Utility of Assessing Nerve Morphology in Central Cornea Versus Whorl Area for Diagnosing Diabetic Peripheral Neuropathy

Pritchard, Nicola; Dehghani, Cirous; Edwards, Katie; Burgin, Edward; Cheang, Nick; Kim, Hannah; Mikhaiel, Merna; Stanton, Gemma; Russell, Anthony; Malik, Rayaz A.; Efron, Nathan

doi:10.1097/ico.0000000000000447

Cited by 36 publications

(28 citation statements)

References 30 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: 54%

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: 54%

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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“…Analysis of the sub-basal nerve plexus 44, 45, 46, 47, 48, 49 can be performed in two regions of the cornea: central cornea and the inferior whorl. 50 For example, it has also been reported that the nerve fiber density at the inferior whorl region is more sensitive to early nerve fiber damage than the central corneal region, in DM patients before development of peripheral neuropathy. 51 …”

Section: Cornea Neuropathymentioning

confidence: 99%

A systematic review on the impact of diabetes mellitus on the ocular surface

2017

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Diabetes mellitus is associated with extensive morbidity and mortality in any human community. It is well understood that the burden of diabetes is attributed to chronic progressive damage in major end-organs, but it is underappreciated that the most superficial and transparent organ affected by diabetes is the cornea. Different corneal components (epithelium, nerves, immune cells and endothelium) underpin specific systemic complications of diabetes. Just as diabetic retinopathy is a marker of more generalized microvascular disease, corneal nerve changes can predict peripheral and autonomic neuropathy, providing a window of opportunity for early treatment. In addition, alterations of immune cells in corneas suggest an inflammatory component in diabetic complications. Furthermore, impaired corneal epithelial wound healing may also imply more widespread disease. The non-invasiveness and improvement in imaging technology facilitates the emergence of new screening tools. Systemic control of diabetes can improve ocular surface health, possibly aided by anti-inflammatory and vasoprotective agents.

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“…37 While IVCM is sensitive in detecting corneal subbasal nerve length changes in diabetic neuropathy, neither central corneal subbasal nerve length nor subbasal whorl nerve length have proven to be strong diagnostic tests for diabetic peripheral neuropathy independently (area under the curve, AUC = 0.76–0.77; specificity = 0.5–0.6). 38 However, when taken together, there was moderate improvement in its specificity (0.71) but without an increase in its utility as a diagnostic test (AUC = 0.75). 37 …”

Section: Corneal Subbasal Nerve Plexusmentioning

confidence: 99%

In Vivo Confocal Microscopy of Corneal Nerves in Health and Disease

2017

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In vivo confocal microscopy (IVCM) is becoming an indispensable tool for studying corneal physiology and disease. Enabling the dissection of corneal architecture at a cellular level, this technique offers fast and noninvasive in vivo imaging of the cornea with images comparable to that of ex vivo histochemical techniques. Corneal nerves bear substantial relevance to clinicians and scientists alike, given their pivotal roles in regulation of corneal sensation, maintenance of epithelial integrity, and proliferation and promotion of wound healing. Thus, IVCM offers a unique method to study corneal nerve alterations in a myriad of conditions, such as ocular and systemic diseases and following corneal surgery, without altering the tissue microenvironment. Of particular interest has been the correlation of corneal subbasal nerves to their function, which has been studied in normal eyes, contact lens wearers, and patients with keratoconus, infectious keratitis, corneal dystrophies, and neurotrophic keratopathy. Longitudinal studies have applied IVCM to investigate the effects of corneal surgery on nerves, demonstrating their regenerative capacity. IVCM is increasingly important in the diagnosis and management of systemic conditions such as peripheral diabetic neuropathy and, more recently, in ocular diseases. In this review, we outline the principles and applications of IVCM in the study of corneal nerves in various ocular and systemic diseases.

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Utility of Assessing Nerve Morphology in Central Cornea Versus Whorl Area for Diagnosing Diabetic Peripheral Neuropathy

Abstract: Small nerve fiber pathology is comparable at the central and whorl anatomical sites of the cornea. Quantification of CNFL from the corneal center is as accurate as CNFL quantification of the whorl area for the diagnosis of DPN.

Cited by 36 publications

References 30 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

A systematic review on the impact of diabetes mellitus on the ocular surface

In Vivo Confocal Microscopy of Corneal Nerves in Health and Disease

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