Growing evidence indicates that the retina is impacted in mild cognitive impairment (MCI)—often a precursor to Alzheimer’s disease—but a new meta-analysis of previous studies suggests quite a range of presentations that might be classified as indicative of MCI. It notes that further investigations are needed to determine if OCT can be used as a biomarker for MCI at the onset of the condition.

This systematic review and meta-analysis evaluated 15 published research papers on retinal thickness measured by OCT and MCI.

Pooling the data, 58.9% of MCI patients showed statistically significant thinning of the peripheral RNFL compared with normal subjects. Additionally, 61.6% showed a statistically significant reduction in macular volume compared with controls, and 50% of macular ganglion cell-inner plexiform layers (GCL-IPL) experienced significant thinning in MCI patients.

While MCI had a large impact on decreased macular thickness, the researchers noted substantial heterogeneity in macular thickness. The other variables didn’t demonstrate a significant difference and also had substantial heterogeneity.

“Several important findings from this review may help to inform future work related to retinal OCT biomarkers for neurodegenerative diseases that present with mild cognitive impairment, specifically Alzheimer’s disease,” the researchers wrote in their paper. They found evidence that differences in inner retinal measures and macular volume between MCI patients and healthy controls can be detected with OCT. Additionally, studies that scanned both the macula and circumpapillary regions showed differences between the study patients and controls in one of the locations, but not both, the investigators noted.

Since they observed significant heterogeneity between studies, the researchers suggested retinal degeneration associated with MCI is itself likely to be heterogeneous, with respect to the degree of degeneration between different regions of the retina and tissue involved (i.e., retinal ganglion cell, retinal ganglion cell axon, optic nerve). “Given what we know about the clinical and pathological heterogeneity of Alzheimer’s disease, this is not surprising,” they wrote.

The researchers suggest the following systemic approach for retinal OCT studies in Alzheimer’s disease-related neurodegeneration:

• consistent use of the same technology platform, specifically spectral-domain OCT
• National Institute on Aging and Alzheimer’s Association diagnostic criteria for healthy controls, MCI and Alzehimer’s patients
• Larger, longitudinal cohort studies or population-based studies
• OCT imaging of both eyes and scanning of the macula and circumpapillary regions to determine circumpapillary RNFL thickness, macular volume and thickness and GCL-IPL thickness
• Alzheimer’s biomarkers that include amyloid, tau and neurodegeneration markers along with other important associations (i.e., age at symptom onset, degree of white matter disease)