LUNet: deep learning for the segmentation of arterioles and venules in high resolution fundus images.

OBJECTIVE: This study aims to automate the segmentation of retinal arterioles and venules (A/V) from digital fundus images (DFI), as changes in the spatial distribution of retinal microvasculature are indicative of cardiovascular diseases, positioning the eyes as windows to cardiovascular health. Approach: We utilized active learning to create a new DFI dataset with 240 crowd-sourced manual A/V segmentations performed by 15 medical students and reviewed by an ophthalmologist. We then developed LUNet, a novel deep learning architecture optimized for high-resolution A/V segmentation. The LUNet model features a double dilated convolutional block to widen the receptive field and reduce parameter count, alongside a high-resolution tail to refine segmentation details. A custom loss function was designed to prioritize the continuity of blood vessel segmentation. Main Results: LUNet significantly outperformed three benchmark A/V segmentation algorithms both on a local test set and on four external test sets that simulated variations in ethnicity, comorbidities and annotators. Significance: The release of the new datasets and the LUNet model (URL upon publication) provides a valuable resource for the advancement of retinal microvasculature analysis. The improvements in A/V segmentation accuracy highlight LUNet's potential as a robust tool for diagnosing and understanding cardiovascular diseases through retinal imaging.

Additional Guidance on the Use of the PRESERFLO™ MicroShunt in the Treatment of Glaucoma: Insights from a Second Delphi Consensus Panel.

INTRODUCTION: The PRESERFLO™ MicroShunt (PMS) has been proven to significantly lower intraocular pressure (IOP) in patients with glaucoma and has been available for use since 2019. With increasing published evidence and growing experience of glaucoma surgeons, the aim of this modified Delphi panel was to build on the findings of a previous Delphi panel conducted in 2021 and provide further guidance on the role of the PMS to treat patients with glaucoma in Europe. METHODS: Thirteen European glaucoma surgeons experienced in the PMS procedure participated in a 3-round modified Delphi panel. A targeted literature review and expert steering committee guided Round 1 questionnaire development. Consensus was pre-defined at a threshold of ≥ 70% of panellists selecting 'strongly agree'/'agree' or 'strongly disagree'/'disagree' for 6-point Likert scale questions or ≥ 70% selecting the same option for multiple or single-choice questions. Questions not reaching consensus were restated/revised for the next round, following guidance from free-text responses/scoping questions. RESULTS: In total, 28% (n = 9/32), 52% (n = 16/31) and 91% (n = 10/11) of statements reached consensus in Rounds 1, 2 and 3, respectively. There was agreement that the PMS may be used in patients with pigmentary, post-trauma or post-vitrectomy glaucoma and for patients with uveitic glaucoma without active inflammation. The PMS may be more suitable for patients with contact lenses than other subconjunctival filtering surgeries, without eliminating bleb-associated risks. Consensus was reached that combining PMS implantation and phacoemulsification may be as safe as standalone PMS surgery, but further efficacy data are required. Following a late rise in IOP ≥ 4 months post-surgery, topical aqueous suppressant drops or bleb revision may be suitable management options. CONCLUSIONS: This Delphi panel builds on the considerations explored in the 2021 Delphi panel and provides further detailed guidance for glaucoma surgeons on the use of the PMS, reflecting the availability of novel evidence and surgical experience. Videos are available for this article.

Preservative-free Bimatoprost 0.01% Ophthalmic Gel for Glaucoma Therapy. A Phase III Randomized Controlled Trial.

PURPOSE: To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of a preservative-free bimatoprost 0.01% ophthalmic gel (PFB 0.01% gel) compared with preserved bimatoprost 0.01% (PB 0.01%). DESIGN: Phase III, international, multicenter, randomized, 2-parallel group, investigator-masked, 3-month treatment duration. METHODS: Patients with glaucoma or ocular hypertension were randomized after a 7 week run-in/washout period to receive once-daily PFB 0.01% gel (n=236) or PB 0.01% (n=249) for 3 months. The primary efficacy measure was change from baseline in IOP at Week 12. Safety measures included adverse events (AEs) and assessment of conjunctival hyperemia. RESULTS: Mean change from baseline in IOP at Week 12 in the PFB 0.01% gel and PB 0.01% were -9.72±2.97 mmHg and -9.47±3.06, respectively at 8 am, -9.41±3.03 and -9.19±3.12 mmHg at 10 am, and -8.99±3.36 and -8.54±3.44 mmHg at 4 pm. Noninferiority of PFB 0.01% gel to PB 0.01% was demonstrated at Week 12 based on predetermined criteria (upper 95% confidence interval margin of 1.5 mmHg at all timepoints). The most frequently reported AE was conjunctival hyperemia; 13 (5.5%) patients with PFB 0.01% gel and 17 (6.8%) patients with PB 0.01%. The percentage of patients experiencing a worsening from baseline in conjunctival hyperemia score was lower with PFB 0.01% gel compared to PB 0.01% at Week 6 (20.1% vs 29.3%, respectively) and Week 12 (18.3% vs 30.4%, respectively). CONCLUSIONS: PFB 0.01% ophthalmic gel has the same efficacy in lowering IOP as PB 0.01% and demonstrated less aggravation of conjunctival hyperemia at Week 6 and Week 12.

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

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).

FAST® questionnaire for identifying glaucoma patients at risk for ocular surface disease.

OBJECTIVES: To evaluate the validity and reliability of the new Fast Assessment of the Ocular Surface Trouble (FAST®) questionnaire for identifying glaucoma or ocular hypertension (OHT) patients at risk of ocular surface disease (OSD). METHODS: A multicenter, international, cross-sectional, epidemiological survey evaluated the most accurate interview items and ocular signs on the initial 14-item version of FAST® to develop a shorter version for routine, quick clinical use. Rasch analysis and least absolute shrinkage and selection operator (LASSO) method was used to reduce the number of items on the questionnaire. Sensitivity and specificity of FAST® were assessed with receiver operating characteristic (ROC) curves for the detection of OSD with the questionnaire and ophthalmic assessment. RESULTS: A total of 2308 eyes (1154 patients) were analyzed in this study by 92 ophthalmologists. The initial version of the FAST® indicated 60% of the subjects had OSD. Rasch analysis allowed removal of some clinical signs. The LASSO method allowed elimination of some items from the original questionnaire for a 9-item and a 6-item version of FAST®. For the 6-item questionnaire, the sensitivity and specificity were 71.9% and 74.3% respectively and the area under the curve was 0.815. CONCLUSIONS: The FAST® questionnaire is a valid and reliable tool for use in routine clinical practice and in clinical trials. The short versions of the questionnaire allow quick detection of the majority of patients with OHT or glaucoma at risk of dry eye.

Differentiating Ischemic Optic Neuropathy from Glaucoma Using Diagnostic Tests.

INTRODUCTION: Anterior ischemic optic neuropathy (AION) can mimic glaucoma and consequently cause difficulties in differential diagnosis. The purpose of this paper was to summarize differences in diagnostic tests that can help perform a correct diagnosis. METHODS: The search strategy was performed according to the PRISMA 2009 guidelines, and four databases were used: MEDLINE, Embase, Web of Science, and Cochrane. Totally, 772 references were eligible; 39 were included after screening with respect to inclusion criteria that included English language and published in the 20 years before search date. RESULTS: Ninety percent (n = 35) of included studies used optical coherence tomography (OCT). Glaucomatous eyes had a significantly greater cup area, volume and depth, cup-to-disk ratio, a lower rim volume and area, and a thinner Bruch's membrane opening-minimum rim width. Retinal nerve fiber layer (RNFL) thinning in glaucomatous eyes occurred primarily at the superotemporal, inferotemporal, and inferonasal sectors, while AION eyes demonstrated mostly superonasal thinning. Glaucoma eyes showed greater macular ganglion cell layer thickness, except at the inferotemporal sector. OCT angiography measurements demonstrated a significant decrease in superficial and deep macular vessel density (VD) in glaucoma compared to AION with similar degree of visual field damage; the parapapillary choroidal VD was spared in AION eyes compared to glaucomatous eyes. CONCLUSION: By use of OCT imaging, optic nerve head parameters seem most informative to distinguish between glaucoma and AION. Although both diseases affect the RNFL thickness, it seems to do so in different sectors. Differences in structure and vascularity of the macula can also help in making the differential diagnosis.

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.

Artificial intelligence for glaucoma: state of the art and future perspectives.

PURPOSE OF REVIEW: To address the current role of artificial intelligence (AI) in the field of glaucoma. RECENT FINDINGS: Current deep learning (DL) models concerning glaucoma diagnosis have shown consistently improving diagnostic capabilities, primarily based on color fundus photography and optical coherence tomography, but also with multimodal strategies. Recent models have also suggested that AI may be helpful in detecting and estimating visual field progression from different input data. Moreover, with the emergence of newer DL architectures and synthetic data, challenges such as model generalizability and explainability have begun to be tackled. SUMMARY: While some challenges remain before AI is routinely employed in clinical practice, new research has expanded the range in which it can be used in the context of glaucoma management and underlined the relevance of this research avenue.

Primary retinal tauopathy: A tauopathy with a distinct molecular pattern.

BACKGROUND: Phosphorylated tau (p-tau) accumulation, a hallmark of Alzheimer's disease (AD), can also be found in the retina. However, it is uncertain whether it is linked to AD or another tauopathy. METHODS: Retinas from 164 individuals, with and without AD, were analyzed for p-tau accumulation and its relationship with age, dementia, and vision impairment. RESULTS: Retinal p-tau pathology showed a consistent pattern with four stages and a molecular composition distinct from that of cerebral tauopathies. The stage of retinal p-tau pathology correlated with age (r = 0.176, P = 0.024) and was associated with AD (odds ratio [OR] 3.193; P = 0.001), and inflammation (OR = 2.605; P = 0.001). Vision impairment was associated with underlying eye diseases (ß = 0.292; P = 0.001) and the stage of retinal p-tau pathology (ß = 0.192; P = 0.030) in a linear regression model. CONCLUSIONS: The results show the presence of a primary retinal tauopathy that is distinct from cerebral tauopathies.

MERCURY-3: a randomized comparison of netarsudil/latanoprost and bimatoprost/timolol in open-angle glaucoma and ocular hypertension.

PURPOSE   : To compare the efficacy and safety of the fixed-dose combination (FDC) of netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (NET/LAT; Roclanda®) with bimatoprost 0.03%/timolol maleate 0.5% (BIM/TIM; Ganfort®) ophthalmic solution in the treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT). METHODS: MERCURY-3 was a 6-month prospective, double-masked, randomized, multicenter, active-controlled, parallel-group, non-inferiority study. Patients (≥ 18 years) with a diagnosis of OAG or OHT in both eyes that was insufficiently controlled with topical medication (IOP ≥ 17 mmHg in ≥ 1 eye and < 28 mmHg in both eyes) were included. Following washout, patients were randomized to once-daily NET/LAT or BIM/TIM for up to 6 months; efficacy was assessed at Week 2, Week 4, and Month 3; safety was evaluated for 6 months. Comparison of NET/LAT relative to BIM/TIM for mean IOP at 08:00, 10:00, and 16:00 h was assessed at Week 2, Week 6, and Month 3. Non-inferiority of NET/LAT to BIM/TIM was defined as a difference of ≤ 1.5 mmHg at all nine time points through Month 3 and ≤ 1.0 mmHg at five or more of nine time points through Month 3. RESULTS: Overall, 430 patients were randomized (NET/LAT, n = 218; BIM/TIM, n = 212), and all received at least one dose of study medication. Efficacy analyses were performed at Month 3 on 388 patients (NET/LAT, n = 184; BIM/TIM, n = 204). NET/LAT demonstrated non-inferiority to BIM/TIM, with a between-treatment difference in IOP of ≤ 1.5 mmHg achieved at all time points and ≤ 1.0 mmHg at the majority of time points (six of nine) through Month 3. Mean diurnal IOP during the study ranged from 15.4 to 15.6 mmHg and 15.2 to 15.6 mmHg in the NET/LAT and BIM/TIM groups respectively, with no between-group statistically significant difference. No significant differences were observed in key secondary endpoints. No serious, treatment-related adverse events (AEs) were observed, and AEs were typically mild/moderate in severity. The most common treatment-related AEs were conjunctival hyperemia (NET/LAT, 30.7%; BIM/TIM, 9.0%) and cornea verticillata (NET/LAT, 11.0%; BIM/TIM, 0%). CONCLUSIONS: Once-daily NET/LAT was non-inferior to BIM/TIM in IOP reduction in OAG and OHT, with AEs consistent with previous findings. NET/LAT offers a compelling alternative FDC treatment option for OAG and OHT.

A prototype protocol for evaluating the real-world data set using a structured electronic health record in glaucoma.

PURPOSE: As the first step in monitoring and evaluating day-to-day glaucoma care, this study reports all real-world data recorded during the first full year after the implementation of a prototype for glaucoma-specific structured electronic healthcare record (EHR). METHODS: In 2019, 4618 patients visited Tays Medical Glaucoma Clinic at Tays Eye Centre, Tampere University Hospital, Finland, that serves a population of 0.53 M. Patient data were entered into a glaucoma-specific EHR by trained nurses to be checked by glaucoma specialists. Tays Eye Centre follows the Finnish Current Care Guideline for glaucoma in which glaucoma is defined using a '2 out of 3' rule, that is, ≥2 findings evaluated as glaucomatous in optic nerve head (ONH), retinal nerve fibre layer (RNFL) and visual field (VF). RESULTS: The clinical evaluations of ONH, RNFL and VF were recorded in 95%-100% of all eyes. ONH was evaluated as glaucomatous more often (44%) than RNFL (33%) and VF tests (30%). Progressive changes in any of the three tests were recorded in 35% of the '≥2/3 glaucoma group' compared to 2%-9% in the other groups. The mean IOP at visit was 15 mmHg. The mean target IOP was 17 mmHg, and it was recorded in 94% of eyes. CONCLUSION: The developed structured data presentation enables comparisons between different population-based real-world glaucoma data sets and glaucoma clinics. Compared to a data set from the UK, the proportion of glaucoma suspicion-related visits was smaller in Tays Eye Centre and test intervals were longer.

The influence of altitude on the differences between Goldmann tonometry and Pascal dynamic contour tonometry: An ecological meta-analysis.

PURPOSE: A meta-analysis found that including atmospheric pressure as altitude in generalized linear models reveals higher differences between Goldmann tonometry and Pascal dynamic contour tonometry at higher altitudes, with the difference increasing in thinner corneas. To examine the difference in intraocular pressure (IOP) measurements by using Goldman applanation tonometry (GAT) and dynamic contour tonometer (DCT) tonometry in published literature and determine the influence of central corneal thickness (CCT), age, and altitude on that difference. METHODS: Articles that compare GAT and DCT were selected for an extensive literature review, and the location and altitude of the research centers were found online. CCT and age were analyzed as covariates, when available. RESULTS: A total of 157 studies including 24,211 eyes of 20,214 patients were included in the study. The results showed that the difference between DCT and GAT was higher at higher altitudes above sea level and increased with thinner corneas. However, the results were different in eyes with corneal transplants, where altitude and CCT had less influence, and in those post-refractive surgery where age was found to influence the difference. Theoretical correction formulas using altitude, CCT, and age were derived from this meta-analysis, but their accuracy and usefulness in clinical practice need validation. CONCLUSION: The findings suggest that there is a higher risk of underestimating IOP when the Goldmann tonometer is used at a higher altitude, particularly in eyes with glaucoma, thinner corneas, or corneal refractive surgery. Further research is needed to validate the accuracy of the correction formulas derived from this meta-analysis in clinical practice.

European Glaucoma Society - A guide on surgical innovation for glaucoma.

PROLOGUE: Glaucoma surgery has been, for many decades now, dominated by the universal gold standard which is trabeculectomy augmented with antimetabolites. Tubes also came into the scene to complement what we use to call conventional or traditional glaucoma surgery. More recently we experienced a changing glaucoma surgery environment with the "advent" of what we have become used to calling Minimally Invasive Glaucoma Surgery (MIGS). What is the unmet need, what is the gap that these newcomers aim to fill? Hippocrates taught us "bring benefit, not harm" and new glaucoma techniques and devices aim to provide safer surgery compared to conventional surgery. For the patient, but also for the clinician, safety is important. Is more safety achieved with new glaucoma surgery and, if so, is it associated with better, equivalent, or worse efficacy? Is new glaucoma surgery intended to replace conventional surgery or to complement it as an 'add-on' to what clinicians already have in their hands to manage glaucoma? Which surgery should be chosen for which patient? What are the options? Are they equivalent? These are too many questions for the clinician! What are the answers to the questions? What is the evidence to support answers? Do we need more evidence and how can we produce high-quality evidence? This EGS Guide explores the changing and challenging glaucoma surgery environment aiming to provide answers to these questions. The EGS uses four words to highlight a continuum: Innovation, Education, Communication, and Implementation. Translating innovation to successful implementation is crucially important and requires high-quality evidence to ensure steps forward to a positive impact on health care when it comes to implementation. The vision of EGS is to provide the best possible well-being and minimal glaucomainduced visual disability in individuals with glaucoma within an affordable healthcare system. In this regard, assessing the changes in glaucoma surgery is a pivotal contribution to better care. As mentioned, this Guide aims to provide answers to the crucial questions above. However, every clinician is aware that answers may differ for every person: an individualised approach is needed. Therefore, there will be no uniform answer for all situations and all patients. Clinicians would need, through the clinical method and possibly some algorithm, to reach answers and decisions at the individual level. In this regard, evidence is needed to support clinicians to make decisions. Of key importance in this Guide is to provide an overview of existing evidence on glaucoma surgery and specifically on recent innovations and novel devices, but also to set standards in surgical design and reporting for future studies on glaucoma surgical innovation. Designing studies in surgery is particularly challenging because of many subtle variations inherent to surgery and hence multiple factors involved in the outcome, but even more because one needs to define carefully outcomes relevant to the research question but also to the future translation into clinical practice. In addition this Guide aims to provide clinical recommendations on novel procedures already in use when insufficient evidence exists. EGS has a long tradition to provide guidance to the ophthalmic community in Europe and worldwide through the EGS Guidelines (now in their 5th Edition). The EGS leadership recognized that the changing environment in glaucoma surgery currently represents a major challenge for the clinician, needing specific guidance. Therefore, the decision was made to issue this Guide on Glaucoma Surgery in order to help clinicians to make appropriate decisions for their patients and also to provide the framework and guidance for researchers to improve the quality of evidence in future studies. Ultimately this Guide will support better Glaucoma Care in accordance with EGS's Vision and Mission. Fotis Topouzis EGS President

Effect of 24-h blood pressure dysregulations and reduced ocular perfusion pressure in open-angle glaucoma progression.

BACKGROUND: Low ocular perfusion pressure (OPP), which depends on the mean arterial pressure (MAP) and intraocular pressure (IOP), is associated with glaucoma. We studied 24-h MAP dysregulations and OPP in relation to the progression of glaucoma damage. METHODS: We retrospectively analyzed 155 normal-tension glaucoma (NTG) and 110 primary open-angle glaucoma (POAG) patients aged 18 years old followed at the University Hospital Leuven with repeated visual field tests ( n  = 7000 measures, including both eyes) who underwent 24-h ambulatory blood pressure monitoring. Twenty-four-hour MAP dysregulations were variability independent of the mean (VIM), and the five lowest dips in MAP readings over 24 h. OPP was the difference between 2/3 of the MAP and IOP. Glaucoma progression was the deterioration of the visual field, expressed as decibel (dB) changes in mean deviation analyzed by applying multivariable linear mixed regression models. RESULTS: The mean age was 68 years (53% were women). High 24-h VIMmap was associated with glaucoma progression in POAG ( P  < 0.001) independently of the 24-h MAP level. The estimated changes in mean deviation in relation to dip MAP measures ranged from -2.84 dB [95% confidence interval (CI) -4.12 to -1.57] to -2.16 dB (95% CI -3.46 to -0.85) in POAG. Reduced OPP along with high variability and dips in MAP resulted in worse mean deviation deterioration. CONCLUSION: The progression of glaucoma damage associates with repetitive and extreme dips in MAP caused by high variability in MAP throughout 24 h. This progression exacerbates if 24-h MAP dysregulations occur along with reduced OPP.

A generalizable deep learning regression model for automated glaucoma screening from fundus images.

A plethora of classification models for the detection of glaucoma from fundus images have been proposed in recent years. Often trained with data from a single glaucoma clinic, they report impressive performance on internal test sets, but tend to struggle in generalizing to external sets. This performance drop can be attributed to data shifts in glaucoma prevalence, fundus camera, and the definition of glaucoma ground truth. In this study, we confirm that a previously described regression network for glaucoma referral (G-RISK) obtains excellent results in a variety of challenging settings. Thirteen different data sources of labeled fundus images were utilized. The data sources include two large population cohorts (Australian Blue Mountains Eye Study, BMES and German Gutenberg Health Study, GHS) and 11 publicly available datasets (AIROGS, ORIGA, REFUGE1, LAG, ODIR, REFUGE2, GAMMA, RIM-ONEr3, RIM-ONE DL, ACRIMA, PAPILA). To minimize data shifts in input data, a standardized image processing strategy was developed to obtain 30° disc-centered images from the original data. A total of 149,455 images were included for model testing. Area under the receiver operating characteristic curve (AUC) for BMES and GHS population cohorts were at 0.976 [95% CI: 0.967-0.986] and 0.984 [95% CI: 0.980-0.991] on participant level, respectively. At a fixed specificity of 95%, sensitivities were at 87.3% and 90.3%, respectively, surpassing the minimum criteria of 85% sensitivity recommended by Prevent Blindness America. AUC values on the eleven publicly available data sets ranged from 0.854 to 0.988. These results confirm the excellent generalizability of a glaucoma risk regression model trained with homogeneous data from a single tertiary referral center. Further validation using prospective cohort studies is warranted.

FundusQ-Net: A regression quality assessment deep learning algorithm for fundus images quality grading.

OBJECTIVE: Ophthalmological pathologies such as glaucoma, diabetic retinopathy and age-related macular degeneration are major causes of blindness and vision impairment. There is a need for novel decision support tools that can simplify and speed up the diagnosis of these pathologies. A key step in this process is to automatically estimate the quality of the fundus images to make sure these are interpretable by a human operator or a machine learning model. We present a novel fundus image quality scale and deep learning (DL) model that can estimate fundus image quality relative to this new scale. METHODS: A total of 1245 images were graded for quality by two ophthalmologists within the range 1-10, with a resolution of 0.5. A DL regression model was trained for fundus image quality assessment. The architecture used was Inception-V3. The model was developed using a total of 89,947 images from 6 databases, of which 1245 were labeled by the specialists and the remaining 88,702 images were used for pre-training and semi-supervised learning. The final DL model was evaluated on an internal test set (n=209) as well as an external test set (n=194). RESULTS: The final DL model, denoted FundusQ-Net, achieved a mean absolute error of 0.61 (0.54-0.68) on the internal test set. When evaluated as a binary classification model on the public DRIMDB database as an external test set the model obtained an accuracy of 99%. SIGNIFICANCE: the proposed algorithm provides a new robust tool for automated quality grading of fundus images.

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.

A randomized clinical trial comparing three fixed combinations of bimatoprost with timolol in patients with open-angle glaucoma or ocular hypertension.

OBJECTIVE: To compare the efficacy and safety of two fixed combination, preservative-free eye drops (bimatoprost 0.01% in combination with either timolol 0.1% or 0.5%) in a gel formulation, with bimatoprost 0.03%/timolol 0.5% in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: Phase II, randomized, investigator-masked, multicenter, 3-arm parallel group (Eudract No. 2017-002823-46). Eighty-six patients aged ≥18 years with OAG or OHT, with intraocular pressure (IOP) initially controlled for at least 6 months by a combination therapy of a dual prostaglandin and timolol or insufficiently controlled by first-line monotherapy were included. Patients were randomized to receive T4030a (bimatoprost 0.01%/timolol 0.1%; N = 29), T4030c (bimatoprost 0.01%/timolol 0.5%; N = 29) or bimatoprost 0.03%/timolol 0.5% (N = 28), administered once daily in the evening for 12 weeks. Primary endpoint was defined as change in IOP from day 1 to week 12 measured at 08:00 (±1 h). Further efficacy, safety and pharmacokinetic endpoints were assessed as secondary outcomes. RESULTS: The mean change in IOP from baseline to week 12 was -9.8 ± 2.1 mmHg for T4030a, -10.1 ± 2.5 mmHg for T4030c and -10.0 ± 2.8 mmHg for bimatoprost 0.03%/timolol 0.5%. All treatments were well tolerated with no safety issues identified in any group. In patients treated with T4030a, the systemic concentration of timolol was significantly lower after 12 weeks than in patients treated with T4030c or bimatoprost 0.03%/timolol0.5%. CONCLUSIONS: These study results suggest that the preservative-free ophthalmic formulation of T4030a (bimatoprost 0.01%/timolol 0.1%) can be regarded as a useful tool in the therapeutic management of OAG and OHT.

Artificial Intelligence Software for Diabetic Eye Screening: Diagnostic Performance and Impact of Stratification.

AIM: To evaluate the MONA.health artificial intelligence screening software for detecting referable diabetic retinopathy (DR) and diabetic macular edema (DME), including subgroup analysis. METHODS: The algorithm's threshold value was fixed at the 90% sensitivity operating point on the receiver operating curve to perform the disease classification. Diagnostic performance was appraised on a private test set and publicly available datasets. Stratification analysis was executed on the private test set considering age, ethnicity, sex, insulin dependency, year of examination, camera type, image quality, and dilatation status. RESULTS: The software displayed an area under the curve (AUC) of 97.28% for DR and 98.08% for DME on the private test set. The specificity and sensitivity for combined DR and DME predictions were 94.24 and 90.91%, respectively. The AUC ranged from 96.91 to 97.99% on the publicly available datasets for DR. AUC values were above 95% in all subgroups, with lower predictive values found for individuals above the age of 65 (82.51% sensitivity) and Caucasians (84.03% sensitivity). CONCLUSION: We report good overall performance of the MONA.health screening software for DR and DME. The software performance remains stable with no significant deterioration of the deep learning models in any studied strata.