Journal of Ocular Pharmacology and Therapeutics (J OCUL PHARMACOL TH )

Publisher: Society for Ocular Pharmacology and Therapeutics, Mary Ann Liebert


This peer-reviewed journal publishes research on all aspects of drug activity pertaining to preventing or controlling diseases of the eye. The official journal of the Society for Ocular Pharmacology and Therapeutics.

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    Journal of ocular pharmacology and therapeutics (Online), Journal of ocular pharmacology and therapeutics
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Mary Ann Liebert

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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: To present effectiveness of intravitreal ranibizumab (IVR) injection for central serous chorioretinopathy (CSC), resistant to intravitreal bevacizumab (IVB) injection. Methods: Files of the patients who had the diagnosis of CSC between 2005 and 2013 were reviewed retrospectively. Eighty-five eyes of 81 patients' files have been investigated. Ten eyes of 10 patients that were resistant to IVB, with no history of photodynamic therapy, were included in to this study. Demographic details, best-corrected visual acuity (BCVA), and central macular thickness (CMT) were studied to analyze the effectiveness of IVR. Results: The mean age of the patients was 38.8 years (SD=4.7 years). The mean follow-up time after first IVR injection was 7.9 months (SD=1.5 months). The mean number of IVB and IVR injections was 2.0 (SD=0.7) and 1.3 (SD=0.4), respectively. The mean CMT before IVR injection was 392.4 μm (SD=66.3) and decreased to 194.1 μm (SD=9.3, P<0.001) at the last visit. The mean BCVA before IVR injection was 0.50logMAR (SD=0.23) and improved to 0.05logMAR (SD=0.06, P<0.001) at the last visit. In all cases after IVR injection, the subretinal fluid almost resolved completely, and leakage disappeared in fundus fluorescein angiography. Conclusion: Ranibizumab might be a promising option for the patients with CSC, resistant to bevacizumab in acute or early chronic stage.
    Journal of Ocular Pharmacology and Therapeutics 09/2014; 2014.
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    ABSTRACT: Objective: To update in new biopolymers and innovations for ocular prostheses and visual implants for visual care. Methodology: The systematic review about biomaterials for ocular prostheses and visual implants was consulted on the following Journals Databases: Investigative Ophthalmology and Visual Science, Nature Eye, Ophthalmology, Br. J. Ophthalmology, Ophthalmic plastic in reconstructive surgery for a total review of 67 articles and 8 e-books were consulted with the following keywords: ocular prostheses and biopolymers, visual and ocular implants, artificial eye. Inclusion criteria: “ocular prostheses”, retinal prostheses systems (RPS) and “visual implants”. Search resources: MEDLINE, PubMed, SciELO, Biblioteca virtual en salud (BVS). Results: The traditional concept of ocular prostheses (ocular, orbital, epithesis, maxillofacial) and visual implants (retinal, optic nerve, cortical, subretinal, epiretinal and cortical implants, artificial silicon retinas and suprachoroidal transretinal stimulation (STS)) among others are changing on now days due to the new advances in technologies and also to the developing of new biomaterials, new microelectrodes and neural devices of several types around the world. Now, real “artificial eyes” are not only the craniofacial, maxillofacial, ocular and orbital prostheses, that replaces an absent eye after an enucleation. But also, new materials such as cryolite glass, gel from cellulose produced by Zoogloea sp., glass, silicone and porous polyethylene, graphene, dental biopolymers among others are being implemented as a materials for heart, eye and other organs implants due to their characteristics to improve good biological compatibility, to be more resistant and to contribute to reduce allergies and improve durability. These implants are used for replacement of the orbital content of the anophthalmic cavities. In addition to this, the existing wearing protocols must be updated, as the three phases model of prosthetic eye wear: establishment of homeostasis deposits builds up, recovery from effects of handling the prosthesis, and the posterior homeostasis´s stabilization for mucus and deposits, must be reduced in a near future by means of surface nanofilm or the inclusion of new biopolymers for fabrication to prevent the adherences and anticipate to immune responses after the implantation of these foreign bodies.
    Journal of Ocular Pharmacology and Therapeutics 07/2014;
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    ABSTRACT: Purpose: In trabecular meshwork (TM) cells, actin geodesic arrangements were measured and then subjected to computational modeling to appreciate the response of different dome shapes to mechanical force. Methods: Polygonal actin arrangements (PAAs) and cross-linked actin networks (CLANs) were induced and imaged by Alexa Flour® 488 Phalloidin in bovine TM and human TM cells. Masked images were examined for size, circularity, and spoke and hub dimensions using ImageJ. Finite element modeling was used to create idealized dome structures and "realistic" PAA and CLAN models. The models were subjected to different loads simulating concentrated force and distortion measured. Results: We provide evidence that PAAs and CLANs are not identical. Both structures formed flattened domes but PAAs were 6 times larger than CLANs, significantly more circular and had greater height. The dimensions of the triangulations of hubs and spokes were, however, remarkably similar. Hubs were around 2 μm2 in area, whereas spokes were about 5 μm in length. Our modeling showed that temporary arrangements of polygonal actin structures (TAPAS) were because of their flattened shape, more resistant to shearing than compression when compared with idealized domes. CLANs were marginally more resistant to shearing than PAAs but because of size much more resistant to compression. Conclusions: Evidence is provided that there are 2 types of actin icosahedrons in cultured TM cells we collectively call TAPAS. Modeling suggests that TAPAS have rigidity and are better at dealing with shearing than compression forces. The 2 types of TAPAS, PAAs, and CLANs, have much in common but there are size and mechanical response differences that need to be taken into account in future experimentation.
    Journal of Ocular Pharmacology and Therapeutics 01/2014;
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    ABSTRACT: Purpose: To compare the 2-year outcomes of photodynamic therapy (PDT) with or without intravitreal ranibizumab (IVR) for polypoidal choroidal vasculopathy (PCV). Methods: Medical charts from 58 patients with PCV, who had been followed up for more than 2 years after initial treatment, were reviewed retrospectively. Visual outcomes were compared between 2 groups, consisting of 34 patients treated with PDT monotherapy without IVR and 24 with the combination of PDT and IVR, and the factors associated with the 2-year visual outcomes were investigated using multiple regression analysis. Results: In the PDT monotherapy group, the logarithm of the minimum angle of resolution (logMAR) of the bestcorrected visual acuity (BCVA) improved significantly at 12 months (P = 0.026), but was not significantly different from the initial logMAR BCVA at 24 months (P = 0.21). By contrast, the logMAR BCVA improved significantly at 12 months and was maintained throughout the second 12-month period (P < 0.001 at all time points) in the combined PDT group. Multiple regression analysis revealed that the initial BCVA (P < 0.001), the greatest linear dimension of the initial PDT (P = 0.006), and the combined PDT (P = 0.039) were predictors of visual outcomes at 24 months. Conclusions: Combined PDT with IVR is a better treatment modality compared with PDT monotherapy, and results in improvement of visual outcomes at 24 months after the initial treatment.
    Journal of Ocular Pharmacology and Therapeutics 11/2013; 29(9):832-6.
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    ABSTRACT: Purpose: To review the existing evidence that supports the subconjunctival use of triamcinolone acetonide (TA) in the treatment of various ophthalmic diseases. Methods: A literature search was performed for published articles about the pharmacokinetic (PK) and pharmacodynamic characteristics of triamcinolone, as well as its potential ophthalmic use, focused mainly in the subconjunctival mode of delivery. Search terms included corticosteroids, triamcinolone, ocular, subconjunctival, and ophthalmic. Results: Corticosteroids represent the mainstay of treatment of ocular inflammation, exerting their action by affecting multiple pathways of the inflammatory response, making them particularly effective in the majority of cases. However, due to the number and severity of the side effects associated with their use, they have to be given with caution. Corticosteroids can be given topically, subconjunctivally, intraocularly, and systemically to treat a variety of ocular diseases with specific pharmacological and PK characteristics. Triamcinolone is one of the most widely used corticosteroids in the treatment of ocular inflammation. This glucocorticoid used subconjunctivally was proven to be particularly safe and effective in some common and important inflammatory ophthalmic diseases such as anterior scleritis, uveitis, and corneal graft rejection. Further, there are other indications for its successful use where data exist, but somehow less abundant. Conclusions: This article highlights the potential of TA to complement the treatment armamentarium of anterior segment inflammation.
    Journal of Ocular Pharmacology and Therapeutics 03/2013;
  • Journal of Ocular Pharmacology and Therapeutics 02/2012;
  • Journal of Ocular Pharmacology and Therapeutics 01/2012;
  • Journal of Ocular Pharmacology and Therapeutics 01/2012;
  • Journal of Ocular Pharmacology and Therapeutics 01/2011;
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    ABSTRACT: Dexamethasone is a corticosteroid with proven efficacy for treating both anterior- and posterior-segment ocular diseases. Delivery of drugs to the back of the eye has always been a challenge, with dexamethasone being no exception. There are multiple delivery routes to the retina, with each exhibiting different pharmacokinetics, depending on the drug molecule and specific route of administration. In this study, we used intravenous (IV), subconjunctival (SC), and intravitreal (IVT) injections in rabbits to determine the pharmacokinetics of dexamethasone phosphate and its metabolic product, dexamethasone, at low (25 microg/kg) and high (250 microg/kg) doses. Plasma samples were collected from each group of animals at different time points up to 24 h after the injection. Using a liquid chromatographic mass spectrometric method with a limit of detection of 0.5 ng/mL, the plasma concentration for dexamethasone and its prodrug compound were quantified. IV delivery showed the fastest plasma elimination, followed by SC delivery. IVT delivery exhibited a depot effect, with very low plasma levels throughout the 24-h time course. At 24 h postinjection, only the high-dose IVT and low- and high-dose SC dexamethasone injections were still detectable in the plasma.
    Journal of Ocular Pharmacology and Therapeutics 07/2008; 24(3):301-8.
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    ABSTRACT: The aim of this study was to determine the efficacy of 0.3% gatifloxacin ophthalmic solution in preventing bacterial endophthalmitis in rabbits. Eighty-four (84) albino phakic rabbits were injected unilaterally with 2 x 10(4) colony forming units of Enterococcus faecalis into the anterior chamber. The eyes received 0.3% ofloxacin ophthalmic ointment or 0.3% gatifloxacin ophthalmic solution with different regimens in three separate experiments: (1) 1 or 3 drops of gatifloxacin every 2 h or a single application of ofloxacin for 1 day; (2) 3 drops/day of gatifloxacin application started at 0, 6, and 24 h postinoculation, or 1 drop at 0 h, and 3 times daily gatifloxacin for the following 3 days; and (3) 1 or 3 drops of gatifloxacin application started at 0 h and no further application for the following 3 days. The control eyes received no treatment in the three experiments. The effectiveness of these different regimens was assessed by slit-lamp biomicroscopy and bacterial colony counts. The ocular penetration of the drugs was determined in a separate experiment, using 36 normal albino rabbits. The concentration-time curves for gatifloxacin and ofloxacin appeared parallel, with mean peak concentrations of 1161 and 219 ng/mL, respectively, at 1 h postinstillation. In Experiment 1, gatifloxacin significantly reduced the inflammation and the number of living bacteria in the aqueous humor, compared with controls, whereas ofloxacin ointment did not. A single application of ofloxacin ointment was not better than 1 drop of gatifloxacin. The results of Experiment 2 showed that the effectiveness of gatifloxacin decreased as the interval between the inoculation and the onset of treatment increased. In Experiment 3, only 3 drops of gatifloxacin on day 1 kept the inflammation significantly lower than that in the control for 4 days. Immediate postoperative prophylaxis would likely be effective in reducing the risk of enterococcal endophthalmitis by topical gatifloxacin.
    Journal of Ocular Pharmacology and Therapeutics 07/2008; 24(3):278-89.
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    ABSTRACT: The aim of this study was to describe a case of sterile endophthalmitis after repeated intravitreal bevacizumab injections for the treatment of choroidal neovascularization secondary to angioid streaks. This study was done as a case report. A 57-year-old man who received a third injection of intravitreal bevacizumab for the treatment of choroidal neovascularization owing to angioid streaks developed sterile endophthalmitis. The patient's condition improved after hourly topical steroid and antibiotic drops without a sequele. The intravitreal injection of bevacizumab has the potential for the development of sterile endophthalmitis. The patients should be warned against this possible adverse reaction, especially after repeated injections.
    Journal of Ocular Pharmacology and Therapeutics 07/2008; 24(3):362-3.
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    ABSTRACT: The impact of P-glycoprotein (P-gp) blockade on the intravenous (i.v.) pharmacokinetics of rhodamine-123 (Rho-123), and the subsequent effect on its disposition in ocular and nonocular tissues, was studied by using rabbits. Three (3) control rabbits received only an i.v. bolus dose of Rho-123 (1.52 mg/kg). Three (3) blocker-pretreated rabbits received an i.v. dose of GF120918 (3.5 mg/kg) 30 min before the i.v. bolus of Rho-123. The plasma concentration of Rho-123 at different time points was subjected to a pharmacokinetic compartmental analysis, using WinNonlin (Scientific Consultants, Lexington, KY). For tissue-distribution study, a drug treatment similar to the i.v. kinetic study was followed by having 5 rabbits in each group. The animals were sacrificed at 30 min with an excess of anesthesia. Plasma and tissues samples were analyzed by using a validated high-performance liquid chromatographic IV method with a fluorescent detector. The method validated was sensitive enough to estimate Rho-123 up to 1.94 ng/mL in plasma. I.v. Rho-123 data fitted well into the three-compartment model, and P-gp blocker treatment changed it into a two-compartment model. The P-gp blockade significantly increased the mean tissue concentrations in the lungs and spleen, whereas the rise in mean tissue levels in the heart, liver, and kidney and in all ocular tissues were found to be statistically insignificant. Increasing the ocular concentration of systemically given drugs may not be possible with the degree of P-gp blockade achieved when using GF120918 at the studied concentration after an i.v. administration.
    Journal of Ocular Pharmacology and Therapeutics 07/2008; 24(3):290-300.
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    ABSTRACT: The aim of this study was to assess the efficacy and safety of adalimumab in treating refractory autoimmune uveitis. This work was a prospective, noncomparative, nonrandomized, clinical trial. Nineteen (19) patients meeting eligibility criteria received a 40-mg subcutaneous (s.c.) injection of adalimumab every other week during 1 year. All patients underwent an outcome assessment at month 12. Visual acuity improved by -0.3 logMar in 12 (31%) eyes of 38, and worsened by +0.3 logMar in 1 (2.6%) eye. All patients had an active intraocular inflammation at baseline, and 12 patients (63%) achieved control of their inflammation with adalimumab at the end of follow-up. After optic coherence tomography, 33 eyes (86%) had cystoid macular edema (CME) at baseline, and at the end of follow-up there was a complete resolution of CME in 18 of these 33 eyes (54.54%). All patients were able to reduce at least 50% of the dose of the concomitant immunosuppressive drugs at the end of follow-up. Adalimumab was well tolerated in all patients, and only local minor side effects at the s.c. injection site were observed. Nevertheless, 8 patients (42.10%) had relapses during the follow-up period that were controlled with 1 periocular steroid injection. Adalimumab seems to be an effective, safe therapy for the management of refractory uveitis and may provide the possibility to reduce the concomitant immunosuppressive drugs in these patients. Further long-term studies are warranted to determine the safety and efficacy of adalimumab in treating intraocular inflammation.
    Journal of Ocular Pharmacology and Therapeutics 07/2008; 24(3):351-61.
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    ABSTRACT: The aim of this study was to evaluate methylprednisolone penetration into ocular structures after low-current trans-scleral hydrogel iontophoresis, as compared with the common intravenous (i.v.) treatment. Methylprednisolone hemisuccinate (MPH) iontophoresis was studied in rabbits, using drug-loaded hydrogels mounted on a portable iontophoretic device. Cathodal iontophoresis of 2.6 mA/cm(2) was applied for 5 min at two opposite sites on the sclera or for 10 min at the same site. Ocular drug levels were determined 2 h after iontophoretic treatment, then compared to mock iontophoresis and i.v. infusion of 10 mg/kg methylprednisolone. Significantly higher methylprednisolone levels were found in ocular tissues after iontophoresis, compared with the control groups, except for the sclera concentrations, which were similar to the concentrations achieved after mock iontophoresis. Two (2) h after the trans-scleral iontophoretic treatment, 178.59 +/- 21.63 microg/g, 6.74 +/- 2.38 microg/ml, and 2.71 +/- 0.57 microg/mL were found in the retina, aqueous humor, and vitreous, respectively. No significant differences were found between one or two site treatments of trans-scleral iontophoresis. Nondetectable concentrations were found 2 h after the i.v. infusion of 10 mg/kg of methylprednisolone in all evaluated ocular tissues and fluids. A short, low-current noninvasive iontophoretic treatment, using methylprednisolone-loaded hydrogels, has potential clinical value in treating ocular inflammatory diseases.
    Journal of Ocular Pharmacology and Therapeutics 07/2008; 24(3):344-50.
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    ABSTRACT: Retinal permeability is one of the important parameters that determine drug distribution during diseased retinal conditions, whose effect is still unclear. Thus, the main aim of this study was to understand the influence of varying retinal permeability (P) on drug distribution under normal (F1) and elevated vitreous outflow pathophysiologic conditions (F10) for a wide variety of drug diffusivities-high: D(-5) and low: D(-7). A computational model of the rabbit eye was developed that took into account the varying effects of convection during normal and pathophysiologic conditions. High retinal permeability, P(-5), is associated with low peak macular concentration and a rapid clearance from the ocular chambers, with the retina as the major route of elimination. For low permeability, P(-7), there is very high peak macular concentration, slow elimination, and a buildup of drug concentration, which depends on vitreous outflow. The variation of t(1/2) with P was found to be of linear and nonlinear trends for F1 and F10 flow cases, respectively. Moreover, for D(-5) diffusivity, there was a 1.5-fold increase and a 1.6-fold decrease in t(1/2) values when the retinal permeability values were P(-5) and P(-7). On the contrary, for D(-7) diffusivity, there was a 2.5-fold decrease and a 1.4-fold increase in t(1/2) values for P(-5) and P(-7), with t(1/2) increasing for P(-6) during both high and low diffusivities. Thus, the combined effect of variables P, D, and F are important factors that should be considered in order to determine drug dosage. This study could be used to estimate the drug distribution and elimination for (1) wide range of physicochemical properties of drugs and (2) normal and abnormally elevated vitreous flows during the diseased condition of the eye. These results could help in obtaining essential information about the treatment protocol for targeted retinal diseases while simultaneously avoiding the toxic effects of these drugs.
    Journal of Ocular Pharmacology and Therapeutics 07/2008; 24(3):255-67.
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    ABSTRACT: The aim of this study was to investigate the absorption, distribution, and excretion of radioactivity in male rabbits after a single or repeated instillation of (14)C-labeled tacrolimus (FK506) ophthalmic suspension or an intravenous (i.v.) administration of (14)C-FK506. The 0.3% (14)C-FK506 suspension was administered in single and repeated (three times, 5-min intervals) instillation studies, and 1 mg/kg of (14)C-FK506 was administered in the i.v. dose study. Results for single and repeated instillation studies were similar. In eyeball microautoradiograms, 15 min after dosing, the level of radioactivity in the cornea was the highest, followed by conjunctiva. After 1 h, little specific distribution was detected in the corneal epithelium, stroma, or Descemet's membrane. At 24 h, the level of radioactivity in the cornea decreased. Whole-body autoradiograms showed that the radioactivity was distributed to the digestive tract through the nasal meatus and esophagus and then was excreted into the feces. In the i.v. dose study, the distribution of radioactivity in whole-body autoradiographs was similar to that in quantitative tissue distribution measurements. The excretion of radioactivity in the urine and feces up to 168 h were 4.5 and 94.9%, respectively. After the ocular instillation, FK506 is first absorbed in the cornea, conjunctiva, and nasolacrimal duct, and then the rest is distributed to digestive tract through the nasal meatus and esophagus, after which it is excreted mainly into the feces.
    Journal of Ocular Pharmacology and Therapeutics 07/2008; 24(3):333-43.
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    ABSTRACT: The use of plasmin for pharmacologic vitreolysis and the creation of a posterior vitreous detachment offers several potential advantages over surgery. The nonclinical pharmacokinetics and safety of human-derived plasmin was evaluated following single or multiple intravitreal injections to rabbits and minipigs. Single intravitreal injections of plasmin at 45-900 microg resulted in a no adverse effect level (NOAEL) of 45 microg in both species; effects at higher doses included chemosis, mucopurulent discharge, mononuclear cell infiltrates in the iris-ciliary body, and reversible changes in electroretinogram waveforms and parameters. No retinal histopathology abnormalities were observed. Following 4 weekly intravitreal injections at 4-423 microg, a NOAEL of 4 microg was identified. Effects at the higher doses included myosis, iritis, iridolenticular synechiae, and changes in electroretinogram waveforms and parameters that were generally not reversible in the present investigation. Vitreal plasmin concentrations were highest at 30 min after dosing and decreased rapidly; measurable concentrations remained, in some animals, at 24 h. Intravitreal plasmin exposure increased in a less-than-dose-proportional manner and tended to be lower in minipigs than in rabbits. The current findings demonstrate acceptable nonclinical safety and pharmacokinetics of intravitreal human plasmin in rabbits and minipigs and support the clinical development of plasmin for ocular diseases.
    Journal of Ocular Pharmacology and Therapeutics 07/2008; 24(3):320-32.
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    ABSTRACT: The aim of this study was to investigate the ocular distribution of tacrolimus (FK506) and absorption into the systemic circulation after a single or repeated topical instillation of FK506 ophthalmic suspension in male New Zealand white rabbits. In the single instillation study (group 1), 29.1-34.8 microL of a 0.1, 0.3, and 1% suspension was administered to each of the 15 rabbits. In the repeated instillation study (group 2), 27.1-39.5 microL of a 0.3% suspension was administered to 27 rabbits q.i.d. (i.e., at 3-h intervals) for 14 days. In the intravenous (i.v.) dose study (group 3), 1 mg/kg of FK506 was administered to 3 rabbits. The amount of FK506 was measured by using a competitive enzyme immunoassay. The results for single and repeated instillation studies were similar. In the single instillation study, blood T(max) after an instillation of the 0.1, 0.3, and 1% suspensions (at 0.8, 1.0, and 1.0 hours) did not differ significantly among these doses. One (1) h after an instillation of the 1% suspension, ocular tissue concentrations, except the retina/choroid, vitreous body, and lens, were higher than the blood concentration (C(max): 2.7 ng/mL). In particular, concentrations in the conjunctiva, cornea, iris, and anterior sclera were much higher than the blood concentration (148, 900, 120, and 145 ng/g tissue). In the repeated instillation study, concentrations in the blood and ocular tissues (except the lens) reached a steady state by the 7th day. In the i.v. dose study, AUC(0-24h) and T(1/2) were 1643 ng h/mL and 18.5 h, respectively. The high-level distribution of FK506 was observed in the conjunctiva, which is desirable because the conjunctiva is the target tissue for pharmacologic effect (i.e., efficacy).
    Journal of Ocular Pharmacology and Therapeutics 07/2008; 24(3):309-19.

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