Clinical and Molecular Studies in Families With Glaucoma and Related Diseases
Clinical and Molecular Studies in Families With Glaucoma and Related Diseases
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 4 and older who have glaucoma or related diseases or whose family members have those
 diseases may be eligible for this study. They will complete a medical history for the doctors
 to verify the diagnosis, inquire about medical problems and surgical operations, and gather
 data about vision problems in a patient's family (by drawing a family tree). The complete eye
 examination may take several hours. Eye drops will be used to dilate, or enlarge, the pupils
 of patients' eyes, and the pupils will stay dilated for 4 to 6 hours. There may be some
 temporary glare in brightly lit areas, which can be reduced by wearing of sunglasses.
 Patients may experience some blurring of vision. There may be a localized allergic reaction
 to the medication used or an increase of pressure inside the eye. If that occurs, medication
 to control the reaction will be given. In addition, photographs of the retina and perhaps
 even the lens will be taken. For that procedure, eye drops will dilate the pupils of the
 eyes. The light that is involved with the specialized photography may cause some mild
 discomfort. 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.
Objective: This project, Clinical and Molecular Studies in Families with Glaucoma and Related
 Diseases, will study the inheritance of glaucoma in families of many nationalities and ethnic
 backgrounds in order to identify the genes that, when mutated, cause glaucoma, elevated
 intraocular pressure, or similar diseases and the pathophysiology through which they act.

 Study Population: The number of subjects to be enrolled has no logical upper limit, but will
 be at least 250 and not more than 2000 during the next 5 years.

 Design: The study consists of ascertaining individuals and especially families with multiple
 individuals, affected by glaucoma or related retinal and anterior chamber diseases. These
 patients and their families will undergo detailed ophthalmological examinations and, where
 indicated, additional non-investigational examinations to characterize disease in their
 families and determine their affectation status. A blood sample will be collected from each
 individual for isolation of DNA and in some individuals biochemical testing or for
 lymphoblastoid transformation to establish a renewable source of DNA. Linkage analysis,
 physical mapping, SNP and microsatellite analysis for association studies, and mutational
 screening will be carried out to identify the specific the gene and the mutations in it that
 are associated with glaucoma in this family. If necessary, the gene product or blood sample
 will be characterized biochemically. The study will enroll subjects at the NEI and at
 collaborating institutions.

 Outcome Measures: Linkage will be determined using the lod score method and mutations in
 specific genes will be assessed using a combination of residue conservation, blosum score,
 and molecular modeling. Biochemical, metabolic, and physiological effects will be
 individualized to the specific assay.
-  INCLUSION CRITERIA:

 Subjects with the following will be recruited:

 1. Individuals or family members of individuals with glaucoma, either congenital,
 childhood, or age related.

 2. Adults must be capable of providing their own consent.

 3. All subjects must be able to cooperate with study examination and phlebotomy.

 4. Older than 4 years of age.

 EXCLUSION CRITERIA:

 1. Diseases, infections, or trauma that mimic primary glaucoma.

 2. Children requiring sedation for study procedures.