Article Text

Download PDFPDF
Identification of presumed corneal neuromas and microneuromas using laser-scanning in vivo confocal microscopy: a systematic review
  1. Holly Rose Chinnery1,
  2. Rajni Rajan1,
  3. Haihan Jiao1,
  4. Mengliang Wu1,
  5. Alexis Ceecee Zhang1,
  6. Manikkuwadura Eranda Harshan De Silva1,
  7. Eve Makrai1,
  8. Mary Ann Stepp2,
  9. Nick Di Girolamo3,
  10. Laura Elizabeth Downie1
  1. 1 Department of Optometry and Vision Sciences, The University of Melbourne, Parkville, Victoria, Australia
  2. 2 School of Medicine & Health Sciences, The George Washington University, Washington, DC, USA
  3. 3 School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia
  1. Correspondence to Associate Professor Laura Elizabeth Downie, Department of Optometry and Vision Sciences, The University of Melbourne, Carlton, VIC 3053, Australia; ldownie{at}


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.

  • cornea
  • imaging

Data availability statement

Data are available upon reasonable request to the corresponding author (Associate Professor Laura Downie,

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Data availability statement

Data are available upon reasonable request to the corresponding author (Associate Professor Laura Downie,

View Full Text


  • Twitter @DrLauraDownie

  • Contributors HRC, MAS, NDG and LED conceived and designed the work. HRC, RR, HJ, MW, ACZ, MEHDS, EM and LED undertook the acquisition and analysis of the data. All authors contributed to interpretation of the data. LED drafted the work, with all other authors revising and/or critically evaluating it for intellectual content.

  • Funding National Health and Medical Research Council of Australia APP1126540 (HRC); Rebecca L Cooper Medical Foundation (LED); NIH/NEI EY08512 (MAS); National Health and Medical Research Council of Australia, APP1101078 and APP1156944 (ND). The funding organisations had no role in the design or conduct of this work.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

Linked Articles

  • At a glance
    Frank Larkin