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

De kristalstructuur van papaïne:een röntgendiffractie-onderzoek met een oplossend vermogen van 4,5 Å

The first stages are described of the determination of the crystal structure of papain (papain C, space group P21 2121 ). This plant proteolytic enzyme of MW 22,000 was extracted from dried papaya latex and crystallized from a mixture of 65% methanol and 35% ·water. The interpretation of the X-ray photographs of papain and three isomorphous heavy-atom derivates resulted in a three-dimensional Fourier map at 4.5 A0 resolution. In this map the protein molecules can easily be distinguished which must be partly due to the low electron density of the medium. The heavy-atom positions are found at the surface of the molecule. In spite of the almost complete knowledge of the ammo acid sequence [87] it was not possible to trace the polypeptide chain in the molecule. There are many intersections and only three of these can represent disulphide bridges.The others are probably due to the 30 aromatic slde chams wh1ch are not resolved at 4.5 A0 resolution. Two regions of high electron density are probably right handed hehces of about three turns each (arrows in fig. 7.1 (a) and 7.3 (d)). The helix content thus seems to be low which is in agreement with ORD measurements [125] and statistical predictions [113] , based on the amino acid sequence. There is an indication in the Fourier map for the position of one of the ends of the polypeptide chain. ... Zie: Summar

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