UC Berkeley

Population-based studies found that approximately 60% of symptomatic dry eye patients presented with visible signs of Meibomian gland dysfunction (MGD), which is considered the most common cause of dry eye symptoms.1,2 The prevalence of MGD varies widely between 3.5%-70%.1–6 An estimated 85% of adolescents and young adults between 12-24 years old suffer from acne and over 13 million people, including children, have been treated with isotretinoin since its availability in 1982.8 Isotretinoin is a vitamin A analogue used to treat severe inflammatory, nodular acne, and has been linked to MGD.7 Lipid mediators, which are biomarkers for normal physiology or pathophysiology in many tissues including ocular surface and lacrimal gland, are among the earliest inflammatory/immune regulators released in response to stress, but their role in MGD has not been investigated.

The research aimed to elucidate the short- and long-term effects of isotretinoin therapy on Meibomian gland structure and function and meibum lipid mediator profiles via (1) a single-visit cohort study to compare past- and non-users of isotretinoin, and (2) a 12-month longitudinal study to compare changes from baseline during and after therapy among isotretinoin and control cohorts.

Among many commonly reported Meibomian gland (MG) characteristics, MG contrast was found to be a repeatable and reliable measure for MG function. Specifcally, low MG contrast was found to be a risk factor for lipid-deficient dry eye. During isotretinoin therapy, MG contrast decreased significantly but returned to baseline by 6-months post treatment. In general, there were significant differences in many meibum-related clinical measures and symptoms between study groups during treatment, and some of those differences persisted six months post-therapy, including number of expressed glands and meibum quality score. Past-users had worse symptoms, worse MG function, and lower levels of prostaglandin D2, a potential biomarker for meibocyte function. Furthermore, elevated docosahexaenoic acid (DHA) levels were significantly correlated with worse symptoms, suggesting that its detection in meibum represents active inflammation and/or a metabolic deficiency preventing the effective and/or efficient conversion of DHA to specialized pro-resolving lipid mediators. In summary, isotretinoin patients develop signs of MGD during isotretinoin therapy that persist long after treatment. Lipidomic results provide potential biomarkers for detecting inflammation, DHA metabolic deficiency, and/or PGD2-related MGD.