A weekly e-newsletter to help increase awareness and support patient education about wAMD.This week’s edition features Nancy M. Holekamp, MD, discussing the risk factors for wAMD. Rahul N. Khurana, MD, discussing anti-VEGF treatment for wAMD. Marc C. Peden, MD, discussing how to help patients with therapy compliance. retina specialist David A. Eichenbaum, MD, discussing how to foster relationships with referring partners so that patients with wAMD achieve best possible outcomes.
Nancy M. Holekamp, MD
Rahul N. Khurana, MD
Marc C. Peden, MD
David A. Eichenbaum, MD
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Vigilance is the watchword when patients have risk factors for age-related macular degeneration.
Of the major known risk factors for wet age-related macular degeneration (AMD), only one, cigarette smoking, is modifiable. Its impact is significant, increasing the risk of advanced AMD by 300%.1,2
Advancing age is the most prominent overall risk factor for AMD.3 In fact, by definition, no one younger than 50 years of age can be diagnosed with the disease we call age-related macular degeneration.
The second most important nonmodifiable risk factor is genetics/family history. Researchers have found that roughly 65% of the risk of AMD is inherited.4 We know that AMD is in the Caucasian gene pool and, consequently, is most prevalent in the white race,5 but we are starting to see more of this disease in black and Hispanic people who are part white or have a family history of interracial marriage.
With effective treatments available for wet AMD, clinicians must be vigilant when caring for this at-risk population, as early detection and treatment improves visual outcomes.
Reinforce the critical need to stop smoking. Researchers have found that quitting smoking reduces the risk of AMD. After 20 years of cessation, the risk is the same as for nonsmokers.1
Encourage regular comprehensive eye examinations. The National Eye Institute recommends a comprehensive dilated eye examination for everyone aged 50 years or older.6 This should include a thorough intake form designed to reveal a family history of AMD as well as diabetes, glaucoma, and other vision-threatening diseases that have a genetic component.
Even patients who report a family history of AMD but show no signs of the disease should be encouraged to have regular dilated eye examinations. Being disease-free at age 50 does not guarantee that AMD will not develop at age 60, 70, or 80. Patients can be reassured, however, that if no disease is present at age 50, the chance of having significant disease is low, although not zero, in 10 years.7
Prescribe AREDS vitamins for appropriate patients. The AREDS vitamins have been shown to slow disease progression for people with moderate or advanced AMD. Therefore, they are indicated for patients who have intermediate AMD in one or both eyes or advanced AMD in only one eye.8
Patients often misunderstand what the AREDS vitamins can and cannot do and who should take them. To them, I explain that nothing, including the AREDS vitamins, can prevent AMD. Therefore, people younger than 50 should not take them, nor should people who are older than 50 years with a family history of AMD but no macular degeneration.
Do not delay referral to a retina specialist. If a patient is older than 50, with or without known risk factors, is found to have bilateral macular drusen (Figure 1) with new symptoms of distortion or vision loss, prompt referral to a retina specialist is indicated. Wet AMD is treatable, and early detection followed by prompt referral and early treatment produce the best results for vision.
Smoking is the most important modifiable risk factor for wet AMD. Thus, all patients with the disease should be encouraged to stop smoking. Age and genetics are the two most important nonmodifiable risk factors for wet AMD. Patients older than 50 years with a family history should receive yearly comprehensive eye examinations to detect the early changes of AMD such as bilateral drusen. Patients with AMD and distortion or recent changes in vision should be promptly referred to a retina specialist.
1. Velilla S, Garcia-Medina JJ, Garcia-Lavana A, et al. Smoking and age-related macular degeneration: review and update. J Ophthalmol. 2013;2013:895147.
2. Meyers KJ, Liu Z, Millen AE, et al. Joint associations of diet, lifestyle, and genes with age-related macular degeneration. Ophthalmology. 2015;122:2286-2294.
3. Velez-Montoya R, Oliver SC, Olson JL, et al. Current knowledge and trends in age-related macular degeneration: genetics, epidemiology, and prevention. Retina. 2014;34:423-441.
4. Black JR, Clark SJ. Age-related macular degeneration: genome-wide association studies to translation. Genet Med. 2016;18:283-289.
5. https://nei.nih.gov/eyedata/amd. Accessed January 22, 2017.
6. https://nei.nih.gov/healthyeyes/aging_eye. Accessed January 22, 2017.
7. Ferris FL, Davis MD, Clemos TE, et al.; Age-Related Eye Disease Study (AREDS) Research Group. A simplified severity scale for age-related macular degeneration: AREDS Report No. 18. Arch Ophthalmol. 2005;123:1570-1574.
8. https://nei.nih.gov/amd/faqs. Accessed January 23, 2017.
Prompt diagnosis and a commitment to long-term management ensure the best visual outcomes.
Advances in the management of neovascular age-related macular degeneration (AMD) during the past decade have been nothing short of revolutionary. With the advent of anti-VEGF agents, outcomes are better than we ever could have imagined for a disease that was once considered a one-way ticket to blindness.
The 5-year results from the CATT study highlight the great benefits of anti-VEGF therapy while also revealing some challenges.1
Five years after starting treatment with ranibizumab (Lucentis, Genentech) or off-label bevacizumab (Avastin, Genentech), 10% of patients in the CATT study had 20/20 visual acuity, which is an amazing outcome for people with wet, or neovascular, AMD. In addition, more than 50% of patients had 20/40 or better visual acuity, an important benchmark that allows our seniors to continue to drive and maintain their independence.
At the same time, however, more than 80% of patients had fluid on OCT imaging (Figure), and the choroidal neovascularization membrane increased in size on fluorescein angiography, so that all of the gains achieved in the first 2 years were essentially lost at 5 years. These sobering facts emphasize how vigilant we must be as we manage these patients, particularly after the first or second year of treatment. AMD is a chronic disease that requires regular follow-up and care. The minute we stop treating and stop monitoring patients closely, they start to lose vision.
We have raised the bar for our patients, which is wonderful, but we have also created new challenges. We know from the landmark studies of anti-VEGF therapy for wet AMD that a regimen of monthly intravitreal injections, although burdensome for some patients, produces the best outcomes.1-4
As we have gained real-world experience with anti-VEGF therapy, we have learned that some patients need monthly injections to achieve optimal results, while others do well with fewer injections. This knowledge has led many clinicians to tailor therapy to each individual patient by varying treatment frequency based on the patient’s response. In fact, more than 70% of retina specialists in the United States use this treat-and-extend regimen,5 and we are starting to see some large clinical trials supporting this type of regimen.6-7
Treat-and-extend alleviates the burden of monthly visits to the retina specialist and offers some flexibility for patients to have a longer break between treatments. If we deviate from a monthly treatment regimen, however, we must be cautious about the length of time between visits. We must regularly monitor patients to detect a recurrence, so we can act quickly to preserve vision.
A diagnosis of wet AMD may trigger fear and anxiety in patients, but we can now offer them hope. Several great therapies are available, and researchers continue to explore new agents and drug delivery devices that will require fewer visits as well as combination treatments that may lead to better outcomes. What’s more, countless studies have shown that the earlier the diagnosis is made — in other words, the better a patient’s vision is at diagnosis — the better the outcomes will be. With regular monitoring and treatment, patients can maintain good vision as they age.
1. Maguire MG, Martin DF, Ying GS, et al; CATT Research Group. Five-year outcomes with anti-vascular endothelial growth factor treatment of neovascular age-related macular degeneration: The Comparison of Age-Related Macular Degeneration Treatments Trials. Ophthalmology. 2016;123:1751-1761.
2. Brown DM, Michels M, Kaiser PK, et al.; ANCHOR Study Group. Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: Two-year results of the ANCHOR study. Ophthalmology. 2009;116:57-65.
3. Rosenfeld PJ, Brown DM, Heier JS, et al.; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419-1431.
4. Ho AC, Busbee BG, Regillo CD, et al.; HARBOR Study Group. Twenty-four-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration. Ophthalmology. 2014;121:2181-2192.
5. Stone TW. American Society of Retina Specialists 2016 Preferences and Trends (PAT) Survey.
6. Berg K, Pedersen TR, Sandvik L, Bragadóttir R. Comparison of ranibizumab and bevacizumab for neovascular age-related macular degeneration according to LUCAS treat-and-extend protocol. Ophthalmology. 2015;122:146-152.
7. Wykoff CC, Croft DE, Brown DM, et al.; TREX-AMD Study Group. Prospective trial of treat-and-extend versus monthly dosing for neovascular age-related macular degeneration: TREX-AMD 1-Year Results. Ophthalmology. 2015;122:2514-2522.
Anti-VEGF therapy produces remarkable results when patients commit to continued treatment.
The advent of anti-VEGF therapy for treating retinal diseases may be unlike anything we will see in our lifetimes. With continued therapy, our patients with wet age-related macular degeneration (AMD) achieve phenomenal visual outcomes. The key phrase here is "with continued therapy."
To avoid losing vision, we cannot overemphasize to patients the importance of receiving treatment on a regular basis, often monthly, for this chronic disease. Multiple studies corroborate the linear correlation between more frequent injections and improved vision,1-4 and early studies reported that 70% of patients who discontinued therapy experienced a recurrence within 2 years.5
As we reassure patients that current therapies will preserve or improve their vision, we also must be mindful of the challenges associated with adhering to this lifelong treatment regimen. Here are three strategies we use in my practice to help patients stay on track.
Create Efficiencies in the Clinic. Keeping a monthly appointment can be difficult for patients, particularly those who must rely on others for transportation. To help streamline the treatment process, we have designated clinics for injections only. We check vision and IOP, numb the eye, and administer the injection, all within 30 to 45 minutes. Patients and their drivers appreciate this predictability.
For many patients, we can perform a comprehensive evaluation and imaging followed by a series of 3 to 4 monthly injections before we need to reevaluate them. Not needing a dilated examination for 4 to 6 months is a plus for patients who have driving vision.
Ensure a Comfortable Experience. While we strive to ensure that anti-VEGF injections cause minimal discomfort, some patients experience an achy, burning sensation in the treated eye for a day or so after the injection. I believe this is related more to the povidone iodine applied at the injection site than to the injection itself. Certainly, we take care to adequately rinse patients’ eyes in the office, but for patients who seem to be sensitive to the povidone iodine, we dilute the standard 5% solution 3- or 4-fold as a precaution. Our patients have reported that this relieves their postinjection discomfort.
Patients sometimes expect discomfort after an intravitreal injection—it is, after all, a needle in the eye—so in my office, we make sure to ask patients specifically if they experienced any burning or soreness after their last treatment. We have also found that rotating injection sites and augmenting anesthesia with subconjunctival lidocaine can greatly improve comfort for patients (Figure). If we can make patients feel more comfortable, they have less anxiety when they return for their next injection.
Offer Continuous Support and Encouragement. Often in medicine, particularly in ophthalmology, patients expect that a treatment will be a cure. The challenge for us, our staff, and our referring partners is to continually stress that AMD is a chronic condition requiring chronic therapy, and that our long-term goal is to maintain vision not necessarily improve it. Periodically, throughout their treatment, patients may become discouraged if their vision is not improving. Sharing the evidence that supports continued therapy for the best visual outcomes is important to do on a regular basis. Also, reminding patients what maintaining their vision means in their lives—whether it is driving, reading, or participating in other activities they enjoy—may help them appreciate the value of continued therapy. We need to be cheerleaders and champions for these patients, letting them know they are doing what is best for their vision.
Holz FG, Tadayoni R, Beatty S, et al. Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration. Br J Ophthalmol. 2015;99:220-226.
Rofagha S, Bhisitkul RB, Boyer DS, et al. Seven-year outcomes in ranibizumab-treated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). Ophthalmology. 2013;120:2292-2299.
Peden MC, Suñer IJ, Hammer ME, Grizzard WS. Long-term outcomes in eyes receiving fixed-interval dosing of anti-vascular endothelial growth factor agents for wet age-related macular degeneration. Ophthalmology. 2015;122:803-808.
Gillies MC, Campain A, Barthelmes D, et al. Long-term outcomes of treatment of neovascular qge-related macular degeneration: data from an observational study. Ophthalmology. 2015;122:1837-1845.
Singer MA, Awh CC, Sadda S, et al. HORIZON: an open-label extension trial of ranibizumab for choroidal neovascularization secondary to age-related macular degeneration. Ophthalmology. 2012;119:1175-1183.
The relationships between retina specialists and their referring partners is key to early detection and successful management of AMD. The role of the general eye care provider is irreplaceable, and needs to remain front-and-center in the routine care of all patients. The strength of our partnership serves patients well.
We make a concerted effort in our retina practice to maintain constant contact with our referring partners in the community. We update them regularly on current treatments and management techniques for all retinal disorders, including, of course, neovascular age-related macular degeneration (nAMD), for which we can achieve excellent outcomes with early detection and appropriate, timely therapy.
Our outreach efforts include quarterly clinical science programs, monthly imaging rounds for the community and residents and an annual retina update course for general ophthalmologists and optometrists, for which they can receive continuing education credit. These courses give us an opportunity educate on treatment updates and current research as well as strengthen our community partnerships. We regularly discuss the following three important pearls when referring wAMD patients:
Ensure that patients use monocular vision checks properly. Monocular vision tests, such as the Amsler grid, remain an important tool for detecting vision changes in AMD (Figure). This test should be performed at every intake visit, and patients should be instructed how to use it correctly, with brief refreshers given at their regular appointments. We have found some patients who have Amsler grids are not completely occluding and testing each eye independently. Periodically reinforcing the proper use of this simple test will help patients appreciate its value to detect disease (Figure).
Have a low threshold for referral. Abnormalities in the Amsler grid, a change in monocular vision, or an eye that abruptly cannot be refracted to a good level of visual acuity without significant anterior segment changes—any of these signs are triggers for referral to a retina specialist. If a newly referred patient does not have significant or treatable retinal pathology, I will often serve as an on-demand resource for that patient and for the referring doctor, rather than maintain a standing retina subspecialty appointment.
Retina specialists appreciate 1-liners. I love receiving from a referring doctor a simple 1-line reason for referral to direct me and increase my index of suspicion for a certain disease. Patients often are not aware why they were sent to see another eye care provider, or they do not understand the difference between their general eye care provider and the retina specialist. For example, an 80-year-old patient may have some minor retina problems, and I appreciate being able to direct the conversation toward the issue for which the patient was referred, so I can be informative to the referring doctor. A simple phrase, such as “patient reported distortion,” “suspected detachment,” “unexplained vision loss,” helps me zero in on the appropriate chief complaint. For my part, I always send a follow-up letter to the referring doctor to report on my findings, and I am always happy to discuss a patient’s examination by phone.
The Value of Our Partnership
The role of the general eye care provider is irreplaceable, and needs to remain front-and-center in the routine care of all patients. As a retina specialist, I do highly specialized, evidence-based retina care and offer innovative clinical science. My goal is to apply the latest retina clinical science to manage patients’ diseases and ultimately improve or preserve vision. The strength of our partnership serves patients well.
Figure. Patients with bilateral macular drusen and new symptoms of distortion or vision loss should be promptly referred to a retina specialist.
Figure. Cystoid macular edema in a patient with active neovascular age-related macular degeneration.
Figure. We have found that rotating injection sites and augmenting anesthesia with subconjunctival lidocaine can greatly improve comfort for patients.
Figure. Amsler grid as it might appear to someone with age-related macular degeneration.
Credit: National Eye Institute, National Institutes of Health
Nancy M. Holekamp, MD
Rahul N. Khurana, MD
Marc C. Peden, MD
David A. Eichenbaum, MD
Retina Today is a publication that delivers the latest research and clinical developments from areas such as medical retina, retinal surgery, vitreous, diabetes, retinal imaging, posterior segment oncology and ocular trauma. Each issue provides insight from well-respected specialists on cutting-edge therapies and surgical techniques that are currently in use and on the horizon.