Visual electrophysiology can provide valuable functional evidence in clinical trials of therapies designed to stimulate, replace, or restore retinal cells. For localized treatments of the macula, multifocal ERG, or mfERG, is particularly useful because it maps retinal responses across many small regions. This allows investigators to evaluate function within and around the treated area rather than relying only on a global measure of retinal activity.
At a Glance
• Multifocal electroretinogram (mfERG) maps retinal function across localized areas, offering more specific insights than global retinal measurements.
• Emerging dry AMD therapies, including stem cells and bioelectrics, require targeted functional testing.
• Multifocal ERG complements structural imaging by confirming whether surviving retinal tissue is electrically responsive.
New approaches to treating geographic atrophy
Several emerging approaches to treatment of dry AMD and geographic atrophy illustrate the need for functional testing. Although these therapies work through very different mechanisms, most are designed to preserve or restore function within a specific region of damaged retina, something that multifocal ERG can measure very well.
Stem cell therapy is both regenerative and localized. This approach aims to replace damaged or lost RPE cells, which normally provide essential support to photoreceptors. Stem cell-derived RPE may be delivered beneath the retina as a cell suspension or as an organized layer grown on a scaffold. The goal is to rebuild enough of the RPE support system to protect surviving photoreceptors and potentially improve the function of remaining retinal tissue. In a localized treatment such as this, mfERG can help determine whether retinal responses are preserved or changed within and around the treated region.
Bioelectric stimulation takes a different approach. Rather than replacing damaged cells, controlled electrical stimulation is used with the goal of encouraging surviving retinal cells to function more effectively and resist further degeneration. Because the treatment is intended to influence cellular function, visual electrophysiology provides a natural way to assess whether retinal responsiveness changes over time. Localized testing with mfERG can also help determine whether functional effects remain confined to the intended area or appear elsewhere in the macula.
Retinal prostheses represent another approach to restoring function in patients with severe central vision loss. Subretinal systems use a small implanted device together with external visual equipment to stimulate remaining retinal neurons and bypass some of the function lost through photoreceptor degeneration. Visual electrophysiology has played a role in the preclinical development of these technologies by helping researchers confirm that electrical stimulation produces measurable responses within the remaining visual pathway.
The growing role of mfERG in AMD trials
Dry AMD can result from a combination of oxidative stress, inflammation, aging, genetic susceptibility, and other processes that progressively damage the RPE and photoreceptors. Because the mechanisms and resulting patterns of damage vary, emerging treatments are taking equally diverse approaches to treatment.
This diversity creates a need for flexible functional measurement. Imaging can show where retinal tissue remains and whether structural changes occur after treatment. Multifocal ERG adds another layer by showing whether localized retinal regions are electrically responsive. As therapies become more targeted to specific areas of the macula, the ability to map function within and around treated areas may become increasingly valuable in clinical trials.