Aged-related macula degeneration is one of the most frustrating and difficult diseases for both patients and doctors, because it causes progressive and irreversible loss of vision. Advanced dry AMD accounts for around 20% of legal blindness in Western countries. Until recently, we had no real treatment options, only supportive care such as low‑vision aids and magnifiers.

In 2023, two new medications—Syfovre and Izervay—were approved in the United States. In 2025, these same drugs were approved for use in Australia. They represent the first medications shown to slow the progression of geographic atrophy, the advanced form of dry AMD.

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1) What is AMD?

Age‑related macular degeneration (AMD) is a progressive condition that damages the macula, the central part of the retina responsible for detailed vision. It is the leading cause of vision loss in adults over 60.

There are two main forms:
• Dry AMD – caused by accumulation of waste material called drusen under the retina, leading over time to cell death and geographic atrophy.
• Wet AMD – caused by abnormal, fragile blood vessels that leak or bleed. This form can cause sudden vision loss but is treatable with anti‑VEGF injections.

Geographic atrophy (GA) is the advanced stage of dry AMD. As GA enlarges, vision progressively worsens, especially if it involves the fovea, the very centre of the macula.

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2) Why Does Dry AMD Progress?

The leading explanation involves dysfunction of the retinal pigment epithelium (RPE), the support cells that clear waste products from photoreceptors. When RPE cells fail, waste accumulates as drusen. Eventually, both RPE cells and photoreceptors die, producing geographic atrophy.

A second major driver is over‑activation of the complement system, a component of the immune system. In AMD, this system becomes dysregulated, causing inflammation and unnecessary retinal cell loss. This discovery led to the development of complement‑inhibiting drugs.

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3) The New Medicines: Syfovre and Izervay

Syfovre inhibits complement component C3, while Izervay inhibits C5. Both aim to dampen the overactive complement pathway seen in dry AMD.

These medications are given as intravitreal injections—one injection into the eye every two months—equating to six injections per year. They do not cure AMD or restore lost vision, but are designed to slow disease progression.

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4) What Did the Clinical Trials and Post‑Hoc Analyses Show?

Initial clinical trials demonstrated that both drugs slow the rate of enlargement of geographic atrophy on specialised retinal imaging.

The original trials did not show a clear improvement in functional vision, such as reading ability or visual acuity, over the first one to two years.  It is for this reason that most countries in the world have not approved these drugs as of late 2025.

However, subsequent post‑hoc subgroup analyses suggest that some patients may benefit more than others. In particular, patients with earlier geographic atrophy that has not yet involved the centre of the macula (the fovea) may experience a meaningful delay before central vision is affected.

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5) Rationale for Australian Approval

Australian regulators approved Syfovre and Izervay in 2025 based on the concept that treatment is most valuable when started early—before geographic atrophy reaches the fovea and while vision is still relatively good.

The aim is preventive rather than restorative: preserving central vision for as long as possible, even if immediate vision improvement is not seen.

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6) Risks and Side Effects

Both medications carry important risks that must be considered:

• Increased risk of developing wet AMD, requiring additional injections.
• Eye inflammation.
• Raised eye pressure (more commonly reported with Izervay).
• Rare but serious complications such as optic nerve damage or retinal vasculitis.

For this reason, careful patient selection and close monitoring are essential.

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7) Cost and Access in Australia

The cost of these medications remains very high, with each injection costing several thousand dollars per eye. Given the dosing schedule of one injection every two months, this equates to six injections per eye per year.

At present, patients may be required to self‑fund treatment. The Australian ophthalmology community is awaiting a decision from the Federal Government regarding potential PBS funding. Until funding decisions are made, cost remains a significant barrier for many patients.

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Dr Davies considers it critically important that assessment of dry AMD and geographic atrophy extends beyond retinal imaging alone. While OCT and fundus autofluorescence are essential for measuring structural changes, they do not fully capture how well the macula is functioning.

For this reason, Dr Davies regards macular microperimetry using the MAIA system as the new standard for assessing macular function. MAIA testing allows precise, point-by-point measurement of retinal sensitivity across the macula, correlating structure with real-world visual performance.

Baseline MAIA testing provides a functional map of the macula before treatment, and repeat testing over time allows objective monitoring of disease progression and the functional impact of complement-inhibitor therapies such as Syfovre and Izervay. This approach helps identify patients who may be functionally benefiting from treatment even when standard visual acuity remains unchanged.

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8) Final Thoughts

Syfovre and Izervay represent an important milestone in the management of dry AMD. For the first time, we have therapies that can slow the progression of geographic atrophy.

However, these treatments:
• Do not restore lost vision
• Appear to work best when started early
• Require ongoing injections
• Are costly and not yet government‑funded

For suitable patients—particularly those with early geographic atrophy sparing the fovea—these drugs may help preserve useful vision for longer. Decisions about treatment should be individualised and made in close discussion with your eye specialist.