Standardized Baseline Human Corneal Subbasal Nerve Density for Clinical Investigations With Laser-Scanning in Vivo Confocal Microscopy

Parissi, Marlen; Karanis, Georgios; Randjelovic, Stefan; Germundsson, Johan; Poletti, Enea; Ruggeri, Alfredo; Utheim, Tor Paaske; Lagali, Neil

doi:10.1167/iovs.13-12999

Cited by 82 publications

(76 citation statements)

References 38 publications

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“…Quantitative assessment of CNFL is regarded as the single most reliable parameter of SBP structural and functional integrity. 24 In the present study, using our quantification software, the mean CNFL value in the IVCM images (21.7 17 The median CNFL values calculated in this study by histology is approximately two times greater than previous high estimates (21.6 ± 5.98 and 25.9 ± 7.0 mm/mm 2 ) based on IVCM observations. 25,26 One explanation for these higher values seen by histology is that the immunochemical staining method dependably detects small diameter sub-basal nerves and interconnecting axons that are too thin or faint to be imaged reliably by IVCM.…”

Section: Discussioncontrasting

confidence: 47%

“…25,26 One explanation for these higher values seen by histology is that the immunochemical staining method dependably detects small diameter sub-basal nerves and interconnecting axons that are too thin or faint to be imaged reliably by IVCM. 24 IVCM, with a limited lateral resolution of 1-2 μm, 27 enables enface imaging of the SBP and its nerve fiber bundles. In contrast, the β-III-tubulin immunohistochemical staining method, by exploiting the phenomenon of histochemical amplification of the avidin-biotinhorseradish peroxidase complex methodology and a strong 'signal to noise' ratio, is able to detect more minute patterns of corneal SBP anatomy including very small diameter nerve fiber bundles, interconnecting single nerve fiber branches and their connection points (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

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Comparative quantitative assessment of the human corneal sub-basal nerve plexus by in vivo confocal microscopy and histological staining

Kowtharapu

Winter

Marfurt

et al. 2016

Eye

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Purpose This study was designed to compare and contrast quantitative data of the human corneal sub-basal nerve plexus (SBP) evaluated by two different methods: in vivo confocal microscopy (IVCM), and immunohistochemical staining of ex vivo donor corneas. Methods Seven parameters of the SBP in large-scale IVCM mosaicking images from healthy subjects were compared with the identical parameters in ex vivo donor corneas stained by β-III-tubulin immunohistochemistry. Corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), average weighted corneal nerve fiber tortuosity (CNFTo), corneal nerve connection points (CNCP), average corneal nerve single-fiber length (CNSFL), and average weighted corneal nerve fiber thickness (CNFTh) were calculated using a dedicated, published algorithm and compared.

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Section: Discussioncontrasting

confidence: 47%

Section: Discussionmentioning

confidence: 99%

Comparative quantitative assessment of the human corneal sub-basal nerve plexus by in vivo confocal microscopy and histological staining

Kowtharapu

Winter

Marfurt

et al. 2016

Eye

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“…Prior studies also typically include subjects widely varying in age, although age is known to impact the SBP. 17,20 Moreover, an image sampling-based strategy is sensitive to selection criteria, the disease state of the SBP, and observer experience/masking. As a result, nerve fiber length density values in various cohorts differ across studies, and it has been noted in systematic reviews that better standardization of methods is required for clinical adoption of IVCM to assess pathologic levels of nerve length density.…”

Section: Resultsmentioning

confidence: 99%

“…Raw image sets obtained by IVCM examination underwent processing by automated methods to produce depth-corrected widearea mosaics with continuous nerve fiber paths and nerve and background intensity levels, as previously reported. 4 Also, nerves in mosaics were traced both manually and by a fully automated method 20 to quantify the total mosaic nerve fiber length density (mCNFL) and nerve fiber length density in the inferocentral whorl region (wCNFL). The total length of all traced nerves in a mosaic was divided by the mosaic area containing subbasal plexus in mm 2 , yielding the mosaic corneal subbasal nerve fiber length density (mCNFL) in mm/ mm 2 .…”

Section: Confocal Microscopy and Mosaic Image Generation And Analysismentioning

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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“…Other studies evaluating the density of fibers per field are shown in Table 3 4, 10,11,12 . Only studies using the same methodology employed here were included.…”

Section: Discussionmentioning

confidence: 99%

Corneal confocal microscopy in a healthy Brazilian sample

Dieckmann

Pupe

Nascimento

2015

Arq. Neuro-Psiquiatr.

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Objective This study aims to evaluate the characteristics of the corneal sub-basal plexus by performing in vivo confocal microscopy of healthy Brazilians to provide reference values for the Brazilian population. Method This study is an observational, cross-sectional, descriptive study comparing corneas from 55 healthy Brazilian individuals across the age span of 20-70 years. Results The average number of fibers was 5.35 ± 1.36, fiber density was 33.4 ± 8.5 fibers per field, and the mean number of Langerhans cells was 5.13 ± 8.10. A correlation between the average number of fibers and age showed an inverse relationship between the number and density of fibers and age for women (p < 0.05). In the multivariate analysis, each annual increase of age showed an average increase of 1.017 (95%CI: 1.008 to 1.026) in the number of Langerhans cells, adjusting for sex and thickness. Conclusion Compared to other samples, this Brazilian population showed a higher average number of fibers, though further studies with a larger sample should be performed.

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Standardized Baseline Human Corneal Subbasal Nerve Density for Clinical Investigations With Laser-Scanning in Vivo Confocal Microscopy

Abstract: A baseline human corneal subbasal nerve density has been determined by laser-scanning IVCM using rigorous methods. The methods and results could aid in the future assessment of corneal nerves in various patient populations.

Cited by 82 publications

References 38 publications

Comparative quantitative assessment of the human corneal sub-basal nerve plexus by in vivo confocal microscopy and histological staining

Comparative quantitative assessment of the human corneal sub-basal nerve plexus by in vivo confocal microscopy and histological staining

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

Corneal confocal microscopy in a healthy Brazilian sample

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