Skip to main content

Advertisement

Log in

Corneal Confocal Microscopy: A New Technique for Early Detection of Diabetic Neuropathy

  • Microvascular Complications-Neuropathy (D Ziegler, Section Editor)
  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Corneal confocal microscopy (CCM) is a noninvasive method for the study of human cornea in vivo. It has increasingly been used to assess the morphology of the sub-basal corneal nerve plexus. CCM has good reproducibility and may contribute to the early diagnosis of diabetic polyneuropathy. It may also be useful to document favorable changes in nerve fiber structure early after therapeutic intervention. Corneal nerve pathology is more pronounced in patients with diabetic polyneuropathy and is associated with its clinical severity. The sensitivity and specificity of CCM for the diagnosis of polyneuropathy is moderate to high. CCM now merits further use in large longitudinal studies to provide more information on the natural history of diabetic neuropathy and effects of treatment. Moreover, there is a need for a larger normative database. Finally, technical progress is expected to enable visualization of larger corneal areas and improve nerve fiber quantification, increasing diagnostic accuracy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Boulton AJ, Vinik AI, Arezzo JC, et al. Diabetic neuropathies: a statement by the American Diabetes Association. Diabetes Care. 2005;28:956–62.

    Article  PubMed  Google Scholar 

  2. Tesfaye S, Boulton AJ, Dyck PJ, et al. Diabetic neuropathies: update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care. 2010;33:2285–93.

    Article  PubMed  Google Scholar 

  3. Papanas N, Ziegler D. New diagnostic tests for diabetic distal symmetric polyneuropathy. J Diabetes Complications. 2011;25:44–51.

    Article  PubMed  Google Scholar 

  4. Papanas N, Papatheodorou K, Papazoglou D, Kotsiou S, Maltezos E. A prospective study on the use of the indicator test Neuropad for the early diagnosis of peripheral neuropathy in type 2 diabetes. Exp Clin Endocrinol Diabetes. 2011;119:122–5.

    Article  PubMed  CAS  Google Scholar 

  5. Papanas N, Boulton AJ, Malik RA, et al. Neuropad: a simple new noninvasive sweat indicator test for the diagnosis of diabetic neuropathy. Diabet Med. 2013;30:525–34.

    Google Scholar 

  6. Ziegler D. Painful diabetic neuropathy: advantage of novel drugs over old drugs? Diabetes Care. 2009;32 Suppl 2:S414–9.

    Article  PubMed  CAS  Google Scholar 

  7. Várkonyi T, Kempler P. Diabetic neuropathy: new strategies for treatment. Diabetes Obes Metab. 2008;10:99–108.

    PubMed  Google Scholar 

  8. Papanas N, Maltezos E. The diabetic foot: established and emerging treatments. Acta Clin Belg. 2007;62:230–8.

    PubMed  CAS  Google Scholar 

  9. Boulton AJ. The diabetic foot: grand overview, epidemiology, and pathogenesis. Diabetes Metab Res Rev. 2008;24 Suppl 1:S3–6.

    Article  PubMed  Google Scholar 

  10. Vinik AI, Maser RE, Ziegler D. Neuropathy: the crystal ball for cardiovascular disease? Diabetes Care. 2010;33:1688–90.

    Article  PubMed  Google Scholar 

  11. Carrington AL, Shaw JE, Van Schie CH, Abbott CA, Vileikyte L, Boulton AJ. Can motor nerve conduction velocity predict foot problems in diabetic subjects over a 6-year outcome period? Diabetes Care. 2002;25:2010–5.

    Article  PubMed  Google Scholar 

  12. Jalbert I, Stapleton F, Papas E, Sweeney DF, Coroneo M. In vivo confocal microscopy of the human cornea. Br J Ophthalmol. 2003;87:225–36.

    Article  PubMed  CAS  Google Scholar 

  13. Guthoff RF, Zhivov A, Stachs O. In vivo confocal microscopy, an inner vision of the cornea - a major review. Clin Exp Ophthalmol. 2009;37:100–17.

    Article  Google Scholar 

  14. Gemignani F, Ferrari G, Vitetta F, Giovanelli M, Macaluso C, Marbini A. Non-length-dependent small fiber neuropathy. Confocal microscopy study of the corneal innervation. J Neurol Neurosurg Psychiatry. 2010;81:731–3.

    Article  PubMed  CAS  Google Scholar 

  15. Zhivov A, Blum M, Guthoff R, Stachs O. Real-time mapping of the subepithelial nerve plexus by in vivo confocal laser scanning microscopy. Br J Ophthalmol. 2010;94:1133–5.

    Article  PubMed  Google Scholar 

  16. Klintworth GK. The cornea — structure and macromolecules in health and disease. A review. Am J Pathol. 1977;89:718–808.

    PubMed  CAS  Google Scholar 

  17. Trotter RR. Cornea and sclera. Arch Ophthalmol. 1968;79:338–48.

    Article  PubMed  CAS  Google Scholar 

  18. Laibson PR. Cornea and sclera. Arch Ophthalmol. 1970;83:637–57.

    Article  PubMed  CAS  Google Scholar 

  19. Trevor-Roper PD. The eye and its diseases: cornea and sclera. Int Opthalmol Clin. 1974;14:422–68.

    Google Scholar 

  20. Mensher JH. Corneal nerves. Surv Ophthalmol. 1974;19:1–18.

    PubMed  CAS  Google Scholar 

  21. Cruzat A, Pavan-Langston D, Hamrah P. In vivo confocal microscopy of corneal nerves: analysis and clinical correlation. Semin Ophthalmol. 2010;25:171–7.

    Article  PubMed  Google Scholar 

  22. Marfurt CF, Cox J, Deek S, Dvorscak L. Anatomy of the human corneal innervation. Exp Eye Res. 2010;90:478–92.

    Article  PubMed  CAS  Google Scholar 

  23. Al-Aqaba MA, Fares U, Suleman H, Lowe J, Dua HS. Architecture and distribution of human corneal nerves. Br J Ophthalmol. 2010;94:784–9.

    Article  PubMed  Google Scholar 

  24. Patel DV, McGhee CN. In vivo confocal microscopy of human corneal nerves in health, in ocular and systemic disease, and following corneal surgery: a review. Br J Ophthalmol. 2009;93:853–60.

    Article  PubMed  CAS  Google Scholar 

  25. Al-Aqaba MA, Alomar T, Miri A, Fares U, Otri AM, Dua HS. Ex vivo confocal microscopy of human corneal nerves. Br J Ophthalmol. 2010;94:1251–7.

    Article  PubMed  Google Scholar 

  26. Visser N, McGhee CN, Patel DV. Laser-scanning in vivo confocal microscopy reveals two morphologically distinct populations of stromal nerves in normal human corneas. Br J Ophthalmol. 2009;93:506–9.

    Article  PubMed  CAS  Google Scholar 

  27. Zhivov A, Stave J, Vollmar B, Guthoff R. In vivo confocal microscopic evaluation of Langerhans cell density and distribution in the normal human corneal epithelium. Graefes Arch Clin Exp Ophthalmol. 2005;243:1056–61.

    Article  PubMed  Google Scholar 

  28. Zhivov A, Stave J, Vollmar B, Guthoff R. In vivo confocal microscopic evaluation of Langerhans cell density and distribution in the corneal epithelium of healthy volunteers and contact lens wearers. Cornea. 2007;26:47–54.

    Article  PubMed  Google Scholar 

  29. Engelmann TW. Über die Hornhaut des Auges. In: Virchow H, editor. Graefe-Saemisch Handbuch der gesamten Augenheilkunde. 2nd ed. Leipzig: Engelmann; 1867. p. 30–1.

    Google Scholar 

  30. Langerhans P. Über die Nerven der menschlichen Haut. Virchows Arch Pathol Anat Physiol. 1868;44:325–37.

    Article  Google Scholar 

  31. Mastropasqua L, Nubile M, Lanzini M, et al. Epithelial dendritic cell distribution in normal and inflamed human cornea: in vivo confocal microscopy study. Am J Ophthalmol. 2006;142:736–44.

    Article  PubMed  Google Scholar 

  32. Tavakoli M, Boulton AJ, Efron N, Malik RA. Increased Langerhans cell density and corneal nerve damage in diabetic patients: role of immune mechanisms in human diabetic neuropathy. Cont Lens Anterior Eye. 2011;34:7–11.

    Article  PubMed  CAS  Google Scholar 

  33. Minsky M. Memoir on inventing the confocal scanning microscope. Scanning. 1988;10:128–38.

    Article  Google Scholar 

  34. Patel DV, McGhee CN. Contemporary in vivo confocal microscopy of the living human cornea using white light and laser scanning techniques: a major review. Clin Exp Ophthalmol. 2007;35:71–88.

    Article  Google Scholar 

  35. Zhivov A, Stachs O, Kraak R, Stave J, Guthoff RF. In vivo confocal microscopy of the ocular surface. Ocul Surf. 2006;4:81–93.

    Article  PubMed  Google Scholar 

  36. Dabbah MA, Graham J, Petropoulos I, Tavakoli M, Malik RA. Dual-model automatic detection of nerve-fibers in corneal confocal microscopy images. Med Image Comput Assist Interv. 2010;13:300–7.

    CAS  Google Scholar 

  37. Dabbah MA, Graham J, Petropoulos IN, Tavakoli M, Malik RA. Automatic analysis of diabetic peripheral neuropathy using multi-scale quantitative morphology of nerve fibers in corneal confocal microscopy imaging. Med Image Anal. 2011;15:738–47.

    Article  PubMed  CAS  Google Scholar 

  38. Stave J, Zinser G, Grümmer G, Guthoff R. Modified Heidelberg Retinal Tomograph HRT. Initial results of in vivo presentation of corneal structures. Ophthalmology. 2002;99:276–80.

    Article  CAS  Google Scholar 

  39. Holmes TJ, Pellegrini M, Miller C, et al. Automated software analysis of corneal micrographs for peripheral neuropathy. Investig Ophthalmol Vis Sci. 2010;51:4480–91.

    Article  Google Scholar 

  40. Hume DA, Lovblom LE, Ahmed A, et al. Higher magnification lenses vs conventional lenses for evaluation of diabetic neuropathy by corneal in vivo confocal microscopy. Diabetes Res Clin Pract. 2012;97:e37–40.

    Article  PubMed  Google Scholar 

  41. Zhivov A, Guthoff R, Stachs O. On-line mapping of corneal structures with in vivo laser scanning microscopy. Klin Monatsbl Augenheilkd. 2009;226:980–3.

    Article  PubMed  CAS  Google Scholar 

  42. • Zhivov A, Blum M, Guthoff R, Stachs O. Real-time mapping of the subepithelial nerve plexus by in vivo confocal laser scanning microscopy. Br J Ophthalmol. 2010;94:1133–5. Important study describing real-time mapping of the subepithelial nerve plexus.

    Article  PubMed  Google Scholar 

  43. Allgeier S, Zhivov A, Eberle F, et al. Image reconstruction of the subbasal nerve plexus with in vivo confocal microscopy. Investig Ophthalmol Vis Sci. 2011;52:5022–8.

    Article  Google Scholar 

  44. • Edwards K, Pritchard N, Gosschalk K, et al. Wide-field assessment of the human corneal subbasal nerve plexus in diabetic neuropathy using a novel mapping technique. Cornea. 2012;31:1078–82. Important study on the development of a rapid optimized technique of wide-field imaging of the human corneal subbasal nerve plexus.

    Article  PubMed  Google Scholar 

  45. Babu K, Narasimha Murthy K, Ramachandra Murthy K. Wavelike epitheliopathy after phacoemulsification: role of in vivo confocal microscopy. Cornea. 2007;26:747–8.

    Article  PubMed  Google Scholar 

  46. Chen WL, Lin CT, Ko PS, Yeh PT, Kuan YH, Hu FR, et al. In vivo confocal microscopic findings of corneal wound healing after corneal epithelial debridement in diabetic vitrectomy. Ophthalmology. 2009;116:1038–47.

    Article  PubMed  Google Scholar 

  47. Davidson EP, Coppey LJ, Yorek MA. Early loss of innervation of cornea epithelium in streptozotocin-induced type 1 diabetic rats: improvement with ilepatril treatment. Investig Ophthalmol Vis Sci. 2012;53:8067–74.

    Article  CAS  Google Scholar 

  48. Davidson EP, Coppey LJ, Holmes A, Yorek MA. Changes in corneal innervation and sensitivity and acetylcholine-mediated vascular relaxation of the posterior ciliary artery in a type 2 diabetic rat. Investig Ophthalmol Vis Sci. 20129;53:1182–7.

  49. Frueh BE, Körner U, Böhnke M. Confocal microscopy of the cornea in patients with diabetes. Klin Monatsbl Augenheilkd. 1995;206:317–9.

    Article  PubMed  CAS  Google Scholar 

  50. Tsubota K, Chiba K, Shimazaki J. Corneal epithelium in diabetic patients. Cornea. 1991;10:156–60.

    Article  PubMed  CAS  Google Scholar 

  51. Schultz RO, Matsuda M, Yee RW, Edelhauser HF, Schultz KJ. Corneal endothelial changes in type I and type II diabetes mellitus. Am J Ophthalmol. 1984;98:401–10.

    Article  PubMed  CAS  Google Scholar 

  52. Busted N, Olsen T, Schmitz O. Clinical observations on the corneal thickness and the corneal endothelium in diabetes mellitus. Br J Ophthalmol. 1981;65:687–90.

    Article  PubMed  CAS  Google Scholar 

  53. 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;25:761–8.

    Article  PubMed  Google Scholar 

  54. Shenoy R, Khandekar R, Bialasiewicz A, Al Muniri A. Corneal endothelium in patients with diabetes mellitus: a historical cohort study. Eur J Ophthalmol. 2009;19:369–75.

    PubMed  Google Scholar 

  55. 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;142:488–90.

    Article  PubMed  Google Scholar 

  56. Tavakoli M, Marshall A, Thompson L, et al. Corneal confocal microscopy: a novel noninvasive means to diagnose neuropathy in patients with Fabry disease. Muscle Nerve. 2009;40:976–84.

    Article  PubMed  Google Scholar 

  57. Tavakoli M, Marshall A, Banka S, et al. Corneal confocal microscopy detects small-fiber neuropathy in Charcot-Marie-Tooth disease type 1A patients. Muscle Nerve. 2012;46:698–704.

    Article  PubMed  Google Scholar 

  58. Borsook D, Rosenthal P. Chronic (neuropathic) corneal pain and blepharospasm: 5 case reports. Pain. 2011;152:2427–31.

    Article  PubMed  Google Scholar 

  59. Ishida N, Rao GN, del Cerro M, Aquavella JV. Corneal nerve alterations in diabetes mellitus. Arch Ophthalmol. 1984;102:1380–4.

    Article  PubMed  CAS  Google Scholar 

  60. Rosenberg ME, Tervo TM, Immonen IJ, Müller LJ, Grönhagen-Riska C, et al. Corneal structure and sensitivity in type 1 diabetes mellitus. Investig Ophthalmol Vis Sci. 2000;41:2915–21.

    CAS  Google Scholar 

  61. Malik RA, Kallinikos P, Abbott CA, et al. Corneal confocal microscopy: a noninvasive surrogate of nerve fibre damage and repair in diabetic patients. Diabetologia. 2003;46:683–8.

    PubMed  CAS  Google Scholar 

  62. Kallinikos P, Berhanu M, O'Donnell C, Boulton AJ, Efron N, Malik RA. Corneal nerve tortuosity in diabetic patients with neuropathy. Investig Ophthalmol Vis Sci. 2004;45:418–22.

    Article  Google Scholar 

  63. Midena E, Brugin E, Ghirlando A, Sommavilla M, Avogaro A. Corneal diabetic neuropathy: a confocal microscopy study. J Refract Surg. 2006;22(9 Suppl):S1047–52.

    PubMed  Google Scholar 

  64. Mocan MC, Durukan I, Irkec M, Orhan M. Morphologic alterations of both the stromal and subbasal nerves in the corneas of patients with diabetes. Cornea. 2006;25:769–73.

    Article  PubMed  Google Scholar 

  65. Li XR, Wang W, Yuan JQ. Distribution and morphological changes of corneal nerves in type 2 diabetic patients detected by confocal microscopy. Zhonghua Yan Ke Za Zhi. 2006;42:896–900.

    PubMed  Google Scholar 

  66. Quattrini C, Tavakoli M, Jeziorska M, et al. Surrogate markers of small fiber damage in human diabetic neuropathy. Diabetes. 2007;56:2148–54.

    Article  PubMed  CAS  Google Scholar 

  67. Mehra S, Tavakoli M, Kallinikos PA, et al. Corneal confocal microscopy detects early nerve regeneration after pancreas transplantation in patients with type 1 diabetes. Diabetes Care. 2007;30:2608–12.

    Article  PubMed  Google Scholar 

  68. De Cillà S, Ranno S, Carini E, et al. Corneal subbasal nerves changes in patients with diabetic retinopathy: an in vivo confocal study. Investig Ophthalmol Vis Sci. 2009;50:5155–8.

    Article  Google Scholar 

  69. • Tavakoli M, Quattrini C, Abbott C, et al. Corneal confocal microscopy: a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy. Diabetes Care. 2010;33:1792–7. Important study providing data on the sensitivity and specificity of corneal confocal microscopy for the diagnosis of diabetic neuropathy.

    Article  PubMed  Google Scholar 

  70. Tavakoli M, Marshall A, Pitceathly R, et al. Corneal confocal microscopy: a novel means to detect nerve fiber damage in idiopathic small fiber neuropathy. Exp Neurol. 2010;223:245–50.

    Article  PubMed  Google Scholar 

  71. Tavakoli M, Quattrini C, Begum P, et al. Neuropad and corneal confocal microscopy: new indications for human diabetic neuropathy. Diabetologia. 2010;53 Suppl 1:A1112.

    Google Scholar 

  72. Quattrini C, Tavakoli M, Kallinikos P, et al. Comparing skin biopsy with corneal confocal microscopy: diagnostic yield of nerve fiber density. Diabetologia. 2010;53 Suppl 1:A1114.

    Google Scholar 

  73. Messmer EM, Schmid-Tannwald C, Zapp D, Kampik A. In vivo confocal microscopy of corneal small fiber damage in diabetes mellitus. Graefes Arch Clin Exp Ophthalmol. 2010;248:1307–12.

    Article  PubMed  Google Scholar 

  74. • Tavakoli M, Kallinikos P, Iqbal A, et al. Corneal confocal microscopy detects improvement in corneal nerve morphology with an improvement in risk factors for diabetic neuropathy. Diabet Med. 2011;28:1261–7. Important study showing that corneal confocal microscopy may be employed in longitudinal studies to assess progression of diabetic neuropathy.

    Article  PubMed  CAS  Google Scholar 

  75. Tavakoli M, Petropoulos I, Fadavi H, et al. Corneal nerve fiber damage defined using corneal confocal microscopy in relation to tear film proteomics. Diabetologia. 2011;54 Suppl 1:A1134.

    Google Scholar 

  76. • Tavakoli M, Mitu-Pretorian M, Petropoulos IN, et al. Corneal confocal microscopy detects early nerve regeneration in diabetic neuropathy after simultaneous pancreas and kidney transplantation. Diabetes. 2013;62:254–60. Important study showing that corneal confocal microscopy enables the detection of early nerve regeneration in diabetic neuropathy after pancreas-kidney transplantation.

  77. Ziegler D, Zhivov A, Allgeier S, et al. Early detection of nerve fiber loss by in vivo corneal confocal microscopy in recently diagnosed type 2 diabetic patients. Diabetes. 2012;61 Suppl 1:565–P.

    Google Scholar 

  78. Ziegler D, Zhivov A, Allgeier S, et al. Early detection of nerve fiber loss by corneal confocal microscopy and skin biopsy in recently diagnosed type 2 diabetic subjects. Diabetologia. 2012;55 Suppl 1:A44.

    Google Scholar 

  79. Nitoda E, Kallinikos P, Pallikaris A, et al. Correlation of diabetic retinopathy and corneal neuropathy using confocal microscopy. Curr Eye Res. 2012;37:898–906.

    Article  PubMed  CAS  Google Scholar 

  80. 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;95:348–54.

    Article  PubMed  Google Scholar 

  81. Ahmed A, Bril V, Orszag A, et al. Detection of diabetic sensorimotor polyneuropathy by corneal confocal microscopy in type 1 diabetes: a concurrent validity study. Diabetes Care. 2012;35:821–8.

    Article  PubMed  CAS  Google Scholar 

  82. Halpern EM, Lovblom LE, Orlov S, Ahmed A, Bril V, Perkins BA. The impact of common variation in the definition of diabetic sensorimotor polyneuropathy on the validity of corneal in vivo confocal microscopy in patients with type 1 diabetes: a brief report. J Diabetes Complicat. 2012;27:240–2.

    Google Scholar 

  83. Zhivov A, Winter K, Hovakimyan M, et al. Imaging and quantification of subbasal nerve plexus in healthy volunteers and diabetic patients with or without retinopathy. PLoS One. 2013;8:e52157.

    Article  PubMed  CAS  Google Scholar 

  84. Tavakoli M, Kallinikos PA, Efron N, Boulton AJ, Malik RA. Corneal sensitivity is reduced and relates to the severity of neuropathy in patients with diabetes. Diabetes Care. 2007;30:1895–7.

    Article  PubMed  Google Scholar 

  85. Spallone V, Ziegler D, Freeman R, et al. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. 2011;27:639–53.

    Article  Google Scholar 

  86. Lauria G, Bakkers M, Schmitz C, et al. Intraepidermal nerve fiber density at the distal leg: a worldwide normative reference study. J Peripher Nerv Syst. 2010;15:202–7.

    Article  PubMed  Google Scholar 

  87. Young MJ, Boulton AJ, MacLeod AF, Williams DR, Sonksen PH. A multicenter study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia. 1993;36:150–4.

    Article  PubMed  CAS  Google Scholar 

  88. Herder C, Lankisch M, Ziegler D, et al. Subclinical inflammation and diabetic polyneuropathy: MONICA/KORA Survey F3 (Augsburg/Germany). Diabetes Care. 2009;32:680–2.

    Article  PubMed  Google Scholar 

  89. Doupis J, Lyons TE, Wu S, Gnardellis C, Dinh T, Veves A. Microvascular reactivity and inflammatory cytokines in painful and painless peripheral diabetic neuropathy. J Clin Endocrinol Metab. 2009;94:2157–63.

    Article  PubMed  CAS  Google Scholar 

  90. Efron N, Edwards K, Roper N, et al. Repeatability of measuring corneal subbasal nerve fiber length in individuals with type 2 diabetes. Eye Contact Lens. 2010;36:245–8.

    Article  PubMed  Google Scholar 

  91. Petropoulos IN, Manzoor T, Morgan P, et al. Repeatability of in vivo corneal confocal microscopy to quantify corneal nerve morphology. Cornea. 2012. [Epub ahead of print].

  92. Hertz P, Bril V, Orszag A, Ahmed A, Ng E, Nwe P, et al. Reproducibility of in vivo corneal confocal microscopy as a novel screening test for early diabetic sensorimotor polyneuropathy. Diabet Med. 2011;28:1253–60.

    Article  PubMed  CAS  Google Scholar 

  93. Callaghan BC, Little AA, Feldman EL, Hughes RA. Enhanced glucose control for preventing and treating diabetic neuropathy. Cochrane Database Syst Rev. 2012;6:CD007543.

    PubMed  Google Scholar 

  94. Wu T, Ahmed A, Bril V, Orszag A, Ng E, Nwe P, et al. Variables associated with corneal confocal microscopy parameters in healthy volunteers: implications for diabetic neuropathy screening. Diabet Med. 2012;29:e297–303.

    Article  PubMed  CAS  Google Scholar 

  95. Ziegler D, Low PA, Litchy WJ, et al. Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care. 2011;34:2054–60.

    Article  PubMed  CAS  Google Scholar 

  96. • Sellers EA, Clark I, Tavakoli M, Dean HJ, McGavock J, Malik RA. The acceptability and feasibility of corneal confocal microscopy to detect early diabetic neuropathy in children: a pilot study. Diabet Med. 2013;30:63. Important pilot study on the utility of corneal confocal microscopy to diagnose diabetic neuropathy in children.

  97. Zhivov A, Winter K, Peschel S, et al. Quantitative analysis of corneal subbasal nerve plexus with in vivo confocal laser scanning microscopy. Klin Monatsbl Augenheilkd. 2011;228:1067–72.

    Article  PubMed  CAS  Google Scholar 

  98. Köhler B, Allgeier S, Eberle F, et al. Image reconstruction of the corneal subbasal nerve plexus with extended field of view from focus image stacks of a confocal laser scanning microscope. Klin Monatsbl Augenheilkd. 2011;228:1060–6.

    Article  PubMed  Google Scholar 

Download references

Conflict of Interest

N. Papanas has board membership with SAB (TrigoCare International, distributor of Neuropad).

D. Ziegler has board membership with SAB (TrigoCare International, distributor of Neuropad).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. Ziegler.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Papanas, N., Ziegler, D. Corneal Confocal Microscopy: A New Technique for Early Detection of Diabetic Neuropathy. Curr Diab Rep 13, 488–499 (2013). https://doi.org/10.1007/s11892-013-0390-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11892-013-0390-z

Keywords

Navigation