The recommendations caution against routine testing in the absence of
proven treatment, while proponents say supportive clinical studies already
The American Academy of Ophthalmology developed a set of
guidelines for genetic testing in individuals with inherited eye disease,
noting the possible risks associated with such testing. However, some
clinicians fear the recommendations may be misinterpreted.
The American Academy of Ophthalmology’s
(AAO’s) guidelines, in summary, recommend: offering genetic testing when
clinical findings suggest a Mendelian disorder whose causative genes have been
identified; using laboratories approved by the Clinical Laboratories
Improvement Amendments; providing the test results to patients; avoiding
direct-to-consumer genetic testing; avoiding parallel testing; and avoiding
testing in most asymptomatic minors with untreatable disorders.
One additional recommendation with which some have taken
issue says clinicians should “avoid routine genetic testing for
genetically complex disorders such as age-related macular degeneration and
late-onset primary open angle glaucoma until specific treatment or surveillance
strategies have been shown in one or more published clinical trials to be of
benefit to individuals with specific disease-associated genotypes.”
Rationale behind release of guidelines
Mathew W. MacCumber
“Over the last few years, there has been a
proliferation of genetic tests for ophthalmology, for multigenic disorders such
as macular degeneration, and there have been efforts by genetic testing
companies to market their products to consumers over the Internet,” Mathew
W. MacCumber, MD, PhD, one of the authors of the AAO guidelines, said in an
interview with Primary Care Optometry News.
“It was felt that there should be some policy
statement made to discourage direct-to-consumer marketing because the
interpretation of these test results can be complex, and there could be
important decisions made based on them,” he said. “The interpretation
of the results should be conducted by a physician, or a genetic counselor, at
“Now, that’s not to say that in the future we
won’t be able to direct care based on genetic tests,” Dr. MacCumber
continued. “I think there are certain situations where genetic tests are
Misinterpretation of guidelines?
Jeffry D. Gerson
Some doctors may misinterpret the guidelines, according
to Jeffry D. Gerson, OD, of WestGlen Eyecare in Shawnee, Kan., told PCON.
The recommendation regarding waiting for “specific
treatment or surveillance strategies” does not seem to be based on
currently available scientific information, he said.
“It is important to recognize the power of genetic
testing,” Dr. Gerson said. “The fact that the AAO has set such
guidelines shows that the group recognizes potential value in it. I agree that
any genetic testing should be used only when scientifically sound and
appropriate, and with the needed follow-up to explain the results to the
Clinical studies support early intervention
However, in the case of dry age-related macular
degeneration (AMD), sufficient published, scientific evidence shows how genetic
testing can help stratify risk of conversion from dry to wet AMD, he said.
Therefore, genetic testing can help clinicians better understand each
patient’s condition and allow for individualized counseling and care, Dr.
According to Brent Zanke, MD, PhD, FRCPC, chief medical
officer at ArcticDx, developer of the genetic test, Macula Risk, “The
ability of AMD genetic testing to identify persons at high risk for progression
has been consistently reported by well-respected investigators publishing in
high impact clinical journals. The use of genetics to predict progression risk
has been established.”
David W. Nelson
“In the case of macular degeneration, there already
exists sound information supporting the use of genetic tests to enable early
intervention,” private practitioner and ArcticDx vice president for
optometry professional relations, David W. Nelson, OD, MBA, told PCON.
“ArcticDx agrees with the AAO guidelines for the most part, but in the
area of AMD, it’s well documented that these tests have a high predictive
“You can really make a difference when you
preventively counsel an AMD patient,” Dr. Nelson added.
“We’re not restricting it,” Dr. MacCumber
clarified. “We’re just making recommendations as a policy statement.
Regarding the multifactorial conditions, such as AMD, it was felt that there
isn’t, at this time, an intervention, or even an improved surveillance
strategy, where genetic testing has been proven by a clinical trial to improve
Michael J. Tolentino
“Until we have an intervention that has been proven
effective, we do not feel that genetic testing should be used routinely in
these more complex disorders,” he said.
“Currently available genetic tests for AMD have
attributable risks greater than 0.80, which is a highly predictive test for
development and progression of the disease,” Michael J. Tolentino, MD, a
member of the PCON Editorial Board, said in an interview. “These tests can
be used to stratify patients who need closer monitoring and more emphatic
counseling on modifiable risk factors.”
Closer monitoring, leading to earlier detection, could
potentially reduce the number of intraocular injections and improve final
visual results for the exudative AMD patient, Dr. Tolentino added.
“The highly predictive, clinically beneficial tests
for AMD should not be clumped together with other genetic tests,” he said.
– by Daniel R. Morgan
For more information:
- AAO Recommendations for Genetic Testing of Inherited Eye Diseases: http://one.aao.org/CE/PracticeGuidelines/ClinicalStatements_Content.aspx?cid=f84ff8ef-9772-42ea-a168-8e096ac24d00.
- Jeffry D. Gerson, OD, FAAO, can be reached at WestGlen Eyecare, 16202 Midland Dr., Shawnee, KS 66217; (913) 962-2010; email@example.com.
- Mathew W. MacCumber, MD, PhD, can be reached at firstname.lastname@example.org.
- David W. Nelson, OD, MBA, can be reached at 7428 Mineral Point Road, Madison, WI 53717; (608) 365-9591; email@example.com.
- Michael J. Tolentino, MD, is a Primary Care Optometry News Editorial Board member and director of research at the Center for Retina and Macular Disease. He can be reached at 250 Avenue K, SW, Winter Haven, FL 33880; (863) 297-5400; firstname.lastname@example.org; www.crmd.net.
- Brent Zanke, MD, PhD, FRCPC, is chief medical officer for ArcticDx. He can be reached at (647) 287-8070; email@example.com.
- Disclosures: Dr. Gerson is on the ArcticDx advisory board. Dr. MacCumber is participating in a clinical trial funded, in part, by ArcticDx and Sequenom. Dr. Nelson is vice president for optometry professional relations for ArcticDx. Dr. Tolentino is a scientific advisor for Sequenom and ArcticDx.