- Editor’s Page
- Genetics and Patients’ Response to AMD Nutritional Supplements
- Science Supports Genome-Directed Therapy for AMD
- Nutritional Supplementation and AMD
- The Role of Nutrition in Ocular Health
- Are We Ready to Embrace Nutrition?
- Debunking Myths About UV Light
- UV Protection From the Patient’s Perspective
- Cosmeceuticals: Sunscreens
- An Insider’s Look at Sunscreen Ingredients and Formulation
- How to Create a Successful Dry Eye Practice
- In Search of the Best Topical Treatment for Allergic Conjunctivitis
- Medical Marijuana for Glaucoma Therapy
- Sidebar: Discussing Medical Marijuana with Glaucoma Patients
- Talking to Your Patients About Cataract Surgery
- What Is Astigmatism? A Review
- Comanagement Can Benefit Rural Patients
- Femtosecond Laser Features: My Rankings
- Does Laser Cataract Surgery Produce Better Outcomes?
- Choosing the Right Implant in Presbyopia-Correcting Cataract Surgery
- When Equal is Not Equal
- Why I Am Glad My Cataract Surgeon Offers Dropless Cataract Surgery
- New Sealant’s Many Uses After Cataract Surgery
- Sidebar: Wound Leakage and Comanagement of Cataract Surgery
- How to Optimize YouTube Marketing for Your Eye Care Practice
- Gonioscopy-Assisted Transluminal Trabeculotomy: Blending Tradition With Innovation
Rarely does a published study have the potential to alter the way we practice eye care on a day-to-day basis as does the recent article by Awh et al.1
It is believed that many optometrists and ophthalmologists have followed and still do follow the recommendation of the National Eye Institute (NEI) and prescribe the Age-Related Eye Study (AREDS) or AREDS2 formula to all of their patients with age-related macular degeneration (AMD), regardless of their genetic profile. The recent article by Awh et al, combined with the same group’s article published a year ago,2 is, in my opinion, a game changer that will result in better visual outcomes for some of our AMD patients. By employing gene-directed therapy, we not only now have the opportunity to provide a higher level of care, but also the responsibility to do so. Failure to utilize an AMD genetic profile clearly has malpractice implications if we choose to ignore it.
Awh et al recently reported the results of a statistical analysis (via publicly available AREDS data and DNA samples) from nearly 1,000 patients in the original AREDS study that dates back more than a decade. The investigators identified complement factor H(CFH) and age-related maculopathy susceptibility 2 (ARMS2 genetic risk markers as significant predictors of an individual’s response to the AREDS formula and its components.1 This study defined four genotype groups (GTGs) based upon lower and higher CFH and ARMS2 risk allele numbers. Patients in group 1 had the lowest combined numbers of risk alleles and those in group 4 had the highest.
The new analysis confirms the most important previous findings by the same group: Patients with two highrisk CFH alleles and no high-risk ARMS2 alleles (defined as GTG2 should not take the AREDS formula. Patients in GTG2 had a 135% increase in disease progression when taking the AREDS formula versus those taking a placebo. Note that the number of patients in GTG2 is not trivial. Of the nearly 1,000 patients analyzed, 131 fell into this category.
Most clinicians would readily agree that their first professional responsibility is to do no harm. Remarkably, by following the NEI’s current recommendation and treating all patients who have intermediate AMD the same, with an AREDS formula, nearly 15% are subjected to far greater risk of progression and blindness than by doing nothing. The component in the AREDS formula responsible for this is high-dose (80 mg) zinc. Subjects in the group that took 80 mg of zinc alone and those in the group that took the AREDS formula containing 80 mg of zinc both did far worse than those in the placebo group.
In three previous articles in this publication,3-5 my colleagues and I criticized the NEI for continuing its recommendation of high-dose zinc even though its own AREDS2 study demonstrated no statistical difference between low-dose (25 mg) zinc and high dose (80 mg). We also pointed out the obvious conflict of interest that exists between big pharma and government with regard to AREDS and AREDS2. Perhaps even more important was the link that we documented between zinc and the same high-risk alleles (CFH) in both AMD and Alzheimer disease. Hence, the admonition to “do no harm” may well extend beyond AMD.
An unfavorable AMD genetic profile increases a patient’s risk of developing advanced AMD by as much as 400-fold compared with those lucky patients without the deleterious alleles. Patients with unfavorable genetic profiles deserve counseling to reduce their risk by improving their diet, exercising, controlling their weight, and stopping smoking. Both internal and external bluelight protection is highly desirable. Supplementation with the three carotinoids that compose the macula lutea is logical and supported by science. Patients in high-risk categories also deserve much more careful clinical monitoring.
I was recently asked to consult on a case of a 60-yearold white man who presented with intermediate AMD in both eyes 18 months ago. He then developed choroidal neovascularization, first in his right eye and then several months later in his left eye (Figures 1 and 2). He was treated multiple times with intravitreal injections of a vascular endothelial growth factor inhibitor in both eyes. When I examined the patient, his visual acuity was 20/400 in the right eye and 20/70 in the left. He was first prescribed the AREDS formulation (without beta-carotene) several years ago and then the AREDS2 formula when it became available. Unfortunately, the patient continues to smoke despite all efforts by doctors, friends, and family.
Let us assume that genetic testing was now obtained and the patient was revealed to be in GTG2 GTG2—the group with two high-risk CFH alleles and no high-risk ARMS2 risk alleles. It is often stated that smoking increases the risk of vision loss by threefold in AMD patients. In this case, with the genetic result proposed above, was it the smoking or the zinc that resulted in the progression from dry to wet AMD? Or was it the combination of both?
I know of a highly successful class-action attorney in the New York area who is pursuing such individual cases. A patient being treated with a nutraceutical containing high levels of zinc who converts from intermediate AMD to central wet AMD (such as in this case) might wonder why he or she worsened so dramatically while taking an NEI-approved supplement. If the patient does not question this, it is likely a family member or friend might. Assume such a patient is then demonstrated to have two high-risk CFH alleles and no ARMS2 risk alleles. Both papers by Awh et al would suggest that this patient should not have been treated with the AREDS formula.
A good attorney can develop a case based upon the science available and could well win a lawsuit. In my experience, a judge will instruct the jury that if a test was available that could have prevented blindness, that test should have been performed. This dates back to the Helling v Carey case many decades ago when an ophthalmologist failed to detect glaucoma in a 33-year-old contact lens patient he had been seeing for more than 10 years. In that case, the judge told the jury to disregard the standard of care (ie, eye pressures only needed in patients aged > 35 years) and find the ophthalmologist culpable of malpractice if a noninvasive available test could have prevented the blindness. The jury found the physician culpable even though he was following the existing standard of care. This case changed the standard of care overnight for optometrists and ophthalmologists.
In my opinion, the two studies by Awh et al reveal dramatic differences in outcomes based upon an individual’s genetic profile. These findings have profound significance and should become the new standard of care in AMD. I believe that big pharma and big government will be shown to be on the wrong side of history.
SUMMARY AND CONCLUSION
Tests to measure markers of AMD genetic risk are now readily available and can predict the response of an individual to the components of the AREDS formula. Personalized medicine has finally arrived in eye care, and this approach could lead to much improved outcomes. It defies comprehension that key individuals in government and industry state that knowing the genetic profile of patients is not necessary for providing optimal care and prescribing nutraceuticals.
The AREDS formula may be a ticking time bomb in patients assigned to GTG2 by genetic testing. Genomedirected therapy benefits both the doctor and the patient by potentially reducing the risk of malpractice allegations while also reducing the risk of severe vision loss. Remember: Do no harm.
Jerome Sherman, OD, is a Distinguished Teaching Professor in the Department of Clinical Education at the State University of New York College of Optometry and he is also in private practice at the Eye Institute and Laser Center, New York, New York. He acknowledged no relevant financial interest. Dr. Sherman may be reached at (212) 938-5862; firstname.lastname@example.org.
- Awh CC, Hawken S, Zanke BW. Treatment response to antioxidants and zinc based on CFH and ARMS2 genetic risk allele number in the Age Related Eye Disease Study [published online ahead of print September 4, 2014]. Ophthalmology. 2014. doi: 10.1016/j.ophtha.2014.07.049.
- Awh CC, Hawken S, Lane AM, Zanke B, Kim I. CFH and ARMS2 genetic polymorphisms predict response to antioxidants and zinc in patients with age-related macular degeneration. Ophthalmology. 2013;120:2317-2323.
- Rapp J, Sherman J. Potential dangers from zinc (and copper) supplementation: implications for Alzheimer disease and AMD. Advanced Ocular Care. 2014;5(4):38-39.
- Sherman J, Rapp J, Nath S. Is this the dawn of pharmacogenetics—or—genomics for AMD? Advanced Ocular Care. 2014;5(1):34-36. 5. Sherman J. Letters to the editor. Advanced Ocular Care. 2014;5(3):14.