Clinical Protocol support contract designed to attain extramural support for developing, designing, interpreting, and evaluating clinical trials, epidemiologic and natural history studies. In addition, it will provide for outcomes research involving eye diseases and visual disorders and some preclinical studies. The focus shall be on the design of studies and the collection, analysis, and interpretation of data emanating from these studies, as well as support, and monitoring patient safety and follow-up. Contractor shall also provide analytical and data management support, as described in the work statement, for specified clinical research data bases, cost-effectiveness and economic analyses, quality of life assessment and outcomes research. This will include, but not be limited to, the following areas: analysis of Medicare and other health care databases;evaluation of existing NEI databases such as, centralized NEI Intramural Research database, the Eye Disease Case Control Study, Early Treatment Diabetic Retinopathy Study, Framingham Eye Study, and intramural AIDS and uveitis databases. Objective of Clinical Protocol: Graft-vs.-Host Disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (SCT) commonly affecting the skin, liver, gastrointestinal tract, and eye. The most common clinical manifestations of ocular GVHD generally result from involvement of the lacrimal gland and the conjunctiva. Lacrimal gland involvement can lead to aqueous tear deficiency resulting in severe keratoconjunctivitis sicca (KCS) which can significantly increase the morbidity of patients with chronic GVHD. Systemic immunosuppressants such as cyclosporine (CsA) can be effective for treating ocular GVHD including lacrimal gland dysfunction. However, systemic immunosuppression is not generally prescribed for patients whose sole manifestation of GVHD is ocular complications as it may negate the overall graft-vs.-tumor effect and decrease patient survival. Topical CsA and corticosteroids are generally not effective for treating aqueous tear deficiency possible due to epithelial barriers preventing penetration of the drugs to the lacrimal gland. A sustained-release subconjunctival CsA implant was developed to bypass these epithelial barriers and significantly increase the CsA concentrations in the lacrimal gland to treat aqueous tear deficiency related to GVHD. The objective of this randomized pilot study is to investigate the safety and potential efficacy of a CsA implant in patients with lacrimal gland involvement and aqueous tear deficiency related to GVHD. Safety will be evaluated in terms of adverse events related to the implant. Efficacy will be evaluated by changes in Schirmer tear test (with anesthesia). Secondary efficacy evaluation will include changes in corneal and conjunctival staining grades, best-corrected visual acuity (BCVA), the Ocular Surface Disease Index (OSDI), changes in conjunctival GVHD grades, tear break-up time and meibomian gland dysfunction.
