Investigational tracers could streamline diagnosis of retinal and systemic disease.

“It is possible that eventually, specific filters may be required to better delineate areas in which the tracers are showing up,” says Dr. Boyer. “I don’t envision that the tracers will be the same for every disease, so retina specialists and ophthalmologists may need to fine-tune which filters will lead to the best results and allow us to best image specific lesions.”

Dr. Boyer and Dr. Schwartz both anticipate the eventual use of retinal tracers in conjunction with optical coherence tomography (OCT) and other imaging modalities to obtain more detailed information. A combination of imaging technologies could be used to create an array of highly informative molecular, structural, and vascular maps.

“In the future, AI will probably be able to analyze information from the retinal tracers in combination with information obtained from OCTs and arrive at a relative risk factor score — one that takes into consideration variables such as the degree of nerve fiber layer thinning and changes in the ganglion layer. As we move into the future, AI will likely play a bigger role, especially as we obtain more and larger data sets and as AI develops greater ability to identify high-risk or low-risk patients based on analyses of data. A number of researchers — including those at Duke University — are already conducting such analyses,” says Dr. Boyer.

Once retinal tracers are approved, they also should prove to be a significant boon in the realm of drug development.

“In combination with OCT and other imaging modalities, retinal tracers may greatly refine our ability to improve inclusion and exclusion criteria in clinical trials,” says Dr. Schwartz. “They also should significantly facilitate our ability to evaluate the progression of disease and to assess the treatment effects of various drugs or biologics. The potential for more accurately tracking the progress of patients throughout their treatment journey is exciting.”

FUTURE DIRECTIONS
Although in the future retinal tracers might give retinal physicians the ability to screen patients for various neurologic diseases, for now, such use of the tracers is not practical.

“At this time, retinal physicians are unlikely to begin to arbitrarily screen people with these tracers, particularly without any idea as to whether a particular patient is likely to have a neurodegenerative disease,” says Dr. Boyer. “Certainly, Medicare and other insurance companies do not currently pay for such screening.”

Dr. Boyer also notes that further validation of retinal tracers will involve methods for ascertaining the functional benefits of treatments used to address various neurodegenerative diseases. “Although a biomarker may show changes on imaging that may hint that a particular drug is resulting in a benefit, the validation of the biomarker also must involve confirmation that a change in the biomarker correlates with functional improvement,” says Dr. Boyer. A drug or a condition such as Alzheimer’s disease, for example, could result in the removal of plaques without improving a patient’s ability to function. A drug for Alzheimer’s disease would have to show some improvement in cognition also. Likewise, a drug for ALS that results in promising changes in a retinal biomarker must also demonstrate a functional improvement, whether that involves lengthening the life of an ALS patient or giving that patient greater physical functioning. “The validation of a biomarker is always going to come down to function,” he says.

Once retinal tracers are approved, however, the uses for such tracers will likely expand, and eventually they may be used to detect a wide range of proteinopathies and neurodegenerative diseases. Indeed, many in the field of Alzheimer’s disease research already anticipate that retinal biomarkers will be used to identify preclinical stages of Alzheimer’s disease and facilitate the use of interventions designed to stop the disease or slow its progression.6 Current biomarker tools used in the Alzheimer’s disease field, such as amyloid PET imaging and CSF testing, tend to be limited in their availability, expensive, time-consuming, and more invasive than retinal tracers.

“Retinal physicians and ophthalmologists aim to evaluate the whole patient,” says Dr. Schwartz, “and we already are intimately involved with multiple subspecialists and generalists to improve outcomes for our patients, whether
they have diabetes or hypertension or collagen vascular diseases or cancer. Some patient conditions are first diagnosed in the eye; in these cases we refer patients out to other specialists. In other cases, conditions are diagnosed by outside specialists and referred in. Regardless of the referral patterns, the availability of exciting new tools such as retinal tracers should be a real step forward when it comes to improving our ability to care for our patients.”