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      The future of canine glaucoma therapy

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          Abstract

          Canine glaucoma is a group of disorders that are generally associated with increased intraocular pressure (IOP) resulting in a characteristic optic neuropathy. Glaucoma is a leading cause of irreversible vision loss in dogs and may be either primary or secondary. Despite the growing spectrum of medical and surgical therapies, there is no cure, and many affected dogs go blind. Often eyes are enucleated because of painfully high, uncontrollable IOP. While progressive vision loss due to primary glaucoma is considered preventable in some humans, this is mostly not true for dogs. There is an urgent need for more effective, affordable treatment options. Because newly developed glaucoma medications are emerging at a very slow rate and may not be effective in dogs, work toward improving surgical options may be the most rewarding approach in the near term. This Viewpoint Article summarizes the discussions and recommended research strategies of both a Think Tank and a Consortium focused on the development of more effective therapies for canine glaucoma; both were organized and funded by the American College of Veterinary Ophthalmologists Vision for Animals Foundation (ACVO‐VAF). The recommendations consist of (a) better understanding of disease mechanisms, (b) early glaucoma diagnosis and disease staging, (c) optimization of IOP‐lowering medical treatment, (d) new surgical therapies to control IOP, and (e) novel treatment strategies, such as gene and stem cell therapies, neuroprotection, and neuroregeneration. In order to address these needs, increases in research funding specifically focused on canine glaucoma are necessary.

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          Most cited references133

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          Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Collaborative Normal-Tension Glaucoma Study Group.

          (1998)
          To determine if intraocular pressure plays a part in the pathogenic process of normal-tension glaucoma. One eye of each eligible subject was randomized either to be untreated as a control or to have intraocular pressure lowered by 30% from baseline. Eyes were randomized if they met criteria for diagnosis of normal-tension glaucoma and showed documented progression or high-risk field defects that threatened fixation or the appearance of a new disk hemorrhage. The clinical course (visual field and optic disk) of the group with lowered intraocular pressure was compared with the clinical course when intraocular pressure remained at its spontaneous untreated level. One hundred-forty eyes of 140 patients were used in this study. Sixty-one were in the treatment group, and 79 were untreated controls. Twenty-eight (35%) of the control eyes and 7 (12%) of the treated eyes reached end points (specifically defined criteria of glaucomatous optic disk progression or visual field loss). An overall survival analysis showed a statistically significant difference between the two groups (P < .0001). The mean survival time +/-SD of the treated group was 2,688 +/- 123 days and for the control group, 1,695 +/- 143 days. Of 34 cataracts developed during the study, 11 (14%) occurred in the control group and 23 (38%) in the treated group (P = .0075), with the highest incidence in those whose treatment included filtration surgery. Intraocular pressure is part of the pathogenic process in normal-tension glaucoma. Therapy that is effective in lowering intraocular pressure and free of adverse effects would be expected to be beneficial in patients who are at risk of disease progression.
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            Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey.

            A detailed ocular examination, including perimetry, was conducted on 5308 black and white subjects aged 40 years and older in a population-based prevalence survey in east Baltimore, Md. Repeated, detailed examinations were carried out on selected subjects. Roughly half of all subjects with optic nerve damage from primary open angle glaucoma, regardless of race, were unaware that they had the condition. The average intraocular pressure (IOP) among black patients with glaucoma who were receiving treatment was virtually identical to that in those black patients who were not receiving treatment (median IOP, 20 mm Hg); treated eyes of white patients had a lower IOP than those eyes of white patients who were not receiving treatment (mean [+/- SD] IOP, 18.69 +/- 3.23 mm Hg vs 24.15 +/- 5.23 mm Hg; P less than .001). The risk of glaucomatous optic nerve damage increased with the height of the screening IOP, particularly at levels of 22 to 29 and 30 mm Hg and above (relative rate compared with IOP of 15 mm Hg or lower, 12.8 and 40.1 mm Hg, respectively). More than half of all glaucomatous eyes had a screening IOP below 21 mm Hg, whether these eyes were receiving treatment or not. The IOP in glaucomatous eyes tended to rise on follow-up, in contrast with nonglaucomatous eyes in which the IOP was as likely to rise as to fall. Results confirmed that IOP is an important factor in glaucoma, but did not support the traditional distinction between "normal" and "elevated" pressure, nor its corollaries, "low-tension" glaucoma and "high-tension" glaucoma.
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              Minimally-invasive glaucoma surgeries (MIGS) for open angle glaucoma: A systematic review and meta-analysis

              Background MIGS have been developed as a surgical alternative for glaucomatous patients. Purpose To analyze the change in intraocular pressure (IOP) and glaucoma medications using different MIGS devices (Trabectome, iStent, Excimer Laser Trabeculotomy (ELT), iStent Supra, CyPass, XEN, Hydrus, Fugo Blade, Ab interno canaloplasty, Goniscopy-assisted transluminal trabeculotomy) as a solo procedure or in association with phacoemulsification. Methods Randomized control trials (RCT) and non-RCT (non randomized comparative studies, NRS, and before-after studies) were included. Studies with at least one year of follow-up in patients affected by primary open angle glaucoma, pseudoexfoliative glaucoma or pigmentary glaucoma were considered. Risk of Bias assessment was performed using the Cochrane Risk of Bias and the ROBINS-I tools. The main outcome was the effect of MIGS devices compared to medical therapy, cataract surgery, other glaucoma surgeries and other MIGS on both IOP and use of glaucoma medications 12 months after surgery. Outcomes measures were the mean difference in the change of IOP and glaucoma medication compared to baseline at one and two years and all ocular adverse events. The current meta-analysis is registered on PROSPERO (reference n° CRD42016037280). Results Over a total of 3,069 studies, nine RCT and 21 case series with a total of 2.928 eyes were included. Main concerns about risk of bias in RCTs were lack of blinding, allocation concealment and attrition bias while in non-RCTs they were represented by patients’ selection, masking of participants and co-intervention management. Limited evidence was found based on both RCTs and non RCTs that compared MIGS surgery with medical therapy or other MIGS. In before-after series, MIGS surgery seemed effective in lowering both IOP and glaucoma drug use. MIGS showed a good safety profile: IOP spikes were the most frequent complications and no cases of infection or BCVA loss due to glaucoma were reported. Conclusions Although MIGS seem efficient in the reduction of the IOP and glaucoma medication and show good safety profile, this evidence is mainly derived from non-comparative studies and further, good quality RCTs are warranted.
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                Author and article information

                Contributors
                komaromy@msu.edu
                Journal
                Vet Ophthalmol
                Vet Ophthalmol
                10.1111/(ISSN)1463-5224
                VOP
                Veterinary Ophthalmology
                John Wiley and Sons Inc. (Hoboken )
                1463-5216
                1463-5224
                20 May 2019
                September 2019
                : 22
                : 5 ( doiID: 10.1111/vop.v22.5 )
                : 726-740
                Affiliations
                [ 1 ] College of Veterinary Medicine Michigan State University East Lansing Michigan
                [ 2 ] Centro de Especialistas Veterinarios de Puerto Rico San Juan Puerto Rico
                [ 3 ] Veterinary Ophthalmic Consulting Irvine California
                [ 4 ] Glaucoma Associates of Texas Dallas Texas
                [ 5 ] Animal Eye Consultants of Iowa Hiawatha Iowa
                [ 6 ] U.S. Food and Drug Administration Silver Spring Maryland
                [ 7 ] New York University School of Medicine New York New York
                [ 8 ] Department of Ophthalmology, School of Medicine University of Maryland Baltimore Maryland
                [ 9 ] School of Veterinary Medicine University of Wisconsin‐Madison Madison Wisconsin
                [ 10 ] Kellogg Eye Center University of Michigan Ann Arbor Michigan
                [ 11 ] College of Veterinary Medicine University of Florida Gainesville Florida
                [ 12 ] Long Island Veterinary Specialists Plainview New York
                [ 13 ] South Atlanta Veterinary Emergency & Specialty Fayetteville Georgia
                [ 14 ] Truhlsen Eye Institute University of Nebraska Medical Center Omaha Nebraska
                [ 15 ] MedVet Medical & Cancer Centers for Pets Worthington Ohio
                Author notes
                [*] [* ] Correspondence

                András M. Komáromy, Michigan State University, Veterinary Medical Center, 736 Wilson Road, Room D‐208, East Lansing, MI 48824.

                Email: komaromy@ 123456msu.edu

                Author information
                https://orcid.org/0000-0002-8845-0588
                https://orcid.org/0000-0001-8961-0187
                https://orcid.org/0000-0003-0917-4130
                https://orcid.org/0000-0001-9960-678X
                https://orcid.org/0000-0003-3794-6142
                Article
                VOP12678
                10.1111/vop.12678
                6744300
                31106969
                be4aed93-db5e-408e-b278-14364bd30f53
                © 2019 The Authors. Veterinary Ophthalmology published by Wiley Periodicals, Inc. on behalf of American College of Veterinary Ophthalmologists

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 11 July 2018
                : 05 April 2019
                : 15 April 2019
                Page count
                Figures: 8, Tables: 2, Pages: 15, Words: 11133
                Funding
                Funded by: ACVO Vision for Animals Foundation
                Funded by: BrightFocus Foundation
                Funded by: Michigan State University College of Veterinary Medicine Endowed Research Funds
                Funded by: National Eye Institute/National Institutes of Health
                Award ID: R01-EY022124
                Award ID: R01-EY025752
                Funded by: Bouvier Health Foundation
                Categories
                Viewpoint Article
                Viewpoint Article
                Custom metadata
                2.0
                vop12678
                September 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.9 mode:remove_FC converted:30.09.2019

                aqueous humor,canine,glaucoma,intraocular pressure,optic nerve,surgery

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