Optical Coherence Tomography in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis

Abstract

The use of optical coherence tomography (OCT) of the retina to detect inner retinal degeneration is being investigated as a potential biomarker for mild cognitive impairment (MCI) and Alzheimer's disease (AD), and an overwhelming body of evidence indicates that discovery of disease-modifying treatments for AD should be aimed at the pre-dementia clinical stage of AD, i.e., MCI. We aimed to perform a systematic review and meta-analysis on retinal OCT in MCI. Methods: We performed a systematic review of the English literature in three databases (PubMed, Embase, and Latindex) for studies that measured retinal thickness using OCT in people with MCI and healthy controls, age 50 or older, between 1 January 2000 and 31 July 2019. Only cohort and case-control studies were reviewed, and independent extraction of quality data and established objective data was performed. We calculated the effect size for studies in the review that met the following criteria: (1) a statistically significant difference between MCI subjects and normal controls for several OCT variables, (2) use of spectral domain OCT, and (3) use of APOSTEL recommendations for OCT reporting. Weighted Hedges' g statistic was used to calculate the pooled effect size for four variables: ganglion cell layer-inner plexiform layer (GCL-IPL) complex thickness in micrometers (µm), circumpapillary retinal nerve fiber layer (pRNFL) thickness in µm, macular thickness in µm, and macular volume in µm 3. For variables with high heterogeneity, a multivariate meta-regression was performed. We followed the PRISMA guidelines for systematic reviews. Results: Fifteen articles met the inclusion criteria. A total of 58.9% of MCI patients had statistically significant thinning of the pRNFL compared with normal subjects, while 61.6% of all MCI patients who had macular volume measured had a statistically significant reduction in volume compared with controls, and 50.0% of the macular GCL-IPL complexes measured demonstrated significant thinning in MCI compared with normal controls. Meta-analysis demonstrated a large effect size for decreased macular thickness in MCI subjects compared with normal controls, but there was a substantial heterogeneity for macular thickness results. Mejia-Vergara et al. OCT in Mild Cognitive Impairment The other variables did not demonstrate a significant difference and also had substantial heterogeneity. Meta-regression analysis did not reveal an explanation for the heterogeneity. Conclusions: A better understanding of the cause of retina degeneration and longitudinal, standardized studies are needed to determine if optical coherence tomography can be used as a biomarker for mild cognitive impairment due to Alzheimer's disease.

Association between retinal markers and cognition in older adults: a systematic review

“…The study concluded that more standardised and longitudinal studies were needed to support the role of OCT in identifying reduced retinal layer and/ or macular thickness as a biomarker for MCI due to AD. 16 The study by Ge et al 17 was broader in scope as the authors included retinal markers per se and not just the RNFL thickness assessed using OCT. The study aimed to identify signature retinal markers in AD, MCI and preclinical AD population.…”

“…AD group also showed reduced peripapillary RNFL (pRNFL) thickness and choroidal thickness. 15 In another systematic review and meta-analysis study by Mejia-Vergara et al , 16 15 studies that included MCI individuals only were included to report that pRNFL and macular GCL-IPL thinning with reduced macular volume was prominent in MCI when compared with the controls. A large effect size was observed for reduced macular thickness in MCI individuals with significant heterogeneity for macular thickness.…”

“…The study concluded that more standardised and longitudinal studies were needed to support the role of OCT in identifying reduced retinal layer and/or macular thickness as a biomarker for MCI due to AD. 16 …”

Changes in retinal multilayer thickness and vascular network of patients with Alzheimer’s disease

“…One of the neurodegenerative biomarkers is the retinal structure, which can be evaluated noninvasively using optical coherence tomography (OCT) [6][7][8]. Retinal changes in AD patients are important for diagnosing and monitoring neurogenerative diseases [9].…”

Changes in Retinal Multilayer Thickness and Vascular Network of Patients With Alzheimer’s Disease

“…One of the neurodegenerative biomarkers was retinal structures, which could be evaluated by noninvasive examination of optical coherence tomography (OCT) [4][5][6]. Retinal changes in AD patient can be an important diagnosis and monitoring pathway to visualize the course of disease [7].…”