It is unknown if the increased incidence of GA found in certain trials after the use of anti-VEGF therapies for nAMD is due to the therapy or is part of the disease’s normal course. Furthermore, estimates of GA incidence vary across studies, which may be explained by changes in anti-VEGF agent, dosage, therapy, and follow-up regimens, as well as patient and ocular characteristics.
Given the uncertainty surrounding the incidence of GA following intravitreal agent treatment, Arshia Eshtiaghi et al. conducted a systematic review and meta-analysis recently published in Retina Journal to identify and synthesize all available evidence for estimating GA incidence and progression, as well as to investigate population and intervention characteristics that may have influenced these estimates.
They conducted a systematic evaluation of the available data on the occurrence and development of GA after repeated anti-VEGF injections in patients with nAMD. They evaluated data from 31 trials including a total of 4,609 eyes that had had anti-VEGF injections.
Over 35.2 months, eyes got an average of 17.7 shots. At baseline, the prevalence of GA was 9.7 percent. At the conclusion of follow-up, the pooled incidence of GA was 30.5 percent.
- Between the mean total number of injections and the GA incidence at the final follow-up, there was a positive, moderate linear connection (R2 = 0.30; P = 0.01).
In aggregate, the prevalence of GA increased from 9.7 percent at baseline to 38.9 percent at end follow-up. There was a 30.5 percent incidence of new-onset GA among persons without GA at baseline.
The positive, moderate connection between the mean number of injections and the frequency of new onset GA suggests a relationship between intravitreal anti-VEGF medication and the development of GA, albeit this does not imply causality. Notably, none of the evaluated publications examined the causation of this association, which may be impacted by the normal course of nAMD. Indeed, more frequently injected eyes may have had more aggressive underlying nAMD, which is a risk factor for a faster natural development of GA. Additionally, several of the eyes that received a significant volume of injections were included in RCTs that required monthly injections in one research arm. Finally, patients who had a greater number of injections were observed for a longer length of time, which is related with an increased risk of GA.
Between the mean total number of injections and the GA incidence at final follow-up, there was a positive, moderate linear connection (R2 = 0.30; P = 0.01).
When extrapolated backwards, the regression line indicates that even in the absence of intravitreal anti-VEGF injections, GA formation occurs at a rate of roughly 20%. The Beaver Dam Eye Research, a pioneering epidemiological study undertaken prior to the development of anti-VEGF medication, revealed a cumulative GA incidence of 13.5 percent in eyes with AMD during a 15-year period.
Monthly therapy was significantly related with an increased chance of developing GA compared to pro re nata (relative risk = 1.40, 95 percent confidence range [1.21–1.61], P 0.001).
- GA development was associated with GA in the fellow eye, retinal angiomatous proliferation, drusen, and reticular pseudodrusen.
The anti-VEGF drug used was noted as a risk factor for the development of GA in many of the publications analysed.
- Cho et al. found that aflibercept was associated with a higher rate of GA formation when compared to ranibizumab, especially in patients with nAMD subtype type 3 neovascularization (aflibercept GA incidence = 42.9 percent vs ranibizumab GA incidence = 19.0 percent, P = 0.045).
- One possible reason for the higher GA development in the aflibercept-treated group is that aflibercept was linked with a larger reduction in choroidal thickness than ranibizumab, which may be a risk factor for GA development.
- In general, utilising aflibercept to treat type 3 neovascularization should be done cautiously in the presence of other risk factors for GA development, such as baseline subfoveal choroidal thinning, reticular pseudodrusen, and baseline GA in the fellow eye.
- In contrast, two investigations found no association between the anti-VEGF drug used and the development of GA.