scholarly journals Laser scanning in vivo confocal microscopy (IVCM) for evaluating human corneal sub-basal nerve plexus parameters: protocol for a systematic review

BMJ Open ◽  
2017 ◽  
Vol 7 (11) ◽  
pp. e018646 ◽  
Author(s):  
Manikkuwadura Eranda Harshan De Silva ◽  
Alexis Ceecee Zhang ◽  
Amalia Karahalios ◽  
Holly Rose Chinnery ◽  
Laura Elizabeth Downie

IntroductionLaser scanning in vivo confocal microscopy (IVCM) enables non-invasive, high-resolution imaging of the cornea. In recent years, there has been a vast increase in researchers using laser scanning IVCM to image and quantify corneal nerve parameters. However, a range of methodological approaches have been adopted. The primary aim of this systematic review is to critically appraise the reported method(s) of primary research studies that have used laser scanning IVCM to quantify corneal sub-basal nerve plexus (SBNP) parameters in humans, and to examine corneal nerve parameters in healthy individuals.Methods and analysisA systematic review of primary studies that have used laser scanning IVCM to quantify SBNP parameters in humans will be conducted. Comprehensive electronic searches will be performed in Ovid MedLine, Embase and the Cochrane Library. Two reviewers will independently assess titles and abstracts, and exclude studies not meeting the inclusion criteria. For studies judged eligible or potentially eligible, full texts will be independently assessed by two reviewers to determine eligibility. A third reviewer will resolve any discrepancies in judgement. Risk of bias will be assessed using a custom tool, covering five methodological domains: participant selection, method of image capture, method of image analysis, data reporting and other sources of bias. A systematic narrative synthesis of findings will be provided. A multilevel random-effects meta-analysis will be performed for corneal nerve parameters derived from healthy participants. This review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.Ethics and disseminationAs this review considers published data, ethical approval is not required. We foresee that this synthesis will serve as a reference for future studies, and can be used to inform best practice standards for using IVCM in clinical research. A manuscript reporting the results of the review will be published and may also be presented at scientific conferences.

2021 ◽  
pp. bjophthalmol-2020-318156
Author(s):  
Holly Rose Chinnery ◽  
Rajni Rajan ◽  
Haihan Jiao ◽  
Mengliang Wu ◽  
Alexis Ceecee Zhang ◽  
...  

Background/aimsThis systematic review critically evaluated peer-reviewed publications describing morphological features consistent with, or using terms related to, a ‘neuroma’ or ‘microneuroma’ in the human cornea using laser-scanning in vivo confocal microscopy (IVCM).MethodsThe review was prospectively registered on PROSPERO (CRD42020160038). Comprehensive literature searches were performed in Ovid MEDLINE, Ovid Embase and the Cochrane Library in November 2019. The review included primary research studies and reviews that described laser-scanning IVCM for examining human corneal nerves. Papers had to include at least one of a pre-specified set of keyword stems, broadly related to neuromas and microneuromas, to describe a corneal nerve feature.ResultsTwenty-five papers (20 original studies; 5 reviews) were eligible. Three original studies evaluated corneal nerve features in healthy eyes. Most papers assessed corneal nerves in ocular and systemic conditions; seven studies did not include a control/comparator group. There was overlap in terminology used to describe nerve features in healthy and diseased corneas (eg, bulb-like/bulbous, penetration, end/s/ing). Inspection of IVCM images within the papers revealed that features termed ‘neuromas’ and ‘microneuromas’ could potentially be physiological corneal stromal-epithelial nerve penetration sites. We identified inconsistent definitions for terms, and limitations in IVCM image acquisition, sampling and/or reporting that may introduce bias and lead to inaccurate representation of physiological nerve characteristics as pathological.ConclusionThese findings identify a need for consistent nomenclature and definitions, and rigorous IVCM scanning and analysis protocols to clarify the prevalence of physiological, as opposed to pathological, corneal nerve features.


2020 ◽  
pp. bjophthalmol-2019-315449 ◽  
Author(s):  
Giuseppe Giannaccare ◽  
Federico Bernabei ◽  
Marco Pellegrini ◽  
Fabio Guaraldi ◽  
Federica Turchi ◽  
...  

AimsTo evaluate bilateral morphometric changes of corneal sub-basal nerve plexus (CSNP) occurring after unilateral cataract surgery by in vivo confocal microscopy (IVCM) images analysed with automated software.MethodsIVCM was performed before (V0) and 1 month after surgery (V1) in both operated eyes (OEs) and unoperated eyes (UEs) of 30 patients. Thirty age and sex-matched subjects acted as controls. Corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD), corneal nerve fibre length (CNFL), corneal nerve total branch density (CTBD), corneal nerve fibre area (CNFA), corneal nerve fibre width, corneal nerve fractal dimension (CNFrD) and dendritic cells density were calculated.ResultsMean CNFD, CNBD, CNFL, CTBD, CNFA and CNFrD significantly decreased at V1 versus V0 in both eyes (respectively, 15.35±7.00 vs 21.21±6.56 n/mm2 in OEs and 20.11±6.69 vs 23.20±7.26 in UEs; 13.57±12.16 vs 26.79±16.91 n/mm2 in OEs and 24.28±14.88 vs 29.76±15.25 in UEs; 9.67±3.44 mm/mm2 vs 13.49±3.42 in OEs and 12.53±3.60 vs 14.02±3.82 in UEs; 22.81±18.77 vs 42.25±24.64 n/mm2 in OEs and 38.06±20.52 vs 43.93±22.27 in UEs; 0.0040±0.0021 vs 0.0058±0.0020 mm2/mm2 in OEs and 0.0049±0.0016 vs 0.0057±0.0019 in UEs; 1.418±0.058 vs 1.470±0.037 in OEs and 1.466±0.040 vs 1.477±0.036 in UEs; always p<0.049).ConclusionPatients undergoing cataract surgery exhibit bilateral alterations of CSNP. This finding could have broad implications in the setting of sequential cataract surgery.


2020 ◽  
pp. 112067212096412
Author(s):  
Marco Pellegrini ◽  
Stefano Sebastiani ◽  
Lorenzo Tucci ◽  
Giuseppe Giannaccare ◽  
Simona Moscatiello ◽  
...  

Purpose: The effect of long-term glycemic variability upon corneal sub-basal nerve plexus (CSNP) morphology analyzed by in vivo confocal microscopy (IVCM) has been poorly investigated in the setting of type 1 diabetes mellitus (T1DM). Our purpose was to analyze the association between morphometric parameters of CSNP and new markers of glycemic variability in a population of patients with T1DM. Methods: Forty patients with T1DM underwent: assessment of diabetic neuropathy (DN); analysis of subcutaneous advanced glycated end-products; IVCM scans of CSNP. The fully automated software ACCMetrics was employed to analyze IVCM images and calculate seven corneal nerve parameters. Data of diabetes duration, mean and standard deviation (SD) of either last-year and all-time glycated hemoglobin (HbA1C) were retrieved. Results: Diabetes duration and all-time SD of HbA1C were independently associated with CNFD (R = –0.26, p = 0.01; R = –0.27, p = 0.047 respectively), CNFL (R = –0.12; p = 0.01; R = –0.17, p = 0.01 respectively) and CNFrD (R = –0.001, p = 0.009; R = –0.002, p = 0.007 respectively). The analysis of the association among IVCM parameters and specific subtypes of DN showed that altered cold sensitivity was independently associated with CNFD (B = –0.24, p = 0.01), CNFL (B = –0.46, p = 0.01) and CNFrD (B = –28.65, p = 0.03). Conclusions: All-time SD of HbA1C and disease duration were found to be independent predictors of damage to CSNP in patients with T1DM.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jaya D. Chidambaram ◽  
Namperumalsamy V. Prajna ◽  
Srikanthi Palepu ◽  
Shruti Lanjewar ◽  
Manisha Shah ◽  
...  

2018 ◽  
Vol 29 (5) ◽  
pp. 555-560 ◽  
Author(s):  
Luca Terracciano ◽  
Michela Cennamo ◽  
Eleonora Favuzza ◽  
Litasova Julia ◽  
Orsola Caporossi ◽  
...  

Purpose: To evaluate, through the in vivo confocal microscopy, the pathological changes of each corneal layer in eyes affected by pseudoexfoliation syndrome. Methods: We studied 40 eyes of 40 patients with diagnosis of unilateral senile cataract associated with pseudoexfoliation syndrome and 40 eyes of 40 control subjects with senile cataract without pseudoexfoliation syndrome. All patients underwent a complete ophthalmic examination including best corrected visual acuity, slit-lamp examination, corneal sensitivity measurement using a Cochet-Bonnet nylon thread esthesiometer, and anterior segment optical coherence tomography (Visante OCT, Carl Zeiss Meditec AG, Germany); in vivo confocal microscopy of corneal sections (endothelium, stroma, sub-basal nerve plexus, and superficial and basal epithelium) was performed with the ConfoScan 4.0 (Nidek, Japan). Results: In pseudoexfoliation syndrome group, the mean corneal sensitivity was 44.1 ± 1.3 mm and in the control group was 55.6 ± 4.7 mm. The corneas of the eyes with pseudoexfoliation syndrome were significantly less sensitive than those of control group eyes (p < 0.001). Pseudoexfoliation syndrome eyes had a lower nerve density and less nerve beadings and a higher degree of tortuosity in sub-basal plexus compared to the control group. The cell density of epithelial and endothelial layers was significantly lower in pseudoexfoliation syndrome eyes than controls. In 80% of pseudoexfoliation syndrome eyes, we found activated keratocytes and inflammatory cells in the anterior stroma. Conclusion: Our study demonstrates the morpho-structural corneal alterations in eyes affected by pseudoexfoliation syndrome, using corneal in vivo confocal microscopy as a non-invasive and high-reproducible technique to evaluate pathophysiology of each corneal layer; the sub-basal nerve plexus alterations are correlated with the lower corneal sensitivity.


Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 970 ◽  
Author(s):  
Gloria Ravegnini ◽  
Sarah Cargnin ◽  
Giulia Sammarini ◽  
Federica Zanotti ◽  
Justo Lorenzo Bermejo ◽  
...  

Background: A wealth of evidence has shown that microRNAs (miRNAs) can modulate specific genes, increasing our knowledge on the fine-tuning regulation of protein expression. miR-221 and miR-222 have been frequently identified as deregulated across different cancer types; however, their prognostic significance in cancer remains controversial. In view of these considerations, we performed an updated systematic review and meta-analysis of published data investigating the effects of miR-221/222 on overall survival (OS) and other secondary outcomes among cancer patients. A systematic search of PubMed, Web of Knowledge, and Cochrane Library databases was performed. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to assess the strength of association. Results: Fifty studies, analyzing 6086 patients, were included in the systematic review. Twenty-five studies for miR-221 and 17 studies for miR-222 which assessed OS were included in the meta-analysis. High expression of miR-221 and miR-222 significantly predicted poor OS (HR: 1.48, 95% CI: 1.14–1.93, p = 0.003 and HR: 1.90, 95% CI: 1.43–2.54, p < 0.001, respectively). Subgroup analysis revealed that the finding on miR-221 was not as robust as the one on miR-222. Furthermore, high miR-222 expression was also associated with worse progression-free survival and disease-free survival pooled with recurrence-free survival. Conclusions: The meta-analysis demonstrated that high expression of miR-222 is associated with poor prognosis in cancer patients, whereas the significance of miR-221 remains unclear. More work is required to fully elucidate the role of miR-221 and miR-222 in cancer prognosis, particularly in view of the limitations of existing results, including the significant heterogeneity and limited number of studies for some cancers.


2011 ◽  
Vol 52 (9) ◽  
pp. 5022 ◽  
Author(s):  
Stephan Allgeier ◽  
Andrey Zhivov ◽  
Franz Eberle ◽  
Bernd Koehler ◽  
Susanne Maier ◽  
...  

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