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Effect of herpes simplex keratitis scar location on bilateral corneal nerve alterations: an in vivo confocal microscopy study
  1. Chareenun Chirapapaisan1,2,
  2. Rodrigo T. Muller1,3,4,
  3. Afsun Sahin3,5,
  4. Andrea Cruzat1,6,
  5. Bernardo M. Cavalcanti1,
  6. Arsia Jamali1,3,
  7. Deborah Pavan-Langston1,
  8. Pedram Hamrah1,3
  1. 1 Ocular Surface Imaging Center, Cornea and Refractive Surgery Service, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, USA
  2. 2 Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
  3. 3 Center for Translational Ocular Immunology and Cornea Service, New England Eye Center, Department of Ophthalmology, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
  4. 4 Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil
  5. 5 Department of Ophthalmology, Koc University School of Medicine, Istanbul, Turkey
  6. 6 Department of Ophthalmology, Pontificia Universidad Católica de Chile, Santiago, Chile
  1. Correspondence to Dr Pedram Hamrah, Tufts Medical Center, Boston, MA 02111, USA; PHamrah{at}


Aims To evaluate the impact of herpes simplex virus (HSV)-induced scar location on bilateral corneal nerve alterations using laser in vivo confocal microscopy (IVCM).

Methods Central and peripheral corneal subbasal nerve density (CSND) were assessed bilaterally in 39 patients with unilateral HSV-induced corneal scars (21 central scars (CS), 18 peripheral scars (PS)) using IVCM. Results were compared between patients and 24 age-matched controls. CSND was correlated to corneal sensation for all locations.

Results Overall patients revealed significant decrease of CSND in the central and peripheral cornea (9.13±0.98 and 6.26±0.53 mm/mm2, p<0.001), compared with controls (22.60±0.77 and 9.88±0.49 mm/mm2). CS group showed a decrease in central (8.09±1.30 mm/mm2) and total peripheral nerves (5.15±0.62 mm/mm2) of the affected eyes, whereas PS group demonstrated a decrease in central (10.34±1.48 mm/mm2) and localised peripheral nerves only in the scar area (4.22±0.77 mm/mm2) (all p<0.001). In contralateral eyes, CSND decreased in the central cornea of the CS group (16.88±1.27, p=0.004), and in the peripheral area, mirroring the scar area in the affected eyes of the PS group (7.20±0.87, p=0.032). Corneal sensation significantly decreased in the whole cornea of the affected, but not in contralateral eyes (p<0.001). A positive correlation between CSND and corneal sensation was found in all locations (p<0.001).

Conclusions Patients with HSV scar demonstrate bilateral CSND decrease as shown by IVCM. CSND and corneal sensation decrease in both central and peripheral cornea in affected eyes, although only in the scar area in PS group. Interestingly, diminishment of CSND was found locally in the contralateral eyes, corresponding and mirroring the scar location in the affected eyes.

  • diagnostic tests/investigation
  • imaging
  • cornea
  • infection

Data availability statement

Data are available upon reasonable request. The data that support the findings of this study are available from the corresponding author (PH), upon reasonable request.

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Data availability statement

Data are available upon reasonable request. The data that support the findings of this study are available from the corresponding author (PH), upon reasonable request.

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  • Correction notice This paper has been updated since it was published online. The second affiliation for author Andrea Cruzat has been updated.

  • Contributors PH designed the study. PH and DP-L provided findings. RM, AC, BC, DP-L and PH recruited the patients. RM, AC and BC evaluated corneal sensitivity. CC and RM selected the images. CC and RM analysed the images. CC, RM and AJ did the statistical analysis. PH supervised the work. CC and AS wrote the draft. All the authors reviewed the manuscript.

  • Funding NIH K08-EY020575 (PH), NIH R01-EY022695 (PH), Research to Prevent Blindness Career Development Award (PH, no grant number), MEEI Foundation (PH, no grant number), Falk Medial Research Trust (PH, no grant number), Johnstone Fund (DP-L, no grant number), Stevens Fund (DP-L, no grant number).

  • Competing interests None declared.

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

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