Focused tortuosity definitions based on expert clinical assessment of corneal subbasal nerves

Neil Lagali, Enea Poletti, Dipika V. Patel, Charles N.J. McGhee, Pedram Hamrah, Ahmad Kheirkhah, Mitra Tavakoli, Ioannis N. Petropoulos, Rayaz A. Malik, Tor Paaske Utheim, Andrey Zhivov, Oliver Stachs, Karen Falke, Sabine Peschel, Rudolf Guthoff, Cecilia Chao, Blanka Golebiowski, Fiona Stapleton, Alfredo Ruggeri

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


PURPOSE. We examined agreement among experts in the assessment of corneal subbasal nerve tortuosity. METHODS. Images of corneal subbasal nerves were obtained from investigators at seven sites (Auckland, Boston, Linköping, Manchester, Oslo, Rostock, and Sydney) using laser-scanning in vivo confocal microscopy. A set of 30 images was assembled and ordered by increasing tortuosity by 10 expert graders from the seven sites. In a first experiment, graders assessed tortuosity without a specific definition and performed grading three times, with at least 1 week between sessions. In a second experiment, graders assessed the same image set using four focused tortuosity definitions. Intersession and intergrader repeatability for the experiments were determined using the Spearman rank correlation. RESULTS. Expert graders without a specific tortuosity definition had high intersession (Spearman correlation coefficient 0.80), but poor intergrader (0.62) repeatability. Specific definitions improved intergrader repeatability to 0.79. In particular, tortuosity defined by frequent small-amplitude directional changes (short range tortuosity) or by infrequent large- amplitude directional changes (long range tortuosity), indicated largely independent measures and resulted in improved repeatability across the graders. A further refinement, grading only the most tortuous nerve in a given image, improved the average correlation of a given grader’s ordering of images with the group average to 0.86 to 0.90. CONCLUSIONS. Definitions of tortuosity specifying short or long-range tortuosity and considering only the most tortuous nerve in an image improved the agreement in tortuosity grading among a group of expert observers. These definitions could improve accuracy and consistency in quantifying subbasal nerve tortuosity in clinical studies.

Original languageEnglish (US)
Pages (from-to)5102-5109
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Issue number9
StatePublished - 2015
Externally publishedYes


  • Corneal nerves
  • In vivo confocal microscopy
  • Plexus
  • Subbasal nerve
  • Tortuosity

ASJC Scopus subject areas

  • Sensory Systems
  • Cellular and Molecular Neuroscience
  • Ophthalmology


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