Reproducibility of In Vivo Corneal Confocal Microscopy Using an Automated Analysis Program for Detection of Diabetic Sensorimotor Polyneuropathy

Ostrovski, Ilia; Lovblom, Leif Erik; Farooqi, Mohammed A.; Scarr, Daniel; Boulet, Geneviève; Hertz, Paul; Wu, Tong; Halpern, Elise M.; Ngo, Mylan; Ng, Eduardo; Orszag, Andrej; Bril, Vera; Perkins, Bruce A.

doi:10.1016/j.jcjd.2015.09.066

Cited by 11 publications

(17 citation statements)

References 35 publications

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“…Certainly in the present study the inter- and intra-observer repeatability was maximal for CNFL. Ostrovski et al have recently shown that corneal nerve parameters differ significantly when using two different protocols; a semi-automated (2 images) and fully automated (all captured images) protocol for the quantification of corneal nerve parameters [ 14 ]. In contrast with Ostrovski et al, our study shows that by following a standardized protocol, corneal nerve parameters did not differ significantly when analyzing 6 images or 12 images.…”

Section: Discussionmentioning

confidence: 99%

“…Different studies use different protocols for selecting the number and type of images used for quantification of corneal nerve parameters. There are very few studies, which have assessed whether or not these protocols are reproducible [ 14 ]. The purpose of this study was to establish the intra and inter-rater reproducibility of a standardized protocol for image selection and to define the optimal image sample size, which could be deployed in multicenter studies.…”

Section: Introductionmentioning

confidence: 99%

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Corneal confocal microscopy is a rapid reproducible ophthalmic technique for quantifying corneal nerve abnormalities

Kalteniece¹,

Ferdousi²,

Adam³

et al. 2017

PLoS ONE

100

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PurposeTo assess the effect of applying a protocol for image selection and the number of images required for adequate quantification of corneal nerve pathology using in vivo corneal confocal microscopy (IVCCM).MethodsIVCCM was performed in 35 participants by a single examiner. For each participant, 4 observers used a standardized protocol to select 6 central corneal nerve images to assess the inter-observer variability. Furthermore, images were selected by a single observer on two occasions to assess intra-observer variability and the effect of sample size was assessed by comparing 6 with 12 images. Corneal nerve fiber density (CNFD), branch density (CNBD) and length (CNFL) were quantified using fully automated software. The data were compared using the intra class correlation coefficient (ICC) and Bland-Altman agreement plots for all experiments.ResultsThe ICC values for CNFD, CNBD and CNFL were 0.93 (P<0.0001), 0.96 (P<0.0001) and 0.95 (P<0.0001) for inter-observer variability and 0.95 (P<0.0001), 0.97 (P<0.001) and 0.97 (P<0.0001) for intra-observer variability. For sample size variability, ICC values were 0.94 (P<0.0001), 0.95 (P<0.0001), and 0.96 (P<0.0001) for CNFD, CNBD and CNFL. Bland-Altman plots showed excellent agreement for all parameters.ConclusionsThis study shows that implementing a standardized protocol to select IVCCM images results in high intra and inter-observer reproducibility for all corneal nerve parameters and 6 images are adequate for analysis. IVCCM could therefore be deployed in large multicenter clinical trials with confidence.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Corneal confocal microscopy is a rapid reproducible ophthalmic technique for quantifying corneal nerve abnormalities

Kalteniece¹,

Ferdousi²,

Adam³

et al. 2017

PLoS ONE

100

View full text Add to dashboard Cite

show abstract

“…In patients with diabetes, CCM can detect loss of corneal nerve fibers in the SBNP of the central cornea, [6][7][8][9][10][11]27,28 which has been associated with the severity of peripheral neuropathy, suggesting that this method can be used as an alternative marker of diabetic peripheral neuropathy. [6][7][8]10,11,28 A previous experimental study using CCM and immunohistochemical staining revealed that the SBNP exhibits no changes in type 1 diabetes, but is reduced in type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…In the last decade, corneal confocal microscopy (CCM) has been used to evaluate small nerve fibers in the cornea. Such studies have revealed that the density of nerve fibers in the subbasal nerve plexus (SBNP) correlates with the severity of diabetic neuropathy in human patients, [6][7][8][9][10][11] suggesting that such analyses represent an alternative, noninvasive marker of peripheral neuropathy in patients with diabetes.…”

mentioning

confidence: 99%

Extended Duration of Hyperglycemia Result in Human-Like Corneal Nerve Lesions in Mice With Alloxan- and Streptozotocin-Induced Type 1 Diabetes

Ozaki

Terayama

Matsuura

2018

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Previous experimental studies assessing corneal nerves as a measure of the severity of diabetic peripheral neuropathy have yielded discordant results; this may have been due to the effect of the short duration of the induced diabetes. We investigated whether increases in the duration of hyperglycemia result in the development of corneal lesions in a mouse model of alloxan (AL)-or streptozotocin (STZ)-induced type 1 diabetes. We further determined whether corneal nerve fiber density, intraepidermal nerve fiber density (IENFD), and sural nerve morphology can be used as morphologic markers of diabetic peripheral neuropathy in rodent models. METHODS. A total of 30 female ICR mice were divided into three groups: those with STZinduced (STZ group) and AL-induced (AL group) diabetes, and a control group. Hyperglycemia was maintained in diabetic mice for 35 weeks. Animals were euthanized at 41 weeks of age. RESULTS. Subbasal nerve plexus density (SBNPD) and terminal epithelial nerve density (TEND) in the cornea, as well as IENFD, were significantly lower, and mean sural nerve axon sizes were smaller in mice in the STZ and AL groups than in the control group. There were significant correlations between IENFD and SBNPD, and between IENFD and TEND. CONCLUSIONS. These results indicate that the TEND and SBNTD of the cornea may be useful morphologic markers for diabetic peripheral neuropathy.

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“…The estimated number of people experiencing the ocular discomfort due to dry eye disorder ranges from 25 till 30 million around the world (Patel and McGhee, 2013). It is more common in women especially over 50 years of age due to autoimmune diseases (Ostrovski et al, 2015). The frequency of dry eye disorder is more prevalent in older age groups (Edwards et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Effect of Blackberry in Managment of Dry Eye in Experimental Animal Model

Salem

Hassan

Badr

et al. 2018

Journal of Scientific Research in Science

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The present study was performed to investigate the protective effect of blackberry as polyphenolic compounds for managing dry eye in experimental animal model. Materials and Methods: The Blackberry was dried in air oven. Dry eye induced by atropine sulphate 1% drops (2 drops in each eye daily) for 2 months, blackberry was taken as 20 % of the main diet. Thirty two rabbits (1000-1300g) were divided into four groups: G1: healthy control, G2: dry eye, G3: normal fed on blackberry, G4: dry eye feed on blackberry. Poly phenolic compounds of blackberry were analyzed by using High Performance Liquid Chromatography (HPLC). Tear production measured using tear break up time (TBUT) and schirmer test. Tears were collected day after day from all groups using 5-μL silanated microcapillary pipettes. At the end of experiments rabbits were fasted overnight and blood was withdrawn. The levels of reduced glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO) and interlukin-1beta (IL-1β) were estimated in the tears and blood. In addition catalase (CAT) and superoxide dismutase (SOD) were determined in the blood. Cornea excised and examined by light microscope. Results: Significant improvements were noticed in tear breakup time and schirmer I score of dry eye rabbits fed on 20% dried blackberry compared to dry eye group. There was a significant (p < 0.05) decrease in serum and tears of IL-1β, NO and a statistically increase in the blood GSH, plasma CAT in dry eye rabbits fed on 20% dried blackberry compared to dry eye rabbit group. In conclusion: Supplementation with dried blackberry is effective against the dry eye syndrome by decreasing ocular inflammation and increasing antioxidant contents in tears of experimental animal model.

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Reproducibility of In Vivo Corneal Confocal Microscopy Using an Automated Analysis Program for Detection of Diabetic Sensorimotor Polyneuropathy

Cited by 11 publications

References 35 publications

Corneal confocal microscopy is a rapid reproducible ophthalmic technique for quantifying corneal nerve abnormalities

Corneal confocal microscopy is a rapid reproducible ophthalmic technique for quantifying corneal nerve abnormalities

Extended Duration of Hyperglycemia Result in Human-Like Corneal Nerve Lesions in Mice With Alloxan- and Streptozotocin-Induced Type 1 Diabetes

Effect of Blackberry in Managment of Dry Eye in Experimental Animal Model

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