New approaches to dry eye

Tear instability is a major cause of ocular discomfort, visual disturbances and dissatisfaction with vision-correcting surgery. Identifying and targeting the underlying causes is essential for successful treatment, Stephen C Pflugfelder MD said in his Binkhorst Lecture to the 2019 ASCRS ASOA Annual Meeting in San Diego, USA. A stable tear film consists of two layers: a hydrated mucous gel consisting of mucin secreted by conjunctival goblet cells mixed with proteins and electrolytes from the lacrimal glands, anchored to the epithelium by glycocalyx mucin and covered by a polar and non-polar lipid layer produced by the meibomian glands. Instability can result from disruption of any of the systems producing these components as well as environmental and anatomic factors that inhibit tear flow. The quest for tear stability starts with the integrated lachrymal functional unit, said Dr Pflugfelder, of Baylor College of Medicine, Houston, USA. Cooling and increased osmolarity at sites of tear break-up activate TRPM8 signalling channels in corneal nociceptors, initiating the neural reflex that drives tearing and blinking. Lacrimal factors including epidermal growth factor and vitamin A support tear-stabilising mucin production by conjunctival goblet cells, which also suppress antigen presenting cells leading to immune tolerance on the ocular surface. Aqueous deficiency leads to goblet cell loss, further destabilising tear film and promoting immune inflammation, stimulating cytokines, chemokines and proteases including MMP-9 that damage apical epithelial cells and decrease surface wetability, leading to irritation, blurred vision and corneal epitheliopathy. By contrast, meibomian gland dysfunction is linked to increased goblet cell density, which may explain the greater severity often seen in cases caused by tear deficiency, Dr Pflugfelder said. Diagnosis and treatment Four fluorescein break-up patterns have been identified that can help identify the root causes of tear instability, Dr Pflugfelder noted (Yokoi N, Georgiev GA. IOVS 2018). Non-invasive assessment of Placido ring patterns provide a kinetic record of tear break-up patterns that helps spot corneal and surface pathologies promoting instability, such as nodular degeneration or epithelial membrane dystrophy, he added. Conjunctivochalasis is a common age-related cause. One-third or more of patients over age 50 could benefit from surgery, Dr Pflugfelder said (Mimura et al. AJO 2009). To stabilise tear film, Dr Pflugfelder recommended increasing humidity and minimising air drafts, and correcting any lid and conjunctival abnormalities. A wide range of therapies targeting specific causes are also available, including thermal meibomian gland expression and essential fatty acid for lipid problems, retinoids, serum plasma and plugs for hydrated mucin gel, and doxycycline and steroids for the epithelium. “It’s important to target therapies to the underlying causes of tear dysfunction,” Dr Pflugfelder concluded. Stephen Pflugfelder: stevenp@bcm.edu

Tags: dry eye