Highly hydrophilic 1,3-oxazol-5-yl benzenesulfonamide inhibitors of carbonic anhydrase II for reduction of glaucoma-related intraocular pressure
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01.11.2019 |
Kalinin S.
Valtari A.
Ruponen M.
Toropainen E.
Kovalenko A.
Nocentini A.
Gureev M.
Dar'in D.
Urtti A.
Supuran C.
Krasavin M.
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Bioorganic and Medicinal Chemistry |
10.1016/j.bmc.2019.115086 |
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© 2019 Elsevier Ltd Four inhibitors of human carbonic anhydrase II (hCA II) were designed based on the previously reported subnanomolar 1,3-oxazole-based sulfonamide inhibitors of the enzyme to incorporate primary and secondary amine functionality in the carboxamide side chain. The new hydrophilic compounds were found to inhibit the target isoform in sub-nanomolar to low nanomolar range with a good degree of selectivity to several other hCA isoforms. The hydrophilic character of these compounds is advantageous for intraocular residence time but not for corneal permeability which generally requires that a drug be sufficiently lipophilic. Two of the four compounds investigated, however, were found to exert comparable efficacy as 1% eye drops in PBS to that of the clinically used 2% dorzolamide (Trusopt®) eye drops. This indicated that the absorption of the compounds may occur via alternative route across conjunctiva and sclera.
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Interchangeability Issues with Glaucoma Medicines Using Latanoprost as an Example
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01.02.2018 |
Bunyatyan N.
Filippova O.
Romanov B.
Prokof’ev A.
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Pharmaceutical Chemistry Journal |
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© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The possible interchangeability of eye drops was analyzed using glaucoma medicines containing latanoprost as examples. It was shown that the reference and generic drugs could be identical with respect to composition of active ingredients when manufactured from the same pharmaceutical substance but could differ in the excipient composition, in particular, have a different buffer and osmolality that could produce differences in their clinical effects. An analysis of the literature showed that the therapeutic efficacy and safety could vary for pharmaceutically equivalent drugs. The lack of therapeutic equivalence on the background of pharmaceutical equivalence could be caused by the use of different packaging and different dosing systems. Therefore, results from clinical trials must be compared to confirm the interchangeability of eye drops.
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Optical coherence tomography for examination of glaucoma surgery site
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01.01.2018 |
Avetisov S.
Petrov S.
Volzhanin A.
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Vestnik oftalmologii |
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The article reviews the results of using optical coherence tomography (OCT) - a non-invasive non-contact examination method for obtaining a tomographic slice image of the site of glaucoma surgery. The method helped reveal the functional relationships between the newly created outflow pathways and various parameters of the filtering bleb such as its linear dimensions, wall structure, presence of microcysts, position of drainage, etc. Due to its high resolution and noninvasiveness, OCT can be reliably used to examine the structure of aqueous outflow pathways in different postoperative periods with accuracy close to morphometric. The amount of data that had been obtained with the method has allowed the creation of new classifications and clarification of OCT-relevant prognostic signs for glaucoma surgery site.
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Influence of cataract phacoemulsification on eye hydrodynamics in patients with prior trabeculectomy
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01.01.2018 |
Avetisov S.
Erichev V.
Petrov S.
Volzhanin A.
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Vestnik Oftalmologii |
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© 2018, Media Sfera. All rights reserved. At present, phacoemulsification and trabeculectomy are the most widespread surgery methods in cataract and glaucoma treatment, generally recognized as the gold standard. Among elderly patients, comorbid glaucoma and cataract are extremely prevalent, so the order of the two surgeries and the time interval between them are pivotal choices when planning treatment strategy. The reason for it is that almost any eye surgery is considered a risk factor for long-term trabeculectomy effectiveness. In attempts to solve this problem, numerous studies have been conducted on the impact of cataract surgery on filtration bleb scarring. The problem of determining the time interval between surgeries, as well as other treatment nuances, remains relevant despite the long history of research and publications. Some results are cited as general recommendations on treatment tactics (increasing the time interval between operations, using antimetabolite and anti-inflammatory therapy, minimizing intraoperative traumatism). However, currently there are no specific recommendations for one of the most important factors - the time interval between cataract extraction and trabeculectomy.
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Effects of artificial tears on ocular surface in glaucomatous patients with long-term instillation of preserved antiglaucoma eye drops
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01.01.2018 |
Makashova N.
Vasilieva A.
Kolosova O.
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Vestnik Oftalmologii |
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© 2018 Media Sfera. All rights reserved. Purpose. To study the effects of long-term instillation of 0.18% sodium hyaluronate artificial tears VISMED multi on ocular surface in glaucomatous patients with long-term instillation of preserved anti-glaucoma drops. Material and methods. The study included 79 patients (40 female and 39 male; 79 eyes in total) with primary open-angle glaucoma (POAG) divided into 3 groups according to disease stage: mild or early (stage I) glaucoma - 15 patients (15 eyes), moderate (stage II) glaucoma - 30 patients (30 eyes), advanced or severe (stage III) glaucoma - 34 patients (34 eyes). Conjunctival and corneal changes were assessed with Norn's test, Schirmer I test and corneal fluorescein staining test. All patients completed Ocular Surface Disease Index (OSDI) questionnaire. Corneal compensated intraocular pressure (IOPcc) was measured using Ocular Response Analyzer (ORA) (Reichert Optics Inc., USA). In addition to hypotensive therapy, all patients received instillations of 0.18% sodium hyaluronate (VISMED multi) three times every day. After 14 days, all examinations were repeated. Results. The condition of eye surface in patients with moderate and advanced (stage II and III) glaucoma depends on the degree of IOPcc compensation. As glaucoma increases in severity, the pathological changes in the ocular surface progress. Instillations of 0.18% sodium hyaluronate solution lead to significant improvement of the test results in all groups, and in early glaucoma patients it restores all objective indicators to normal values. Conclusion. Treatment with 0.18% sodium hyaluronate solution (VISMED multi) leads to statistically significant (p<0.05) improvement of ocular surface condition in glaucoma patients with long-term instillation of preserved antiglaucoma eye drops.
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Specific features of collagen implant biodegradation after glaucoma surgery in rabbit eye (experimental study)
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01.01.2018 |
Mamikonyan V.
Fisenko N.
Demura T.
Kogan E.
Kazaryan E.
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Eksperimental'naya i Klinicheskaya Farmakologiya |
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© 2018 Izdatel'stvo Meditsina. All rights reserved. The healing process in the adult rabbit conjunctiva and sclera tissues after translimbal microdrainage with the use of either biodegradable antiglaucomatous drainage (BDAD) or iGen was studied. Wound areas showed similar acute inflammatory response to the implantation of both matrixes on the 7th day. Complete lysis degradation of iGen and BDAD was observed on 30th day and 60th day, respectively. Within 60 - 90 days after BDAD implantation, the wound areas of conjunctiva and sclera showed intensive angiogenesis and poor extracellular matrix scarring. In contrast, on the 90th day after iGen implantation, a decrease in angiogenesis and intensive extracellular matrix scar formation were observed. As a result of scarring the thin-walled vessels were compressed, which led to the reduction of aqueous humor outflow.
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