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Introduction A great deal of spatial information is required for the modeling of karstic aquifers, owing to their high degree of heterogeneity. Frequently, however, the only hydrological information available is [...]

Hydropower generation represents an important contribution to meeting the challenges of today's increasing world energy needs. It uses about 44% of water in Europe and it is the main user of water in most OECD countries. However, in most cases, the energy sector is not a water consumer. The largest part of these withdrawals is immediately returned into the environment, being able to be used by other sectors, which is its most prominent characteristic. In order to understand the waterenergy nexus and the challenges that the environment and other water users face, the European Commission proposed the use of water accounts in order to measure the influence of each water user, infrastructure and management decision to the total economic value of water resources in a given basin. In this sense, the SEEA-W is the most well-known approach of hybrid accounting as it provides a standard approach to compare results between different regions. This research analyses hydropower production in the Jucar River Basin (Spain), which is currently water-stressed by consumptive demands, within the SEEA-W approach. The results demonstrate that the SEEA-W approach needs some improvement in order to represent hydropower production properly. [ABSTRACT FROM AUTHOR]

Background: Patients with craniosynostosis are at high risk of developing elevated intracranial pressure (ICP) causing papilledema and secondary optic atrophy. Diagnosing and monitoring optic neuropathy is challenging because of multiple causes of vision loss including exposure keratopathy, amblyopia, and cognitive delays that limit examination. Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are an optical coherence tomography (OCT) finding reported in association with papilledema and optic neuropathy. We investigated the prevalence of PHOMS in patients with syndromic craniosynostosis and the relationship with known risk factors of optic neuropathy., Methods: This was a cross-sectional retrospective study was performed at Boston Children's Hospital and included 118 eyes (60 patients) with syndromic craniosynostosis that had at least one good quality optic nerve OCT volumetry scan between January 2010 and December 2023. Testing was reviewed by 2 neuro-ophthalmologists to determine the presence of PHOMS. Information collected included demographics, and clinical course including possible Chiari malformation, obstructive sleep apnea (OSA), history of elevated ICP, best-corrected visual acuity (VA), spherical equivalent (SE), retinal nerve fiber layer thickness, macular ganglion cell layer volume, and funduscopic examination. Our primary outcome measure was presence of PHOMS, and secondary outcome measure was the relationship between clinical characteristics and the presence of PHOMS., Results: Mean age at imaged OCT was 9.8 ± 5.2 years and 41/60 (68.3%) patients were female. The prevalence of PHOMS was 17/60 patients (28.3%) or 26/118 eyes (22.0%), higher than previously reported in children without craniosynostosis (P < 0.001). PHOMS were significantly associated with a history of elevated ICP (odds ratio [OR] 14.4, 95% CI: 1.9-111.0, P < 0.001) and with concurrent papilledema (OR 40.4, 95% CI: 6.6-248.0, P < 0.001). OSA, Chiari malformation, best-corrected VA, craniosynostosis variant, and SE were not independently associated with PHOMS., Conclusions: Eyes in children with craniosynostosis had a higher prevalence of PHOMS than reported in children without craniosynostosis. PHOMS were significantly more common with a history of elevated ICP and with concurrent papilledema. PHOMS may serve as a clinically useful indicator of optic neuropathy, and of recurrence of papilledema in patients with craniosynostosis and in other populations characterized by multiple sources of vision loss and cognitive changes that limit evaluation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2025 by North American Neuro-Ophthalmology Society.)

Background: Topiramate is often considered as a second-line medication for the treatment of pseudotumor cerebri syndrome (PTCS), but limited studies exist that evaluate its efficacy in children., Methods: Retrospective study of patients aged <21 years with PTCS who were treated with topiramate alone or in combination with acetazolamide was performed. Data regarding clinical courses and visual outcomes were recorded., Results: A total of 46 patients were identified. Three (6.5%) patients were treated with topiramate alone, 31 (67.4%) transitioned to topiramate from acetazolamide, and 12 (26.1%) took both topiramate and acetazolamide concurrently. The median time to resolution of papilledema on topiramate was 0.57 years (interquartile range 0.32 to 0.84). Among eyes with papilledema graded on the Frisen scale at topiramate initiation, 40 of 57 (70.2%) were grade 1, nine of 57 (15.8%) were grade 2, and eight of 57 (14.0%) were grade 3. Twenty-seven of 46 (58.7%) reported headache improvement after starting topiramate. The mean dose of topiramate was 1.3 ± 0.8 mg/kg/day. The most common side effect was patient report of cognitive slowing (10 of 46 [21.7%]). All patients on topiramate monotherapy who were compliant with treatment and follow-up had resolution of papilledema with no evidence of visual function loss., Conclusions: Topiramate can effectively treat PTCS in children with mild to moderate papilledema or in those unable to tolerate acetazolamide. More research is needed to assess the efficacy of topiramate for higher grade papilledema., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Anecdotal experience raised the possibility that semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA) with rapidly increasing use, is associated with nonarteritic anterior ischemic optic neuropathy (NAION)., Objective: To investigate whether there is an association between semaglutide and risk of NAION., Design, Setting, and Participants: In a retrospective matched cohort study using data from a centralized data registry of patients evaluated by neuro-ophthalmologists at 1 academic institution from December 1, 2017, through November 30, 2023, a search for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code H47.01 (ischemic optic neuropathy) and text search yielded 16 827 patients with no history of NAION. Propensity matching was used to assess whether prescribed semaglutide was associated with NAION in patients with type 2 diabetes (T2D) or overweight/obesity, in each case accounting for covarying factors (sex, age, systemic hypertension, T2D, obstructive sleep apnea, obesity, hyperlipidemia, and coronary artery disease) and contraindications for use of semaglutide. The cumulative incidence of NAION was determined with the Kaplan-Meier method and a Cox proportional hazards regression model adjusted for potential confounding comorbidities. Data were analyzed from December 1, 2017, through November 30, 2023., Exposures: Prescriptions for semaglutide vs non-GLP-1 RA medications to manage either T2D or weight., Main Outcomes and Measures: Cumulative incidence and hazard ratio of NAION., Results: Among 16 827 patients, 710 had T2D (194 prescribed semaglutide; 516 prescribed non-GLP-1 RA antidiabetic medications; median [IQR] age, 59 [49-68] years; 369 [52%] female) and 979 were overweight or obese (361 prescribed semaglutide; 618 prescribed non-GLP-1 RA weight-loss medications; median [IQR] age, 47 [32-59] years; 708 [72%] female). In the population with T2D, 17 NAION events occurred in patients prescribed semaglutide vs 6 in the non-GLP-1 RA antidiabetes cohort. The cumulative incidence of NAION for the semaglutide and non-GLP-1 RA cohorts over 36 months was 8.9% (95% CI, 4.5%-13.1%) and 1.8% (95% CI, 0%-3.5%), respectively. A Cox proportional hazards regression model showed higher risk of NAION for patients receiving semaglutide (hazard ratio [HR], 4.28; 95% CI, 1.62-11.29); P < .001). In the population of patients who were overweight or obese, 20 NAION events occurred in the prescribed semaglutide cohort vs 3 in the non-GLP-1 RA cohort. The cumulative incidence of NAION for the semaglutide vs non-GLP-1 RA cohorts over 36 months was 6.7% (95% CI, 3.6%-9.7%) and 0.8% (95% CI, 0%-1.8%), respectively. A Cox proportional hazards regression model showed a higher risk of NAION for patients prescribed semaglutide (HR, 7.64; 95% CI, 2.21-26.36; P < .001)., Conclusions and Relevance: This study's findings suggest an association between semaglutide and NAION. As this was an observational study, future study is required to assess causality.

Background: Peripapillary hyperreflective ovoid mass-like structures (PHOMS) are a recently defined optical coherence tomography (OCT) finding. The purpose of this study was to characterize the presence of PHOMS and their visual significance in pediatric patients with and without optic nerve pathologies., Methods: This retrospective study evaluated 400 patients (<18 years of age) including normal control subjects and patients with optic neuritis, papillitis, optic nerve head drusen (ONHD), and papilledema. Information on demographics, visual function, and structural parameters were obtained., Results: PHOMS were found in 7 of 258 normal control eyes (2.7%), 9 of 59 eyes with optic neuritis (15.3%), 58 of 76 eyes with ONHD (76.3%), 3 of 11 eyes with papillitis (27.3%), and 180 of 308 eyes with papilledema (58.4%). PHOMS were more prevalent in the papilledema (P < 0.001), ONHD (P < 0.001), and optic neuritis (P = 0.028) eyes than in control eyes. We identified 5 cases where PHOMS developed de novo. This occurred over an average of 2.3 years (range, 0.2-7.4 years). Sixteen cases of PHOMS resolved over an average of 1.1 years (range, 0.3-4.0 years). Cross-sectionally, PHOMS were not associated with visual acuity (P = 0.551), retinal nerve fiber layer thickness (P = 0.068), ganglion cell volume (P = 0.375), or visual field mean deviation (P = 0.795)., Conclusions: PHOMS are present in a majority of children with papilledema or ONHD. PHOMS are dynamic and may form de novo over time with optic nerve pathology and may resolve either through treatment or atrophy. There was no relationship between the presence of PHOMS and poor visual function in our study cohort., (Copyright © 2024 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)

Background: Although cupping of the optic nerve is classically a sign of glaucomatous optic neuropathy, it has been shown that cupping can sometimes occur after an episode of optic neuritis (ON). The purpose of this study was to compare cupping in patients after ON from multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and to investigate the relationship between cupping and retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thinning., Methods: This was a retrospective cohort involving patients (≥18 years) with ON from 3 institutions. Patients were eligible if they had optical coherence tomography (Cirrus, OCT) performed ≥6 months after a single unilateral ON. The amount of thinning and cupping was estimated from the difference in the OCT parameters between affected and unaffected eyes. Univariable and multivariable regressions were used to investigate the relationship between cupping and ON etiology. Pearson correlation was used to investigate the relationship between cupping and RNFL and GCC., Results: Eighty-six subjects (MS: 35, NMOSD: 26, and MOGAD: 25) were included. There was no significant difference in gender and race between the groups, and most patients (86.1%) were female. Patients with NMOSD were significantly older than patients with MS or MOGAD (P = 0.002). In the univariate model, cupping was significantly higher in the NMOSD group (P = 0.017); however, after adjusting for age, GCC, and RNFL of the affected eye, the difference was no longer statistically significant (P = 0.949). The correlation between cupping asymmetry and RNFL and GCC of the affected eye was inversely strong in patients with MS (R = -0.60 and R = -0.64, respectively), inversely moderate in patients with MOGAD (R = -0.34 and R = -0.40, respectively), and weak in patients with NMOSD (R = -0.03 and R = -0.17, respectively)., Conclusions: Our results demonstrated that cupping after ON is correlated with RNFL and GCC thinning; although cupping was overall greater in the NMOSD group, once adjusted for age, RNFL, and GCC, it did not differ among patients with MS, NMOSD, and MOGAD., Competing Interests: A. D. Henderson reports a relationship with Horizon Therapeutics/Amgen; E. P. Flanagan reports NIH Grant R01NS113828; and J. J. Chen reports a consultant relationship with Horizon and UCB. The remaining authors report no conflicts of interest., (Copyright © 2024 by North American Neuro-Ophthalmology Society.)

Purpose: Cerebral venous sinus thrombosis (CVST) is a rare but life-threatening event with significant neurologic and visual morbidity. In this study, we report on the natural history and visual outcomes of papilledema in children with CVST., Design: Retrospective case series., Methods: Patients with CVST evaluated by the Department of Ophthalmology between 2000 and 2023 were included. Records were reviewed for presence and course of papilledema, treatment, and final visual outcomes following papilledema resolution., Results: The study included 35 patients with a mean age of 9 ± 5 years and 40% were female. The most common risk factors for CVST were infection (69%), dehydration (26%), and hypercoagulability (23%). 31 patients (89%) had papilledema. Of these patients, 9 (29%) had progression of papilledema despite treatment, 17 patients (55%) did not have progression, and 5 patients (16%) lacked follow-up records. Initial Frisén grade among all cases was 2 ± 1, and cases with progression reached a grade of 4 ± 1 between 10 and 32 days following initial identification. Most patients (97%) were treated with anticoagulation and 100% required acetazolamide and/or lumbar puncture. Among 26 patients with follow-up, papilledema resolved in 107 ± 128 days. Fifty-four percent of patients had permanent ophthalmic sequelae. An initial Frisén grade ≥3 (odds ratio 7.54, 95% confidence interval 6.53-8.70, P< .001) was significantly associated with eventual optic atrophy., Conclusions: Children with CVST are at high risk for ophthalmologic sequelae. Papilledema can progress despite appropriate therapy. Our results highlight the importance of ophthalmologic follow-up during treatment course to prevent irreversible vision loss., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Choroidal abnormalities (CAs) visualized on near-infrared reflectance (NIR) imaging are a new diagnostic criterion for neurofibromatosis type 1 (NF1), but the association between the presence of CAs and visual function remains unknown. This study evaluated the relationship between visual acuity (VA) with the presence, number, or total area of CAs visualized by NIR in children with NF1-associated optic pathway gliomas (NF1-OPGs)., Methods: Patients (<18 years) enrolled in a prospective longitudinal study of children with NF1-associated OPGs from 3 institutions were eligible if they had optical coherence tomography (OCT) of the macula (Heidelberg Spectralis) with ≥1 year of follow-up. The central 30° NIR images were reviewed by 2 neuro-ophthalmologists who manually calculated the number and total area of CAs. VA (logMAR) was measured using a standardized protocol. Cross-sectional associations of presence, number, and total area of CAs with VA, retinal nerve fiber layer thickness (RNFL), and ganglion cell-inner plexiform layer thickness were evaluated at the first and most recent visits using regression models. Intereye correlation was accounted for using generalized estimating equations., Results: Eighty-two eyes of 41 children (56% female) were included. The mean ± SD age at the first OCT was 10.1 ± 3.3 years, with a mean follow-up of 20.4 ± 7.2 months. At study entry, CAs were present in 46% of eyes with a mean number of 2.1 ± 1.7 and a mean total area of 2.0 ± 1.7 mm 2 per eye. At the most recent follow-up, CAs were present in 48% of eyes with a mean number of 2.2 ± 1.8 lesions and a mean total area of 2.3 ± 2.1 mm 2 per eye. Neither VA nor OCT parameters at first and follow-up visits were associated with the presence, number, or total area of CAs (all P > 0.05)., Conclusions: CAs are prevalent but not ubiquitous, in children with NF1-OPGs. Although CAs are a diagnostic criterion for NF1, their presence and size do not appear to be associated with visual function., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by North American Neuro-Ophthalmology Society.)

Craniosynostosis (CS) or the premature fusion of one or more cranial sutures in utero , or during the first years of life, can present in isolation or as a multisystem clinical disorder with a particular impact on visual function. Among ophthalmic complications, optic neuropathy is a significant cause of irreversible vision loss in these patients. Children with CS are at higher risk of developing elevated intracranial pressure which can lead to papilledema and, ultimately, optic atrophy. In addition, sometimes associated obstructive sleep apnea, abnormalities in central nervous system venous development, and Chiari malformation may contribute to optic neuropathy. Ophthalmologists have an important role in managing a number of coexistent ophthalmologic complications such as strabismus, anisometropia, amblyopia, ptosis, and exposure keratopathy in addition to maintaining surveillance for early signs of optic neuropathy; they play a critical consultative role contributing to the decision for primary or repeat decompressive surgery. In this article, we aim to review the etiology, diagnostic approach, and management of optic neuropathies in patients with craniosynostosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Estrela and Dagi.)

Background: Optic disc drusen (ODD) are calcified deposits in the prelaminar portion of the optic nerve head. Although often asymptomatic, these deposits can cause progressive visual field defects and vision loss. The purpose of this study was to evaluate rates of functional loss in eyes with ODD and to investigate risk factors associated with rates of visual field progression., Methods: This was a retrospective cohort study including 65 eyes of 43 patients with ODD from the Duke Ophthalmic Registry. All eyes had at least 12 months of follow-up and at least 3 reliable standard automated perimetry (SAP) tests. Linear mixed models were used to estimate rates of SAP mean deviation (MD) loss over time. Univariable and multivariable models were used to assess the effect of clinical variables and intraocular pressure (IOP) on rates of change., Results: Subjects were followed for an average of 7.6 ± 5.3 years. The mean rate of SAP MD change was -0.23 ± 0.26 dB/year, ranging from -1.19 to 0.13 dB/year. Fifty-seven eyes (87.7%) had slow progression (slower than -0.5 dB/year), 6 eyes (9.2%) had moderate progression (between -0.5 dB/year and -1 dB/year), and 2 eyes (3.1%) had fast progression (faster than -1 dB/year). In multivariable models, older age and worse SAP MD at baseline were significantly associated with faster rates of change. Mean IOP was not associated with faster rates of MD change in both univariable and multivariable analyses., Conclusions: Most eyes with ODD had slow rates of visual field loss over time. Age and baseline severity were significantly associated with faster rates of visual field loss., Competing Interests: T. Estrela, A. A. Jammal, and M. El-Dairi have no conflicts of interest to report. F. A. Medeiros reports the following: Aerie Pharmaceuticals, Allergan, Annexon, Biogen, Carl Zeiss Meditec, Galimedix, Google Inc., Heidelberg Engineering, nGoggle Inc., Novartis, Stealth Biotherapeutics, Reichert, Genentech, Stuart Therapeutics., (Copyright © 2023 by North American Neuro-Ophthalmology Society.)

Purpose: To evaluate the effect of intraocular pressure (IOP) on the rates of macular thickness (ganglion cell layer [GCL] and ganglion cell-inner plexiform layer [GCIPL]) change over time measured by spectral-domain (SD) OCT., Design: Retrospective cohort study., Participants: Overall, 451 eyes of 256 patients with primary open-angle glaucoma., Methods: Data were extracted from the Duke Ophthalmic Registry, a database of electronic medical records of patients observed under routine clinical care at the Duke Eye Center, and satellite clinics. All records from patients with a minimum of 6 months of follow-up and at least 2 good-quality Spectralis SD-OCT macula scans were included. Linear mixed models were used to investigate the relationship between average IOP during follow-up and rates of GCL and GCIPL thickness change over time., Main Outcome Measures: The effect of IOP on the rates of GCL and GCIPL thickness loss measured by SD-OCT., Results: Eyes had a mean follow-up of 1.8 ± 1.3 years, ranging from 0.5 to 10.2 years. The average rate of change for GCL thickness was -0.220 μm/year (95% confidence interval [CI], -0.268 to -0.172 μm/year) and for GCIPL thickness was -0.231 μm/year (95% CI, -0.302 to -0.160 μm/year). Each 1-mmHg higher mean IOP during follow-up was associated with an additional loss of -0.021 μm/year of GCL thickness (P = 0.001) and -0.032 μm/year of GCIPL thickness (P = 0.001) after adjusting for potentially confounding factors, such as baseline age, disease severity, sex, race, central corneal thickness, and follow-up time., Conclusions: Higher IOP was significantly associated with faster rates of GCL and GCIPL loss over time measured by SD-OCT, even during relatively short follow-up times. These findings support the use of SD-OCT GCL and GCIPL thickness measurements as structural biomarkers for the evaluation of the efficacy of IOP-lowering therapies in slowing down the progression of glaucoma., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2023 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare the performance of the 10-2 test versus 24-2 standard automated perimetry (SAP) test for the diagnosis of glaucoma using OCT as an independent standard for glaucomatous damage., Design: Cross-sectional study., Participants: A total of 1375 pairs of 10-2 and 24-2 SAP tests from 569 eyes of 339 subjects were used for the analysis. A total of 440 (77%) eyes had a diagnosis of glaucoma, and 129 (23%) eyes were normal. All participants underwent 10-2 and 24-2 SAP tests within 30 days., Methods: Glaucomatous severity was quantified based on OCT macula ganglion cell layer (mGCL) and circumpapillary retinal nerve fiber layer. The area under the receiver operating characteristic (ROC) curve (AUC) was used to compare 10-2 and 24-2 metrics for discriminating healthy eyes from those of glaucoma, at different levels of disease severity., Main Outcome Measures: Areas under the ROC curves and sensitivities at fixed specificities of 80% and 95%., Results: The overall AUC for mean deviation (MD) for the 24-2 test (0.808) was significantly higher than that of the 10-2 test (0.742; P < 0.001). When compared at different stages of the disease, the 24-2 test performed generally better than the 10-2 test, notably in the earlier stages of the disease. For early damage (first quartile), the 24-2 MD had an AUC of 0.658 versus 0.590 for 10-2 MD (P = 0.018). For advanced damage (fourth quartile), corresponding values were 0.954 vs. 0.903 (P = 0.013). Similar trends were observed when glaucoma severity was defined based on structural macular damage with mGCL thickness., Conclusions: The 24-2 SAP test had better diagnostic accuracy compared with that of the 10-2 test for detecting equivalent levels of glaucomatous damage, as measured by quantitative assessment of retinal nerve fiber layer and macula by OCT., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare self-reported quality-of-life (QoL) outcomes of patients diagnosed as normal, glaucoma suspect, and glaucoma based on an objective reference standard for glaucomatous optic neuropathy (GON)., Design: Cross-sectional study., Participants: 1884 eyes of 1019 patients were included in the study., Methods: The data was sourced from the Duke Glaucoma Registry. Eyes were classified according to the presence and topographic correspondence of functional and structural damage, as assessed by parameters from standard automated perimetry (SAP) and spectral-domain OCT (SD-OCT). The objective diagnosis of the worse eye was used to define patient-level diagnosis. To assess QoL in the diagnostic groups, 14 unidimensional vision-related items of the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) were used to assess QoL in the diagnostic groups. Association between NEI VFQ-25 Rasch-calibrated scores and diagnostic groups was assessed through multivariable regression that controlled for confounding demographic and socioeconomic variables such as age, sex, race, income, marriage status, insurance status, and highest education level., Main Outcome Measures: NEI VFQ-25 Rasch scores compared with objective criteria diagnosis based on SAP mean deviation (MD) and SD-OCT retinal nerve fiber layer (RNFL) thickness., Results: Overall, eyes classified as normal, glaucoma suspect, and glaucoma had decreasing mean scores in SAP MD (0.2 ± 1.0 dB, -0.9 ± 2.4 dB, -6.2 ± 7.0 dB, respectively; P < 0.001) and SD-OCT RNFL thickness (97.8 ± 9.5 μm, 89.0 ± 13.1 μm, 64.5 ± 12.8 μm, respectively; P < 0.001). The mean Rasch-calibrated NEI VFQ-25 score was significantly different among normal, suspect, and glaucoma groups (82.9 ± 13.0, 78.2 ± 14.8, and 72.6 ± 16.2, respectively; P < 0.001). When adjusted for confounding socioeconomic variables, glaucoma patients had significantly worse QoL than those classified as normal (β = -6.8 Rasch score units; P < 0.001)., Conclusion: A glaucoma diagnosis, based on an objective reference standard for GON, was significantly associated with worse Rasch-adjusted scores of QoL. Utilization of such objective criteria may provide clinically relevant metrics with potential to improve comparability of research findings and validation of newly proposed diagnostic tools., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate rates of structural and functional change in a large clinical population of glaucoma and glaucoma suspect patients., Design: Retrospective cohort., Methods: Twenty-nine thousand five hundred forty-eight spectral-domain optical coherence tomography (OCT) and 19,812 standard automated perimetry (SAP) tests from 6138 eyes of 3669 patients with ≥6 months of follow-up, 2 good quality spectral-domain OCT peripapillary retinal nerve fiber layer scans, and 2 reliable SAP tests were included. Data were extracted from the Duke Glaucoma Registry, a large database of electronic health records of patients from the Duke Eye Center and satellite clinics. Rates of change for the 2 metrics were obtained using linear mixed models, categorized according to pre-established cutoffs, and analyzed according to the severity of the disease., Results: Average rates of change were -0.73 ± 0.80 μm per year for global retinal nerve fiber layer thickness and -0.09 ± 0.36 dB per year for SAP mean deviation. More than one quarter (26.6%) of eyes were classified as having at least a moderate rate of change by spectral-domain OCT vs 9.1% by SAP (P < .001). In eyes with severe disease, 31.6% were classified as progressing at moderate or faster rates by SAP vs 26.5% by spectral-domain OCT (P = .055). Most eyes classified as fast by spectral-domain OCT were classified as slow by SAP and vice versa., Conclusion: Although most patients under routine care had slow rates of progression, a substantial proportion had rates that could potentially result in major losses if sustained over time. Both structural and functional tests should be used to monitor glaucoma, and spectral-domain OCT still has a relevant role in detecting fast progressors in advanced disease., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: To investigate the impact of intraocular pressure (IOP) control on rates of change of spectral-domain OCT (SD-OCT) retinal nerve fiber layer (RNFL) thickness in a large clinical population., Design: Retrospective cohort study., Participants: A total of 85 835 IOP measurements and 60 223 SD-OCT tests from 14 790 eyes of 7844 patients., Methods: Data were extracted from the Duke Glaucoma Registry, a large database of electronic medical records of patients with glaucoma and suspected disease followed over time at the Duke Eye Center and satellite clinics. All records from patients with a minimum of 6 months of follow-up and at least 2 good-quality SD-OCT scans and 2 clinical visits with Goldmann applanation tonometry were included. Eyes were categorized according to the frequency of visits with IOP below cutoffs of 21 mmHg, 18 mmHg, and 15 mmHg over time. Rates of change for global RNFL thickness were obtained using linear mixed models and classified as slow if change was slower than -1.0 μm/year; moderate if between -1.0 and -2.0 μm/year; and fast if faster than -2.0 μm/year. Multivariable models were adjusted for age, gender, race, diagnosis, central corneal thickness, follow-up time, and baseline disease severity., Main Outcome Measures: Rates of change in SD-OCT RNFL thickness according to levels of IOP control., Results: Eyes had a mean follow-up of 3.5±1.9 years. Average rate of change in RNFL thickness was -0.68±0.59 μm/year. Each 1 mmHg higher mean IOP was associated with 0.05 μm/year faster RNFL loss (P < 0.001) after adjustment for potentially confounding variables. For eyes that had fast progression, 41% of them had IOP <21 mmHg in all visits during follow-up, whereas 20% of them had all visits with IOP <18 mmHg, but only 9% of them had all visits with IOP <15 mmHg., Conclusions: Intraocular pressure was significantly associated with rates of progressive RNFL loss in a large clinical population. Eyes with stricter IOP control over follow-up visits had a smaller chance of exhibiting fast deterioration. Our findings may assist clinicians in establishing target pressures in clinical practice., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: The rule of 5 is a simple rule for detecting retinal nerve fiber layer (RNFL) change on spectral-domain OCT (SD-OCT), in which a loss of 5 μm of global RNFL on a follow-up test is considered evidence of significant change when compared with the baseline. The rule is based on short-term test-retest variability of SD-OCT and is often used in clinical practice. The purpose of this study was to compare the rule of 5 with trend-based analysis of global RNFL thickness over time for detecting glaucomatous progression., Design: Prospective cohort., Participants: A total of 300 eyes of 210 glaucoma subjects followed for an average of 5.4±1.5 years with a median of 11 (interquartile range, 7-14) visits., Methods: Trend-based analysis was performed by ordinary least-squares (OLS) linear regression of global RNFL thickness over time. For estimation of specificity, false-positives were obtained by assessing for progression on series of randomly permutated follow-up visits for each eye, which removes any systematic trend over time. The specificity of trend-based analysis was matched to that of the rule of 5 to allow meaningful comparison of the "hit rate," or the proportion of glaucoma eyes categorized as progressing at each time point, using the original sequence of visits., Main Outcome Measures: Comparison between hit rates of trend-analysis versus rule of 5 at matched specificity., Results: After 5 years, the simple rule of 5 identified 37.5% of eyes as progressing at a specificity of 81.1%. At the same specificity, the hit rate for trend-based analysis was significantly greater than that of the rule of 5 (62.9% vs. 37.5%; P < 0.001). If the rule of 5 was required to be repeatable on a consecutive test, specificity improved to 93.4%, but hit rate decreased to 21.0%. At this higher specificity, trend-based analysis still had a significantly greater hit rate than the rule of 5 (47.4% vs. 21.0%, respectively; P < 0.001)., Conclusions: Trend-based analysis was superior to the simple rule of 5 for identifying progression in glaucoma eyes and should be preferred as a method for longitudinal assessment of global SD-OCT RNFL change over time., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

PRéCIS:: In this study, asymmetries in corneal hysteresis (CH) between eyes of glaucoma patients were significantly associated with asymmetries in rates of visual field loss, suggesting a role of hysteresis as a risk factor for disease progression., Purpose: The purpose of this study was to investigate the relationship between asymmetries in rates of glaucoma progression and asymmetries of corneal properties between eyes of subjects with primary open-angle glaucoma., Participants and Methods: This prospective study followed 126 binocular subjects with glaucoma for an average of 4.3±0.8 years. CH was measured at baseline using the Ocular Response Analyzer. Standard automated perimetry (SAP) and intraocular pressure were measured at baseline and every 6 months. Rates of visual field progression were calculated using ordinary least square regression of SAP mean deviation (MD) values over time for each eye. Eyes were defined as "better" and "worse" based on the slopes of SAP MD. Pearson correlation test, and univariable and multivariable regression models were used to investigate the relationship between inter-eye asymmetry in CH and central corneal thickness and inter-eye differences in rates of visual field progression., Results: Only asymmetry of CH was significantly associated with the asymmetry in SAP MD rates of change between eyes (r=0.22; P=0.01). In a multivariable model adjusting for age, race, central corneal thickness, mean intraocular pressure and baseline disease severity, CH asymmetry remained significantly associated with asymmetric progression (P=0.032)., Conclusion: CH asymmetry between eyes was associated with asymmetry on rates of visual field change, providing further support for the role of CH as a risk factor for glaucoma progression.

Purpose: To compare the diagnostic performance of human gradings vs predictions provided by a machine-to-machine (M2M) deep learning (DL) algorithm trained to quantify retinal nerve fiber layer (RNFL) damage on fundus photographs., Design: Evaluation of a machine learning algorithm., Methods: An M2M DL algorithm trained with RNFL thickness parameters from spectral-domain optical coherence tomography was applied to a subset of 490 fundus photos of 490 eyes of 370 subjects graded by 2 glaucoma specialists for the probability of glaucomatous optical neuropathy (GON), and estimates of cup-to-disc (C/D) ratios. Spearman correlations with standard automated perimetry (SAP) global indices were compared between the human gradings vs the M2M DL-predicted RNFL thickness values. The area under the receiver operating characteristic curves (AUC) and partial AUC for the region of clinically meaningful specificity (85%-100%) were used to compare the ability of each output to discriminate eyes with repeatable glaucomatous SAP defects vs eyes with normal fields., Results: The M2M DL-predicted RNFL thickness had a significantly stronger absolute correlation with SAP mean deviation (rho=0.54) than the probability of GON given by human graders (rho=0.48; P < .001). The partial AUC for the M2M DL algorithm was significantly higher than that for the probability of GON by human graders (partial AUC = 0.529 vs 0.411, respectively; P = .016)., Conclusion: An M2M DL algorithm performed as well as, if not better than, human graders at detecting eyes with repeatable glaucomatous visual field loss. This DL algorithm could potentially replace human graders in population screening efforts for glaucoma., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To assess short- and long-term variability on standard automated perimetry (SAP) and spectral domain optical coherence tomography (SD-OCT) in glaucoma., Design: Prospective cohort., Methods: Ordinary least squares linear regression of SAP mean deviation (MD) and SD-OCT global retinal nerve fiber layer (RNFL) thickness were fitted over time for sequential tests conducted within 5 weeks (short-term testing) and annually (long-term testing). Residuals were obtained by subtracting the predicted and observed values, and each patient's standard deviation (SD) of the residuals was used as a measure of variability. Wilcoxon signed-rank test was performed to test the hypothesis of equality between short- and long-term variability., Results: A total of 43 eyes of 43 glaucoma subjects were included. Subjects had a mean 4.5 ± 0.8 SAP and OCT tests for short-term variability assessment. For long-term variability, the same number of tests were performed and results annually collected over an average of 4.0 ± 0.8 years. The average SD of the residuals was significantly higher in the long-term than in the short-term period for both tests: 1.05 ± 0.70 dB vs. 0.61 ± 0.34 dB, respectively (P < 0.001) for SAP MD and 1.95 ± 1.86 μm vs. 0.81 ± 0.56 μm, respectively (P < 0.001) for SD-OCT RNFL thickness., Conclusions: Long-term variability was higher than short-term variability on SD-OCT and SAP. Because current event-based algorithms for detection of glaucoma progression on SAP and SD-OCT have relied on short-term variability data to establish their normative databases, these algorithms may be underestimating the variability in the long-term and thus may overestimate progression over time., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This study describes a segmentation-free deep learning (DL) algorithm for measuring retinal nerve fibre layer (RNFL) thickness on spectral-domain optical coherence tomography (SDOCT). The study included 25,285 B-scans from 1,338 eyes of 706 subjects. Training was done to predict RNFL thickness from raw unsegmented scans using conventional RNFL thickness measurements from good quality images as targets, forcing the DL algorithm to learn its own representation of RNFL. The algorithm was tested in three different sets: (1) images without segmentation errors or artefacts, (2) low-quality images with segmentation errors, and (3) images with other artefacts. In test set 1, segmentation-free RNFL predictions were highly correlated with conventional RNFL thickness (r = 0.983, P < 0.001). In test set 2, segmentation-free predictions had higher correlation with the best available estimate (tests with good quality taken in the same date) compared to those from the conventional algorithm (r = 0.972 vs. r = 0.829, respectively; P < 0.001). Segmentation-free predictions were also better in test set 3 (r = 0.940 vs. r = 0.640, P < 0.001). In conclusion, a novel segmentation-free algorithm to extract RNFL thickness performed similarly to the conventional method in good quality images and better in images with errors or other artefacts.

The Water Framework Directive 2000/60/EC implemented by the European Union established as the main objectives to achieve a "good ecological and chemical status" of the surface water and a "good quantitative and chemical status" of groundwater bodies. One of the major pressures affecting water bodies comes from the use of pesticides and their potential presence in the water ecosystems. For this purpose, the reliable determination of pesticides and their transformation products (TPs) in natural waters (both surface and groundwater) is required. The high number of compounds potentially reaching the aquatic environment makes extraordinary difficult, if not impossible, to investigate all these compounds even using the most powerful analytical techniques. Among these, liquid chromatography coupled to high-resolution mass spectrometry is emphasized due to its strong potential for detection and identification of many organic contaminants thanks to the accurate-mass full spectrum acquisition data. This work focuses on wide-scope screening of many pesticides and their TPs in surface water and groundwater samples, collected between March and May 2017, in the Júcar River Hydrographical Basin, Spain. For this purpose, a home-made database containing more than 500 pesticides and TPs was employed. Analyses performed by liquid chromatography coupled to quadrupole-time of flight mass spectrometry (LC-QTOF MS) allowed the identification of up to 27 pesticides and 6 TPs. The most detected compounds in groundwater were the herbicides atrazine, simazine, terbuthylazine, and their TPs (atrazine-desethyl, terbumeton-desethyl and terbuthylazine-desethyl). Regarding surface water, the fungicides carbendazim, thiabendazole and imazalil, the herbicide terbutryn and the TP terbumeton-desethyl were also detected. These results illustrate the wide use of these compounds (in the present or in the recent past) in the area under study and the vulnerability of the water bodies, and are in accordance with previous findings in other water bodies of the different Spanish Hydrographic systems., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Droughts are one of the gravest natural threats currently existing in the world and their occurrence and intensity might be exacerbated in the coming years due to climate change. The severe impacts that droughts cause to inland water resources and to the associated socio-economic activities justify the continuous monitoring of the drought. The case study presented shows a practical application of a distributed drought monitoring system implemented in a real river basin district, the Júcar River Basin District (43,000km 2 ), where drought periods of marked intensity have occurred historically and the climate ranges from humid in the north to semiarid in the south. Five drought indices have been applied: Standardised Precipitation Index (SPI) for meteorological drought; Palmer Drought Severity Index (PDSI) and a new soil moisture index (HI), for edaphic drought; Normalised Difference Vegetation Index (NDVI) for the vegetation activity; and Spanish Status Index (SI), for the operational drought. All indices are standardised to compare them. The relationship between the standardised operational drought index SI and the long-term meteorological indices, SPI-12 or SPI-24, show that in a medium size basin the concept of "prolonged drought" required by the European Commission under the Water Framework Directive could be defined by the use of accumulated precipitation indices. The number of months to be accumulated depends on the size of the basin and the water management system properties. In large basins, such as the Júcar river basin (22,000km 2 ), there are significant deviations due to the spatial distribution of the drought. The use of a unique aggregated indicator could hide a significant drought in a specific area, or on the other hand show a non-real drought. Evolution of drought indices for each water management system must be accompanied by spatially distributed drought maps to better understand the drought status and its evolution., (Copyright © 2017 Elsevier B.V. All rights reserved.)

When the regime of a river is not perennial, there are four main difficulties with the use of hydrographs for assessing hydrological alteration: i) the main hydrological features relevant for biological communities are not quantitative (discharges) but qualitative (phases such as flowing water, stagnant pools or lack of surface water), ii) stream flow records do not inform on the temporal occurrence of stagnant pools, iii) as most of the temporary streams are ungauged, their regime has to be evaluated by alternative methods such as remote sensing or citizen science, and iv) the biological quality assessment of the ecological status of a temporary stream must follow a sampling schedule and references adapted to the flow- pool-dry regime. To overcome these challenges within an operational approach, the freely available software tool TREHS has been developed within the EU LIFE TRIVERS project. This software permits the input of information from flow simulations obtained with any rainfall-runoff model (to set an unimpacted reference stream regime) and compares this with the information obtained from flow gauging records (if available) and interviews with local people, as well as instantaneous observations by individuals and interpretation of ground-level or aerial photographs. Up to six metrics defining the permanence of water flow, the presence of stagnant pools and their temporal patterns of occurrence are used to determine natural and observed river regimes and to assess the degree of hydrological alteration. A new regime classification specifically designed for temporary rivers was developed using the metrics that measure the relative permanence of the three main phases: flow, disconnected pools and dry stream bed. Finally, the software characterizes the differences between the natural and actual regimes, diagnoses the hydrological status (degree of hydrological alteration), assesses the significance and robustness of the diagnosis and recommends the best periods for biological quality samplings., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Water planning and the Integrated Water Resources Management (IWRM) represent the best way to help decision makers to identify and choose the most adequate alternatives among other possible ones. The System of Environmental-Economic Accounting for Water (SEEA-W) is displayed as a tool for the building of water balances in a river basin, providing a standard approach to achieve comparability of the results between different territories. The target of this paper is to present the building up of a tool that enables the combined use of hydrological models and water resources models to fill in the SEEA-W tables. At every step of the modelling chain, we are capable to build the asset accounts and the physical water supply and use tables according to SEEA-W approach along with an estimation of the water services costs. The case study is the Jucar River Basin District (RBD), located in the eastern part of the Iberian Peninsula in Spain which as in other many Mediterranean basins is currently water-stressed. To guide this work we have used PATRICAL model in combination with AQUATOOL Decision Support System (DSS). The results indicate that for the average year the total use of water in the district amounts to 15,143hm(3)/year, being the Total Water Renewable Water Resources 3909hm(3)/year. On the other hand, the water service costs in Jucar RBD amounts to 1634 million € per year at constant 2012 prices. It is noteworthy that 9% of these costs correspond to non-conventional resources, such as desalinated water, reused water and water transferred from other regions., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Intensive groundwater development is a common circumstance in semiarid and arid areas. Often abstraction exceeds recharge, thus continuously depleting reserves. There is groundwater mining when the recovery of aquifer reserves needs more than 50years. The MASE project has been carried out to compile what is known about Spain and specifically about the south-eastern Iberian Peninsula and the Canary Islands. The objective was the synthetic analysis of available data on the hydrological, economic, managerial, social, and ethical aspects of groundwater mining. Since the mid-20th century, intensive use of groundwater in south-eastern Spain allowed extending and securing the areas with traditional surface water irrigation of cash crops and their extension to former dry lands, taking advantage of good soils and climate. This fostered a huge economic and social development. Intensive agriculture is a main activity, although tourism plays currently an increasing economic role in the coasts. Many aquifers are relatively high yielding small carbonate units where the total groundwater level drawdown may currently exceed 300m. Groundwater storage depletion is estimated about 15km(3). This volume is close to the total contribution of the Tagus-Segura water transfer, but without large investments paid for with public funds. Seawater desalination complements urban supply and part of cash crop cultivation. Reclaimed urban waste water is used for irrigation. Groundwater mining produces benefits but associated to sometimes serious economic, administrative, legal and environmental problems. The use of an exhaustible vital resource raises ethical concerns. It cannot continue under the current legal conditions. A progressive change of water use paradigm is the way out, but this is not in the mind of most water managers and politicians. The positive and negative results observed in south-eastern Spain may help to analyse other areas under similar hydrogeological conditions in a less advanced stage of water use evolution., (Copyright © 2016 Elsevier B.V. All rights reserved.)

One of the major difficulties in water planning is to determine the water availability in a water resource system in order to distribute water sustainably. In this paper, we analyze the key issues for determining the exploitable water resources as an indicator of water availability in a Mediterranean river basin. Historically, these territories are characterized by heavily regulated water resources and the extensive use of unconventional resources (desalination and wastewater reuse); hence, emulating the hydrological cycle is not enough. This analysis considers the Jucar River Basin as a case study. We have analyzed the different possible combinations between the streamflow time series, the length of the simulation period and the reliability criteria. As expected, the results show a wide dispersion, proving the great influence of the reliability criteria used for the quantification and localization of the exploitable water resources in the system. Therefore, it is considered risky to provide a single value to represent the water availability in the Jucar water resource system. In this sense, it is necessary that policymakers and stakeholders make a decision about the methodology used to determine the exploitable water resources in a river basin., (Copyright © 2014 Elsevier B.V. All rights reserved.)

This paper describes two different GIS models - one stationary (GeoImpress) and the other non-stationary (Patrical) - that assess water quantity and quality in the Júcar River Basin District, a large river basin district (43,000km(2)) located in Spain. It aims to analyze the status of surface water (SW) and groundwater (GW) bodies in relation to the European Water Framework Directive (WFD) and to support measures to achieve the WFD objectives. The non-stationary model is used for quantitative analysis of water resources, including long-term water resource assessment; estimation of available GW resources; and evaluation of climate change impact on water resources. The main results obtained are the following: recent water resources have been reduced by approximately 18% compared to the reference period 1961-1990; the GW environmental volume required to accomplish the WFD objectives is approximately 30% of the GW annual resources; and the climate change impact on water resources for the short-term (2010-2040), based on a dynamic downscaling A1B scenario, implies a reduction in water resources by approximately 19% compared to 1990-2000 and a reduction of approximately 40-50% for the long-term (2070-2100), based on dynamic downscaling A2 and B2 scenarios. The model also assesses the impact of various fertilizer application scenarios on the status of future GW quality (nitrate) and if these future statuses will meet the WFD requirements. The stationary model generates data on the actual and future chemical status of SW bodies in the river basin according to the modeled scenarios and reflects the implementation of different types of measures to accomplish the Urban Waste Water Treatment Directive and the WFD. Finally, the selection and prioritization of additional measures to accomplish the WFD are based on cost-effectiveness analysis., (Copyright © 2012 Elsevier B.V. All rights reserved.)