Retina specialists have long trusted that treat-and-extend is a medically valid approach for administering anti-VEGF agents in neovascular age-related macular degeneration, but with the publication of two-year results of the CANTREAT trial they now have Level 1 randomized clinical trial evidence that validates the treatment approach long term.1
“This gives us good long-term evidence to support what we do in practice,” lead author Peter J. Kertes, MD, CM, of the Sunnybrook Health Sciences Centre and University of Toronto tells Retina Specialist. “It should give us a little bit more comfort in doing what we think is best for patients.”
CANTREAT stands for the Canadian Treat-and-Extend Analysis Trial with Ranibizumab in Patients with Neovascular Age-Related Macular Degeneration. The trial randomized 580 patients to ranibizumab (Lucentis, Roche/Genentech) either monthly or T&E. At two years, 466 patients had completed the study. Patients in the T&E arm received an average of 17.6 injections compared with 23.5 in the monthly arm (p<0.001). The study also found that about 40 percent of patients could be extended out to 12 weeks maximum.
The following visual acuity outcomes were similar in both arms:
- a mean improvement of 6.8 and 6 letters in the T&E and monthly dosing arms (p=0.21);
- a gain of 15 or more letters in 25.5 and 23.1 percent of the respective arms (p=0.59); and
- a loss of 15 or more letters in 6.5 and 5.8 percent (p=085).
Dr. Kertes notes that the TREND2 study in Europe also provides convincing evidence of the effectiveness and safety of T&E, but that trial was stopped after one year. TREND, with 650 patients, and CANTREAT are similarly powered.
Two important elements of CANTREAT’s design validate its findings, Dr. Kertes says: The randomization eliminated a bias in treatment allocation; and it took into account the nature of dropouts in an elderly population over two years. “I feel confident it was an adequately powered study.”
He emphasizes that the CANTREAT findings don’t invalidate monthly dosing with ranibizumab. “There are retina specialists who routinely treat every month, and that’s not an unreasonable way to manage patients,” he says. “The registry trials used monthly treatment.”
Patients who require monthly treatment shouldn't be considered failures, Dr. Kertes says. “Different patients will have different intervals at which their disease remains quiescent. The goal is to never let that disease get ahead of you; hopefully it’s less than every month, but if monthly dosing is necessary, that’s acceptable.”
Going forward, Dr. Kertes says the CANTREAT investigators expect to publish data on a cohort that has been followed out to three years. Other parameters they expect to explore are geographic atrophy, long-term intraocular pressure and predictive patient characteristics.
While the maximum extension in CANTREAT was 12 weeks, some patients may be extended out even longer, Dr. Kertes says. “As new agents come online and we’re looking for more durable therapies, we have to think about those in the context of what we can achieve in many patients with a treat-and-extend regimen with ranibizumab,” he says.
1. Kertes PJ, Galic IJ, Greve M, et al. Efficacy of a treat-and-extend regimen with ranibizumab in patients with neovascular age-related macular disease: A randomized clinical trial. JAMA Ophthalmol. 2020 Jan 9. doi: 10.1001/jamaophthalmol.2019.5540. [Epub ahead of print]
2. Silva R, Berta A, Larsen M, Macfadden W, Feller C, Monés J; TREND Study Group. Treat-and-extend versus monthly regimen in neovascular age-related macular degeneration: results with ranibizumab from the TREND Study. Ophthalmology. 2018;125:57-65.
Atherosclerosis study hints at link between bad diet and late-stage AMD
For generations researchers have worked to better understand the role of diet in age-related macular degeneration. Recently published results of a large study of people with atherosclerosis has potentially identified a link between unhealthy diets and late-stage AMD.1
A cohort study of the Atherosclerosis Risk in Communities (ARIC) study has reported that patients with characteristics of an unhealthy diet, labeled “Western” diet in the study, had a threefold higher odds of incident late AMD than people who leaned toward a healthy, or “prudent,” diet in the study.
Lead author Amy Millen, MD, an epidemiologist at the State University of New York at Buffalo, describes how the two dietary patterns differ. “In our study, the Western pattern consisted of a high intake of processed and red meat, fried food, dessert, eggs, refined grains, high-fat dairy and sugar-sweetened beverages, and low intake of yogurt, low-fat dairy, fresh fruit, cruciferous vegetables, whole grains and carotene vegetables,” she tells Retina Specialist. “The prudent pattern was defined by high consumption of all vegetables, including dark leafy vegetables, legumes, poultry, fish and seafood and by low intake of sugar sweetened beverages, fried food, coffee, processed meat, sweets and candy, eggs, ice cream and desserts.”
The study focused on the link between dietary patterns and the 18-year incidence of AMD. It included ARIC patients who showed changes in AMD lesions on retinal photographs taken at two separate visits 18 years apart (117 patients had early AMD and 27 had late AMD). Patients were also asked to answer a 66-line item food questionnaire.
The study also found that the prudent diet was associated with a lower risk of developing AMD, but it was not statistically significant. However, the overall risk was 0.51 (p=0.954). Other work in Europe has generated supportive evidence that healthy diets are associated with decreased incident late AMD. This study points to a need for more cohort studies to better understand the risk between diet ant late AMD, Dr. Millen says.
“If we continue to see protective associations against the development or progression of disease in those consuming prudent-type diets and increased incidence of early or late AMD among those consuming Western-type diets, our next steps should focus on dietary modification trials to reduce vision loss,” she says. “We should study how to motivate dietary change among those at high risk for AMD incidence or progression to help maintain vision over time.” RS
1. Dighe S, Zhao J, Steffen L, et al. Diet patterns and the incidence of age-related macular degeneration in the Atherosclerosis Risk in Communities (ARIC) study. Br J Ophthalmol. 2019 Dec 6. pii: bjophthalmol-2019-314813. doi: 10.1136/bjophthalmol-2019-314813. [Epub ahead of print]