Alterations in corneal sensitivity and nerve morphology in patients with primary Sjögren's syndrome

The aim of the study was to assess subjective symptoms and objective clinical signs of dry eye in relation to corneal nerve morphology and sensitivity in primary Sjögren's syndrome. Twenty eyes of 20 primary Sjögren's syndrome patients and ten eyes of 10 healthy age- and sex-matched controls were included in the study. Ocular surface disease index (OSDI) questionnaire and visual analog scales were used to assess subjective symptoms. The mechanical sensitivity of the central cornea was measured using a modified Belmonte non-contact esthesiometer followed by an analysis of corneal nerve morphology using scanning slit confocal microscopy (ConfoScan 3). OSDI symptom scores were high in primary Sjögren's syndrome patients, compared with controls. Accordingly, the mean corneal detection threshold was low in patients implicating corneal mechanical hypersensitivity (54.5+/-40.1ml/min vs. 85.0+/-24.6ml/min, P=0.036). However, nerve densities were similar, and no correlation was present between corneal sensitivity and nerve density. In contrast, alterations in nerve morphology were found; stromal nerves appeared thicker, and nerve growth cone-like structures were seen in 20% of patients, often associated with dendritic antigen-presenting cells. Sjögren's syndrome patients presented with corneal mechanical hypersensitivity, although corneal nerve density did not differ from controls. However, alterations in corneal nerve morphology (nerve sprouting and thickened stromal nerves) and an increased amount of antigen-presenting cells, implicating the role of inflammation, were observed. These observations offer an explanation for the corneal mechanical hypersensitivity, or even hyperalgesia often observed in these patients. We hypothesize that patients with primary Sjögren's syndrome dry eye suffer from neuropathic corneal mechanical hypersensitivity induced by ocular surface inflammation.