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      Subconjunctival sustained-release dexamethasone implant as an adjunct to trabeculectomy for primary open angle glaucoma

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          Abstract

          Sir, In the present study, we described the first case series of intraoperative positioning of subconjunctival dexamethasone implant as adjunctive antiscarring agent in patients undergone trabeculectomy for primary open angle glaucoma (POAG). The rationale of subconjunctival dexamethasone implant injection was to reduce the postsurgical overscarring at the site of the bleb, by limiting the first acute inflammatory reaction that represents the primum movens for conjunctival healing. Three eyes of three consecutive patients (three female) with a mean age of 61 ± 14.5 years taking a maximum tolerated dose of intraocular pressure (IOP)-lowering medication for POAG with a recorded IOP of ≥18 mmHg, glaucomatous damage on visual field and underwent trabeculectomy: All patients underwent a limbus-based conjunctival flap with one circumferential and one radial incision, antimetabolite sponge application, and scleral rectangular flap which was sutured with 10-0 nylon suture, sclerostomy with punch a peripheral iridectomy. Before the conjunctival suture with 9-0 vicryl was performed, a subconjunctival apposition without fixation of 0.7 mg sustained-release dexamethasone implant (Ozurdex, Allergan, Inc., Irvine, USA) was obtained. The implant was softly leaned on the sclera posterior to the flap. After 7 days, 1 month, and 2 months, the implant seemed to fragment reducing progressively its dimensions and was no more detectable after 2 months in all eyes [Fig. 1]. Figure 1 Patient with primary open angle glaucoma undergone trabeculectomy and subconjunctival apposition of 0.7 mg sustained-release dexamethasone implant at day 1 (a), day 7 (b), month 1 (c), and month 2 (d). The implant seemed to fragment reducing progressively its dimensions and was no more detectable after 2 months After 2 months, IOP not quite significantly (P = 0.056, nonparametric Mann–Whitney U-test) decreased from 19.3 ± 2.3 mmHg (median: 18, interquartile range [IQR]: 4) at baseline to 15.7 ± 0.6 mmHg (median: 16, IQR: 1) without any glaucoma medication. In all eyes, IOP was ≤16 mmHg (range: 15–16). After 2 months in all the cases, conjunctival scarring at the site of the filtering bleb was not observed. No ocular adverse event or postoperative complications were observed. Corticosteroids have long been used as inflammation modulators of posttrabeculectomy conjunctival healing with significantly success rates, since they act on vascular permeability, as well as white blood cell chemotaxis and function.[1] First evidence of steroids effects in glaucoma surgery came from Starita et al.,[2 3] who investigated the effects of topical and systemic steroids in a randomized prospective trial. They found that topical steroids significantly improved trabeculectomy outcome as compared to the group without steroids at 5 and 10 years. There are studies about the intraoperative subconjunctival injection of triamcinolone acetonide (TA) after bleb-forming filtration surgery.[4] TA injections appeared to be safe in both studies, with no significant adverse events, even if results of a randomized controlled trial about long-term clinical benefits in patients receiving intrableb TA against whom receiving topical steroids only, have not been published yet. The rationale of intraoperative subconjunctival corticosteroid injection was to find a more direct, sustained, and convenient mode of steroid delivery in the operated patients; moreover, the bulk of injected TA would also serve as a barrier between the inflamed conjunctiva and sclera, to avoid adherence in between. In this view, Ozurdex implant would be even more effective than TA, lasting longer and interposing a bigger volume in the conjunctival layers. Subconjunctival implant appears to be well tolerated by operated eyes. However, use of Ozurdex has been associated with several adverse events including posterior subcapsular cataract and a higher risk of eye infections;[5] reasonably, the most threatening glaucoma surgery success is eye pressure increase that may need supplementary IOP lowering medical therapy after trabeculectomy. Effective success of surgery should therefore be taken only several weeks after the operation, when the insert is completely reabsorbed. Limitations of this study were the small sample size and the absence of a control group. The data of this pilot study showed that no serious side effects were noted, subconjunctival Ozurdex was well tolerated and that a controlled study is required to establish the efficacy of this easy to perform the technique. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

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          The dexamethasone drug delivery system: indications and evidence.

          The Ozurdex(®) (Allergan Inc., Irvine, CA, USA) dexamethasone drug delivery system (DDS) was recently developed as a biodegradable intravitreal implant to provide sustained delivery of 700 μg of preservativefree dexamethasone to the retina and vitreous, and is approved by the United States Food and Drug Administration (FDA) for the treatment of macular edema associated with retinal vein occlusion, as well as for noninfectious posterior uveitis. This review summarizes the rationale behind the development of the dexamethasone DDS, evidence for its use in various clinical scenarios, and compares its efficacy to other available treatment options. Published data regarding the dexamethasone DDS as well as unpublished data that has been presented at national meetings were reviewed. The dexamethasone DDS has evidence for efficacy in multiple clinical situations, including macular edema associated with retinal vein occlusion (RVO), macular edema associated with uveitis or Irvine-Gass syndrome, diabetic macular edema in vitrectomized eyes, persistent macular edema, noninfectious vitritis, and as adjunctive therapy for age-related macular degeneration. Safety concerns include cataract formation and intraocular pressure elevation that is most often temporary and amenable to medical management. The dexamethasone DDS is one of the most recent additions to the armamentarium against macular edema, and is intriguing for its potency, dose consistency, potential for extended duration of action, and favorable safety profile. Early evidence shows clinical utility for several conditions, the most well established being for macular edema associated with RVO. Future studies and, in particular, head-to-head comparisons with other treatment modalities will elucidate the precise role for the dexamethasone DDS in clinical practice.
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            A ten-year follow-up on a prospective, randomized trial of postoperative corticosteroids after trabeculectomy.

            Patients prospectively enrolled in a clinical trial to evaluate the effect of corticosteroid use after guarded filtration procedure (trabeculectomy) were re-evaluated after 10 years to determine whether (1) there were differences in intraocular pressure (IOP) level and stability of glaucoma between treated and nontreated eyes, (2) surgery had altered the clinical course of the patients, and (3) there was any relation between level of IOP and glaucoma control. Forty-six eyes of 35 patients were evaluated individually. Stabilization/ progression of glaucoma was established based on IOP, clinical evaluation of visual fields, and stereoscopic analysis of disc using ophthalmoscopy and photography. The nonsteroid-treated eyes underwent more additional glaucoma surgeries, were treated with more glaucoma medicines, and had higher IOPs. Glaucoma was stabilized in 82.8% of the steroid-treated eyes and 67% of the nonsteroid-treated eyes. There was a direct correlation between level of IOP and stabilization of optic nerve and visual field in both groups. The use of corticosteroids after guarded filtration procedure was correlated with better glaucoma control. Patients with lower IOPs were more likely to be stabilized than those with higher pressures.
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              Conjunctiva and subconjunctival tissue in primary open-angle glaucoma after long-term topical treatment: an immunohistochemical and ultrastructural study.

              Primary open-angle glaucoma is commonly treated with long-term hypotensive medical therapy. When this approach becomes inadequate, therapy proceeds with surgery. The present study investigates morphological changes in the conjunctival and subconjunctival tissues induced by short- and long-term topical medical therapy of primary open-angle glaucoma. Comparisons were made between biopsy specimens from glaucomatous patients, who received specific eyedrop therapy (timolol and pilocarpine) for various periods of time, and control patients with no conjunctival pathology or topical treatment. Histological, immunohistochemical and ultrastructural parameters were investigated. The morphometric analysis of histological sections and immunohistochemistry (anti-fibronectin antibody) in medium- and long-term therapy patients showed: (a) significant increases in the thickness and number of epithelial cell layers; (b) significant increases in the fibroblast density in both subepithelial and deep connective tissue; and (c) a more compact connective tissue, richer in collagen fibers arranged in whirls, with some inflammatory elements. These findings were confirmed by the ultrastructural analysis. In the same patients, the other immunohistochemical parameters investigated (anti-HLA-DR, anti-CD1a, anti-CD4, anti-CD8, anti-IL2 and C3b antibodies) revealed a tendency to chronic inflammation. Following specific surgery, this tendency manifested itself in a diffuse immune response, especially in those patients who underwent medium- and long-term medical therapy. According to these results, antiglaucomatous surgery should be rehabilitated and considered as an alternative to long-term medical therapy in the first-instance treatment of primary open-angle glaucoma.
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                Author and article information

                Journal
                Indian J Ophthalmol
                Indian J Ophthalmol
                IJO
                Indian Journal of Ophthalmology
                Medknow Publications & Media Pvt Ltd (India )
                0301-4738
                1998-3689
                March 2016
                : 64
                : 3
                : 251-252
                Affiliations
                [1]Department of Ophthalmology, University of Bari, Bari, Italy
                [1 ]Department of Ophthalmology, Eye Clinic, University of Sassari, Sassari, Italy
                Author notes
                Correspondence to: Dr. Claudio Furino, Department of Ophthalmology, University of Bari, Piazza Giulio Cesare 11, 70124 Bari, Italy. E-mail: claudiofurino@ 123456gmail.com
                Article
                IJO-64-251
                10.4103/0301-4738.181735
                4869472
                27146944
                8645e0ba-6586-4f43-9174-656dbe7415aa
                Copyright: © Indian Journal of Ophthalmology

                This is an open access article distributed under the terms of the Creative Commons Attribution NonCommercial ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non commercially, as long as the author is credited and the new creations are licensed under the identical terms.

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                Ophthalmology & Optometry

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