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Treatment of neurotrophic keratopathy with minimally invasive corneal neurotisation: long-term clinical outcomes and evidence of corneal reinnervation
  1. Joseph Catapano1,2,3,
  2. Simon S M Fung3,4,5,
  3. William Halliday3,6,
  4. Cecilia Jobst2,
  5. Douglas Cheyne2,
  6. Emily S Ho1,
  7. Ronald M Zuker1,3,
  8. Gregory H Borschel1,2,3,
  9. Asim Ali3,4
  1. 1 Division of Plastic and Reconstructive Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
  2. 2 Program in Neurosciences and Mental Health, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
  3. 3 Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
  4. 4 Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada
  5. 5 Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles, California, USA
  6. 6 Department of Pathology, The Hospital for Sick Children, Toronto, Ontario, Canada
  1. Correspondence to Dr Asim Ali, Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; asim.ali{at}


Aim To report clinical outcomes and evidence of corneal innervation in patients with neurotrophic keratopathy (NK) treated with minimally invasive corneal neurotisation (MICN) using a sural nerve graft and donor sensory nerves from the face.

Methods Patients undergoing MICN at The Hospital for Sick Children, Toronto, Canada were prospectively recruited. Data on central corneal sensation (CCS, measured with Cochet-Bonnet aesthesiometer), best-corrected visual acuity (BCVA) and corneal epithelial integrity were collected. In four patients who subsequently underwent keratoplasty, immunohistochemical analysis was performed on the corneal explants. One patient underwent magnetoencephalography (MEG) after MICN to characterise the neurophysiological pathways involved.

Results Between November 2012 and February 2017, 19 eyes of 16 patients underwent MICN. Mean follow-up was 24.0±16.1 months (range, 6–53). Mean CCS significantly improved from 0.8±2.5 mm to 49.7±15.5 mm at final follow-up (p<0.001). Mean BCVA remained stable, and the number of episodes of corneal epithelial defects after MICN was significantly reduced compared with the year leading up to the procedure (21% vs 89%, respectively; p<0.0001). In the four eyes that underwent keratoplasties after MICN, all transplants fully re-epithelialised and regained sensation subsequently. Immunohistochemistry of the corneal explants demonstrated evidence of corneal reinnervation. In one patient who was 8 months after MICN, novel neuroactivity was detected on MEG in the ipsilateral somatosensory cortex on mechanical stimulation of the reinnervated cornea.

Conclusions By providing an alternative source of innervation, MICN improves corneal sensation and stabilises the corneal epithelium, permitting optical keratoplasty for patients with NK-related corneal opacity.

  • neurotrophic keratopathy
  • corneal sensation
  • neurotization
  • corneal neurotization

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  • JC and SSMF are joint first authors.

  • GHB and AA are joint senior authors.

  • JC and SSMF contributed equally.

  • Contributors JC and SSMF made equal contribution in the acquisition, analysis and interpretation of data, and in drafting and revising the manuscript of the study. WH, CJ and DC contributed in data acquisition and interpretation, namely the immunohistochemical analysis and magnetoencephalography. RMZ conducted the study. GHB and AA conducted the study, critically evaluated and approved the manuscript, and are the guarantors of the study.

  • Funding Supported in part by grants from the Plastic Surgery Foundation (PSF) and American Society of Peripheral Nerve (ASPN) (grant no. 415663, JC and GHB); Moorfields Eye Charity (grant no. ST1507N, SSMF); and HCA International Foundation (grant no. 1107145, SSMF).

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Ethics approval This study was approved by the Institutional Research Ethics Board in keeping with the Declaration of Helsinki.

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

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