RETINAL NERVE FIBER LAYER THICKNESS ASSOCIATED WITH SEVERITY OF DIABETIC PERIPHERAL NEUROPATHY IN DIABETES MELLITUS TYPE 2
Article Sidebar
Published
Mar 4, 2025
Main Article Content
Abstract
Purpose: To identify whether the Retinal Nerve Fiber Layer is useful in detecting severity of peripheral neurodegeneration in diabetic patients
Methods: A cross-sectional study was conducted. 36 people were enrolled in this study which is divided into two groups. 18 people with type 2 diabetes mellitus (DM) with Diabetic Peripheral Neuropathy (DPN) and 18 people with type 2 DM non-DPN. All subjects were 40-60 years old, and the best corrected visual acuity was better than 0,2 logMAR. An Optical Coherence Tomography (OCT) examination was carried out to determine the Retinal Nerve Fiber Layer (RNFL) thickness, and an Electroneuromyography examination was applied to establish a diagnosis of DPN. Data were analyzed with independent T-test and Spearman correlation analysis.
Results: The average RNFL thickness in the DM with DPN was thinner than the RNFL thickness in the DM non-DPN group (100.22 ± 38; vs 102.61±9.11; p 0.444). At temporal quadrant and nasal quadrant, RNFL was also thinner in DM DPN group than DM non-DPN group (71.78±12.21, vs 76.33 ± 8.53, p 0.203; and 75.11±11.38 vs 77.39 ± 14, p 0.596). Sural and tibial amplitude (14.44±2.87 and 6.85± 4.98) , were the most significant predictor values in determining the severity of DPN (p=0.000). Average, temporal, and nasal RNFL thinning has an inverse association with DPN severity (r=-0,285; -0,258;and -0,126)
Conclusion: RNFL was thinner at average, temporal, nasal quadrant in the DM group with DPN compared to DM non-DPN group. RNFL thickness has an inverse association with the severity of the DPN although they were not statistically significant.
Keywords: Diabetes Mellitus, Diabetic Peripheral Neuropathy, Retinal Nerve Fiber Layer
Article Details
How to Cite
PUTRI, Mutiara Kristiani et al.
RETINAL NERVE FIBER LAYER THICKNESS ASSOCIATED WITH SEVERITY OF DIABETIC PERIPHERAL NEUROPATHY IN DIABETES MELLITUS TYPE 2.
International Journal of Retina, [S.l.], v. 8, n. 1, p. 26, mar. 2025.
ISSN 2614-8536.
Available at: <https://www.ijretina.com/index.php/ijretina/article/view/320>. Date accessed: 28 mar. 2025.
doi: https://doi.org/10.35479/ijretina.2025.vol008.iss001.320.
Section
Research Articles
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
References
1. Penerbit PB PERKENI. Pedoman Pengelolaan dan Pencegahan Diabetes Mellitus Tipe 2 Dewasa di Indonesia. 2021. PB PERKENI. https://pbperkeni.or.id/unduhan
2. Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018 Apr 1;138:271–81.
3. Cheloni R, Gandolfi SA, Signorelli C, Odone A. Global prevalence of diabetic retinopathy: Protocol for a systematic review and meta-analysis. Vol. 9, BMJ Open. BMJ Publishing Group; 2019.
4. Yang H, Sloan G, Ye Y, Wang S, Duan B, Tesfaye S, et al. New Perspective in Diabetic Neuropathy: From the Periphery to the Brain, a Call for Early Detection, and Precision Medicine. Vol. 10, Frontiers in Endocrinology. Frontiers Media S.A.; 2020.
5. Simó R, Hernández C. Neurodegeneration is an early event in diabetic retinopathy: Therapeutic implications. Vol. 96, British Journal of Ophthalmology. 2012. p. 1285–90.
6. Ciarambino T, Crispino P, Leto G, Mastrolorenzo E, Para O, Giordano
M. Influence of Gender in Diabetes Mellitus and Its Complication. Vol. 23, International Journal of Molecular Sciences. MDPI; 2022.
7. Simó R, Stitt AW, Gardner TW. Neurodegeneration in diabetic retinopathy: does it really matter? Vol. 61, Diabetologia. Springer Verlag; 2018. p. 1902–12.
8. Ibrahim AS, El-Remessy AB, Matragoon S, Zhang W, Patel Y, Khan S, et al. Retinal microglial activation and inflammation induced by amadori-glycated albumin in a rat model of diabetes. Diabetes. 2011 Apr;60(4):1122–33.
9. Hartanti R, Wayan Arsana Wiyasa I, Putu Putra Suryana B, -kr S. EAS Journal of Nursing and Midwifery Abbreviated Key Title: EAS J Nurs Midwifery Menopause-Specific Quality of Life among Indonesian Women: A Descriptive Study. 2020; Available from:
https://www.easpublisher.com/easjn m
10. Li D, Rauscher FG, Choi EY, Wang M, Baniasadi N, Wirkner K, et al. Sex-Specific Differences in Circumpapillary Retinal Nerve Fiber Layer Thickness. Ophthalmology. 2020 Mar 1;127(3):357–68.
11. Srinivasan S, Pritchard N, Vagenas D, Edwards K, Sampson GP, Russell AW, et al. Retinal Tissue Thickness is Reduced in Diabetic Peripheral Neuropathy. Curr Eye Res. 2016 Oct 2;41(10):1359–66.
12. Buño B, Santiago D, Oftalmologico S, Rizal J, Rizal OJ. Comparison of Retinal Nerve Fiber Layer Thickness in Elderly Diabetic Patients with and without Peripheral Neuropathy. Vol. 43, Philipp J Ophthalmol. 2018.
13. Barber AJ. Diabetic retinopathy: recent advances towards understanding neurodegeneration and vision loss. Vol. 58, Science
China Life Sciences. Science in China Press; 2015. p. 541–9.
14. Garcia-Martin E, Cipres M, Melchor I, Gil-Arribas L, Vilades E, Polo V, et al. Neurodegeneration in Patients with Type 2 Diabetes Mellitus without Diabetic Retinopathy. J Ophthalmol. 2019;2019.
15. Kim K, Kim ES, Yu SY. Longitudinal Relationship Between Retinal Diabetic Neurodegeneration and Progression of Diabetic Retinopathy in Patients With Type 2 Diabetes. Am J Ophthalmol. 2018 Dec 1;196:165–72.
16. Figueroa-Romero C, Sadidi M, Feldman EL. Mechanisms of disease: The oxidative stress theory of diabetic neuropathy. Vol. 9, Reviews in Endocrine and Metabolic Disorders. 2008. p. 301–14.
17. Zenker J, Ziegler D, Chrast R. Novel pathogenic pathways in diabetic neuropathy. Vol. 36, Trends in Neurosciences. 2013. p. 439–49.
18. Rahmasari H, Dewi NA, Kurniawan SN, Rosandi R. Peran Visual Evoked Potential (VEP) Sebagai Deteksi Neurodegenerasi Retina Pada Pasien Diabetes Melitus Tipe
2 Tanpa Retinopati. Malang. Fakultas Kedokteran Universitas Brawijaya; 2023.
19. Sohn EH, Van Dijk HW, Jiao C, Kok PHB, Jeong W, Demirkaya N, et al. Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus. Proc Natl Acad Sci U S A. 2016 May 10;113(19):E2655–64.
20. Abramoff MD, Fort PE, Han IC, Thiran Jayasundera K, Sohn EH, Gardner TW. Approach for a clinically useful comprehensive classification of vascular and neural aspects of diabetic retinal disease. Invest Ophthalmol Vis Sci. 2018 Jan 1;59(1):519–27.
21. Savini G, Zanini M, Carelli V, Sadun AA, Ross-Cisneros FN, Barboni P.
Correlation between retinal nerve fibre layer thickness and optic nerve head size: An optical coherence tomography study. British Journal of Ophthalmology. 2005
Apr;89(4):489–92.
22. Hood DC, Fortune B, Arthur SN, Xing D, Salant JA, Ritch R, et al. Blood vessel contributions to retinal nerve fiber layer thickness profiles measured with optical coherence tomography. J Glaucoma. 2008 Oct;17(7):519–28.
23. Neriyanuri S, Pardhan S, Gella L, Saumya Pal S, Ganesan S, Sharma T, et al. Retinal sensitivity changes associated with diabetic neuropathy in the absence of diabetic retinopathy.
24. Obrosova IG, Chung SSM, Kador PF. Diabetic cataracts: Mechanisms and management. Vol. 26, Diabetes/Metabolism Research and Reviews. 2010. p. 172–80.
25. Kobayashi M, Zochodne DW. Diabetic neuropathy and the sensory neuron: New aspects of pathogenesis and their treatment implications. Vol. 9, Journal of Diabetes Investigation. Blackwell Publishing; 2018. p. 1239–54.
26. Dobretsov M, Romanovsky D, Stimers JR. Early diabetic neuropathy: Triggers and mechanisms TOPIC HIGHLIGHT. World J Gastroenterol [Internet]. 2007;13(2):175–91. Available from: www.wjgnet.comK
27. Kobayashi M, Zochodne DW. Diabetic neuropathy and the sensory neuron: New aspects of pathogenesis and their treatment implications. Vol. 9, Journal of Diabetes Investigation. Blackwell Publishing; 2018. p. 1239–54.
28. Picon AP, Ortega NRS, Watari R, Sartor C, Sacco ICN. Classification of the severity of diabetic neuropathy: A new approach taking uncertainties into account using fuzzy logic. Clinics. 2012;67(2):151–6.
29. Lai YR, Huang CC, Chiu WC, Liu RT, Tsai NW, Wang HC, et al. Sural nerve sensory response in diabetic distal symmetrical polyneuropathy. Muscle Nerve. 2020 Jan 1;61(1):88–
94.
30. Killian JM, Jay Foreman P. CLINICAL UTILITY OF DORSAL SURAL NERVE CONDUCTION STUDIES. 2001.
31. Rathi N, Taksande B, Kumar S. Nerve conduction studies of peripheral motor and sensory nerves in the subjects with prediabetes. J Endocrinol Metab. 2019 Oct 1;9(5):147–50.
32. Sepat P, Wasnik S. Sensory nerve conduction study of median ulnar and radial nerves in type 2 diabetic individuals in the age group 40–80 years. Heliyon. 2020 Oct 1;6(10).
33. Suljic E, Drnda S. Type of diabetes mellitus has influence on electrophysiological parameters. Acta Informatica Medica. 2019;27(2):108–13.
34. Mythili A, Kumar KD, Subrahmanyam KAV, Venkateswarlu K, Butchi RG. A comparative study of examination scores and quantitative sensory testing in diagnosis of diabetic polyneuropathy. Int J Diabetes Dev Ctries. 2010 Jan 1;30(1):43–8.
35. Fawzy Khalil H, El-Mongy El-Saied Ali A, Mohamed Aly Ibrahim M, Fathi Mohammed Hatata A. Assessment of Retinal Nerve Fiber Layer Thickness Using Optical Coherence Tomography in Patients with Type 2 Diabetes Mellitus. Vol. 76, The Egyptian Journal of Hospital Medicine. 2019.
36. Nurlaela S, Kurniawan SN, Husna M. ELECTRONEUROMYOGRAPHY EXAMINATION OF DIABETIC POLYNEUROPATHY PATIENTS.
MNJ (Malang Neurology Journal). 2019 Jan 1;5(1):1–4.
37. Ibrahim AS, El-Remessy AB, Matragoon S, Zhang W, Patel Y,
2. Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018 Apr 1;138:271–81.
3. Cheloni R, Gandolfi SA, Signorelli C, Odone A. Global prevalence of diabetic retinopathy: Protocol for a systematic review and meta-analysis. Vol. 9, BMJ Open. BMJ Publishing Group; 2019.
4. Yang H, Sloan G, Ye Y, Wang S, Duan B, Tesfaye S, et al. New Perspective in Diabetic Neuropathy: From the Periphery to the Brain, a Call for Early Detection, and Precision Medicine. Vol. 10, Frontiers in Endocrinology. Frontiers Media S.A.; 2020.
5. Simó R, Hernández C. Neurodegeneration is an early event in diabetic retinopathy: Therapeutic implications. Vol. 96, British Journal of Ophthalmology. 2012. p. 1285–90.
6. Ciarambino T, Crispino P, Leto G, Mastrolorenzo E, Para O, Giordano
M. Influence of Gender in Diabetes Mellitus and Its Complication. Vol. 23, International Journal of Molecular Sciences. MDPI; 2022.
7. Simó R, Stitt AW, Gardner TW. Neurodegeneration in diabetic retinopathy: does it really matter? Vol. 61, Diabetologia. Springer Verlag; 2018. p. 1902–12.
8. Ibrahim AS, El-Remessy AB, Matragoon S, Zhang W, Patel Y, Khan S, et al. Retinal microglial activation and inflammation induced by amadori-glycated albumin in a rat model of diabetes. Diabetes. 2011 Apr;60(4):1122–33.
9. Hartanti R, Wayan Arsana Wiyasa I, Putu Putra Suryana B, -kr S. EAS Journal of Nursing and Midwifery Abbreviated Key Title: EAS J Nurs Midwifery Menopause-Specific Quality of Life among Indonesian Women: A Descriptive Study. 2020; Available from:
https://www.easpublisher.com/easjn m
10. Li D, Rauscher FG, Choi EY, Wang M, Baniasadi N, Wirkner K, et al. Sex-Specific Differences in Circumpapillary Retinal Nerve Fiber Layer Thickness. Ophthalmology. 2020 Mar 1;127(3):357–68.
11. Srinivasan S, Pritchard N, Vagenas D, Edwards K, Sampson GP, Russell AW, et al. Retinal Tissue Thickness is Reduced in Diabetic Peripheral Neuropathy. Curr Eye Res. 2016 Oct 2;41(10):1359–66.
12. Buño B, Santiago D, Oftalmologico S, Rizal J, Rizal OJ. Comparison of Retinal Nerve Fiber Layer Thickness in Elderly Diabetic Patients with and without Peripheral Neuropathy. Vol. 43, Philipp J Ophthalmol. 2018.
13. Barber AJ. Diabetic retinopathy: recent advances towards understanding neurodegeneration and vision loss. Vol. 58, Science
China Life Sciences. Science in China Press; 2015. p. 541–9.
14. Garcia-Martin E, Cipres M, Melchor I, Gil-Arribas L, Vilades E, Polo V, et al. Neurodegeneration in Patients with Type 2 Diabetes Mellitus without Diabetic Retinopathy. J Ophthalmol. 2019;2019.
15. Kim K, Kim ES, Yu SY. Longitudinal Relationship Between Retinal Diabetic Neurodegeneration and Progression of Diabetic Retinopathy in Patients With Type 2 Diabetes. Am J Ophthalmol. 2018 Dec 1;196:165–72.
16. Figueroa-Romero C, Sadidi M, Feldman EL. Mechanisms of disease: The oxidative stress theory of diabetic neuropathy. Vol. 9, Reviews in Endocrine and Metabolic Disorders. 2008. p. 301–14.
17. Zenker J, Ziegler D, Chrast R. Novel pathogenic pathways in diabetic neuropathy. Vol. 36, Trends in Neurosciences. 2013. p. 439–49.
18. Rahmasari H, Dewi NA, Kurniawan SN, Rosandi R. Peran Visual Evoked Potential (VEP) Sebagai Deteksi Neurodegenerasi Retina Pada Pasien Diabetes Melitus Tipe
2 Tanpa Retinopati. Malang. Fakultas Kedokteran Universitas Brawijaya; 2023.
19. Sohn EH, Van Dijk HW, Jiao C, Kok PHB, Jeong W, Demirkaya N, et al. Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus. Proc Natl Acad Sci U S A. 2016 May 10;113(19):E2655–64.
20. Abramoff MD, Fort PE, Han IC, Thiran Jayasundera K, Sohn EH, Gardner TW. Approach for a clinically useful comprehensive classification of vascular and neural aspects of diabetic retinal disease. Invest Ophthalmol Vis Sci. 2018 Jan 1;59(1):519–27.
21. Savini G, Zanini M, Carelli V, Sadun AA, Ross-Cisneros FN, Barboni P.
Correlation between retinal nerve fibre layer thickness and optic nerve head size: An optical coherence tomography study. British Journal of Ophthalmology. 2005
Apr;89(4):489–92.
22. Hood DC, Fortune B, Arthur SN, Xing D, Salant JA, Ritch R, et al. Blood vessel contributions to retinal nerve fiber layer thickness profiles measured with optical coherence tomography. J Glaucoma. 2008 Oct;17(7):519–28.
23. Neriyanuri S, Pardhan S, Gella L, Saumya Pal S, Ganesan S, Sharma T, et al. Retinal sensitivity changes associated with diabetic neuropathy in the absence of diabetic retinopathy.
24. Obrosova IG, Chung SSM, Kador PF. Diabetic cataracts: Mechanisms and management. Vol. 26, Diabetes/Metabolism Research and Reviews. 2010. p. 172–80.
25. Kobayashi M, Zochodne DW. Diabetic neuropathy and the sensory neuron: New aspects of pathogenesis and their treatment implications. Vol. 9, Journal of Diabetes Investigation. Blackwell Publishing; 2018. p. 1239–54.
26. Dobretsov M, Romanovsky D, Stimers JR. Early diabetic neuropathy: Triggers and mechanisms TOPIC HIGHLIGHT. World J Gastroenterol [Internet]. 2007;13(2):175–91. Available from: www.wjgnet.comK
27. Kobayashi M, Zochodne DW. Diabetic neuropathy and the sensory neuron: New aspects of pathogenesis and their treatment implications. Vol. 9, Journal of Diabetes Investigation. Blackwell Publishing; 2018. p. 1239–54.
28. Picon AP, Ortega NRS, Watari R, Sartor C, Sacco ICN. Classification of the severity of diabetic neuropathy: A new approach taking uncertainties into account using fuzzy logic. Clinics. 2012;67(2):151–6.
29. Lai YR, Huang CC, Chiu WC, Liu RT, Tsai NW, Wang HC, et al. Sural nerve sensory response in diabetic distal symmetrical polyneuropathy. Muscle Nerve. 2020 Jan 1;61(1):88–
94.
30. Killian JM, Jay Foreman P. CLINICAL UTILITY OF DORSAL SURAL NERVE CONDUCTION STUDIES. 2001.
31. Rathi N, Taksande B, Kumar S. Nerve conduction studies of peripheral motor and sensory nerves in the subjects with prediabetes. J Endocrinol Metab. 2019 Oct 1;9(5):147–50.
32. Sepat P, Wasnik S. Sensory nerve conduction study of median ulnar and radial nerves in type 2 diabetic individuals in the age group 40–80 years. Heliyon. 2020 Oct 1;6(10).
33. Suljic E, Drnda S. Type of diabetes mellitus has influence on electrophysiological parameters. Acta Informatica Medica. 2019;27(2):108–13.
34. Mythili A, Kumar KD, Subrahmanyam KAV, Venkateswarlu K, Butchi RG. A comparative study of examination scores and quantitative sensory testing in diagnosis of diabetic polyneuropathy. Int J Diabetes Dev Ctries. 2010 Jan 1;30(1):43–8.
35. Fawzy Khalil H, El-Mongy El-Saied Ali A, Mohamed Aly Ibrahim M, Fathi Mohammed Hatata A. Assessment of Retinal Nerve Fiber Layer Thickness Using Optical Coherence Tomography in Patients with Type 2 Diabetes Mellitus. Vol. 76, The Egyptian Journal of Hospital Medicine. 2019.
36. Nurlaela S, Kurniawan SN, Husna M. ELECTRONEUROMYOGRAPHY EXAMINATION OF DIABETIC POLYNEUROPATHY PATIENTS.
MNJ (Malang Neurology Journal). 2019 Jan 1;5(1):1–4.
37. Ibrahim AS, El-Remessy AB, Matragoon S, Zhang W, Patel Y,