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 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

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 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

Microcirculatory model predicts blood flow and autoregulation range in the human retina:in vivo investigation with laser speckle flowgraphy

In this study, we mathematically predict retinal vascular resistance (RVR) and retinal blood flow (RBF), we test predictions using laser speckle flowgraphy (LSFG), we estimate the range of vascular autoregulation, and we examine the relationship of RBF with the retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC). Fundus, optical coherence tomography (OCT), and OCT-angiography images, systolic/diastolic blood pressure (SBP/DBP), and intraocular pressure (IOP) measurements were obtained float 36 human subjects. We modeled two circulation markers (RVR and RBF) and estimated individualized lower/higher autoregula tion limits (LARL/HARL), using retinal vessel calibers, fractal dimen- sion, perfusion pressure, and population-based hematocrit values. Quantitative LSFG waveforms were extracted from vessels of the same eyes, before and during IOP elevation. LSFG metrics explained most variance in RVR (R-2 =0.77/P = 6.9.10(-9)) and RBF (R-2 =0.65/P = 1.0.10(-6)), suggesting that the markers strongly reflect blood flow physiology. Higher RBF was associated with thicker RNFL (P = 4.0.10(-4)) and GCC (P = 0.003), thus also verifying agreement with structural measurements. LARL was at SBP/DBP of 105/65 mmHg for the average subject without arterial hypertension and at 115/75 mmHg for the average hypertensive subject. Moreover, during IOP elevation, changes in RBF were more pronounced than changes in RVR. These observations physiologically imply that healthy subjects are already close to LARL, thus prone to hypoperfusion. In conclusion, we modeled two clinical markers and described a novel method to predict individualized autoregulation limits. These findings could improve understanding of retinal perfusion and pave the way for personalized intervention decisions, when treating patients with coexisting ophthalmic and cardiovascular pathologies. NEW & NOTEWORTHY We describe and test a new approach to quantify retinal blood flow, based on standard clinical examinations and imaging techniques, linked together with a physiological model. We use these findings to generate individualized estimates of the autoregulation range. We provide evidence that healthy subjects are closer to the lower autoregulation limit than thought before. This suggests that some retinas are less prepared to withstand hypoperfusion, even after small intraocular pressure rises or blood pressure drops