eyeGENE: Linking Patients and Clinicians to Genetic Testing and Research

eyeGENE: Linking Patients and Clinicians to Genetic Testing and Research


In 2003, a meeting was convened by the National Eye Institute (NEI) to consider setting up a National Ophthalmic Disease Genotyping Network. Such a network’s guiding philosophy was that access to patient samples coupled to anonymous phenotypic data would augment the pace of ophthalmic genetics research, leading to improved medical decision making, clinical trials, and treatments for genetic eye disease.

The meeting included experts in ophthalmic genetics, genetic counseling, and medical ethics, as well as representatives from federal regulatory bodies and non-profit organizations interested in advancing the investigation and treatment of rare disorders.

Now known as eyeGENE, this network links a coordinating center, where a centralized repository for patient DNA samples and a secure prospective database of phenotypic data are housed, with laboratories nationwide that have been certified under the Clinical Laboratory Improvement Amendment of 1988 (CLIA).

Specific goals and outcomes of the network are to:

  • facilitate research on the discovery of the genetic causes of ocular diseases
  • provide accurate diagnostic genotyping to patients with inherited eye diseases
  • develop public and professional awareness of genotype/phenotype resources for people with inherited diseases that affect the visual system, their clinicians, and for scientists studying these diseases
  • identify and engage broad patient populations in therapeutic clinical trials designed to diagnose, prevent, and treat genetic eye diseases

    Ian M. MacDonald MD, CM is branch chief of ophthalmic genetics at the National Eye Institute (NEI) of the National Institutes of Health. Brian P. Brooks MD, PhD, is director of the National Ophthalmic Genotypic Network and staff clinician at the NEI. Neither author has a financial interest in any of the information contained in this article. Dr. MacDonald or Dr. Brooks can be contacted at (301) 496-3577
  • allow for the analysis of larger data sets necessary to identify novel heritable traits for ocular diseases
  • drive refinement/standardization of clinical phenotypic descriptors, especially for complex ocular diseases
  • develop and validate cutting-edge genomic technologies and resources for the diagnosis of inherited ocular diseases
  • develop a shared database of genotype/phenotype information
  • provide a repository of DNA coupled to anonymous phenotypic information for researchers.


A clinician acts as the primary contact for the network. After pretest genetic counseling and consenting, the clinician submits a blood sample to eyeGENE, along with specified clinical information that becomes part of the central database (Figure 1). Patients are asked in advance whether they wish to know the results of their molecular testing and whether they would like to be recontacted in the future for clinical studies on their disorders. Molecular testing is then performed at 1 or more of the network laboratories, and a report is sent back to the clinician via the eyeGENE coordinating center. The clinician then explains the outcome of the testing and provides genetic counseling.

Figure 1. An example of how eyeGENE looks.

Patient confidentiality is maintained throughout the process. A lab within the network receives a coded sample, determines the genotype, and deposits that information into the central database. The coordinating center certifies the report and forwards the results back to the referring clinician. This system therefore limits the number of people who have access to readily identifiable patient information. The database server is maintained by the Center for Information Technology, National Institutes of Health (NIH). The eyeGENE network is accessed via a secure Web browser session, indicated by the “s” in eyeGENE’s “https” Web address. Data is encrypted when sent between the eyeGENE user and NEI/NIH servers.

Therefore, the immediate effect of eyeGENE will be to put the tools of molecular medicine in the hands of clinicians. The long-term goals of this project, however, are to facilitate research and clinical trials on inherited eye diseases. In the future, registered researchers will be able to view deidentified genotypic and phenotypic information in the database and be able to request DNA samples for use in their research on inherited eye disease. In the event of a clinical study or trial, those patients who have consented to being recontacted will be informed of the opportunity.

Paul A. Sieving, MD, PhD, director of NEI, is quoted as saying, “EyeGENE is a nationwide program that will enhance our ability to connect genes to specific diseases, accelerate the pace of gene discovery, and speed research on treatments for blinding eye diseases. This coordinated effort will help move ophthalmology into the era of molecular medicine, in which disease is diagnosed and treated at the cellular and subcellular levels.”1 The network may eventually provide answers to questions regarding the prevalence of eye diseases and the effect of drugs on the genes underlying these diseases.


Over 38 million individuals in the US have a visual impairment from a number of causes, including cataracts, glaucoma, age-related macular degeneration, and diabetic retinopathy. The genetic predisposition toward many of these eye disorders has long been recognized. With the advent of modern tools of molecular genetics beginning in the early 1980s, major genes involved in retinoblastoma and retinitis pigmentosa (RP) were first identified. Since then, the pace of discovery has accelerated over the last 2 decades such that publicly accessible databases have a wealth of genetic material that can be applied to the understanding of the inheritance of genetic eye disorders. A recent editorial2 and accompanying articles in the Archives of Ophthalmology highlight how genetic information is transforming our approach to ocular disease. Now, the opportunity and the possibility of personalized molecular medicine have caught the attention of the major players in healthcare delivery.

Several gene-based therapies are on the horizon that target specific genetic ocular conditions such as Leber congenital amaurosis and translate many years of collaborative research by groups of investigators.3 With the opportunities presented by these gene-based therapies, we now face the challenge of identifying those individuals with inherited blinding disorders who could potentially benefit from these treatments. The ability to detect disease-causing mutations in many individuals with inherited eye diseases is a great accomplishment, with significant benefits to those people and their families. Genetic testing remains, however, expensive, time-consuming, and not readily available to either the practicing clinician or the general patient who is concerned about his or her risks. One of the driving forces behind the network is the frequent request from patients for a better understanding of a heritable ocular condition and their relative risk. For example, how would you counsel a patient whose parent had lost vision from RP and now wants to know the risk of developing RP?

In September 2006, the eyeGENE coordinating center received and processed its first blood sample through the eyeGENE Network. An example of how eyeGENE works is exemplified by the following: A patient with a clinical diagnosis of Stargardt disease was recently referred to the Network by a clinician (Figure 2). The phenotypic data on this patient were recorded into the database, including vision, visual field, and electroretinography results. The patient provided a blood sample that was then coded and sent to one of the CLIA-certified laboratories, which then confirmed that the patient had mutations in the ABCA4 gene that is known to underlie Stargardt disease and other retinopathies.4 A banked sample remains within the repository along with the phenotype data that can then be used by future researchers. In this case, the genetic mutation was found. If no mutations had been found, the sample could conceivably provide an opportunity to find as yet unknown genes involved in genetic eye disease.

Figure 2. A case of Stargardt disease logged in the eyeGENE Network.

The NEI has helped build a foundation for collecting genetic information, and will continue to coordinate what information is already available in the ophthalmology and vision science community. Primarily a research program, eyeGENE will also provide medically useful information on genotypes and phenotypes to people with inherited eye diseases and their physicians. RP

More information regarding this resource can be found by accessing

The National Ophthalmic Disease Genotyping Network, eyeGENE, is supported by the National Eye Institute.


1. NEI Program targets genetic eye diseases. NIH Rec. 2007;59:5.

2. Hyman L, Klein B, Nemesure B, Wiggs J. Ophthalmic genetics: at the dawn of discovery. Arch Ophthalmol. 2007;125:9–10.

3. Acland GM, Aguirre GD, Ray J, et al. Gene therapy restores vision in a canine model of childhood blindness. Nat Genet. 2001;28:92–95.

4. Allikmets R. Simple and complex ABCR: genetic predisposition to retinal disease. Am J Hum Genet. 2000;67:793–799.

Members of the NEI working group who oversee the day-to-day operations of the eyeGEN Network include Delphine Blain, MS, MBA, CGC, genetics counselor; Brian Brooks, MD, PhD, Chair, eyeGENE Steering Committee; Hemin Chin, PhD, NEI Extramural Program Director, Ocular Genetics; Ian MacDonald, MD, CM, Chief, Ophthalmic Genetics, NEI; Ajaina Nezhuvingal, MS, eyeGENE Coordinator; David Scheim, PhD, database development; Nizar Smaoui, MD, NEI DNA Diagnostic Laboratory; Don Smith, MS, Information Technology Security; and Santa Tumminia, PhD, eyeGENETM Project Officer.

The current list of CLIA laboratories within the network are:

  • Rando Allikmets, PhD, Columbia University, New York
  • Radha Ayyagari, PhD, University of Michigan Medical School, Ann Arbor
  • David Birch, PhD, and Stephen Daiger, PhD, Retina Foundation and University of Texas Health Science Center, Houston
  • Elizabeth Engel, MD, Children´┐Żs Hospital, Boston
  • Susan Hayflick, MD, Oregon Health and Science University, Portland
  • Joan O’Brien, MD, University of California, San Francisco
  • Nizar Smaoui MD, and Fielding Hejtmancik MD, PhD, National Eye Institute, Bethesda, Md
  • Alan Shiels, PhD, Washington University Medical Center, St. Louis, Mo (in progress)
  • Janey Wiggs, MD, PhD, Harvard Medical School, Boston
  • Richard Yee, MD, University of Texas Medical School, Houston
  • Kang Zhang, MD, PhD, University of Utah, Salt Lake City