Pegcetacoplan slowed atrophy by 41% over two years, and vision still declined by eight letters

Design

retrospective interventional case series within a prospective imaging study

Population

77 eyes of 58 patients with geographic atrophy completing two years of intravitreal pegcetacoplan; 49 eyes had pre-treatment annual imaging

Primary outcome

square-root geographic atrophy growth rate and best-corrected visual acuity over two years

Effect

growth 0.33 ± 0.21 to 0.19 ± 0.11 mm/year, a 41% reduction (P<0.001); acuity 63 ± 14 to 55 ± 16 letters (P<0.001)

Complement inhibition for geographic atrophy is the most argued-about decision in medical retina, because the trials slowed lesion growth without showing a functional benefit. This retrospective series followed 77 eyes of 58 patients treated at one centre from April 2023, all enrolled in a prospective swept-source OCT angiography imaging study, who completed two years on 15 mg intravitreal pegcetacoplan - an average of 18 injections at 1.3-month intervals.

In the 49 eyes with prior annual imaging, the square-root atrophy growth rate fell from 0.33 ± 0.21 mm/year before treatment to 0.19 ± 0.11 mm/year after two years, a 41% reduction (P<0.001). Of 72 eyes with two-year follow-up, 71 either slowed further or held steady in the second year; the single eye that accelerated was also receiving anti-VEGF for exudative neovascularisation. Growth did not differ between foveal and non-foveal atrophy. Eyes with faster pre-treatment growth showed greater percentage inhibition (r=0.40 at two years, P=0.007).

And best-corrected visual acuity fell from 63 to 55 letters over the same two years (P<0.001). That is the whole difficulty, restated in real-world data: the anatomical endpoint responds, the functional one does not, and the treatment costs monthly injections. The one genuinely new signal is the accumulating effect in year two and the correlation with pre-treatment growth rate, which together suggest that if this drug benefits anyone it is the patient with fast-growing atrophy treated early. In India, where pegcetacoplan is not available and geographic atrophy is managed with observation and low-vision support, this is a paper to understand rather than to act on.

• Present the trade-off explicitly: a 41% reduction in lesion growth alongside an eight-letter acuity loss over two years
• Where the drug is available and being considered, the faster-growing lesion and the earlier patient are the better candidates
• Count the burden honestly - about 18 injections over two years, roughly monthly
• Monitor for exudative conversion; the one eye that accelerated had developed neovascularisation
• In settings where the drug is unavailable, focus on low-vision rehabilitation and smoking cessation rather than on access advocacy for an uncertain benefit

Why it matters

It is the two-year real-world version of the question the trials left open, and the answer has not changed.

Don't overread it

A single-centre retrospective series with no untreated control group - growth rate reduction is measured against each eye's own prior rate, not against untreated eyes.

The statistics, in plain English

Square-root transformation of lesion area is used because atrophy grows at the lesion edge, so untransformed area growth accelerates simply as the lesion gets bigger - the transformation makes rates comparable between eyes. The 41% figure comes from a before-and-after comparison within 49 eyes, not a randomised control, so regression to the mean is a live alternative explanation, particularly given that faster pre-treatment growers showed the most inhibition. The acuity decline of eight letters has no comparator at all here; untreated eyes were not followed.

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