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      Emerging nonsurgical methods for the treatment of vitreomacular adhesion: a review

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          Abstract

          With the dissemination of optical coherence tomography over the past two decades, the role of persistent vitreomacular adhesion (VMA) in the development of numerous macular pathologies – including idiopathic macular hole, vitreomacular traction syndrome, cystoid and diabetic macular edema, neovascularization in diabetic retinopathy and retinal vein occlusion, exudative age-related macular degeneration, and myopic traction maculopathy – has been established. While invasive vitreoretinal procedures have long been utilized to address complications related to these disorders, such an approach is hampered by incomplete vitreoretinal separation and vitreous removal, surgical complications, and high costs. In light of such limitations, investigators have increasingly looked to nonsurgical means for the treatment of persistent pathologic VMA. Chief among these alternative measures is the intravitreal application of pharmacologic agents for the induction of vitreous liquefaction and/or vitreoretinal separation, an approach termed pharmacologic vitreolysis. This article aims to review the available evidence regarding the use of pharmacologic agents in the treatment of VMA-related pathology. In addition, a discussion of vitreous molecular organization and principles of physiologic posterior vitreous detachment is provided to allow for a consideration of vitreolytic agent mode of action and molecular targets.

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          Most cited references159

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          Structural macromolecules and supramolecular organisation of the vitreous gel.

          The vitreous gel is a transparent extracellular matrix that fills the cavity behind the lens of the eye and is surrounded by and attached to the retina. This gel liquefies during ageing and in 25-30% of the oppulation the residual gel structure eventually collapses away from the posterior retina in a process called posterior retina in a process called posterior vitreous detachment. This process plays a pivotal role in a number of common blinding conditions including rhegmatogenous retinal detachment, proliferative diabetic retinopathy and macular hole formation. In order to understand the molecular events underlying vitreous liquefaction and posterior vitreous detachment and to develop new therapies it is important to understand the molecular basis of normal vitreous gel structure and how this is altered during ageing. It has previously been established that a dilute dispersion of thin (heterotypic) collagen fibrils is essential to the gel structure and that age-related vitreous liquefaction is intimately related to a process whereby these collagen fibrils aggregate. Collagen fibrils have a natural tendency to aggregate so a key question that has to be addressed is: what normally maintains the spacing of the collagen fibrils? In mammalian vitreous a network of hyaluronan normally fills the spaces between these collagen fibrils. This hyaluronan network can be removed without destroying the gel structure, so the hyaluronan is not essential for maintaining the spacing of the collagen fibrils although it probably does increase the mechanical resilience of the gel. The thin heterotypic collagen fibrils have a coating of non-covalently bound macromolecules which, along with the surface features of the collagen fibrils themselves, probably play a fundamental role in maintaining gel stability. They are likely to both maintain the short-range spacing of vitreous collagen fibrils and to link the fibrils together to form a contiguous network. A collagen fibril-associated macromolecule that may contribute to the maintenance of short-range spacing is opticin, a newly discovered extracellular matrix leucine-rich repeat protein. In addition, surface features of the collagen fibrils such as the chondroitin sulphate glycosaminoglycan chains of type IX collagen proteoglycan may also play an important role in maintaining fibril spacing. Furthering our knowledge of these and other components related to the surface of the heterotypic collagen fibrils will allow us to make important strides in understanding the macromolecular organisation of this unique and fascinating tissue. In addition, it will open up new therapeutic opportunities as it will allow the development of therapeutic reagents that can be used to modulate vitreous gel structure and thus treat a number of common, potentially blinding, ocular conditions.
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            A new 25-gauge instrument system for transconjunctival sutureless vitrectomy surgery.

            To introduce and evaluate the infusion and aspiration rates and operative times of the 25-gauge transconjunctival sutureless vitrectomy system (TSV) DESIGN: In vitro experimental and comparative interventional study. Twenty eyes of 20 patients underwent a variety of vitreoretinal procedures using the 25-gauge TSV, including idiopathic epiretinal membrane (n = 10), macular hole (n = 4), rhegmatogenous retinal detachment (n = 3), branch retinal vein occlusion (n = 2), diabetic vitreous hemorrhage (n = 1), and 20 cases similar in diagnosis and severity were matched to provide comparison between duration of individual portions of the surgical procedures with the existing 20-gauge vitrectomy system. Description of the 25-gauge TSV is provided; infusion and aspiration rates of the 25-gauge and standard 20-gauge vitrectomy system were measured in vitro using balanced saline solution and porcine vitreous for several levels of aspirating power and bottle height, and operating times of individual portions of surgical procedures were measured for the 25-gauge and 20-gauge vitrectomy system. Infusion, aspiration rates, and operative times of the 20-gauge and 25-gauge vitrectomy system. Infusion and aspiration rates of the 25-gauge TSV system were reduced by an average of 6.9 and 6.6 times, respectively, compared with the 20-gauge system when balanced saline solution was used. The average flow rate of the Storz 25-gauge cutter (at 500 mmHg, 1500 cuts per minute [cpm]) was 40% greater than that of the 20-gauge pneumatic cutter (at 250 mmHg, 750 cpm) but about 2.3 times less than the 20-gauge high-speed cutter (at 250 mmHg, 1500 cpm). Mean total operative time was significantly greater for the 20-gauge high-speed cutter (26 minutes, 7 seconds) than for the 25-gauge vitrectomy system (17 minutes, 17 seconds) (P = 0.011). Although the infusion and aspiration rates of the 25-gauge instruments are lower than those for the 20-gauge high-speed vitrectomy system, the use of 25-gauge TVS may effectively reduce operative times of select cases that do not require the full capability of conventional vitrectomy.
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              Posterior vitreous detachment: evolution and complications of its early stages.

              To summarize emerging concepts regarding the onset and progression, traction effects, and complications of the early stages of age-related posterior vitreous detachment (PVD). Interpretive essay. Review and synthesis of selected literature, with clinical illustrations, interpretation, and perspective. Imaging of the vitreoretinal interface with optical coherence tomography has shown that PVD begins in the perifoveal macula. Recent longitudinal studies have demonstrated conclusively that early PVD stages persist chronically and progress slowly over months to years. Vitreous traction forces resulting from perifoveal PVD with a small vitreofoveolar adhesion (500 microm or less) may cause localized cystoid foveal thickening or one of several macular hole conditions. Traction associated with larger adhesion zones may cause or exacerbate a separate group of macular disorders. Ultrastructural studies suggest that epiretinal membrane develops from cortical vitreous remnants left on the retinal surface after PVD and plays an important role in traction vitreomaculopathies. Age-related PVD is an insidious, chronic event that begins in the perifoveal macula and evolves over a prolonged period before vitreopapillary separation. Although asymptomatic in most individuals, its early stages may be complicated by a variety of macular and optic disc pathologic features, determined in part by the size and strength of the residual vitreoretinal adhesion. (c) 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Clin Ophthalmol
                Clinical Ophthalmology
                Clinical Ophthalmology (Auckland, N.Z.)
                Dove Medical Press
                1177-5467
                1177-5483
                2011
                2011
                18 August 2011
                : 5
                : 1151-1165
                Affiliations
                Department of Ophthalmology and Visual Sciences, University of Michigan, WK Kellogg Eye Center, Ann Arbor, MI, USA
                Author notes
                Correspondence: Mark W Johnson, University of Michigan, Department of Ophthalmology and Visual Sciences, 1000 Wall St, Ann Arbor, MI 48105, USA, Tel +1 734 936 7760, Fax +1 734 936 2340, Email markwj@ 123456med.umich.edu
                Article
                opth-5-1151
                10.2147/OPTH.S14840
                3162296
                21887098
                a1990337-1c46-4194-9ec6-063df29f1e08
                © 2011 Schneider and Johnson, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                History
                : 17 August 2011
                Categories
                Review

                Ophthalmology & Optometry
                macular edema,macular hole,microplasmin,pharmacologic vitreolysis,posterior vitreous detachment,vitreomacular traction syndrome

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