Table 2.
Outcomes of studies focusing on neurodegenerative pathology and cognition.
| Author, year | RVP(s) analyzed | Imaging device | FD ROI(s) | FD calculation | Results FD |
|---|---|---|---|---|---|
| Cabrera DeBuc et al. (2018) |
FD0, FD1, FD2 (multifractal) CRAE, CRVE cTORTa, cTORTv BCa, BCv AFa, AFv LDRa, LDRv AVR [Also: electroretinography, color vision quantification, visual performance test] |
45° digital SLO camera (EasyScan, iOptics, Netherlands) | Whole area of visible retina permitted by each image (from the OD boundary out toward the periphery) | SIVAImageJ (http://rsb.info.nih.gov/ij) together with the FracLac plug-in was used to calculate the multifractal properties of the retinal vasculature network | The vascular FD, assessed with a multifractal approach, was lower in individuals with CI (capacity, information and correlation dimensions: FD0, FD1, and FD2) vs. controls |
| Cheung et al. (2014a) |
FDt (monofractal) CRAE, CRVE cTORTa, cTORTv BAa, BAv |
45° digital retinal camera (Canon CR-DGi with a 10D SLR digital camera back; Canon, Japan) | 0.5–2.0 DD from disc margin | SIVA | Participants with lower retinal vascular FD values were more likely to have cognitive dysfunction |
| Cheung et al. (2014b) |
FDt, FDa, FDv (monofractal) CRAE, CRVE cTORTa, cTORTv BAa, BAv |
45° digital retinal camera (Canon CR-DGi 10D or Canon CR-1 40D; Canon, Japan) | 0.5–2.0 DD from disc margin | SIVA | Compared with the normal controls, the AD patients had smaller total and FDa. Persons with smaller FDt, FDa and FDv were more likely to have AD, controlling for potential confounders. These associations were still persistent after only AD cases without history of cerebrovascular disease were included |
| Csincsik et al. (2018) |
FDa, FDv (monofractal) WGa, WGv TORTa, TORTv (algorithm NS) … (not explicitly stated) [Also: peripheral drusen] |
Optomap P200C UWF-SLO (Optos Plc, Dunfermline, UK) | 0.5–1.0 DD from the disk margin 0.5–2.0 DD from the disk margin Whole area of visible retina permitted by each image (from the OD boundary out toward the periphery) |
Automated segmentation of the vasculature by algorithm developed by Pellegrini et al. (2014). Manual refinement removed artefacts (i.e., spurious vessel detections) and separated out the arteriolar and venular components of the vascular tree by labeling vessels and marking crossing points by hand. RVPs were measured using software specially designed to handle UWF imaging, VAMPIRE for UWF-SLO (v1, Universities of Edinburgh and Dundee, United Kingdom) | There was a significant decrease in FDa in AD at baseline with a trend at FU. The most consistent differences between AD patients and controls were observed when the entire image was considered |
| Frost et al. (2013) |
FDa, FDv (monofractal) CRAE, CRVE AVR BSTDa, BSTDv cTORTa, cTORTv Num1stBa, Num1stBv BCa, BCv AFa, AFv JEa, JEv LDRa, LDRv |
45° digital retinal camera (Canon CR-1 non-mydriatic camera, Canon USA, Lake Success, NY, USA) | 0.5–2.0 DD from the disk margin | SIVA | Reduced complexity of the branching pattern in AD (FD, Num1stB). No association between FD and (high) plaque burden in healthy individuals |
| Hilal et al. (2014) |
FDa, FDv (monofractal) CRAE, CRVE cTORTa, cTORTv |
45° digital retinal camera (Canon CR-DGi 10D or Canon CR-1 40D; Canon, Japan) | NS (most likely 0.5–2.0 DD from disc margin) | SIVA | Smaller FDa was associated with presence of multiple CMB. No association was found with lacunar infarcts and WML volume. After multivariate adjustments, association remained statistically significant |
| Jiang et al. (2018) |
FDrvn, FDsvp, FDdvp (monofractal) Representing microvascular density [Also: GC-IPL thickness] |
Zeiss Angioplex OCTA (Carl Zeiss Meditec, Dublin, CA), covering a retinal area of 3 x 3 mm2 centered on the fovea | The area between circles centered on the fovea and diameters of 0.6–2.5 mm was defined as the annular zone. The annular zone was then divided into 4 quadrantal sectors, named the superior temporal, inferior temporal, superior nasal, and inferior nasal. The annular zone was also divided into 6 thin annuli with a width of ~0.16 mm (C1-C6). Fractal analysis was performed in each sector or annular zone. | Automated segmentation of the vasculature by algorithm developed by Jiang et al. (2013). Fractal analysis was performed in each sector or annular zone using the box counting method with the fractal analysis toolbox (Benoit, Trusoft Benoit Fractal Analysis Toolbox; Trusoft International, Inc, St. Petersburg, USA). | Patients with AD had lower densities of RVN, SVP, and DVP in the annular zone, in comparison with controls. Patients with MCI had lower density of DVP in the superior nasal quadrant than that of the controls. There was a trend of vascular density loss from control to MCI then AD |
| Jung et al. (2019) |
FDt, FDa, FDv (monofractal) CRAE, CRVE BAa, BAv |
45° digital retinal camera (TRC-50DX; Topcon Medical Systems, Inc., USA) | 0.5–2.0 DD from disc margin | SIVA | Compared to NCI individuals, the SVCI patients had smaller FDt and FDa, whereas there was no significant difference of FD between ADCI and NCI |
| Naidu et al. (2016) |
FDt, FDa, FDv (monofractal) CRAE, CRVE AVR sTORTt, sTORTa, sTORTv, cTORTt, cTORTa, cTORTv |
45° digital retinal camera Topcon Fundus Camera (TRC 50-VT; Tokyo Optical, Tokyo, Japan) | 0.5–2.0 DD from disc margin | SIVA | No significant differences between cases and controls in FD |
| Ong et al. (2014) |
FDa, FDv (monofractal) CRAE, CRVE cTORTa, cTORTv |
Non-mydriatic digital camera (NS) | 0.5–2.0 DD from disc margin | SIVA | Reduced retinal FDa and FDv were associated with an increased risk of CIND-mild and CIND-moderate. Reduced FD was associated with poorer cognitive performance globally and in the specific domains of verbal memory, visuoconstruction and visuomotor speed |
| Shi et al. (2019) | In annular zone + per quadrant: FDsvp, FDdvp (monofractal) retinal capillary perfusion density Retinal capillary skeleton density |
CommercialSD-OCT system (Optovue RTVue XR Avanti; Optovue, Inc, Fremont, CA, OCT-A images derived from the built-in software [Angiovue, Version 2015.1.90)], covering a retinal area of 3 x 3 mm2 centered on the fovea | The area between circles centered on the fovea and diameters of 0.6–2.5 mm was defined as the annular zone. The annular zone was then divided into 4 quadrantal sectors, named the superior, inferior, nasal, and temporal. | FD was calculated based on skeletonized images of the retinal capillary network in the OCT-A images, using the following series of image processing procedures to create binary images of the vessels: bicubic interpolation, segmentation, detection of the FAZ boundary, and determination of the background signal-to-noise ratio. Fractal analysis software (Benoit, Trusoft Benoit Fractal Analysis Toolbox; Trusoft International, Inc, St. Petersburg, USA) was applied to the image analysis | The superficial retinal capillary plexus in PD patients had lower capillary complexity in the total annular zone and all quadrant sectors compared with healthy control subjects. The deep retinal capillary plexus complexity was decreased in the total annular zone and the superior and inferior quadrants. The retinal capillary complexity in the inferior quadrant was negatively correlated with the best-corrected visual acuity and disease duration |
| Taylor et al. (2015) |
FDt (monofractal) FD0, FD1, FD2 (multifractal) |
45° digital retinal camera (CRDGi; Canon USA Inc., Lake Success, NY) | Whole area of visible retina permitted by each image (from the OD boundary out toward the periphery) | Automated segmentation of the retinal microvascular network was performed using an algorithm described previously by Soares et al. (2006). Images were analyzed by an expert retinal image analyst using VAMPIRE custom software (School of Computing, University of Dundee, United Kingdom) built in Matlab (The MathWorks, Natwick, MA) | Only three out of 24 comparisons were found to be significant. No association survived Bonferroni correction for multiple statistical testing. Significant unadjusted associations were weakened and lost significance after covarying for IQ at age 11 and cardiovascular risk factors, and not one association was verified by an equivalent finding using measurements from the contralateral eye |
| Williams et al. (2015) |
FDt, FDa, FDv (monofractal) CRAE, CRVE cTORTa, cTORTv BAa, BAv |
45° digital retinal camera (500 Canon CR-DGi; Canon, Japan) | 0.5–2.0 DD from disc margin | SIVA | AD patients have a sparser retinal microvascular network with significantly lower FDt, FDa and FDv. Subjects with lower FDv were more likely to have AD. A secondary analysis failed to detect any significant associations between retinal microvascular parameters and MMSE score |
AD, Alzheimer's disease; ADCI, Alzheimer's disease cognitive impairment; AFa/v, arteriolar/venular asymmetry factor; AVR, artery-vein ratio; BAa/v, arteriolar/venular branching angle; BCa/v, arteriolar/venular branching coefficient; BSTDa/v, zone B standard deviation of arteriolar/venular width; CRAE, central retinal arteriolar equivalent; CRVE, central retinal venular equivalent; CI, cognitive impairment; CIND, cognitive impairment no dementia; CMB, cerebral microbleeds; cTORTa/v, curvature arteriolar/venular tortuosity; DD, disc diameter; DVP, deep vascular plexus; FAZ, foveal avascular zone; FD, fractal dimension; FDt/a/v, total/arteriolar/venular fractal dimension; FD0, capacity dimension; FD1, information dimension; FD2, correlation dimension; IQ, intelligence quotient; JEa/v, junctional exponent deviation for arterioles/venules; LDRa/v, arteriolar/venular length-diameter ratio; MCI, mild cognitive impairment; MMSE, Mini-Mental State Examination; NCI, noncognitive impairment; NS, not specified; Num1stBa/v, number of first branching arterioles/venules; OCT-A, optical coherence tomography angiography; OD, optic disc; PD, Parkinson's disease; RVN, retinal vascular network; ROI, region of interest; SD-OCT, spectral domain optical coherence tomography; SIVA, Singapore I Vessel Assessment; SLO, scanning laser ophthalmoscopy; sTORTa/v, simple arteriolar/venular tortuosity; SVCI, subcortical vascular cognitive impairment; SVP, superficial vascular plexus; UWF, ultra-widefield; VAMPIRE, Vessel Assessment and Measurement Platform for Images of the REtina; WGa/v, arteriolar/venular width gradient; WML, white matter lesions.