Long-term follow-up from the Comparison of Age-Related Macular Degeneration Treatment Trials (CATT) released this week show that vision gained during the first 2 years of treatment with bevacizumab or ranibizumab were not maintained at 5 years. Still, half of patients could see 20/40 or better.
The landmark study both confirms anti-VEGF therapy as a tremendous therapeutic advance in wet AMD and reveals the limitations of current treatment.
"When we first treat wet AMD patients, they typically gain about two lines worth of visual acuity on the eye chart, and what we've seen in this study is that between year 2 and about year 5 of anti-VEGF treatment they lose most of that improvement," said Maureen G. Maguire, PhD, lead author and professor of ophthalmology at the Perelman School of Medicine at the University of Pennsylvania. These findings were presented at ARVO 2016 by Daniel F. Martin, MD, study co-author and chair of the Cleveland Clinic Cole Eye Institute.
Investigators followed 647 AMD patients, about 70.8% of survivors from the original CATT trial who were randomized to receive ranibizumab or bevacizumab with monthly or PRN dosing regimens. After 2 years of treatment, participants were free to choose their own course of therapy, although it appears that participants in the 5-year visit following enrollment were seemingly under-treated with anti-VEGF intravitreal injections during years 3, 4 and 5. The mean number of treatments was 15.4.
At 5 years, mean visual acuity was 3 letters worse compared with baseline and 11 letters worse than at 2 years. Between 2 and 5 years, the group originally assigned to ranibizumab lost 4 more letters than the bevacizumab group (P=0.008). Otherwise, there were no significant differences in VA or morphologic outcomes between drug or regimen groups.
The rate of geographic atrophy increased from 20% of participants at 2 years to 41% at 5 years, with the average lesion size increasing by more than 50% during that time period, highlighting the need for new agents that can prevent or minimize geographic atrophy and expansion of the total neovascular lesion.
Despite the adverse morphologic changes, only 20% had visual acuity of 20/200 or worse. These data are remarkable when considering the VA outcomes in wet AMD before the development of anti-VEGF treatment. Two years after diagnosis, less than 10% of patients retained vision of 20/40 or better with no treatment and less than 15% of patients treated with photodynamic therapy retained 20/40 or better vision.
With most patients changing drugs over time, the ability to identify differential safety effects of the 2 drugs was compromised. But the authors noted no new safety signals after 5 years of treatment. While these results would have been unimaginable before the availability of anti-VEGF therapy, the path for future improvement is clear, the authors write.
"Although anti-VEGF treatment has greatly improved the prognosis for patients overall, we still need to find ways to avoid poor vision in these patients and to decrease the burden of ongoing treatment," said Maguire.