U-shaped effect of blood pressure on structural OCT metrics and retinal perfusion in ophthalmologically healthy subjects

PURPOSE: We wanted to investigate the association of blood pressure (BP) status with the ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) thickness of nonglaucomatous eyes and to elucidate whether this effect is related to vascular metrics proxying retinal perfusion. METHODS: For this case-control study, we prospectively included 96 eyes of 96 healthy subjects (age 50–65) from a large-scale population-based cohort in the northern Netherlands (n = 167,000) and allocated them to four groups (low BP, normal BP [controls], treated arterial hypertension [AHT], untreated AHT). We measured macular GCIPL and RNFL (mRNFL) and peripapillary RNFL (pRNFL) thicknesses with optical coherence tomography (OCT). We estimated retinal blood flow (RBF), retinal vascular resistance (RVR), and autoregulatory reserve (AR) from quantitative OCT-angiography, fundus imaging, BP, and intraocular pressure. We compared structural and vascular metrics across groups and performed mediation analysis. RESULTS: Compared to controls, GCIPL was thinner in the low BP group (P = 0.013), treated hypertensives (P = 0.007), and untreated hypertensives (P = 0.007). Treated hypertensives exhibited the thinnest mRNFL (P = 0.001), temporal pRNFL (P = 0.045), and inferior pRNFL (P = 0.034). The association of GCIPL thickness with BP was mediated by RBF within the combined low BP group and controls (P = 0.003), by RVR and AR within the combined treated hypertensives and controls (P = 0.001, P = 0.032), and by RVR within the combined untreated antihypertensives and controls (P = 0.022). CONCLUSIONS: Inner retinal thinning was associated with both tails of the BP distribution and with ineffective autoregulation. Longitudinal studies could clarify whether these defects can explain the reported glaucomatous predisposition of these population groups

Retinal Vessel Caliber Measurement Bias in Fundus Images in the Presence of the Central Light Reflex

Purpose: To investigate the agreement between a fundus camera and a scanning laser ophthalmoscope in retinal vessel caliber measurements and to identify whether the presence of the central light reflex (CLR) explains potential discrepancies. Methods: For this cross-sectional study, we obtained fundus camera and scanning laser ophthalmoscope images from 85 eyes of 85 healthy individuals (aged 50-65 years) with different blood pressure status. We measured the central retinal artery equivalent (CRAE) and central retinal artery vein equivalent (CRVE) with the Knudtson-Parr-Hubbard algorithm and assessed the CLR using a semiautomatic grading method. We used Bland-Altman plots, 95% limits of agreement, and the two-way mixed effects intraclass correlation coefficient for consistency [ICC(3, 1)] to describe interdevice agreement. We usedmultivariable regression to identify factors associated with differences in between-device measurements. Results: The between-device difference in CRAE (9. 5 μm; 95% confidence interval, 8. 0-11. 1 μm) was larger than the between-device difference in CRVE (2. 9 μm; 95% confidence interval, 1. 3-4. 5 μm), with the fundus camera yielding highermeasurements (both P &lt; 0. 001). The 95% fundus camera-scanning laser ophthalmoscope limits of agreement were -4. 8 to 23. 9 μm for CRAE and -12. 0 to 17. 8 μm for CRVE. The corresponding ICCs(3, 1) were 0. 89 (95% confidence interval, 0. 83-0. 92) and 0. 91 (95% confidence interval, 0. 86-0. 94). The between-device CRAE difference was positively associated with the presence of a CLR (P = 0. 002). Conclusions: Fundus cameras and scanning laser ophthalmoscopes yield correlated but not interchangeable caliber measurements. The CLR induces bias in arteriolar caliber in fundus camera images, compared with scanning laser ophthalmoscope images. Translational Relevance: Refined measurements could yield better estimates of the association between retinal vessel caliber and ophthalmic or systemic disease.</p

Retinal Vessel Caliber Measurement Bias in Fundus Images in the Presence of the Central Light Reflex

Purpose: To investigate the agreement between a fundus camera and a scanning laser ophthalmoscope in retinal vessel caliber measurements and to identify whether the presence of the central light reflex (CLR) explains potential discrepancies. Methods: For this cross-sectional study, we obtained fundus camera and scanning laser ophthalmoscope images from 85 eyes of 85 healthy individuals (aged 50-65 years) with different blood pressure status. We measured the central retinal artery equivalent (CRAE) and central retinal artery vein equivalent (CRVE) with the Knudtson-Parr-Hubbard algorithm and assessed the CLR using a semiautomatic grading method. We used Bland-Altman plots, 95% limits of agreement, and the two-way mixed effects intraclass correlation coefficient for consistency [ICC(3, 1)] to describe interdevice agreement. We usedmultivariable regression to identify factors associated with differences in between-device measurements. Results: The between-device difference in CRAE (9. 5 μm; 95% confidence interval, 8. 0-11. 1 μm) was larger than the between-device difference in CRVE (2. 9 μm; 95% confidence interval, 1. 3-4. 5 μm), with the fundus camera yielding highermeasurements (both P &lt; 0. 001). The 95% fundus camera-scanning laser ophthalmoscope limits of agreement were -4. 8 to 23. 9 μm for CRAE and -12. 0 to 17. 8 μm for CRVE. The corresponding ICCs(3, 1) were 0. 89 (95% confidence interval, 0. 83-0. 92) and 0. 91 (95% confidence interval, 0. 86-0. 94). The between-device CRAE difference was positively associated with the presence of a CLR (P = 0. 002). Conclusions: Fundus cameras and scanning laser ophthalmoscopes yield correlated but not interchangeable caliber measurements. The CLR induces bias in arteriolar caliber in fundus camera images, compared with scanning laser ophthalmoscope images. Translational Relevance: Refined measurements could yield better estimates of the association between retinal vessel caliber and ophthalmic or systemic disease.</p

Retinal Oxygen Delivery and Extraction in Ophthalmologically Healthy Subjects With Different Blood Pressure Status

PURPOSE: To compare retinal oxygen delivery (DO(2)) and oxygen extraction (VO(2)) in ophthalmologically healthy subjects with different blood pressure (BP) status. METHODS: In this case-control study, we prospectively included 93 eyes of 93 subjects (aged 50–65 years) from a Dutch cohort (n = 167,000) and allocated them to four groups (low BP, normal BP [controls], treated arterial hypertension [AHT], untreated AHT). We estimated vascular calibers from fundus images and fractal dimension from optical coherence tomography angiography scans. We combined calibers, fractal dimension, BP, and intraocular pressure measurements in a proxy of retinal blood flow (RBF), using a Poiseuille-based model. We measured arterial and venous oxygen saturations (S(a)O(2), S(v)O(2)) with a scanning laser ophthalmoscope. We calculated the DO(2) and VO(2) from the RBF, S(a)O(2), and S(v)O(2). We compared the DO(2) and VO(2) between groups and investigated the DO(2)–VO(2) association. RESULTS: DO(2) and VO(2) were different between groups (P = 0.009, P = 0.036, respectively). In a post hoc analysis, the low BP group had lower DO(2) than the untreated AHT group (P = 4.9 × 10(−4)). The low BP group and the treated AHT group had a lower VO(2) than the untreated AHT group (P = 0.021 and P = 0.034, respectively). There was a significant DO(2)–VO(2) correlation (R(obs) = 0.65, b(obs) = 0.51, P = 2.4 × 10(−12)). After correcting for shared measurement error, the slope was not significant. CONCLUSIONS: The DO(2) and VO(2) were altered in ophthalmologically healthy subjects with different BP status. Future studies could elucidate whether these changes can explain the increased risk of ophthalmic pathologies in those subjects. TRANSLATIONAL RELEVANCE: Understanding the baseline interplay between BP, retinal perfusion, and oxygenation allows for improved evaluation of retinal disease manifestation

Retinal Vessel Caliber Measurement Bias in Fundus Images in the Presence of the Central Light Reflex

Purpose: To investigate the agreement between a fundus camera and a scanning laser ophthalmoscope in retinal vessel caliber measurements and to identify whether the presence of the central light reflex (CLR) explains potential discrepancies. Methods: For this cross-sectional study, we obtained fundus camera and scanning laser ophthalmoscope images from 85 eyes of 85 healthy individuals (aged 50-65 years) with different blood pressure status. We measured the central retinal artery equivalent (CRAE) and central retinal artery vein equivalent (CRVE) with the Knudtson-Parr-Hubbard algorithm and assessed the CLR using a semiautomatic grading method. We used Bland-Altman plots, 95% limits of agreement, and the two-way mixed effects intraclass correlation coefficient for consistency [ICC(3, 1)] to describe interdevice agreement. We usedmultivariable regression to identify factors associated with differences in between-device measurements. Results: The between-device difference in CRAE (9. 5 μm; 95% confidence interval, 8. 0-11. 1 μm) was larger than the between-device difference in CRVE (2. 9 μm; 95% confidence interval, 1. 3-4. 5 μm), with the fundus camera yielding highermeasurements (both P &lt; 0. 001). The 95% fundus camera-scanning laser ophthalmoscope limits of agreement were -4. 8 to 23. 9 μm for CRAE and -12. 0 to 17. 8 μm for CRVE. The corresponding ICCs(3, 1) were 0. 89 (95% confidence interval, 0. 83-0. 92) and 0. 91 (95% confidence interval, 0. 86-0. 94). The between-device CRAE difference was positively associated with the presence of a CLR (P = 0. 002). Conclusions: Fundus cameras and scanning laser ophthalmoscopes yield correlated but not interchangeable caliber measurements. The CLR induces bias in arteriolar caliber in fundus camera images, compared with scanning laser ophthalmoscope images. Translational Relevance: Refined measurements could yield better estimates of the association between retinal vessel caliber and ophthalmic or systemic disease.</p

Retinal Vessel Caliber Measurement Bias in Fundus Images in the Presence of the Central Light Reflex

Purpose: To investigate the agreement between a fundus camera and a scanning laser ophthalmoscope in retinal vessel caliber measurements and to identify whether the presence of the central light reflex (CLR) explains potential discrepancies. Methods: For this cross-sectional study, we obtained fundus camera and scanning laser ophthalmoscope images from 85 eyes of 85 healthy individuals (aged 50-65 years) with different blood pressure status. We measured the central retinal artery equivalent (CRAE) and central retinal artery vein equivalent (CRVE) with the Knudtson-Parr-Hubbard algorithm and assessed the CLR using a semiautomatic grading method. We used Bland-Altman plots, 95% limits of agreement, and the two-way mixed effects intraclass correlation coefficient for consistency [ICC(3, 1)] to describe interdevice agreement. We usedmultivariable regression to identify factors associated with differences in between-device measurements. Results: The between-device difference in CRAE (9. 5 μm; 95% confidence interval, 8. 0-11. 1 μm) was larger than the between-device difference in CRVE (2. 9 μm; 95% confidence interval, 1. 3-4. 5 μm), with the fundus camera yielding highermeasurements (both P &lt; 0. 001). The 95% fundus camera-scanning laser ophthalmoscope limits of agreement were -4. 8 to 23. 9 μm for CRAE and -12. 0 to 17. 8 μm for CRVE. The corresponding ICCs(3, 1) were 0. 89 (95% confidence interval, 0. 83-0. 92) and 0. 91 (95% confidence interval, 0. 86-0. 94). The between-device CRAE difference was positively associated with the presence of a CLR (P = 0. 002). Conclusions: Fundus cameras and scanning laser ophthalmoscopes yield correlated but not interchangeable caliber measurements. The CLR induces bias in arteriolar caliber in fundus camera images, compared with scanning laser ophthalmoscope images. Translational Relevance: Refined measurements could yield better estimates of the association between retinal vessel caliber and ophthalmic or systemic disease.</p

Retinal layer thicknesses retrieved with different segmentation algorithms from optical coherence tomography scans acquired under different signal-to-noise ratio conditions

Glaucomatous damage can be quantified by measuring the thickness of different retinal layers. However, poor image quality may hamper the accuracy of the layer thickness measurement. We determined the effect of poor image quality (low signal-to-noise ratio) on the different layer thicknesses and compared different segmentation algorithms regarding their robustness against this degrading effect. For this purpose, we performed OCT measurements in the macular area of healthy subjects and degraded the image quality by employing neutral density filters. We also analysed OCT scans from glaucoma patients with different disease severity. The algorithms used were: The Canon HS-100's built-in algorithm, DOCTRAP, IOWA, and FWHM, an approach we developed. We showed that the four algorithms used were all susceptible to noise at a varying degree, depending on the retinal layer assessed, and the results between different algorithms were not interchangeable. The algorithms also differed in their ability to differentiate between young healthy eyes and older glaucoma eyes and failed to accurately separate different glaucoma stages from each other. (c) 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreemen

Retinal layers in Parkinson's disease::A meta-analysis of spectral-domain optical coherence tomography studies

Background: Patients with Parkinson's disease experience visual symptoms, partially originating from retinal changes. Since 2011, multiple case-control studies using spectral-domain OCT, which allows for studying individual retinal layers, have been published. The aim of this study was to substantiate the occurrence, extent, and location of retinal degeneration in Parkinson's by meta-analysis. Methods: Spectral-domain OCT case-control data were collected by performing a search in PubMed and Embase with terms: “optical coherence tomography” and “parkinson”, up to November 5th, 2018. Studies with fewer than 10 patients or controls were excluded. We performed a random effects meta-analysis. Heterogeneity was evaluated with I2 statistics; publication bias with Egger's and Begg's tests. Results: Out of 77 identified studies, 36 were included, totaling 1916 patients and 2006 controls. A significant thinning of the peripapillary retinal nerve fiber layer (d = −0.42; 95% confidence interval −0.54 to −0.29) and the combined ganglion cell and inner plexiform layers (d = −0.40; −0.72, to −0.07) was found. The inner nuclear layer and outer plexiform layer did not show significant changes. Heterogeneity ranged from 3 to 92%; no publication bias was found. Conclusions: Parkinson's patients show significant thinning of the inner retinal layers, resembling changes found in glaucoma and other neurodegenerative diseases like Alzheimer's. Study of different cell layers in-vivo is possible by moving from time-to spectral domain OCT. Retinal degeneration may be affiliated with neurodegenerative pathology overall, and could serve as a biomarker in neurodegenerative disorders. Longitudinal research including clinical correlations is needed to determine usefulness in Parkinson's disease

Investigating changes in axonal density and morphology of glaucomatous optic nerves using fixel-based analysis

PURPOSE: To characterize neurodegeneration of glaucomatous optic nerves (ONs) in terms of changes in axonal density and morphology using fixel-based analysis (FBA), a novel framework for analyzing diffusion-weighted MRI (DWI). Furthermore, we aimed to explore the potential of FBA measures as biomarkers of glaucomatous ON degeneration. METHODS: DWI scans were obtained from 15 glaucoma patients and 15 controls. ONs were tracked and segmented into their three anatomical segments; intraorbital (IO), intracanalicular (ICAN) and intracranial (ICRAN). For each segment, FBA measures were computed, which included fiber density (FD; a measure of axonal density), fiber-bundle cross-section (FC; an estimate of morphological changes), and fiber density and cross-section (FDC). Peripapillary retinal nerve fiber layer (pRNFL) thickness and visual field mean deviation (VFMD) were assessed for glaucoma patients. ANCOVA was used to compare FBA values between the two groups, and Spearman's correlation analysis was used to test the correlation between FBA measures and pRNFL thickness and VFMD. RESULTS: All glaucomatous ON segments showed a significant loss of FD and FDC compared to the controls, while a loss of FC was found in the IO and ICRAN segments only. FD and FDC values of the IO and ICAN segments of glaucomatous ONs showed significant correlations with pRNFL thickness and VFMD. CONCLUSIONS: Glaucomatous ONs exhibit lower FD and FC compared to controls, indicating axonal loss and gross atrophy. The correlation between FBA measures of glaucomatous ONs and established clinical tests of glaucoma demonstrates the potential of FBA measures as biomarkers of glaucomatous ON degeneration