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      Preoperative, Intraoperative and Postoperative Corticosteroid Use as an Adjunctive Treatment for Rhegmatogenous Retinal Detachment

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          Abstract

          The treatment for rhegmatogenous retinal detachment (RRD) is surgery, including pars plana vitrectomy (PPV) and scleral buckling (SB). Despite surgical advances, degeneration of the photoreceptors and post-operative complications, such as proliferative vitreoretinopathy (PVR), often occurs as the result of inflammation, preventing complete visual recovery or causing RRD recurrence. There is increasing evidence that in the presence of RRD, the activation of inflammatory processes occurs and the surgery itself induces an inflammatory response. This comprehensive review focuses on the use of different formulations of corticosteroids (CCS), as an adjunctive treatment to surgery, either PPV or SB, for RRD repair. The purpose was to review the efficacy and safety of CCS in improving functional and anatomical outcomes and in preventing postoperative complications. This review is organized according to the timing of CCS administration: preoperative, intraoperative, and postoperative. The evidence reviewed supported the role of the pre-operative use of CCS in the treatment of combined RRD and choroidal detachment (CD), reducing CD height. No solid consensus exists on intraoperative and postoperative use of CCS to treat and prevent postoperative complications. However, a large randomized clinical trial including more than 200 eyes suggested that oral prednisone after surgery decreases the rate of postoperative grade B PVR.

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          Dose-related patterns of glucocorticoid-induced side effects.

          To identify patterns of self-reported health problems relating to dose and duration of glucocorticoid intake in unselected patients with rheumatoid arthritis from routine practice. Data from 1066 patients were analysed. The clinical status and drug treatment were reported by the physician, health problems during the past 6 months by the patient using a comprehensive list of symptoms. Patients with ongoing glucocorticoid treatment for more than 6 months and current doses of less than 5, 5-7.5 and over 7.5 mg/day prednisone equivalent were compared with a group without any glucocorticoid treatment for at least 12 months. The frequency of self-reported health problems was lowest in the group without glucocorticoid exposition and increased with dosage. Two distinct dose-related patterns of adverse events were observed. A "linear" rising with increasing dose was found for cushingoid phenotype, ecchymosis, leg oedema, mycosis, parchment-like skin, shortness of breath and sleep disturbance. A "threshold pattern" describing an elevated frequency of events beyond a certain threshold value was observed at dosages of over 7.5 mg/day for glaucoma, depression/listlessness and increase in blood pressure. Dosages of 5 mg/day or more were associated with epistaxis and weight gain. A very low threshold was seen for eye cataract (<5 mg/day). The associations found are in agreement with biological mechanisms and clinical observations. As there is a paucity of real-life data on adverse effects of glucocorticoids prescribed to unselected groups of patients, these data may help the clinician to adapt therapy with glucocorticoids accordingly and improve the benefit-risk ratio.
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            Intraocular concentration and pharmacokinetics of triamcinolone acetonide after a single intravitreal injection.

            To describe the pharmacokinetics occurring after the direct injection of triamcinolone acetonide into the vitreous humor of humans. Interventional case series. Five patients who received a single 4-mg intravitreal injection of triamcinolone acetonide. An aqueous humor sample was obtained from 5 eyes via an anterior chamber paracentesis at days 1, 3, 10, 17, and 31 after injection. At each visit, visual acuity and intraocular pressure were measured and indirect ophthalmoscopy was performed. A fluorescein angiogram was carried out at day 10. Concentrations were determined using high performance liquid chromatography; pharmacokinetic analysis was carried out using PK Analyst, an iterative, nonlinear, weighted, least-squares regression program. Intraocular concentrations of triamcinolone were measured and population pharmacokinetic parameters were calculated. Pharmacokinetic data followed a two-compartment model. Peak aqueous humor concentrations ranged from 2151 to 7202 ng/ml, half-lives from 76 to 635 hours, and the integral of the area under the concentration-time curve (AUC(0-t)) from 231 to 1911 ng/h per milliliter. After a single intravitreal injection of triamcinolone, the mean elimination half-life was 18.6 days in nonvitrectomized patients. The half-life in a patient who had undergone a vitrectomy was shorter at 3.2 days. There was considerable intrasubject variation among peak concentration, AUC(0-t) values, and elimination half-lives. After intravitreal injection, measurable concentrations of triamcinolone would be expected to last for approximately 3 months (93 +/- 28 days) in the absence of a vitrectomy. Because triamcinolone pharmacokinetics were characterized only in elderly patients with macular edema, the results cannot be extrapolated to other patient populations.
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              Pharmacokinetics of a sustained-release dexamethasone intravitreal implant in vitrectomized and nonvitrectomized eyes.

              To evaluate dexamethasone pharmacokinetics after implantation of a sustained-release dexamethasone (DEX) intravitreal implant in nonvitrectomized and vitrectomized eyes. The right eyes of 25 rabbits underwent vitrectomy; contralateral eyes served as nonvitrectomy controls. The 0.7-mg DEX implant was injected into both eyes, and drug concentrations were determined in the vitreous humor and retina for 31 days (on days 2, 8, 15, 22, and 31). DEX was present in nonvitrectomized and vitrectomized eyes for at least 31 days. There were no statistically significant differences in DEX concentration between nonvitrectomized and vitrectomized eyes at any time point (P > 0.05). The maximum concentration of DEX in nonvitrectomized versus vitrectomized eyes for vitreous humor was 791 ng/mL (day 22) versus 731 ng/mL (day 22), respectively, and for retina it was 4110 ng/mL (day 15) versus 3670 ng/mL (day 22), respectively. Mean absorption (AUC(0-tlast)) of dexamethasone in nonvitrectomized and vitrectomized eyes was not different for both the vitreous humor (13,600 vs. 15,000 ng/day/mL; P = 0.73) and retina (67,600 vs. 50,200 ng/day/mL; P = 0.47). The vitreoretinal pharmacokinetic profiles were similar between nonvitrectomized and vitrectomized eyes. These observations are consistent with clinical findings of the DEX implant in patients who have undergone vitrectomy and should reduce concerns about the use of the DEX implant in eyes that have undergone vitrectomy.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                21 May 2020
                May 2020
                : 9
                : 5
                : 1556
                Affiliations
                [1 ]Department of Experimental Biomedicine and Clinical Neuroscience, Ophthalmology Section, University of Palermo, 90127 Palermo, Italy; enzabonfiglio@ 123456gmail.com (V.B.); clarapatane@ 123456hotmail.it (C.P.); giovannicillino@ 123456libero.it (G.C.); salvatore.cillino@ 123456unipa.it (S.C.); maria.vadala@ 123456unipa.it (M.V.)
                [2 ]Department of Ophthalmology, University of Catania, 95100 Catania, Italy; iacopomacchi@ 123456gmail.com (I.M.); matteofallico@ 123456hotmail.com (M.F.); corradopizzo@ 123456hotmail.it (C.P.); andrearusso2000@ 123456hotmail.com (A.R.); antlongo@ 123456unict.it (A.L.); alepizzo@ 123456hotmail.it (A.P.); t.avitabile@ 123456unict.it (T.A.); elinaortisi@ 123456gmail.com (E.O.)
                [3 ]Department of Surgical Sciences, Eye Clinic Section, University of Turin, 10122 Turin, Italy
                [4 ]Department of Ophthalmology, Second University of Naples, 80131 Naples, Italy; michele.rinaldi@ 123456unina2.it
                [5 ]Department of General Ophthalmology, Medical University of Lublin, 20079 Lublin, Poland; robertrejdak@ 123456yahoo.com (R.R.); katarzyna.nowomiejska@ 123456umlub.pl (K.N.); toro.mario@ 123456email.it (M.D.T.)
                [6 ]Faculty of Medical Sciences, Collegium Medicum Cardinal Stefan Wyszyński University, 01815 Warsaw, Poland
                Author notes
                [* ]Correspondence: mreibaldi@ 123456libero.it
                Author information
                https://orcid.org/0000-0003-1368-6729
                https://orcid.org/0000-0002-7725-5971
                https://orcid.org/0000-0002-9525-1800
                https://orcid.org/0000-0002-5721-6772
                https://orcid.org/0000-0001-7152-2613
                Article
                jcm-09-01556
                10.3390/jcm9051556
                7290919
                32455658
                4c7ed7b7-3a7d-44b8-85be-99dcd1144186
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 07 April 2020
                : 14 May 2020
                Categories
                Review

                rhegmatogenous retinal detachment,vitrectomy,scleral buckling,dexamethasone,triamcinolone,fluocinolone,corticosteroids

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