How AMD patients are treated in the 'real world'

Real-world treatment of patients with newly diagnosed age-related macular degeneration (AMD) is correlated with visual acuity outcomes, and fewer injections may result in the undertreatment of some patients, said David F. Williams, MD, MBA.

According to the 2015 PAT survey of ASRS members, "the vast majority of retinal specialists use PRN or treat-and-extend treatment regimens in our clinic settings, and only 1% of retinal specialists treat monthly with intravitreal injections," said Dr. Williams, in practice in Minneapolis, MN.

Dr. Williams presented on data from 49,485 eyes culled from a large database of aggregated, longitudinal electronic medical records from a demographically diverse sample of U.S. retina specialists (Vestrum Health). The database included more than 1.1 million patients, with more than 7.2 million visits.

"We wanted to determine how patients are actually treated in the real world," Dr. Williams said, noting that most clinical trials have strict exclusion criteria that often are not reflective of real-world clinical settings and that most patients would be excluded from trials.

Real-World Analysis 

Treatment naïve neovascular AMD patients who underwent anti-vascular endothelial growth factor (VEGF) injections between Jan. 1, 2012 and Oct. 31, 2016 were eligible if follow-up data was available through Oct. 31, 2017. Primary outcomes of this analysis were visual acuity outcomes and number of injections received over the first year of treatment.

The mean age of patients receiving anti-VEGF injections was 80.9 years, and there were more females than males (64% and 36%, respectively).

Overall, there were 361,362 injections. There were 19,501 eyes that received bevacizumab, 17,464 received ranibizumab, and 12,520 received aflibercept. There were an average of eight injections per year for eyes receiving bevacizumab, and seven injections per year for eyes receiving either aflibercept or ranibizumab. Baseline visual acuity was 53.8 letters.

"What we found in almost 50,000 eyes was that the mean number of injections was 7.3 in the first year," Dr. Williams said, with patients averaging a 1-letter gain, substantially fewer than reported from the clinical trials.

About 7,000 eyes received 7 injections in the first year of treatment, and fewer than 15% of patients were treated monthly, he said.  There was a similar number of eyes receiving 13 injections (n = 802) as that received one injection (n = 1,291).

"We found a linear relationship between mean letters gained and mean number of injections, up to 10 injections over 1 year, after which the relationship plateaued," Dr. Williams said.

There were 2,313 eyes that received a mean of 3 injections in the first year, with a decrease in visual acuity letter change of -1.7 letters. There were 5,250 patients who received a mean of 6 injections in the first year, with a decrease in visual acuity letter change of -0.4 letters.

There were 6,212 patients who received a mean of 9 injections in the first year, and gained an average of 2.5 letters. Finally, there were 2,134 patients who were dosed monthly and gained an average of 3.0 letters.

Of particular interest was that patients with worse baseline visual acuity received fewer injections in the first year, and that older patients received fewer injections.

"Those eyes that received fewer than 5 injections in the first year will lose vision, and those who received more injections improved vision, although not as robust as seen in the clinical trials," Dr. Williams said.

Injection frequency "plays a large role in visual acuity outcomes," Dr. Williams said. "However, there does seem to be a ceiling effect at 10 injections."

Finally, he said attempts by clinicians to reduce treatment burden "may be counterproductive to vision outcomes."

During a question-and-answer session, Dr. Williams noted that those with poorer vision when first diagnosed and treated may be discouraged with initial vision outcomes post-injection and decide not to return. There was also a suggestion that younger patients may be able to rely on spouses, friends, and family for transportation to the clinic, but patients older than 80 may be limited in their ability to return to the clinic monthly.

It was also suggested that patients with worse vision may be receiving fewer injections as a means of suppressing the amount of exudation and bleeding with an understanding that vision improvement would not be an expected outcome.

Disclosures:

Dr. Williams listed the following financial disclosures: Covalent Medical, Regeneron, Vestrum Health, and Winning Pitch Challenge.