This contract is 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. The 46 active trials in 2011 are listed below: For more info: http://clinicalstudies.info.nih.gov/cgi/protinstitute.cgi?NEI.0.html Title: A Pilot Study for the Evaluation of Minocycline as a Microglia Inhibitor in the Treatment of Central Retinal Vein Occlusions Number: 11-EI-0264 Background: - Central retinal vein occlusion (CRVO) is a blockage of the main vein that carries blood away from the retina in the back of the eye. It can lead to macular edema, a swelling of the retina that is a common source of vision loss. Studies suggest that inflammation might be a cause. Minocycline is a drug that might help prevent cells involved in inflammation from becoming activated. It is approved for use as an antibiotic, but it has not yet been tested to see if it can treat CRVO. Objectives: - To test the safety and effectiveness of minocycline as a treatment for central retinal vein occlusion. Design: - This study lasts 2 years, with at least 25 visits to the National Eye Institute. Participants must agree to protect themselves from sunlight or artificial ultraviolet rays while in this study. - Participants will be screened with a physical exam and medical history. They will also have blood tests and an eye exam. One eye will be selected as the study eye to receive the medicine. - Participants will take minocycline or a placebo pill twice a day, about 12 hours apart, for 2 years. - Participants will have monthly visits for blood tests and full eye exams to study the effect of the treatment. Other exams may include thyroid tests and eye imaging studies. Those in the study may also receive injections of a drug to prevent the growth of new blood vessels in the eye. Title: A Pilot Study for the Evaluation of Minocycline as a Microglia Inhibitor in the Treatment of Branched Retinal Vein Occlusions Number: 11-EI-0263 Background: - Branch retinal vein occlusion (BRVO) is a blockage of the small veins that carry blood away from the retina in the back of the eye. It often leads to macular edema, a swelling of the retina that is a common source of vision loss. Studies suggest that inflammation might be a cause. Minocycline is a drug that might help prevent cells involved in inflammation from becoming activated. It is approved for use as an antibiotic, but it has not yet been tested to see if it can treat BRVO. Objectives: - To test the safety and effectiveness of minocycline as a treatment for branch retinal vein occlusion. Design: - This study lasts 2 years, with at least 25 visits to the National Eye Institute. Participants must agree to protect themselves from sunlight or artificial ultraviolet rays while in this study. - Participants will be screened with a physical exam and medical history. They will also have blood tests and an eye exam. One eye will be selected as the study eye to receive the medicine. - Those in the study will take minocycline or a placebo pill twice a day, about 12 hours apart, for 2 years. - Participants will have monthly visits for blood tests and full eye exams to study the effect of the treatment. Other exams may include thyroid tests and eye imaging studies. Those in the study may also receive injections of a drug to prevent the growth of new blood vessels in the eye. Title: Pilot Study of the Evaluation of Intravitreal Sirolimus in the Treatment of Bilateral Geographic Atrophy Associated with Age-Related Macular Degeneration Number: 11-EI-0249 Summary: Background: - Age-related macular degeneration (AMD) is a leading cause of blindness in older people. It affects the macula, the part of the retina needed for clear vision. An advanced form of AMD, called geographic atrophy (GA), may be partly caused by inflammation. Sirolimus is a drug that can help prevent inflammation. Researchers want to see if sirolimus can help prevent vision loss in people with GA. Objectives: - To determine if sirolimus can help prevent vision loss in people with geographic atrophy. Design: - This study requires at least 15 visits to the National Eye Institute over 2 years. Study visits will be every 2 months for 2 years. - Participants will be screened with a medical history and physical exam. They will also have blood and urine tests, and eye exams. One eye will be selected as the study eye to receive the study drug. - Participants will have a sirolimus injection into the study eye. There will be a followup exam 1 month later, with an eye exam but no injection. - Participants will have regular visits with eye exams and injections for 2 years. - Two months after the final injection, participants will have a final clinic visit with an eye exam. Title: Generation of Induced Pluripotent Stem (iPS) Cell Lines From Somatic Cells of Best Disease, Late-Onset Retinal Degeneration (L-ORD), and Age-Related Macular Degeneration (AMD) Patients Number: 11-EI-0245 Summary: Background: - Best Vitelliform Dystrophy (Best disease), Late-Onset Retinal Degeneration (L-ORD), and Age-Related Macular Degeneration (AMD) all affect the retina, the light sensing area at the back of the eye. Doctors cannot safely obtain retinal cells to study these diseases. However, cells collected from hair follicles, skin, and blood can be used for research. Researchers want to collect cells from people with Best disease, L-ORD, and AMD, and compare their cells with those of healthy volunteers. Objectives: - To collect hair, skin, and blood samples to study three eye diseases that affect the retina: Best disease, L-ORD, and AMD. Design: - The study requires one visit to the National Eye Institute. - Participants will be screened with a medical and eye disease history. They will also have an eye exam. - Participants will provide a hair sample, a blood sample, and a skin biopsy. The hair will be collected from the back of the head, and the skin will be collected from the inside of the upper arm. Title: A Pilot Phase I/II Study for the Evaluation of Dextromethorphan as a Microglia Inhibitor in the Treatment of Diabetic Macular Edema (MiDME2) Number: 11-EI-0244 Summary: Background: - Many people with diabetes have macular edema (swelling) at the back of the eye. Macular edema can cause loss of vision. Studies suggest that inflammation may be involved in the swelling. A drug called dextromethorphan may help prevent the inflammation and the swelling. Dextromethorphan is approved for use as a cough medicine, but it has not been studied to see if it can help in diabetic macular edema. Objectives: - To see if dextromethorphan can help treat diabetic macular edema. Design: - This study lasts 2 years, and will require at least 14 visits to the National Eye Institute outpatient clinic. Study visits will be every month for the first 2 months and then every other month. Each visit will take about 2 to 4 hours. - Participants will be screened with a physical exam, medical history, eye exam, and blood tests. One eye with macular edema will be chosen as the study eye for testing. - Participants will take dextromethorphan twice a day, about 12 hours apart, for 2 years. A study diary will help keep track of the date, time, and number of pills taken. - Participants will have study visits once a month for the first 2 months and then every other month for the rest of the study. Each study visit will involve eye exams and blood and urine tests. - Four months after starting the study medication, participants may have laser surgery or other treatments for the macular edema, if it is needed. Title: The Natural History of Ocular Graft-Versus Host Disease Number: 11-EI-0173 Summary: Background: - Stem cell transplantation (SCT) is used to treat some kinds of cancer, blood cell disorders, and immune disorders. Stem cells from a donor's blood are used to replace the recipient's stem cells in the bone marrow. The recipient's bone marrow can then produce new blood cells. Some of these new cells involved in the immune system are like the donor's cells. Sometimes immune cells from the SCT attack the recipient's normal tissues, including the eyes. This type of immune attack is called graft-versus-host disease, or GVHD. -The symptoms of ocular GVHD include eye pain, irritation, dryness, and inflammation. When it is severe and if it does not respond well to treatment, ocular GVHD may also cause vision loss. Objective: - To learn more about graft-versus-host disease (GVHD) of the eyes in people who have had stem cell transplantation. Design: -The study lasts for 1 year and includes six visits to the National Eye Institute. (There is an optional visit about 1 month before your SCT.) When possible, visits for this study will be scheduled so that they can be done on the same day as your visits for the NCI or NHLBI protocol that you are taking part in. -At each visit, participants will have a medical exam and an eye history will be taken. They will have an eye exam and a test to measure the ability to make tears. Those in the study will also have tear fluid collected for analysis in a lab. Tear fluid collection is a painless process. Blood will be drawn during certain visits if it has not already been collected by the transplant team. Title: The Treatment of Macular Edema Secondary to Uveitis using Topical Interferon Gamma Number: 11-EI-0167 Summary: Background: - Uveitis is a serious eye condition in which the immune system attacks the eye and can cause vision loss. A common problem related to uveitis is macular edema. This is a swelling of the central part of the retina. This part of the retina is needed for sharp, clear vision. This swelling can lead to more vision loss. - Interferon gamma-1b is a lab-created protein that acts like the material made by the white blood cells that help fight infection. It changes the way the immune system reacts to the cells in the eye and may help to lessen the swelling in the back of the eye. It has been used as an injection to treat other immune diseases, but it has not been tested as an eye drop for use in uveitis other than a safety trial done at NIH in 2010. Objectives: - To test the effectiveness of interferon gamma eye drops to treat macular edema caused by uveitis. Design: - This study requires three visits to the study clinic over about 2 weeks. Each visit will last 1 to 2 hours. - Participants will be screened with a physical exam, medical history, and a full eye exam. One eye will be designated as the study eye. - Participants will place eye drops in the study eye four times a day for 1 week. - At the second study visit (after 1 week), participants will have an eye exam and a physical exam, and will return the eye drops. - Participants will have a final study visit 1 week after the second visit, with a final eye exam. Title: Longitudinal Investigation of Dark Adaptation in Participants with Age-Related Macular Degeneration Number: 11-EI-0147 Summary: Background: - Age-related macular degeneration (AMD) is a leading cause of vision loss in individuals over 55 years of age. It can cause permanent loss of central vision, which is important for seeing fine details and long distances. AMD has two forms: wet AMD and dry AMD. Most people with AMD have dry AMD. But dry AMD can progress to wet AMD. Wet AMD is the more serious form and can result in severe vision loss. - A method to identify and monitor the early to middle stages of AMD may help researchers develop new treatments to stop the disease before it becomes severe. In early dry AMD, people cannot see well at night. Researchers want to study whether a procedure that measures how the eye adjusts to the dark can help to identify and monitor early to middle dry AMD. Objectives: - To evaluate the effectiveness of using a dark adaptation protocol to identify and monitor early to middle dry age-related macular degeneration. Design: - People will be screened with a physical examination, medical history, blood and urine tests, and a full eye exam. - This study will last 5 years and require at least 9 visits to NIH. (First visit;study visits at months 3, 6, 12, 18, and 24;and 3 yearly followup visits). -Up to 10 people will be asked to come back to the clinic 1 week after their first visit. They will be asked to test the device to be used in the study. - Participants will have baseline exams. These questions will be about problems that affect their eyes under different lighting conditions. - At every visit, participants will answer questions about general health and current medications (including any vitamins or supplements). They will also have a full eye exam and a 20- to 40-minute test. This test measures how fast the eyes recover in response to decreasing levels of light. The test also measures how sensitive the eyes are to these conditions. - Participants will continue to have these tests at the yearly followup examinations. They will be treated with the standard of care for any eye conditions they have or may develop during the study. Title: Home Vision Monitoring in AREDS2 for Progression to Neovascular AMD Using the Foresee Home Device Number: 11-EI-0124 Summary: Background: - In the wet form of age-related macular degeneration (AMD), new blood vessels grow and cause fluid leaks into the retina, which leads to loss of vision. Some studies suggest that if the development of new blood vessels (choroidal neovascularization, or CNV) is detected early, treatment could be started sooner, which may help prevent visual loss. One possible method of early detection is the ForeseeHome device, which is part of a program designed to allow individuals to monitor their eyes for vision changes at home. Researchers are interested in comparing eye disease progression in people using the ForeseeHome device with those not using the device. Objectives: - To determine if home monitoring of age-related macular degeneration using the ForeseeHome device can help detect progression of disease earlier than standard care. Design: - Participants will be screened with a physical examination, medical history, and eye examinations. Participants will also be introduced to the device in order to determine if they will be able to use it for the duration of the study. - Half of the study participants will receive the ForeseeHome device;the other half will have standard of care monitoring. Participants will be asked only to monitor the eye(s) that are at risk for progression to wet AMD. - Participants assigned to the device monitoring group will receive the ForeseeHome device, a personal monitor that has a head unit with a viewer and internal screen, and a modem connected to a telephone cord. This cord must be attached to a land telephone line so that it can send data to the sponsor. Set-up instructions will be included with the device. - Participants will use the ForeseeHome device daily by looking at a screen and identifying certain patterns presented on the screen. The test takes about 4 minutes for each eye at risk. Test results will be transmitted by the modem to the sponsor, and the results will be reviewed by trained personnel. If the testing suggests a change in eye condition, participants and their AREDS2 clinic site will be notified by telephone and asked to schedule an appointment for an examination within 3 days of the call. - Participants in the standard care group should continue to have regular clinic visits and the required AREDS2 study visits, and will monitor eye symptoms using the instructions provided by the eye doctor for identifying possible CNV. Participants should contact the AREDS2 clinic promptly and come to the clinic within 3 days of any
