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Clinical and in vivo confocal microscopic features of neuropathic corneal pain
  1. Andrew R Ross1,
  2. Mouhamed Ali Al-Aqaba1,
  3. Amna Almaazmi1,
  4. Marco Messina1,
  5. Mario Nubile2,
  6. Leonardo Mastropasqua2,
  7. Harminder S Dua1,
  8. Dalia G Said1,3
  1. 1 Academic Ophthalmology, Division of Clinical Neurosciences, The University of Nottingham, Nottingham, UK
  2. 2 Department of Medicine and Aging Science, University Gabriele d'Annunzio of Chieti Pescara, Chieti, Italy
  3. 3 Ophthalmology Department, Nottingham University Hospitals NHS Trust, Nottingham, UK
  1. Correspondence to Professor Harminder S Dua, Ophthalmology, University of Nottingham, Nottingham NG7 2UH, UK; harminder.dua{at}


Aims To describe clinical and in vivo confocal microscopy (IVCM) features of neuropathic corneal pain (NCP) without clinically visible signs.

Methods Prospective, observational study of 27 eyes of 14 patients who had continuous severe ocular pain for one or more years, with minimal or no ocular surface signs and were non-responsive to topical lubricants, steroids and/or ciclosporin. All patients were evaluated using Ocular Surface Disease Index, Oxford grading scale, Schirmer test 1, Cochet Bonnet esthesiometry and response to topical anaesthesia. Central and paracentral regions of the cornea of patients and seven healthy controls were studied by IVCM. Corneal epithelial thickness and sub-basal nerve density were measured in patients and controls.

Results Four patients responded to topical anaesthesia (responsive group (RG)), indicating peripheral NCP while 10 patients did not show any improvement (non-responsive group (NRG)), indicating central NCP. Schirmer-1 test was within normal limits in the RG but significantly greater in the NRG (p<0.001). None of the other clinical parameters nor corneal epithelial thickness were statistically significantly different. The sub-basal nerve density was significantly reduced (p<0.008) in patients compared with controls. Stroma of all patients demonstrated activated keratocytes and spindle, lateral and stump microneuromas. There was a statistically significant greater number of microneuromas (p<0.0001) and activated keratocytes in RG compared with NRG.

Conclusion NCP without visible clinical signs does not represent typical dry eye disease. Distinct signs demonstrated on IVCM suggest that peripheral NCP, which responds to topical anaesthesia, and central NCP, which does not, are separate entities.

  • cornea
  • imaging
  • ocular surface
  • diagnostic tests/investigation

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  • ARR and MAA-A are joint first authors.

  • HSD and DGS are joint senior authors.

  • Correction notice This paper has been amended since it was published Online First. The third author's name has been corrected.

  • Contributors HSSD, DGS, MAA-A and ARR conceived the study and performed the clinical examination. MAA-A carried out the IVCM examination of subjects. AA, MM, MN and LM contributed to data analysis and revision of the manuscript. HSSD, DGS, MAA-A and ARR contributed to design of the work; analysis and interpretation of data, drafting the work. All authors read and approved the final manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Disclaimer HSD: Honoraria and Travel expenses from Dompe, Croma, Santen, Allergan, Thea. Shares in NuVision and Glaxosmithkline.

  • Competing interests None declared.

  • Patient consent for publication Not required.

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

  • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.

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