The Relevance of Arterial Blood Pressure in the Management of Glaucoma Progression: A Systematic Review.

BACKGROUND: Glaucoma is one of the leading causes of global blindness and is expected to co-occur more frequently with vascular morbidities in the upcoming years, as both are aging-related diseases. Yet, the pathogenesis of glaucoma is not entirely elucidated and the interplay between intraocular pressure, arterial blood pressure (BP) and ocular perfusion pressure is poorly understood. OBJECTIVES: This systematic review aims to provide clinicians with the latest literature regarding the management of arterial BP in glaucoma patients. METHODS: A systematic search was performed in Medline, Embase, Web of Science and Cochrane Library. Articles written in English assessing the influence of arterial BP and systemic antihypertensive treatment of glaucoma and its management were eligible for inclusion. Additional studies were identified by revising references included in selected articles. RESULTS: 80 Articles were included in this systemic review. A bimodal relation between BP and glaucoma progression was found. Both high and low BP increase the risk of glaucoma. Glaucoma progression was, possibly via ocular perfusion pressure variation, strongly associated with nocturnal dipping and high variability in the BP over 24 h. CONCLUSIONS: We concluded that systemic BP level associates with glaucomatous damage and provided recommendations for the management and study of arterial BP in glaucoma. Prospective clinical trials are needed to further support these recommendations.

Five-year follow-up of a posterior chamber phakic intraocular lens with a central hole for correction of myopia.

PURPOSE: To evaluate intermediate and long-term visual outcomes and safety of a phakic intraocular posterior chamber lens with a central hole (ICL V4c) for myopic eyes. METHODS: Retrospective, consecutive case study of patients that uneventfully received a ICL V4c for myopia correction, with a 5-year postoperative follow-up. Department of Ophthalmology, Goethe University Frankfurt, Germany. RESULTS: From 241 eyes that underwent ICL implantation, we included 45 eyes with a mean age at surgery of 33 years ± 6 (18-48 years), with a 5 years follow-up. CDVA improved from 0.05logMAR ± 0.15 CDVA preoperatively to - 0.00 ± 0,07 at 5 years and did not change significantly from 3 to 5 years' time (p = 0.266). The mean spherical equivalent (SE) improved from -10.13D ± 3.39 to - 0.45D ± 0.69. The change in endothelial cell count showed a mean decrease of 1.9% per year throughout the follow-up. Safety and efficacy index were 1.16 and 0.78, respectively. Cataract formation was seen in 2 of 241 eyes (0.8%), but in none of the 45 eyes that finished the 5-year follow-up. CONCLUSIONS: Our data show a good intermediate and long-term stability, efficiency, and safety of ICL V4c phakic lenses in myopic eyes comparable to other known literature.

Postoperative vault prediction for phakic implantable collamer lens surgery: LASSO formulas.

PURPOSE: To develop and evaluate reliable formulas for predicting postoperative vault more accurately after implantable collamer lens (ICL) surgery in a White patient population with varying degrees of ametropia. SETTING: Private clinical practice. DESIGN: Retrospective analysis on dataset split into a separate training and test set. METHODS: 115 eyes of 59 patients were used to train regression models predicting postoperative vault based on anterior segment optical coherence tomography (OCT) parameters (Least Absolute Shrinkage and Selection Operator [LASSO]-OCT formula), ocular biometry data (LASSO-Biometry formula), or data from both devices (LASSO-Full formula). The performance of these models was evaluated against the manufacturer's nomogram (Online Calculation and Ordering System [OCOS]) and Nakamura 1 (NK1) and 2 (NK2) formulas on a matched separate test set of 37 eyes of 19 patients. RESULTS: The mean preoperative spherical equivalent was -5.32 ± 3.37 (range: +3.75 to -17.375 diopters). The mean absolute errors of the estimated vs achieved postoperative vault for the LASSO-Biometry, LASSO-OCT, and LASSO-Full formulas were 144.1 ± 107.9 µm, 145.6 ± 100.6 µm, and 132.0 ± 86.6 µm, respectively. These results were significantly lower compared with the OCOS, NK1, and NK2 formulas ( P < .006). Postoperative vault could be estimated within 500 µm in 97.3% (LASSO-Biometry) to 100% of cases (LASSO-OCT and LASSO-Full). CONCLUSIONS: The LASSO suite provided a set of powerful, reproducible yet convenient ICL sizing formulas with state-of-the-art performance in White patients, including those with low to moderate degrees of myopia. The calculator can be accessed at http://icl.emmetropia.be .

Corneal Lenticule Creation Using a New Solid-State Femtosecond Laser Measured by Spectral Domain OCT in a Porcine Eye Model.

Purpose: To determine the accuracy and precision of corneal lenticule creation with a new solid-state femtosecond laser in a porcine eye model. Methods: Corneal lenticule creation was performed using a new solid-state femtosecond laser on 60 porcine eyes with 10 subgroups. Optical coherence tomography images were acquired immediately after laser treatment. Cap thickness (CT), cap diameter (CD), and lenticule thickness (LT) were measured manually by three independent readers. Additionally, CT and LT were measured by an automated algorithm (aLT, aCT). Results: Measured LT was significantly greater than the intended LT (average difference 14.3 ± 5.6 µm, P < 0.001). aLT was closer but still significantly different from the intended LT (-2.9 ± 5.8 µm, P < 0.001). Measured CT showed no significant difference from the intended CT (2.6 ± 13.3, P = 0.145). aCT was significantly smaller compared to the intended CT (-9.6 ± 13.6, P < 0.001). Measured CD was significantly smaller compared to the intended CD (-0.21 ± 0.20 mm, P < 0.001). All lenticules were cut as planned with no laser-related complications. Conclusions: This new solid-state femtosecond laser used in our trial provides corneal lenticule creation in a porcine eye model comparable to other established systems. However, measuring those lenticules in the provided setting seems too challenging even when using semiautomated algorithms, which seems to be due to the experimental setting of the trial. Translational Relevance: This trial shows the precision and repeatability of corneal cuts performed by a new femtosecond laser that could translate to refractive corneal lenticule surgery.

Age-related changes in the fractal dimension of the retinal microvasculature, effects of cardiovascular risk factors and smoking behaviour.

PURPOSE: This cross-sectional study investigates the association between retinal vessel complexity and age and studies the effects of cardiovascular health determinants. METHODS: Retinal vessel complexity was assessed by calculating the box-counting fractal dimension (Df ) from digital fundus photographs of 850 subjects (3-97 years). All photographs were labelled as 'non-pathological' by the treating ophthalmologist. RESULTS: Statistical models showed a significantly decreasing relationship between age and Df (linear: R-squared = 0.1897, p < 0.0001; quadratic: R-squared = 0.2343, p < 0.0001; cubic: R-squared = 0.2721, p < 0.0001), with the cubic regression model offering the best compromise between accuracy and model simplicity. Multivariate cubic regression showed that age, spherical equivalent and smoking behaviour have an effect (p < 0.0001) on Df . A significantly increasing effect of the number of pack-years on Df was observed (effect: 0.0004, p = 0.0017), as well as a significantly decreasing effect of years since tobacco abstinence (effect: -0.0149, p < 0.0001). CONCLUSION: We propose using a cubic trend with age, refractive error and smoking behaviour when interpreting retinal vessel complexity.

Ray-tracing Calculation Using Scheimpflug Tomography of Diffractive Extended Depth of Focus IOLs Following Myopic LASIK.

PURPOSE: To evaluate a ray-tracing formula for intraocular lens (IOL) calculation of diffractive extended depth of focus IOLs after myopic laser in situ keratomileusis (LASIK) compared to formulas from an established online calculator. METHODS: This retrospective, consecutive case series included patients after cataract surgery with implantation of an extended depth of focus (EDOF) IOL (AT LARA, Carl Zeiss Meditec; Symfony, Johnson & Johnson) and a history of myopic LASIK. Preoperative assessments included biometry (IOLMaster; Carl Zeiss Meditec) and corneal tomography, including true net power (TNP) (Pentacam; Oculus Optikgeräte GmbH). To evaluate the measurements, the simulated keratometry values (SimK) were compared to the TNP. Regarding IOL calculation, the mean prediction error, mean and median absolute prediction error (MAE and MedAE), and number of eyes within ±0.50, ±1.00, and ±2.00 diopters (D) from the Haigis-L, Shammas, and Barrett True K No History formulas to the Potvin-Hill and Haigis with TNP (Pentacam) formulas were compared. RESULTS: Thirty-six eyes matched the inclusion criteria with a mean spherical equivalent of -6.26 ± 3.25 diopters (D) preoperatively and -0.79 ± 0.75 D postoperatively. The mean difference from SimK and TNP was significantly different from zero (P < .001; -1.24 ± 0.81 D). The best performing formulas by MedAE were the Potvin-Hill and Barrett True K No History (0.39 ± 0.78 and 0.64 ± 1.00 D). The formula with the most eyes within ±0.50 D was the Potvin-Hill (64%), followed by the Barrett True K No History (44%). For MAE and percentage of eyes within ±0.50 D, the Potvin-Hill formula was significantly better than the Haigis-L, Shammas, and Haigis-TNP formulas (P < .05). CONCLUSIONS: Calculation of IOLs in patients who had LASIK remains less predicable than calculations for virgin eyes. Using ray-tracing to calculate diffractive EDOF IOLs after myopic LASIK, the Potvin-Hill formula outperformed established formulas in terms of the percentage within target refraction and the MAE. [J Refract Surg. 2021;37(4):231-239.].

Combination of snapshot hyperspectral retinal imaging and optical coherence tomography to identify Alzheimer's disease patients.

INTRODUCTION: The eye offers potential for the diagnosis of Alzheimer's disease (AD) with retinal imaging techniques being explored to quantify amyloid accumulation and aspects of neurodegeneration. To assess these changes, this proof-of-concept study combined hyperspectral imaging and optical coherence tomography to build a classification model to differentiate between AD patients and controls. METHODS: In a memory clinic setting, patients with a diagnosis of clinically probable AD (n = 10) or biomarker-proven AD (n = 7) and controls (n = 22) underwent non-invasive retinal imaging with an easy-to-use hyperspectral snapshot camera that collects information from 16 spectral bands (460-620 nm, 10-nm bandwidth) in one capture. The individuals were also imaged using optical coherence tomography for assessing retinal nerve fiber layer thickness (RNFL). Dedicated image preprocessing analysis was followed by machine learning to discriminate between both groups. RESULTS: Hyperspectral data and retinal nerve fiber layer thickness data were used in a linear discriminant classification model to discriminate between AD patients and controls. Nested leave-one-out cross-validation resulted in a fair accuracy, providing an area under the receiver operating characteristic curve of 0.74 (95% confidence interval [0.60-0.89]). Inner loop results showed that the inclusion of the RNFL features resulted in an improvement of the area under the receiver operating characteristic curve: for the most informative region assessed, the average area under the receiver operating characteristic curve was 0.70 (95% confidence interval [0.55, 0.86]) and 0.79 (95% confidence interval [0.65, 0.93]), respectively. The robust statistics used in this study reduces the risk of overfitting and partly compensates for the limited sample size. CONCLUSIONS: This study in a memory-clinic-based cohort supports the potential of hyperspectral imaging and suggests an added value of combining retinal imaging modalities. Standardization and longitudinal data on fully amyloid-phenotyped cohorts are required to elucidate the relationship between retinal structure and cognitive function and to evaluate the robustness of the classification model.

Hyperspectral Imaging and the Retina: Worth the Wave?

Purpose: Hyperspectral imaging is gaining attention in the biomedical field because it generates additional spectral information to study physiological and clinical processes. Several technologies have been described; however an independent, systematic literature overview is lacking, especially in the field of ophthalmology. This investigation is the first to systematically overview scientific literature specifically regarding retinal hyperspectral imaging. Methods: A systematic literature review was conducted, in accordance with PRISMA Statement 2009 criteria, in four bibliographic databases: Medline, Embase, Cochrane Database of Systematic Reviews, and Web of Science. Results: Fifty-six articles were found that meet the review criteria. A range of techniques was reported: Fourier analysis, liquid crystal tunable filters, tunable laser sources, dual-slit monochromators, dispersive prisms and gratings, computed tomography, fiber optics, and Fabry-Perrot cavity filter covered complementary metal oxide semiconductor. We present a narrative synthesis and summary tables of findings of the included articles, because methodologic heterogeneity and diverse research topics prevented a meta-analysis being conducted. Conclusions: Application in ophthalmology is still in its infancy. Most previous experiments have been performed in the field of retinal oximetry, providing valuable information in the diagnosis and monitoring of various ocular diseases. To date, none of these applications have graduated to clinical practice owing to the lack of sufficiently large validation studies. Translational Relevance: Given the promising results that smaller studies show for hyperspectral imaging (e.g., in Alzheimer's disease), advanced research in larger validation studies is warranted to determine its true clinical potential.

Systematic Review on Fractal Dimension of the Retinal Vasculature in Neurodegeneration and Stroke: Assessment of a Potential Biomarker.

Introduction: Ocular manifestations in several neurological pathologies accentuate the strong relationship between the eye and the brain. Retinal alterations in particular can serve as surrogates for cerebral changes. Offering a "window to the brain," the transparent eye enables non-invasive imaging of these changes in retinal structure and vasculature. Fractal dimension (FD) reflects the overall complexity of the retinal vasculature. Changes in FD could reflect subtle changes in the cerebral vasculature that correspond to preclinical stages of neurodegenerative diseases. In this review, the potential of this retinal vessel metric to serve as a biomarker in neurodegeneration and stroke will be explored. Methods: A literature search was conducted, following the PRISMA Statement 2009 criteria, in four large bibliographic databases (Pubmed, Embase, Web Of Science and Cochrane Library) up to 12 October 2019. Articles have been included based upon their relevance. Wherever possible, level of evidence (LOE) has been assessed by means of the Oxford Centre for Evidence-based Medicine Level of Evidence classification. Results: Twenty-one studies were included for qualitative synthesis. We performed a narrative synthesis and produced summary tables of findings of included papers because methodological heterogeneity precluded a meta-analysis. A significant association was found between decreased FD and neurodegenerative disease, mainly addressing cognitive impairment (CI) and dementia. In acute, subacute as well as chronic settings, decreased FD seems to be associated with stroke. Differences in FD between subtypes of ischemic stroke remain unclear. Conclusions: This review provides a summary of the scientific literature regarding the association between retinal FD and neurodegenerative disease and stroke. Central pathology is associated with a decreased FD, as a measure of microvascular network complexity. As retinal FD reflects the global integrity of the cerebral microvasculature, it is an attractive parameter to explore. Despite obvious concerns, mainly due to a lack of methodological standardization, retinal FD remains a promising non-invasive and low-cost diagnostic biomarker for neurodegenerative and cerebrovascular disease. Before FD can be implemented in clinic as a diagnostic biomarker, the research community should strive for uniformization and standardization.

Structural analysis of retinal blood vessels in patients with COPD during a pulmonary rehabilitation program.

Cardiovascular diseases are frequently present in chronic obstructive pulmonary disease (COPD). Population-based studies found associations between retinal vessel diameters and cardiovascular health, but it is unknown whether this also applies to COPD patients. Therefore, we measured retinal vessel diameters in COPD patients and aimed to determine the association with cardiovascular risk factors, lung function, and functional outcomes. In addition, we investigated whether an exercise-based pulmonary rehabilitation (PR) program would change retinal vessel diameters, as a proxy for improved microvascular health. Demographics and clinical characteristics, including pulmonary function, exercise capacity, blood pressure, blood measurements and level of systemic inflammation were obtained from 246 patients during routine assessment before and after PR. Retinal vessel diameters were measured from digital retinal images. Older age and higher systolic blood pressure were associated with narrower retinal arterioles (ß: -0.224; p = 0.042 and ß: -0.136; p < 0.001, respectively). Older age, higher systolic blood pressure and lower level of systemic inflammation were associated with narrower retinal venules (ß: -0.654; -0.229; and -13.767, respectively; p < 0.05). No associations were found between retinal vessel diameters and lung function parameters or functional outcomes. After PR, no significant changes in retinal venular or arteriolar diameter were found. To conclude, retinal vessel diameters of COPD patients were significantly associated with systolic blood pressure and systemic inflammation, whilst there was no evidence for an association with lung function parameters, functional outcomes or other cardiovascular risk factors. Furthermore, an exercise-based PR program did not affect retinal vessel diameter.

The Prevalence of Undiagnosed Age-Related Sight-Threatening Diseases in Self-Proclaimed Healthy Individuals.

BACKGROUND: Age-related conditions such as glaucoma, age-related macular degeneration, diabetic retinopathy, and cataract have become the major cause of visual impairment and blindness in high-income countries. The aim of the current study is to investigate the prevalence of these eye diseases in a cohort of self-proclaimed healthy elderly and thus get a rough estimation of the prevalence of undiagnosed age-related eye conditions in the Belgian population. METHODS: Individuals aged 55 and older without ophthalmological complaints were asked to fill in a general medical questionnaire and underwent an ophthalmological examination, which included a biomicroscopic examination, intraocular pressure measurement, axial length measurement, and acquisition of fundus pictures and optical coherence tomography scans. Information regarding follow-up was collected in those who received the advice of referral to an ophthalmologist or the advice to have more frequent follow-up visits, based on their study evaluation. RESULTS: The cohort included 102 people and comprised 46% men (median age 70 years, range 57-85 years). Referral for additional examinations was made in 26 participants (25%). The advice to have more regular follow-up ophthalmologist visits was given to nine additional participants (9%). No significant correlations between baseline characteristics and the need for referral could be identified. Follow-up information was available for 25 out of 26 referred volunteers. Out of these, four underwent a therapeutic intervention based on study referral, up until 18 months after study participation. All four interventions took place in the age group 65-74 years. CONCLUSIONS: This study shows that, even in an elderly population with self-proclaimed healthy eyes and good general health, a significant proportion of subjects showed ocular findings that need regular follow-up and/or intervention. The frequency of prior ophthalmological examinations does not seem to be relevant to this proportion, meaning that everyone above 55 years old needs a routine ophthalmological evaluation.

REFUGE Challenge: A unified framework for evaluating automated methods for glaucoma assessment from fundus photographs.

Glaucoma is one of the leading causes of irreversible but preventable blindness in working age populations. Color fundus photography (CFP) is the most cost-effective imaging modality to screen for retinal disorders. However, its application to glaucoma has been limited to the computation of a few related biomarkers such as the vertical cup-to-disc ratio. Deep learning approaches, although widely applied for medical image analysis, have not been extensively used for glaucoma assessment due to the limited size of the available data sets. Furthermore, the lack of a standardize benchmark strategy makes difficult to compare existing methods in a uniform way. In order to overcome these issues we set up the Retinal Fundus Glaucoma Challenge, REFUGE (https://refuge.grand-challenge.org), held in conjunction with MICCAI 2018. The challenge consisted of two primary tasks, namely optic disc/cup segmentation and glaucoma classification. As part of REFUGE, we have publicly released a data set of 1200 fundus images with ground truth segmentations and clinical glaucoma labels, currently the largest existing one. We have also built an evaluation framework to ease and ensure fairness in the comparison of different models, encouraging the development of novel techniques in the field. 12 teams qualified and participated in the online challenge. This paper summarizes their methods and analyzes their corresponding results. In particular, we observed that two of the top-ranked teams outperformed two human experts in the glaucoma classification task. Furthermore, the segmentation results were in general consistent with the ground truth annotations, with complementary outcomes that can be further exploited by ensembling the results.

Ophthalmic Outcome in a Belgian Cohort of Cystinosis Patients Treated with a Compounded Preparation of Cysteamine Eye Drops: Retrospective Analysis.

INTRODUCTION: Treatment of the anterior segment problems in cystinosis is challenging as oral cysteamine is ineffective in the treatment of corneal problems because of its avascular structure. Although cysteamine eye drops have been formulated to counter this issue, the stability of cysteamine in these off-licensed formulations and treatment compliance are major problems. The aim of this retrospective study was to determine the efficacy of a compounded preparation of aqueous 0.5% cysteamine eye drops in the management of corneal complications of cystinosis. METHODS: Data of patients attending the multidisciplinary cystinosis clinic at the University Hospitals Leuven, Belgium between January 2015 and December 2018 were analyzed. All cystinosis patients were treated with the compounded preparation of aqueous 0.5% cysteamine eye drops and oral cysteamine. RESULTS: A total of 12 patients were treated with the compounded preparation of aqueous 0.5% cysteamine eye drops, of whom 75% were aged > 18 years (n = 9). The mean instillation frequency of the cysteamine eye drops was 3.3 drops/eye per day, and the mean number of hospital visits was two per year. All patients showed photophobia, > 30% corneal infiltration, blepharospasm, eye pain and conjunctival hyperemia during the study period. None of these symptoms improved with treatment with aqueous compounded 0.5% cysteamine eye drops. The corneal cystine crystal score was ≥ 2 in all patients at the last  visit. CONCLUSION: Treatment with the compounded preparation of aqueous 0.5% cysteamine eye drops, combined with oral cysteamine, was not effective in reducing corneal cystine crystal deposition and other ocular symptoms in these patients with cystinosis. FUNDING: Recordati Rare Diseases.

Artery-vein segmentation in fundus images using a fully convolutional network.

Epidemiological studies demonstrate that dimensions of retinal vessels change with ocular diseases, coronary heart disease and stroke. Different metrics have been described to quantify these changes in fundus images, with arteriolar and venular calibers among the most widely used. The analysis often includes a manual procedure during which a trained grader differentiates between arterioles and venules. This step can be time-consuming and can introduce variability, especially when large volumes of images need to be analyzed. In light of the recent successes of fully convolutional networks (FCNs) applied to biomedical image segmentation, we assess its potential in the context of retinal artery-vein (A/V) discrimination. To the best of our knowledge, a deep learning (DL) architecture for simultaneous vessel extraction and A/V discrimination has not been previously employed. With the aim of improving the automation of vessel analysis, a novel application of the U-Net semantic segmentation architecture (based on FCNs) on the discrimination of arteries and veins in fundus images is presented. By utilizing DL, results are obtained that exceed accuracies reported in the literature. Our model was trained and tested on the public DRIVE and HRF datasets. For DRIVE, measuring performance on vessels wider than two pixels, the FCN achieved accuracies of 94.42% and 94.11% on arteries and veins, respectively. This represents a decrease in error of 25% over the previous state of the art reported by Xu et al. (2017). Additionally, we introduce the HRF A/V ground truth, on which our model achieves 96.98% accuracy on all discovered centerline pixels. HRF A/V ground truth validated by an ophthalmologist, predicted A/V annotations and evaluation code are available at https://github.com/rubenhx/av-segmentation.

Retinal oximetry: Metabolic imaging for diseases of the retina and brain.

Retinal oximetry imaging of retinal blood vessels measures oxygen saturation of hemoglobin. The imaging technology is non-invasive and reproducible with remarkably low variability on test-retest studies and in healthy cohorts. Pathophysiological principles and novel biomarkers in several retinal diseases have been discovered, as well as possible applications for systemic and brain disease. In diabetic retinopathy, retinal venous oxygen saturation is elevated and arteriovenous difference progressively reduced in advanced stages of retinopathy compared with healthy persons. This correlates with pathophysiology of diabetic retinopathy where hypoxia stimulates VEGF production. Laser treatment and vitrectomy both improve retinal oximetry values, which correlate with clinical outcome. The oximetry biomarker may allow automatic measurement of severity of diabetic retinopathy and predict its response to treatment. Central retinal vein occlusion is characterized by retinal hypoxia, which is evident in retinal oximetry. The retinal hypoxia seen on oximetry correlates with the extent of peripheral ischemia, visual acuity and thickness of macular edema. This biomarker may help diagnose and measure severity of vein occlusion and degree of retinal ischemia. Glaucomatous retinal atrophy is associated with reduced oxygen consumption resulting in reduced arteriovenous difference and higher retinal venous saturation. The oximetry findings correlate with worse visual field, thinner nerve fiber layer and smaller optic disc rim. This provides an objective biomarker for glaucomatous damage. In retinitis pigmentosa, an association exists between advanced atrophy, worse visual field and higher retinal venous oxygen saturation, lower arteriovenous difference. This biomarker may allow measurement of severity and progression of retinitis pigmentosa and other atrophic retinal diseases. Retinal oximetry offers visible light imaging of systemic and central nervous system vessels. It senses hypoxia in cardiac and pulmonary diseases. Oximetry biomarkers have been discovered in Alzheimer's disease and multiple sclerosis and oxygen levels in the retina correspond well with brain.

Semi-automated kinetic perimetry: Comparison of the Octopus 900 and Humphrey visual field analyzer 3 versus Goldmann perimetry.

PURPOSE: To evaluate the clinical usefulness and reproducibility of (semi-)automated kinetic perimetry of the Octopus 900 and Humphrey field analyzer 3 (HFA3) compared to Goldmann perimetry as reference technique. METHODS: A prospective interventional study of two study groups, divided into three subgroups. The first study group consisted of 28 patients, performing one visual field examination on each of the three devices. A second group of 30 patients performed four examinations, one on Goldmann and three on Octopus 900 with the following testing strategies: (1) with reaction time (RT) vector, no headphone; (2) without RT vector, no headphone; and (3) without RT vector, with headphone. Comparisons for V4e and I4e stimuli were made of the mean isopter radius (MIR) and of the distances of the isopter to the central visual axis in four directions. Statistical analysis was made with the R software version 3.2.2. RESULTS: For V4e stimuli, the mean isopter radius showed no statistic significant difference comparing Goldmann to HFA3 [p-value = 0.144; confidence interval (CI) -0.152 to 0.019] and comparing Goldmann to Octopus 900 without RT vector, either with (p-value = 0.347; CI -0.023 to 0.081) or without headphone (p-value = 0.130; CI -0.011 to 0.095). Octopus 900 with RT vector produced a significantly larger MIR for V4e stimuli in comparison to Goldmann (p-value < 0.001). I4e stimuli produced statistically significantly larger visual field areas when comparing HFA3 and Octopus 900 to Goldmann perimetry. CONCLUSION: Humphrey field analyzer 3 and Octopus 900 without RT vector are promising successors of Goldmann perimetry.

Improved discrimination between normal-tension and primary open-angle glaucoma with advanced vascular examinations - the Leuven Eye Study.

PURPOSE: Vascular factors have been suggested to influence the development and progression of glaucoma. They are thought to be especially relevant for normal-tension glaucoma (NTG) patients. We aim to investigate which vascular factors, including advanced vascular examinations, better describe patients with NTG comparing to those with primary open-angle glaucoma (POAG). METHODS: The Leuven Eye Study database (182 NTG and 202 POAG patients; similar structural and functional damage) was used to compute three multivariate logistic regression models: a conventional model (conventional parameters only, including vascular-related self-reported phenomena, such as migraine or peripheral vasospasm); an advanced vascular model (advanced vascular parameters only: colour Doppler imaging (CDI), retinal oximetry, ocular pulse amplitude and choroidal thickness); and a global model, in which both types of parameters were allowed. Receiver operating characteristic (ROC) curves and corresponding areas under the curve (AUC) were calculated and compared between models. RESULTS: Patients with NTG had a higher resistive index and lower early systolic acceleration (ESA) in their retrobulbar vessels and a smaller arteriovenous retinal oxygen saturation difference. The global model (AUC 0.743) showed a significantly better discriminative ability when compared to either the conventional (AUC 0.687, p = 0.049) or the advanced vascular (AUC 0.677, p = 0.005) models. Also, the conventional and the advanced vascular models showed a similar discriminative ability (p = 0.823). CONCLUSION: Patients with NTG have more signs of vascular dysfunction. Clinical conventional parameters, such as asking simple vascular-related questions, combined with advanced vascular examinations provide information to better understand the value that non-IOP-related factors play in NTG.

Quantitative automated circumpapillary microvascular density measurements: a new angioOCT-based methodology.

PURPOSE: To develop a new methodology to detect glaucoma damage based on circumpapillary microvascular density (cpmVD) as measured by optical coherence tomography angiography (angioOCT). METHODS: AngioOCT scans from a random eye of 40 healthy subjects (aged 63 ± 14 years) and 82 glaucoma patients (aged 66 ± 9 years with an average visual field loss of -7.8 ± 6.5 dB) were used to develop a new angioOCT evaluation methodology. Optic disc-centred 3 × 3 mm images were collected (Angioplex®, Zeiss Cirrus 5000 HD-OCT). An annular area with an inner radius of 1.16 mm and outer radius of 1.44 mm was chosen as the region of interest (ROI), with cpmVD calculated through lower envelope modulation avoiding the influence of the major retinal vessels. Additionally, the cpmVD and the microvascular density (mVD), stratified by sectors, were compared with the respective retinal nerve fibre layer (RNFL) thickness. RESULTS: A significantly lower cpmVD was observed in the glaucoma group, for all visual field sectors (p < 0.001), when comparing to the healthy group. The inferior and superior mVD sectors showed the largest differences between groups. Moreover, glaucoma was linked to a reduction of cpmVD variation when compared to the healthy group. Lastly, a comparison between two healthy subgroups showed that the method is not biased by the presence of slight movement artefacts, optic disc dimensions and vessel crowding (p > 0.05). CONCLUSIONS: The presented open-source methodology provides a robust quantitative analysis of the 360˚ mVD. It shows that cpmVD, and mVD sectors measured by angioOCT, can be used in everyday glaucoma practice.

Heterogeneity in arterial hypertension and ocular perfusion pressure definitions: Towards a consensus on blood pressure-related parameters for glaucoma studies.

PURPOSE: Glaucoma studies have long taken into account the blood pressure (BP) status of patients. This study summarizes and evaluates the impact of the different criteria that have been used for BP-related variables in glaucoma research. METHODS: Studies included in two meta-analyses that reviewed the role of BP in glaucoma were analyzed. Additional studies published after the search periods of the meta-analyses were also included. Criteria for the definition of arterial hypertension and other BP-related variables, such as mean arterial pressure (MAP) and mean ocular perfusion pressure (MOPP), were retrieved. RESULTS: Sixty-four studies were evaluated. One-third used 140 mmHg as a systolic BP cut-off to define hypertension, 20% used 160 mmHg and the remaining half used various other criteria. Less than 20% of studies reported MAP and/or MOPP. While eight of the ten studies reporting MAP used a correct formula that only happened for five of the eleven studies reporting MOPP. Using as an example average blood pressure values, incorrectly used formulas could have led to an overestimation of more than 100% of the expected values. CONCLUSION: Considerable heterogeneity exists in BP-related variables in glaucoma research and different definitions can lead to large disparities. Glaucoma research would benefit from a consensus regarding blood pressure parameters.

Retinal oxygen saturation as a non-invasive estimate for mixed venous oxygen saturation and cardiac output.

PURPOSE: To investigate the correlation between retinal vessel oxygen saturation and mixed venous oxygen saturation (SvO2-mixed ) and cardiac output (CO). METHODS: Retinal arterial (SaO2-retinal ) and venous (SvO2-retinal ) oxygen saturation were measured non-invasively with dual-wavelength retinal oximetry in subjects receiving invasive measurements of SvO2-mixed and CO through right heart catheterization. Correlations were analysed using Spearman's rank correlation coefficients and linear regression models. RESULTS: Fourteen patients (median age 62.7 years, range: 21-77) were included in the analysis. When adjusted for age, SvO2-retinal showed a positive correlation with SvO2-mixed (ß = 0.80, p = 0.003). Retinal arteriovenous oxygen saturation difference was significantly correlated with the inverse of CO (Spearman's ρ = 0.59, p = 0.026). CONCLUSION: This pilot study provides proof of concept for the use of retinal oximetry as a non-invasive tool to assess systemic cardiovascular function.