Syfovre and Izervay: What the Vision Loss Safety Warnings Mean
Syfovre and Izervay Safety Warnings at a Glance
Most of these eye injections pass without trouble. A few people get a serious problem in the days after a shot, and those problems do best when they are caught early. The Syfovre label tells you to seek care right away if the eye turns red, hurts or becomes sensitive to light, or if your sight changes in any way, such as flashing lights or blurred vision.1 Call your retina office the same day, or go to an emergency room if you cannot reach them, when you notice any of these:
- New blurred vision, decreased vision, or a sudden loss of vision.
- Severe eye pain, or pain that grows worse instead of easing.
- An eye that keeps getting redder after the first day.
- New floaters, a shower of floaters, or flashing lights.
- Light sensitivity that is new or getting worse.
These signs can point to swelling or an infection inside the eye. Both labels warn about infection inside the eye, and the Syfovre label also warns about swollen or blocked retinal blood vessels.12 Your retina team can start treatment the same day you call. Most people never see any of these signs, and waiting to see if one passes on its own is the choice that costs sight.
Syfovre and Izervay are FDA-approved for geographic atrophy, the late, dry form of age-related macular degeneration. Both are given as an injection into the eye, and both aim to slow how fast the patch of damage spreads across the macula, the small central part of the retina.12 Neither is a one-time fix. Both are ongoing treatments, given on a schedule, for as long as you and your retina specialist choose.
A safety warning is not a prediction about you. It lists problems that showed up often enough, in studies or in real use, that the FDA required the maker to name them. The Syfovre label warns about infection inside the eye and retinal detachment, retinal vasculitis or blocked retinal vessels, inflammation inside the eye, new wet macular degeneration, and a rise in eye pressure.1 The Izervay label carries the same list without the vasculitis and inflammation warnings.2 Most are uncommon, and the few that are serious are printed where you can read them.
How These Two Drugs Work Inside the Eye
Geographic atrophy is an area of the retina where the light-sensing cells and their support layer have thinned and died. Macular degeneration affects about 11 million people in the United States and takes the central vision you use for reading and faces, while side vision usually stays, so it does not cause total blindness.3 The patch widens slowly over years, and once a spot of retina is gone, it does not grow back.
Both drugs are complement inhibitors (clinical: they block part of the complement system, a branch of the immune system that clears debris and can also injure retinal cells when it stays switched on). Syfovre blocks a protein called C3. Izervay blocks a protein further down the same chain called C5.12 Damping that activity slows the spread of atrophy without switching the process off.
These drugs act at the edge of the damage, not in the middle of it. The American Academy of Ophthalmology tells patients plainly that neither drug has been shown to improve eyesight or to bring back vision that is already lost.4 The realistic goal is a smaller patch of loss five years from now, which is not the same as getting better.
How the Injections Are Given
The Syfovre dose is 15 mg, a tenth of a milliliter injected into the jelly of the eye, into each affected eye, once every 25 to 60 days.1 That window lets you and your retina specialist choose monthly or every-other-month dosing. Monthly dosing slowed the atrophy slightly more in the trials, and it also carried the higher rate of new wet macular degeneration on the label.51
The Izervay dose is 2 mg, also a tenth of a milliliter, injected into the eye once a month, about every 28 days.2 There is no every-other-month option on the Izervay label. If travel or caregiving makes a monthly visit hard to sustain, say so before you start.
Your eye is numbed, the surface is cleaned, a small clip holds the lids open, and the injection takes a second or two. Most people feel pressure rather than pain. Your vision can be blurry afterward, so the label advises against driving or using machines until your sight has recovered.1 A red patch on the white of the eye is one of the most common effects reported.2 It fades on its own.
Stopping is your decision, and it is best made out loud with your retina specialist rather than by missing appointments. The Syfovre label directs that treatment stop in an eye that develops retinal vasculitis or a blocked retinal vessel, and that injections wait until inflammation inside the eye has settled.1 Neither drug has been studied as a stop-and-restart treatment, so ask what a pause would mean for your eye.
The Warnings on the Syfovre Label
This is the most serious warning on the label. Retinal vasculitis, meaning inflamed retinal blood vessels that sometimes close off, has been reported with Syfovre after approval. It can begin with the first dose and can cause severe sight loss.1 In the retina safety committee review of the earliest cases, 14 eyes in 13 people were affected, every case followed a first injection, symptoms began around 10 days later on average, the vessels had closed off in 11 of the 14 eyes, and 8 of the 14 eyes had lost more than three lines on the vision chart at the last check.6 Those numbers describe the people it happened to, not your odds.
The honest answer is a rough one. No cases of retinal vasculitis appeared in the Syfovre trials, which is why the warning was added from reports that came in after the drug reached patients.1 The specialists who reviewed the first cases wrote that the true rate stays unclear, because the number of injections actually given was not known.6 More than 100,000 vials had been shipped by the time of that review, against reported cases in the tens.6
Inflammation without that vessel damage is the more common version of this problem. The Syfovre trials recorded inflammation inside the eye, including vitritis, iritis and uveitis, and the label allows treatment to resume after it clears.1 It usually shows up as blurring, floaters, aching or light sensitivity in the days after a shot. Much of it settles with drops, and it is why your team wants a call.
Any injection into the eye carries a small risk of endophthalmitis (clinical: a bacterial infection inside the eyeball) and of the retina pulling away from the back wall. Each occurred in fewer than 1 of every 100 people across the Syfovre trials, which enrolled 839 people, and the label ties the risk to injection technique.1 Infection inside the eye is a same-day emergency, which is why the warning signs at the top of this page are worth memorizing.
Some people on these drugs develop the wet form of macular degeneration, where new leaky vessels grow under the retina. By month 24 in the Syfovre trials, this happened in about 12 of every 100 eyes on monthly dosing and about 7 of every 100 on every-other-month dosing, against about 3 of every 100 in the sham group.1 Your retina specialist watches for it at every visit, and it is managed differently.
Putting extra fluid into a closed eye raises the pressure inside it. Pressure can climb within minutes of the injection, so the label calls for the pressure and the optic nerve blood supply to be checked afterward.1 For most people it settles during the same visit. If you have glaucoma, tell the person doing the injection.
The Warnings on the Izervay Label
Izervay carries fewer label warnings than Syfovre. It warns about infection inside the eye and retinal detachment, new wet macular degeneration, and short-lived rises in eye pressure. Retinal vasculitis does not appear on it.2 A review of 20 years of reports to the FDA safety reporting system found occlusive retinal vasculitis, bacterial infection inside the eye and new vessel growth reported far more often than expected for the drug in Syfovre, and found no retinal vasculitis reports for the drug in Izervay.7 That is a real difference in the signal so far, though Izervay has been in use for less time and that system counts reports, not rates.
This risk sits on both labels. In the Izervay studies, wet macular degeneration or new vessel growth appeared by month 12 in about 7 of every 100 people given the drug and about 4 of every 100 given sham injections, and by month 24 in about 12 of every 100 against about 9 of every 100.2 The gap is real but narrow, and eyes with advanced macular degeneration are prone to this anyway.
Here are the effects reported most often in the first year, set against the sham group. Across 292 people on Izervay and 332 given sham injections, bleeding under the surface of the eye, raised pressure, blurred vision and eye pain were reported most.2
| Effect in the first year | On Izervay | On sham |
|---|---|---|
| Red patch on the white of the eye | About 13 of every 100. | About 9 of every 100. |
| Raised pressure inside the eye | About 9 of every 100. | About 1 of every 100. |
| Blurred vision | About 8 of every 100. | About 5 of every 100. |
| New vessel growth under the retina | About 7 of every 100. | About 4 of every 100. |
| Eye pain | About 4 of every 100. | About 3 of every 100. |
Who Should Not Get These Injections Right Now
Both labels rule out an injection when there is an infection in or around the eye, or active inflammation inside the eye, and the Syfovre label adds a known allergy to the drug or its ingredients.12 A stye, a case of pink eye or a flare of uveitis pushes the appointment back until it clears. The Syfovre schedule itself allows up to 60 days between doses, so a short delay sits inside the way the drug is meant to be given.1
Bring the details that change the safety picture: past inflammation inside the eye, any eye surgery or injections you have had, glaucoma or high eye pressure, blood thinners, and drug allergies. Mention any eye that is currently red or sore, even mildly. If one eye is your only working eye, say so directly and ask how that changes the plan.
If both eyes need treatment, the timing between them is a safety decision. After reviewing the first vasculitis cases, the retina safety committee advised waiting at least a month after the first eye before injecting the fellow eye, since every case in that series followed a first injection.6 Ask your retina specialist how they space the two eyes and why.
Weighing the Benefit Against the Risk
The benefit is measured as slower growth of the atrophy patch, not as better vision. Over 24 months in the two Syfovre trials, the patch grew about 22 and 18 percent more slowly on monthly and every-other-month dosing in one trial, and about 19 and 16 percent more slowly in the other, compared with sham injections.5 In the larger Izervay trial, the measured growth rate over 12 months was 0.336 mm a year with the drug and 0.392 mm a year with sham, a gap of about 14 percent.8 In everyday terms, that is a fraction of a millimeter a year.
In the Syfovre trials, the treated and sham groups did not differ on the key secondary vision-function measures at 24 months.5 The Academy puts the slowing at roughly 14 to 20 percent and states that neither drug has been shown to improve eyesight or restore lost vision.4 Slowing a process that steals reading vision is worth something, but it is not the same as reading better next year.
You are weighing an injection every month or two, indefinitely, against a benefit you cannot feel and can only see on a scan. Retina specialists writing in the Academy's magazine call the benefit modest, note that two years of pegcetacoplan injections did not postpone the loss of best-corrected vision, and some of them say they do not yet consider these drugs safe and effective.9 Some people take that trade readily. Others decide the visits cost more than the slowing is worth. Neither choice needs justifying.
When to Call and Who to Call
Treat these as same-day, not next-visit. The label instruction is to seek care immediately for a red eye, light sensitivity, pain, or any change in vision such as flashing lights, blurred vision or straight lines that look bent.1 If your retina office is closed, use its after-hours line, and go to an emergency room if you cannot reach anyone. Both infection and inflammation are easier to control when caught early.
Not everything after an injection is urgent. A red patch on the white of the eye, mild scratchiness, a few new specks that drift and settle, and watering that fades are common and settle on their own. Call during office hours if they last beyond a week or bother you. The dividing line is direction of travel: anything getting worse day over day belongs in the same-day column.
An urgent care clinic cannot see inside your eye. Sorting inflammation from infection or a blocked retinal vessel needs a slit lamp, a dilated exam and retinal imaging, which live in an eye clinic. Call the practice that gave the injection first, since they have your scans. An emergency room is the right fallback when you cannot reach them, and ask there for the on-call ophthalmologist.
Questions People Ask About Syfovre and Izervay Safety
Severe sight loss in a treated eye has happened, and it is rare. The label warns that retinal vasculitis or a blocked retinal vessel can cause severe vision loss, and 8 of the first 14 affected eyes reviewed had lost more than three lines of vision.6 Those cases numbered in the tens against more than 100,000 vials shipped.6 Total blindness is not what is being described, since macular degeneration takes central vision and spares side vision.3
On the evidence available now, Izervay carries fewer label warnings and no reported retinal vasculitis, which is a genuine difference. A 20-year review of FDA safety reports found occlusive retinal vasculitis reported far more often than expected for the drug in Syfovre and not at all for the drug in Izervay.7 Two cautions belong with that: Izervay has been in use for less time, and that system counts reports rather than rates.
For the events counted in trials, the numbers are small. Infection inside the eye and retinal detachment each occurred in fewer than 1 of every 100 people across the 839 people in the Syfovre trials.1 For retinal vasculitis, no exact figure exists. The committee that reviewed the first cases said the rate remains unclear because the number of injections given was unknown.6 Rare with serious consequences is the fair summary.
No, and no study has shown that they do. The two Syfovre trials found no difference between treated and sham groups on the key secondary vision-function measures at 24 months, and the Academy states that neither drug has been shown to improve eyesight.54 The treatment aims at a slower spread of the damage. If reading vision matters most to you now, ask about low-vision rehabilitation alongside this decision.
Not necessarily, and it depends on what kind of inflammation it was. The Syfovre label allows treatment to resume once inflammation inside the eye has cleared, and directs that treatment stop in an eye that has developed retinal vasculitis or a blocked retinal vessel.1 Your retina specialist uses the exam and imaging from that episode to tell them apart. Ask which one you had.
Yes. This is an elective, ongoing treatment for a condition that moves over years, not an emergency medicine. Nothing is lost by pausing to think it over with someone you trust. Specialists describe the benefit as modest, and some question whether it is worth the burden of an injection every one or two months.9 Say it out loud at your next visit rather than quietly missing appointments.
More Questions About Living With These Injections
There is no set end date. Both labels describe ongoing dosing, every 25 to 60 days for Syfovre and about every 28 days for Izervay, with no stopping point built in.12 You and your retina specialist review it at intervals, looking at how the atrophy is moving on your scans and how well the visits fit your life.
Plan not to. Vision can be temporarily blurred after an injection into the eye, and the label advises against driving or operating machinery until sight has recovered.1 Arrange a ride for the first few visits, then judge from your own experience. If your vision has not cleared by the next day, call the office.
Two things: the warning signs listed at the top of this page, and any change in the shape of what you see. Straight lines that look wavy are a warning sign of trouble in the macula, and bent lines are among the changes the label says should send you back to your eye doctor.31 An Amsler grid on the refrigerator, checked one eye at a time, catches changes the other eye would otherwise cover up.
It can matter, particularly for the first dose. Every case in the first reviewed group of vasculitis cases followed a first injection, and the safety committee advised leaving at least a month between starting one eye and starting the other.6 That spacing lets one eye get through a first dose before the other is committed.
- Given my scans, how fast is my atrophy actually moving right now?
- Which of the two drugs do you recommend for me, and what makes you prefer it?
- How many cases of severe inflammation or vasculitis has this practice seen?
- How will we space treatment between my two eyes?
- What exactly should I call about, and what number do I use after hours?
- What are my options if I decide the injections are not worth it for me?
- US prescribing information via DailyMed, National Library of Medicine (label revised 07/2025) (2025). SYFOVRE (pegcetacoplan injection), for intravitreal use: full prescribing information.
- US prescribing information via DailyMed, National Library of Medicine (label revised 02/2026) (2026). IZERVAY (avacincaptad pegol intravitreal solution): full prescribing information.
- National Eye Institute, National Institutes of Health (2021). Age-Related Macular Degeneration (AMD).
- American Academy of Ophthalmology, EyeSmart patient education (2024). What to Know About Syfovre and Izervay for Geographic Atrophy.
- Heier JS and colleagues, The Lancet (2023). Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials.
- Witkin AJ and colleagues, Journal of Vitreoretinal Diseases (American Society of Retina Specialists safety committee case series) (2024). Retinal Vasculitis After Intravitreal Pegcetacoplan: Report From the ASRS Research and Safety in Therapeutics (ReST) Committee.
- Kailani Z, Mihalache A, Popovic M, Kertes PJ, Muni RH, American Journal of Ophthalmology (FDA Adverse Event Reporting System disproportionality analysis) (2025). Ocular Adverse Events Associated with Pegcetacoplan and Avacincaptad Pegol for Geographic Atrophy: A Population-Based Pharmacovigilance Study.
- Khanani AM and colleagues, The Lancet (2023). Efficacy and safety of avacincaptad pegol in patients with geographic atrophy (GATHER2): 12-month results from a randomised, double-masked, phase 3 trial.
- EyeNet Magazine, American Academy of Ophthalmology (retina specialist commentary) (2023). New Geographic Atrophy Drugs: The Good, the Bad, and the Unknown.