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 50 active trials in 2012 are listed below: For more info: http://clinicalstudies.info.nih.gov/cgi/protinstitute.cgi?NEI.0.html Title: A Pilot Study to Investigate Ustekinumab (StelaraTM) for the Treatment of Active Sight-Threatening Uveitis Number: 12-EI-0168 Background: - Uveitis is an eye inflammation that can cause vision loss. It is treated with eye drops, drugs and sometimes surgery. In some people, treatment may not prevent vision loss. A type of white blood cells called T-cells often have a role in causing uveitis. In some cases of uveitis, T-cells attack the eye and cause inflammation. A drug called ustekinumab reduces inflammation from these T-cells. Researchers want to see if ustekinumab can be used to treat uveitis. Objectives: - To see if ustekinumab can be used to treat uveitis. Eligibility: - Individuals at least 18 years of age who have active uveitis that needs treatment. Design: - Participants will be screened with a physical exam, eye exam, and medical history. Blood and urine samples will be taken. - Participants will have at least eight clinic visits during the 64-week study period. After the first visit, visits will occur at 2, 4, and 8 weeks, and then every 12 weeks. - Participants will have a ustekinumab injection at the first study visit. They will have additional doses at the second and third visits, and then every 12 weeks until 1 year after the first dose (Week 52). - Treatment will be monitored with frequent blood tests and eye exams. Other standard treatments for uveitis may be given as needed. - There will be a final study visit 3 months after the last injection. Title: A Phase I/II Study of the NT-501 Intraocular Implant Releasing Ciliary Neurotrophic Factor (CNTF) in Participants with CNGB3 Achromatopsia Number: 12-EI-0167 Background: - Achromatopsia is an inherited condition that causes vision loss because cells in the retina do not work properly. It causes loss of acuity, sensitivity to light, and loss of color vision. There are no effective treatments for achromatopsia. - Four genes currently are known to cause achromatopsia. One of these, the CNGB3 gene, is the cause in about 50 percent of people. - CNTF is a natural chemical found in the body that promotes survival and function of nerve cells. CNTF has been shown to be effective in treating retinal disease in animals and can slow vision loss. - CNTF has also been studied in over 250 people with retinal disease other than achromatopsia. In these studies, a CNTF implant was placed into the eye during a simple surgery. The implant releases CNTF inside the eye, near the retina. These studies suggested that a CNTF implant might help vision in some eye diseases. Objectives: - To learn whether a CNTF implant is safe for people with CNGB3 achromatopsia. - To learn whether CNTF can improve visual acuity or color vision, and whether it may reduce sensitivity to light in people with CNGB3 achromatopsia. Eligibility: You may be able to take part in this study if you: - Are at least 18 years old. - Test positive for mutations in the CNGB3 gene and have no mutations in another achromatopsia gene. - Have 20/100 vision or worse in at least one eye. - Are not pregnant or nursing. Design: - To determine if you can take part, we will ask about your medical history and do a physical examination and an eye examination. Blood and urine samples will be taken. - This study requires 11 visits to the National Eye Institute over 3 years. - One visit will be for the implant surgery. The implant will be placed in one eye only. - Study visits will take place 1 day after implant surgery, and again 1 week later and 1 month, 3 months, 6 months, 1 year, 1.5 years and 3 years later. These visits will help us evaluate the safety and benefit of the implant on your eye. - At the 3 year visit, you can choose to keep the CNTF implant in your eye, or you can have us remove it. Title: A Phase II Randomized Study to Compare Anti-VEGF Agents in the Treatment of Diabetic Macular Edema (CADME) Number: 12-EI-0134 Background: - Diabetic macular edema is a common eye complication of diabetes. It causes the blood vessels in the retina at the back of the eye to leak, causing swelling. The macula is the center part of the retina that is important for seeing fine details and for tasks such as reading, driving, or sewing. Swelling of the macula leads to vision loss and possible blindness. Inflammation may play a role in diabetic macular edema. It is also possible that there is a problem with the blood vessels and the blood supply to cells of the retina. - A chemical in the body called VEGF is important in the formation of blood vessels in the body. Lowering VEGF levels may help treat diabetic macular edema by reducing abnormal leaking blood vessels in the eye. Drugs that can lower or block VEGF include ranibizumab and bevacizumab. Both drugs have been shown to help treat diabetic macular edema. Researchers want to see if one of the drugs works better than the other. Objectives: - To compare the effectiveness of ranibizumab and bevacizumab injections for diabetic macular edema. Eligibility: - Individuals at least 18 years of age who have diabetic macular edema in at least one eye. Design: - Participants will be screened with a physical exam and medical history. A full eye exam will be performed. Blood and urine samples will be collected. - One eye will be selected as the study eye to receive treatment. If both eyes are affected, both eyes may be enrolled in the study and receive different drug treatments. - The main part of the study will last for 9 months. At each study visit, participants will have physical exams and eye exams. They will answer questions about their health and any side effects from the drugs. - Participants will be assigned to one of four groups. Two groups will have two series of ranibizumab and one series of bevacizumab shots. The other two groups will have two series of bevacizumab and one series of ranibizumab shots. A series is three eye injections of the same drug every 4 weeks. The injections will be given at these study visits. The series order will vary for the different groups. - After 9 months, participants will continue to have additional study visits. If the treatment seems to be successful, the study doctor may increase the time between visits. Study injections may be given as needed every 4 weeks for up to 3 years. - Participants may have laser treatments in a study eye if needed. After being in the study for 1 year, they may also have steroid injections or other treatments as directed for the macular edema. Title: Phase II, Randomized, Placebo-Controlled Study for the Evaluation of Finasteride in the Treatment of Chronic Central Serous Chorioretinopathy Number: 12-EI-0119 Background: - Central serous chorioretinopathy (CSC) is a disease that causes fluid to collect under the retina. It affects the macula, which is in the center of the retina and is needed for sharp, clear vision. In many cases, CSC resolves on its own and does not need treatment. However, in some cases it does not go away or comes back after treatment. This is known as chronic CSC. - Chronic CSC may be caused by hormones called androgens. Finasteride is a drug that can alter the effects certain of androgens. Researchers want to compare finasteride with a placebo to see if it is a safe and effective treatment for chronic CSC. Objectives: - To see if finasteride is a safe and effective treatment for chronic CSC. Eligibility: - Individuals at least 18 years of age who have chronic CSC in one or both eyes. Design: - Participants will be screened with a physical exam and medical history. A full eye exam will be performed. Blood and urine samples will also be collected. - Some participants may have photodynamic therapy (PDT), the standard treatment for CSC. PDT helps to reduce the amount of fluid in the eye. Participants will need to wait for 3 months after PDT before starting the finasteride study. - Participants will be separated into two groups. One group will take finasteride; the other group will take a placebo pill. They will take these pills for 3 months. - After 3 months on the assigned pill (finasteride or placebo), all participants will have the opportunity to take finasteride for at least another 4 years and 9 months. - Participants will have regular study visits. At each visit, they will have physical exams and eye exams. They will also provide blood and urine samples. Title: Blood and Saliva Sample Collection and Submission to the Age-Related Eye Disease Study 2 (AREDS2) Genetic Repository Number: 12-EI-0085 Background: - The Age-Related Eye Disease Study 2 (AREDS 2) is looking at different eye diseases. Study participants will provide blood and saliva samples. The samples will be stored for research on eye diseases. Objectives: - To collect blood and saliva samples for AREDS 2 research. Eligibility: - AREDS 2 research study participants. Design: - Participants will provide blood and saliva samples. - The samples will be submitted with personal and medical information. This information will be collected during the AREDS 2 procedures. Title: A Phase I Study to Investigate Subconjunctival Sirolimus for the Treatment of Active Autoimmune Non-Necrotizing Anterior Scleritis Number: 12-EI-0057 Background: - Autoimmune scleritis is an inflammatory disease that affects the white outer part of the eye. It is associated with immune system disorders like rheumatoid arthritis. It can cause blindness in severe cases. Most treatments for scleritis involve steroid or immune-suppressing drugs, but these can cause side effects in the whole body. - Sirolimus is a drug used to help prevent transplant rejection. It helps prevent the immune system from attacking the body. Researchers want to try giving sirolimus injections into the eye to treat severe scleritis. Objectives: - To see if sirolimus is a safe and effective treatment for autoimmune scleritis. Eligibility: - Individuals at least 18 years of age with autoimmune scleritis in at least one eye that has not responded to standard treatments. Design: - Participants will be screened with a medical history, physical exam, and eye exam. Blood and urine samples will also be collected. - One eye will be selected as the study eye to receive injections. - Participants will have six study visits over 4 months (initial visit and weeks 2, 4, 8, 12, and 16). The injection will be given at the first visit. If the study eye responds to the treatment, participants may have injections in the other eye at the second visit. - If there is still inflammation after the first injection, or if the scleritis improves but then returns, participants may have a second injection at Week 4. - Treatment will be monitored with blood tests and eye exams. - Participants may have study visits and injections for up to 1 year if the treatment seems to be working. Title: NEI Intramural Biorepository for Retinal Diseases Number: 12-EI-0042 Background: - To understand diseases of the retina and the eye, information is needed about people with and without such diseases. Researchers want to study these people and follow them over time. They also want to study body tissues and blood to understand the nature of eye disease. Studying genes, cells, and tissues may help them understand why some people get eye problems and others do not, or why some people respond to treatment while others do not. Researchers want to collect physical samples and personal data to develop a National Eye Institute database. Objectives: - To collect health information and blood and tissue samples from people with and without eye diseases, to be used in research studies. Eligibility: - Individuals of any age with different types of eye disease. - Healthy volunteers with no history of eye disease. Design: - Participants may be recruited from National Eye Institute studies or may be referred from other sources. - Participants will be screened with a physical exam and medical history. They will also have a full eye exam. Questions will be asked about family medical history, especially about eye disease. - Blood samples will be collected. Other samples, such as saliva, tears, hair, stool, and urine, may be collected as needed. Adult participants may also provide a skin sample. - Tissue or fluid from eye collected as part of eye care or treatment may also be added to the database. - No treatment will be provided as part of this study. Title: Pilot Phase I/II study of the Treatment of Classic Central Serous Chorioretinopathy with Topical Interferon Gamma-1b Number: 12-EI-0013 Background: - In the eye disease central serous chorioretinopathy (CSC), fluid collects under the retina at the back of the eye. CSC can resolve on its own, but in some people it lasts for several months or can come back. The fluid buildup during CSC can cause vision loss. The drug interferon gamma-1b can help reduce fluid accumulation in the retina. Researchers want to see if interferon gamma-1b can help treat and prevent vision loss from CSC. Objectives: - To see interferon gamma-1b eye drops are a safe and effective treatment for CSC. Eligibility: - Individuals at least 18 years of age who have CSC in at least one eye. Design: - Participants will be screened with a physical exam and medical history. They will also have an eye exam and blood tests. - This study will require at least six visits to the National Institutes of Health eye clinic over 8 weeks. Each visit will last up to 4 hours. - Participants will receive the study eye drops at the initial visit. The drops must be used three or four times a day for 2 weeks. They must be stored in a cool place (like a refrigerator). - Participants will return to the eye clinic 2 days after the first visit and 1, 2, 4, and 8 weeks after starting the study eye drops. These visits will involve blood tests and eye exams. - If the CSC does not improve after the first 2 weeks, participants will receive another 2 weeks of eye drops. This set will start 4 weeks after the initial study visit. - The study will end with the final visit, 8 weeks after the initial study visit. 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 changes in vision. - The ForeseeHome device will be returned (1) after progression to CNV of the eye at risk, (2) at the end of the study, or (3) if use of the device produces unreliable results such that monitoring with the device becomes unreliable. Title: Treatment of Non-infectious Panuveitis, Intermediate and Posterior Uveitis Associated Macular Edema with Intravitreal Methotrexate Number: 11-EI-0107 Summary: Background: - Uveitis comprises of a group of diseases associated with inflammation of the eye that can lead to vision loss. Some people with uveitis also have macular edema (swelling of the retina at the back of the eye). Uveitis and macular edema are treated with medications and sometimes surgery, but treatment does not always prevent vision loss. Previous research has shown that injections of methotrexate into the eye of people with eye disease other than uveitis can help relieve the inflammation, or swelling, that causes macular edema and can slow visual loss. However, it has not yet been approved as a treatment for macular edema associated with uveitis. Objectives: - To evaluate the safety and effectiveness of methotrexate injections as a treatment for macular edema associated with uveitis. Design: - This study requires at least nine visits to the National Eye Institute study clinic over a period of 6 months (24 weeks). - Participants will be screened with a full physical and ophthalmic examination, a medical history, blood and urine tests, and additional eye and other tests as needed. - Participants will receive a methotrexate injection in a selected treatment eye. After the injection, participants will receive antibiotic eye drops to place in the eye three times a day for the 3 days following the injection, leucovorin (folic acid) drops to place in the eye four times a day for 1 week following the injection, and a dose of folic acid to be taken by mouth the day after the injection. - Participants who tolerate the initial injection may continue to receive injections in their study eye every month for 6 months. After 6 months, participants who show improvement from the injections may be evaluated to receive additional injections every 4 to 8 weeks until researchers end the study. Title: A Phase I Unmasked Study to Investigate the Safety and Tolerability of Subconjunctival Injections of Palomid 529 in Patients with Neovascular Age-Related Macular Degeneration Number: 11-EI-0066 Summary: Background: - Wet age-related macular degeneration (AMD) occurs when abnormal blood vessels grow in the back of the eye, and leak blood and other fluids that damage the eye, produce scarring, and lead to blindness. People diagnosed with wet AMD have increased production of a body chemical called vascular endothelial growth factor (VEGF). VEGF is important in the formation of blood vessels in the body, and decreasing the production of VEGF is believed to help wet AMD patients by preventing or slowing the growth of the abnormal blood vessels. Anti-VEGF drugs have been used to decrease the production of VEGF, but some people do not respond completely to these drugs. - A protein in the body called mTOR also plays a critical role in regulating how cells divide and grow and obtain their blood supply. The experimental chemical Palomid 529 inhibits the production of mTOR. Researchers are interested in determining whether Palomid 529 is safe and can help individuals with wet AMD who have not completely responded to anti-VEGF treatments. Objectives: - To evaluate the safety and effectiveness of Palomid 529 as a treatment for wet age-related macular degeneration in individuals who have not responded to standard anti-VEGF treatments. Design: - Prior to the first visit, participants should have been seen at the National Eye Institute clinic under a screening or teaching protocol, or NIH protocol 08-EI-0103, High Speed Indocyanine Green Angiography Findings in Induction Regimen of Intravitreal Ranibizumab Injection for Neovascular Age Related Macular Degeneration. One eye will be designated as the study eye to receive the Palomid 529 treatment. - Participants will have a full physical examination and medical history, a full eye examination to evaluate eye health and vision, angiography to examine the blood vessels in the eyes, and blood and urine tests during the study - Participants will receive an injection of Palomid 529 into the study eye every 4 weeks during the study, for a total of three injections. Participants may also receive anti-VEGF injections such as ranibizumab (Lucentis(Registered Trademark)) or bevacizumab (Avastin(Registered Trademark)) in the study eye 12 days before and 12 days after the Palomid 529 injection. - Participants may have standard-of-care treatments for the non-study eye if it has wet AMD as well, but may not receive experimental treatments in the non-study eye while they are in this study. - Participants will return for long-term follow-up examinations as directed by the study researchers. Title: Peptide B27PD (Optiquel) as Corticosteroid-Sparing Therapy for Chronic Non-Infectious Autoimmune Uveitis (BOOTS) Number: 10-EI-0191 Summary: Background: - Uveitis is a serious inflammatory condition in which the body's immune system attacks parts of the eye, often causing vision loss. Uveitis treatments involve various drugs that suppress the immune system, but these medicines sometimes do not work or may cause serious side effects. Researchers are interested in developing new treatments for uveitis that are more effective and have fewer side effects. - Optiquel(Trademark) is a natural product. It is an experimental medication being tested for its effectiveness again uveitis. It contains B27PD, a small protein fragment, which is similar to proteins in the parts of the eye being attacked by the immune system. Taking B27PD by mouth may induce oral tolerance, in which the immune system is taught to recognize and not attack normal parts of the human body. Objectives: - To evaluate the safety and effectiveness of B27PD (Optiquel(Trademark)) as a treatment for uveitis. Design: - Participants will be screened with a physical examination, medical history, blood and urine tests, and an eye exam. - This study will last 52 weeks, with at least 17 study visits. - Participants will be divided into three groups, and will randomly be selected to receive one of two different doses of B27PD or a placebo. During the study, participants will also have their dose of prednisone or other steroid medication reduced. - Participants will take one pill three times per week on Monday, Wednesday, and Friday, for a total of 26 weeks. The pill should be taken in the morning (at least 4 hours after eating and at least 30 minutes before eating). Participants may take the pill with water, but should not consume any other beverages or any kind of food until at least 30 minutes have passed to prevent stomach upset. The pills should be stored in the refrigerator. - During the first 12 weeks of the study, participants will have a study visit every 2 weeks. For the remainder of the study, participants will have a study visit every 4 weeks. Participants will have frequent blood and urine tests, and will also have eye examinations and special procedures (fluorescein angiography and indocyanine green angiography) to evaluate the effectiveness of the treatment. Title: Microplasmin Intravitreal Administration in Participants with Uveitic Macular Edema Number: 10-EI-0186 Summary: Background: - Uveitis is a serious inflammatory condition in which the body's immune system attacks parts of the eye, often causing vision loss. Some people with uveitis also have macular edema (swelling of the retina at the back of the eye). Uveitis and macular edema are treated with medications and sometimes surgery, but in many people treatment does not prevent vision loss. - Research has shown that injection of the lab-made protein microplasmin into the eye of people with eye disease other than uveitis can help treat macular edema and can slow visual loss. Microplasmin has not been approved to treat uveitis; however, researchers are interested in determining if it can be a safe and effective treatment for macular edema related to uveitis. Objectives: - To investigate the safety, tolerability and potential efficacy of an intravitreal injection of microplasmin as a possible treatment for macular edema secondary to uveitis. Design: - Participants will be screened with a physical examination, medical history, blood and urine tests, and an eye exam. - The study will last 6 months, and will require eight visits to the National Eye Institute outpatient clinic. Each visit will take about 3 to 4 hours. - At the first study visit, participants will have a complete physical and eye examination, medical history, blood tests, and two eye imaging studies (B-scan ultrasound and fluorescein angiography). After the tests are complete, participants will receive an injection of microplasmin directly into the eye. Participants will be given antibiotic eye drops to use three times a day for 3 days following the injection. - Participants will have regular follow-up visits for 6 months to evaluate the results of the microplasmin injection. These visits will include complete physical and eye examination, blood tests, and eye imaging studies (B-scan ultrasound and fluorescein angiography). Title: Evaluation of Single Nucleotide Polymorphisms (SNPs) in Patients with and without Diabetic Macular Edema Number: 10-EI-0169 Summary: Background: - Diabetic macular edema (DME) is a common condition in people with diabetes. DME occurs when blood vessels in the eye leak fluid, resulting in swelling inside the back of the eye and progressive vision loss. Research has shown that good blood sugar control can reduce the risk and severity of DME. However, not all diabetic patients with poor blood sugar control develop DME, and some patients develop DME despite excellent blood sugar control. This suggests that other factors, such as genes or inherited traits, may predispose or protect a diabetic patient from developing DME. Objectives: - To investigate genetic factors that may influence the development of diabetic macular edema. Design: - The study will require one visit to the National Institutes of Health eye clinic. - Participants will be screened with a medical history and basic eye examination. Individuals who have certain eye diseases other than DME may not be allowed to enroll in the study. - Participants will provide a blood sample, and will receive fluorescein angiography (an injection of fluorescein dye, after which a camera will take pictures of the dye as it flows through the blood vessels in the eye). - No treatment will be provided as part of this protocol. Title: Genotype-Phenotype Study of Patients with Plaquenil(Registered Trademark)-Induced Retinal Toxicity, with Evaluation of the ABCA4 Gene Number: 10-EI-0140 Summary: Background: - Plaquenil (hydroxychloroquine) is an anti-inflammatory drug that is used to treat some autoimmune diseases such as lupus and rheumatoid arthritis. This drug can damage the retina by causing a condition called plaquenil-induced retinal toxicity, which may lead to vision loss. However, most people taking plaquenil do not develop this problem. Researchers are interested in studying whether differences in a person's genes explain why some people develop plaquenil-induced retinal toxicity while others do not. Objectives: - To investigate possible correlations between certain genes or genetic mutations and plaquenil-induced retinal toxicity. Design: - The study requires one or two visits to the National Eye Institute or an outpatient study clinic over a maximum 2-year period. - Participants will provide a personal and family medical history, and will have a full eye examination. - Participants will also provide blood samples for testing. - No treatment will be provided as part of this protocol. Title: A Pilot Study for the Evaluation of Minocycline as a Microglia Inhibitor in the Treatment of Diabetic Macular Edema Number: 10-EI-0098 Summary: Background: - Diabetic retinopathy, or damage to the small blood vessels at the back of the eye, is a frequent complication of diabetes, and is a leading cause of blindness. Diabetic retinopathy can lead to swelling within the eye, known as diabetic macular edema which causes vision loss. - Chronic inflammation has been implicated in diabetic macular edema. Microglia are cells in the retina involved in inflammation in the retina. For these reasons, microglia represent a promising cellular target for forms of therapy that limit the harmful inflammatory changes found in diabetic retinopathy. Minocycline, a drug that is currently approved for use as an antibiotic, may be able to inhibit microglia and thus reduce their contribution to chronic inflammation. Researchers are interested in examining whether minocycline may be used to treat or slow the progress of diabetic macular edema. Objectives: - To test the safety and effectiveness of minocycline as a treatment for diabetic macular edema. Design: - This study will last 2 years and 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 take minocycline tablets twice daily for 24 months. - During each study visit, participants will have full eye examinations to measure visual activity, retinal thickness, and blood flow to the eye. Participants will also have regular blood tests, including blood sugar tests. - Patients enrolled will have been previously treated with focal laser, or not amenable to focal laser treatment. At the Month 6, Month 12 and Month 18 visits, participants will be offered laser treatment if they are eligible, unless they have shown significant improvement in retinal thickness or visual acuity. - After the end of the study, follow-up care will be arranged with an outside ophthalmologist. Title: Immunogenetic Mechanisms in Behcet's Disease Number: 10-EI-0093 Summary: Background: - Uveitis, the inflammation of the interior of the eye, is responsible for numerous new cases of legal blindness every year. Uveitis can be caused by Beh et's disease (BD), a chronic inflammatory disorder that can affect the eye, mucous membranes, and other body organs such as the joints, intestinal tract, blood vessels, and central nervous system. Objectives: The purpose of this study is to see how genes affect Beh et's disease and if there are differences in Beh et's disease among people of different backgrounds. Design: - As part of the study, blood samples will be drawn from participants when an exacerbation in disease activity occurs and before and after any significant change in treatment for BD. - No treatments will be provided in this study. Title: Rituximab for Autoimmune Retinopathy Number: 10-EI-0040 Summary: Background: - Autoimmune retinopathy (AIR) is an inflammatory condition in which the patient's own immune system is attacking his or her eyes and causing vision loss. Patients with AIR are generally treated with immunosuppressive agents to treat the eye inflammation; however, the standard treatment for this disease is still being developed. - Rituximab, an immunosuppressive agent, is a monoclonal antibody that is directed against a part of the immune system that may be an important cause of AIR. Rituximab is approved for the treatment of non-Hodgkin's lymphoma and rheumatoid arthritis, but is not approved for the treatment of AIR. Researchers are interested in determining whether rituximab may be used to treat AIR. Objectives: - To to investigate the safety, tolerability and possible efficacy of rituximab as a treatment for AIR. Design: - Before the start of the study, participants will be screened with a medical history, immunization records, a series of eye examinations, a chest X-ray, an electrocardiogram, and blood tests. - Participants will receive a maximum of two cycles of rituximab during the 18-month study. Each cycle will involve two separate intravenous infusions of rituximab given 2 weeks apart. - Participants will return to the clinic 6 weeks after the first cycle of rituximab for a safety visit, which will include a routine eye and physical examinations. They will also provide blood and other samples for study. - After the safety visit, participants will return every 3 months for follow-up visits. - At the 6-month visit, participants who have successfully or partially responded to rituximab will receive another cycle of treatment. Those who do not respond will not receive another cycle, but will continue to be monitored until the end of the study. Title: Internal Monitoring of Eye Movement in Schizophrenia Number: 10-EI-0016 Summary: Background: - Researchers are studying how humans are able to move our eyes to a remembered region even when the target has disappeared. The ability to do this suggests that the brain can keep track of where the eyes have looked, without an external target for continued reference. This is called corollary discharge. - Other research has indicated that patients with schizophrenia might have difficulty monitoring their eye movements. The corollary discharge process may be defective in patients with schizophrenia, and perhaps delayed in time. Researchers have developed a test to examine this possibility in the hope of learning more about schizophrenia and eye movement. Objectives: - To assess whether there is a defect in internal monitoring of eye movements in patients with schizophrenia. Design: - Researchers will check participants' vision in each eye, and ask them to sit at a machine that measures eye movement in order to complete research tasks. Researchers will monitor participants' ability to complete these tasks. - The first task involves simply following a target that jumps to different parts of the screen. - The second is a 2-step task, in which a participant is asked to look at two separate light targets and then look at the remembered target positions when the lights are off. - This protocol does not provide treatment. Participants will remain under the care of their own physicians during participation in this protocol. Title: Evaluation and Treatment Protocol for Potential Research Participants with Ocular Diseases Number: 08-EI-0169 Summary: This study will evaluate and provide standard treatments for people with various eye conditions. It will provide a resource for enrollment into new research protocols throughout the Eye Institute and will allow institute specialists the opportunity to maintain their expertise and gain additional knowledge of the course of various eye disorders. The information obtained will allow for the evaluation of standard treatments and may lead to ideas for future research. Title: High Speed Indocyanine Green Angiography Findings in Induction/PRN Regimen of Intravitreal Ranibizumab Injection for Neovascular Age-Related Macular Degeneration Number: 08-EI-0103 Summary: This study will use an eye imaging test called high speed indocyanine green angiography (HS-ICG), which examines leaky vessels in the eye, to try to find out why individuals respond differently to ranibizumab (Lucentis) treatment for wet age-related macular degeneration (AMD). The drug was recently approved by the Food and Drug Administration to treat this disease, but the response to the treatment varies markedly among individuals. Ranibizumab injections in the study eye once a month for 4 months. Additional injections are given only if the study eye shows signs of bleeding or leaking fluid. The eye is numbed before the injection and the eye area is cleaned with an antiseptic. Antibiotic drops are used for 3 days following the injection to prevent infection. Clinic visits once a month for 2 years for evaluations to monitor the response to treatment. The evaluations may include the following examinations and tests: -Eye examination with dilation, optical coherence tomography and photography: The examination measures visual acuity, thickness of your retina (the back of the eye) andeye pressure. Bright lights will also be used so that the doctor can see the back of your eye. Photographs of the eye may be taken. -Fluorescein angiography to examine the blood vessels in the eye: A dye called fluorescein is injected into a vein in the arm. The dye travels through the veins to the blood vessels in the eyes. A camera takes pictures of the dye as it flows through the blood vessels. This test is done eight times during the study. -Indocyanine green angiography to examine the blood vessels in the eye: The procedure is the same as for fluorescein angiography, but it uses a dye called indocyanine green. This test is done once a month for the first year of the study and then every 3 months. Title: Screening Study for the Evaluation and Diagnosis of Potential Research Participants Number: 08-EI-0102 Summary: This study will allow National Eye Institute (NEI) doctors the opportunity to examine people with eye disease, whether the diagnosis is known or not, to determine if they are eligible for other NEI research studies. No treatment is offered in this study. Participants undergo various tests and procedures to diagnose or evaluate their eye disease. The procedures may include the following: -Personal and family medical history -Physical examination and blood tests, including genetic testing. -Eye examination with dilation to measure visual acuity and eye pressure and to examine the front and back parts of the eye. -Questionnaire about vision and daily activities. -Conjunctival swab or lacrimal bland biopsy, or both: A sample of cells from the eyes is collected by swabbing the surface of the eye or by surgically removing a small sample of the surface of the eye or tear gland. -Electroretinogram to examine retinal function: The subject sits in the dark with his or her eyes patched for 30 minutes. The patches are removed, the surface of the eyes is numbed, and contact lenses that can sense signals from the retina are placed on the eyes. The subject then watches flashing lights. -Fluorescein angiography to examine the blood vessels in the eye: A dye is injected into a vein in the arm. The dye travels through the veins to the blood vessels in the eyes. A camera takes pictures of the dye as it flows through the blood vessels. -Optical coherence tomography to measure retinal thickness: A machine used to examine the eyes produces cross-sectional pictures of the retina. -Microperimetry to test how sensitive different parts of the retina are to changing levels of light. The subject sits in front of a computer and presses a button when he or she sees a light on the screen. -Oculography to record eye movements: Eye movements are measured by contact lenses or goggles that the subject wears while watching a series of spots on a computer screen. Title: Epigenetics, Molecular Genetics, and Biomarkers of Degenerative and Inflammatory Ocular Diseases Number: 08-EI-0099 Summary: This study will identify genes that are associated with inflammation or degeneration of the retina (membrane lining the back of the eye that relays vision signals to the brain). It is thought that many retinal conditions are due to an altered immune system and are based on how the person's genes function and communicate. Participants undergo the following tests and procedures: -Eye examination to assess visual acuity (eye chart test) and eye pressure, and to examine the pupils, lenses, retina and eye movements. Photographs of the inside of the eye may also be taken. The pupils are dilated with drops for this examination. -Blood draw for genetic testing. Participants may also undergo one or more of the following tests: -Optical coherence tomography. This is a type of photograph of the back of the eye to measure thickness of the retina. -Fluorescein angiography and indocyanine green angiography. Pictures of the eye's blood vessels are taken using either a fluorescein or indocyanine green dye. The dye is injected into a vein in an arm and travels to the blood vessels in the eyes. A camera takes pictures of the dye as it flows through the blood vessels. -Electroretinogram (ERG) to measure retinal function. The patient sits in a dark room for 30 minutes with his or her eyes patched. Then, a small metal disk electrode is taped to the forehead, the eye patches are removed, the surface of the eye is numbed with eye drops, and contact lenses are placed on the eyes. The patient then watches flashing lights. The contact lenses sense small electrical signals generated by the retina when the light flashes. Title: Age-Related Eye Disease Study (AREDS) Follow-Up Number: 08-EI-0043 Summary: This study is a 5-year extension of the AREDS protocol, in which investigators followed the natural course of age-related macular degeneration (AMD) and cataracts. Participants have a complete eye examination once a year and are contacted at least once a year between visits to check on their status. The eye examination includes measurement of visual acuity (vision chart test) and examination of the inside of the eye after the pupils have been dilated with eye drops. Photographs of the inside of the eye may be taken using a special camera that flashes a bright light in the eye. A blood sample may be obtained to test for cholesterol level and genes related to inflammation. Title: Visual Motor Coordination Number: 08-EI-0031 Summary: Background: -The relation between eye movement and brain function is a subject of interest to the National Eye Institute. -By comparing eye movement in healthy volunteers to research conducted on patients who have difficulty moving their eyes, the National Eye Institute hopes to develop and improve diagnostic procedures for people with eye diseases. Objectives: -To study eye movement in 100 healthy adult and child volunteers. -To understand how individuals see visual patterns and how eye movement affects the ability to see. Design: -Participants will visit the National Eye Institute outpatient clinic for examination and testing. -Participants will be screened with a medical history and eye examination (including eye pressure and eye movement tests). -Participants with healthy eyes will participate in eye movement testing experiments: --One or more sessions lasting less than three hours each. --Eye movements will be recorded with either a special contact lens or a video/infrared camera system. --For the majority of the studies done under this protocol, only one or two sessions will be required. A few studies recording very small eye movements will require three or more sessions. Title: Ocular Impact of X Chromosome Karyotype and Sex Hormones in Turner Syndrome and Premature Ovarian Failure Number: 07-EI-0145 Summary: Women with premature ovarian failure (POF) are at risk for dry eye. In addition, some women with Turner syndrome (TS) report dry eye symptoms. This study will determine how many women with TS have dry eye, compared to women with POF and women without these conditions. -Medical history: Subjects are asked about their current and previous medical conditions and treatments they have had in the past. They complete forms with information about how their eyes feel and if dry eye has bothered them. -Assessment of tears and eye surface: The amount of tears the eyes can produce is measured by placing a small piece of sterile paper in the corner of the eye for 5 minutes. Orange and green dyes are also placed in the eyes to determine the health of the surface of the eye. -Eye examination: Visual acuity (the ability to see the vision chart) and eye pressure (fluid pressure in the eye) are measured. Pupils and eye movements are examined. The structures inside the eye are examined through a microscope. The lens and retina (back of the eye) are examined after drops have been placed in the eyes to widen the pupils. The retina is examined with an ophthalmoscope (instrument with a strong light and magnifying lens). -Blood drawing: Blood samples are drawn through a needle in the arm to test for the level of sex hormones. -Conjunctival swab and tear fluid collection: A small sample of tears may be collected in a small tube to study their consistency and makeup. The top layer of cells from the surface of one eye may be removed with a swab or filter paper for study. Title: National Ophthalmic Genotyping and Phenotyping Network, Stage 1 - Creation of DNA Repository for Inherited Ophthalmic Diseases Number: 06-EI-0236 Summary: This study will collect blood and DNA samples from patients with inherited eye diseases to be used in research to identify genetic factors responsible for these conditions. In recent years, nearly 500 genes that contribute to inherited eye diseases have been identified. Disease-causing mutations are associated with many eye diseases, including glaucoma, cataracts, strabismus, corneal dystrophies and a number of forms of retinal degenerations. As a result, gene-based therapies are being pursued to treat eye genetic diseases that were once considered untreatable. The National Ophthalmic Genotyping Network (eyeGENE(Trademark)) is creating a national tissue repository to further advance genetic research on inherited eye disease, while at the same time providing clinically-useful information back to patients and physicians who request it.. Physicians in collaborating institutions will recruit patients to participate in the study. Patients will provide a blood sample and undergo a standard eye examination. The blood sample and clinical information will then be sent to the NEI for testing, processing and storing in the tissue repository. Patients are given the option to receive results back and/or to be re-contacted in the event of future clinical studies. Information supplied to the testing laboratories includes a unique identification number, the patient gender, and the patient date of birth. The stored samples will be made available to researchers along with information about the patient's disease, but without patient identifiers. Title: Family Studies of Uveal Coloboma Number: 06-EI-0230 Summary: This study will identify the genes responsible for uveal coloboma, an abnormal development of the eye caused by incomplete closure of a normally-occurring gap in the eye (the optic fissure) after the fifth week of life in a human embryo. There have been studies of families in which more than one person has been affected by this disorder. Coloboma occurs in about 1 of 10,000 live births and may cause significant vision loss. Researchers seek a better understanding of the genes responsible for this disorder. Patients will undergo a detailed medical history and eye examination appropriate for their age. The pupils will be dilated, through the use of eye drops. Dilation will continue for 4 to 6 hours, and wearing of sunglasses can reduce temporary glare that many patients may experience in brightly lit areas. In addition, pictures will be taken of the front or back of the eye, a procedure that also involves dilation of the pupils. Patients who have coloboma will undergo a complete physical examination. Blood samples will be collected, with a total of about 2 tablespoons from patients ages 10 and older and about 1 teaspoon for each 5 pounds of body weight for younger patients. Also, patients with coloboma may be asked to undergo X-rays , ultrasound, or other tests that are medically indicated. To have enough DNA to study, the researchers may create a cell line to grow more DNA. Laboratory samples will be coded so that there is no identifying information about participants in this study. No other testing or research will be done on blood samples collected unless patients give permission. The researchers will not provide information about patients' health to other people without your express permission. Title: The Vitreous Proteome and Inflammatory Mediators in Ocular Inflammatory Disease Number: 06-EI-0068 Summary: This study will examine the proteins of people with uveitis, or inflammation of the eyes. Evaluating the vitreous, the colorless transparent substance that fills the eyeball in back of the lens, is now possible with the use of new microtechnology. There is an opportunity to evaluate the kinds of proteins that are present in severe, noninfectious sight-threatening uveitis. Researchers will study the vitreous that will be removed from patients' eyes during an operation to insert a steroid implant. The steroid implant is used instead of immunosuppressive therapy, a way to reduce the action of the immune system. Patients will undergo a procedure involving a small hole made in the eye into which the implant is placed. Normally a small amount of the vitreous comes out during that procedure, and in this study, the vitreous specimen will be taken for testing of inflammatory products. At the same time, a small sample of blood, about 1-1/2 tablespoons, will be collected so that the researchers can compare inflammatory products that may be in the blood with those in the vitreous. If a patient needs to have the implant placed again during the study, he or she would be asked permission for collection of the vitreous and blood samples, as previously. Samples collected will not be used to diagnose patients' conditions or to change any treatments being done. All samples will be labeled with special code numbers so that there is no identifying information about patients. This study will not involve examinations or scheduled visits of patients. Title: Clinical and Molecular Studies in Families with Glaucoma and Related Diseases Number: 06-EI-0059 Summary: This study will document the clinical and genetic features of glaucoma and related diseases, including normal tension glaucoma (NTG). Researchers would like to define genetic influences and eventually isolate the genes causing those diseases. Glaucoma is an important cause of vision loss in the United States and worldwide. The disease is marked by a wearing down of the retina and optic nerve, often associated with increased pressure in the eye. It is often an inherited trait. This study will involve between 250 and 2,000 patients over a 5-year period. It will examine the natural history of the genotype, or genetic makeup, of a person and the phenotype, that is, visible situations produced by the interaction of the genotype and one's environment. Patients will undergo eye tests regarding color vision, field of vision, and ability to see the dark. Also, there will be a measurement of pressure in the eye and thickness of the cornea. To study patients' DNA, the researchers will obtain a blood sample of about 4 teaspoons from patients 10 years or older. A smaller amount of about 1 teaspoon for each 5 lb. of body weight will be collected from younger patients. Those DNA samples will be used only for research in the genetic disorder in a patient's family. No other testing or research will be conducted on the blood samples without patients' separate permission. Also, the DNA will be stored by codes that the researchers define and contained in a secured building. In this study, researchers will not provide information about a patient's health to patient family members or to other people. They will not discuss information such as adoption or biological fatherhood unless it has medical implications for the patient or the patient's family members. If information obtained from this study may be important to patients' health, they will be informed when it is available. There are no plans to give patients the results of any medical tests, evaluations, or other research data. Further research may be needed before such results become meaningful. Title: Clinical and Molecular Studies in Families with Myopia and Related Diseases Number: 06-EI-0058 Summary: This study will examine the inheritance of myopia in families of various nationalities and ethnic backgrounds to identify gene changes that cause myopia or similar diseases and to better understand these conditions. In patients with myopia, the eye does not focus light accurately on the retina (tissue that lines the back of the eye), so that objects at a distance appear blurry. Myopia may occur alone, with other vision problems such as retinal dislocations, cataract or glaucoma, or with other problems such as joint or skin problems. Each participant undergoes the following procedures: -Blood draw for genetic testing related to the disorders under study -Medical and family history, including drawing a family tree to explore vision problems in the family -Complete eye examination, including refraction (pupil dilation) and visual acuity testing, photographs of the retina and possibly lens, and specialized tests to measure field of vision, color vision and ability to see in the dark Title: Molecular Genetics of Retinal Degenerations Number: 05-EI-0143 Summary: This multinational study will investigate the inheritance of genetic retinal degeneration in families of different nationalities and ethnic backgrounds in order to identify the genes that, when altered, cause retinal degeneration. The retina is a light-sensitive membrane lining the back part of the eye. It relays vision signals to the brain, which the brain interprets into sight. When the retina degenerates, vision is altered and possibly lost. The findings of this study should help improve diagnosis and methods of treatment for these disorders. Participating institutions include: the National Institutes for Health in Bethesda, Maryland; the University of Miami in Florida; the Casey Eye Institute in Portland, Oregon; the Byrd Health Sciences Center in Morgantown, West Virginia; the University of Texas Southwestern Medical School in Dallas, Texas; the University of Tennessee Health Sciences Center in Memphis; the Prasad Eye Institute in Hyderabad, India; National Center of Excellence in Molecular Biology in Lahore, Pakistan; and the Jules Gonin Hospital in Lausanne, Switzerland. Participants undergo the following tests and procedures: -Medical and surgical history, including family history of vision problems. -Examination to clarify the type of retinal degeneration. -Eye examination, including tests of color vision, field of vision and ability to see in the dark -Electroretinogram to test the function of visual cells. For this test, the patient sits in a dark room for 30 minutes with his or her eyes patched. Then, a small electrode (silver disk) is taped to the forehead and the eye patches are removed. The surface the eyes is numbed with eye drops, and contact lenses are placed on the eyes. The patient looks inside a large dark globe that emits a series of light flashes. Then a light is turned on inside the globe and more lights flash. The contact lenses sense small electrical signals generated by the retina when the light flashes. -Hearing tests for patients with a personal or family history of deafness. Tests include an audiogram, ear examination and test of middle ear function. For middle ear function testing, the patient feels a little air pressure change for a moment and hears some tones. Another test requires the patient to sit quietly with electrodes on the head, forehead and earlobes. -Balance testing, including walking in a straight line, standing with eyes closed in the dark and other tests of coordination, and caloric testing. For the caloric testing, any ear wax in the ear canal is removed before the test begins. Then, electrodes are placed on the skin near the eyes and on the forehead. A small amount of cool (sometimes cold) or warm water is instilled into each ear canal, first one and then the other. -Blood sample collection for genetic testing. Title: Natural History and Genetic Studies of Usher Syndrome Number: 05-EI-0096 Summary: This study will explore clinical and genetic aspects of Usher syndrome, an inherited disease causing deafness or impaired hearing, visual problems, and, in some cases, unsteadiness or balance problems. Patients with type 1 Usher syndrome usually are deaf from birth and have speech and balance problems. Patients with type 2 disease generally are hearing impaired but have no balance problems. Patients with type 3 disease have progressive hearing loss and balance problems. All patients develop retinitis pigmentosa, an eye disease that causes poor night vision and eventually, blindness. Patients who have not been evaluated previously have the following tests and procedures at NIH: -Family medical history, especially regarding eye disease. A family tree is drawn. -Blood draw for genetic studies of Usher syndrome. -Eye examination to assess visual acuity and eye pressure, and to examine pupils, lens, retina, and eye movements. -Electroretinogram (ERG) to test the function of visual cells. Wearing eye patches, the patient sits in a dark room for 30 minutes. Electrodes are taped to the forehead and the eye patches are removed. The surface of the eye is numbed with eye drops and contact lenses are placed on the eyes. The patient looks inside a hollow, dark globe and sees a series of light flashes. Then a light is turned on inside the globe and more flashes appear. The contact lenses sense small electrical signals generated by the retina when the light flashes. -Fluorescein angiography to evaluate the eye's blood vessels. A yellow dye is injected into an arm vein and travels to the blood vessels in the eyes. Pictures of the retina are taken using a camera that flashes a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating possible blood vessel abnormality. -Hearing tests to help determine the patient's type of Usher syndrome. Tests to evaluate hearing include examination of both ears with an otoscope, evaluation of the middle ear and inner ear, and hearing tests using earphones that deliver tones and words the subject listens and responds to. -Vestibular testing for balance function. Balance testing involves three procedures: Videonystagmography: This test records eye movements with little cameras. First the patient follows the movements of some small lights. Next, while wearing goggles, the patient lies on an exam table and turns to the right and left. Lastly, a soft stream of air is blown into the patient's ears four times, once in each ear with cool air and once in each ear with warm air. Rotary chair test: With electrodes placed on the forehead, the patient sits in a rotary chair in a dark room. Several red lights appear on the wall of the room and the patient follows the lights as they move back and forth. Then the chair turns at several speeds, all slower than a merry-go-round. Vestibular evoked potential: Electrodes are placed behind the patient's ear and at the base of the neck. Seated in a reclining chair and wearing earphones, the patient hears a brief series of loud clicking sounds. When the sounds are on, the patient is asked to lift his or her head up a few inches from the chair. The electrodes record information from the muscles in the neck as the sounds enter the ear. Title: Clinical and Molecular Studies in Families with Corneal Dystrophy or Other Inherited Corneal Diseases Number: 04-EI-0008 Summary: This study will explore the clinical and hereditary (genetic) features of corneal dystrophy and other inherited corneal disease. Corneal dystrophy is clouding of the cornea - the transparent part of the eye covering the iris and pupil that passes light to the back of the eye. When the cornea becomes cloudy, interfering with the passage of light, vision may be impaired or lost. Corneal problems may occur with vision problems alone, or with other problems, such as changes in facial appearance or bone or joint problems. A better understanding of these genetic conditions may help in the development of better diagnostic tests and methods of disease management. Participants will undergo the following tests and procedures: - Medical and surgical history - Verification of diagnosis - Construction of a family tree regarding familial vision problems - Complete eye examination, including dilation of the pupils and photography of the cornea, tests of color vision, field of vision, and the ability to see in the dark, and photographs of the eye. - Blood sample collection to identify the genes responsible for corneal disease and ascertain how they cause disease. Title: Evaluation of Single Nucleotide Polymorphism (SNP) in Patients with and Subjects without Age-Related Macular Degeneration (AMD) Number: 03-EI-0155 Summary: This study will examine whether certain polymorphisms (small gene variances) predispose people to develop age-related macular degeneration (AMD). This eye condition affects people over 50 years of age and can cause permanent loss of central vision. The study will examine and compare the frequency of polymorphisms in patients with AMD to that of individuals without AMD. This information will help identify genetic risk factors for the AMD and may lead to the development of more effective treatments. All participants will provide an eye health history and will have 10 milliliters (2 teaspoons) of blood drawn from an arm vein. The DNA in the blood will be isolated and tested for certain genes that other research indicates are important in aging and age-related diseases. The normal and polymorphic gene sequences will be identified and compared in patients with AMD and control subjects to determine if any of the polymorphisms are related to development of AMD. In addition, control subjects will have a routine eye examination, including dilation of the pupils for examination of the back of the eye. Title: Clinical and Molecular Studies in Families with Congenital or Hereditary Cataracts Number: 03-EI-0123 Summary: This study will explore the clinical and hereditary (genetic) features of inherited cataracts. A cataract is a clouding of the eye lens, which focuses light on the back of the eye. When the lens becomes cloudy and does not let light through, vision is impaired. Cataracts may be associated with vision problems alone, or with other problems, such as changes in facial appearance or skin problems. A better understanding of these genetic conditions may help in the development of better diagnostic tests. Participants will undergo the following tests and procedures: - Medical and surgical history; - Verification of diagnosis; - Construction of a family tree regarding familial vision problems; - Complete eye examination, including dilation of the pupils and photography of the lens, tests of color vision and field of vision, and of the ability to see in the dark; - Blood sample collection (20 ml, or 4 teaspoons) for genetic studies of hereditary cataracts. Title: Evaluation of Immune Responses to Different Antigens in Non Infectious Ocular Inflammatory Diseases Number: 03-EI-0122 Summary: This study will collect blood samples from patients with non-infectious eye inflammatory diseases-a spectrum of eye disorders that can produce sight-threatening vision loss. The blood will be analyzed for substances that may provide a better understanding of the nature of these disorders, possibly leading to improved treatments. Treatment is not offered under this protocol. Title: X-Linked Juvenile Retinoschisis - Clinical and Molecular Studies Number: 03-EI-0033 Summary: This study will explore the causes and eye problems of X-linked juvenile retinoschisis (XLRS), an inherited disease that causes vision loss primarily in young males. The vision loss, which worsens over time, is a result of schisis, or splitting, of the layers of the retina (tissue that lines the back of the eye). A better understanding of why and how XLRS develops might lead to improved treatments. Patients will undergo the following tests and procedures: - Personal and family medical history to review past and current medical conditions and treatments, particularly regarding eye disease, and to construct a family tree. - Eye examination to assess visual acuity (eye chart test) and examine pupils, lens, retina, and eye movements. The pupils will be dilated with drops for this examination. - Photography of the retina to help evaluate the status of the retina. - Specialized eye tests to evaluate color vision, field of vision, and ability to see in the dark. - Electroretinogram (ERG) to examine what happens to the eyes after a flash of bright light. For this test, the patient sits in a dark room for 30 minutes with his or her eyes patched. Then, a small silver disk electrode is taped to the forehead, the eye patches are removed, the surface of the eye is numbed with eye drops and contact lenses are placed on the eyes. The patient looks inside a large empty bowl and then a light flashes, first in the dark and then with a light turned on inside the bowl. The contact lenses sense small electrical signals generated by the retina when the light flashes. - Blood test to examine DNA for genetic study of XLRS. Family members will provide a blood sample for genetic study. Title: Immunopathology and Molecular Pathology of Ocular Diseases in Humans Number: 92-EI-0113 Summary: The purpose of this project is to diagnose and evaluate ocular and related tissues with various diseases such as conjunctival, corneal, uveal, vitreoretinal and optic nerve disorders, ocular degenerative, metabolic or genetic diseases and tumors. These will be studied using light microscopy, electron microscopy, confocal microscopy, immunohistochemistry, molecular pathological including polymerase chain reaction and in situ hybridization, as well as measuring the functions of cellular organelles, e.g., mitochondrial function. Lymphocytes in the peripheral blood as well as other involved biopsied tissues and ocular tissue will be compared and categorized by disease. Cytokines, chemokines or growth factors and/or other released molecules in the blood and ocular fluids will be also analyzed. Elucidating the relationship between the infiltrating cells, ocular resident cells, and their products in various diseases will help us to make diagnoses and increase our understanding of human ocular disorders. Patients who require eye surgery to treat an eye disease or other disease in which the eye is involved may participate in this study. Samples of eye tissue and fluid that are normally removed and discarded during eye surgery will instead be given to researchers for study. The tissues will be examined under microscope and studied using sophisticated chemical and biological tests. Immune cells from blood samples may also be examined. These studies will help better understand and diagnose the various eye diseases and to develop more attractive therapies. Title: Trial of Topical Cysteamine in the Treatment of Corneal Cystine Crystal Accumulation in Cystinosis Number: 86-EI-0062 Summary: This study will continue to evaluate the long term safety and effectiveness of cysteamine eye drops for treating cystine crystals in the corneas of patients with cystinosis. These drops are not sold commercially and are available only through this study. New patients may enroll in the study to obtain them. Cystinosis is an inherited disease that results in poor growth and kidney disease, among other things. The damage to the kidneys and other organs is thought to be due to accumulation of cystine inside the cells of various body tissues. This chemical also accumulates in the cornea-the covering of the eye over the pupil and iris. After 10 to 20 years, the corneas of some patients become so packed with crystals that the surfaces may become irregular, occasionally causing small, painful breaks. Patients enrolled in a NIH study on cystinosis are receiving the drug cysteamine. Taken by mouth, this drug reduces cystine in some tissues, but not in the cornea, perhaps because it does not reach the corneal cells. The current study was begun to test whether cysteamine eye drops could prevent or reduce corneal cystine crystals in these patients. The drops have been very effective in removing crystals and reducing pain in patients who take the medication as directed. Patients who do not take the medication as prescribed do not benefit. New patients in this study will undergo an eye examination that includes tests of retinal function and evaluation of visual acuity, night vision and color vision, age permitting. They will take cysteamine eye drops in both eyes every hour during waking hours. For the first week of treatment, patients will be followed daily for possible side effects. Thereafter, eye examinations will be done every 12 months, and photographs will be taken of the eyes to assess the effects of treatment. Title: Extension Study for the Evaluation of Finasteride in the Treatment of Chronic Central Serous Chorioretinopathy Number: 11-EI-0012 Summary: Background: - Central serous chorioretinopathy (CSC) is a disease in which fluid accumulates under the retina and can cause distorted vision. CSC often resolves on its own without treatment, but in chronic CSC the persists and can lead to permanent visual loss. Chronic CSC may partly be caused by hormones called androgens, such as testosterone. - Finasteride is a drug that can block the effects of androgens; currently it is marketed as a treatment for male pattern baldness and benign prostate enlargement. The results of a previous brief study suggest that finasteride is safe and may help reduce the effects of chronic CSC. However, more long-term data are needed to evaluate whether finasteride is a safe and effective treatment for chronic CSC. Objectives: - To collect more data on the safety and effectiveness of finasteride as a treatment for chronic central serous chorioretinopathy. Design: - The study requires 11 visits to the NEI outpatient clinic over 5 years, with visits occurring every 6 months. Participants will be screened with a medical history, physical examination, eye examination, and blood and urine tests. - At each visit, participants will receive a supply of finasteride pills to take every day and will need to bring any leftover finasteride pills to the following visit. - Participants will have eye examinations to test vision, eye pressure, eye movements, and retinal thickness. Additional eye examinations will evaluate the retina's sensitivity to light and study the blood vessels and flow of blood in the eyes. - Blood and urine samples will be taken throughout the study. - After the end of the study, participants may be able to speak to their doctor about continuing finasteride treatments with a prescription. Title: Pilot Study of the Evaluation of Subconjunctival Sirolimus in the Treatment of Bilateral Geographic Atrophy Associated with Age-Related Macular Degeneration Number: 09-EI-0008 Summary: This study will determine if a drug called sirolimus is safe to give to people with geographic atrophy GA and if it can help preserve vision in patients. GA is an advanced form of dry age-related macular degeneration (AMD). AMD affects the macula, the central part of the retina needed for sharp, clear vision. There are two types of AMD, wet and dry. In dry AMD, cells in the macula die.GA may at least partly be caused by inflammation. Sirolimus helps prevent inflammation and therefore may help treat GA. Participants undergo the following tests and procedures: - Sirolimus injections in the study eye at each 3-month clinic visit. The drug is injected under the outer layer of the eye after the patient receives antiseptic and numbing drops. Antibiotic drops are continued for 2 days after the injection. - Eye examinations before the first injection, 1 month after the first injection, during each clinic visit (11 to 15 visits over 2 to 3 years) and 3 months after the final injection. The examination includes testing visual acuity, measuring eye pressure and checking eye movements. To examine the inside of the eye, the pupil is dilated with eye drops. Regular photographs of the inside of the eye and optical coherence tomography photographs, which allow measurement of the thickness of the retina, may be taken during the eye examination. - Autofluorescence imaging. The patient sits in a chair with his or her head placed in a chin rest in front of a camera. A light in the camera is used to scan the eye. - Blood tests. Blood is drawn at the first visit and at up to seven study visits to check blood chemistries, such as liver and kidney function. - Urine pregnancy test for women who are able to become pregnant. Title: Pilot Validation Study of Computer Administration of Vision Targeted Quality of Life Instruments Number: 08-EI-0135 Summary: This study will test and compare computerized and paper versions of eye questionnaires. Questionnaires are used in medicine to gain a better understanding of how a disease can impact a person's quality of life. Computerized versions of such questionnaires are often as good as or better than paper versions, but there has been no direct comparison of the two. This study may help in the development of eye questionnaires used to understand symptoms and monitor patients in clinical trials. All participants undergo the following procedures: -Medical and eye history. -Vision test and examination of the front part of the eye. -Tear measurement: A small piece of paper is placed on the surface of the eye to measure the amount of tears produced. The consistency of the tears is measured by looking at how fast they evaporate from the surface of the eye. -Completion of either paper-based or computer-based version of a questionnaire 15 minutes after the eye examination and completion of the other version within 1 week at home. (Subjects who complete the paper version in the clinic are told how to access the computer version online at home or on a library computer; those who complete the computer version in the clinic are given a paper version to take home.) Title: Laboratory of Immunology/National Eye Institute Repository Number: 07-EI-0213 Summary: This protocol will enable IRB (institutional review board) review of proposed research using human samples and data collected under the terminated NIH studies 04-EI-0065 and 96-EI-0096. Data and samples may include demographic and personal health information, psychological or psychiatric testing, blood, urine, CSF or other body fluids or tissues and results of medical and physiological evaluation and medical imaging. Data and sample analyses are limited to those approved under the original protocols unless additional specific institutional review board approval is obtained. Title: The Age-Related Eye Disease Study 2 (AREDS2): A Multi-Center, Randomized Trial of Lutein, Zeaxanthin, and Omega-3 Long-Chain Polyunsaturated Fatty Acids (Docosahexaenoic Acid [DHA] and Eicosapentaenoic Acid [EPA]) in Age-Related Macular Degeneration Number: 07-EI-0025 Summary: Among the estimated 937,000 blind people in the United States, approximately 90% are age 60 and older. One of the leading causes of vision loss in this age group is age-related macular degeneration. This study will evaluate whether certain vitamins and fatty acids can help prevent or slow down the progress of age-related macular degeneration. Researchers also want to learn if nutrients have effects on the development of cataracts. About 4,000 people will participate for 5 years. At the first clinic visit, patients will have an eye examination, have their eyes photographed, and learn about the study. They will receive a supply of placebos (sugar pills) and the standard formulation of the Age-Related Eye Disease Study supplement, which has vitamin C, vitamin E, beta-carotene, zinc oxide, and cupric oxide (copper). Patients who have smoked within the past year will not receive the standard formulation, for there is an increased risk of lung cancer for people taking beta-carotene. The second visit, 1 to 3 months later, involves an eye examination, vision check, and blood sample taken if patients agree to enter a substudy of other nutrient formulations. This study uses omega-3 long-chain polyunsaturated fatty acids (fish oils): docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Patients are placed randomly into four groups: receiving a placebo; lutein and zeaxanthin only; fatty acids only; and lutein and zeaxanthin plus fatty acids. During study visits and phone calls, patients will be asked about possible side effects. After 1 year, they will have an eye examination and photographs of the eyes, and will be asked about side effects from the pills they have been taking. There will be annual follow-ups for the study's 5 year duration. Risks include those involved in any routine eye examination such as discomfort or allergic reaction to eye drops used during eye examinations and drops for dilating the eyes that can cause a sudden increase in pressure in very few individuals. The supplements taken can also involve some symptoms. Fatty acids can cause mild gastrointestinal problems. Vitamin E side effects are rare but include fatigue and muscle weakness. In people without enough vitamin K, high doses of vitamin E may slow down clotting of blood. High doses of zinc can sometimes causes stomach upset. This study may have direct benefits for participants. They can learn more about their own eyes and eye disease. Knowledge gained can also help other people at risk for developing eye diseases in the future. Title: Multicenter Uveitis Steroid Treatment (MUST) Trial Protocol Number: 06-EI-0050 Summary: This study will test whether a new corticosteroid implant is more effective for reducing eye inflammation in patients with uveitis than the standard treatment with oral corticosteroids. Uveitis is an inflammation in the eye that, left untreated, can impair vision. Candidates are screened with a medical history, blood tests, measurement of blood pressure, height and weight, bone density scans of the spine and hip, and an eye examination. The eye examination includes a test of vision and eye pressure, photographs of the eye lens, fluorescein angiography (photographs of blood vessels in the back of the eye), and optical coherence tomography. For the fluorescein angiography, a dye is injected through a vein in the arm or hand. It travels through the bloodstream to the blood vessels in the back of the eye. A series of pictures are taken that reveal the location and severity of inflammation in the back of the eye. Optical coherence tomography uses light to measure the thickness of the central part of the retina (back part of the eye) to look for swelling. Participants are randomly assigned to receive oral corticosteroid treatment or the corticosteroid implant, as follows: -Corticosteroid implant Patients receive implants in one or both eyes, depending on whether one or both eyes need treatment. If both eyes are to receive implants, the second surgery is usually scheduled within 2 weeks after the first. The surgery is usually done under local anesthesia, with medication given through a vein to relax the patient and keep him or her comfortable during the procedure. A numbing medicine is injected around the eye to prevent pain. The implant is placed behind the iris (colored part of the eye), and a patch is placed over the eye until the day after the surgery. Patients are examined the day after surgery and once or twice more for checkups. The implant slowly releases a corticosteroid medicine called fluocinolone acetonide. It lasts about 2-1/2 years and can be replaced after that, if needed. -Oral corticosteroids Patients assigned to standard therapy take corticosteroids by mouth, with the dose being slowly decreased. If the dose cannot be reduced to a sufficiently low level because the inflammation returns, an immune-modulating drug is added to the treatment. Total treatment time varies, but, because uveitis often recurs, treatment may continue for two years or more. OR Patients assigned to standard therapy take corticosteroids by mouth, combined with other immunosuppressive agents, based on the individual patient's condition. The steroid dose is slowly decreased. Total treatment time varies, but, because uveitis often recurs, treatment may continue for two years or more. In addition to their assigned treatment, patients may receive corticosteroid eye drops, ointments, or injections next to the eye as needed for the most effective control of swelling and inflammation. Patients have clinic visits at weeks 4 and 12 after enrollment and every 12 weeks after that for up to 4 years. At each visit, patients provide a medical history, have an eye examination, complete questionnaires, have a blood test, and have their blood pressure and weight measured. They have fluorescein angiography and digital imaging of the eyes at weeks 4, 24, and 52 and then once a year. Color photographs of the eye are taken once a year. A scan of the spine and hip bones is done once a year. Visits to treat the uveitis may be required as often as once a month.