STATEMENT OF NEED

The goal of this continuing medical education (CME) supplement is to improve patient care by retina specialists and other ophthalmologists when they are managing symptomatic vitreomacular adhesion and traction.

Symptomatic vitreomacular adhesion is a condition when the vitreous gel adheres in an abnormally strong manner to the retina. VMA can lead to vitreomacular traction (VMT) and subsequent loss or distortion of visual acuity. Anomalous posterior vitreous detachment PVD is linked to several retinal disorders including macular pucker, macular hole, age-related macular generation (AMD), macular edema, and retinal tears and detachment.

The incidence of VMA has been reported to be as high as 84% in cases of macular hole; 74% in vitreomacular traction syndrome; and 56% in idiopathic epimacular membrane.1 The incidence of VMA in macular edema appears to depend on the severity of the underlying condition.2,3 In AMD, the rates vary3-12 but have been reported to be as high as 59% in exudative AMD.12

Currently, pars plana vitrectomy (PPV) is used to surgically induce PVD and release the traction on the retina for selected cases. A vitrectomy procedure, however, is not without risk. Complications with standard PPV12-15 and more recently with small-gauge PPV16-20 have been reported and include retinal detachment, retinal tears, endophthalmitis, and postoperative cataract formation. Additionally, PPV may result in incomplete separation and it may potentially leave a nidus for vasoactive and vasoproliferative substances or it may induce development of fibrovascular membranes. Further, as is with any invasive surgical procedure, PPV introduces more trauma to the vitreous and surrounding tissues.21,22

There are data showing that pharmacological induction of PVD using ocriplasmin (formerly known as microplasmin), a proteolytic human enzyme with activity against the protein matrix that comprises the vitreoretinal interface, has the following advantages over PPV: It induces complete separation, creates a more physiologic state of the vitreomacular interface, prevents the development of fibrovascular membranes, is less traumatic to the vitreous, and is potentially prophylactic.21,22 Additionally, vitreolysis obviates the costs associated with surgery and allows for earlier intervention, whereas surgery is reserved for more advanced cases. In two phase 3 studies, a single injection of ocriplasmin was shown to be safe and effective for PVD induction, 23,24 providing further evidence that pharmacologic vitreolysis with ocriplasmin may provide an safe and effective alternative to PPV for inducing PVD.

To address these gaps, retina specialists and other ophthalmologists must master insights on the pathogenesis of VMA, the role that VMA plays in various retinal pathologies, and the benefits of induced PVD vs anomalous PVD. Mastery includes knowledge of the clinical implications of VMA and the results of recent clinical trials on both surgical and pharmacologic PVD induction, an understanding of vitreolysis agents and their differences, and the ability to identify patients who may benefit from PVD induction.

  1. Koerner F, Garweg J. [Diseases of the vitreo-macular interface]. Klin Monbl Augenheilkd. 1999;214(5):305-310.
  2. Takahashi MK, Hikichi T, Akiba J, Yoshida A, Trempe CL. Role of the vitreous and macular edema in branch retinal vein occlusion. Ophthalmic Surg Lasers. 1997;28(4):294-299.
  3. Kado M, Jalkh AE, Yoshida A, et al. Vitreous changes and macular edema in central retinal vein occlusion. Ophthalmic Surg. 1990;21(8):544-549.
  4. Lambert HM, Capone A, Jr., Aaberg TM, et al. Surgical excision of subfoveal neovascular membranes in age-related macular degeneration. Am J Ophthalmol. 1992;113(3):257-262
  5. Weber-Krause B, Eckardt U. [Incidence of posterior vitreous detachment in eyes with and without age-related macular degeneration. An ultrasonic study]. Ophthalmologe. 1996;93(6):660-665.
  6. Ondes F, Yilmaz G, Acar MA, et al. Role of the vitreous in age-related macular degeneration. Jpn J Ophthalmol. 2000;44(1):91-93.
  7. Krebs I, Brannath W, Glittenberg C, et al. Posterior vitreomacular adhesion: a potential risk factor for exudative age-related macular degeneration? Am J Ophthalmol. 2007;144(5):741- 746.
  8. Lee SJ, Lee CS, Koh HJ. Posterior vitreomacular adhesion and risk of exudative agerelated macular degeneration: paired eye study. Am J Ophthalmol. 2009;147(4):621-626 e1.
  9. Robison CD, Krebs I, Binder S, et al. Vitreomacular adhesion in active and end-stage agerelated macular degeneration. Am J Ophthalmol. 2009;148(1):79-82.
  10. Wheatley HM. Posterior vitreomacular adhesion and exudative age-related macular degeneration. Am J Ophthalmol. 2008;145(4):765; author reply -6.
  11. Schmidt JC, Mennel S, Meyer CH, Kroll P. Posterior vitreomacular adhesion: a potential risk factor for exudative age-related macular degeneration. Am J Ophthalmol. 2008;145(6):1107; author reply -8.
  12. Mojana F, Cheng L, Bartsch DU, et al. The role of abnormal vitreomacular adhesion in age-related macular degeneration: spectral optical coherence tomography and surgical results. Am J Ophthalmol. 2008;146(2):218-227.
  13. Doft BH, Wisniewski SR, Kelsey SF, Groer-Fitzgerald S; Endophthalmitis Vitrectomy Study Group. Diabetes and postcataract extraction endophthalmitis. Curr Opin Ophthalmol. 2002;13(3):147-151.
  14. Doft BM, Kelsey SF, Wisniewski SR. Retinal detachment in the endophthalmitis vitrectomy study. Arch Ophthalmol. 2000;118(12):1661-1665.
  15. Wisniewski SR, Capone A, Kelsey SF, et al. Characteristics after cataract extraction or secondary lens implantation among patients screened for the Endophthalmitis Vitrectomy Study. Ophthalmology. 2000;107(7):1274-1282.
  16. Gupta OP, Weichel ED, Regillo CD, et al. Postoperative complications associated with 25- gauge pars plana vitrectomy. Ophthalmic Surg Lasers Imaging. 2007;38(4):270–275.
  17. Liu DT, Chan CK, Fan DS, Lam SW, Lam DS, Chan WM. Choroidal folds after 25 gauge transconjunctival sutureless vitrectomy. Eye. 2005;19(7):825–827.
  18. Scott IU, Flynn HW Jr, Dev S, et al. Endophthalmitis after 25-gauge and 20-gauge pars plana vitrectomy: incidence and outcomes. Retina. 2008;28(1):138–142.
  19. Kunimoto DY, Kaiser RS; Wills Eye Retina Service. Incidence of endophthalmitis after 20- and 25-gauge vitrectomy. Ophthalmology. 2007;114(12):2133–2137.
  20. Kaiser RS. Complications of sutureless vitrectomy and the findings of the Micro-Surgical Safety Task Force. Paper presented at: Retina Subspecialty Day, Annual Meeting of the American Academy of Ophthalmology; November 7-8, 2008; Atlanta, GA.
  21. de Smet MD, Gandorfer A, Stalmans P, et al. Microplasmin intravitreal administration in patients with vitreomacular traction scheduled for vitrectomy: the MIVI I trial. Ophthalmology. 2009;116(7):1349-1355.
  22. Goldenberg DT, Trese MT. Pharmacologic vitreodynamics and molecular flux. Dev Ophthalmol. 2009;44:31-36.
  23. Jumper J, Pakola S. The MIVI-007 trial. Phase 3 evaluation of single intravitreous injection of microplasmin or placebo for treatment of focal vitreomacular adhesion. Paper presented at: the American Society of Retina Specialists; August 31, 2010; Vancouver, BC.
  24. Packo K, Pakola S. The MIVI-006 trial. Phase 3 evaluation of single intravitreous injection of microplasmin or placebo for treatment of focal vitreomacular adhesion. Paper presented at: the American Society of Retina Specialists; August 31, 2010; Vancouver, BC.

TARGET AUDIENCE

This certified CME activity is designed for retina specialists and general ophthalmologists involved in the management of patients with retinal disease.

LEARNING OBJECTIVES

Upon completion of this activity, the participant should be able to:

  • Explain the process by which VMA occurs
  • Identify the disease states with which VMA is associated
  • Identify the clinical implications of anomalous PVD
  • Identify the risks of performing vitrectomy to induce PVD
  • Explain the mechanism of action of pharmacologic vitreolysis
  • Differentiate between the various agents that can be used for pharmacologic vitreolysis in terms of their composition, advantages, and disadvantages
  • Discuss the available data on the safety and efficacy of vitreolysis agents for PVD induction

METHOD OF INSTRUCTION

Participants should read the CME activity in its entirety. After reviewing the material, please complete the selfassessment test, which consists of a series of multiplechoice questions. To answer these questions online and receive realtime results, please visit http://www.dulaneyfoundation.org and click “Online Courses.” Upon completing the activity and achieving a passing score of over 70% on the self-assessment test, you may print out a CME credit letter awarding 1 AMA PRA Category 1 Credit.™ The estimated time to complete this activity is 1 hour.

ACCREDITATION AND DESIGNATION

This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the Dulaney Foundation and Retina Today. The Dulaney Foundation is accredited by the ACCME to provide continuing education for physicians. The Dulaney Foundation designates this enduring material for a maximum of 1 AMA PRA Category 1 Credit.™ Physicians should claim only the credit commensurate with the extent of their participation in the activity.

DISCLOSURE

In accordance with the disclosure policies of the Dulaney Foundation and to conform with ACCME and US Food and Drug Administration guidelines, anyone in a position to affect the content of a CME activity is required to disclose to the activity participants (1) the existence of any financial interest or other relationships with the manufacturers of any commercial products/devices or providers of commercial services and (2) identification of a commercial product/device that is unlabeled for use or an investigational use of a product/device not yet approved.

FACULTY CREDENTIALS

David M. Brown, MD, is the director of the Greater Houston Retina Research Center and practices at Retina Consultants of Houston and the Methodist Hospital in Houston, TX. He is a member of the Retina Today Editorial Board.

Pravin U. Dugel, MD, is Managing Partner of Retinal Consultants of Arizona in Phoenix; Clinical Associate Professor of Ophthalmology, Doheny Eye Institute, Keck School of Medicine at the University of Southern California, Los Angeles; and Founding Member of the Spectra Eye Institute in Sun City, AZ. He is a member of the Retina Today Editorial Board.

Mark S. Humayun, MD, PhD, is Professor of Ophthalmology, Biomedical Engineering, Cell and Neurobiology, Keck School of Medicine of the University of Southern California and is Associate Director of Research at the Doheny Retina Institute in Los Angeles.

Peter K. Kaiser, MD is Professor of Ophthalmology at the Cleveland Clinic Lerner College of Medicine and a staff surgeon in the Vitreoretinal Department at the Cole Eye Institute, Cleveland Clinic. He is the Founding Director of the Digital Optical Coherence Tomography Reading Center (DOCTR) at the Cole Eye Institute. He is a member of the Retina Today Editorial Board.

Michael T. Trese, MD, is Clinical Professor of Biomedical Sciences at The Eye Research Institute of Oakland University, Clinical Associate Professor at Wayne State University School of Medicine, and Chief of Pediatric and Adult Vitreoretinal Surgery at William Beaumont Hospital.

FACULTY/STAFF DISCLOSURE DECLARATIONS

David M. Brown, MD, reports that he receives financial support from Alcon, Alimera, Allergan, Eli Lilly, Genentech, Molecular Partners, Ophthotech, Paloma, Regeneron, Steba Biotech, and Thrombogenics; honoraria and/or travel reimbursement from Allergan, Genentech, and Regeneron; and is a consultant to Alcon, Alimera, Allergan, Genentech, Molecular Partners, Paloma, Regeneron, Steba Biotech, and Thrombogenics.

Pravin U. Dugel, MD, reports that he is a consultant to Abbott Medical Optics, Alcon, Allergan, Arctic Dx, Bausch + Lomb, Genentech, Macusight, Neovista, ORA, QLT, Regeneron, and Santen.

Mark S. Humayun, MD, PhD, reports that he is a consultant to, shareholder of, receives honoraria and/or travel reimbursement from, and holds patents with Second Sight Medical Products.

Peter K. Kaiser, MD, reports that he is a consultant to Alcon, Arctic Dx, Bausch + Lomb, Bayer, Genentech, Kang Hong Biotech, Novartis, Opthotec, Oraya, and Regeneron; and is a shareholder in SKS Ocular.

Michael T. Trese, MD, reports that he is an investor/shareholder with Nu-Vue Technologies; holds patents with Nu- Vue Technologies, and Thrombogenics; and is a consultant to Synergetics.

All of those involved in the planning, editing, and peer review of this educational activity report no financial relationships.