Pooled human immunoglobulin eye drops may potentially be the first biologic in a whole new class of immunotherapies for treating dry eye disease (DED), according to researchers from the University of Illinois at Chicago. Their clinical trial showed a significant reduction in the signs and symptoms of the disease after administering immunoglobulin drops (4mg/mL) twice a day for eight weeks. They detected significantly higher amounts of immunoglobulin and the presence of several species of anti-citrullinated protein autoantibodies (ACPAs) in the ocular surface wash collected from patients. They also suggest that neutrophils may play a more prominent role in dry eye’s pathophysiology than has been previously recognized.

The study’s data shows high levels of ACPAs in the ocular surface wash of several DED subtypes, such as Sjögren’s syndrome, ocular graft-vs.-host disease, meibomian gland dysfunction and discordant DED. ACPAs being present in these subtypes suggests local production of these autoantibodies.

The team found that neutrophils are a source of citrullinated proteins on the ocular surface of DED patients. Citrullinated proteins stimulate the production of ACPA, which not only causes ocular surface disease but also stimulates formation of neutrophil extracellular traps, creating a self-perpetuating cycle of chronic inflammation on the ocular surface. Adding immunoglobin drops to the ocular surface can limit this cycle. The study concluded that its findings could help shift the current paradigm that focuses on T-cell mediated inflammation as central to the pathophysiology of DED to also include autoimmune inflammation.

Kwon J, Surenkhuu B, Raju I, et al. Pathological consequences of anti-citrullinated protein antibodies in tear fluid and therapeutic potential of pooled human immune globulin-eye drops in dry eye disease. Ocul Surf. October 10, 2019. [Epub ahead of print.]