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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)
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).
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.
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.
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.
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