Decreased Density of Corneal Basal Epithelium and Subbasal Corneal Nerve Bundle Changes in Patients with Diabetic Retinopathy

Chang, Po‐Yuan; Carrel, Hyman; Huang, Jen-Shang; Wang, I‐Jong; Hou, Yu-Chih; Chen, Wei-Li; Wang, Jiun‐Yi; Hu, Fung‐Rong

doi:10.1016/j.ajo.2006.04.033

Cited by 92 publications

(75 citation statements)

References 4 publications

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“…The finding that corneal nerve pathology is related to neuropathic severity is in keeping with our previously published study (21) and other data from type 1 diabetic patients in whom a reduction in the number of CNF bundles correlated significantly with the severity of somatic neuropathy (19). A recent study has also shown that CNF loss is associated with the severity of retinopathy in diabetic patients (31).…”

Section: Discussionmentioning

confidence: 99%

Surrogate Markers of Small Fiber Damage in Human Diabetic Neuropathy

et al. 2007

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Surrogate markers of diabetic neuropathy are being actively sought to facilitate the diagnosis, measure the progression, and assess the benefits of therapeutic intervention in patients with diabetic neuropathy. We have quantified small nerve fiber pathological changes using the technique of intraepidermal nerve fiber (IENF) assessment and the novel in vivo technique of corneal confocal microscopy (CCM). Fiftyfour diabetic patients stratified for neuropathy, using neurological evaluation, neurophysiology, and quantitative sensory testing, and 15 control subjects were studied. They underwent a punch skin biopsy to quantify IENFs and CCM to quantify corneal nerve fibers. IENF density (IENFD), branch density, and branch length showed a progressive reduction with increasing severity of neuropathy, which was significant in patients with mild, moderate, and severe neuropathy. CCM also showed a progressive reduction in corneal nerve fiber density (CNFD) and branch density, but the latter was significantly reduced even in diabetic patients without neuropathy. Both IENFD and CNFD correlated significantly with cold detection and heat as pain thresholds. Intraepidermal and corneal nerve fiber lengths were reduced in patients with painful compared with painless diabetic neuropathy. Both IENF and CCM assessment accurately quantify small nerve fiber damage in diabetic patients. However, CCM quantifies small fiber damage rapidly and noninvasively and detects earlier stages of nerve damage compared with IENF pathology. This may make it an ideal technique to accurately diagnose and assess progression of human diabetic neuropathy. Diabetes

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Section: Discussionmentioning

confidence: 99%

Surrogate Markers of Small Fiber Damage in Human Diabetic Neuropathy

et al. 2007

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“…While nerve branch density (NBD) measured as the number of nerve branches per mm 2 is an IVCM parameter that has been shown to be reduced in diabetes in several studies, 4,6,8,15,34,35 the level of reduction is highly variable, 21 and NBD reflects only the number of branching points and not the actual length of the secondary branches. Secondary nerve branch length outside the apical region may therefore be an interesting parameter to concisely define and quantify in future studies, provided that a method is used to reliably image as many such branches as possible.…”

Section: Discussionmentioning

confidence: 99%

Reduced Corneal Nerve Fiber Density in Type 2 Diabetes by Wide-Area Mosaic Analysis

Lagali

Allgeier

Guimarães

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Lagali NS, Allgeier S, Guimarães P, et al. Reduced corneal nerve fiber density in type 2 diabetes by wide-area mosaic analysis. Invest Ophthalmol Vis Sci. 2017;58:6318-6327. DOI:10.1167/iovs.17-22257 PURPOSE. To determine if corneal subbasal nerve plexus (SBP) parameters derived from widearea depth-corrected mosaic images are associated with type 2 diabetes. METHODS.One hundred sixty-three mosaics were produced from eyes of 82 subjects by laserscanning in vivo confocal microscopy (IVCM). Subjects were of the same age, without (43 subjects) or with type 2 diabetes (39 subjects). Mosaic corneal nerve fiber length density (mCNFL) and apical whorl corneal nerve fiber length density (wCNFL) were quantified and related to the presence and duration of diabetes (short duration < 10 years and long duration ‡ 10 years).RESULTS. In mosaics with a mean size of 6 mm 2 in subjects aged 69.1 6 1.2 years, mCNFL in type 2 diabetes was reduced relative to nondiabetic subjects (13.1 6 4.2 vs. 15.0 6 3.2 mm/ mm 2 , P ¼ 0.018). Also reduced relative to nondiabetic subjects was mCNFL in both shortduration (14.0 6 4.0 mm/mm 2 , 3.2 6 3.9 years since diagnosis) and long-duration diabetes (12.7 6 4.2 mm/mm 2 , 15.4 6 4.2 years since diagnosis; ANOVA P ¼ 0.023). Lower mCNFL was associated with presence of diabetes (P ¼ 0.032) and increased hemoglobin A1c (HbA1c) levels (P ¼ 0.047). By contrast, wCNFL was unaffected by diabetes or HbA1c (P > 0.05). Global SBP patterns revealed marked degeneration of secondary nerve fiber branches outside the whorl region in long-duration diabetes.CONCLUSIONS. Wide-area mosaic images provide reference values for mCNFL and wCNFL and reveal a progressive degeneration of the SBP with increasing duration of type 2 diabetes.

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“…CCM is capable of demonstrating neuronal regeneration after intervention such as pancreatic or kidney transplantation 22 and in predicting the future development of diabetic neuropathy. 23 Interestingly, CCM-derived corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), and corneal nerve branch density (CNBD) are reduced in patients with diabetes and no DR and are further compromised with the severity of DR. [24][25][26] However, it is not known if these corneal neuronal and retinal neuronal ''markers'' can differentiate patients with early stages of DR. In this report, we specifically investigate the utility of OCT and CCM in persons with nonproliferative diabetic retinopathy (NPDR) in comparison to nondiabetic individuals.…”

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confidence: 99%

Corneal and Retinal Neuronal Degeneration in Early Stages of Diabetic Retinopathy

Srinivasan

Dehghani

Pritchard

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To examine the neuronal structural integrity of cornea and retina as markers for neuronal degeneration in nonproliferative diabetic retinopathy (NPDR).METHODS. Participants were recruited from the broader Brisbane community, Queensland, Australia. Two hundred forty-one participants (187 with diabetes and 54 nondiabetic controls) were examined. Diabetic retinopathy (DR) was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. Corneal nerve fiber length (CNFL), corneal nerve branch density (CNBD), corneal nerve fiber tortuosity (CNFT), full retinal thickness, retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), focal (FLV) and global loss volumes (GLV), hemoglobin A 1c (HbA 1c ), nephropathy, neuropathy, and cardiovascular measures were examined.RESULTS. The central zone (P ¼ 0.174), parafoveal thickness (P ¼ 0.090), perifovea (P ¼ 0.592), RNFL (P ¼ 0.866), GCC (P ¼ 0.798), and GCC GLV (P ¼ 0.338) did not differ significantly between the groups. In comparison to the control group, those with very mild NPDR and those with mild NPDR had significantly higher focal loss in GCC volume (P ¼ 0.036). CNFL was significantly lower in those with mild NPDR (P ¼ 0.004) in comparison to the control group and those with no DR. The CNBD (P ¼ 0.094) and CNFT (P ¼ 0.458) did not differ between the groups.CONCLUSIONS. Both corneal and retinal neuronal degeneration may occur in early stages of diabetic retinopathy. Further studies are required to examine these potential markers for neuronal degeneration in the absence of clinical signs of DR.

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Decreased Density of Corneal Basal Epithelium and Subbasal Corneal Nerve Bundle Changes in Patients with Diabetic Retinopathy

Cited by 92 publications

References 4 publications

Surrogate Markers of Small Fiber Damage in Human Diabetic Neuropathy

Surrogate Markers of Small Fiber Damage in Human Diabetic Neuropathy

Reduced Corneal Nerve Fiber Density in Type 2 Diabetes by Wide-Area Mosaic Analysis

Corneal and Retinal Neuronal Degeneration in Early Stages of Diabetic Retinopathy

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