“Tomorrow, I’m off to the Seychelles!” announces my patient with a flourish. “The islands are gorgeous—turquoise waters and pristine white sand beaches. You should really visit them sometime.” As always, she is impeccably dressed, a Hermès scarf draped casually over her shoulders. She loves to update me each visit with a litany of exotic places she has visited and thrilling adventures she has undertaken since she has seen me last. Spur-of-the-moment jaunts by private jet are commonplace in her life, and she often provides me with effusive recommendations for “little” trips that would undoubtedly bankrupt me almost immediately.
The first time we met, I diagnosed her with choroidal neovascularization due to pathologic myopia. She had noticed recent metamorphopsia in that eye. Optical coherence tomography imaging revealed a trace amount of subfoveal subretinal fluid. I recommended anti-vascular endothelial growth factor (anti-VEGF) therapy and we discussed options of aflibercept, bevacizumab, or ranibizumab. She asked me which one was the best. I reviewed the 1-year results that were available at the time from the Comparison of Age-Related Macular Degeneration (AMD) Treatments Trials (CATT), which suggested no clinically relevant difference in outcomes on neovascular AMD from bevacizumab and ranibizumab when each were given monthly, but I let her know there was no similar comparative study to guide our choice of agent for her specific type of choroidal neovascularization or retreatment regimen that I might choose. She asked me if there were any other differences between the medications and we talked about the cost of each drug. Ranibizumab recently received FDA approval for the treatment of myopic choroidal neovascularization in January of this year (2017). At that time, however, none of the anti-VEGF therapies were FDA-approved at that time for her eye condition. I warned her that since I would be using them off-label, she might be charged out of pocket for their cost, but she was somehow confident that her insurance, a premium plan, would cover any of the 3 agents. Because cost didn’t seem an issue for her personally, I assumed that she, like many of my patients, would choose one of the medications FDA-approved for use in the eye for a similar indication.
It was clear that she did not deprive herself in other areas of life. I was surprised, therefore, at the end of our discussion to hear her say “Dr Sun, give me the cheap drug.” When I asked her what had motivated her decision, her response was, “You tell me that there is a good chance any of the 3 drugs will be helpful for what I’ve got. I pay enough for my insurance that I’m pretty sure it will cover any of these, but I know how bad health care costs are in this country. Why should I add to the health care debt if my eye can be treated with something that’s probably just as good and a lot cheaper? And you know what? If the cheap drug doesn’t fix this problem right away but I can still switch to another drug. I’m willing to do that.”
I was impressed and humbled by her answer. Most patients faced with their first intraocular injection are understandably anxious enough to optimize their own personal results that they give little thought to the societal consequences of their decision making. The decision as to which anti-VEGF agent to use as first-line treatment for various retinal conditions can be a challenging one for both patients and physicians. The strictures under which retinal physicians operate in terms of third-party payer regulations vary tremendously from area to area. I cannot keep track of the bewildering array of coverage options that my patients face. I don’t have any answer to solve the economic crisis of our health care system. However, especially in light of the tremendous public health impact of our treatment decisions, we as physicians need to clearly understand the scientific data as to the relative efficacy of these agents to best counsel our patients.
The most comprehensive comparison of different anti-VEGF therapies to date has been the Diabetic Retinopathy Clinical Research Network “Protocol T” trial of aflibercept, bevacizumab, and ranibizumab for diabetic macular edema (DME). This study clearly demonstrated that all 3 anti-VEGF medications are highly effective for the treatment of DME. Eyes with good baseline visual acuity of 20/32 to 20/40 responded similarly to the 3 agents over 2 years. However, in eyes that started with visual acuity of 20/50 or worse, aflibercept was clearly superior to bevacizumab and ranibizumab in mean change in acuity from baseline to 1 year and in average acuity gained over 2 years. Based on these results, many of us use aflibercept as first-line therapy in eyes with DME, especially in those with worse baseline vision. Yet it is worthwhile remembering that many patients who received bevacizumab in Protocol T still did extremely well. The initial use of bevacizumab with a switch to another anti-VEGF only if an eye fails to respond completely and successfully is a treatment strategy that should be evaluated in future clinical trials.
Some anti-VEGF comparison data is available for other, nondiabetic retinal diseases, but there has not been a large-scale comparative effectiveness study to compare aflibercept with the other 2 agents. Results from the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2) will be forthcoming in 2017, and should shed light on any differences between aflibercept and bevacizumab in the treatment of macular edema from central retinal vein occlusion.
My patient, like many patients with pathologic myopia, has done extremely well. After an initial series of intravitreous injections with bevacizumab, the subretinal fluid resolved and her metamorphopsia went away. She hasn’t needed injections for several years now. She is thrilled that she can once again see clearly and appreciate whatever local fauna—African gazelles, Antarctic penguins or Amazonian river dolphins—she encounters on her journeys. On an academic physician’s salary, I don’t think I’ll ever be able to emulate her extravagant lifestyle. But every now and then, I remember and am inspired by the example of her altruism.