Loss of Follow-Up Predictors in Wet AMD

A fifth of patients receiving treatment for neovascular (wet) age-related macular degeneration (AMD) stopped care without explanation during long-term follow-up in a large multicenter Canadian cohort.

Overall, 527 of the 2,556 (21%) patients stopped showing up for care during a mean follow-up of 65.5 months. The strongest predictor was longer travel distance, which more than doubled the odds of being lost to follow-up (LTFU). Additionally, Black patients were twice as likely as white patients to be LTFU, and Hispanic patients were 70% more likely to stop showing up. A multivariable analysis showed that men and patients with multiple comorbidities were also significantly more likely to be LTFU.

On the other hand, older age reduced the odds, as did having pseudophakia, bilateral wet AMD, and worse baseline visual acuity. Perhaps counterintuitively, the data also showed a reduced likelihood of being LTFU among patients with a higher anti-VEGF treatment burden during the first year.

“These findings underscore the multifactorial nature of treatment adherence in [neovascular] AMD and inform the identification of high-risk groups that may benefit from targeted retention strategies,” concluded Radha P. Kohly, MD, PhD, of the University of Toronto, and colleagues in the Canadian Journal of Ophthalmology.

Global Issue

The findings generally align with previous reports showing LTFU rates ranging from 8-26%, the authors noted. However, the analysis also yielded some surprises.

“One interesting finding was that patients ages 90 and older were less likely to be lost to follow-up, despite the potential burdens and challenges of attending frequent appointments at an advanced age,” study co-author Marko Popovic, MD, MPH, also of the University of Toronto, told MedPage Today. “Patients with worse baseline vision, bilateral disease, and a greater injection burden in the first year were also less likely to be lost to follow-up. This may reflect greater perceived need for treatment, a need for follow-up given perceived benefit, or stronger integration into ongoing care, although our study cannot determine the reasons for these associations.”

“Perhaps the most important finding is the scale of the problem: approximately one in five patients in our cohort became lost to follow-up,” he added. “In neovascular AMD, where interruptions in treatment can lead to irreversible vision loss, this is clinically significant. Our findings also reinforce that loss to follow-up is multifactorial. Rather than viewing missed care simply as a patient adherence issue, we should consider the medical, geographic, social, and healthcare-system barriers that can make it difficult for patients to remain in care.”

The authors acknowledged that the cost of anti-VEGF therapy and associated ophthalmologic care did not figure into the analysis, as those costs are covered by the various Canadian provinces’ healthcare systems. In contrast, cost is a major issue in the management of wet AMD in the U.S., recently exacerbated for many patients by the loss of copay assistance.

“Because the study was conducted in Toronto under Ontario’s single-payer system, medication cost and insurance-type barriers are far less variable than in the U.S. context, which likely explains their absence as modeled predictors,” Rahul Khurana, MD, of Northern California Retina Vitreous Associates in Mountain View, told MedPage Today. In a study cited by the Canadian authors, “we found the odds of LTFU were higher with Medicaid and lower with Medicare compared to private insurance in the United States.”

The study from a single Canadian province “confirms what we found on a national level in the United States through the IRIS Registry,” Khurana added. “Both studies highlighted risk factors for loss to follow-up in neovascular AMD: male sex, Black and Hispanic race/ethnicity, and unilateral disease. They were able to examine travel distance and found that patients further away were at higher risk for loss to follow-up.”

Despite the proven efficacy of anti-VEGF therapy for wet AMD, the chronic nature of the condition necessitates regular monitoring and repeated intravitreal injections, imposing a substantial treatment burden on patients, Kohly and colleagues noted in their introduction. Clinical trials have shown that the best results come with consistent, scheduled treatment regimens.

The authors noted that several analyses of real-world evidence suggest that a substantial proportion of patients with wet AMD are LTFU, contributing greatly to suboptimal outcomes. In addition to the study by Khurana and colleagues, a recent analysis of 1,328 British patients with wet AMD showed that half had stopped coming to clinics for treatment after 5 years.

A systematic review published earlier this year evaluated global trends in LTFU, gleaned from 52 studies. Including both short- and long-term adherence, the studies showed LTFU rates ranging from <5% to >75% at 10 years. Older age, male sex, greater distance to treatment site, and caregiver/transportation dependence were associated with higher rates of LTFU.

“Treat-and-extend” protocols, which reduce treatment burden, were associated with lower rates of LTFU. Consistent with several individual studies, the analysis showed that patients who were LTFU had worse vision outcomes, even after resuming treatment.

Key Findings

Aiming to examine factors associated with LTFU in a diverse population, Kohly and colleagues performed a multicenter retrospective study of patients treated for wet AMD in Toronto from January 2012 to December 2021. They defined LTFU as absence of an ophthalmic visit within 1 year of the last appointment with a retina specialist.

Results of the multivariable analysis identified factors with significantly increased odds of LTFU and those associated with decreased odds:

• Travel distance >200 km: OR 2.51, P<0.001
• Black race: OR 2.07, P<0.001
• Hispanic ethnicity: OR 1.70, P<0.001
• Male sex: OR 1.40, P<0.001
• Three or more systemic comorbidities: OR 1.39, P=0.01
• Age ≥90: OR 0.53, P<0.001
• Higher first-year anti-VEGF injection burden: OR 0.55, P<0.001
• Worse baseline visual acuity (>20/200): OR 0.72, P=0.03
• Bilateral disease: OR 0.72, P=0.01
• Pseudophakia: OR 0.80, P=0.04

“These findings may help clinicians identify patients at higher risk of being lost to follow-up and provide additional support earlier,” said Popovic. “Potential interventions could include proactive appointment reminders, rapid follow-up after missed visits, caregiver involvement, and helping patients access treatment closer to home when possible. Longer-acting therapies and treatment regimens that safely reduce visit burden may also help.”