The efficacy of adjunctive mitomycin C and/or anti-VEGF agents on glaucoma tube shunt drainage device surgeries: a systematic review.

PURPOSE: The effectiveness of mitomycin C (MMC) in trabeculectomy has long been established. The aim of this review is to evaluate the efficacy and safety of adjunctive agents in tube shunt drainage device surgery for glaucoma or ocular hypertension, since controversy still exists regarding their benefit. METHODS: We searched CENTRAL, PubMed, Embase, Web of Science, Scopus, and BASE for RCTs, which have used adjuvant antimetabolites-either MMC or 5-Fluorouracil (5-FU)-and/or anti-vascular endothelial growth factors (anti-VEGF) agents. The main outcome was IOP reduction at 12 months. RESULTS: Ten studies met our inclusion criteria. Nine used the Ahmed Glaucoma Valve (AGV) implant, while the double-plate Molteno implant was used in one study. Four studies used MMC. The remaining six studies used an anti-VEGF drug - either bevacizumab, ranibizumab or conbercept. Only one MMC-study reported a significant difference in the IOP reduction between groups at 12 months, favouring the MMC group (55% and 51%; p < 0.01). A significant difference was also reported by two out of five bevacizumab-studies, both favouring the bevacizumab group (55% and 51%, p < 0.05; 58% and 27%, p < 0.05), with the highest benefit seen in neovascular glaucoma cases, especially when panretinal photocoagulation (PRP) was also used. Neither ranibizumab nor conbercept were found to produce significant differences between groups regarding IOP reduction. CONCLUSION: There is no high-quality evidence to support the use of MMC in tube shunt surgery. As for anti-VEGF agents, specifically bevacizumab, significant benefit seems to exist in neovascular glaucoma patients, especially if combined with PRP.

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.

Management of ocular arterial ischemic diseases: a review.

PURPOSE: To summarize the existing treatment options regarding central retinal artery occlusion (CRAO), branch retinal artery occlusion (BRAO), arteritic anterior ischemic optic neuropathy (AAION), non-arteritic anterior ischemic optic neuropathy (NAION), and ocular ischemic syndrome (OIS), proposing an approach to manage and treat these patients. METHODS: A systematic literature search of articles published since 1st January 2010 until 31st December 2020 was conducted using MEDLINE (PubMed), Scopus, and Web of Science. Exclusion criteria included case reports, non-English references, articles not conducted in humans, and articles not including diagnostic or therapeutic options. Further references were gathered through citation tracking, by hand search of the reference lists of included studies, as well as topic-related European society guidelines. RESULTS: Acute ocular ischemia, with consequent visual loss, has a variety of causes and clinical presentations, with prognosis depending on an accurate diagnosis and timely therapeutic implementation. Unfortunately, most of the addressed entities do not have a standardized management, especially regarding their treatment, which often lacks good quality evidence on whether it should or not be used to treat patients. CONCLUSION: Ophthalmologic signs and symptoms may be a warning sign of cardiovascular or cerebrovascular events, namely stroke. Most causes of acute ocular ischemia do not have a standardized management, especially regarding their treatment. Timely intervention is essential to improve the visual, and possibly vital, prognosis. Awareness must be raised among non-ophthalmologist clinicians that might encounter these patients. Further research should focus on assessing the benefit of the management strategies already being employed .

Metabolomic profiling of aqueous humor from glaucoma patients - The metabolomics in surgical ophthalmological patients (MISO) study.

Glaucoma is still a poorly understood disease with a clear need for new biomarkers to help in diagnosis and potentially offer new therapeutic targets. We aimed to determine if the metabolic profile of aqueous humor (AH) as determined by nuclear magnetic resonance (NMR) spectroscopy allows the distinction between primary open-angle glaucoma patients and control subjects, and to distinguish between high-tension (POAG) and normal-tension glaucoma (NTG). We analysed the AH of patients with POAG, NTG and control subjects (n = 30/group). 1H NMR spectra were acquired using a 400 MHz spectrometer. Principle component analysis (PCA), machine learning algorithms and descriptive statistics were applied to analyse the metabolic variance between groups, identify the spectral regions, and hereby potential metabolites that can act as biomarkers for glaucoma. According to PCA, fourteen regions of the NMR spectra were significant in explaining the metabolic variance between the glaucoma and control groups, with no differences found between POAG and NTG groups. These regions were further used in building a classifier for separating glaucoma from control patients, which achieved an AUC of 0.93. Peak integration was performed on these regions and a statistical analysis, after false discovery rate correction and adjustment for the different perioperative topical drug regimen, revealed that five of them were significantly different between groups. The glaucoma group showed a higher content in regions typical for betaine and taurine, possibly linked to neuroprotective mechanisms, and also a higher content in regions that are typical for glutamate, which can indicate damaged neurons and oxidative stress. These results show how aqueous humor metabolomics based on NMR spectroscopy can distinguish glaucoma patients from controls with a high accuracy. Further studies are needed to validate these results in order to incorporate them in clinical practice.

Optical Coherence Tomography Angiography in Glaucoma: A Review.

BACKGROUND: Glaucoma is the leading cause of irreversible blindness worldwide. Several techniques exist for the diagnosis and follow-up of patients. Optical coherence tomography (OCT) angiography (OCTA) is a recently developed technique that provides a quantitative assessment of the microcirculation of the retina and choroid in a fast, noninvasive way. Despite it being a novel technique, several publications have already been done in the glaucoma field. However, a summary of findings is currently lacking. AIMS: To perform a literature review to assess the role of OCTA in glaucoma diagnosis and follow-up. METHODS: A database search was carried out using MEDLINE, Embase, and Web of Science, including all original works registered until July 23, 2017. RESULTS: OCTA (1) has a high repeatability and reproducibility, (2) has good discriminatory power to differentiate normal eyes from glaucoma eyes, (3) is more strongly correlated with visual function than conventional OCT, (4) has good discriminatory power to differentiate early-glaucoma eyes from normal eyes (i.e., at least equal to that of OCT), (5) reaches a floor effect at a more advanced disease stage than OCT, and (6) is able to detect progression in glaucoma eyes. CONCLUSION: OCTA shows potential to become a part of everyday glaucoma management.

Clinical Metabolomics and Glaucoma.

Glaucoma is one of the leading causes of irreversible blindness worldwide. However, there are no biomarkers that accurately help clinicians perform an early diagnosis or detect patients with a high risk of progression. Metabolomics is the study of all metabolites in an organism, and it has the potential to provide a biomarker. This review summarizes the findings of metabolomics in glaucoma patients and explains why this field is promising for new research. We identified published studies that focused on metabolomics and ophthalmology. After providing an overview of metabolomics in ophthalmology, we focused on human glaucoma studies. Five studies have been conducted in glaucoma patients and all compared patients to healthy controls. Using mass spectrometry, significant differences were found in blood plasma in the metabolic pathways that involve palmitoylcarnitine, sphingolipids, vitamin D-related compounds, and steroid precursors. For nuclear magnetic resonance spectroscopy, a high glutamine-glutamate/creatine ratio was found in the vitreous and lateral geniculate body; no differences were detected in the optic radiations, and a lower N-acetylaspartate/choline ratio was observed in the geniculocalcarine and striate areas. Metabolomics can move glaucoma care towards a personalized approach and provide new knowledge concerning the pathophysiology of glaucoma, which can lead to new therapeutic options.

Peripapillary Retinoschisis in Glaucoma: A Systematic Review.

PRCIS: Peripapillary retinoschisis may bias optical coherence tomography's monitoring of glaucoma progression. Its impact on glaucoma still remains uncertain. Only two out of the ten included studies illustrated a correlation between peripapillary retinoschisis and glaucoma progression. PURPOSE: The frequent use of optical coherence tomography increased the detection of peripapillary retinoschisis, which poses challenges in the follow-up of glaucoma patients. This systematic review aims to summarize the literature regarding peripapillary retinoschisis in glaucoma, exploring its prevalence, impact on disease, and clinical management implications. METHODS: We searched PubMed, Embase, Web of Science and Scopus with tailored search queries for each platform. All studies had to report peripapillary retinoschisis in glaucoma patients. Exclusion criteria included studies with less than 10 eyes, studies focusing on schisis outside the disc area, with concomitant retinal or optic nerve lesions, with animals, reviews, studies written in non-English language and congress abstracts. RESULTS: Ten studies were included, of which 7 were case-control, one was a cohort study and two were case series.Six studies showed that peripapillary retinoschisis often overlapped pre-existing retinal nerve fiber layer defects. One study reported that the de novo development of peripapillary retinoschisis was more frequent in eyes with glaucoma progression than in eyes without progression.Visual field findings were inconsistent, with just one study (out of six) showing that glaucoma patients with peripapillary retinoschisis experienced faster visual field deterioration than those without it. Overall, solely two studies (out of seven) associated peripapillary retinoschisis with faster glaucoma progression. CONCLUSIONS: Peripapillary retinoschisis biases optical coherence tomography analysis in glaucoma. Caution is needed against overestimation of retinal nerve fiber layer thickness when peripapillary retinoschisis develops, and misinterpretation of its resolution as rapid progression. Peripapillary retinoschisis' exact impact on glaucoma progression remains unclear.

Nationwide consensus on quality indicators to assess glaucoma care: A modified Delphi approach.

PURPOSE: Performance assessments are essential to tracking and improving quality in health care systems. Key aspects of the care process that act as indicators must be measured in order to gain an in-depth understanding of a care unit's operation. Without standardized quality indicators (QIs), it is difficult to characterize and compare the abilities of institutions to achieve excellence. The aim of this study is to reach a consensus among glaucoma specialists concerning the development of a set of QIs to assess the performance of glaucoma care units. METHODS: A two-round Delphi technique was performed among glaucoma specialists in Portugal, using a 7-point Likert scale. Fifty-three initial statements (comprising process, structure, and outcome indicators) were evaluated and participants had to agree on which ones would be part of the final set of QIs. RESULTS: By the end of both rounds, 28 glaucoma specialists reached consensus on 30/53 (57%) statements, including 19 (63%) process indicators (mainly relating to the proper implementation of complementary exams and the setting of follow-up intervals), 6 (20%) structure indicators, and 5 (17%) outcome indicators. Of the indicators that were part of the final list, functional and structural aspects of glaucoma progression and the availability of surgical/laser procedures were the most prevalent. CONCLUSIONS: A set of 30 QIs for measuring the performance of glaucoma units was developed using a consensus methodology involving experts in the field. Their use as measurement standards would provide important information about unit operations and allow further implementation of quality improvements.

Predictors of Glaucoma After Pediatric Cataract Surgery.

PRCIS: Glaucoma after pediatric cataract surgery is common and challenging. Age at surgery and the presence of microcornea or other anterior segment (AS) abnormalities can be used to identify those at greatest risk. OBJECTIVE: To establish risk factors for developing glaucoma after pediatric cataract surgery [glaucoma following cataract surgery (GFCS)]. METHODS: Single-center, retrospective, longitudinal study of patients who underwent lensectomy for pediatric cataracts from 2008 to 2020. Included eyes presented with congenital or acquired pediatric cataracts or an anterior form of persistent fetal vasculature, and a follow-up of at least 1 year. Exclusion criteria were the presence of preexisting intraocular pressure elevation, congenital glaucoma, syndromic cataracts, and a history of trauma or uveitis. Demographic and clinical data were collected. Our primary outcome was the development of GFCS. Multivariable logistic regression with generalized estimating equations was used to model the association between potential predictors and the risk of GFCS. RESULTS: A total of 110 eyes from 74 patients were included, 38 with unilateral and 36 with bilateral pediatric cataract surgery. The average surgery age was 24.71 ± 37.26 months, with 74 eyes (67.3%) undergoing surgery ≤12 weeks of age. Patients were followed for 9.96 ± 3.64 years after surgery. Twenty-eight eyes (25.45%) developed GFCS, all requiring glaucoma surgery. In multivariable analysis, surgery before 12 weeks of age [odds ratio (OR): 34.74; P < 0.001], presence of microcornea (OR: 12.90; P = 0.002), and presence of other AS abnormalities (OR: 52.71; P < 0.001) were significantly associated with the development of GFCS. CONCLUSIONS: The development of GFCS is a common and relevant adverse event after pediatric cataract surgery whose management is challenging. Age at surgery, the presence of microcornea, and the presence of other AS abnormalities can be used to identify those at greatest risk.

The natural history of untreated ocular hypertension and glaucoma.

Glaucoma is a chronic, progressive disease leading to irreversible blindness if left untreated; however, since reducing intraocular pressure has proven to be successful in slowing disease progression, little is known about the natural history of untreated glaucoma. This knowledge can be valuable in guiding management decisions in the era of personalized medicine. A systematic search was performed in Medline (PubMed), Embase, and Web of Science in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRIMSA) guidelines. The rate of structural and/or functional progression and conversion to glaucoma or to a more advanced stage of glaucoma are discussed for ocular hypertension and different types of open-angle glaucoma. Forty-three studies were included. Different rates of progression were found both among and within the different diagnostic groups that belong to the open-angle glaucoma spectrum. The highest rate was found in pseudoexfoliation glaucoma, followed by high tension glaucoma, normal tension glaucoma, and ocular hypertension, in decreasing order. The lowest rate was observed in glaucoma suspects. The known rates of progression provide valuable prognostic information for ophthalmologists and patients. Nonetheless, due to high variability among patients, individual progression cannot be accurately predicted and repeated follow-up examinations are required to estimate individual progression.

[Evaluation of the Manchester Triage System in Patients with Acute Primary Angle Closure Attack: A Retrospective Study]. / Avaliação do Sistema de Triagem de Manchester em Doentes com Crise de Encerramento Agudo Primário do Ângulo Iridocorneano: Um Estudo Retrospetivo.

INTRODUCTION: Acute primary angle closure attack is an ophthalmological emergency. The aim of this study was to describe the cases diagnosed in the Emergency Department, by correlating the initial complaint with the Manchester triage level and ultimately the time needed until ophthalmological evaluation and iridotomy. MATERIAL AND METHODS: Retrospective analysis of the electronic medical records of patients with acute primary angle closure attack that attended the Ophthalmology Emergency Department of our tertiary center between January 2010 and December 2020. Overall, 2228 Emergency Department episodes coded with the diagnoses glaucoma or ocular hypertension were retrieved, followed by screening of each episode for correct identification of true acute primary angle closure attacks. Clinical data was gathered, including Manchester triage level, presenting complaint, intraocular pressure at presentation, first medical specialty that observed the patient, time until observation by Ophthalmology and time until laser iridotomy. RESULTS: Among the 120 patients identified, 84 (70%) were female and the mean age was 68 ± 12 years. Mean intraocular pressure at admission was 53.4 ± 12.4 mmHg, and 9.2% of patients presented only non-ocular complaints, while 9.2% presented mixed complaints (ocular and non-ocular). Most patients (68.1%) with only non-ocular or mixed complaints were triaged to a non-ophthalmologist (p < 0.001). Concerning the triage system, at admission, most patients (66.7%) were labelled yellow (urgent), while 9.2% and none were labelled as orange (very urgent) or red (emergent), respectively. Most patients (83.3%) were directly sent to Ophthalmology (properly triaged), while the remaining were incorrectly assigned to a non-ophthalmologist. Median time until observation by Ophthalmology was 49 minutes in the properly triaged group (min. 15, max. 404), while it was 288 minutes (min. 45, max. 871) in those who were incorrectly triaged (p < 0.001). Likewise, median time until treatment with laser iridotomy was 203 minutes in the properly triaged group (min. 22, max. 1440) and 353 minutes in the incorrectly triaged group (min.112, max. 947) (p < 0.001). CONCLUSION: Most patients with acute primary angle closure attack were not properly triaged according to the level of the Manchester triage system. There was a significant delay in the diagnosis and treatment of those patients who were first assigned to non-ophthalmologists. There is a need to raise awareness regarding the presenting signs and symptoms of an acute primary angle closure attack in order to avoid preventable vision loss.

Introdução: A crise de encerramento agudo primário do ângulo iridocorneano é uma emergência oftalmológica. O objetivo deste estudo foi descrever os casos admitidos no Serviço de Urgência do Centro Hospitalar Universitário São João, correlacionando a queixa inicial com o nível de triagem de Manchester atribuído e o tempo até observação por Oftalmologia e realização de iridotomia. Material e Métodos: Análise retrospetiva dos registos clínicos dos doentes com encerramento agudo primário do ângulo, admitidos no Serviço de Urgência entre janeiro de 2010 e dezembro de 2020. Foram revistos 2228 episódios com diagnóstico de glaucoma ou hipertensão ocular para identificação correta dos casos de crise de encerramento do ângulo. Foram extraídas variáveis, nomeadamente o nível de triagem de Manchester atribuído, queixa principal, pressão intraocular à admissão, especialidade responsável pelo primeiro contacto médico e tempos até observação por Oftalmologia e até iridotomia. Resultados: Foram identificados 120 doentes, 84 (70%) do sexo feminino, com idade média de 68 ± 12 (desvio padrão) anos. A pressão intraocular média à admissão foi de 53,4 ± 12,4 mmHg. Em 9,2% dos doentes a queixa principal foi não-ocular, enquanto 9,2% apresentavam queixas não-oculares e oculares associadas. A maioria (68,1%) dos doentes com queixas não-oculares ou mistas foi triada para um não-oftalmologista. Segundo o sistema de triagem, a maioria (66,7%) dos doentes foi triada com nível amarelo (urgente), 9,2% foram triados com laranja (muito urgente) e nenhum vermelho (emergente). O primeiro especialista a observar os doentes após a triagem foi um oftalmologista em 83,3% dos casos (corretamente triados), enquanto os restantes foram inicialmente observados por outra especialidade. O tempo mediano até observação por Oftalmologia foi de 288 minutos (min. 45, máx. 871) num doente incorretamente triado e 49 minutos (min. 15, máx. 404) (p < 0,001) em doentes corretamente triados. O tempo mediano até realização de iridotomia laser foi de 353 minutos (min. 112, máx. 947) nos doentes incorretamente triados e 203 minutos (min. 22, máx. 1440) nos corretamente triados (p < 0,001). Conclusão: A maioria dos doentes com crise de encerramento agudo primário do ângulo iridocorneano não foi triada de acordo com o grau de prioridade apropriado segundo o sistema de triagem de Manchester. Nos doentes que não foram imediatamente seguidos por Oftalmologia verificou-se um atraso significativo no diagnóstico e início do tratamento. Torna-se premente a consciencialização dos profissionais de saúde sobre esta condição clínica e a otimização do processo de triagem para minimizar a perda de visão.

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.

Comparison of Trabeculectomy Outcomes Performed by Residents in Training and Ophthalmologists.

PRCIS: Resident-performed trabeculectomies present higher intraocular pressure and lower complete success rate at 1 year. PURPOSE: To compare the 1-year outcomes of ab externo trabeculectomy between residents in training and staff ophthalmologists. PATIENTS AND METHODS: This retrospective study included all consecutive eyes submitted to ab externo trabeculectomy between January 2015 to June 2020. A 1-year complete success rate was considered using all the following criteria: intraocular pressure (IOP)≤21 mm Hg and ≥6mm Hg without ocular hypotensive medications; IOP reduction≥30%; without loss of light perception, phthisis bulbi, and further glaucoma surgery (excluding suture lysis and bleb needling). RESULTS: One hundred and ten eyes from 99 patients were included. Thirty percent (n=33) of the trabeculectomies were performed by residents. There were no significant preoperative differences between groups, apart from age at surgery, which was higher in the residents' group (72.39±6.83 vs. 62.00±15.07 years, P<0.001), and visual field index (Humphrey Field Analyzer), which was lower in the ophthalmologists' group (51.81±34.74% vs. 32.04±33.83%, P=0.013). IOP at 1-, 3-, 6 months, and 1 year after surgery was significantly higher in the resident's group (P<0.05). Resident-performed trabeculectomies achieved a significantly lower complete success rate when compared with the ophthalmologists' group (39.39% vs. 64.94%, P=0.013). The overall rate of the postoperative complications and reintervention did not differ between groups, but the occurrence of a shallow anterior chamber was more frequent in the residents' group (15.15% vs. 4.05%, P=0.037). CONCLUSIONS: Resident-performed trabeculectomies present significantly higher postoperative IOP levels and a lower complete success rate when compared with staff ophthalmologists. It is, therefore, fundamental to adopt strategies to change this gap, improve patient safety, and strengthen resident confidence.

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.

Effect of Repeated Intravitreal Injections in Glaucoma Spectrum Diseases.

Purpose: To evaluate whether repeated intravitreal injections (IVI) with an anti-vascular endothelial growth factor (anti-VEGF) agent are associated with glaucomatous progression in eyes with glaucoma spectrum diseases (GSD). Methods: Single-center, retrospective, longitudinal study of patients with bilateral and similar GSD who: (1) received ≥8 IVI in only one eye during the study period; (2) had ≥2 retinal nerve fiber layer thickness (RNFL) measurements obtained by spectral-domain optical coherence tomography (SD-OCT) at least 12 months apart. The primary outcome was the absolute RNFL thickness change, comparing injected and fellow uninjected eyes. Linear mixed effects models were constructed, including a multivariable model. Results: Sixty-eight eyes from 34 patients were included, 34 injected and 34 fellow uninjected eyes. Average baseline age was 67.68±21.77 years with a follow-up of 3.66±1.89 years and 25.12±14.49 IVI. RNFL thickness decreased significantly from 80.92±15.78 to 77.20±17.35 µm (p<0.001; -1.18±1.93 µm/year) in injected eyes and from 79.95±17.91 to 76.61±17.97 µm (p<0.001; -1.07±0.98 µm/year) in uninjected eyes. In a multivariable linear mixed model of injected eyes, only higher baseline RNFL thickness (p < 0.001) significantly predicted higher absolute RNFL thickness loss. Neither absolute RNFL thickness variation (p=0.716) nor RNFL rate (p=0.779) was significantly different between paired injected and uninjected eyes. Absolute IOP variation was not significantly different between groups (16.62±4.77 to 15.09±4.34 mmHg in injected eyes and 17.68±5.01 to 14.50±3.39 mmHg in fellow uninjected eyes; p=0.248). The proportion of eyes receiving glaucoma medical treatment increased significantly in both groups (55.9% to 76.5% in injected eyes; p=0.039; 58.8% to 76.5% in uninjected eyes; p = 0.031). The number of glaucoma medications also increased significantly in both groups (1.03±1.11 to 1.59±1.18 glaucoma medications in injected eyes; p=0.003; 1.09±1.11 to 1.56±1.19 glaucoma medications in uninjected eyes; p=0.003). Conclusion: Repeated IVI do not seem to accelerate glaucomatous progression. Future studies with a longer follow-up are needed.

Optical coherence tomography angiography changes in cardiovascular systemic diseases and risk factors: A Review.

Cardiovascular (CV) disease (CVD) is the main cause of death around the world, and assessing a patient's CV risk factors (CVRF) can play a major role in its prevention. Since it has been shown that retinal vascular alterations may reflect several systemic processes such as CVRF, we conducted a systematic review in order to summarize which ocular microvasculature changes can be found using Optical Coherence Tomography Angiography (OCTA) in patients without ocular diseases and with systemic pathologies/conditions that affect the CV system when compared to healthy subjects. We searched on online databases, namely PubMed, Scopus, Cochrane and Web of Science, and obtained additional studies through citation tracking. Case reports and review articles were excluded. A total of 47 articles were included in our review. We describe that patients with hypertension, diabetes mellitus, kidney disease, preeclampsia, coronary artery disease, carotid artery stenosis and obstructive sleep apnoea syndrome have, in general, lower retinal and choroidal Vessel Density (VD) and Length (VL), as well as an increased foveal avascular zone area and perimeter. Additionally, several characteristics and/or conditions in healthy subjects, such as smoking status, hyper or hypoxia conditions, race, among others, are also related to ocular vascular changes and should be accounted for. We concluded that OCTA could be a useful tool to assess a patient's CV risk profile in a non-invasive way, possibly integrating the diagnostic and prognostic algorithms of the most prevalent CV diseases in the future.

Effect of Prior Phacoemulsification Surgery in Trabeculectomy Surgery Outcomes.

PURPOSE: To evaluate whether previous clear-cornea phacoemulsification surgery affects the surgical outcomes of trabeculectomy in open-angle glaucoma (OAG). METHODS: We performed a retrospective cohort study, which included 82 patients with OAG that underwent trabeculectomy between January 1, 2010, and December 31, 2017. The primary outcome was the probability of surgical failure. Failure was defined as IOP >21 mmHg or reduced <20% from baseline, IOP ≤5 mmHg in three consecutive visits, need for further glaucoma surgery, phthisis or loss of light perception vision due to glaucoma. RESULTS: Eighty-two eyes (58 phakic and 24 pseudophakic) were included. Phakic group patients were younger than those in the pseudophakic group, 65.8 ± 11.7 vs 76.2 ± 7.9 years (p < 0.001). The most common type of glaucoma was primary OAG [59% (n = 34) phakic vs 63% (n = 15) pseudophakic], followed by exfoliative and pigmentary glaucomas. The mean preoperative IOP was not significantly different between groups nor was the number of preoperative hypotensive medications. The rate of surgical failure was not significantly different between groups at year 1 [17% (n = 10) phakic vs 29% (n = 7) pseudophakic; p = 0.361] nor at year 2 [28% (n = 16) phakic vs 46% (n = 11) pseudophakic; p = 0.110]. No significant differences were observed regarding the postoperative IOP or any secondary outcome measures at year 1 or 2. CONCLUSION: Previous clear-cornea phacoemulsification surgery does not lead to statistically significant differences in the rate of trabeculectomy failure. Despite not being significant, clinically relevant differences were observed between groups. Future studies with a larger sample and/or randomized are needed to clarify this association.

Bilateral Episcleral Corkscrew Vessels: Expedition into the Unknown - Case Report.

We aim to report a case of a middle-aged woman with bilateral idiopathic elevated episcleral venous pressure (IEEVP) and its difficulties in the diagnostic approach. Particularly in this case, the atypical feature of ocular hypertension without glaucomatous optic nerve damage may be misleading. We present a 66-year-old woman with longstanding bilateral "red eyes." Clinical findings included bilateral episcleral vessel engorgement and tortuosity and raised intraocular pressure with open iridocorneal angles. Despite ocular hypertension, glaucomatous neuropathy was absent and confirmed by normal structural (optical coherence tomography) and functional (standard automated perimetry) tests. The systemic workup was unremarkable. Magnetic resonance angiography showed bilateral dilated superior ophthalmic veins. Cerebral digital subtraction angiography was requested, and no carotid-cavernous fistula (or other significant vascular findings) was identified. The diagnosis of IEEVP was assumed. In conclusion, our case highlights the systematic investigation necessary in cases of bilateral episcleral vessel engorgement and tortuosity and the possible differential diagnosis to be considered to rule out life-threatening causes of elevated episcleral venous pressure. It is important for clinicians to be aware of IEEVP even in patients with atypical features that despite significative ocular hypertension had no glaucomatous damage.

OCT-angiography detects longitudinal microvascular changes in glaucoma: a systematic review.

BACKGROUND/AIMS: Optical coherence tomography angiography (OCTA) allows the study of vessel density (VD). We intended to perform a systematic review of studies focusing on longitudinal changes in peripapillary and macular VD measurements in glaucoma. METHODS: A search was performed across MEDLINE, Scopus, ISI Web of Science and Google Scholar, using the following query from inception until 20 September 2019: (("optical coherence tomography angiography"[tiab]) OR (optical coherence tomography angiography[MeSH]) OR ("OCTA"[tiab]) OR ("OCT-A"[tiab]) OR ("angio-OCT"[tiab]) OR ("OCT- angiography"[tiab]) OR ("OCT-angio"[tiab]) OR ("OCT-angiographie"[tiab])) AND (glaucom*[tiab] OR glaucoma[MeSH]). Prospective studies that quantitatively assessed the longitudinal changes in VD in glaucoma with at least 3 months of follow-up were included. RESULTS: Ten out of 4516 studies were included. The rate of VD change in glaucoma varied from 0.036/year to 1.08/year and 1.3% to 3.2% per year, with significantly different rates between glaucoma and healthy controls. Five studies assessed VD change after glaucoma surgery, obtaining variable results, ranging from a temporary VD decrease to increase after 3 months. Meta-analysis was not possible due to a wide variation in methods, measurements and region of VD. CONCLUSION: OCTA is a non-invasive technology, which shows promise in glaucoma. Measures should be taken to increase the quality and standardise the methodology of VD measures in OCTA longitudinal studies, for future meta-analyses.