Impact of Missed Visits, Injections on AMD Treatment Outcomes

Brian VanderBeek, MD

While the negative impact lack of treatment and visit adherence can have on the outcomes of age-related macular degeneration (AMD) is well-documented, a new study from Penn Medicine has broken down just how large of an impact missing a visit can have on visual outcomes.

Results of the study indicated each missed visit was associated with an average decline of 0.7 letters of visual acuity and longer gaps between visits directly correlated to greater losses in visual acuity—with those who averaged between 36 to 60 days between visits losing an average of 6.1 letters, and those who went more than 60 days between visits losing an average of 12.5 letters of visual acuity.

“Anti-VEGF therapy can only be administered by an ophthalmologist, making visit adherence even more critical for those with macular degeneration," said Brian VanderBeek, MD, a professor of Ophthalmology at the University of Pennsylvania's Perelman School of Medicine, in a statement. “I wanted to quantify the link between regular visits to the eye doctor and visual outcomes for these patients."

Vanderbeek and 2 colleagues from Penn Medicine conducted a secondary analysis of data from the Comparison of Age-Related Macular Degeneration Treatment Trial (CATT), which was a 2-year study examining the effectiveness of bevacizumab versus ranibizumab and of monthly versus as-needed treatments, in hopes of quantifying the association between adherence to randomized clinical trial visits and visual acuity in patients with neovascular AMD.

To thoroughly evaluate the impact of visit adherence, the National Eye Institute-funded study was designed to examine 4 different metrics: total number of missed visits, average days between each visit, longest duration in days between visits, and visits constancy.

Investigators defined length of visit as average days in between each visits while visit constancy was a tally of three-month periods with at least 1 visit taking place. When assessing duration in days between visits, categories were defined as on time (28-35 days), late (36-60 days), and very late (>60 days).

The primary outcome measure for the study was change in ETDRS letters between the baseline and last visit of the study. Investigators used liner multivariate regression models, which accounted for age, sex, baseline VA, anti-VEGF drug, number of injections, and dosing methods, to assess associations between visit adherence and change in visual acuity.

A total of 1178 patients from the CATT cohort were analyzed in the current study—mean age of the cohort was 79.1 years and 61.7% of participants were women. Of note, 90% of patients adhered to an appointment every 28 to 35 days, mean days between appointments was 31.9 days, and 92.6% had at least 1 visit in each three-month interval.

In full-adjusted analyses, patients in the late groups had a visual acuity that was -6.1 letters worse (95% CI, −9.6 to −2.8) and the very late group was -12.5 letters worse (95% CI, −23.0 to −2.1) than patients in the on-time group (P <.001). Assessments of max days between visits warranted similar results to comparisons of average days between visits. Patients with a max time between visits between 36 and 60 days lost an average of 2 letters (95% CI, −4.6 to 0.6) of visual acuity while those with more than 60 days between visits had an average of 5.9 letters lost (95% CI, −9.2 to −2.7) (P <.001).

Furthermore, results indicated have 1 or more 3-month period without a visit was associated with a loss of 5.1 letters when compared with 100% visit constancy (95% CI, -8.9 to -1.3; P = .009). Failure to attend at least a single visit in 1 or more 3-month intervals was linked to a 5.8-letter (95% CI, −9.6 to −2.0; P = .003) decrease in visual acuity.

Investigators noted multiple limitations in their study. Limitations included metrics only being assessed in the setting of monthly and pro re data treatment regimens, the study population not allowing for application of results to a real-world population, and the study length only allowed for the assessment of 2 years of AMD management.

In an invited commentary published simultaneously in JAMA Ophthalmology, Shriji Patel, MD, and Paul Sternberg Jr, MD, of the Vanderbilt Eye Institute and Vanderbilt University Medical Center, complimented investigators on the results of their analyses but also commented on the difficulty of applying results in a real-world setting—where treat-and-extend regimens are fairly common.

“The most commonly used method for treating these patients is a treat-and extend regimen…A treat-and-extend regimen simultaneously relieves logistical pressures on busy physician practices. However, in the pursuit of a reduced injection burden, this regimen may adversely affect patient outcomes,” the authors wrote. “As illustrated by this analysis, missed treatment opportunities (whether attributable to poor patient adherence or treatment interval extension) can have real consequences on visual function.”

This study, titled “Association of Visit Adherence and Visual Acuity in Patients With Neovascular Age-Related Macular Degeneration Secondary Analysis of the Comparison of Age-Related Macular Degeneration Treatment Trial,” was published online in JAMA Ophthalmology.