Lessons Learned From Ocular Graft versus Host Disease: An Ocular Surface Inflammatory Disease of Known Time of Onset.

ABSTRACT: The ocular surface inflammatory disorders (OSIDs) comprise a group of conditions characterized by persistent inflammation of the ocular surface and adnexal tissues. Systemic autoimmune diseases and hypersensitivity reactions cause them, and, if left untreated, can result in severe inflammatory dry eye, corneal damage, and vision loss. Ocular graft-versus-host disease (oGVHD) forms part of the ocular surface inflammatory disease umbrella. It is a condition occurring after allogeneic hematopoietic stem cell or bone marrow transplantation, usually in chronic graft-versus-host disease. oGVHD can virtually affect any ocular adnexal tissue, especially the meibomian glands, and cause persistent inflammation, tissue fibrosis, and subsequent chronic, severe dry eye disease. Among the OSIDs, oGVHD has the particularity that it has a "time zero," meaning we know when the disease started. As such, preclinical models have leveraged this to investigate the molecular mechanisms involved in the damage oGVHD causes to the ocular surface. In oGVHD, establishing a "time zero" allows for predicting the clinical course and establishing adequate treatment. This is also possible because the inflammatory infiltration occurs in ocular surface tissues, which are readily accessible. Using oGVHD, we might be able to understand the immune response mechanisms in other OSIDs better (i.e., Sjögren syndrome, Stevens-Johnson syndrome, among others). This review presents an up-to-date overview of the pathogenesis, clinical presentation, and treatment of oGVHD. In addition, we will discuss the value of the "time zero" concept in the study of oGVHD.

Gonadotropins in Keratoconus: The Unexpected Suspects.

Keratoconus (KC) is the most common ectatic corneal disease with a significant visual acuity burden. The actual burden is intangible given that KC can disrupt daily activities (reading, driving, and various career paths). Despite decades of research and clinical studies, the etiology, onset, and pathobiology of KC remain a mystery. The purpose of this study was to investigate the role of gonadotropins in KC. We recruited 86 KC patients (63 males, 23 female), and 45 healthy controls (22 male, 23 female). Plasma samples were collected and analyzed using an enzyme-linked immunosorbent assay. Corneal stromal cells from KC and healthy controls, and human epithelial corneal cells, were also investigated for gonadotropin-related markers. Our results show significant alterations of LH/FSH in KCs, compared to healthy controls. Our data also reveals, for the first time, the existence of gonadotropins and their receptors in KC. Our study is the first to demonstrate the role of LH/FSH in KCs, and expand the list of organs known to express gonadotropins, or their receptors, to include the human cornea. Our findings suggest that the human cornea is capable of responding to gonadotropins, and propose an intriguing mechanism for the onset and/or progression of KC.