In Vivo Confocal Microscopy of Corneal Nerves: An Ocular Biomarker for Peripheral and Cardiac Autonomic Neuropathy in Type 1 Diabetes Mellitus

Misra, Stuti; Craig, Jennifer P.; Patel, Dipika V.; McGhee, Charles N J; Pradhan, Monika; Ellyett, Kevin; Kilfoyle, Dean; Braatvedt, Geoffrey

doi:10.1167/iovs.15-16711

Cited by 76 publications

(79 citation statements)

References 48 publications

(55 reference statements)

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“…NIBUT was observed to be lower in females than in males in both the control ( P = 0.06) and DM ( P < 0.01) groups. The patients with DM exhibited reduced corneal sensitivity compared to controls ( P < 0.0001) (corneal sensitivity and subbasal nerve density reported in detail elsewhere) [20]. The total neuropathy score (maximum possible score 40) ranged between 0 and 21 (5.3 ± 5.1) in the patients with diabetes.…”

Section: Resultsmentioning

confidence: 96%

Peripheral Neuropathy and Tear Film Dysfunction in Type 1 Diabetes Mellitus

Misra

Patel

McGhee

et al. 2014

Journal of Diabetes Research

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Purpose. To compare tear film metrics in patients with type 1 diabetes mellitus (DM) and healthy controls and investigate the association between peripheral neuropathy and ocular surface quality. Methods. Dry eye symptoms were quantified in 53 patients with type 1 DM and 40 age-matched controls. Ocular examination included tear film lipid layer thickness grading, tear film stability and quantity measurement, and retinal photography. DM individuals additionally underwent a detailed neuropathy assessment. Results. Neither mean age nor dry eye symptom scores differed significantly between the DM and control groups (P = 0.12 and P = 0.33, resp.). Tear lipid thickness (P = 0.02), stability (P < 0.0001), and quantity (P = 0.01) were significantly lower in the DM group. Corneal sensitivity was also reduced in the DM group (P < 0.001) and tear film stability was inversely associated with total neuropathy score (r = −0.29, P = 0.03). Conclusion. The DM group exhibited significantly reduced tear film stability, secretion, and lipid layer quality relative to the age-matched control group. The negative correlation between tear film parameters and total neuropathy score suggests that ocular surface abnormalities occur in parallel with diabetic peripheral neuropathy.

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Section: Resultsmentioning

confidence: 96%

Peripheral Neuropathy and Tear Film Dysfunction in Type 1 Diabetes Mellitus

Misra

Patel

McGhee

et al. 2014

Journal of Diabetes Research

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“…Keywords: confocal microscopy, corneal nerves, subbasal nerve, diabetes mellitus R ecognition of the fact that the nerve fibers of the corneal subbasal nerve plexus (SBP) are axons of the peripheral nervous system has led to an increased effort in imaging, quantifying, and relating corneal nerves to the status of individuals with diabetes suffering from (or at risk of developing) diabetic peripheral neuropathy [1][2][3][4][5] or diabetic retinopathy. [6][7][8][9] Reduced corneal subbasal nerve fiber length density (CNFL) has been reported in subjects with type 1 and type 2 diabetes relative to healthy control subjects, 4,6,8,[10][11][12][13][14][15][16][17][18][19] but reported values are based on small areas of the SBP (typically 0.16 mm 2 in size) sampled using a small number of raw in vivo confocal microscopy (IVCM) images.…”

Section: Resultsmentioning

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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“…To assess the nerve plexus, we determined nerve density according to Misra et al ,8 Tavakoli et al 9 and Hertz et al 16. We used the HRT-II confocal microscope with the Rostock cornea module, given its laser scanning ability, to assess nerve density.…”

Section: Discussionmentioning

confidence: 99%