Corneal complexity

  The cornea is far more complex than traditionally thought, and is actually a highly responsive tissue that is actively involved in the regulation of immunity and inflammation, the 2016 Irish College of Ophthalmologists Annual Conference in Killarney, Ireland, heard. Reza Dana MD, MSc, MPH, Professor of Ophthalmology and Director of the Cornea Service at Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, USA, gave the Annual Mooney Lecture entitled ‘Regulation of Corneal Inflammation and Immunity’. He noted that corneal disease is second only to cataracts as the leading cause of non-refractive visual impairment across all age groups globally. Corneal angiogenesis is not only a common complication of corneal inflammation, but also helps amplify the inflammatory response in the cornea, “but it is not always a bad thing”, Dr Dana explained. He said that in active infections, especially chronic fungal infections, growth of corneal neovascularisation can help clear the infection by facilitating delivery of immune cells. TRANSPLANTATION In corneal transplantation, the immune response often interferes with success rates. Nearly 100,000 corneal transplants are performed worldwide every year, he said, with an increasing number done using endothelial keratoplasty. In low-risk transplants, done in host beds with no inflammation or vascularisation, there is 85-90 per cent graft survival. However, in high-risk transplants, with an inflamed host bed, there is less than 50 per cent survival despite maximum immune suppression. While corticosteroids have been a treatment revolution, in high-risk transplants they are not as successful. Dr Dana urged caution in the use of systemic immune suppression in keratoplasty, saying while it works, there are risks and side effects, with clinician skill and experience vital for a successful outcome. He then discussed the successful use of anti-vascular endothelial growth factor (anti-VEGF) treatments for increasing the survival of corneal grafts. Other modalities could include use of low-dose interleukin-2 to expand regulatory immune cells which are potently anti-inflammatory. “In chronic disease the regulatory immune cells do not function normally, but again you can use biologic strategies to amplify their function and restore that normal balance,” he explained. MYTHS In his presentation Dr Dana debunked a number of old concepts, or “myths”, which had become popularised over the ages. The first was the idea of the cornea not having any resident immune cells. "We now know that the cornea has 
many immune cells that are highly relevant, both for quietening inflammation as well as promoting immunity,” he told EuroTimes. He explained that 5-8% of the resident cells of the cornea in all species evaluated to date are bone marrow-derived, thus the cornea is “much more than just epithelial cells, stromal keratocytes, and endothelial cells, which is the old view”. He thus stated: “We now know that through these bone marrow-derived cells there is a constant communication and interchange between the cornea and the lymphoid tissues of the body.” Dr Dana said a key message is the manipulation of the VEGF pathway, not only for suppressing angiogenesis, but also regulating immune cell traffic to the cornea since several VEGF pathways also regulate immune cell activation and trafficking. “Although there are a whole array of inflammatory conditions that can lead to dysregulation of the cornea to regulate inflammatory response, there are treatment strategies such as blocking certain VEGF pathways and using interleukin-2 to promote regulatory pathways. The beauty of the immune system is that it can be modulated since the host immune response is highly plastic and modifiable,” he concluded. Reza Dana: reza_dana@meei.harvard.edu