Systematic review and network meta-analysis of retinal imaging biomarkers in neurodegenerative diseases: Correlation...

The retina and brain share a common embryonic origin and neural composition. Both undergo structural, vascular, and physiological changes in neurodegenerative diseases (NDs). This Systematic and network meta-analysis (NMA) aims to identify retinal-brain biomarkers across the spectrum of NDs.

We conducted an NMA using random-effects models to assess retinal layer thickness changes in Alzheimer's disease (AD) and mild cognitive impairment (MCI). Data from 225 AD patients, 97 MCI patients, and 345 cognitively normal (CN) individuals, published between 2016 and 2023, were analyzed. Brain imaging findings were also evaluated for comparison.

Compared to controls, the MCI group exhibited significant thinning in the inferior and superior peripapillary retinal nerve fiber layer (pRNFL) and inner macular thickness. Specifically, reductions were observed in Right Eye Inferior pRNFL (SMD = -21.5306), Right Eye Superior pRNFL (SMD = -11.5011), Left Eye Inferior pRNFL (SMD = -27.6244), Left Eye Superior pRNFL (SMD = -9.8137), and Inner Macular Thickness (SMD = -4.8791). When comparing AD to MCI, Right Eye Nasal pRNFL (SMD = 5.95), Left Eye Superior pRNFL (SMD = -9.1786), and Outer Macular Thickness (SMD = -4.1046) were significantly thinner in AD. No significant differences were found between AD and CN in most retinal regions.

Thinning of the superior and inferior pRNFL and inner macular layer may serve as early biomarkers of MCI. In AD, retinal layer thinning is accompanied by hippocampal, entorhinal cortex, and temporal lobe atrophy, with macular volume (EZ-RPE) correlating with total brain volume.