April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Corneal subbasal nerve morphology and regeneration in keratoconus and 4 years after UVA-riboflavin collagen cross-linking.
Author Affiliations & Notes
  • Marlen Parissi
    Department for Medical Biochemistry, Oslo University Hospital, Oslo, Norway
  • Stefan Randjelovic
    Department for Medical Biochemistry, Oslo University Hospital, Oslo, Norway
  • Thu Ba Wihlmark
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
  • Tor Paaske Utheim
    Department for Medical Biochemistry, Oslo University Hospital, Oslo, Norway
  • Neil S Lagali
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
  • Footnotes
    Commercial Relationships Marlen Parissi, None; Stefan Randjelovic, None; Thu Ba Wihlmark, None; Tor Utheim, None; Neil Lagali, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 4860. doi:
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      Marlen Parissi, Stefan Randjelovic, Thu Ba Wihlmark, Tor Paaske Utheim, Neil S Lagali; Corneal subbasal nerve morphology and regeneration in keratoconus and 4 years after UVA-riboflavin collagen cross-linking.. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4860.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: To describe corneal subbasal nerve regeneration and morphology in the central cornea in early-stage keratoconus and up to 4 years after UVA-riboflavin collagen crosslinking (CXL).

Methods: 19 keratoconus patients (19 eyes) and 19 age healthy age-matched controls underwent ophthalmic examination by laser-scanning in vivo confocal microscopy (IVCM) of the central cornea to image the subbasal nerve plexus. Controls were examined on one occasion, while patients were examined preoperatively and longitudinally up to 45 months after CXL treatment. Two human observers traced nerves in IVCM images by a manual method. New parameters describing specific subbasal nerve morphology in keratoconus patients were also explored.

Results: Following a standard subbasal nerve selection and analysis protocol, a mean of 3 images/eye from each examination were analyzed. Subbasal nerve density in early-stage, untreated keratoconus (10.3 ± 5.6 mm/mm2, mean ± SD) was significantly reduced relative to healthy, age-matched controls (21.0 ± 4.2 mm/mm2 , t-test, P < 0.001). In keratoconus patients, a significant decline in nerve density from preoperative occurred up to 6 months after CXL. A significant increase to preoperative levels then occurred by one year, with no further significant increase up to 4 years. Even after 4 years, however, nerve density in patients was significantly reduced relative to healthy corneas (P = 0.003). Interestingly, keratoconus patients had an architecture of subbasal nerves that differed from healthy subjects, with an apparent disruption in nerve guidance cues resulting in main nerve branches crossing paths. Such crossings were significantly more frequent in keratoconus than in healthy corneas, and crossing angles were closer to a right angle in keratoconus.

Conclusions: Subbasal nerves are pathologically reduced in early-stage keratoconus, and clinical resolution of keratoconus progression by CXL treatment does not restore a healthy density of subbasal nerves. Additionally, keratoconus disrupts the guidance of main nerve branches in the subbasal nerve plexus.

Keywords: 574 keratoconus • 596 microscopy: confocal/tunneling • 610 nerve fiber layer  
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