What is Syfovre?
Before talking about how to reduce the risk of wet AMD from Syfovre, we must learn about AMD and Syfovre. Syfovre is the first FDA-approved treatment to reduce the risk of losing vision from dry age-related macular degeneration (AMD) due to geographic atrophy. In the phase 2 study, eyes treated by monthly injection of Syfovre showed a reduction in the rate of progression of 29%. It is important to note that Syfovre does not reverse past damage from dry AMD, and it is not a cure for dry AMD.
Does Syfovre increase the risk of wet AMD?
A major concern of treatment is the adverse effect of new wet AMD developing in eyes treated with Syfovre. Wet AMD is another form of advanced AMD in which abnormal blood vessels start to grow under the center of the retina (the macula). The abnormal vessels in wet AMD will cause a large central blind spot in the vision unless treated with regular injections of antiVEGF medicines. Among eyes treated with Syfovre in the phase 2 study, 20.9% of treated eyes developed new wet AMD compared with 1.2% of eyes in the study who did not receive this treatment. Therefore, in an effort to prevent loss of vision from dry AMD, Syfovre raises the risk of vision loss from new wet AMD.
How can we reduce the risk of wet AMD in eyes treated with Syfovre?
There are several things to consider that may be helpful in reducing risk. Table 1 shows the effect of avoiding the use of Syfovre in eyes whose fellow eye already has wet AMD. This is a risk factor for developing wet AMD in the second eye. The risk of the second eye developing wet AMD appears to be further increased with the use of Syfovre. Among eyes undergoing monthly Syfovre injection, the risk of new wet AMD is reduced to 12% compared with 20.9% of all study eyes and 33.3% of eyes with wet AMD in the fellow eye. Similarly, in eyes undergoing Syfovre injection every other month, the risk of new wet AMD is reduced to 3.9% compared with 8.9% of all study eyes and 17.9% of eyes with wet AMD in the fellow eye. Therefore, patients who already have one eye with wet AMD may wish to reduce their risk of developing wet AMD in their second eye by avoiding the use of Syfovre.
Table 1: FILLY phase 2 study: New wet AMD among study eyes. Studying the effect of wet AMD in the fellow eye
| Parameters | Sham (no drug) | Monthly drug injection | Every other Month drug injection |
| All study eyes | 1.2% | 20.9% | 8.9% |
| Fellow wAMD | 0% | 33.3% | 17.9% |
| No fellow wAMD | 1.9% | 12% | 3.9% |
Table 2 (below) shows the difference among study eyes with and without a known risk factor for developing wet AMD…the double layer sign (DLS). The risk of an eye with DLS in developing wet AMD appears to be further increased with the use of Syfovre. Therefore, among eyes undergoing monthly Syfovre injection, the risk of new wet AMD is reduced to 13.3% among eyes without the DLS compared with 20.9% of all study eyes and 30% of eyes with the double layer sign. Similarly, in eyes undergoing Syfovre injection every other month, the risk of new wet AMD is reduced to 2% among eyes without the DLS compared with 8.9% of all study eyes and 17.9% of eyes with DLS. Therefore, patients who have the double layer sign may wish to reduce their risk of developing wet AMD by avoiding the use of Syfovre.
Table 2: FILLY phase 2 study: New wet AMD among study eyes. Studying the effect of the double layer sign (DLS) which elevates the risk of wet AMD
| Parameters | Sham (no drug) | Monthly drug injection | Every other Month drug injection |
| All study eyes | 1.2% | 20.9% | 8.9% |
| DLS present | 4.2% | 30% | 24% |
| DLS absent | 0% | 13.3% | 2% |
Comments on the use of Syfovre:
Studies show that It may take over two years of treatment in order to see a benefit in vision. Patient selection may reduce the risk of new wet AMD in treated eyes. However, patient selection alone will not reduce the risk of other adverse effects including inflammation, infection, hemorrhage, retinal detachment, and ischemic optic neuropathy. Further risk reduction may be possible by reducing treatment frequency from monthly to every other month, but this reduces the effectiveness of the treatment in slowing the rate of progression of GA from 29% to 20%. Careful assessment is warranted for each patient to determine if the benefits of Syfovre outweigh the potential risks.
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