Identification of presumed corneal neuromas and microneuromas using laser-scanning in vivo confocal microscopy: A systematic review

Holly Rose Chinnery, Rajni Rajan, Haihan Jiao, Mengliang Wu, Alexis Ceecee Zhang, Manikkuwadura Eranda Harshan De Silva, Eve Makrai, Mary Ann Stepp, Nick Di Girolamo, Laura Elizabeth Downie

Research output: Contribution to journalReview articlepeer-review

22 Citations (Scopus)


Background/aims This 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). Methods The 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. Results Twenty-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. Conclusion These 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.

Original languageEnglish
Pages (from-to)765-771
Number of pages7
JournalBritish Journal of Ophthalmology
Issue number6
Publication statusPublished - 1 Jun 2022
Externally publishedYes


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