Corneal Confocal Microscopy to Image Small Nerve Fiber Degeneration: Ophthalmology Meets Neurology

Petropoulos, Ioannis N.; Bitirgen, Gülfidan; Ferdousi, Maryam; Kalteniece, Alise; Azmi, Shazli; D’Onofrio, Luca; Lim, Sze Hway; Ponirakis, Georgios; Khan, Adnan; Gad, Hoda; Mohammed, Ibrahim; Mohammadi, Yacob E.; Malik, Ayesha; Gosal, David; Kobylecki, Christopher; Silverdale, Monty; Soran, Handrean; Alam, Uazman; Malik, Rayaz A.

doi:10.3389/fpain.2021.725363

Cited by 20 publications

(15 citation statements)

References 126 publications

(125 reference statements)

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“…Similar to nerve fiber density in skin, this technique assesses corneal nerve fiber density. In addition, branch density, fiber length, and inferior whorl length can be assessed (Lukashenko et al, 2021;Petropoulos et al, 2021). Compared to skin biopsies, CCM has the advantage that it is non-invasive.…”

Section: Corneal Confocal Microscopymentioning

confidence: 99%

Measuring pain and nociception: Through the glasses of a computational scientist. Transdisciplinary overview of methods

Kutafina

Becker²,

Namer³

2023

Front. Netw. Physiol.

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In a healthy state, pain plays an important role in natural biofeedback loops and helps to detect and prevent potentially harmful stimuli and situations. However, pain can become chronic and as such a pathological condition, losing its informative and adaptive function. Efficient pain treatment remains a largely unmet clinical need. One promising route to improve the characterization of pain, and with that the potential for more effective pain therapies, is the integration of different data modalities through cutting edge computational methods. Using these methods, multiscale, complex, and network models of pain signaling can be created and utilized for the benefit of patients. Such models require collaborative work of experts from different research domains such as medicine, biology, physiology, psychology as well as mathematics and data science. Efficient work of collaborative teams requires developing of a common language and common level of understanding as a prerequisite. One of ways to meet this need is to provide easy to comprehend overviews of certain topics within the pain research domain. Here, we propose such an overview on the topic of pain assessment in humans for computational researchers. Quantifications related to pain are necessary for building computational models. However, as defined by the International Association of the Study of Pain (IASP), pain is a sensory and emotional experience and thus, it cannot be measured and quantified objectively. This results in a need for clear distinctions between nociception, pain and correlates of pain. Therefore, here we review methods to assess pain as a percept and nociception as a biological basis for this percept in humans, with the goal of creating a roadmap of modelling options.

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Section: Corneal Confocal Microscopymentioning

confidence: 99%

Measuring pain and nociception: Through the glasses of a computational scientist. Transdisciplinary overview of methods

Kutafina

Becker²,

Namer³

2023

Front. Netw. Physiol.

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“…We have pioneered the technique of corneal confocal microscopy (CCM), a rapid non‐invasive ophthalmic imaging technique that enables quantification of corneal nerve morphology as a surrogate imaging marker for neurodegeneration in a range of peripheral neuropathies 12 and central neurodegenerative diseases 13 . We have previously shown evidence of corneal nerve loss in participants with MCI and dementia and demonstrated that CCM had a better diagnostic capability for identifying people with MCI compared to MRI brain volumetry 14–16 .…”

Section: Introductionmentioning

confidence: 99%

Corneal nerve loss predicts dementia in patients with mild cognitive impairment

Ponirakis

Hamad

Omar

et al. 2023

Ann Clin Transl Neurol

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Objectives This study compared the utility of corneal nerve measures with brain volumetry for predicting progression to dementia in individuals with mild cognitive impairment (MCI). Methods Participants with no cognitive impairment (NCI) and MCI underwent assessment of cognitive function, brain volumetry of thirteen brain structures, including the hippocampus and corneal confocal microscopy (CCM). Participants with MCI were followed up in the clinic to identify progression to dementia. Results Of 107 participants with MCI aged 68.4 ± 7.7 years, 33 (30.8%) progressed to dementia over 2.6‐years of follow‐up. Compared to participants with NCI (n = 12), participants who remained with MCI (n = 74) or progressed to dementia had lower corneal nerve measures (p < 0.0001). Progressors had lower corneal nerve measures, hippocampal, and whole brain volume (all p < 0.0001). However, CCM had a higher prognostic accuracy (72%–75% vs 68%–69%) for identifying individuals who progressed to dementia compared to hippocampus and whole brain volume. The adjusted odds ratio for progression to dementia was 6.1 (95% CI: 1.6–23.8) and 4.1 (95% CI: 1.2–14.2) higher with abnormal CCM measures, but was not significant for abnormal brain volume. Interpretation Abnormal CCM measures have a higher prognostic accuracy than brain volumetry for predicting progression from MCI to dementia. Further work is required to validate the predictive ability of CCM compared to other established biomarkers of dementia.

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“…Recent studies utilizing CCM in patients with central neurodegenerative disease have challenged long‐held beliefs that neurodegeneration only occurs centrally. Thus, corneal nerve loss occurs in amyotrophic lateral sclerosis and has been associated with neurological disability, especially in patients with bulbar involvement [2]. In Parkinson's disease corneal nerve loss is associated with autonomic and motor disability, and more rapid motor deterioration at follow‐up [3].…”

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confidence: 99%

“…Furthermore, corneal nerve loss precedes and predicts the development of clinically‐defined diabetic neuropathy, progressively worsens with increasing neuropathic severity, and is greater in painful diabetic neuropathy. In clinical trials, early corneal nerve regeneration precedes improvement in symptoms and nerve conduction [2]. Both intra‐epidermal nerve fibre density and corneal nerve loss have been reported in a range of peripheral neuropathies including chronic inflammatory demyelinating polyradiculoneuropathy, amyloid neuropathy, chemotherapy induced peripheral neuropathy and human immunodeficiency virus‐associated sensory neuropathy [2].…”

mentioning

confidence: 99%

“…In clinical trials, early corneal nerve regeneration precedes improvement in symptoms and nerve conduction [2]. Both intra‐epidermal nerve fibre density and corneal nerve loss have been reported in a range of peripheral neuropathies including chronic inflammatory demyelinating polyradiculoneuropathy, amyloid neuropathy, chemotherapy induced peripheral neuropathy and human immunodeficiency virus‐associated sensory neuropathy [2].…”

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