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      Rhegmatogenous retinal detachment following intravitreal ocriplasmin

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          Abstract

          Purpose

          To describe the characteristics and outcomes of patients presenting with rhegmatogenous retinal detachment (RRD) after ocriplasmin (OCP) injection.

          Methods

          Retrospective, multi-centre, observational case series with case note review.

          Results

          Eight patients with symptomatic vitreomacular traction (six with concomitant macular hole) were diagnosed with RRD after a median of 16 days (range 3–131 days) post-OCP injection. Presentation was within 3 weeks of the OCP injection in six of the cases. Five patients presented with symptoms post-OCP, and three were diagnosed asymptomatically on planned visits. Seven cases were phakic, one had high myopia (>8 dioptres), and two cases had lattice degeneration. Following RRD surgery, hole closure was achieved in 5/6 MH cases. The final median BCVA at 7 months was 20/80 (range 20/40–20/1200) similar to the baseline BCVA 20/80, with four patients gaining ≥1 line of vision compared to baseline but three losing ≥3 lines.

          Conclusions

          RRD is a non-negligible risk associated with intravitreal OCP, and it should be used with caution in eyes with high myopia and peripheral retinal pathology predisposing to RRD. Detailed peripheral retinal examination is recommended pre- and postoperatively at all visits. Patients should be advised to seek attention if symptoms recur after initial presentation.

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          Most cited references30

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          Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular holes.

          Vitreomacular adhesion can lead to pathologic traction and macular hole. The standard treatment for severe, symptomatic vitreomacular adhesion is vitrectomy. Ocriplasmin is a recombinant protease with activity against fibronectin and laminin, components of the vitreoretinal interface. We conducted two multicenter, randomized, double-blind, phase 3 clinical trials to compare a single intravitreal injection of ocriplasmin (125 μg) with a placebo injection in patients with symptomatic vitreomacular adhesion. The primary end point was resolution of vitreomacular adhesion at day 28. Secondary end points were total posterior vitreous detachment and nonsurgical closure of a macular hole at 28 days, avoidance of vitrectomy, and change in best-corrected visual acuity. Overall, 652 eyes were treated: 464 with ocriplasmin and 188 with placebo. Vitreomacular adhesion resolved in 26.5% of ocriplasmin-injected eyes and in 10.1% of placebo-injected eyes (P<0.001). Total posterior vitreous detachment was more prevalent among the eyes treated with ocriplasmin than among those injected with placebo (13.4% vs. 3.7%, P<0.001). Nonsurgical closure of macular holes was achieved in 40.6% of ocriplasmin-injected eyes, as compared with 10.6% of placebo-injected eyes (P<0.001). The best-corrected visual acuity was more likely to improve by a gain of at least three lines on the eye chart with ocriplasmin than with placebo. Ocular adverse events (e.g., vitreous floaters, photopsia, or injection-related eye pain--all self-reported--or conjunctival hemorrhage) occurred in 68.4% of ocriplasmin-injected eyes and in 53.5% of placebo-injected eyes (P<0.001), and the incidence of serious ocular adverse events was similar in the two groups (P=0.26). Intravitreal injection of the vitreolytic agent ocriplasmin resolved vitreomacular traction and closed macular holes in significantly more patients than did injection of placebo and was associated with a higher incidence of ocular adverse events, which were mainly transient. (Funded by ThromboGenics; ClinicalTrials.gov numbers, NCT00781859 and NCT00798317.).
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            Anatomical and visual outcomes following ocriplasmin treatment for symptomatic vitreomacular traction syndrome.

            To evaluate the anatomical and visual outcomes of patients treated with ocriplasmin for the treatment of symptomatic vitreomacular adhesion (sVMA), including vitreomacular traction syndrome and macular holes.
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              Microplasmin intravitreal administration in patients with vitreomacular traction scheduled for vitrectomy: the MIVI I trial.

              To evaluate the safety and preliminary efficacy of 4 doses and several exposure times of intravitreal microplasmin given before pars plana vitrectomy for vitreomacular traction maculopathy. A multicenter, prospective, uncontrolled, dose-escalation, phase I/II clinical trial. Sixty patients enrolled into 6 successive cohorts. A single intravitreal injection of microplasmin at 1 of 4 doses (25, 50, 75, or 125 microg in 100 microl) administered either 1 to 2 hours, 24 hours, or 7 days before planned pars plana vitrectomy. For safety, a complete ophthalmologic examination, fundus photography, fluorescein angiography, Humphrey visual fields, and electrophysiology; for efficacy, posterior vitreous detachment (PVD) induction as assessed by B-scan ultrasound and ease of PVD induction at the time of vitrectomy. The use of microplasmin led to a progressively higher incidence of PVD induction on ultrasonography with increasing time exposure. A PVD before surgery was observed with 25 microg microplasmin in 0, 2, and 5 patients with increasing exposures (2 hours, 24 hours, 7 days). With increasing dose, a PVD before surgery was observed by ultrasound as follows: 25 microg, 0; 50 microg, 1; 75 microg, 2; 125 microg, 3. However, at surgery, with a 125-microg dose, these patients had a discontinuous layer of vitreous present on the retinal surface resulting from the induction of an anomalous PVD in the form of vitreoschisis. One retinal detachment developed shortly after administration of microplasmin. Two developed after surgery. There were no other safety concerns. Results from this initial clinical trial evaluating intravitreal microplasmin show the drug to be well tolerated and capable of inducing a pharmacologic PVD in some patients. These results warrant evaluation of microplasmin in larger, controlled trials.
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                Author and article information

                Contributors
                +44 1915699065 , +44 1915699060 , David.steel@ncl.ac.uk
                Journal
                Graefes Arch Clin Exp Ophthalmol
                Graefes Arch. Clin. Exp. Ophthalmol
                Graefe's Archive for Clinical and Experimental Ophthalmology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0721-832X
                1435-702X
                8 June 2016
                8 June 2016
                2016
                : 254
                : 12
                : 2333-2338
                Affiliations
                [1 ]Sunderland Eye Infirmary, Queen Alexandra Road, Sunderland, SR2 9HP UK
                [2 ]Bristol Eye Hospital, Lower Maudlin Street, Bristol, UK
                [3 ]Ophthalmology Department, Cumberland Infirmary, Carlisle, UK
                [4 ]Eye Department, Rigshospitalet, Glostrup, Ndr. Ringvej 57, 2600 Glostrup, Denmark
                [5 ]Department of Ophthalmology, Academic Medical Centre, Meibergdreef 9, 1100 DD Amsterdam, The Netherlands
                [6 ]Vitreoretinal Service, Moorfields Eye Hospital, City Road, London, UK
                [7 ]Manchester Royal Eye Hospital, Oxford Road, Manchester, UK
                [8 ]Royal Wolverhampton NHS Trust, Wolverhampton & Midland Counties Eye Infirmary, Wolverhampton, UK
                [9 ]Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, UK
                Article
                3398
                10.1007/s00417-016-3398-7
                5116307
                27278373
                35ed3f48-604a-441b-bcf5-8d7ee52fa257
                © The Author(s) 2016

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 8 January 2016
                : 3 May 2016
                : 24 May 2016
                Categories
                Retinal Disorders
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2016

                Ophthalmology & Optometry
                macular hole,ocriplasmin,pharmacological vitreolysis,retinal detachment,retinal tears,vitreomacular traction

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