Real-World Study Highlights Undertreatment of nAMD

Thomas A. Ciulla, MD, MBA, volunteer clinical professor of ophthalmology, Indiana University School of Medicine

Thomas A. Ciulla, MD, MBA

Outcomes for patients with neovascular age-related macular degeneration (nAMD) in the real-world were inferior to randomized controlled trials due to significant undertreatment, according to a large database analysis presented at the 2018 ARVO Annual Meeting.

For the retrospective database study, outcomes were analyzed for 361,362 injections given to the nearly 50,000 patients. Approximately 13% of patients received 11 to 13 injections over the course of the first year while 17% were extremely under-treated, having received just 1 to 4 injections in a year.

There was a clear correlation between the number of injections received and improvements in best corrected visual acuity (BCVA). Those who received fewer than 5 injections experienced a decline in BCVA while patients receiving 7 or more saw improvements. Moreover, there was a linear improvement with each additional injection from the 4th injection to the 10th.

"The number one predictor of response was injection frequency, and patients who receive 10 or more injections actually experience a ceiling effect, suggesting a treat-and-extend regimen may do equally as well," lead investigator Thomas A. Ciulla, MD, MBA, volunteer clinical professor of ophthalmology, Indiana University School of Medicine, told attendees at the ARVO Annual Meeting. "What we see in those patients who are woefully undertreated is that they actually lose vision, which is no surprise."

In randomized clinical trials for nAMD across regimens, the mean age of patients was 76.9 years and the mean baseline BCVA was 54.5 letters. In these studies, anti-VEGF therapy was injected monthly, resulting in an 8.5 letter mean change. "In the real-world, we know there are multiple treatment regimens, and very few patients are treated monthly," said Ciulla. "An extraordinarily small number of patients are treated monthly."

For the real-world study, de-identified patient data were analyzed from the Vestrum Health Retina Database, which includes information from hundreds of US doctors' electronic medical records. The inclusion criteria were left broad, as to capture a real-world treatment population. "Real-world patients differ significantly from clinical trials," Ciulla noted.

Overall, patients in the real-world have scars/fibrosis or subretinal hemorrhage in more than 50% of lesions. They also have significant subfoveal hemorrhage and central photoreceptor or retinal pigment epithelium (RPE) atrophy, he added.

In the database study, there were 49,485 eyes included across a broad demographic region. The mean age of patients was 80.9 years and the mean injections per patient was 7.3. Patients received bevacizumab (39.4%), aflibercept (25.3%), and ranibizumab (35.3%). The average starting BCVA was 53.8 letters and the mean change from baseline was 0.95 (95% CI, 0.77-1.13; P <.001).

"We can see that the baseline visual acuity is the same as our randomized studies, but the mean change here is just 1 letter," said Ciulla. "And this is highly statistically significant."

When looking at trends, those with a worse baseline BCVA received fewer injections over the first year. Those receiving 1 to 3 injections had a BCVA of between 40 and 50 letters whereas patients receiving 12 or 13 injections had BCVAs in the 55 to 60 range.

"Those who received the fewest injections had the worse baseline visual acuity, very much worse, in fact nearly 3 lines worse," said Ciulla. "The interesting paradox about this is that we know that the patients with poor visual acuity actual gain the most vision."

Moreover, patients who were older (≥81.5 years), tended to receive fewer injections than younger participants (78.5 years). "Three years might not seem like very much, but around your 80s three years is a very significant difference in age," said Ciulla. This age difference could lead to transportation or other obstacles that prevent treatment.

Overall, findings from the analysis highlight the need for improved care among patients with lower baseline visual acuity. Additionally, the findings indicate that the number of injections may be more important than the type of regimen selected, Ciulla noted.

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