossRefPubMedGoogle Scholar
  66. 66.
    Saini JS, Khandalavia B. Corneal epithelial fragility in diabetes mellitus. Can J Ophthalmol. 1995;30(3):142–146.PubMedGoogle Scholar
  67. 67.
    Schultz RO, Peters MA, Sobocinski K, et al. Diabetic keratopathy as a manifestation of peripheral neuropathy. Am J Ophthalmol. 1983;96:368–371.PubMedGoogle Scholar
  68. 68.
    Ishida N, Rao GN, Del Cerro M, Aquaella JV. Corneal nerve alterations in diabetes mellitus. Arch Ophthalmol. 1984;102(9):1380–1384.PubMedGoogle Scholar
  69. 69.
    Beuerman RW, Schimmelpfennig B, Burstein N. Anatomy of the denervated corneal epithelium. Invest Ophthalmol Vis Sci. 1979;18(suppl):126.Google Scholar
  70. 70.
    Paton L. The trigeminal and its ocular lesions. Br J Ophthalmol. 1926;10:305–342.CrossRefPubMedGoogle Scholar
  71. 71.
    Diaz-Valle D, Benitez del Castillo Sanchez JM, Castillo A, Sayagues O, Moriche M. Endothelial damage with cataract surgery techniques. J Cataract Refract Surg. 1998;24:951–955.Google Scholar
  72. 72.
    Walkow T, Anders N, Klebe S. Endothelial cell loss after phacoemulsification: relation to preoperative and intraoperative parameters. J Cataract Refract Surg. 2000;26(5):727–732.CrossRefPubMedGoogle Scholar
  73. 73.
    Dick HB, Kohnen T, Jacobi FK, Jacobi KW. Long-term endothelial cell loss following phacoemulsification through a temporal clear corneal incision. J Cataract Refract Surg. 1996;22:63–71.PubMedGoogle Scholar
  74. 74.
    Morikubo S, Takamura Y, Kubo E, Tsuzuki S, Akagi Y. Corneal changes after small-incision cataract surgery in patients with diabetes mellitus. Arch Ophthalmol. 2004;122(7):966–969.CrossRefPubMedGoogle Scholar
  75. 75.
    Lee JS, Lee JE, Choi HY, et al. Corneal endothelial cell change after phacoemulsification relative to the severity of diabetic retinopathy. J Cataract Ref Surg. 2005;31:742–749.CrossRefGoogle Scholar
  76. 76.
    Faulborn J, Conway BP, Machemer, R. Surgical complications of pars plana vitreous surgery. Ophthalmology. 1978;185:116–125.Google Scholar
  77. 77.
    Perry HD, Foulks GN, Thoft RA, Tolentino FI. Corneal complications following closed vitrectomy through the pars plana. Arch Ophthalmol. 1978;96:1401–1403.PubMedGoogle Scholar
  78. 78.
    Mandelcorn MS, Blankenship J, Machemer R. Pars plana vitrectomy for the management of severe diabetic retinopathy. Am J Opthalmol. 1976;81:561–570.Google Scholar
  79. 79.
    Foulks GN, et al. Factors related to corneal epithelial complications after closed vitrectomy in diabetics. Arch Ophthalmol. 1979;97:1076–1078.PubMedGoogle Scholar
  80. 80.
    Brightbill FS. Myers FL. Bresnick GH. Postvitrectomy keratopathy. Am J Ophthalmol. 1978;85:651–655.PubMedGoogle Scholar
  81. 81.
    Chung H, Tolentino FI, Cajita VN, Acosta J, Refojo MF. Reevaluation of corneal complications after closed vitrectomy. Arch Ophthalmol. 1988;106(7):916–919.PubMedGoogle Scholar
  82. 82.
    Friberg TR, Doran DL, Lazenby FL. The effect of vitreous and retinal surgery on corneal endothelial cell density. Ophthalmology. 1984;91:1166–1169.PubMedGoogle Scholar
  83. 83.
    Schachat AP, Oyakawa RT, Michels RG, Rice TA. Complications of vitreous surgery for diabetic retinopathy. II. Postoperative complications. Ophthalmology. 1983;90:522–530.PubMedGoogle Scholar
  84. 84.
    Virata SR, Kylstra JA, Singh HT. Corneal epithelial defects following vitrectomy surgery using hand-held, sew-on, and noncontact viewing lenses. Retina. 1999;19(4):287–290.CrossRefPubMedGoogle Scholar
  85. 85.
    Garcia-Valenzuela E, et al. Reduced need for corneal epithelial debridement during vitreo-retinal surgery using two different viscous surface lubricants. Am J Ophthalmol. 2003;136(6):1062–1066.CrossRefPubMedGoogle Scholar
  86. 86.
    McDermott M, et al. Effects of intraocular irrigants on the preserved human corneal endothelium. Cornea. 1991;10(5):402–407.CrossRefPubMedGoogle Scholar
  87. 87.
    Benson WE, Diamond JG, Tasman W. Intraocular irrigating solutions for pars plana vitrectomy: a prospective, randomized, double-blind study. Arch Ophthalmol. 1981;99(6):1013–1015.PubMedGoogle Scholar
  88. 88.
    Diddie KR, Schanzlin DJ. Specular microscopy in pars plana vitrectomy. Arch Ophthalmol. 1983;101(3):408–409.PubMedGoogle Scholar
  89. 89.
    Mittl RN, et al. Endothelial cell counts following pars plana vitrectomy in pseudophakic and aphakic eyes. Ophthalmic Surg. 1989;20(1):13–16.PubMedGoogle Scholar
  90. 90.
    Mitamura Y, Yamamoto S, Yamazaki S. Corneal endothelial cell loss in eyes undergoing lensectomy with and without anterior lens capsule removal combined with pars plana vitrectomy and gas tamponade. Retina. 2000;20(1):59–62.CrossRefPubMedGoogle Scholar
  91. 91.
    Sternberg Jr P, et al. The effect of silicone oil on the cornea. Arch Ophthalmol. 1985;103(1):90–94.PubMedGoogle Scholar
  92. 92.
    Abrams GW, et al. The incidence of corneal abnormalities in the silicone study: silicone study report 7. Arch Ophthalmol. 1995;113(6):764–769.Google Scholar
  93. 93.
    Makitie J, Koskenvuo M, Vannas A, et al. Corneal endothelium after photocoagulation in diabetic patients. Acta Ophthalmol. 1985;63:355–360.Google Scholar
  94. 94.
    Irvine WD, Smiddy WE, Nicholson DH. Corneal and iris burns with the laser indirect ophthalmoscope. Am J Ophthalmol. 1990;110(3):311–313.PubMedGoogle Scholar
  95. 95.
    Cobo-Soriano R, Beltran J, Baviera J. LASIK outcomes in patients with underlying systemic contraindications: a preliminary study. Ophthalmology. 2006;113(7):1124.e1.Google Scholar
  96. 96.
    Halkiadakis I, Belfair N, Gimbel HV. Laser in situ keratomileusis in patients with diabetes. J Cataract Refract Surg. 2005;31(10):1895–1898.CrossRefPubMedGoogle Scholar
  97. 97.
    Fraunfelder FW, Rich LF. Laser-assisted in situ keratomileusis complications in diabetes mellitus. Cornea. 2002;21(3):246–248.CrossRefPubMedGoogle Scholar
  98. 98.
    Pflugfelder SC. Antiinflammatory therapy for dry eye. Am J Ophthalmol. 2004;137(2):337–342.CrossRefPubMedGoogle Scholar
  99. 99.
    Laibovitz RA, Solch S, Andrianao J. Pilot trial of cyclosporin 1% ophthalmic ointment in the treatment of keratoconjunctivitis sicca. Cornea. 1993;12:315–323.CrossRefPubMedGoogle Scholar
  100. 100.
    Frucht-Pery J, Sagi E, Hemo I, Ever-Hadani P. Efficacy of doxycycline and tetracycline in ocular rosacea. Am J Ophthalmol. 1993;116:88–92.PubMedGoogle Scholar
  101. 101.
    Marsh P, Pflugfelder SC. Topical non-preserved methylprednisolone therapy of keratoconjunctivitis sicca in Sjogren's syndrome. Ophthalmology. 1999;106:811–816.CrossRefPubMedGoogle Scholar
  102. 102.
    Prabhasawat P, Tesavibul N, Komolsuradej W. Single and multilayer amniotic membrane transplantation for persistent corneal epithelial defect with and without stromal thinning and perforation. Br J Ophthalmol. 2001;85(12):1455–1463.CrossRefPubMedGoogle Scholar
  103. 103.
    Khokhar S, Natung T, Sony P, Sharma N, Agarwal N, Vajpayee RB. Amniotic membrane transplantation in refractory neurotrophic corneal ulcers: a randomized, controlled clinical trial. Cornea. 2005;24(6):654–660.CrossRefPubMedGoogle Scholar
  104. 104.
    Cosar CB, Cohen EJ, Rapuano CJ, Maus M, Penne RP, Flanagan JC, Laibson PR. Tarsorrhaphy: clinical experience from a cornea practice. Cornea. 2001;20(8):787–791.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of OphthalmologyMayo ClinicJacksonvilleUSA

Personalised recommendations