Abnormalities in the meibomian glands in patients with oral administration of anticancer combination drug-capsule TS-1®: a case report

Abstract

BackgroundThe anticancer TS-1® combination capsules of tegafur, gimeracil, and oteracil potassium (Taiho Pharmaceutical Co. Ltd, Japan) causes side effects, i. e., corneal epithelial disorder and dacryostenosis. However, its side effect on meibomian gland had not been reported. We observed morphological changes in the meibomian gland in patients taking TS-1® who exhibited punctate corneal epithelial defects to examine if dysfunction of meibomian glands is involved in the corneal epitheliopathy.Case presentationPatients comprised two males and one female (age, 59–81 years). After starting oral TS-1® administration, patients developed subjective symptoms such as decreased visual acuity. Corneal epithelial disorder was seen in all six eyes of the three subjects exhibited, and lacrimal duct disorder was seen in one eye. Furthermore, meibomian gland loss and contraction were observed in all six eyes that exhibited meibomian gland disorder upon examination by using the MeiboPen®.ConclusionsResults suggested that oral administration of TS-1® may cause meibomian gland disorder which potentially affect corneal epithelial homeostasis.

Ocular surface inflammation impairs structure and function of meibomian gland

“…However, it was suggested that systemic medication also could damage the gland or impair its secretory function. We reported patients with loss of meibomian glands with superficial punctate epitheliopathy during treatment of cancer with an anticancer TS-1 ® combination capsules of tegafur, gimeracil, and oteracil potassium (Taiho Pharmaceutical Co. Ltd, Japan) (Mizoguchi et al, 2015) (Fig. 2).…”

“…To address this issue, we developed a model of ocular surface alkali burn in C57BL/6 mice (Mizoguchi, 2015). Severe inflammation in ocular surface including lid margin epithelium is induced by an exposure to alkali.…”

“…The meibo-score (Arita et al, 2008) are 3 in all of upper and lower eyelids of both eyes. A, B: right; C, D: left; A, C: upper eyelids; B, D: lower eyelids (reproduced from Mizoguchi et al, 2015). …”

“…Meibomian glands of which orifices locate to the burned area (red circles) gradually disappeared at day 10 and 40 (reproduced from Mizoguchi, 2015). …”

Ocular surface alkali injury damages meibomian glands in mice

“…Recently, we reported that inflammation associated with severe allergic conjunctivitis is associated with abnormal morphology of meibomian glands 3 . We also reported that conjunctival inflammation caused by systemic TS-1 anticancer therapy may cause obstruction of the gland orifice, leading to damage of the gland 4 . Because ocular surface alkali injury causes damage to both the conjunctiva and lid margin, leading to severe inflammation, it would seem likely that alkali injury may effect meibomian gland function either through direct damage to the meibomian gland, leading to scarring and plugging of the gland orifice or mediated through palpebral inflammation.…”