A systematic review of the clinical evidence on biomarkers of diabetic retinal disease identified imaging modalities beyond color fundus photography—specifically spectral-domain optical coherence tomography (SD-OCT)—may be ready for incorporation into an updated staging system, while others show promise for future incorporation.
Give me some background first.
As a leading cause of global blindness, diabetes mellitus (DM) can lead to diabetic retinal disease (DRD). If left untreated, DRD can result in vision loss and blindness.
Diabetic macular edema (DME) and diabetic retinal neurodegeneration (DRN) are known factors in DRD; however, they are measured using different staging metrics than the Early Treatment Diabetic Retinopathy Study (ETDRS), the current standard for DRD staging.
As such, the proliferation of metrics for staging DRD, the study authors argued, means that a new framework for staging the disease is required.
Now, talk about the study.
This paper—“a systematic review of current and emerging biomarkers to quantify DRD, related to DRN and DME”—was based on findings from the Mary Tyler Moore (MTM) Vision Initiative’s Diabetic Retinal Disease Staging (DRDS) Update Project.
Current research, according to the study authors, has shown that DRN can precede vascular manifestations of DRD while simultaneously affecting the development of the disease, whether in ischemic or exudative forms.
What exactly is a biomarker?
A biomarker was specified as “defined characteristic that is measured as an indicator of normal biological processes, or pathogenic processes,” per the National Institutes of Health and U.S. Food and Drug Administration.
The four primary biomarkers for measuring DRN and DME and their dimensions were:
- Neuroretinal function
- Retinal sensitivity measured with microperimetry
- Implicit time and oscillatory potentials measured with full-field flash electroretinogram (ERG)
- Neuroretinal structure
- Qualitative and quantitative evaluation of neuroretina measured with SD-OCT
- Other parameters measured with Adaptive Optics Scanning Laser Ophthalmoscopy
- Retinal structural changes associated with DME
- Central subfield thickness (CST) plus additional parameters measured with SD-OCT
- Retinal vascular changes associated with DME
- Vessel densities, foveal avascular zone, and others measured with OCT angiography (OCT-A)
Findings?
Based on the review, the study authors found that for all stages of subclinical or clinical DRD, SD-OCT with analytics was ready for current use or within the next 1-2 years.
OCTA and full-field flash ERG microperimetry were not yet ready for full implementation, but did have unmet but defined research needs that could be accomplished in the next five years.
Adaptive optics had potential, they noted, but would likely take longer than 5 years to accrue clinical evidence for implementation.
Take home.
As research continues into updating the DRD staging metric, new imaging modalities such as OCT-A, SD-OCT, microperimetry, and so on will be further evaluated for their predictive power in order to identify an accurate and low-resource parameter.
The study authors noted that “given that many of our protocols, standards of care, diagnostics, and therapeutics, as well as estimates of clinical outcomes were developed based on the ETDRS system, it is important that the new classification scheme retain continuity.”