Corneal confocal microscopy identifies a reduction in corneal keratocyte density and sub-basal nerves in children with type 1 diabetes mellitus

Gad, Hoda; Al-Jarrah, Bara; Saraswathi, Saras; Mohamed, Sara Elamin Osman; Kalteniece, Alise; Petropoulos, Ioannis N.; Khan, Adnan; Ponirakis, Georgios; Singh, Parul; Khodor, Souhaila Al; Elawad, Mamoun; Almasri, Wesam; Hendaus, Mohamed A.; Akobeng, Anthony K; Hussain, Khalid; Malik, Rayaz A.

doi:10.1136/bjophthalmol-2021-319057

Cited by 9 publications

(8 citation statements)

References 35 publications

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“…This may reflect the range of altered sensory phenotypes with both hypo and hyper responsiveness in ASD. We show reduced tortuosity of the corneal nerves in subjects with ASD, comparable to children with celiac disease [ 23 ], but this contrasts with studies showing increased tortuosity in adults with diabetic neuropathy [ 42 ] and no change in children with type 1 diabetes [ 25 ]. This reduced nerve fibre tortuosity may represent an alteration in corneal nerve morphology which may be unique to subjects with ASD.…”

Section: Discussioncontrasting

confidence: 80%

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Corneal confocal microscopy demonstrates sensory nerve loss in children with autism spectrum disorder

Khan,

Kamal,

Alhothi

et al. 2023

PLoS ONE

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Autism spectrum disorder (ASD) is a developmental disorder characterized by difficulty in communication and interaction with others. Postmortem studies have shown cerebral neuronal loss and neuroimaging studies show neuronal loss in the amygdala, cerebellum and inter-hemispheric regions of the brain. Recent studies have shown altered tactile discrimination and allodynia on the face, mouth, hands and feet and intraepidermal nerve fiber loss in the legs of subjects with ASD. Fifteen children with ASD (age: 12.00 ± 3.55 years) and twenty age-matched healthy controls (age: 12.83 ± 1.91 years) underwent corneal confocal microscopy (CCM) and quantification of corneal nerve fiber morphology. Corneal nerve fibre density (fibers/mm2) (28.61 ± 5.74 vs. 40.42 ± 8.95, p = 0.000), corneal nerve fibre length (mm/mm2) (16.61 ± 3.26 vs. 21.44 ± 4.44, p = 0.001), corneal nerve branch density (branches/mm2) (43.68 ± 22.71 vs. 62.39 ± 21.58, p = 0.018) and corneal nerve fibre tortuosity (0.037 ± 0.023 vs. 0.074 ± 0.017, p = 0.000) were significantly lower and inferior whorl length (mm/mm2) (21.06 ± 6.12 vs. 23.43 ± 3.95, p = 0.255) was comparable in children with ASD compared to controls. CCM identifies central corneal nerve fiber loss in children with ASD. These findings, urge the need for larger longitudinal studies to determine the utility of CCM as an imaging biomarker for neuronal loss in different subtypes of ASD and in relation to disease progression.

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Section: Discussioncontrasting

confidence: 80%

“…We have pioneered the use of corneal confocal microscopy (CCM) to demonstrate corneal nerve loss in a range of peripheral [ 18 , 19 ] and central [ 20 – 22 ] neurodegenerative diseases. Furthermore, we and others have shown corneal nerve fiber loss in children with diabetic neuropathy [ 23 – 25 ].…”

Section: Introductionmentioning

confidence: 85%

Corneal confocal microscopy demonstrates sensory nerve loss in children with autism spectrum disorder

Khan,

Kamal,

Alhothi

et al. 2023

PLoS ONE

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“…Quality rating scores ranged from 5 to 9 (mean: 7.24, SD : 1.04). Thus, a total of 37 studies were eligible for the final meta-analysis which included 1,423 patients and 1,059 healthy controls ( 16 , 27 – 61 ).…”

Section: Resultsmentioning

confidence: 99%

Corneal in vivo Confocal Microscopy for Assessment of Non-Neurological Autoimmune Diseases: A Meta-Analysis

Liu

et al. 2022

Front. Med.

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PurposeThis study aimed to evaluate the features of corneal nerve with in vivo confocal microscopy (IVCM) among patients with non-neurological autoimmune (NNAI) diseases.MethodsWe systematically searched PubMed, Web of Science, and Cochrane Central Register of Controlled Trials for studies published until May 2021. The weighted mean differences (WMDs) of corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), tortuosity, reflectivity, and beadings per 100 μm with a 95% CI between NNAI and control group were analyzed using a random-effects model.ResultsThe results showed 37 studies involving collective totals of 1,423 patients and 1,059 healthy controls were ultimately included in this meta-analysis. The pooled results manifested significantly decreased CNFL (WMD: −3.94, 95% CI: −4.77–−3.12), CNFD (WMD: −6.62, 95% CI: −8.4–−4.85), and CNBD (WMD: −9.89, 95% CI: −14–−5.79) in NNAI patients. In addition, the NNAI group showed more tortuous corneal nerve (WMD: 1.19, 95% CI:0.57–1.81). The comparison between NNAI patients and healthy controls in beadings per 100 μm corneal nerve length was inconsistent. No significant difference was found in the corneal nerve fiber reflectivity between NNAI and the control group (WMD: −0.21, 95% CI: −0.65–0.24, P = 0.361).ConclusionsThe parameters and morphology of corneal nerves observed by IVCM proved to be different in NNAI patients from healthy controls, suggesting that IVCM may be a non-invasive technique for identification and surveillance of NNAI diseases.

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“…Otherwise, it was completely or partially invisible because of corneal scarring, which is mostly related to exposure keratopathy. Reductions in sub-basal nerves have also been described in congenital diseases, such as congenital corneal anesthesia (CCA) and corneal dystrophies, and acquired diseases, such as dry eye, diabetes, and infectious keratitis, as well as herpes simplex, and bacterial, fungal, and Acanthamoeba keratitis [ 38 , 39 , 40 , 41 ]. In ichthyoses, nerve plexus abnormalities may be caused by dry eyes, keratopathy, excessive scarring, and limbal stem cell deficiency.…”

Section: Discussionmentioning

confidence: 99%

Advanced Anterior Eye Segment Imaging for Ichthyosis

Micińska,

Nowińska,

Teper

et al. 2023

JCM

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The purpose of this study was to describe ocular surface and anterior eye segment findings in various types of ichthyoses. Methods: This was a single-center prospective observational study. The study group consisted of five patients (P1–P5) aged 13–66 years. Multimodal imaging was performed, including slit-lamp examinations, swept-source optical coherence tomography (SS-OCT), and in vivo confocal microscopy (IVCM). Results: All patients were diagnosed with moderate-to-severe dry eye disease (DED). The corneas showed a significant pattern of irregularity, with a significant difference between the corneal thickness at the apex (CAT) and the corneal thinnest thickness (CTT), exceeding 375 µm. Three patients were diagnosed with ectasia patterns based on SS-OCT. All patients showed abnormalities in at least one Fourier index parameter for at least one eye at 3 or 6 mm in the keratometric, anterior, or posterior analyses. IVCM examinations revealed changes in all corneal layers. Conclusions: By combining the results of multimodal imaging, we were able to detect preclinical abnormalities, distinguish characteristic changes common to ichthyosis, and reveal the depth and characteristics of corneal abnormalities. Therefore, patients with ichthyosis should be examined for DED and ectatic disorders early in clinical practice.

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Corneal confocal microscopy identifies a reduction in corneal keratocyte density and sub-basal nerves in children with type 1 diabetes mellitus

Cited by 9 publications

References 35 publications

Corneal confocal microscopy demonstrates sensory nerve loss in children with autism spectrum disorder

Corneal confocal microscopy demonstrates sensory nerve loss in children with autism spectrum disorder

Corneal in vivo Confocal Microscopy for Assessment of Non-Neurological Autoimmune Diseases: A Meta-Analysis

Advanced Anterior Eye Segment Imaging for Ichthyosis

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