Pooled human immunoglobulin-containing eye drops revolutionize dry eye therapy for rheumatism

At ARVO 2015, a scientific paper was published that examined the prevalence of dry eye in rheumatism patients. New research brings an opportunity for a necessary update.

Ophthalmology Blog
By Dr. med. Annabelle Eckert

In the 2015 scientific paper, of the 286 study participants with rheumatoid arthritis, 96% showed dry eye symptoms. Only 44% of the study participants had been diagnosed with dry eye before the study started.1 Only recently - in October 2019 to be precise - a scientific article on a new dry eye therapy option for rheumatoid arthritis was published. Autoantibodies against citrullinated proteins play a crucial role in this. More on this in today's blog post.2

Where do we actually know the ACPAs from?

The serological determination of anti-citrullinated protein antibodies (ACPAs) represents an essential step in the diagnosis of rheumatoid arthritis. Rheumatoid arthritis is one of the most common autoimmune diseases. ACPAs are highly specific for rheumatoid arthritis. They can be detected in the early phase of the disease, long before the irreversible joint destruction has occurred. At the same time, the autoantibodies have a function as prognostic markers. They correlate with disease aggressiveness.3

How exactly does rheumatoid arthritis manifest itself in the human eye?

In principle, all structures of the eye can be damaged in the course of rheumatoid arthritis. The ocular manifestation includes episcleritis, keratitis, iridocyclitis, retinal vasculitis, and the most common keratoconjunctivitis sicca. It is based on immunologically induced destruction of the lacrimal gland and the resulting reduced tear secretion.4

What is the latest research on the treatment of dry eye in rheumatoid arthritis?

Last month a scientific article was published about a new dry eye therapy option for rheumatoid arthritis.  The research team from Chicago was the first to demonstrate the presence of ACPAs in the tear film. Intensive research work was necessary for the development of the new therapeutic agent. Using conjunctival impression cytology and examination of the tear film, the research team searched for ACPAs in patients with rheumatoid arthritis. The aim of these investigations was to determine whether a high concentration of ACPAs may be associated with pathological ocular consequences.

A positive correlation was found between the concentration of ACPAs and dry eye syndrome. They found that neutrophils are the source of autoantibodies against citrullinated proteins in the eye. At the same time, the neutrophils secreted DNA strands, which in turn formed net-like structures on the eye surface, the so-called NETs (Neutrophil Extracellular Traps). These networks contributed to the inflammatory reaction. In in vitro and in vivo models, the research team investigated the effectiveness of eye drops containing pooled human immunoglobulins to capture ACPAs. In a Phase II study, the application (twice daily for 8 weeks) of pooled human immunoglobulin-containing eye drops (IVIG 4 mg/ml) significantly improved dry eye symptoms. A total of 27 rheumatism patients have participated in this study so far.2

References:
1. Yumori J. Wong et al. (2015). Prevalence of Dry Eye Disease in Rheumatoid Arthritis Patients. ARVO Annual Meeting Abstract  |   June 2015. Investigative Ophthalmology & Visual Science June 2015, Vol.56, 4437.
2. Kwon J. et al. (2019).  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.  2019 Oct 10.
3.  Kemer E. et al. (2017). Dry Eye in Rheumatoid Arthritis. International Ophthalmology Clinics: Spring 2017 - Volume 57 - Issue 2 - p 89–99.
4. Feist E, Pleyer U (2010). Diseases of the outer eye in rheumatoid arthritis. Z Rheumatol 2010;69:403-10.