Clinical safety and efficacy of vitamin D3 analog ointment for treatment of obstructive meibomian gland dysfunction

Abstract

Background: Hyperkeratinization is a major cause of obstructive meibomian gland dysfunction (oMGD) and results in degenerative gland dilation and atrophy without inflammation. Ointment containing 1,25-dihydroxy-22-oxavitamin D3 (maxacalcitol), a noncalcemic analog of the active form of vitamin D3, is applied for the treatment of hyperkeratotic cutaneous conditions such as psoriasis and ichtyosis because it suppresses the proliferation and promotes the differentiation of keratinocytes through interaction with the vitamin D receptor. The aim of the present study was to evaluate the safety and efficacy of maxacalcitol ointment for the treatment of oMGD.

Methods: Six eyes of six healthy male subjects (mean age ± SD, 36.4 ± 10.8 years) and 12 eyes of eight oMGD patients (five men and three women; mean age ± SD, 55.6 ± 13.2 years) were enrolled in the study. Maxacalcitol ointment was applied to the upper and lower lid margins twice a day for 8 weeks. Subjective symptoms, lid margin abnormalities, tear film breakup time (BUT), ocular surface staining, meibum grade, Schirmer test value, and meibomian gland area were evaluated in the oMGD patients before, during, and after the treatment period.

Results: Severe adverse effects of ointment application were not observed in the healthy subjects or oMGD patients. The clinical scores for plugging of meibomian gland orifices and lid margin vascularity as well as BUT, meibum grade, and meibomian gland area were significantly improved in oMGD patients after the 8-week treatment period compared with pretreatment values (P values of <0.001, 0.020, 0.030, 0.020, and 0.017, respectively).

Conclusions: Topical eyelid application of an analog of the active form of vitamin D3 was found to be safe as well as to improve the condition of patients with oMGD. Such ointment thus warrants further evaluation as a potential new treatment option for this condition.

Trial registration: This study was registered with the UMIN database (ID: UMIN000016230 ) on 16 January 2015.

Keywords: Meibomian gland dysfunction; Meibomian gland obstruction; Ointment; Vitamin D3.

Fig. 1

Lid margin abnormalities in a 65-year-old man with oMGD. The right eye of a 65-year-old man with oMGD is shown before as well as 4 and 8 weeks after the onset of treatment with maxacalcitol ointment. Note that plugging of meibomian gland orifices as well as lid margin vascularity were ameliorated after treatment for 8 weeks

Fig. 2

Meibomian gland area for the same patient as in Fig. 1. Regions shown in green represent meibomian glands and dilated gland ducts as revealed by noninvasive meibography and analysis software. Meibomian gland area in the upper eyelid (upper two panels) was 11.9% before treatment, 12.4% after treatment for 4 weeks, and 36.3% after treatment for 8 weeks. The corresponding values for the lower eyelid (bottom two panels) were 16.6% before treatment, 15.8% after treatment for 4 weeks, and 26.5% after treatment for 8 weeks