January 19, 2016
6 min read

Questions abound when faced with issue of genetic testing

Lisa K. Feulner, MD, PhD, explores how ophthalmologists may approach genetic testing in terms of treatment recommendations.

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Welcome to another edition of CEDARS/ASPENS Debates. CEDARS/ASPENS is a joint society of cornea, cataract and refractive surgery specialists, here to discuss some of the latest hot topics in ophthalmology.

Genetic testing has long been a controversial topic for numerous reasons. What do we do with the information? Will it affect our decision making? Is it even appropriate for us to obtain this information? This month, Lisa K. Feulner, MD, PhD, discusses the pros and cons of genetic testing. We hope you enjoy the discussion.

Kenneth A. Beckman, MD, FACS

To test or not to test? That is the question

My initial response to the question of genetic testing was a resounding “yes.” However, after deciding to write this article and researching the depths of this question, my thoughts have now led me down a different path. I strongly believe that we are headed into an age of customized and personalized health care. If we have the tools to determine a person’s risk for a disease, response to a medication or genetic risk factors for general health concerns, then we absolutely should use those tools to guide our patient care. As surgeons, we have not hesitated to invest in cutting-edge, state-of-the-art technology to provide the absolute best outcomes for our patients.

Lisa K. Feulner

We would not question ourselves or our peers for embracing the latest or newest technology for treatment of dry eye, glaucoma, corneal, retinal and refractive disorders, or cataract. Why, then, are we so resistant to accepting and implementing the available genetic tools for well-known ophthalmic diseases? Is it because we are appropriately cautious, do not understand the technology, do not know how to interpret the results or are not sure what to do with the information once we have it? Is it because at this point we have few therapeutic options to offer to change the genetic outcome or because there may be moral, ethical, psychological or social issues that arise from the knowledge of the genetic findings? Would we be comfortable anymore putting a multifocal implant into a person without evaluating their astigmatism, corneal surface, tear film or macula? We now have the technology to fine-tune our patient selection, IOL choice and therapeutic intervention to optimize our outcomes and would consider it unethical or ill-advised to ignore this available information. As physicians, we are comfortable with treating diseases. These diseases are sometimes the phenotypic expression of the genotypic makeup of the person. Determining and understanding the genetic risk factors and associations should allow us to better inform and treat our patients.

Evolution of genetic testing

Over the last decade, direct-to-consumer DNA-based tests have been pitched to patients, and as a result, these patients have come to our offices asking about this technology. In addition, physicians have been asked to embrace the use of genetic testing when considering genetic counseling, risk assessment and therapeutic intervention. A simple saliva sample or cheek swab can be used to calculate a person’s risk of developing everything from macular degeneration to his or her ability to appropriately absorb or metabolize a particular antihypertensive or pain medication. Genetic testing traditionally has been used in diagnostic medicine to analyze single gene mutations to identify individuals who are at risk for particular diseases such as autosomal dominant retinitis pigmentosa or Stargardt’s disease.

More recently, newer genetic analysis has been promoted for use in predictive medicine to determine an individual’s risk for certain diseases. This less specific form of genetic analysis usually describes the probability of developing a disease and is based on evaluation of trends in inheritance of allelic variations, which have been associated with a disease. This type of screening is much less definitive and does not take into account environmental, lifestyle or other genetic influences. Well-known examples of this type of screening using single nucleotide polymorphisms include the BRCA gene for breast cancer and, in our own specialty, AMD.


Sequencing of the human genome is now public knowledge, and as of June 13, 2013, human genes can no longer be patented. As a result, many companies now offer whole-genome and whole-exome (parallel) sequencing to identify genetic alterations in asymptomatic individuals, which may predict the predisposition for certain diseases. Much like whole body MRIs to look for occult disease, this potentially raises a multitude of moral and ethical questions.

Lastly, an exciting new field of pharmacogenomics, which looks at genomic variations predictive of drug metabolism and absorption, is being utilized by industry to offer testing, which may help us understand why some pharmacological agents work better in one patient vs. another and why some drugs are therapeutic in some people while toxic in others. We are moving into an era in which we will no longer have to trial and error our therapeutic interventions, but will be able to quickly determine which medication is most appropriate for a patient based on an individual’s unique genetic makeup. A future can be imagined in which a physician will be able to choose the most appropriate antihypertensive medication, from among the many classes, based on the individual’s DNA instead of trialing one or more before determining the most appropriate course of action. Ultimately, knowledge of the genetic basis of human physiology and disease will allow us to customize our approach to individual screening, monitoring and disease therapy.

But are we there yet? Have we done our due diligence before accepting these innovations? Are we prepared to be genetic counselors, deal with the potential discriminatory implications, or address the moral, ethical and social issues related to knowledge of an individual’s genetic risk factors? If there is no cure or significant therapeutic alternative to offer a person, is advising nutritional, behavioral or lifestyle changes to reduce associated risk factors or alleviate symptoms with early prediction enough? On the other hand, do we do our patients a disservice if we do not embrace genetic testing? For example, some would argue that the available tests for AMD are predictive of the likelihood of developing the disease and may help us alleviate the concerns in those with a family history of AMD while improving our ability to determine who needs closer surveillance, lifestyle changes or nutritional supplements. Others would argue that we should be doing this anyway and that the knowledge of the risk may cause undue psychological stress.

Guidelines on genetic testing

The American Academy of Ophthalmology published “Recommendations for genetic testing of inherited diseases: Report of the AAO task force on genetic testing” in 2012, which was revised in 2014 to emphasize the need for physicians to work closely with certified medical geneticists and/or certified genetic counselors when advising patients to undergo genetic testing. The task force acknowledged both the value of genetic testing in ocular disease as well as the potential risks and implications related to the results. The article summarizes seven specific recommendations put forth by the AAO task force, which include guidelines for which tests we should do, what laboratories should run the tests, the requirements for obtaining consent and reporting the results to patients, its position on direct-to-consumer and parallel testing, routine testing of genetically complex disorders, and testing asymptomatic minors for untreatable diseases.

In this fledgling era of genetic testing and pharmacogenetics, these guidelines are invaluable. Although I end this journey with a new respect and cautious approach to genetic testing, I still believe that customizing our approach to disease and therapeutics based on an individual’s genetic makeup is the future of medicine. It is essential that we develop a mechanism to modify our clinical approach to disease based on human genetics while being mindful of the moral, ethical, psychological and social consequences of this knowledge. The task force’s recommendations are a step in this direction.


With decreasing funding available for basic science research in the private sector, industry has assumed a greater role in providing important groundbreaking discoveries. Often this information is biased and restricted to financially rewarding pipelines; however, without this vital proprietary information, scientific breakthroughs would be decades behind where we are today. With that in mind, we must embrace the information we receive from all sources and continue our vigilance in interpreting and incorporating these innovations into our care of patients. The future holds promise as science continues to draw correlations between genotype and phenotypic manifestations of disease and propels us forward to a future that will allow us to use pharmacogenetics to more precisely dictate our therapeutic recommendations.

Disclosure: Feulner reports no relevant financial disclosures.