2025 - 3 Issue

Original article

Modern Biomarkers for Early Diagnosis of Ocular Surface Disease in Type 1 Diabetes. A Pilot Study

Full Text links

Summary

Patients with dry eye syndrome form a significant proportion of those treated in everyday ophthalmology practice. Diabetes mellitus is a major risk factor for the development of dry eye syndrome. Changes in tear film homeostasis, chronic inflammation and subsequent corneal nerve fiber pathology play a key role in its progression.
The aim of this study was to describe the status of modern biomarkers of ocular surface damage in patients with type 1 diabetes and asses their utility in early diagnosis of dry eye syndrome.

Material and methods: In total the pilot study included 19 patients with type 1 diabetes (T1D) and 15 patients in the control group. All patients underwent a detailed ocular surface examination, sample collection for matrix metalloproteinase-9 (MMP-9) laboratory analysis and epithelial HLA-DR expression evaluation, and in-vivo corneal confocal microscopy.

Results: T1D patients showed statistically significantly reduced corneal nerve fiber length (p = 0.0482). The differences between the groups in terms of osmolarity, corneal sensitivity, Oxford score, tear break-up time and MMP-9 level were not statistically significant (p = 0.8272, p = 0.6029, p = 0.3507, p = 0.7561 and p = 0.0826 respectively). HLA-DR expression was examined in 10 T1D patients and 8 patients in the control group. Both groups showed minimal or no expression (p > 0.9999).

Conclusion: The previously published literature supports our finding of corneal nerve fiber length reduction in T1D patients compared to controls. However, we did not find any significant changes in standard or modern ocular surface markers (MMP-9 levels, HLA-DR expression) measured in patients with dry eye syndrome.

References

  1. Shih KC, Lam KSL, Tong L. A systematic review on the impact of diabetes mellitus on the ocular surface. Nutr Diabetes. 2017;7(3):e251–e251.
  2. Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, et al. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017;15(3):276- 283.
  3. Jirsova K, Stangova PS, Palos M, et al. Aberrant HLA-DR expression in the conjunctival epithelium after autologous serum treatment in patients with graft-versus-host disease or Sjögren’s syndrome. Plos One. 2020;15(4):e0231473.
  4. Brignole-Baudouin F, Riancho L, Ismail D, Deniaud M, Amrane M, Baudouin C. Correlation Between the Inflammatory Marker HLA- DR and Signs and Symptoms in Moderate to Severe Dry Eye Disease. Inv Opth Vis Sci. 2017;58(4):2438.
  5. Bron AJ, Paiva CS de, Chauhan SK, et al. TFOS DEWS II pathophysiology report. Ocul Surf. 2017;15(3):438-510.
  6. Smith VA, Rishmawi H, Hussein H, Easty DL. Tear film MMP accumulation and corneal disease. Br J Ophthalmol. 2001;85(2):147.
  7. Akinci A, Cetinkaya E, Aycan Z. Dry Eye Syndrome in Diabetic Children. Eur J Ophthalmol 2007;17(6):873-878.
  8. Humphreys-Beher MG, Hu Y, Nakagawa Y, Wang PL, Purushotham KR. Lacrimal Gland, Tear Film, and Dry Eye Syndromes, Basic Science and Clinical Relevance. Adv Exp Med Biol. 1994;350:631-636.
  9. Minaříková M, Fík Z, Štorm J, Helisová K, Ferrová K, Mahelková G. Tear matrix metalloproteinase-9 levels may help to follow a ocular surface injury in lagophthalmic eyes. Plos One .2022;17(9):e0274173.
  10. Jirsova K, Juklova K, Vesela V, Filipec M. Morphological and immunocytochemical characterization of snake-like chromatin cells. Histol Histopathol. 2006;21(4):355-360.
  11. Petropoulos IN, Alam U, Fadavi H, et al. Rapid Automated Diagnosis of Diabetic Peripheral Neuropathy With In Vivo Corneal Confocal MicroscopyAutomated Detection of Diabetic Neuropathy. Inv Oph Vis Sci. 2014;55(4):2071-2078.
  12. Tavakoli M, Ferdousi M, Petropoulos IN, et al. Normative Values for Corneal Nerve Morphology Assessed Using Corneal Confocal Microscopy: A Multinational Normative Data Set. Diabetes Care. 2015;38(5):838-843.
  13. Kim J, Kim CS, Sohn E, Jeong IH, Kim H, Kim JS. Involvement of advanced glycation end products, oxidative stress and nuclear factor-kappaB in the development of diabetic keratopathy. Graefe’s Arch Clin Exp Ophthalmol. 2011;249(4):529-536.
  14. 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.
  15. Ding J, Liu Y, Sullivan DA. Effects of Insulin and High Glucose on Human Meibomian Gland Epithelial Cells. Inv Opth Vis Sci. 2015;56(13):7814.
  16. Epstein SP, Gadaria-Rathod N, Wei Y, Maguire MG, Asbell PA. HLA- DR expression as a biomarker of inflammation for multicenter clinical trials of ocular surface disease. Exp Eye Res. 2013;111:95- 104.
  17. Cabral-Pacheco GA, Garza-Veloz I, Rosa CCD, et al. The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. Int J Mol Sci. 2020;21(24):9739.
  18. Markoulli M, Papas E, Cole N, Holden BA. The Diurnal Variation of Matrix Metalloproteinase-9 and Its Associated Factors in Human Tears. Inv Opth Vis Sci. 2012;53(3):1479.