Closely monitoring neovascular AMD (nAMD) activity is key for controlling the disease and preventing further vision loss. A recent study noted the lack of research on long-term outcomes and performed an analysis of real-world clinical findings. They found that eyes with higher and lower levels of disease activity fared worse than those with moderate activity.

The researchers obtained data from 2,109 eyes treated with anti-VEGF monotherapy from the prospectively defined Fight Retinal Blindness! registry. They divided the eyes into three groups (low, moderate and high) based on the proportion of clinic visits in a five-year period in which choroidal neovascular lesions were active.

In the sample, the adjusted mean visual acuity change was significant, at 0.5 letters, 1.8 letters and -2.5 letters in the low, moderate and high activity groups, respectively. The researchers noted that eyes in the lower activity group were significantly more likely to develop macular atrophy (56% vs. 47% and 26%)  and less likely to develop subretinal fibrosis (27% vs. 35% and 42%).

“Our results are consistent with the concept that disease control is important for favorable visual outcomes,” the authors wrote in their paper. “We found that long-term visual outcomes were poorer in eyes with more active disease. However, we also found that eyes in the low activity group had poorer visual outcomes than those in the moderate activity group, which had the best outcomes. The difference between the moderate and high activity group was almost one line (five letters) at five years, which is clinically meaningful.”

The researchers explained that this finding was due to the relationship between activity levels and end-stage phenotypes of nAMD linked to poor vision. “Our findings indicate that poor vision in the high activity group is likely due to the prevalence of subretinal fibrosis rather than macular atrophy. On the other hand, poor vision in the low activity group was associated with a higher prevalence of macular atrophy and a lower prevalence of subretinal fibrosis.”

They explain that these associations of disease activity and end-stage sequelae can only be detected in long-term, longitudinal analyses, such as the one they performed, because the rate of subretinal fibrosis and macular atrophy is often too low to affect visual outcomes during shorter-term studies. “The natural progression of subretinal fibrosis may be delayed by VEGF inhibition therapy, but around 30% to 40% of eyes were found to develop fibrosis after two years of treatment. The progression to macular atrophy takes even longer, with a prevalence of 18% at two years and 40% to 50% at five years.”

The team concluded that both low and high disease activity result in worse long-term visual acuity outcomes, compared with moderate disease activity. “While we continue to advocate tight disease activity control as per the current gold standard treatment, our observations suggest that further work is necessary to examine the effects of anti-VEGF treatment on end stage phenotypes of nAMD.”

Teo KY, Nguyen V, Cheung CG, et al. The impact of disease activity on five year outcomes in patients undergoing treatment for neovascular age related macular degeneration. Retina. July 16, 2021. [Epub ahead of print].