Next-generation sequencing-based gene panel tests for the detection of rare variants and hypomorphic alleles associated with primary open-angle glaucoma.

Primary open-angle glaucoma (POAG) is a complex disease with a strong hereditably component. Several genetic variants have recently been associated with POAG, partially due to technological improvements such as next-generation sequencing (NGS). The aim of this study was to genetically analyze patients with POAG to determine the contribution of rare variants and hypomorphic alleles associated with glaucoma as a future method of diagnosis and early treatment. Seventy-two genes potentially associated with adult glaucoma were studied in 61 patients with POAG. Additionally, we sequenced the coding sequence of CYP1B1 gene in 13 independent patients to deep analyze the potential association of hypomorphic CYP1B1 alleles in the pathogenesis of POAG. We detected nine rare variants in 16% of POAG patients studied by NGS. Those rare variants are located in CYP1B1, SIX6, CARD10, MFN1, OPTC, OPTN, and WDR36 glaucoma-related genes. Hypomorphic variants in CYP1B1 and SIX6 genes have been identified in 8% of the total POAG patient assessed. Our findings suggest that NGS could be a valuable tool to clarify the impact of genetic component on adult glaucoma. However, in order to demonstrate the contribution of these rare variants and hypomorphic alleles to glaucoma, segregation and functional studies would be necessary. The identification of new variants and hypomorphic alleles in glaucoma patients will help to configure the genetic identity of these patients, in order to make an early and precise molecular diagnosis.

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.

Classifying glaucoma exclusively with OCT: comparison of three clustering algorithms derived from machine learning.

BACKGROUND/AIMS: To objectively classify eyes as either healthy or glaucoma based exclusively on data provided by peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform (GCIPL) measurements derived from spectral-domain optical coherence tomography (SD-OCT) using machine learning algorithms. METHODS: Three clustering methods (k-means, hierarchical cluster analysis -HCA- and model-based clustering-MBC-) were used separately to classify a training sample of 109 eyes as either healthy or glaucomatous using solely 13 SD-OCT parameters: pRNFL average and sector thicknesses and GCIPL average and minimum values together with the six macular wedge-shaped regions. Then, the best-performing algorithm was applied to an independent test sample of 102 eyes to derive close estimates of its actual performance (external validation). RESULTS: In the training sample, accuracy was 91.7% for MBC, 81.7% for k-means and 78.9% for HCA (p value = 0.02). The best MBC model was that in which subgroups were allowed to have variable volume and shape and equal orientation. The MBC algorithm in the independent test sample correctly classified 98 out of 102 cases for an overall accuracy of 96.1% (95% CI, 92.3-99.8%), with a sensitivity of 94.3 and 100% specificity. The accuracy for pRNFL was 92.2% (95% CI, 86.9-97.4%) and for GCIPL 98.0% (95% CI, 95.3-100%). CONCLUSIONS: Clustering algorithms in general (and MBC in particular) seem promising methods to help discriminate between healthy and glaucomatous eyes using exclusively SD-OCT-derived parameters. Understanding the relative merits of one method over others may also provide insights into the nature of the disease.

One-pot synthesis of bimetallic Fe-Cu metal-organic frameworks composite for the elimination of organic pollutants via peroxymonosulphate activation.

A series of bimetallic of FeCu metal-organic frameworks (MOFs) have been synthesised using a solvothermal process by varying the ratio between the two metals. Further, the bimetallic MOF catalysts were characterised by X-ray powder diffraction, scanning electron microscopy, and infrared spectroscopy techniques. Their catalytic properties for activation of peroxymonosulphate (PMS) have been tested by the removal of a model dye, rhodamine B. As a result, NH2-Fe2.4Cu1-MOF demonstrated the highest degradation, the effect of the ratio NH2-Fe2.4Cu1-MOF/PMS has been studied, and the main reactive species have been assessed. The application of these MOFs in powder form is difficult to handle in successive batch or flow systems. Thus, this study assessed the feasibility of growing NH2-Fe2,4Cu1-MOF on polyacrylonitrile (PAN) spheres using the one-pot solvothermal synthesis method. The optimisation of the catalytic activity of the synthesised composite (NH2-Fe2.4Cu1-MOF@PAN) has been evaluated by response surface methodology using a central composite face-centred experimental design matrix and selecting as independent variables: time, PMS concentration, and catalyst dosage. Based on the results, the optimisation of the operational conditions has been validated. At 2.5 mM PMS, 90 min, and 1.19 g·L-1 of catalyst dosage, maximum degradation (80.92%) has been achieved, which doubles the removal values obtained in previous studies with other MOFs. In addition, under these conditions, the catalyst has been proven to maintain its activity and stability for several cycles without activity loss.

From Waste to Resource: Valorization of Lignocellulosic Agri-Food Residues through Engineered Hydrochar and Biochar for Environmental and Clean Energy Applications-A Comprehensive Review.

Agri-food residues or by-products have increased their contribution to the global tally of unsustainably generated waste. These residues, characterized by their inherent physicochemical properties and rich in lignocellulosic composition, are progressively being recognized as valuable products that align with the principles of zero waste and circular economy advocated for by different government entities. Consequently, they are utilized as raw materials in other industrial sectors, such as the notable case of environmental remediation. This review highlights the substantial potential of thermochemical valorized agri-food residues, transformed into biochar and hydrochar, as versatile adsorbents in wastewater treatment and as promising alternatives in various environmental and energy-related applications. These materials, with their enhanced properties achieved through tailored engineering techniques, offer competent solutions with cost-effective and satisfactory results in applications in various environmental contexts such as removing pollutants from wastewater or green energy generation. This sustainable approach not only addresses environmental concerns but also paves the way for a more eco-friendly and resource-efficient future, making it an exciting prospect for diverse applications.

Nanostructured copper-organic frameworks for the generation of sulphate radicals: application in wastewater disinfection.

In recent years, the presence of pathogens in the environment has become an issue of widespread concern in society. Thus, new research lines have been developed regarding the removal of pathogens and persistent pollutants in water. In this research, the efficacy of nanostructure copper-organic framework, HKUST-1, has been evaluated for its ability to eliminate Escherichia coli and generate sulphate radicals as catalyst for the treatment of effluents with a high microbiological load via peroxymonosulphate (PMS) activation. The disinfection process has been optimized, achieving complete elimination of Escherichia coli growth after 30 min of testing using a concentration of 60.5 mg/L HKUST-1 and 0.1 mM of PMS. To overcome the operational limitations of this system and facilitate its handling and reutilization in a flow disinfection process, HKUST-1 has been efficiently encapsulated on polyacrylonitrile as a novel development that could be scaled up to achieve continuous treatment.

Intravitreal fluocinolone acetonide 0.19 mg (ILUVIEN®) in patients with non-infectious uveitis: real-world effectiveness and safety outcomes at 12 months.

PURPOSE: This study assessed the effectiveness of the 0.19-mg fluocinolone acetonide (FAc) implant by multimodal measurements in patients with non-infectious uveitis (NIU) in a real-world setting in Spain. METHODS: A prospective study of patients who had NIU including uveitic macular oedema (UME) with ≥ 12 months follow-up was done. Exclusion criteria include infectious uveitis and uncontrolled glaucoma or ocular hypertension requiring more than 2 medications. Effectiveness was assessed using a multicomponent outcome measure that included nine outcomes. Effectiveness was defined as all components being met at every timepoint. Secondary outcome measures were onset or progression of glaucoma and investigator-reported adverse events. RESULTS: Twenty-six eyes from 22 patients were included, with 96.2% having an indication including UME. During the 12-month study, the FAc implant was effective in 15 (57.7%) eyes, reaching effectiveness as soon as 2 weeks post-implantation. Mean best-corrected visual acuity and mean central macular thickness (CMT) were significantly improved vs. baseline at all timepoints (all comparisons p < 0.01). During the 12-month study, inflammation markers (anterior chamber cells and vitreous haze) had also significantly declined. Factors predicting effectiveness at month 12 were systemic corticosteroid dose pre-FAc, higher immunomodulatory therapy (IMT) load at baseline and thicker retinal nerve fibre layer (RNFL) at baseline (all p < 0.05). Factors predicting failure were male gender, thinner RNFL at baseline and treatment ineffectiveness at 1 month (all p < 0.05). In parallel, corticosteroid and IMT use also declined significantly. No significant increase in IOP was detected. CONCLUSION: The FAc implant is safe and effective at treating NIU over 12 months in a real-world setting in Spain.

Agreement between Five Experts and the Laguna ONhE Automatic Colourimetric Application Interpreting the Glaucomatous Aspect of the Optic Nerve.

BACKGROUND: Optic nerve head (ONH) interpretation is a glaucoma screening method which may be influenced by criteria variability. Laguna ONhE software is a low-cost and non-invasive method of ONH analysis. METHODS: We analysed the results of the Laguna ONhE application, interpreting 552 ONH images from the ACRIMA database, publicly available on the Internet, and compared them with the opinion of five experts. Diagnostic agreement was investigated using Cohen's kappa (κ) with 95% confidence. RESULTS: The kappa concordance index obtained with Laguna ONhE and the majority of the experts' criterion (0.77) was significantly higher compared to that obtained with ACRIMA and the majority of the experts' criterion (0.61). In 44.7% of the cases there was absolute agreement among the 5 experts and the Laguna ONhE program. Removing borderline cases from the analysis yielded increased diagnostic agreement (0.81). The area under the receiver operating characteristic (AUROC) of the Laguna ONhE program (0.953, p < 0.001) was not significantly different than AUROC of the majority of the experts' criterion (0.925, p < 0.001), p = 0.052. Individually obtained expert's AUROCs were significantly lower (0.636 to 0.913; p < 0.01). CONCLUSIONS: Laguna ONhE's agreement with the experts is high, particularly where the diagnosis may be more obvious by the appearance of the ONH.

Heterogeneous electro-Fenton system using Fe-MOF as catalyst and electrocatalyst for degradation of pharmaceuticals.

In recent years, heterogeneous electro-Fenton processes have gained considerable attention as an alternative to homogeneous processes. In this context, the aim of this study is the use of a commercial iron metal-organic framework (Fe-MOF), Basolite® F-300, as a base material for the design of a heterogeneous electro-Fenton treatment system for the removal of antipyrine. Initially, the catalyst was applied as powder in aqueous solution and three key parameters of the electro-Fenton process (pH, Fe-MOF concentration and current density) were evaluated and optimized by a Central Composite Design Face Centred (CCD-FC) using antipyrine removal and energy consumption as response functions. Near complete antipyrine removal (94%) was achieved under optimal conditions: pH 3, Fe-MOF 157.78 mg/L and current density 6.67 mA/cm2, obtaining an energy consumption of 0.29 W·h per mg of antipyrine removed. Later, two electrocatalysts (Fe-MOF functionalized cathodes), prepared by different Fe-MOF immobilisation approaches (composite of carbon black/polytetrafluoroethylene or by electrospinning on Ni foam), were synthesized. Their characterisation showed notable Fe-MOF incorporation into the material and favourable properties as electrocatalysts. Both Fe-MOF functionalized cathodes were evaluated in the removal of antipyrine at different pH (acidic and natural) and current density (27.78 and 55.56 mA/cm2), achieving in the best conditions removal levels around 80% in 1 h without any operational problems. In addition, several intermediates generated during the treatment were identified and their toxicity estimated. According to the obtained results, the degradation compounds have less toxicity than the parent compounds, confirming the effectiveness of the treatment.

Differential Gene and Protein Expression of Conjunctival Bleb Hyperfibrosis in Early Failure of Glaucoma Surgery.

The early failure of glaucoma surgery is mainly caused by over-fibrosis at the subconjunctival space, causing obliteration of the filtration bleb. Because fibrosis has a suspected basis of genetic predisposition, we have undertaken a prospective study to identify upregulated profibrotic genes in a population of glaucoma patients with signs of conjunctival fibrosis and early postoperative surgical failure. Clinical data of re-operated fibrosis patients, hyperfibrosis patients who re-operated more than once in a short time, and control patients with no fibrosis were recorded and analyzed at each follow-up visit. Conjunctival-Tenon surgical specimens were obtained intraoperatively to evaluate the local expression of a panel of genes potentially associated with fibrosis. In order to correlate gene expression signatures with protein levels, we quantified secreted proteins in primary cultures of fibroblasts from patients. Expression of VEGFA, CXCL8, MYC, and CDKN1A was induced in the conjunctiva of hyperfibrosis patients. VEGFA and IL8 protein levels were also increased in fibroblast supernatants. We propose that an increase in these proteins could be useful in detecting conjunctival fibrosis in glaucoma patients undergoing filtering surgery. Molecular markers could be crucial for early detection of patients at high risk of failure of filtration surgery, leading to more optimal and personalized treatments.

Photocatalytic solid-phase degradation of polyethylene with fluoride-doped titania under low consumption ultraviolet radiation.

Photodegradation of plastic in solid-phase requires the polymer to be composited with an efficient photocatalyst. We report herein the successful synthesis and characterization of fluoride-doped-TiO2 and its applicability, for the first time, on solid-phase photodegradation of polyethylene films. Nearly half weight loss of polyethylene, containing only 2% of the photocatalyst, is eliminated after three weeks of ultraviolet A radiation using a low consumption light emitting diode lamp, defeating previously reported data. The half-life time of the plastic was around 3 weeks, highlighting the viability of this process for real applications. Results were compared to raw PE and PE composite with well-known TiO2, resulting in, respectively, 0 and 26% of weight loss. The degradation process was monitored by optical microscopy, scanning electron microscopy, X-ray diffraction, thermogravimetric analysis, Fourier transform infrared and X-ray photoelectron spectroscopy, which revealed the formation of plastic cracks, loss of polyethylene crystallinity and thus stability, the oxidation of C-H bonds and the oxidized state of the surface compounds during photodegradation. The obtained results open a path for the future production of cleaner and self-photodegradable plastics, where the photocatalyst would be introduced in all the manufactured plastics, making possible the quicker photodegradation of the plastics that end up on the environment and the plastics reaching wastewater treatment plants.

AVASCULAR OVERHANGING BLEB REDUCTION WITH MODIFIED SUTURELESS TECHNIQUE.

A late postoperative trabeculectomy complication could be the overhanging bleb, especially when antimetabolites are used. It can be associated with hypotony, foreign body sensation, dellen, and visual compromise. We report a case of an avascular overhanging bleb successfully reduced with a modified sutureless technique. Nine years before, our patient had trabeculectomy using mitomycin C. After the surgery, the intraocular pressure was correct, without progression in the visual field, but on slit-lamp examination, a large avascular overhanging bleb was noted. Partial excision was performed with dissection from the cornea, overhanging conjunctival trimming, leakage checking and Bandage Contact lens placement. Topical antibiotic and steroid treatment was administered for three weeks. The excised conjunctival histopathology showed avascular metaplastic epithelium. Six months after the surgery, the patient's visual acuity improved, with intraocular pressure of 12 mm Hg and a Seidel negative asymptomatic bleb. In conclusion, this less invasive technique preserves better bleb function without ripping the surrounding ischemic tissue. The procedure is safe and easy to perform, with less surgical time and fast recovery.

GO-TiO2 as a Highly Performant Photocatalyst Maximized by Proper Parameters Selection.

The synthesis and characterization of novel graphene oxide coupled to TiO2 (GO-TiO2) was carried out in order to better understand the performance of this photocatalyst, when compared to well-known TiO2 (P25) from Degussa. Thus, its physical-chemical characterization (FTIR, XRD, N2 isotherms and electrochemical measurements) describes high porosity, suitable charge and high electron mobility, which enhance pollutant degradation. In addition, the importance of the reactor set up was highlighted, testing the effect of both the irradiated area and distance between lamp and bulb solution. Under optimal conditions, the model drug methylthioninium chloride (MC) was degraded and several parameters were assessed, such as the water matrix and the catalyst reutilization, a possibility given the addition of H2O2. The results in terms of energy consumption compete with those attained for the treatment of this model pollutant, opening a path for further research.

Continuous treatment of diethyl hexyl and dibutyl phthalates by fixed-bed reactor: Comparison of two esterase bionanocomposites.

The removal of Diethyl hexyl phthalate (DEHP) and Dibutyl phthalate (DBP) is of great importance due to their potential adverse effects on the environment and human health. In this study, two bionanocomposites prepared by immobilization of Bacillus subtilis esterase by crosslinking to halloysite and supported in chitosan and alginate beads were studied and proposed as a green approach. The esterase immobilization was confirmed by physical-chemical characterization. Bionanocomposite using chitosan showed the best degradation levels in batch tests attaining complete degradation of DBP and around 90% of DEHP. To determine the operational stability and efficiency of the system, two fixed bed reactors filled with both bionanocomposites were carried out operating in continuous mode. Chitosan based bionanocomposite showed the best performance being able to completely remove DBP and more than 85% of DEHP at the different flowrates. These results proved the potential of these synthesized bionanocomposites to effectively remove Phthalic Acid Esters.

Disinfection through Advance Oxidation Processes: Optimization and Application on Real Wastewater Matrices.

Disinfection is an essential and significant process for water treatment to protect the environment and human beings from pathogenic infections. In this study, disinfection through the generation of hydroxyl (Fenton process (FP)) and sulfate (Fenton-like process (FLP)) radicals was validated and optimized. The optimization was carried out in synthetic water through an experimental design methodology using the bacteria Escherichia coli as a model microorganism. Different variables were evaluated in both processes: precursor concentration (peroxymonosulfate (PMS) and H2O2), catalyst concentration (Fe+2), and pH in the Fenton process. After that, the optimized conditions (FP: 132.36 mM H2O2, 0.56 mM Fe+2 and 3.26 pH; FLP: 3.82 mM PMS and 0.40 mM Fe+2) were applied to real matrices from wastewater treatment plants. The obtained results suggest that both processes are promising for disinfection due to the high oxidant power of hydroxyl and sulfate radicals.

External Validation and Clinical Applicability of Two Optical Coherence Tomography-Based Risk Calculators for Detecting Glaucoma.

Purpose: To clinically validate the diagnostic ability of two optical coherence tomography (OCT)-based glaucoma diagnostic calculators (GDCs). Methods: We conducted a retrospective, consecutive sampling of 76 patients with primary open-angle glaucoma, 107 glaucoma suspects, and 67 controls. Demographics, reliable visual field testing, and macular and optic disc OCT were collected. The reference diagnosis was compared against the probability of having glaucoma obtained from two GDCs derived from multivariate logistic regressions using quantitative and qualitative (GDC1) or only quantitative (GDC2) OCT data. The discrimination (area under the curve [AUC]) and calibration (calibration plots) were compared for both calculators and the best OCT parameters. Results: GDC2 was able to identify 46.9% more suspects and 14.7% more glaucomatous eyes than GDC1. Both GDCs obtained the highest discriminative ability in glaucomatous eyes (GDC1 AUC = 0.949; GDC2 = 0.943 vs inferior peripapillary retinal nerve fiber layer [pRNFL] = 0.931; P = 0.43). The discriminating ability was not as good for glaucoma suspects, but the GDCs were not inferior to pRNFL (GDC 1 AUC = 0.739; GDC2 = 0.730; inferior pRNFL = 0.760; P = 0.54) and GDC2 was still able to correctly identify up to 30.8% more cases than the conventional OCT classification. Calibration showed risk underestimation for both groups and calculators, but it was better in GDC2 and in patients with glaucoma. Conclusions: OCT-based calculators showed an excellent diagnostic performance in glaucomatous eyes. GDC2 was able to identify approximately 30% more cases than the conventional pRNFL inferior OCT classification in both groups, suggesting a potential role of these composite scores in clinical practice. Translational Relevance: These OCT-based calculators may improve glaucoma diagnosis in clinical care.

Peroxymonosulphate Activation by Basolite® F-300 for Escherichia coli Disinfection and Antipyrine Degradation.

In this study, the removal of persistent emerging and dangerous pollutants (pharmaceuticals and pathogens) in synthetic wastewater was evaluated by the application of heterogeneous Advanced Oxidation Processes. To do that, a Metal-Organic Framework (MOF), Basolite® F-300 was selected as a catalyst and combined with peroxymonosulfate (PMS) as oxidants in order to generate sulphate radicals. Several key parameters such as the PMS and Basolite® F-300 concentration were evaluated and optimized using a Central Composite Experimental Design for response surface methodology for the inactivation of Escherichia coli. The assessment of the degradation of an analgesic and antipyretic pharmaceutical, antipyrine, revealed that is necessary to increase the concentration of PMS and amount of Basolite® F-300, in order to diminish the treatment time. Finally, the PMS-Basolite® F-300 system can be used for at least four cycles without a reduction in its ability to disinfect and degrade persistent emerging and dangerous pollutants such as pharmaceuticals and pathogens.

Intravitreal anti-vascular endothelial growth factor injections to treat post-trabeculectomy Swan syndrome.

PURPOSE: To report a case of wound neovascularization (Swan syndrome) one year after trabeculectomy favorably treated with two intravitreal ranibizumab injections. OBSERVATIONS: A 79-year-old woman under coumadin treatment for atrial fibrillation experienced relapsing decreased vision in her left eye due to vitreous hemorrhage. She had had a past history of ocular hypertension corneal decompensation after phacoemulsification that required a Descemet Membrane Endothelial Keratoplasty and a subsequent trabeculectomy. After clearance of the hemorrhage, examination showed neovascularization not in the retina but surrounding the sclerostomy wound of the trabeculectomy, being diagnosed as a Swan syndrome. After two intravitreal injections of ranibizumab, gonioscopy showed complete resolution of the new vessels. No further recurrences have been reported and IOP has remained controlled without glaucomatous changes 7 months after the last injection. Clinical features and patient characteristics are described. CONCLUSION AND IMPORTANCE: Anti-vascular endothelial growth factor intravitreal injections may be a good and safe alternative to manage vitreous hemorrhage secondary to wound neovascularization of the trabeculectomy site.

Surgical Approach and Outcomes of Uveitic Glaucoma in a Tertiary Hospital.

AIM AND OBJECTIVE: This study aimed to evaluate the performance of and indication for different surgical techniques in the management of uveitic glaucoma (UG). MATERIALS AND METHODS: A retrospective audit of records of all patients with UG who underwent ≥1 glaucoma surgery, between January 2007 and December 2016. The main outcomes were intraocular pressure (IOP) and the need for antihypertensive medication at each follow-up visit. The total number of surgical interventions needed to control IOP was recorded. Postoperative interventions and complications were analyzed. RESULTS: Forty eyes from 34 patients were assessed. Overall, baseline IOP was 30.7 ± 8.2 mm Hg, and postoperative mean IOP at the last visit was 16.4 ± 2.0 mm Hg, with a mean follow-up of 28 months. Antihypertensive medications were reduced from 2.8 ± 0.8 to 0.8 ± 1.2. During the follow-up, 61.8% of the eyes required only one glaucoma surgery. There was no correlation between the location of uveitis and the total number of glaucoma surgeries required. The greatest IOP reductions were in cases treated with non-penetrating deep sclerectomy (21%), Ahmed valve (23%), and cyclophotocoagulation (CPC) (51%); in cases where an Ahmed implant was the first surgical option, a 43% reduction was achieved. CONCLUSION: Filtering procedures, glaucoma drainage devices, and CPC are all good options for IOP control in UG, but all are prone to failure over time. With respect to IOP reduction, the safety profile, and postoperative care, Ahmed implants and CPC might be the best first surgical option. CLINICAL SIGNIFICANCE: The article highlights the versatility of the surgical techniques required to treat UG, which is one of the most difficult types of glaucoma to manage. HOW TO CITE THIS ARTICLE: Ventura-Abreu N, Mendes-Pereira J, Pazos M, et al. Surgical Approach and Outcomes of Uveitic Glaucoma in a Tertiary Hospital. J Curr Glaucoma Pract 2021;15(2):52-57.