The phase 3 OAKS and DERBY trials examined the efficacy of pegcetacoplan for slowing geographic atrophy secondary to age-related macular degeneration. This study analyzed geographic atrophy lesion growth using spectral-domain optical coherence tomography features in 936 of 1,258 OAKS and DERBY participants to provide insights into retinal pigment epithelium loss and photoreceptor degeneration with pegcetacoplan treatment.
While short-wavelength fundus autofluorescence (FAF) is the current standard for detecting geographic atrophy (GA) lesions in clinical trial, optimal interpretation of these images can be challenging, the investigators note in their JAMA Ophthalmology article. While hypoautofluorescence can indicate the expected retinal pigment epithelium (RPE) loss in GA, FAF signals are reduced in the foveal region due to luteal pigment's natural blue light absorption, making precise definition of lesion boundaries difficult.
As an alternative, the investigators suggest the use of spectral-domain optical coherence tomography (SD-OCT) which is used regularly in clinical practice and provides a high resolution cross-sectional image set of the retinal layers, RPE and often the choroid.
While GA lesions treated with pegcetacoplan initially were assessed in OAKS and DERBY with FAF imaging, researchers in this post-hoc analysis used a deep-learning OCT platform to analyze protective associations between pegcetacoplan and GA features from SD-OCT volume scans from the OAKS and DERBY trials.
They found the SD-OCT data highlighted slower growth rates in GA features such as hypertransmission and photoreceptor degeneration (PRD) with pegcetacoplan treatment, especially in the first 18 months, but a “negative growth rate observed from 18 months onward suggests RPE loss was occurring faster than PRD,” the researchers wrote. “Based on the model that PRD preceded RPE loss, we propose pegcetacoplan may be protective of both photoreceptors and RPE, and that protection of photoreceptors can be observed more readily than with RPE.” The OCT analysis of the monthly and every-other-month treatment groups found greater reductions in RPE loss than were found with FAF in OAKS and DERBY.
The reduction in lesion growth was more prominent in the parafoveal and perifoveal regions, but the researchers also noted that while FAF imaging showed involvement of the central foveal point in 63% of cases, imaging using SD-OCT showed a rate greater than 95%. Additionally, PRD of the central foveal point was seen in 89% of cases. They suggested that foveal involvement and extent of disease may lead to a ceiling effect for treatment.
Visual acuity remained relatively stable in both the pegcetacoplan and sham groups, but the treatment group showed less structural damage progression in retinal layers, particularly in areas of photoreceptor degeneration and hypertransmission. However, the investigators concluded, “studies that include participants with a diverse range of foveal region occupancy of GA features are needed to fully assess pegcetacoplan effects on GA growth in each of the macula regions. This may impact the observed treatment effects on clinical outcomes that measure foveal health, such as BCVA.”
A full list of author disclosures can be found in the published research