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Updates on The Management of AMD and RVO: An Evidence-based Approach

By: Richard S. Kaiser, MD, Brandon G. Busbee, MD, Baruch D. Kuppermann, MD, PhD, Carl D. Regillo, MD

This course has expired. You can still review the content but course credit is no longer available.

Supplement Credits: 1

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

Expiration Date: Monday, June 30, 2014
Release Date: June 2013

Learning Objectives

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

  • recognize various forms of macular edema and inflammation, using the latest developments in the medical literature and new insights from case-based learning;
  • understand the new data available on treatments for AMD and RVO and how to apply this information in monotherapy and combination therapy treatment schemes; and
  • treat various forms of macular edema and inflammation, based on assessment of patient need, latest developments in the medical literature and insights from case-based learning.

Accreditation and Designation Statement

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.

Statement of Need

Neovascular age-related macular degeneration (AMD) is
characterized by a loss of vision in the center of the visual field and typically affects older people. Considered the most severe form of AMD, it has been designated as 1 of the leading causes of vision loss on a global scale.1-4 Ranibizumab (Lucentis, Genentech) was approved by the US Food and Drug Administration (FDA) in 2006, and has been shown to stabilize or improve vision in those with neovascular AMD,5,6 but a common complaint is that dosing must be monthly for the effects to be maintained. The PrONTO study evaluated patients treated with 3 monthly injections of
ranibizumab, and then dosing on an as-needed (prn) basis. The preliminary results suggested patients maintained visual acuity gains, and were able to halve their monthly dosing schedule.7
Some retina specialists have used bevacizumab (Avastin,
Genentech), which is a full-length recombinant humanized
monoclonal antibody directed against VEGF first approved
for the treatment of metastatic colorectal cancer, off-label as a compounded ophthalmic preparation, for the treatment of neovascular AMD. There have been questions, however, as to how safe and effective off-label use of bevacizumab is compared with ranibiuzmab. A recent analysis of Part B Medicare expenditures suggests that this off-label use is prevalent.8
To address the questions of efficacy and safety of this offlabel use in comparison with the on-label treatment of wet AMD with ranibizumab, the National Eye Institute funded a large multicenter study to compare the 2 treatments. The results of the Comparison of AMD Treatments Trial (CATT), which were recently made available, demonstrated noninferiority of intravitreally injected bevacizumab in comparison
to ranibizumab for the treatment of wet AMD.9 The study
authors noted, however, that differences in rates of serious systemic adverse events require further study.
Aflibercept (Eylea, Regeneron) is the most recent addition to available treatments for wet AMD. Alflibercept was approved for the treatment of AMD by the FDA in 2011. VIEW 1 and 2 were parallel phase 3 clinical trials evaluating the efficacy of
aflibercept for the treatment of wet AMD.10,11 VIEW 1 and 2 showed that aflibercept dosed every other month after 3 loading doses was noninferior to ranibizumab.
Most recently, data from the phase 3 HARBOR study were
released. This trial evaluated the effects of a higher dose of ranibizumab, 2.0 mg, vs the FDA-approved dose of 0.5 mg in monthly and prn dosing formats. The results did not meet the efficacy endpoint for superiority of 2 mg ranibizumab monthly, nor did they meet the secondary endpoint of noninferiority in
the prn arm.12 Retinal vein occlusion (RVO) is a common ocular disease that remains poorly understood due to the multifactorial nature of its presentation and contributing systemic factors.
Several associated systemic factors have been identified and continue to be studied for their impacts on RVO, including hypertension, diabetes, hypercholesterolemia, thyroid disorder, and ischemic heart disease. Increased intraocular pressure and
axial length also play roles in this disease.13,14
For many years, clinicians have followed the recommendations set forth by the Branch Vein Occlusion Study15 and the Central Vein Occlusion Study for managing branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO), respectively.16 The former study demonstrated that grid laser
photocoagulation leads to more improvement of visual acuity than natural history, but the latter showed that grid laser photocoagulation did not improve visual acuity even though the macular edema decreased.
The SCORE CRVO trial found that patients treated with
intravitreal steroid experienced a substantial visual acuity gain of 3 or more lines that persisted for up to 2 years.17
The dexamethasone intravitreal implant 0.7 mg (Ozurdex,
Allergan) was approved by the FDA for the treatment of
macular edema secondary to RVO in 2009. Treated patients
in the GENEVA study had visual acuity gains and reduction in macular edema at 2 months that was not observed in those in the placebo arm of the study.18
Ranibizumab was FDA-approved for macular edema following
both BRVO and CRVO in 2010, based on the positive
results of the BRAVO19 and CRUISE20 studies.
Aflibercept was approved by the FDA in 2012 for the
treatment of macular edema secondary to CRVO. The
COPERNICUS study evaluated aflibercept for the treatment of macular edema secondary to CRVO and found that patients in the treatment arms gained a significantly higher number of letters of vision than those receiving placebo.21
1. Klein R, Klein BE, Linton KL. Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology.
1992;99(6):933-943.
2. Mitchell P, Smith W, Attebo K, Wang JJ. Prevalence of age-related maculopathy in Australia. The Blue Mountains Eye Study.
Ophthalmology. 1995;102(10):1450-1460.
3. Vingerling JR, Dielemans I, Bots ML, et al. Age-related macular degeneration is associated with atherosclerosis. The Rotterdam
Study. Am J Epidemiol. 1995;142(4):404-409.
4. Vingerling JR, Dielemans I, Hofman A, et al. The prevalence of age-related maculopathy in the Rotterdam Study. Ophthalmology.
1995;102(2):205-210.
5. Rosenfeld PJ, Brown DM, Heier JS, et al; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration.
N Engl J Med. 2006;355(14):1419-1431.
6. Brown DM, Kaiser PK, Michels M, et al; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1432-1444.
7. Fung AE, Lalwani GA, Rosenfeld PJ, et al. An optical coherence tomography-guided, variable dosing regimen with intravitreal ranibizumab (Lucentis) for neovascular age-related macular degeneration. Am J Ophthalmol. 2007;143(4):566-583.
8. Brechner RJ, Rosenfeld PJ, Babish JD, Caplan S. Pharmacotherapy for neovascular age-related macular degeneration: an analysis of the 100% 2008 medicare fee-for-service part B claims file. Am J Ophthalmol. 2011;151(5):887-895.
9. CATT Research Group, Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, Jaffe GJ. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011;364(20):1897-1908.
10. Heier JS. VEGF Trap-Eye Phase III Trial Results. VIEW 1 results. Paper presented at: Angiogenesis, Exudation, and Degeneration 2011; Miami; February 12, 2011.
11. Schmidt-Erfurth U. VEGF Trap-Eye Phase III Trial Results. VIEW 2 results. Paper presented at: Angiogenesis, Exudation, and Degeneration 2011; Miami; February 12, 2011.
12. Ho A. Results of HARBOR phase III study the efficacy of 2 mg ranibizumab. Paper presented at Retina Subspecialty Day at the American Academy of Ophthalmology. October 2011; Orlando, FL.
13. Klein R, Moss SE, Meuer SM, Klein BE. The 15-year cumulative incidence of retinal vein occlusion: the Beaver Dam Eye Study.
Arch Ophthalmol. 2008;126(4):513-518.
14. Aritürk N, Oge Y, Erkan D, Süllü Y, Mohajer F. Relation between retinal vein occlusions and axial length. Br J Ophthalmol.
1996;80(7):633-636.]]
15. Argon laser photocoagulation for macular edema in branch vein occlusion. The Branch Vein Occlusion Study Group. Am J Ophthalmol. 1984;98(3):271-282.
16. Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. The Central Vein Occlusion Study
Group M report. Ophthalmology. 1995;102(10):1425-1433.
17. Standard Care vs. Corticosteroid for Retinal Vein Occlusion (SCORE) Study Results. Washington, D.C.: National Eye Institute,2011; v. 2011.
18. Haller JA, Bandello F, Belfort R, Jr., et al. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology. 2010;117(6):1134-1146 e3.
19. Campochiaro PA, Heier JS, Feiner L, et al. Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010;117(6):1102-1112 e1.
20. Brown DM, Campochiaro PA, Singh RP, et al. Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010;117(6):1124-1133 e1.
21. Boyer DM. Anti-VEGF therapy for CRVO: COPERNICUS study. Paper presented at: Angiogenesis, Exudation and Degeneration 2011; February 12, 2011; Miami, FL.

Faculty and Disclosures

Brandon G. Busbee, MD, is with Tennessee Retina, which is based in Nashville.
Richard S. Kaiser, MD, is an Associate Surgeon at Wills Eye Hospital, an Associate Professor of Ophthalmology at Thomas Jefferson University Hospital, and a partner in Mid Atlantic Retina.
Baruch D. Kuppermann, MD, PhD, is Professor, Chief of
the Retina Service, and Vice Chairman of Clinical Research at the Gavin Herbert Eye Institute in the Department of Ophthalmology, University of California, Irvine.
Carl D. Regillo, MD, is the Director of the Retina Service of Wills Eye Institute and a Professor of Ophthalmology at Jefferson Medical College of Thomas Jefferson University Hospital in Philadelphia, and a partner in Mid Atlantic Retina.
<p><b>FACULTY/STAFF DISCLOSURE DECLARATIONS</b>
Dr. Busbee states that he receives grants/research support from Genentech and Regeneron Pharmaceuticals, Inc.; is a consultant to Synergetics, Genentech, Regeneron Pharmaceuticals, Inc., and Thrombogenics; is a speaker for Genentech, Regeneron Pharmaceuticals, Inc., and Thrombogenics; and receives royalty payments from Akorn.
Dr. Kaiser states that he receives grants/research support from Wills Eye Research Fund and J Arch McNamara
Research Fund; is a consultant to Pan Optica and Regeneron Pharmaceuticals, Inc.; and is a stock/shareholder in Ophthotech.
Dr. Kuppermann states that he is a consultant to
Alimera Sciences; Allegro Ophthalmolics; Allergan, Inc.;
Fovea Pharmaceuticals; Glaukos Corporation; Neurotech
Pharmaceuticals; Novagali Pharma; Novartis Pharmaceuticals; OptoTech, Regeneron Pharmaceuticals, Inc.; Santen; Second Sight; Teva Pharmaceuticals; and Thrombogenics.
Dr. Regillo states that he receives grant research support from Allergan, Inc.; Genentech; GlaxoSmithKline; Opthotech; and Regeneron Pharmaceuticals, Inc.; and that he is a consultant
to Genentech; GlaxoSmithKline; and Regeneron
Pharmaceuticals, Inc.
All of those involved in the planning, editing, and
peer review of this educational activity report no relevant financial relationships.

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Updates on The Management of AMD and RVO: An Evidence-based Approach

Richard S. Kaiser, MD, Brandon G. Busbee, MD, Baruch D. Kuppermann, MD, PhD, Carl D. Regillo, MD

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