Optical Coherence Tomography in Alzheimer’s Disease: A Meta-Analysis

Abstract

BackgroundAlzheimer’s disease (AD) is a neurodegenerative disorder, which is likely to start as mild cognitive impairment (MCI) several years before the its full-blown clinical manifestation. Optical coherence tomography (OCT) has been used to detect a loss in peripapillary retina nerve fiber layer (RNFL) and a reduction in macular thickness and volume of people affected by MCI or AD. Here, we performed an aggregate meta-analysis combining results from different studies.Methods and FindingsData sources were case-control studies published between January 2001 and August 2014 (identified through PubMed and Google Scholar databases) that examined the RNFL thickness by means of OCT in AD and MCI patients compared with cognitively healthy controls.Results11 studies were identified, including 380 patients with AD, 68 with MCI and 293 healthy controls (HC). The studies suggest that the mean RNFL thickness is reduced in MCI (weighted mean differences in μm, WMD = -13.39, 95% CI: -17.34 to -9.45, p = 0.031) and, even more so, in AD (WMD = -15.95, 95% CI: -21.65 to -10.21, p<0.0001) patients compared to HC. RNFL in the 4 quadrants were all significantly thinner in AD superior (superior WMD = -24.0, 95% CI: -34.9 to -13.1, p<0.0001; inferior WMD = -20.8, 95% CI: -32.0 to -9.7, p<0.0001; nasal WMD = -14.7, 95% CI: -23.9 to -5.5, p<0.0001; and temporal WMD = -10.7, 95% CI: -19.9 to -1.4, p<0.0001); the same significant reduction in quadrant RNFL was observed in MCI patients compared with HC (Inferior WMD = -20.22, 95% CI: -30.41 to -10.03, p = 0.0001; nasal WMD = -7.4, 95% CI: -10.08 to -4.7, p = 0.0000; and temporal WMD = -6.88, 95% CI: -12.62 to -1.13, p = 0.01), with the exception of superior quadrant (WMD = -19.45, 95% CI: -40.23 to 1.32, p = 0.06).ConclusionResults from the meta-analysis support the important role of OCT for RNFL analysis in monitoring the progression of AD and in assessing the effectiveness of purported AD treatments.

Alzheimer’s disease: A review of its visual system neuropathology. Optical coherence tomography—a potential role as a study tool in vivo

“…However, more recent SD-OCT studies have reported different findings, with most SD-OCT studies suggesting selective superior RNFL thinning [39,54,70]. Two more recent meta-analyses, which used both TD-OCT and SD-OCT studies, aimed to determine the diagnostic utility of OCT measurements of RNFL thickness in AD [74,75]. While confirming significant peripapillary RNFL thinning in AD, these meta-analyses reached different conclusions regarding which quadrants are most affected.…”

“…The metaanalyses by K.L. Thomson et al and G. Coppola et al [74,75] also tried to determine the utility of OCT as a tool for evaluating disease progression, and prognostic significance of GC-IPL and RNFL thickness in MCI and AD. Both meta-analyses concluded that OCT can be used to detect early abnormalities in MCI, but their conclusions regarding which retinal quadrants are affected in MCI were conflicting-one concluded that MCI patients have selective superior quadrant RNFL thinning [74], while the other concluded that all quadrants but the superior one were affected [75].…”

Retinal amyloid pathology and proof-of-concept imaging trial in Alzheimer’s disease

“…In addition to afflicting the brain, AD also affects the retina, a developmental outgrowth of the brain (12)(13)(14), possibly causing these symptoms. The retinas of AD patients display pathologies such as nerve fiber layer (NFL) thinning, retinal ganglion cell (RGC) degeneration, reduction of blood flow and vascular alterations, astrogliosis, and abnormal electroretinogram patterns (11,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). Among the many characteristics it shares with the brain, the retina contains neurons, astroglia, microglia, microvasculature with similar morphological and physiological properties, and a blood barrier (12-14, 34, 35).…”

Temporal Resolution of Misfolded Prion Protein Transport, Accumulation, Glial Activation, and Neuronal Death in the Retinas of Mice Inoculated with Scrapie

“…The retina is part of the CNS and is affected by numerous protein misfolding diseases, including Alzheimer disease, 9 Parkinson disease, 10e12 and numerous TSEs, including scrapie in sheep, 13,14 chronic wasting disease in…”

“…The retina is part of the CNS and is affected by numerous protein misfolding diseases, including Alzheimer disease, 9 Parkinson disease, 10e12 and numerous TSEs, including scrapie in sheep, 13,14 chronic wasting disease in cervids, 15e17 bovine spongiform encephalopathy in cattle, 18,19 and Creutzfeldt-Jakob disease in humans. 20,21 The retina and associated visual structures provide an excellent model to study the transport of misfolded proteins from one CNS structure to another.…”