Increased visibility of the nerve fibers on clinical examination is one of the characteristic signs of keratoconus,
1 38 and prominent corneal nerve fibers have been reported in 34% to 91% of subjects.
18 38 39 It was initially postulated that nerves were more visible in keratoconus, due to thinning of the cornea
40 ; however, in a subsequent ex vivo study, our research group has observed localized nerve thickenings in close proximity to breaks in Bowman’s membrane with wrapping of anterior keratocytes around the nerve,
21 24 41 and a small IVCM study of 13 subjects showed an increase in stromal nerve fiber diameter in keratoconus.
23 The subbasal nerve plexus architecture is altered in keratoconus, with fragmentation of the plexus, reduced central nerve fiber density,
22 23 and wrapping of the corneal nerves around the contour of the base of the cone.
22 In the present study, we examined only the central cornea, and thus we cannot comment on the spatiotemporal relationship of nerve changes to corneal thinning outside this area; however, previous mapping of the subbasal nerve plexus in keratoconus has noted lower subbasal nerve density at the site of corneal thinning. Two other groups
22 24 observed thickening of corneal nerve fibers at the site of destructive changes of the cornea. It has been suggested that corneal nerves may play a role in development and progression of keratoconus,
24 with support for this hypothesis coming from the close proximity of stromal nerve changes to breaks in Bowman’s membrane
24 41 and progression of keratoconus observed in a patient with unilateral CNV palsy.
42 In the present study, we did not assess corneal sensation; however, previous work from our research group demonstrated a reduction in corneal sensation in keratoconus correlated to the severity of keratoconus (Patel DV, unpublished data, 2005). In the present study, we quantitatively documented significant alteration in corneal nerves in keratoconus, with subbasal nerve fiber density 52.7% lower than in control eyes, increased subbasal nerve tortuosity, increased thickness of stromal nerves, and a correlation between nerve density and severity of disease, although whether these alterations play a causative role or are secondary manifestations of the underlying disease remains unknown.