Imaging of the Corneal Subbasal Whorl-like Nerve Plexus: More Accurate Depiction of the Extent of Corneal Nerve Damage in Patients With Diabetes

Utsunomiya, Tsugiaki; Nagaoka, Taiji; Hanada, Kazuomi; Omae, Tsuneaki; Yokota, Harumasa; Abiko, Atsuko; Haneda, Masakazu; Yoshida, Akitoshi

doi:10.1167/iovs.15-16609

Cited by 44 publications

(38 citation statements)

References 41 publications

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“…30 Interestingly, the whorl density wCNFL did not vary with presence or duration of diabetes or HbA1c, but was largely preserved. In three recent studies that did not employ widefield mosaicking or depth correction techniques, [31][32][33] reduced CNFL in the whorl region was reported in diabetes-a finding that could not be confirmed in our cohort. In another study, mosaic images indicated a decline in whorl density in diabetes, although the study was limited to only two subjects.…”

Section: Discussioncontrasting

confidence: 92%

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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Section: Discussioncontrasting

confidence: 92%

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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“…We found that the density of basal epithelial cells increased with age. Previous studies failed to find a significant correlation between basal epithelial cell density and age (Gambato et al 2015, Niederer et al Vanathi et al 2003), although there was a trend in a study by Niederer et al (2007) andVantahi et al (2003). However, according to our results, the association with age disappeared after the DM1 diagnosis was established, which may indicate the opposite influence of DM1 on epithelial cell density.…”

Section: Discussionmentioning

confidence: 87%

“…The diabetic patients were subdivided, based on a fundus examination (using biomicroscopy and fundus photography) and need of therapy intervention, into three groups: 1) without retinopathy, 2) mild retinopathy, and 3) severe retinopathy. Patients with no signs of retinopathy were included in the "no DR" group, patients with mild or moderate non-proliferative retinopathy (NPDR), according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) (Wilkinson et al 2003, Utsunomiya et al 2015 were assigned to the "mild DR" group, and patients with severe NPDR or proliferative retinopathy (PDR) were placed in the "severe DR" group.…”

Section: Evaluation Of Retinal Statusmentioning

confidence: 99%

Effect of Diabetes Mellitus Type 1 Diagnosis on the Corneal Cell Densities and Nerve Fibers

Burdová

Kulich²,

Dotrelová³

et al. 2018

Physiol Res

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Relation of diabetes mellitus (DM) to the various stages of corneal nerve fiber damage is well accepted. A possible association between changes in the cornea of diabetic patients and diabetic retinopathy (DR), DM duration, and age at the time of DM diagnosis were evaluated. The study included 60 patients with DM type 1 (DM1) and 20 healthy control subjects. The density of basal epithelial cells, keratocytes and endothelial cells, and the status of the subbasal nerve fibers were evaluated using in vivo corneal confocal microscopy. Basal epithelial cell density increased with age (p=0.026), while stromal and endothelial cell density decreased with age (p=0.003, p=0.0005, p<0.0001).After the DM1 diagnosis was established, this association with age weaken. We showed nerve fiber damage in DM1 patients (p˂0.0001). The damage correlated with the degree of DR. DM1 patients with higher age at DM1 diagnosis had a higher nerve fiber density (p=0.0021). These results indicated that age at DM1 diagnosis potentially has an important effect on final nerve fiber and corneal cell density.

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“…Accumulation of sorbitol and fructose leads to reduced nerve myoinositol, decreased sodium-potassium ATPase activity, 44 alteration in protein kinase C subunits, and slowed nerve CV in the peripheral nerves in diabetes. 45 It is likely that a similar mechanism occurs in the corneal nerves.…”

Section: Discussionmentioning

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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Imaging of the Corneal Subbasal Whorl-like Nerve Plexus: More Accurate Depiction of the Extent of Corneal Nerve Damage in Patients With Diabetes

Abstract: Our findings indicated that IVCM measurements of the whorl-like patterns may accurately define the extent of corneal nerve damage in order to monitor diabetic peripheral neuropathy.

Cited by 44 publications

References 41 publications

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

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

Effect of Diabetes Mellitus Type 1 Diagnosis on the Corneal Cell Densities and Nerve Fibers

Corneal and Retinal Neuronal Degeneration in Early Stages of Diabetic Retinopathy

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