Altered Corneal Nerves in Aqueous Tear Deficiency Viewed by In Vivo Confocal Microscopy

Abstract

Abnormal morphologic changes are observed in aqueous tear deficiency that are more severe in Sjögren syndrome. The distinct changes of corneal nerves include increased nerve number, tortuosity, and chances of branching, suggesting an attempted nerve regeneration. A strong correlation exists between the changes of nerve morphology and the degree of dry eye. These results provide some possible evidence for the abnormal corneal sensation in dry eye.

Effect of Autologous Serum Eye Drops in Patients with Sjögren Syndrome-related Dry Eye: Clinical and In Vivo Confocal Microscopy Evaluation of the Ocular Surface

“…However, there is not agreement regarding IVCM findings in the literature. When evaluating sub-basal nerve density, some authors observed a decrease (2-10, 33, 34), while others found no change (35,36), or, in accordance with our study, an increase in density (37). However, most of these studies were conducted on groups with unequal numbers of patients with SSDE and NSSDE, making the comparison between studies difficult.…”

“…However, previous literature does not show a unique relationship between these aspects and, most articles emphasize a scant association between the signs and symptoms in DE disease (28)(29)(30)37), while few others report occasional associations (2,31) or inverse correlations (32). Such heterogeneous data are probably due to the small sample size used in many past studies, and because of the characteristics of the different questionnaires used.…”

“…Benitez del Castillo et al highlighted the key role played by keratocytes in the inflammatory process linked with DE disease (2). As a matter of fact, the activated keratocytes produce nervous growth factors that are a contribution to the processes of activation and reorganization of the nerve fibers of the subbasal plexus (37). A past study revealed a significantly higher number of hyper-reflective stromal cells, believed to be keratocytes, in a specific stage of metabolic activation in patients with DE disease (5).…”

“…The bead-like formations are characteristic of metabolically active nerve fibers containing transmitters, and the increased number found in DE disease cases indicates an attempt to improve the abnormal epithelial tropism (34,36,37,40). The chronic inflammation and diminished volume and clearance of tears enriched with pro-inflammatory cytokines such as interleukin (IL)-1 and IL6 lead to the activation of keratocytes, which synthesize nerve growth factor and other factors of nerve growth.…”

“…Moreover, AS contains immunoglobulins (Ig) such as IgG and IgA, and lysozyme, which provide bactericidal and bacteriostatic effects (35). It is also free of preservatives (36) which could potentially induce toxic or allergic reactions (37), and its osmolality and biomechanical properties are similar to those of natural tears.…”