Lirot.ai: A Novel Platform for Crowd-Sourcing Retinal Image Segmentations

Introduction: For supervised deep learning (DL) tasks, researchers need a large annotated dataset. In medical data science, one of the major limitations to develop DL models is the lack of annotated examples in large quantity. This is most often due to the time and expertise required to annotate. We introduce Lirot. ai, a novel platform for facilitating and crowd-sourcing image segmentations. Methods: Lirot. ai is composed of three components; an iPadOS client application named Lirot. ai-app, a backend server named Lirot. ai-server and a python API name Lirot. ai-API. Lirot. ai-app was developed in Swift 5.6 and Lirot. ai-server is a firebase backend. Lirot. ai-API allows the management of the database. Lirot. ai-app can be installed on as many iPadOS devices as needed so that annotators may be able to perform their segmentation simultaneously and remotely. We incorporate Apple Pencil compatibility, making the segmentation faster, more accurate, and more intuitive for the expert than any other computer-based alternative. Results: We demonstrate the usage of Lirot. ai for the creation of a retinal fundus dataset with reference vasculature segmentations. Discussion and future work: We will use active learning strategies to continue enlarging our retinal fundus dataset by including a more efficient process to select the images to be annotated and distribute them to annotators

Normal tension glaucoma: A dynamic optical coherence tomography angiography study

PurposeVascular dysregulation seems to play a role in the pathogenesis of glaucoma, in particular normal tension glaucoma (NTG). The development of optical coherence tomography angiography (OCTA) enabled the measurement of the retinal microvasculature non-invasively and with high repeatability. Nonetheless, only a few studies transformed OCTA into a dynamic examination employing a sympathomimetic stimulus. The goal of this study was to use this dynamic OCTA exam (1) to differentiate healthy individuals from glaucoma patients and (2) to distinguish glaucoma subcategories, NTG and high-tension primary open angle glaucoma (POAG).MethodsRetinal vessel density (VD) in NTG patients (n = 16), POAG patients (n = 12), and healthy controls (n = 14) was compared before and during a hand grip test with a hydraulic dynamometer.ResultsAt baseline, mean peripapillary VD was lower in POAG and NTG (42.6 and 48.5%) compared to healthy controls (58.1%; p < 0.001) and higher in NTG compared to POAG (p = 0.024) when corrected for mean arterial pressure (MAP). Peripapillary and macular (superficial and deep) VD differences were found for gender, age, and baseline MAP. No change in VD occurred (pre-/post-stimulus) in any of the groups.ConclusionRetinal VD loss in glaucoma patients was confirmed and the necessity to correct for gender, age and especially MAP was established. Although replication in a larger population is necessary, OCTA might not be the most suitable method to dynamically evaluate the retinal microvasculature

High-intensity interval training in patients with glaucoma (HIT-GLAUCOMA): protocol for a multicenter randomized controlled exercise trial

BackgroundGlaucoma stands as a prominent global cause of irreversible blindness and the primary treatment approach involves reducing intraocular pressure (IOP). However, around one-third of patients exhibit disease progression despite effective IOP reduction. Microvascular endothelial function, chronic inflammation, and oxidative stress are known to affect retinal neuronal networks and have been associated with disease severity and progression. Exercise training has the potential to counteract these mechanisms as add-on treatment to usual care.AimsThe HIT-GLAUCOMA study will investigate the effects of a 6-month high-intensity interval training (HIIT) on intermediate endpoints such as local retinal microvascular and systemic large artery function, inflammation, and oxidative stress as well as clinical endpoints such as visual field indices, optic nerve rim assessment, retinal nerve fiber layer thickness, IOP, number of eye drops, vision-related quality of life and ocular surface disease symptomatology.MethodsThe study is a multi-center randomized controlled clinical trial in patients with both normal tension and high-tension primary open angle glaucoma. Across two study centers, 128 patients will be enrolled and randomized on a 1:1 basis into an exercise intervention group and a usual care control group. The primary microvascular endpoints are retinal arteriolar and venular flicker light-induced dilation at 6 months. The primary endpoint in the systemic circulation is brachial artery flow-mediated dilation at 6 months.Anticipated resultsWe hypothesize that exercise therapy will improve retinal microvascular function and thus ocular blood flow in patients with glaucoma. As clinical outcomes, we will investigate the effect of exercise on visual field indices, optic nerve rim assessment, retinal nerve fiber layer thickness, IOP, number of eye drops, vision-related quality of life and ocular surface disease symptomatology.DiscussionHIT-GLAUCOMA is a blueprint trial design to study the effect of exercise training on neurodegenerative and cardiovascular diseases. Importantly, patients are also expected to benefit from improvements in general health and cardiovascular co-morbidities. If proven effective, exercise may offer a new add-on treatment strategy to slow glaucoma progression.Clinical Trial Registration NumberThe trial is registered at Clinicaltrials.gov under the identifier NCT06058598 and is currently in the recruitment stage

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 and ocular perfusion pressure is poorly understood. Objective This systematic review aims to provide clinicians with the latest literature regarding the management of arterial blood pressure 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 blood pressure 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 blood pressure and glaucoma progression was found. Both high and low blood pressure increase the risk of glaucoma. Glaucoma progression was, possibly via ocular perfusion pressure variation, strongly associated with nocturnal dipping and high variability in the blood pressure over 24-hours. Conclusions We concluded that systemic blood pressure level associates with glaucomatous damage and provided recommendations for the management and study of arterial blood pressure in glaucoma. Prospective clinical trials are needed to further support these recommendations

Retinal OCT speckle as a biomarker for glaucoma diagnosis and staging

This paper presents a novel image analysis strategy that increases the potential of macular Optical Coherence Tomography (OCT) by using speckle features as biomarkers in different stages of glaucoma. A large pool of features (480) were computed for a subset of macular OCT volumes of the Leuven eye study cohort. The dataset contained 258 subjects that were divided into four groups based on their glaucoma severity: Healthy (56), Mild (94), Moderate (48), and Severe (60). The OCT speckle features were categorized as statistical properties, statistical distributions, contrast, spatial gray-level dependence matrices, and frequency domain features. The averaged thicknesses of ten retinal layers were also collected. Kruskal-Wallis H test and multivariable regression models were used to infer the most significant features related to glaucoma severity classification and to the correlation with visual field mean deviation. Four features were selected as being the most relevant: the ganglion cell layer (GCL) and the inner plexiform layer (IPL) thicknesses, and two OCT speckle features, the data skewness computed on the retinal nerve fiber layer (RNFL) and the scale parameter (a) of the generalized gamma distribution fitted to the GCL data. Based on a significance level of 0.05, the regression models revealed that RNFL skewness exhibited the highest significance among the features considered for glaucoma severity staging (p-values of 8.6×10-6 for the logistic model and 2.8×10-7 for the linear model). Furthermore, it demonstrated a strong negative correlation with the visual field mean deviation (ρ=-0.64). The post hoc analysis revealed that, when distinguishing healthy controls from glaucoma subjects, GCL thickness is the most relevant feature (p-value of 8.7×10-5). Conversely, when comparing the Mild versus Moderate stages of glaucoma, RNFL skewness emerged as the only feature exhibiting statistical significance (p-value = 0.001). This work shows that macular OCT speckle contains information that is currently not used in clinical practice, and not only complements structural measurements (thickness) but also has a potential for glaucoma staging

Progression of functional and structural glaucomatous damage in relation to diurnal and nocturnal dips in mean arterial pressure

BackgroundSystemic hypoperfusion plays a pivotal role in the pathogenesis of primary open-angle glaucoma (POAG). Extreme dips in mean arterial pressure (MAP) due to high 24-h variability are associated with POAG, however, whether this is driven by diurnal or nocturnal dips remains undocumented. We aimed this study to investigate the association of POAG damage with variability and dips in the diurnal and nocturnal MAP.MethodsWe conducted a retrospective longitudinal study that included 110 POAG patients who underwent 24-h ambulatory blood pressure monitoring. Our outcomes included (i) functional [visual field defects expressed as mean deviation (MD)] and (ii) structural (optic disc cupping obtained from cup-to-disc ratio) glaucoma damage. MAP variability independent of the mean (VIMmap) was computed for diurnal and nocturnal MAP. Dips were the five diurnal and three nocturnal lowest drops in MAP. We also calculated the night-to-day ratio. We applied mixed models to evaluate the progression of visual field defects and optic disc cupping in relation to diurnal and nocturnal MAP measures.ResultsThe mean age was 64.0 y (53% women). The median follow-up was 9 years. In adjusted mixed models, functional progression of glaucoma damage was associated with VIMmap (−2.57 dB change in MD per every 3 mmHg increase in VIMmap; P < 0.001) and diurnal MAP dips (changes in the MD ranged from −2.56 to −3.19 dB; P < 0.001). Every 5 mmHg decrease in the nocturnal MAP level was associated with −1.14 dB changes in MD [95% confidence interval (CI), −1.90 to −0.40] and 0.01 larger optic disc cupping (95% CI, 0.01–0.02). Lower night-to-day ratio was also related to both outcomes (P ≤ 0.012). Functional glaucoma damage worsened if nocturnal hypotension was combined with high variability or extreme dips in the diurnal MAP (P ≤ 0.022).ConclusionProgression of glaucoma damage in POAG associates with high variability and extreme dips in the diurnal MAP. Structural glaucoma damage seems more vulnerable to nocturnal hypotension. Ambulatory blood pressure monitoring allows the assessment of sporadic diurnal and persistent nocturnal hypotension episodes. These phenotypes might offer an opportunity to improve the risk-stratification of open-angle glaucoma (OAG)

Leuven-Haifa High-Resolution Fundus Image Dataset for Retinal Blood Vessel Segmentation and Glaucoma Diagnosis

Abstract The Leuven-Haifa dataset contains 240 disc-centered fundus images of 224 unique patients (75 patients with normal tension glaucoma, 63 patients with high tension glaucoma, 30 patients with other eye diseases and 56 healthy controls) from the University Hospitals of Leuven. The arterioles and venules of these images were both annotated by master students in medicine and corrected by a senior annotator. All senior segmentation corrections are provided as well as the junior segmentations of the test set. An open-source toolbox for the parametrization of segmentations was developed. Diagnosis, age, sex, vascular parameters as well as a quality score are provided as metadata. Potential reuse is envisioned as the development or external validation of blood vessels segmentation algorithms or study of the vasculature in glaucoma and the development of glaucoma diagnosis algorithms. The dataset is available on the KU Leuven Research Data Repository (RDR)

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.status: publishe

Automatic Segmentation of the Optic Nerve Head Region in Optical Coherence Tomography: A Methodological Review

The optic nerve head (ONH) represents the intraocular section of the optic nerve, which is prone to damage by intraocular pressure (IOP). The advent of optical coherence tomography (OCT) has enabled the evaluation of novel ONH parameters, namely the depth and curvature of the lamina cribrosa (LC). Together with the Bruch's membrane minimum-rim-width (BMO-MRW), these seem to be promising ONH parameters for diagnosis and monitoring of retinal diseases such as glaucoma. Nonetheless, these OCT derived biomarkers are mostly extracted through manual segmentation, which is time-consuming and prone to bias, thus limiting their usability in clinical practice. The automatic segmentation of ONH in OCT scans could further improve the current clinical management of glaucoma and other diseases. This review summarizes the current state-of-the-art in automatic segmentation of the ONH in OCT. PubMed and Scopus were used to perform a systematic review. Additional works from other databases (IEEE, Google Scholar and ARVO IOVS) were also included, resulting in a total of 29 reviewed studies. For each algorithm, the methods, the size and type of dataset used for validation, and the respective results were carefully analysed. The results show a lack of consensus regarding the definition of segmented regions, extracted parameters and validation approaches, highlighting the importance and need of standardized methodologies for ONH segmentation. Only with a concrete set of guidelines, these automatic segmentation algorithms will build trust in data-driven segmentation models and be able to enter clinical practice