Patients with early age-related macular degeneration exhibit signs of macro- and micro-vascular disease and abnormal blood glutathione levels.

BACKGROUND: This pilot study aimed to investigate systemic and retinal vascular function and their relationship to circulatory markers of cardiovascular risk in early age-related macular degeneration (AMD) patients without any already diagnosed systemic vascular pathologies. METHODS: Fourteen patients diagnosed with early AMD and 14 age- and gender-matched healthy controls underwent blood pressure, carotid intima-media thickness (C-IMT) and peripheral arterial stiffness measurements. Retinal vascular reactivity was assessed by means of dynamic retinal vessel analysis (DVA) using a modified protocol. Blood analyses were conducted for glutathione levels and plasma levels of total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). RESULTS: The AMD patients showed significantly greater C-IMT (p = 0.029) and augmentation index (AIx) (p = 0.042) than the age-matched controls. In addition, they demonstrated a shallower retinal arterial dilation slope (Slope AD) (p = 0.005) and a longer retinal venous reaction time (RT) to flickering light (p = 0.026). Blood analyses also revealed that AMD patients exhibited higher oxidized glutathione (GSSG) (p = 0.024), lower redox index (p = 0.043) and higher LDL-C (p = 0.033) levels than the controls. Venous RT parameter correlated positively with blood GSSG levels (r = 0.58, p = 0.038) in AMD subjects, but not in the controls (p > 0.05). CONCLUSIONS: Patients diagnosed with early AMD exhibit signs of systemic and retinal vascular alterations that correlated with known risk markers for future cardiovascular morbidity.

The effect of simulated cataract light scatter on retinal vessel oximetry.

To assess the impact of light scatter, similar to that introduced by cataract on retinal vessel blood oxygen saturation measurements using poly-bead solutions of varying concentrations. Eight healthy, young, non-smoking individuals were enrolled for this study. All subjects underwent digital blood pressure measurements, assessment of non-contact intraocular pressure, pupil dilation and retinal vessel oximetry using dual wavelength photography (Oximetry Module, Imedos Systems, Germany). To simulate light scatter, cells comprising a plastic collar and two plano lenses were filled with solutions of differing concentrations (0.001, 0.002 and 0.004%) of polystyrene microspheres (Polysciences Inc., USA). The adopted light scatter model showed an artifactual increase in venous optical density ratio (p = 0.036), with the 0.004% condition producing significantly higher venous optical density ratio values when compared to images without a cell in place. Spectrophotometric analysis, and thus retinal vessel oximetry of the retinal vessels, is altered by artificial light scatter.

White Paper on European Patient Needs and Suggestions on Chronic Type 2 Inflammation of Airways and Skin by EUFOREA.

Background: Type 2 inflammation underlies the chronicity of disease in subgroups of patients with asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and atopic dermatitis (AD), that often co-exist. Although several studies have investigated the unmet needs of asthma, AD and CRSwNP as such, little is known about the similarities and differences in experiences and perspectives of the current management of patients with comorbid Type 2 inflammatory diseases. Aims: To improve insight into the common and organ-specific needs of patients with Type 2 inflammation and comorbidities, allowing the formulation of recommendations to better address these needs in the future. Methodology: This qualitative study was conducted between July 2021 and December 2021 using semi-structured face-to-face or telephone interviews with patients suffering from year-long severe chronic Type 2 inflammation and at least one co-morbid inflammatory condition. Seven participating academic centers in Europe interviewed asthma (Copenhagen and Leuven), CRSwNP (London, Amsterdam and Crete) and/or AD (Oldenburg and Zurich) patients on patient characteristics, disease severity, shortcomings of current care pathways and suggestions for improvement of care. Transcripts were analyzed using an inductive thematic analysis approach. Results: Eighty-one patients with severe Type 2 inflammation and comorbidities were interviewed. Similar needs were recognized by patients with Type 2 inflammation, with both a lack of coordination in care and a lack of a real cure reported as being most frustrating. However, several needs are specific to asthma, CRSwNP and AD. Suggestions for improvement of care were generic across diseases, such as the implementation of a multidisciplinary approach, the improved facilitation of access to better treatments, the increase of general awareness on disease burden, and better educational programs for healthcare providers and patients. Of note, patients with CRSwNP also stated the need for alternatives to sinus surgery, whereas patients with asthma requested better medical care to prevent exacerbations and patients with AD would warmly welcome the reimbursement of emollients. Conclusion: Patients with asthma, CRSwNP and AD have shared unmet needs that need to be addressed by physicians, the academic community and health policy makers. This survey provides unique recommendations made by patients for the implementation of better care.

Corrigendum on: White paper on European patient needs and suggestions on chronic type 2 inflammation of airways and skin by EUFOREA.

[This corrects the article DOI: 10.3389/falgy.2022.889221.].

Objective Scatter Index: Working Toward a New Quantification of Cataract?

PURPOSE: To investigate the associations between clinical cataract classifications, quality of life (QOL), and the objective loss of ocular transparency in patients presenting with clinical cataracts. METHODS: In this prospective, multicenter, cross-sectional study, 1,768 eyes of 1,768 patients (mean age: 72.5 years; range: 28 to 93 years) referred for cataract assessment were enrolled. Visual acuity was measured before slit-lamp examination to determine the severity of lens opacification using the Lens Opacities Classification System III. Patients were asked to complete the Visual Function Index (VF-14) questionnaire. Ocular transparency was quantified by Objective Scatter Index (OSI) and was measured by the HD Analyzer (Visiometrics SL, Terrassa, Spain). Association and categorical data analysis were performed between each measured parameter alongside cross-tabulation analyses to determine sensitivity and efficiency of the HD Analyzer. RESULTS: High OSI levels corresponded slightly with a lower visual acuity value and corresponded better with lower VF-14 scores. OSI scores were strongly associated with cataract classification and severity. Cross-tabulation analysis revealed a high sensitivity and efficiency index for the OSI with these clinically validated parameters illustrating good agreement overall for the OSI in determining cataract. CONCLUSIONS: The OSI measured by the HD Analyzer is a sensitive and efficient tool to be considered in the early detection of cataract in patients.

Correlational Analysis of Objective and Subjective Measures of Cataract Quantification.

PURPOSE: To evaluate whether correlations exist between objective and subjective measures of vision quality as a consequence of cataract and whether this may qualify the Objective Scatter Index as a supplementary means of cataract assessment. METHODS: A prospective multicenter, cross-sectional study was conducted in 10 centers across France in patients undergoing cataract extraction surgery (lens opacity evaluated with the Lens Opacities Classification System III). A quality of life assessment using the Visual Function Index-14 (VF-14) (14 questions scored from 0 to 4) and measurement of visual acuity and evaluation of the Objective Scatter Index (HD Analyzer, Visiometrics SL, Terrassa, Spain) to assess the alteration of light scatter were used as measures in the study. RESULTS: The study included 1,768 eyes of 1,768 patients (mean age: 72.5 years; range: 28 to 93 years). The average OSI score was 4.97 ± 3.13 (range: 0.4 to 20.5). There was good correlation between visual acuity and OSI (r = -0.47, P < .001) and between OSI and VF-14 (r = -0.11, P < .001). CONCLUSIONS: The results presented in this study confirm that the Objective Scatter Index has sufficient correlations with visual acuity and VF-14 to supplement existing cataract diagnosis in a large population encompassing a broad spectrum of cataract presentations.

Overweight status is associated with extensive signs of microvascular dysfunction and cardiovascular risk.

The aim of this present study was to investigate if overweight individuals exhibit signs of vascular dysfunction associated with a high risk for cardiovascular disease (CVD). One hundred lean and 100 overweight participants were recruited for the present study. Retinal microvascular function was assessed using the Dynamic Retinal Vessel Analyser (DVA), and systemic macrovascular function by means of flow-mediated dilation (FMD). Investigations also included body composition, carotid intimal-media thickness (c-IMT), ambulatory blood pressure monitoring (BP), fasting plasma glucose, triglycerides (TG), cholesterol levels (HDL-C and LDL-C), and plasma von Willebrand factor (vWF). Overweight individuals presented with higher right and left c-IMT (p = 0.005 and p = 0.002, respectively), average 24-h BP values (all p < 0.001), plasma glucose (p = 0.008), TG (p = 0.003), TG: HDL-C ratio (p = 0.010), and vWF levels (p = 0.004). Moreover, overweight individuals showed lower retinal arterial microvascular dilation (p = 0.039) and baseline-corrected flicker (bFR) responses (p = 0.022), as well as, prolonged dilation reaction time (RT, p = 0.047). These observations emphasise the importance of vascular screening and consideration of preventive interventions to decrease vascular risk in all individuals with adiposity above normal range.

Comparison Between Mix-and-Match Implantation of Bifocal Intraocular Lenses and Bilateral Implantation of Trifocal Intraocular Lenses.

PURPOSE: To investigate the visual outcomes between mix-and-match bifocal intraocular lenses (IOLs) (ReSTOR +2.50 and +3.00 diopters [D]; Alcon Laboratories, Inc., Fort Worth, TX) versus bilateral implantation of a trifocal IOL (FineVision; PhysIOL, Liège, Belgium). METHODS: Twenty-three patients (average age: 56.3 ± 6.9 years; range: 45 to 71 years) referred for lens phacoemulsification and IOL implantation were included in this study. Patients were randomly assigned to two groups. The FineVision group was bilaterally implanted with the FineVision trifocal IOL and the ReSTOR group was implanted with mix-and-match bifocal ReSTOR +2.50 and +3.00 D IOLs. A 3-month postoperative check was performed, and manifest refraction and logMAR uncorrected (UDVA) and corrected (CDVA) distance and near visual acuities were recorded. Monocular and binocular defocus curve testing was performed under photopic (85 cd/m2) conditions in 0.50-D defocus steps. Contrast sensitivity was measured monocularly and binocularly under mesopic conditions at spatial frequencies of 3, 6, 12, and 18 cycles per degree using the CSV-1000 contrast test (VectorVision, Greenville, OH). RESULTS: There were no reported differences in monocular distance visual acuity or refractive outcomes between groups (P > .05). Furthermore, there were no significant differences in contrast sensitivity between the three IOLs (P > .05). The FineVision group achieved better monocular and binocular near and intermediate visual acuities under defocus curve testing than the ReSTOR group (P < .05). CONCLUSIONS: Binocular implantation of the FineVision trifocal IOL provided a better range of visual acuities at near and intermediate distances than mix-and-match bifocal IOL implantation. [J Refract Surg. 2016;32(10):659-663.].

Comparison of subjective and objective methods to determine the retinal arterio-venous ratio using fundus photography.

PURPOSE: To assess the inter and intra observer variability of subjective grading of the retinal arterio-venous ratio (AVR) using a visual grading and to compare the subjectively derived grades to an objective method using a semi-automated computer program. METHODS: Following intraocular pressure and blood pressure measurements all subjects underwent dilated fundus photography. 86 monochromatic retinal images with the optic nerve head centred (52 healthy volunteers) were obtained using a Zeiss FF450+ fundus camera. Arterio-venous ratios (AVR), central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE) were calculated on three separate occasions by one single observer semi-automatically using the software VesselMap (ImedosSystems, Jena, Germany). Following the automated grading, three examiners graded the AVR visually on three separate occasions in order to assess their agreement. RESULTS: Reproducibility of the semi-automatic parameters was excellent (ICCs: 0.97 (CRAE); 0.985 (CRVE) and 0.952 (AVR)). However, visual grading of AVR showed inter grader differences as well as discrepancies between subjectively derived and objectively calculated AVR (all p<0.000001). CONCLUSION: Grader education and experience leads to inter-grader differences but more importantly, subjective grading is not capable to pick up subtle differences across healthy individuals and does not represent true AVR when compared with an objective assessment method. Technology advancements mean we no longer rely on opthalmoscopic evaluation but can capture and store fundus images with retinal cameras, enabling us to measure vessel calibre more accurately compared to visual estimation; hence it should be integrated in optometric practise for improved accuracy and reliability of clinical assessments of retinal vessel calibres.

Assessment of total retinal blood flow using Doppler Fourier Domain Optical Coherence Tomography during systemic hypercapnia and hypocapnia.

The purpose of this study was to investigate changes in total retinal blood flow (RBF) using Doppler Fourier Domain Optical Coherence Tomography (Doppler FD-OCT) in response to the manipulation of systemic partial pressure of CO2 (PETCO2). Double circular Doppler blood flow scans were captured in nine healthy individuals (mean age ± standard deviation: 27.1 ± 4.1, six males) using the RTVue(™) FD-OCT (Optovue). PETCO2 was manipulated using a custom-designed computer-controlled gas blender (RespirAct(™)) connected to a sequential gas delivery rebreathing circuit. Doppler FD-OCT measurements were captured at baseline, during stages of hypercapnia (+5/+10/+15 mmHg PETCO2), return to baseline and during stages of hypocapnia (-5/-10/-15 mmHg PETCO2). Repeated measures analysis of variance (reANOVA) and Tukey's post hoc analysis were used to compare Doppler FD-OCT measurements between the various PETCO2 levels relative to baseline. The effect of PETCO2 on TRBF was also investigated using linear regression models. The average RBF significantly increased by 15% (P < 0.0001) with an increase in PETCO2 and decreased significantly by 10% with a decrease in PETCO2 (P = 0.001). Venous velocity significantly increased by 3.11% from baseline to extreme hypercapnia (P < 0.001) and reduced significantly by 2.01% at extreme hypocapnia (P = 0.012). No significant changes were found in the average venous area measurements under hypercapnia (P = 0.36) or hypocapnia (P = 0.40). Overall, increased and decreased PETCO2 values had a significant effect on RBF outcomes (P < 0.002). In healthy individuals, altered end-tidal CO2 levels significantly changed RBF as measured by Doppler FD-OCT.

Retinal blood flow and vascular reactivity in chronic smokers.

PURPOSE: The aim of this study was to investigate the impact of cigarette smoking in otherwise healthy young individuals on retinal blood flow (RBF) and vascular reactivity (RVR). METHODS: An automated gas flow controller (RespirAct) was used to achieve normoxic hypercapnia in 10 nonsmokers (mean age 28.9; SD 4.6 years) and nine smokers (mean age 27.55; SD 4.7 years). Retinal blood flow measurements were obtained using a prototype Doppler spectral-domain optical coherence tomographer (SD-OCT) and bidirectional laser Doppler velocimetry and simultaneous vessel densitometry during baseline, normoxic hypercapnia, and recovery. Group mean PETCO2 (end-tidal partial pressure of CO2) was increased by 15.9% in the nonsmoking group and by 15.7% in the smoking group, with a concomitant increase in PETO2 (end-tidal partial pressure of O2) by approximately 1.5% to 2% in both groups. RESULTS: In nonsmokers, retinal arteriolar diameter (P < 0.0001), centerline velocity (P = 0.0004), and blood flow (P < 0.0001) significantly increased during normoxic hypercapnia. Similarly, the venous area (P = 0.0418), venous velocity (P = 0.0068), and total venous RBF (P < 0.0001), as measured by the prototype Doppler SD-OCT, significantly increased. In smokers, normoxic hypercapnia resulted in a significant increase in velocity (P = 0.0019), flow (P = 0.0029), and total venous RBF (P = 0.002). Comparing smokers and nonsmokers, the percentage change in arteriolar diameter (P = 0.0379) and blood flow (P = 0.0101) was significantly lower in the smoking group. There was no significant difference in baseline PETCO2 level between smokers and nonsmokers. CONCLUSIONS: Retinal vascular reactivity in response to normoxic hypercapnia is significantly reduced in young, healthy smokers compared with nonsmokers.

Primary open-angle glaucoma vs normal-tension glaucoma: the vascular perspective.

OBJECTIVE: To compare and contrast the presence of ocular and systemic vascular function in patients with newly diagnosed and previously untreated primary open-angle glaucoma (POAG) vs those with normal-tension glaucoma (NTG) and comparable early-stage, functional loss. METHODS: The systemic vascular function of 19 patients with POAG, 19 patients with NTG, and 20 healthy individuals serving as controls was assessed using 24-hour ambulatory blood pressure monitoring, peripheral pulse-wave analysis, and carotid intima-media thickness. Retinal vascular reactivity to flicker light was assessed using dynamic retinal vessel analysis (Imedos, GmbH). RESULTS: Compared with controls, patients with POAG and those with NTG exhibited similarly increased nocturnal systemic blood pressure variability (P = .01), peripheral arterial stiffness (P = .02), carotid intima-media thickness (P = .04), and reduced ocular perfusion pressure (P < .001). Furthermore, on dynamic retinal vessel analysis, both glaucoma groups exhibited steeper retinal arterial constriction slopes after cessation of flicker (P = .007) and a similarly increased fluctuation in arterial and venous baseline diameter (P = .008 and P = .009, respectively) compared with controls. CONCLUSIONS: Patients with POAG or NTG exhibit similar alterations in ocular and systemic circulation in the early stages of their disease process. This finding highlights the importance of considering vascular risk factors in both conditions and raises questions about the current separation of the two conditions into distinct clinical entities.

A prototype hyperspectral system with a tunable laser source for retinal vessel imaging.

PURPOSE: To describe the technology and determine the within-session repeatability of manual retinal reflectance measurements of arterioles and venules using a prototype hyperspectral retinal camera. METHODS: Six healthy young volunteers (three males, average age 26 ± 4 years) had five repeated sets of retinal images captured between 500 and 600 nm at 5-nm intervals using a newly developed hyperspectral retinal camera. Optical densities were manually extracted for first-degree arterioles and venules and the repeatability of retinal reflectance was compared sequentially. The SDs of the differences between sequential mean values were used as an indication of the variance, while the coefficient of repeatability (COR) and intraclass correlation coefficient (ICC) were used to assess repeatability. RESULTS: The mean difference between each sequential measure was calculated using 21 images from each of the five spectral cubes. The SDs of these values ranged from 0.01 to 0.06 OD units and from 0.01 to 0.07 OD units for first-degree arterioles and venules, respectively. The COR ranged from 0.02 to 0.11 OD units (relative to a mean OD of 0.15 [0.06-0.23] OD units) for arterioles and 0.03 to 0.14 OD units (relative to a mean OD of 0.25 [0.17-0.31] OD units) for venules. Good reliability (P < 0.001) was found for arterioles (ICC: 78.8%-94.4% with a Cronbach's α of 89.6%-97.6%) and for venules (ICC: 63.7%-92.1% with a Cronbach's α of 86.2%-98.1%). CONCLUSIONS: Manual optical density determination with this novel hyperspectral camera showed very good intrasession (and intraobserver) repeatability with a small degree of variance that should form the basis of reliable retinal oxygen saturation values in future imaging research studies. Future automation of retinal vessel reflectance image analyses will likely further improve this repeatability.

Cerebral oxygen saturation: graded response to carbon dioxide with isoxia and graded response to oxygen with isocapnia.

BACKGROUND: Monitoring cerebral saturation is increasingly seen as an aid to management of patients in the operating room and in neurocritical care. How best to manipulate cerebral saturation is not fully known. We examined cerebral saturation with graded changes in carbon dioxide tension while isoxic and with graded changes in oxygen tension while isocapnic. METHODOLOGY/PRINCIPAL FINDINGS: The study was approved by the Research Ethics Board of the University Health Network at the University of Toronto. Thirteen studies were undertaken in healthy adults with cerebral oximetry by near infrared spectroscopy. End-tidal gas concentrations were manipulated using a model-based prospective end-tidal targeting device. End-tidal carbon dioxide was altered ±15 mmHg from baseline in 5 mmHg increments with isoxia (clamped at 110±4 mmHg). End-tidal oxygen was changed to 300, 400, 500, 80, 60 and 50 mmHg under isocapnia (37±2 mmHg). Twelve studies were completed. The end-tidal carbon dioxide versus cerebral saturation fit a linear relationship (R(2) = 0.92±0.06). The end-tidal oxygen versus cerebral saturation followed log-linear behaviour and best fit a hyperbolic relationship (R(2) = 0.85±0.10). Cerebral saturation was maximized in isoxia at end-tidal carbon dioxide of baseline +15 mmHg (77±3 percent). Cerebral saturation was minimal in isocapnia at an end-tidal oxygen tension of 50 mmHg (61±3 percent). The cerebral saturation during normoxic hypocapnia was equivalent to normocapnic hypoxia of 60 mmHg. CONCLUSIONS/SIGNIFICANCE: Hypocapnia reduces cerebral saturation to an extent equivalent to moderate hypoxia.

Abnormal retinal vascular reactivity in individuals with impaired glucose tolerance: a preliminary study.

PURPOSE: To investigate the relationship between vascular function parameters measured at the retinal and systemic level and known markers for cardiovascular risk in patients with impaired glucose tolerance (IGT). METHODS: Sixty age- and sex-matched white European adults (30 with IGT and 30 with normal glucose tolerance [NGT]) were recruited for the study. Fasting plasma glucose, lipids, and 24-hour blood pressure (BP) were measured in all subjects. Systemic vascular and endothelial function was assessed by using carotid-artery intimal media thickness (cIMT) and flow-mediated dilation (FMD). Retinal vascular reactivity was assessed by the dynamic retinal vessel analyzer. Additionally, blood glutathione (reduced glutathione [GSH], glutathione disulfide [GSSG], and total glutathione [tGSH]) and plasma von Willebrand (vWF) factor levels were also measured. RESULTS: Individuals with IGT demonstrated higher BP values (P < 0.001), fasting triglyceride (TG) levels and TG:high-density lipoprotein (HDL) ratios (P < 0.001) than NGT subjects. Furthermore, total:HDL-cholesterol (HDL-C) ratios and Framingham scores were raised (P = 0.010 and P < 0.001, respectively). Blood glutathione levels (GSH, GSSG, and tGSH) were lower (P < 0.001, P = 0.039, and P < 0.001, respectively) while plasma vWF was increased (P = 0.014) in IGT subjects compared to controls. IGT individuals also demonstrated higher IMT in right and left carotid arteries (P = 0.017 and P = 0.005, respectively) alongside larger brachial artery diameter (P = 0.015) and lower FMD percentage (P = 0.026) and glyceryl trinitrate-induced dilation (P = 0.012) than healthy controls. At the retinal arterial level, the IGT subjects showed higher baseline diameter fluctuations (BDFs) (P = 0.026), longer reaction time (RT) (P = 0.032), and reduced baseline-corrected flicker response (bFR) (P = 0.045). In IGT subjects, retinal BDF correlated with total:HDL (P = 0.003) and HDL-C (P = 0.004). Arterial RT also correlated with FMD (P = 0.017) in IGT but not NGT subjects. CONCLUSIONS: In IGT individuals there is a relationship between macro- and microvascular function, as well as a direct correlation between the observed retinal microcirculatory changes and established plasma markers for cardiovascular diseases. Multifactorial preventive interventions to decrease vascular risk in these individuals should be considered.

Coexistence of macro- and micro-vascular abnormalities in newly diagnosed normal tension glaucoma patients.

PURPOSE: To investigate the coexistence of ocular microvascular and systemic macrovascular abnormalities in early stage, newly diagnosed and previously untreated normal tension glaucoma patients (NTG). METHODS: Retinal vascular reactivity to flickering light was assessed in 19 NTG and 28 age-matched controls by means of dynamic retinal vessel analysis (IMEDOS GmbH, Jena, Germany). Using a newly developed computational model, the entire dynamic vascular response profile to flicker light was imaged and used for analysis. In addition, assessments of carotid intima-media thickness (IMT) and pulse wave analysis (PWA) were conducted on all participants, along with blood pressure (BP) measurements and blood analyses for lipid metabolism markers. RESULTS: Patients with NTG demonstrated an increased right and left carotid IMT (p = 0.015, p = 0.045) and an elevated PWA augmentation index (p = 0.017) in comparison with healthy controls, along with an enhanced retinal arterial constriction response (p = 0.028), a steeper retinal arterial constriction slope (p = 0.031) and a reduced retinal venous dilation response (p = 0.026) following flicker light stimulation. CONCLUSIONS: Early stage, newly diagnosed, NTG patients showed signs of subclinical vascular abnormalities at both macro- and micro-vascular levels, highlighting the need to consider multi-level circulation-related pathologies in the development and progression of this type of glaucoma.