A new approach of ocular nebulization with vitamin B12 versus oxytocin for the treatment of dry eye disease: an in vivo confocal microscopy study

Abstract

Purpose: To present a new ocular nebulization therapy for the treatment of dry eye disease (DED) and investigate the efficacy of vitamin B12 (VB12) and oxytocin (OXT) nebulization with clinical parameters and in vivo confocal microscopy (IVCM). Patients and methods: Thirty-eight patients with DED were enrolled, with 19 receiving VB12 nebulization and 19 receiving OXT nebulization twice weekly for 3 months. Clinical signs and symptoms including Ocular Surface Disease Index, self-assessment of light sensitivity and dryness, tear meniscus height, tear break-up time (BUT), and corneal staining, along with IVCM data of basal epithelial cell density, sub-basal dendritic cell (DC) density, nerve density, and nerve tortuosity were acquired at baseline, 1 month, and 3 months after starting treatment. Results: Patients treated with VB12 improved significantly in all signs and symptoms except for nerve tortuosity during the three-month treatment, while OXT demonstrated similar effects apart from BUT and nerve tortuosity. VB12 group revealed a higher BUT at 1 month and 3 months with a higher basal epithelial cell density at 3 months compared with OXT group, and a lower DC density was observed in OXT group at 1 month. Change of basal epithelial cell density was more significant at 3 months in VB12 group, with OXT group showing a significantly higher DC reduction at 1 month. Conclusion: The nebulization therapy delivering VB12 and OXT appears to be effective in improving the symptoms and signs of dry eye, with a relatively stronger effect of BUT elevation and epithelial repair in VB12 and anti-inflammation in OXT nebulization.

Keywords: dry eye; in vivo confocal microscopy; nebulization; oxytocin; vitamin B12.

Figure 1

Ultrasonic nebulization system developed in this study.

Figure 2

IVCM images at each follow-up between VB12 and OXT groups. Notes: Frames show basal epithelial cell with bright polygonal borders and nonhomogenous cytoplasmic reflectivity immediately anterior to Bowman layer, sub-basal nerve plexus fibers running roughly in parallel and dendritic bright cells (DC) with different densities (arrows). VB12 group: (A–C) basal epithelial cell layer at baseline, 1 month, and 3 months after treatment: showed an increased basal epithelial cell density. (D–F) DC and sub-basal nerve plexus at baseline, 1 month, and 3 months after treatment: showed a decreased DC density and a notably increased sub-basal nerve density. OXT group: (G–I) basal epithelial cell layer at baseline, 1 month, and 3 months after treatment: showed an increased basal epithelial cell density. (J–L) DC and sub-basal nerve plexus at baseline, 1 month, and 3 months after treatment: showed a notably decreased DC density and increased sub-basal nerve density and tortuosity. Abbreviations: OXT, oxytocin; IVCM, in vivo confocal microscopy; VB12, vitamin B12.

Figure 3

Clinical and IVCM results at each follow-up between VB12 and OXT groups. Notes: *P<0.05 between groups. **P<0.01 between groups. Abbreviations: BUT, tear break-up time; IVCM, in vivo confocal microscopy; OSDI, Ocular Surface Disease Index; OXT, oxytocin; S, seconds; TMH, tear meniscus height; VB12, vitamin B12.

Figure 4

Changes in clinical and IVCM results at each follow-up between VB12 and OXT groups. Notes: *P<0.05 between groups. **P<0.01 between groups. Abbreviations: BUT, tear break-up time; IVCM, in vivo confocal microscopy; OSDI, Ocular Surface Disease Index; OXT, oxytocin; S, seconds; TMH, tear meniscus height; VB12, vitamin B12.