Treatment of dry eye disease

Several treatments are available and in development that modulate ocular surface immune responses and help break the cycle of chronic inflammation that perpetuates severe dry eye without shutting down beneficial immune function, Stefano Barabino MD, PhD, of the University of Milan, Italy, told the 2018 Cornea Subspecialty Day at the 36th Congress of the ESCRS in Vienna.

“We don’t want to eradicate inflammation, we want to control inflammation. A medium level of inflammation can have a positive effect. If the inflammation becomes chronic then we have problems,” said Dr Barabino, delivering his own paper and one on behalf of Elisabeth Messmer MD of the University of Munich.

The immune cascade driving dry eye disease is complex and can be interrupted at several points, Dr Barabino noted.

Corticosteroids, including loteprednol etabonate, rimexolone and hydrocortisone, interrupt the inflammatory cycle by directly regulating gene expression of inflammatory factors and inhibiting many inflammatory pathways. Steroids inhibit cytokine and chemokine production, decrease expression of cell adhesion molecules, and decrease synthesis of matrix metalloproteinases (MMP) and lipid inflammation mediators such as prostaglandins.

Corticosteroids also stimulate lymphocyte apoptosis. Dr Barabino recommended preservative-free preparations delivered in a tapering or pulsed regimen to disrupt but not eradicate immune responses, and to minimise side-effects including cataracts, ocular hypertension, glaucoma and infections.

RELIEVES SYMPTOMS
Cyclosporine A inhibits T cell activation and decreases IL-6 and HLA-DR, which cause ocular surface cells to recruit more immune cells and increases goblet cells. It improves dry eye signs and relieves symptoms, but takes eight-to-12 weeks to work. It also causes irritation on installation for 8-to-10% of patients, Dr Barabino noted. Topical cyclosporine A is available in 0.05% preparations in the USA and 0.1% in Europe.

Lifitegrast inhibits T cell-mediated inflammation by blocking the binding of lymphocyte function-associated antigen 1 (LFA-1) and intracellular adhesion molecule 1 (ICAM-1), Dr Barabino said. It significantly improves dry eye disease signs and symptoms in about two weeks. However, lifitegrast also may burn on installation and is not yet available in Europe.

Tetracycline derivatives reduce MMP activity and synthesis and reduce collagenases and B cell activity. They have a positive effect on ocular surface inflammation associated with rosacea, Dr Barabino said.

Future immunomodulator candidates include compounds that block CD-4, VLA-4, chemokine receptor 2, DA-6034, IL-17 and VEGF-C.

“What we really want is a treatment that can break the inflammatory cascade without side-effects,” Dr Barabino said.

Stefano Barabino: stebarabi@gmail.com