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      Treatment Course of Patients with Exudative Age-Related Macular Degeneration Using Ocular Hypotensives

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          Abstract

          Purpose

          To characterize the visual outcomes and the treatment course of patients with exudative age-related macular degeneration (AMD) based on ocular hypotensive use.

          Design

          A matched retrospective cohort study of patients enrolled in Kaiser Permanente Southern California health plan was conducted. Patients taking ocular hypotensives were identified using pharmacy dispensing data and were matched to controls to compare visual acuity, number of anti-VEGF injections, and conversation to secondary anti-VEGF agents in the first year of treatment. Subgroup analysis was performed based on the number of ocular hypotensive agents (0, 1, 2 or 3+ agents) and drug class (aqueous suppressants and prostaglandin analogs).

          Results

          A total of 234 patients patients were examined. Baseline and final visual acuity did not significantly differ between drop users and controls, including on subgroup analysis. The average number of anti-VEGF injections did not differ between drop users and controls (6.1 vs 6.2, p=0.97), nor did the percentage of patients who were switched to a second-line anti-VEGF agent (23.9% vs 17.9%, p=0.26). Subgroup analysis did not reveal significant differences in the number of anti-VEGF injections and the percentage of patients switched to secondary agents, with patients receiving 6 ±1 injections across regardless of the number or class of ocular hypotensive agents used.

          Conclusion

          Patients with concurrent glaucoma and exudative AMD have similar visual outcomes and treatment courses compared to those not taking ocular hypotensives. Although aqueous suppressants have been suggested to prolong anti-VEGF residence time, patients using these agents did not demonstrate visual benefit or a reduced injection burden in this series.

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          Most cited references18

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          Pharmacokinetics of intravitreal bevacizumab (Avastin).

          To describe the pharmacokinetics of 1.25 mg of intravitreal bevacizumab (Avastin). Experimental animal study. Twenty Dutch-belted rabbits. One eye of each of 20 rabbits was injected with 1.25 mg of intravitreal bevacizumab. Both eyes of each of 4 rabbits were enucleated at days 1, 3, 8, 15, and 29. Bevacizumab concentrations were measured in aqueous fluid, whole vitreous, and serum. Bevacizumab concentrations in the aqueous, vitreous, and serum. Whereas vitreous concentrations of bevacizumab declined in a monoexponential fashion with a half-life of 4.32 days, concentrations of >10 microg/ml bevacizumab were maintained in the vitreous humor for 30 days. Bevacizumab concentrations in the aqueous humor of the injected eye reached a peak concentration of 37.7 microg/ml 3 days after drug administration. A maximum serum concentration of 3.3 mug/ml was achieved 8 days after intravitreal injection and the concentration fell below 1 microg/ml 29 days after injection. Elimination of bevacizumab from the aqueous humor and serum paralleled that found in the vitreous humor, with half-life values of 4.88 days and 6.86 days, respectively. Very low concentrations of bevacizumab were detected in the fellow uninjected eye. Concentrations of bevacizumab in the vitreous of the fellow eye varied incrementally, from 0.35 ng/ml at 1 day to 11.17 ng/ml at 4 weeks. Concentrations of bevacizumab in the aqueous humor of the fellow eye reached their peak at 1 week, at 29.4 ng/ml, and declined to 4.56 ng/ml at 4 weeks. The vitreous half-life of 1.25 mg intravitreal bevacizumab is 4.32 days in a rabbit eye. Very small amounts of bevacizumab were detected in the serum and in the fellow uninjected eye.
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            Preclinical pharmacokinetics of Ranibizumab (rhuFabV2) after a single intravitreal administration.

            Ranibizumab (rhuFab V2; Lucentis, Genentech, South San Francisco, CA) is a humanized monoclonal antibody fragment designed to bind all forms of VEGF, thereby blocking vessel permeability and angiogenesis in neovascular age-related macular degeneration. This study evaluated the pharmacokinetic (PK) and serum bioavailability of ranibizumab after a single intravitreal (ITV) or intravenous (IV) dose in cynomolgus monkeys. Monkeys received ranibizumab as either a bilateral ITV dose (500 or 2000 microg/eye; n = 6/group) or a single IV dose (1000 or 4000 microg/animal; n = 4/group). After ITV administration, ranibizumab concentrations were measured in several ocular compartments and in serum for 10 days and, after IV administration, for 48 hours. Pharmacokinetic parameters were estimated by compartmental and noncompartmental methods. Ranibizumab cleared in parallel from all ocular compartments, with a terminal half-life of approximately 3 days. It distributed rapidly to the retina (6-24 hours), and concentrations were approximately one third that in the vitreous. After ITV injection, bioavailability (F) was 50% to 60%. Serum concentrations were very low, reflecting wider distribution and faster clearance when ranibizumab reached the serum. After IV administration, the terminal half-life was approximately 0.5 day. This study demonstrates that ranibizumab has a PK profile that is favorable for its clinical use in treating neovascular AMD by monthly ITV injection.
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              Pharmacokinetics of intravitreally injected bevacizumab in vitrectomized eyes.

              To compare the pharmacokinetics (PKs) of intravitreally injected bevacizumab in vitrectomized versus nonvitrectomized control rabbit eyes.
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                Author and article information

                Journal
                Clin Ophthalmol
                Clin Ophthalmol
                OPTH
                clinop
                Clinical Ophthalmology (Auckland, N.Z.)
                Dove
                1177-5467
                1177-5483
                22 January 2020
                2020
                : 14
                : 187-195
                Affiliations
                [1 ] Eye Monitoring Center, Kaiser Permanente Southern California , Baldwin Park, CA, USA
                [2 ] Department of Ophthalmology, Southern California Permanente Medical Group , Baldwin Park, CA, USA
                [3 ] Department of Research and Evaluation, Southern California Permanente Medical Group , Pasadena, CA, USA
                [4 ] Glaucoma Service, Massachusetts Eye and Ear Infirmary , Boston, MA, USA
                Author notes
                Correspondence: Bobeck S Modjtahedi Eye Monitoring Center, Kaiser Permanente Southern California , 1011 Baldwin Park Blvd, Baldwin Park, CA91706, USA Email BobModj@gmail.com
                Author information
                http://orcid.org/0000-0002-5825-9248
                Article
                228618
                10.2147/OPTH.S228618
                6985978
                32158177
                6481aa65-4faf-4f3b-ba7d-e3f1d59edaa1
                © 2020 Modjtahedi et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 25 August 2019
                : 05 November 2019
                Page count
                Tables: 4, References: 19, Pages: 9
                Funding
                Funded by: Regional Research Committee, Southern California Permanente Medical Group
                This project was funded by an internal grant from the Regional Research Committee, Southern California Permanente Medical Group, Pasadena, CA.
                Categories
                Original Research

                Ophthalmology & Optometry
                age-related macular degeneration,bevacizumab,glaucoma,aqueous suppressant,pharmacology,pharmacokinetics,vascular endothelial growth factor,intravitreal injection

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