Corneal nerve fiber damage in different stage of diabetic retinopathy patients with type 2 diabetes_Chinese Journal of Ocular Fundus Diseases

Authors：

Fan Wei , Xiong Xiangwei , Zou Huan , Zhang Cong ,  Yuan Rongdi

Department of Ophthalmology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China;

Corresponding author：

Yuan Rongdi, Email: yuanrongdi@126.com

Keywords：

Cornea; Diabetic neuropathies/diagnosis; Microscopy, confocal; Diabetic retinopathy/complications

DOI：

10.3760/cma.j.issn.1005-1015.2017.02.011

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To observe the corneal nerve fibres damage in different stage of diabetic retinopathy (DR) with type 2 diabetes. Methods A cross-sectional study. One hundred and twenty eyes of 120 patients with type 2 diabetes served as diabetes group. According to International Clinical Diabetic Retinopathy Disease Severity Scales (2002), diabetes patients were classified into 4 subgroups: patients without diabetic retinopathy (NDR), patients with mild or moderate non-proliferative diabetic retinopathy (mNPDR), patients with severe non-proliferative diabetic retinopathy (sNPDR) and patients with proliferative diabetic retinopathy (PDR), each subgroup has 30 eyes of 30 patients. Another 30 eyes of 30 healthy participants served as control group. All eyes were scanned with HRT3 in vivo corneal confocal microscopy. Images of sub-basal nerve plexus were quantified including nerve fiber length (NFL), nerve fiber density (NFD), nerve fiber branch density (NFB), and nerve tortuosity (NT). The correlations of corneal nerve fiber with age, duration of diabetes and glycated hemoglobin (HbA1c) were analyzed using Spearman correlation analysis. Results NFL, NFD and NFB were found to be significantly lower in diabetic patients (F=147.315, 142.586, 65.898;P=0.000, 0.000, 0.000), NT was significantly greater in diabetic patients (F=39.431,P=0.000), when compared to control group. In diabetic patients, NFL, NFD and NFB were gradually reduced with DR severity, NT was gradually increased with DR severity. While the difference of NFL, NFD, NFB, NT was not statistically significant between sNPDR and PDR subgroups (P＞0.05), but was statistically significant between other subgroups (P＜0.05). Spearman correlation analysis results showed that age (r=－0.071, －0.080, 0.001, 0.100;P=0.391, 0.328, 0.991, 0.224) and HbA1c (r=－0.109, －0.115, －0.126, 0.025;P=0.238, 0.211, 0.169, 0.781) had no correlation with NFL, NFD, NFB, NT. Duration of diabetes was negatively correlated with the NFL, NFD (r=－0.212, －0.264;P= 0.020, 0.004), positive correlated with NT (r=0.261,P=0.004), and had no correlation with NFB (r=－0.119,P=0.194). Conclusions Corneal nerve fiber loss and nerve tortuosity increased were found in patients with type 2 diabetes, and even without diabetic retinopathy. The progress of corneal neuropathy was correlated with the severity of DR, but it was not change significantly between sNPDR and PDR.

Citation： Fan Wei, Xiong Xiangwei, Zou Huan, Zhang Cong, Yuan Rongdi. Corneal nerve fiber damage in different stage of diabetic retinopathy patients with type 2 diabetes. Chinese Journal of Ocular Fundus Diseases, 2017, 33(2): 157-161. doi: 10.3760/cma.j.issn.1005-1015.2017.02.011 Copy

1.	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[J]. Diabetes Care, 2010, 33: 1792-1297. DOI: 10.2337/dc10-0253.
2.	Edwards K, Pritchard N, Vagenas D, et al. Utility of corneal confocal microscopy for assessing mild diabetic neuropathy: baseline findings of the LANDMark study[J]. Clin Exp Optom, 2012, 95(3): 348-354. DOI: 10.1111/j.1444-0938.2012.00740.x.
3.	Petropoulos IN, Alam U, Fadavi H, et al. Rapid automated diagnosis of diabetic peripheral neuropathy with in vivo corneal confocal microscopy[J]. Invest Ophthalmol Vis Sci, 2014, 55(4): 2071-2078. DOI: 10.1167/iovs.13-13787.
4.	Sato E, Mori F, Igarashi S, et al. Corneal advanced glycation end products increase in patients with proliferative diabetic retinopathy[J]. Diabetes Care, 2001, 24(3): 479-482. DOI: 10.2337/ diacare.24.3.479.
5.	Barr EL, Wong TY, Tapp RJ, et al. Is peripheral neuropathy associated with retinopathy and albuminuria in individuals with impaired glucose metabolism? The 1999-2000 AusDiab[J]. Diabetes Care, 2006, 29(5): 1114-1116. DOI: 10.2337/diacare.2951114.
6.	Rahimi Z, Moradi M, Nasri H. A systematic review of the role of renin angiotensin aldosterone system genes in diabetes mellitus, diabetic retinopathy and diabetic neuropathy[J]. J Res Med Sci, 2014, 19(11): 1090-1098.
7.	Huang CC, Lee JJ, Lin TK, et al. Diabetic retinopathy is strongly predictive of cardiovascular autonomic neuropathy in type 2 diabetes[J/OL]. J Diabetes Res, 2016, 2016: 6090749[2016-02-03]. . DOI: 10.1155/2016/ 6090749.
8.	Tomita M, Kabeya Y, Okisugi M, et al. Diabetic microangiopathy is an independent predictor of incident diabetic foot ulcer[J/OL]. J Diabetes Res, 2016, 2016: 5938540[2016-02-29]. . DOI: 10.1155/2016/5938540.
9.	American Diabetes Association. Standards of medical care in diabetes--2012[J]. Diabetes Care, 2012, 35 Suppl 1: S11-63. DOI: 10.2337/dc12-s011.
10.	Wilkinson CP, Ferris FL 3rd, Klein RE, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales[J]. Ophthalmology, 2003, 110(9): 1677-1682. DOI: 10.1016/S0161-6420(03)00475-5.
11.	Malik RA, Kallinikos P, Abbott CA, et al. Corneal confocal microscopy: a non-invasive surrogate of nerve fibre damage and repair in diabetic patients[J]. Diabetologia, 2003, 46(5): 683-688. DOI: 10.1007/s00125-003-1086-8.
12.	Oliveira-Soto L, Efron N. Morphology of corneal nerves using confocal microscopy[J]. Cornea, 2001, 20(4): 374-384.
13.	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[J/OL]. PLoS One, 2013, 8(1): 52157[2013-01-15]. . DOI: 10.1371/journal.pone.0052157.
14.	Petropoulos IN, Green P, Chan AW, et al. Corneal confocal microscopy detects neuropathy in patients with type 1 diabetes without retinopathy or microalbuminuria[J/OL]. PLoS One, 2015, 10(4): 0123517. . DOI: 10.1371/journal.pone.0123517.
15.	de Cilla S, Ranno S, Carini E, et al. Corneal subbasal nerves changes in patients with diabetic retinopathy: an in vivo confocal study[J]. Invest Ophthalmol Vis Sci, 2009, 50(11): 5155-5158. DOI: 10.1167/iovs.09-3384.
16.	Bouheraoua N, Hrarat L, Parsa CF, et al. Decreased corneal sensation and subbasal nerve density, and thinned corneal epithelium as a result of 360-degree laser retinopexy[J]. Ophthalmology, 2015, 122(10): 2095-2102. DOI: 10.1016/j.ophtha.2015.06.010.
17.	Erie JC, McLaren JW, Hodge DO, et al. The effect of age on the corneal subbasal nerve plexus[J]. Cornea, 2005, 24(6): 705-709.
18.	Cruzat A, Pavan-Langston D, Hamrah P. In vivo confocal microscopy of corneal nerves: analysis and clinical correlation[J]. Semin Ophthalmol, 2010, 25(5-6): 171-177. DOI: 10.3109/ 08820538.2010.518133.

1. 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[J]. Diabetes Care, 2010, 33: 1792-1297. DOI: 10.2337/dc10-0253.
2. Edwards K, Pritchard N, Vagenas D, et al. Utility of corneal confocal microscopy for assessing mild diabetic neuropathy: baseline findings of the LANDMark study[J]. Clin Exp Optom, 2012, 95(3): 348-354. DOI: 10.1111/j.1444-0938.2012.00740.x.
3. Petropoulos IN, Alam U, Fadavi H, et al. Rapid automated diagnosis of diabetic peripheral neuropathy with in vivo corneal confocal microscopy[J]. Invest Ophthalmol Vis Sci, 2014, 55(4): 2071-2078. DOI: 10.1167/iovs.13-13787.
4. Sato E, Mori F, Igarashi S, et al. Corneal advanced glycation end products increase in patients with proliferative diabetic retinopathy[J]. Diabetes Care, 2001, 24(3): 479-482. DOI: 10.2337/ diacare.24.3.479.
5. Barr EL, Wong TY, Tapp RJ, et al. Is peripheral neuropathy associated with retinopathy and albuminuria in individuals with impaired glucose metabolism? The 1999-2000 AusDiab[J]. Diabetes Care, 2006, 29(5): 1114-1116. DOI: 10.2337/diacare.2951114.
6. Rahimi Z, Moradi M, Nasri H. A systematic review of the role of renin angiotensin aldosterone system genes in diabetes mellitus, diabetic retinopathy and diabetic neuropathy[J]. J Res Med Sci, 2014, 19(11): 1090-1098.
7. Huang CC, Lee JJ, Lin TK, et al. Diabetic retinopathy is strongly predictive of cardiovascular autonomic neuropathy in type 2 diabetes[J/OL]. J Diabetes Res, 2016, 2016: 6090749[2016-02-03]. . DOI: 10.1155/2016/ 6090749.
8. Tomita M, Kabeya Y, Okisugi M, et al. Diabetic microangiopathy is an independent predictor of incident diabetic foot ulcer[J/OL]. J Diabetes Res, 2016, 2016: 5938540[2016-02-29]. . DOI: 10.1155/2016/5938540.
9. American Diabetes Association. Standards of medical care in diabetes--2012[J]. Diabetes Care, 2012, 35 Suppl 1: S11-63. DOI: 10.2337/dc12-s011.
10. Wilkinson CP, Ferris FL 3rd, Klein RE, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales[J]. Ophthalmology, 2003, 110(9): 1677-1682. DOI: 10.1016/S0161-6420(03)00475-5.
11. Malik RA, Kallinikos P, Abbott CA, et al. Corneal confocal microscopy: a non-invasive surrogate of nerve fibre damage and repair in diabetic patients[J]. Diabetologia, 2003, 46(5): 683-688. DOI: 10.1007/s00125-003-1086-8.
12. Oliveira-Soto L, Efron N. Morphology of corneal nerves using confocal microscopy[J]. Cornea, 2001, 20(4): 374-384.
13. 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[J/OL]. PLoS One, 2013, 8(1): 52157[2013-01-15]. . DOI: 10.1371/journal.pone.0052157.
14. Petropoulos IN, Green P, Chan AW, et al. Corneal confocal microscopy detects neuropathy in patients with type 1 diabetes without retinopathy or microalbuminuria[J/OL]. PLoS One, 2015, 10(4): 0123517. . DOI: 10.1371/journal.pone.0123517.
15. de Cilla S, Ranno S, Carini E, et al. Corneal subbasal nerves changes in patients with diabetic retinopathy: an in vivo confocal study[J]. Invest Ophthalmol Vis Sci, 2009, 50(11): 5155-5158. DOI: 10.1167/iovs.09-3384.
16. Bouheraoua N, Hrarat L, Parsa CF, et al. Decreased corneal sensation and subbasal nerve density, and thinned corneal epithelium as a result of 360-degree laser retinopexy[J]. Ophthalmology, 2015, 122(10): 2095-2102. DOI: 10.1016/j.ophtha.2015.06.010.
17. Erie JC, McLaren JW, Hodge DO, et al. The effect of age on the corneal subbasal nerve plexus[J]. Cornea, 2005, 24(6): 705-709.
18. Cruzat A, Pavan-Langston D, Hamrah P. In vivo confocal microscopy of corneal nerves: analysis and clinical correlation[J]. Semin Ophthalmol, 2010, 25(5-6): 171-177. DOI: 10.3109/ 08820538.2010.518133.

Chinese Journal of Ocular Fundus Diseases

Corneal nerve fiber damage in different stage of diabetic retinopathy patients with type 2 diabetes

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content