Pegcetacoplan Linked to Slower Lesion Progression in Eyes with Geographic Atrophy

Ursula Schmidt-Erfurth, MD

Eyes treated with pegcetacoplan showed significantly slower geographic atrophy (GA) lesion progression and slower growth rate toward the fovea compared with sham, according to new research.

The investigator team, led by Ursula Schmidt-Erfurth, MD, Chair, Department of Ophthalmology, University Eye Hospital, cited the assessment of GA progression on a topographic level as essential to capture the pathognomonic heterogeneity in individual lesion growth and therapeutic response.

“This study may help to identify patient cohorts with faster progressing lesions, in which pegcetacoplan treatment would be particularly beneficial,” wrote investigators.

The retrospective analysis of the FILLY trial aimed to identify disease activity and the effects of intravitreal pegcetacoplan treatment on the topographic progression of GA secondary to age-related macular degeneration (AMD) quantified in spectral-domain OCT (SD-OCT) by automated deep learning assessment.

It included SD-OCT scans of 57 eyes with monthly treatment, 46 eyes with every-other-month treatment, and 53 eyes with sham injection from baseline and 12-month follow-ups were included, in a total of 312 scans.

Using validated deep learning algorithms, retinal pigment epithelium loss, photoreceptor integrity, and hyperreflective foci were automatically segmented. Then, local progression rate was determined from a growth model measuring the local expansion of GA margins between baseline and 1 year.

Moreover, for each individual margin point, the eccentricity to the foveal center, the progression direction, mean photoreceptor thickness, and hyperreflective foci concentration in the junctional zone. Then, mean local progression rate in disease activity and treatment effects conditioned on these properties were estimated by spatial generalized additive mixed-effect models.

The main outcomes were local progression rates of GA, photoreceptor thickness, and hyperreflective foci concentration in mm. A total of 31,527 local GA margin locations were analyzed.

The findings suggest local progression rate was higher for areas with low eccentricity to the fovea, thinner photoreceptor layer thickness, or higher hyperreflective concentration in the GA junctional zone.

Then, when controlling for topographic and structural risk factors, investigators found on average a significantly lower local progression rate by –28.0% (95% CI, –42.8 to –9.4; P = .0051) and –23.9% (95% CI, –40.2% to –3.0; P = .027) for monthly and every-other-month treated eyes, respectively, compared with sham.

Investigators noted the assessment of GA progression on a topographic level is essential to capture the pathognomonic heterogeneity in individual lesion growth and therapeutic response.

“Automated artificial intelligence–based tools will provide reliable guidance for the management of GA in clinical practice,” they wrote.

The abstract, “Predicting Topographic Disease Progression and Treatment Response of Pegcetacoplan in Geographic Atrophy Quantified by Deep Learning,” was published in Ophthalmology Retina.