遺伝性眼疾患の遺伝学

OBJECTIVE:

Molecular genetics and genomics are revolutionizing the delivery of medicine in general and ophthalmology in particular. New treatment and prevention strategies rely on a detailed understanding of the genetics and molecular pathogenesis of vision-threatening disease. In addition, in order to determine whether an intervention is therapeutic, we must first have some understanding of what the best clinical outcome variables are for measuring a treatment effect. Because our ultimate goal is to develop disease-specific protocols for specific inherited conditions, establishing this protocol will help us establish an initial critical mass of patients and of knowledge to write such protocols; as such, this protocol will be hypothesis generating. A secondary aim of this protocol is to provide a mechanism for obtaining research samples from subjects that may be used for laboratory investigations; in this case, the basic research may be both hypothesis generating and/or hypothesis testing. Lastly, the Ophthalmic Genetics Branch, as a leader in the field and a sponsor of a clinical training program, should have the ability to serve as a tertiary referral center for the nation in the area of undiagnosed genetic eye diseases.

STUDY POPULATION:

One thousand one hundred (1100) individuals with inherited eye diseases and 400 healthy volunteers (the unaffected relatives of affected participants) will be enrolled.

DESIGN:

This is a combined evaluation/treatment protocol and a genetic repository study. In general, participants will undergo a complete, age-appropriate, baseline examination and may provide a blood or saliva sample. Some participants may undergo more specialized ophthalmic and/or systemic testing, if clinically indicated by the investigator. Data and specimens generated through clinical care procedures may be collected and analyzed. The data and images obtained from these tests may be used for determining eligibility into another NEI protocol. Additionally, the collection of these data will help meet the primary research objectives of this study. Participants may be asked to complete optional participant reported outcome (PRO) questionnaires which will be assigned based on current diagnosis and previous testing. In a small number of cases, collection of blood, readily available biospecimens and body fluids (e.g., urine, saliva, tear fluid, stool, hair or cheek swab samples), conjunctival swab or lacrimal gland biopsy, impression cytology, and/or a punch skin biopsy may also be performed for research purposes.

OUTCOME MEASURES:

Given the breadth of ages and disease processes covered under this protocol, we will not systematically obtain any single outcome variable beyond visual acuity on research subjects. However, detailed, disease-specific findings will be collected through the NEI electronic medical record. Findings from systemic testing and from outside exams may be tabulated in a separate, secure database in the laboratory of the Principal Investigator (PI).