Journal List > J Korean Diabetes Assoc > v.31(4) > 1062458

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Nam, Cho, Noh, Kim, Park, Cho, Kim, Yoon, Jung, Kang, Rhee, Lee, Ahn, Cha, Lee, Lim, Kim, and Lee: In vivo Corneal Confocal Microscopy and Nerve Growth Factor in Diabetic Microvascular Complications
Original Article
The Journal of Korean Diabetes Association

The Journal of Korean Diabetes Association 2007; 31(4): 351-361.

Published online: 31 July 2007

DOI: https://doi.org/10.4093/jkda.2007.31.4.351

In vivo Corneal Confocal Microscopy and Nerve Growth Factor in Diabetic Microvascular Complications

Ji Sun Nam, Young Jae Cho1, Tae Woong Noh, Chul Sik Kim, Jong Suk Park, Min ho Cho, Hai Jin Kim, Ji Eun Yoon, Han Young Jung, Eun Seok Kang, Yu Mie Rhee, Hyung Keun Lee1, Chul Woo Ahn, Bong Soo Cha, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee

Department of Internal Medicine, Yonsei University College of Medicine, Korea.

1Department of Opthalmology, Yonsei University College of Medicine, Korea.

Received 21 February 2007       Accepted 22 May 2007

Copyright © 2007 Korean Diabetes Association

Abstract

Background

In vivo corneal confocal microscopy (IVCCM) is being recognized as a non-invasive, early diagnostic tool for diabetic neuropathy, for it provides a clear image of corneal subbasal nerve plexus in detail. Nerve growth factors (NGF) are believed to regulate peripheral and central nervous system, neuronal differentiation, and regeneration of damaged nerves, and their role in diabetic neuropathy is being emphasized these days. Moreover, NGFs and receptors are also expressed in retina and renal mesangial cells, suggesting their possible role in the common pathogenesis of diabetic microvascular complications. We plan to examine corneal structures of diabetic patients and compare IVCCM with conventional tools and analyze their serum and tear NGF levels.

Methods

IVCCM, nerve conduction velocity (NCV), and serum, urine, and tear samplings were done to 42 diabetic patients. From IVCCM, we measured corneal nerve density, branch, and tortuosity, total corneal/epithelial thickness, and the number of endothelial/keratocyte cells, and we checked patients' biochemical profiles and serum and tear NGF levels.

Results

Patients with more severe neuropathy had less corneal endothelial cells (3105 ± 218 vs. 2537 ± 142 vs. 2350 ± 73/mm3 vs. 1914 ± 465/mm3, P = 0.02), higher serum NGF (36 ± 15 vs. 60 ± 57.66 vs. 80 ± 57.63 vs. 109 ± 60.81 pg/mL, P = 0.39) and tear NGF levels (135.00 ± 11.94 vs. 304.29 ± 242.44 vs. 538.50 ± 251.92 vs. 719.50 ± 92.63 pg/mL, P = 0.01). There was a positive correlation between neuropathy and corneal nerve tortuosity (r2 = 0.479, P = 0.044) and negative correlation between neuropathy and endothelial cell count (r2 = -0.709, P = 0.002). Interestingly, similar changes were seen in other microvascular complications as well.

Conclusion

Our results provide a possibility of using novel tools, IVCCM and NGF, as common diagnostic tools for diabetic microvascular complications, but it should be followed by a large population study.

Keywords: Diabetic microvascular complications, In vivo corneal confocal microscopy, Nerve growth factor

Figures and Tables

Fig. 1
Corneal subbasal nerve plexus of a patient with mild diabetic neuropathy by in vivo corneal confocal microscopy. Two nerve fibers are seen with no nerve fiber branching and mild tortuosity.
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Fig. 2
Relationships between endothelial cell count (A) and tortuosity (B) and severity of neuropathy. There is a negative correlation between endothelial cell count and severity of neuropathy and a positive correlation between tortuosity and severity of neuropathy. NCV: O, normal; 1, mild neuropathy; 2, moderate neuropathy; 3, severe neuropathy.
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Fig. 3
Relationship between tear NGF level and neuropathy. There is a positive correlation between tear NGF level and neuropathy.
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Fig. 4
Relationships between serum and tear NGF and other microvascular complications. (A, serum NGF vs. DMR; B, serum NGF vs. DMN; C, tear NGF vs. DMN; D, tear NGF vs. 24-hour albuminuria, DMR: O, normal, 1, non-proliferative retinopathy; 2, proliferative retinopathy)
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Table 1
Baseline characteristics of patients based on the severity of neuropathy
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Data are expressed by means ± SD, except for frequency data. BMI, body mass index; FBS, fasting blood glucose; TC, total cholesterol; LDL-C, Low density lipoprotein-cholesterol; HDL-C, High density lipoprotein-cholesterol; TG, triglyceride; DMN, DM nephropathy; nl, normal; micro, microalbuminuria; overt, overt proteinuria; DMR, DM retinopathy; NP, non-proliferative; P, proliferative; NS, not significant.

Table 2
Confocal parameters according to theseverity of neuropathy
jkda-31-351-i002

Data are expressed by means ± SD. P-value < 0.05 represents a significant difference in each confocal parameter among groups of different degrees of neuropathy. No, number; NFD, nerve fiber density; NFB, nerve fiber branch; Mod, moderate; NS, not significant.

Table 3
Serum and tear NGF levels according to the severity of neuropathy
jkda-31-351-i003

Data are expressed by means ± SD, P-value < 0.05 represents a significant difference in serum or tear NGF levels among groups of different degrees of neuropathy. NS, not significant.

Table 4
Relationship between confocal parameters and diabetic microvascular complications
jkda-31-351-i004

Data are expressed by means ± SD, P-value < 0.05 represents a significant correlation between each confocal parameter and the degree of DM retinopathy or nephropathy. r2, Pearson correlation; NFD, nerve fiber density; NFB, nerve fiber branch.

Table 5
Confocal parameters and NGF levels according to diabetic retinopathy
jkda-31-351-i005

Data are expressed by means ± SD. P-value < 0.05 represents a significant difference in confocal parameters or NGF levels among groups of different degrees of DM retinopathy. NPDR, non-proliferative DM retinopathy; PDR, proliferative DM retinopathy; NFD, nerve fiber density; NFB, nerve fiber branch; ant, anterior; pos, posterior; NS, not significant.

Table 6
Confocal parameters and NGF levels according to diabetic nephropathy
jkda-31-351-i006

Data are expressed by means ± SD. P-value < 0.05 represents a significant difference in confocal parameters or NGF levels among groups of different degrees of nephropathy. Microalb, microalbuminuria; Overt, overt proteinuria; NFD, nerve fiber density; NFB, nerve fiber branch; ant, anterior; pos, posterior; NS, not significant.

Table 7
Relationship between confocal parameters and serum and tear NGF
jkda-31-351-i007

P-value < 0.05 represents a significance in the correlation between each confocal parameters and serum or tear NGF levels. r2, Pearson correlation; NFD, nerve fiber density; NFB, nerve fiber branch.

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