Decreased Geometric Complexity of Corneal Nerve Fibers Distribution in Sjogren’s syndrome Patients

Objective: Dry eye affects many individuals worldwide and a significant portion of patient with dry eye present the Sjogren’s syndrome (SS), a progressive, autoimmune condition. In order to choose and follow the best therapy it’s necessary to have noninvasive quantitative methods able to characterize the status of the corneal nerve fibers of the patients.

Methods: Local fractal dimension by box-counting (evaluation of geometric complexity) of the nerve corneal fibers distribution observed by confocal microscopy was performed in patients with primary SS (n=36: 6 males, 30 females, 21- 81 years), diagnosed by biopsy of salivary gland and blood tests and in sex- age-matched healthy subjects (n=12). In selected patients salivary glands atrophy degree was also evaluated.

Results: Fractal analysis reveals that the nerve corneal distribution is fractal. In healthy subjects the fractal dimension of the corneal nerve distribution is close to the value of the Diffusion Limited Aggregation Process, a typical value of geometric complexity in normal individuals. Geometric complexity statistically distinguishes between Sjogren’s syndrome patients and healthy subjects: patients present a lower value of geometric complexity of the corneal nerve fibers distribution than healthy individuals (p<0.001). The percentage of grouped cases classified by geometric complexity (D cut-off =1.40) according to the subjects (SS patients vs healthy) showed a 100% ratio between the number of correctly classified cases and all cases, p<0.001. The nonlinear index correlates with salivary glands atrophy degree (p<0.01).

Conclusions: Fractal analysis of the cornea observed by a laser confocal microscopy appears able to quantitatively and nonivasively characterize the SS patient in relation to the recognition of an impairment of the ocular surface. The analysis is inexpensive and not time-consuming, of relevance in order to choose the best therapy.