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Geographic Atrophy Treatment: Comparing Izervay and Syfovre
How Each Drug Works and How It Is Given
Both medications are given as injections directly into the eye, a procedure called an intravitreal injection. Understanding how each drug is administered and how often helps set realistic expectations before starting treatment.
Izervay contains a medicine called avacincaptad pegol, which blocks a complement protein called C5 to slow the destruction of retinal cells. The standard dose is 2 mg injected into each affected eye once a month, approximately every 28 days. There is no set maximum duration of treatment. Before each injection, the eye is numbed and cleaned with an antiseptic solution, and the injection itself takes only seconds. A brief pressure check typically follows before you leave the office.
Syfovre contains a medicine called pegcetacoplan, which blocks a complement protein called C3, one step earlier along the same immune pathway that Izervay targets. The dose is 15 mg injected into each affected eye, and the approved interval is every 25 to 60 days. That range allows for either a monthly or an every-other-month schedule, which your retina specialist sets with you based on your situation. The injection procedure is identical in appearance to an Izervay visit.
Neither drug improves vision or restores sight that has already been lost. Both were shown in clinical trials to slow the growth of the atrophic patch on retinal imaging, compared with a sham injection. Treatment is ongoing with no defined end point, meaning it continues for as long as you and your retina specialist agree the benefit outweighs the burden and risks.
What the Clinical Trials Found
Both medications were studied in large randomized trials that measured how quickly the area of geographic atrophy grew on retinal images, compared with a sham injection. Reading these numbers with care is important, because the trials are not directly comparable.
Syfovre was studied in two trials called OAKS and DERBY, both measuring lesion growth over 24 months. In the OAKS trial, monthly Syfovre was associated with approximately a 22 percent reduction in the rate of lesion growth compared with sham injection. In the DERBY trial, the reduction was approximately 18 percent. These results reflect a measurable slowing effect on the retina, not an improvement in visual acuity.
Izervay was studied in two trials called GATHER1 and GATHER2, both measuring lesion growth over 12 months. In GATHER1, Izervay was associated with a slowing of lesion growth of approximately 35 percent compared with sham. In GATHER2 the figure was approximately 18 percent. The 12-month measurement window differs from the 24-month window used in the Syfovre trials, which is one reason these numbers cannot be meaningfully compared side by side.
No clinical trial has ever enrolled patients in both groups simultaneously to compare Izervay and Syfovre against each other. The two programs enrolled different patient populations, used different follow-up lengths, and applied different statistical models. Placing a percentage from one program next to a percentage from the other and declaring a winner is not supported by the evidence. Indirect statistical comparisons have been attempted, but those are estimates built on assumptions rather than direct results.
Neither drug has been shown to improve eyesight or halt progression entirely. The effect measured in both programs works out to a modest slowing of the growth of the atrophic area over time. For a patient considering treatment, the honest framing is that vision will most likely continue to decline, but the timeline may be extended compared with no treatment. This is a real and meaningful effect for many patients, but it is important to understand it clearly before starting.
Risks and Side Effects
Like all injections into the eye, both medications carry a small set of shared risks as well as some risks that differ between the two drugs. Understanding them before treatment starts helps you recognize warning signs promptly.
Every intravitreal injection carries a small risk of infection inside the eye, known as endophthalmitis, as well as a risk of retinal detachment, bleeding at the injection site, and a temporary rise in eye pressure immediately after the procedure. These events were reported in fewer than 1 in 100 patients in the clinical trials. Rare does not mean impossible, and identifying these problems early greatly improves outcomes.
After any injection, mild soreness, a small red spot on the white of the eye, and a few extra floaters for a day or two are common and usually settle on their own. The following symptoms are different and require a same-day call to the office that gave the injection.
- Sudden or worsening vision loss
- Severe eye pain, or pain that increases rather than fades over time
- A red eye with discharge, or new sensitivity to light
- A sudden shower of new floaters or flashing lights
If you cannot reach the treating office, go to an emergency room. Do not wait for your next scheduled visit.
Both drugs raise the chance of converting from dry to wet macular degeneration, a complication that requires its own separate injection treatment. In the Syfovre trials, new wet macular degeneration appeared in approximately 12 out of every 100 eyes treated monthly by month 24, compared with approximately 3 out of every 100 in the sham group. In the Izervay trials, the conversion rate at 12 months was approximately 7 out of every 100 on treatment versus approximately 4 out of every 100 on sham. Because the sham rates differ between the two programs, these figures cannot be subtracted from each other to compare the drugs. Wet macular degeneration is treatable, and catching it early is one of the reasons frequent monitoring visits are part of treatment.
One safety concern is specific to Syfovre. Inflammation of the retinal blood vessels, a condition called retinal vasculitis, has been reported following Syfovre injections. This can occur after the very first injection, with or without a blockage of those vessels, and can cause severe vision loss. A safety committee of the American Society of Retina Specialists confirmed 14 affected eyes in 13 patients, with cases appearing a median of approximately 10 days after the first injection. Two eyes were subsequently removed. The true rate of this complication is not known because the total number of injections given was not counted. The number of reported cases is small, but the severity of outcomes in those cases makes it an important part of the treatment decision.
A good outcome with either medication is quiet and invisible. Scan after scan will show the atrophic area growing more slowly than it otherwise would have. You will not feel the drug working, and you will not gain reading vision because of it. The yardstick is slowing, not reversal. If your goal is to protect the central vision you still have for as long as possible, treatment can be worth the commitment. If you were hoping to recover vision already lost, neither of these medications is designed to do that.
Deciding With Your Retina Specialist
The choice between these two medications, or the decision not to treat, involves your scan findings, your health history, your schedule, and your own priorities. No recommendation applies to every patient equally.
Both drugs are approved specifically for geographic atrophy caused by age-related macular degeneration. They are not indicated for early or intermediate dry macular degeneration, wet macular degeneration, or atrophy from any other cause. Your retina specialist confirms the diagnosis and maps the size and location of the atrophic area using retinal imaging, typically including optical coherence tomography, before recommending treatment. Where the atrophy sits in relation to the center of vision affects how urgent treatment may be.
If travel to the clinic every single month is difficult due to distance, transportation, or other commitments, the every-other-month option available with Syfovre may be an important practical advantage. On the other hand, if you have a history of inflammation inside the eye, or if the retinal vasculitis reports weigh heavily in your decision, your retina specialist may favor Izervay. Being specific about which of these factors is most significant for you helps make the conversation more useful.
Treatment with either medication is not a fixed course with a defined end. Both are intended to continue indefinitely, with injections roughly every four to eight weeks for as long as the benefit is felt to outweigh the burden and risks. Before starting, it is worth honestly accounting for what that commitment involves. That includes transportation to and from each visit, time taken by a companion if one is needed, and recovery time the day of each injection. Out-of-pocket costs also vary by insurance plan, and both drugs are typically billed through medical benefits rather than a pharmacy plan because they are administered in a clinic. Confirming your coverage before the first appointment is strongly recommended.
Going into your appointment with specific questions leads to clearer answers and a more confident decision.
- How large is my atrophy now, how fast has it grown on my scans, and how close is it to the center of my vision?
- Given my history and scan findings, which drug do you recommend for me and why?
- What schedule would I be committing to, and how long before we reassess?
- What is my risk of converting to wet macular degeneration, and how would we catch it early?
- What symptoms should prompt a same-day call, and what number do I use after hours?
Frequently Asked Questions
These answers address practical decisions and situations that come up most often for patients considering or already receiving treatment for geographic atrophy.
No head-to-head trial has ever compared these two drugs directly, so there is no evidence that one outperforms the other. The choice is best made on practical fit: the injection schedule you can realistically maintain, your personal history with eye inflammation, how much the retinal vasculitis reports factor into your thinking, and what your retina specialist sees on your imaging. Choosing based on fit rather than on a ranking that does not yet exist is the most evidence-based approach available.
Both drug labels describe treating each affected eye, so bilateral treatment is possible when geographic atrophy is present in both eyes. Some retina specialists prefer to stagger the two eyes across separate visits so that a complication in one eye does not put both at risk at the same time. Others treat both on the same day. The approach varies by practice and by your individual circumstances, so ask your retina specialist how they handle second-eye treatment and what reasoning guides that choice.
Do not stop or change any supplement on your own. The question of nutritional supplements and the question of injection therapy are separate decisions supported by different bodies of evidence. Starting one of these medications is not automatically a reason to stop a supplement your doctor previously recommended. Bring the actual bottle to your appointment so the exact formula can be reviewed alongside your other medications. Your retina specialist needs the full list before your first injection.
Choosing not to treat is a legitimate option. Geographic atrophy typically expands slowly over years whether or not it is treated, and both medications change the pace rather than the direction of that progression. Declining treatment means avoiding the injection schedule, the associated risks, and the elevated chance of converting to wet macular degeneration. What is given up is the modest slowing of lesion growth. Regular monitoring, home vision checks with an Amsler grid, and low-vision rehabilitation referrals all remain available options and should be discussed with your retina specialist regardless of your treatment decision.
Checking an Amsler grid daily, one eye at a time with your glasses on in good light, is the most commonly recommended approach for home monitoring. New waviness, blurriness, a new dark patch, or a change in how straight lines appear should prompt a same-day call to your retina specialist, not a wait until your next scheduled visit. This monitoring is relevant whether or not you are on treatment, because a conversion to wet macular degeneration can occur at any stage and benefits from early detection.
Arrange a ride, because your eye will be dilated and vision will be blurry for several hours after the visit. Bring sunglasses, a list of all current medications and eye drops, and your glasses. The visit typically takes longer than the injection itself because imaging, dilation, and a pressure check are part of the appointment. Before you leave, confirm which symptoms should prompt a same-day call and what number to use outside of office hours, and write that number somewhere you can easily find it.
See Our Team at Atlantic Retina Center
At Atlantic Retina Center, our fellowship-trained, board-certified retina specialists focus exclusively on diseases of the retina, vitreous, and macula, with offices serving patients throughout the Eastern Shore of Maryland and central and southern Delaware. If you have been diagnosed with geographic atrophy or have been referred for evaluation, we are here to review your imaging, explain your options honestly, and support whatever decision you make. We would welcome the opportunity to be part of your care.