Assessing the Reproducibility of Quantitative In Vivo Confocal Microscopy of Corneal Nerves in Different Corneal Locations

Kim, Gene; Singleton, J. Robinson; Mifflin, Mark D.; Digre, Kathleen B.; Porzio, Michael T.; Smith, A. Gordon

doi:10.1097/ico.0b013e31829dd7f8

Cited by 16 publications

(20 citation statements)

References 22 publications

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“…To date, different numbers of standard images have been analyzed by various research groups. 21,23,24,33 More recently, three to five images were suggested for the analysis at the Corneal Nerve Quantification consensus meeting in Rostock, Germany, March 17, 2013. However, to date it is not clear whether the nerve and DC densities in this sample number are comparable to the widefield composite map of the subbasal area.…”

Section: Discussionmentioning

confidence: 99%

“…To compensate for such a limited imaging area, multiple locations in the cornea are generally scanned and a number of representative images of the subbasal layer from these locations are used to estimate the density of nerves and DCs in the subbasal layer. 23,24 Alternatively, a wide-field mapping of composite images of a larger area has recently been employed for the subbasal layer. [25][26][27][28][29][30][31] The wide-field composite images are generated by mapping a number of the standard IVCM images manually or by using automated software.…”

Section: Purposementioning

confidence: 99%

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Comparison of Standard Versus Wide-Field Composite Images of the Corneal Subbasal Layer by In Vivo Confocal Microscopy

Kheirkhah

Müller

Mikolajczak

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To evaluate whether the densities of corneal subbasal nerves and epithelial immune dendritiform cells (DCs) are comparable between a set of three representative standard images of in vivo confocal microscopy (IVCM) and the wide-field mapped composite IVCM images.METHODS. This prospective, cross-sectional, and masked study included 110 eyes of 58 patients seen in a neurology clinic who underwent laser-scanning IVCM (Heidelberg Retina Tomograph 3) of the central cornea. Densities of subbasal corneal nerves and DCs were compared between the average of three representative standard images and the wide-field mapped composite images, which were reconstructed by automated mapping.RESULTS. There were no statistically significant differences between the average of three representative standard images (0.16 mm 2 each) and the wide-field composite images (1.29 6 0.64 mm 2 ) in terms of mean subbasal nerve density (17.10 6 6.10 vs. 17.17 6 5.60 mm/mm 2 , respectively, P ¼ 0.87) and mean subbasal DC density (53.2 6 67.8 vs. 49.0 6 54.3 cells/mm 2 , respectively, P ¼ 0.43). However, there were notable differences in subbasal nerve and DC densities between these two methods in eyes with very low nerve density or very high DC density.CONCLUSIONS. There are no significant differences in the mean subbasal nerve and DC densities between the average values of three representative standard IVCM images and wide-field mapped composite images. Therefore, these standard images can be used in clinical studies to accurately measure cellular structures in the subbasal layer.

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Section: Discussionmentioning

confidence: 99%

Section: Purposementioning

confidence: 99%

Comparison of Standard Versus Wide-Field Composite Images of the Corneal Subbasal Layer by In Vivo Confocal Microscopy

Kheirkhah

Müller

Mikolajczak

et al. 2015

Invest. Ophthalmol. Vis. Sci.

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“…Their axons synapse in the brainstem and subserve nociceptive, protective, and trophic functions . The sub‐basal corneal nerve plexus is a dynamic structure that is similar between the right and left eyes …”

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confidence: 99%

Chronic Migraine Is Associated With Reduced Corneal Nerve Fiber Density and Symptoms of Dry Eye

et al. 2015

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Background We used in vivo corneal confocal microscopy to investigate structural differences in the sub-basal corneal nerve plexus in chronic migraine patients and a normal population. We used a validated questionnaire and tests of lacrimal function to determine the prevalence of dry eye in the same group of chronic migraine patients. Activation of the trigeminal system is involved in migraine. Corneal nociceptive sensation is mediated by trigeminal axons that synapse in the gasserian ganglion and the brainstem, and serve nociceptive, protective, and trophic functions. Noninvasive imaging of the corneal sub-basal nerve plexus is possible with in vivo corneal confocal microscopy. Methods For this case–control study, we recruited chronic migraine patients and compared them with a sex- and age-similar group of control subjects. Patients with peripheral neuropathy, a disease known to be associated with a peripheral neuropathy, or prior corneal or intraocular surgery were excluded. Participants underwent in vivo corneal confocal microscopy using a Heidelberg Retinal Tomography III confocal microscope with a Rostock Cornea Module. Nerve fiber length, nerve branch density, nerve fiber density, and tortuosity coefficient were measured using established methodologies. Migraine participants underwent testing of basal tear production with proparacaine, corneal sensitivity assessment with a cotton-tip applicator, measurement of tear break-up time, and completion of a validated dry eye questionnaire. Results A total of 19 chronic migraine patients and 30 control participants completed the study. There were no significant differences in age or sex. Nerve fiber density was significantly lower in migraine patients compared with controls (48.4 ± 23.5 vs 71.0 ± 15.0 fibers/mm2, P < .001). Nerve fiber length was decreased in the chronic migraine group compared with the control group, but this difference was not statistically significant (21.5 ± 11.8 vs 26.8 ± 5.9 mm/mm2, P < .084). Nerve branch density was similar in the two groups (114.0 ± 92.4 vs 118.1 ± 55.9 branches/mm2, P < .864). Tortuosity coefficient and log tortuosity coefficient also were similar in the chronic migraine and control groups. All migraine subjects had symptoms consistent with a diagnosis of dry eye syndrome. Conclusions We found that in the sample used in this study, the presence of structural changes in nociceptive corneal axons lends further support to the hypothesis that the trigeminal system plays a critical role in the pathogenesis of migraine. In vivo corneal confocal microscopy holds promise as a biomarker for future migraine research as well as for studies examining alterations of corneal innervation. Dry eye symptoms appear to be extremely prevalent in this population. The interrelationships between migraine, corneal nerve architecture, and dry eye will be the subject of future investigations.

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“…The more sound "study-level reproducibility" involves the analysis of images obtained from repeated patient IVCCM examinations and is a more clinically relevant measure of reproducibility as it accounts for the variation inherent in conducting multiple examinations. Such study-level reproducibility was later reported for the manual analysis technique, which revealed ICC levels in the good to very good range (exceeding levels of 0.7) [22,37,38]; quantification of nerves in the inferior whorl region of the cornea has also shown good studylevel reproducibility. [39] However, to date, only the image-level reproducibility for automated image analysis has been reported (ICC level 1.0 indicating perfect reproducibility).…”

Section: Discussionmentioning

confidence: 89%

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

Ostrovski¹,

Lovblom²,

Farooqi³

et al. 2015

Canadian Journal of Diabetes

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Assessing the Reproducibility of Quantitative In Vivo Confocal Microscopy of Corneal Nerves in Different Corneal Locations

Cited by 16 publications

References 22 publications

Comparison of Standard Versus Wide-Field Composite Images of the Corneal Subbasal Layer by In Vivo Confocal Microscopy

Comparison of Standard Versus Wide-Field Composite Images of the Corneal Subbasal Layer by In Vivo Confocal Microscopy

Chronic Migraine Is Associated With Reduced Corneal Nerve Fiber Density and Symptoms of Dry Eye

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

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