Inherited retinal disease (IRD) treatment is entering a new era. Once limited largely to supportive care, the field is rapidly advancing toward therapies targeting specific genes, mutations, and retinal pathways. Gene augmentation is leading this wave of genetic medicine, with gene editing, optogenetics, and mutation-specific treatments expanding the possibilities.
But as these innovative therapies move into clinical trials, a critical question remains: How do we know whether a treatment is preserving, restoring, or changing retinal function?
The 2017 FDA approval of Luxturna demonstrated that a genetic disease could be matched with a targeted gene therapy to produce meaningful functional improvements in affected patients, helping accelerate the development of additional treatments.
As novel therapies become increasingly tailored to specific genotypes and phenotypes, clinical trial patient selection and outcome measurements must evolve alongside them. Choosing the right functional assessments requires understanding the gene, cell type, retinal pathway, and stage of disease being treated.
From Disease Characterization to Genetic Diagnosis
For much of the twentieth century, patient care centered around distinguishing one clinical condition from another by characterizing patterns of vision loss, describing retinal appearance, and recording family history.
Once a diagnosis was established, care was largely supportive. Patients were offered genetic counseling, education, visual aids, mobility training, workplace or school accommodations, and low-vision rehabilitation, but there was little that could be done to alter the underlying disease.
Before targeted treatments were available, visual electrophysiology played an important role in distinguishing rod- from cone-mediated disease, identifying where retinal dysfunction was occurring, and supporting diagnosis.
Later, genetic testing revealed that the relationship between a genetic variant and the disease a patient develops is not always straightforward. Different genetic causes can produce similar retinal conditions, while variations in the same gene can affect patients differently.
This is where visual electrophysiology remains particularly valuable: genetic testing identifies the underlying cause, while electrophysiology provides an objective measure of how the retina is functioning.
Visual Electrophysiology in IRD Clinical Trials
Today, genetic testing can identify the gene or mutation responsible for an inherited retinal disease, while visual electrophysiology shows how that disease is affecting the retina’s function.
Together with other clinical findings, this information helps determine whether a patient is appropriate for a particular therapy or clinical trial.
Because IRDs affect different genes, cell types, and retinal pathways, a single set of endpoints cannot be generalized across every study. The functional test must match both the biological target of the therapy and the function it is intended to preserve, restore, or change.
For example, clinical trials targeting conditions such as X-linked retinoschisis (XLRS), retinitis pigmentosa (RP), Leber congenital amaurosis type 10 (LCA10), and Usher syndrome type 2A may incorporate full-field electroretinography (ERG) and full-field stimulus threshold testing (FST), depending on the treatment and study objectives.
These complementary tests provide different perspectives on visual function. Full-field ERG objectively measures the retina’s electrical responses to light, while FST measures light detection sensitivity, including in patients with very limited vision.
Together, they can help investigators characterize retinal function, establish meaningful baselines, and monitor functional changes throughout treatment.
Measuring Progress in a New Era of Treatment
The development of new treatments for inherited retinal diseases continues to rely on established methods of functional testing for validation.
As therapies become more targeted and clinical trials more specialized, visual electrophysiology and complementary psychophysical testing remain valuable for:
- Characterizing patients and supporting clinical trial selection
- Establishing pretreatment baselines against which functional change can be evaluated
- Monitoring safety and identifying potential retinal toxicity
- Evaluating treatment response by detecting changes in retinal function over time
Genetic medicine is transforming what may be possible for patients with inherited retinal diseases. But identifying the genetic target is only part of the story.
To understand whether a therapy is making a functional difference, researchers must be able to measure the retina’s response.
Visual electrophysiology, alongside complementary tests such as FST, continues to provide essential insights as the field moves from identifying disease to evaluating treatments designed to change its course.