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      Numerical model to predict and compare the hypotensive efficacy and safety of minimally invasive glaucoma surgery devices

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          Abstract

          Purpose

          To predict and compare the hypotensive efficacy of three minimally-invasive glaucoma surgery (MIGS) implants through a numerical model.

          Methods

          Post-implant hypotensive efficacy was evaluated by using a numerical model and a computational fluid dynamics simulation. Three different devices were compared: the XEN 45 stent (tube diameter, 45 μm), the XEN 63 stent (63 μm) and the PreserFlo microshunt (70 μm). The influence of the filtration bleb pressure (Bp) and tube diameter, length, and position within the anterior chamber (AC) on intraocular pressure (IOP) were evaluated.

          Results

          Using baseline IOPs of 25, 30 and 50 mmHg, respectively, the corresponding computed post-implant IOPs for each device were as follows: XEN 45: 17 mmHg (29% decrease), 19 mmHg (45%) and 20 mmHg (59%) respectively; XEN 63: 13 mmHg (48%), 13 mmHg (62%), and 13 mmHg (73%); PreserFlo: 12 mmHg (59%), 13 mmHg (73%) and 13 mmHg (73%). At a baseline IOP of 35 mmHg with an increase in the outflow resistance within the Bp from 5 to 17 mmHg, the hypotensive efficacy for each device was reduced as follows: XEN45: 54% to 37%; XEN 63: 74% to 46%; and PreserFlo: 75% to 47%. The length and the position of the tube in the AC had only a minimal (non-significant) effect on IOP (<0.1 mmHg).

          Conclusions

          This hydrodynamic/numerical model showed that implant diameter and bleb pressure are the two most pertinent determinants of hypotensive efficacy. In distinction, tube length and position in the AC do not significantly influence IOP.

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          Most cited references58

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          Causes and prevalence of visual impairment among adults in the United States.

          To estimate the cause-specific prevalence and distribution of blindness and low vision in the United States by age, race/ethnicity, and gender, and to estimate the change in these prevalence figures over the next 20 years. Summary prevalence estimates of blindness (both according to the US definition of < or =6/60 [< or =20/200] best-corrected visual acuity in the better-seeing eye and the World Health Organization standard of < 6/120 [< 20/400]) and low vision (< 6/12 [< 20/40] best-corrected vision in the better-seeing eye) were prepared separately for black, Hispanic, and white persons in 5-year age intervals starting at 40 years. The estimated prevalences were based on recent population-based studies in the United States, Australia, and Europe. These estimates were applied to 2000 US Census data, and to projected US population figures for 2020, to estimate the number of Americans with visual impairment. Cause-specific prevalences of blindness and low vision were also estimated for the different racial/ethnic groups. Based on demographics from the 2000 US Census, an estimated 937 000 (0.78%) Americans older than 40 years were blind (US definition). An additional 2.4 million Americans (1.98%) had low vision. The leading cause of blindness among white persons was age-related macular degeneration (54.4% of the cases), while among black persons, cataract and glaucoma accounted for more than 60% of blindness. Cataract was the leading cause of low vision, responsible for approximately 50% of bilateral vision worse than 6/12 (20/40) among white, black, and Hispanic persons. The number of blind persons in the US is projected to increase by 70% to 1.6 million by 2020, with a similar rise projected for low vision. Blindness or low vision affects approximately 1 in 28 Americans older than 40 years. The specific causes of visual impairment, and especially blindness, vary greatly by race/ethnicity. The prevalence of visual disabilities will increase markedly during the next 20 years, owing largely to the aging of the US population.
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            Micro-invasive glaucoma surgery: current perspectives and future directions.

            There is an increasing interest and availability of micro-invasive glaucoma surgery (MIGS) procedures. It is important that this increase is supported by sound, peer-reviewed evidence. This article will define MIGS, review relevant publications in the period of annual review and discuss future directions. The results of the pivotal trial comparing a trabecular micro-bypass stent (iStent, Glaukos Corporation, Laguna Hills, CA, USA) combined with phacoemulsification to phacoemulsification alone showed a significantly higher percentage of patients with unmedicated intraocular pressure (IOP) ≤ 21 mmHg, and a comparable safety profile. Initial results are published regarding a second-generation micro-bypass stent (iStent inject, Glaukos Corporation, Laguna Hills, CA, USA), a canalicular scaffold (Hydrus, Ivantis Inc., Irvine, CA, USA) and an ab interno suprachoroidal microstent (CyPass, Transcend Medical, Menlo Park, CA, USA), showing a decrease in mean postoperative IOP. Phaco-Trabectome (Ab interno trabeculectomy Trabectome, NeoMedix Inc., Tustin, CA, USA) was compared to phacotrabeculectomy and showed less IOP reduction, less postoperative complications, and a similar success rate. Similar success rates were found with the comparison of excimer laser trabeculostomy (ELT, AIDA, Glautec AG, Nurnberg, Germany) and selective laser trabeculoplasty. A number of publications review the importance of the location of implantable devices, intraoperative gonioscopy, cost-effectiveness and quality-of-life studies, and randomized clinical trials. MIGS procedures offer reduction in IOP, decrease in dependence on glaucoma medications and an excellent safety profile. Their role within our glaucoma treatment algorithm continues to be clarified and differs from the role of more invasive glaucoma surgeries such as trabeculectomy or glaucoma drainage devices.
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              Current understanding of conventional outflow dysfunction in glaucoma.

              Regulation of intraocular pressure by the conventional (trabecular) outflow pathway is complicated, involving a myriad of mechanical and chemical signals. In most, intraocular pressure is maintained within a tight range over a lifetime. Unfortunately in some, dysfunction results in ocular hypertension and open-angle glaucoma. In the context of established knowledge, this review summarizes recent investigations of conventional outflow function, with the goal of identifying areas for future inquiry and therapeutic targeting. Mechanical stimulation of conventional outflow cells due to intraocular pressure fluctuations impacts contractility, gene expression, pore formation, enzyme activity, and signaling. Numerous local signaling mediators in the conventional pathway such as bioactive lipids, cytokines, nitric oxide, and nucleotides participate in the regulation of outflow. Interestingly outflow through the conventional pathway is not uniform, but segmental, with passageways constantly changing due to focal protease activity of trabecular cells clearing extracellular matrix materials. The relationship between extracellular matrix expression and trabecular meshwork contractility appears to coordinately impact outflow resistance and is the target of a new class of drugs, the Rho kinase inhibitors. The conventional outflow pathway is a dynamic, pressure-sensitive tissue that is vulnerable to pathology on many fronts, each representing a therapeutic opportunity.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: SoftwareRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: SoftwareRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                29 September 2020
                2020
                : 15
                : 9
                : e0239324
                Affiliations
                [1 ] Department of Ophthalmology, Puerta de Hierro University Hospital, Majadahonda, Madrid, Spain
                [2 ] International Center of Advanced Ophthalmology, Madrid, Spain
                [3 ] Department of Ophthalmology, San Carlos Clinical Hospital, Health Research Institute (IdISSC), Universidad Complutense, Oftared, Madrid, Spain
                [4 ] Department of Mechanical, Energy and Materials Engineering and Advanced Scientific Computing Institute (ICCAEx), University of Extremadura, Badajoz, Spain
                [5 ] Department of Medical-Surgical Therapy, Ophthalmology Area, Faculty of Medicine, University of Extremadura, Badajoz, Spain
                Faculty of Medicine, Cairo University, EGYPT
                Author notes

                Competing Interests: The authors have declared that no competing interests exist

                Author information
                http://orcid.org/0000-0002-2600-8233
                http://orcid.org/0000-0002-7772-5718
                Article
                PONE-D-20-11285
                10.1371/journal.pone.0239324
                7523982
                32991588
                72f8be0a-5c26-4e48-8274-1df045934ab1
                © 2020 Kudsieh et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 19 April 2020
                : 4 September 2020
                Page count
                Figures: 6, Tables: 4, Pages: 17
                Funding
                Funded by: Health Research Institute (IdISSC), Madrid, Spain.
                Award Recipient :
                Funded by: Health Research Institute Puerta De Hierro-Segovia Arana, Madrid, Spain.
                Award Recipient :
                The publication of this work is funded by the normative grant of the community of Madrid,Spain. The work has been funded by a research grant from the San Carlos Clinical Hospital, Health Research Institute (IdISSC), Madrid, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript".
                Categories
                Research Article
                Biology and Life Sciences
                Bioengineering
                Biotechnology
                Medical Devices and Equipment
                Medical Implants
                Engineering and Technology
                Bioengineering
                Biotechnology
                Medical Devices and Equipment
                Medical Implants
                Medicine and Health Sciences
                Medical Devices and Equipment
                Medical Implants
                Medicine and Health Sciences
                Medical Conditions
                Eye Diseases
                Glaucoma
                Medicine and Health Sciences
                Ophthalmology
                Eye Diseases
                Glaucoma
                Biology and Life Sciences
                Bioengineering
                Biotechnology
                Medical Devices and Equipment
                Engineering and Technology
                Bioengineering
                Biotechnology
                Medical Devices and Equipment
                Medicine and Health Sciences
                Medical Devices and Equipment
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Ophthalmic Procedures
                Physical Sciences
                Physics
                Classical Mechanics
                Continuum Mechanics
                Fluid Mechanics
                Fluid Dynamics
                Flow Rate
                Biology and Life Sciences
                Anatomy
                Ocular System
                Ocular Anatomy
                Cornea
                Medicine and Health Sciences
                Anatomy
                Ocular System
                Ocular Anatomy
                Cornea
                Biology and Life Sciences
                Anatomy
                Ocular System
                Ocular Anatomy
                Trabecular Meshwork
                Medicine and Health Sciences
                Anatomy
                Ocular System
                Ocular Anatomy
                Trabecular Meshwork
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Stent Implantation
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                All relevant data are within the paper and its Supporting Information files.

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