Retinal vein occlusion (RVO) is a common ocular disease that remains poorly understood due to the multifactorial nature of the presentation and contributing systemic factors. Several associated systemic factors have been identified and continue to be studied for their impact on RVO, including hypertension, diabetes, hypercholesterolemia, thyroid disorder, and ischemic heart disease. Increased intraocular pressure and axial length are other factors that play roles in this disease.1,2

For many years, clinicians have followed the recommendations set forth by the Branch Vein Occlusion Study3 and the Central Vein Occlusion Study.4 The former demonstrated that grid laser photocoagulation leads to a greater improvement of visual acuity than natural history, but the latter showed grid laser photocoagulation did not improve visual acuity even though the macular edema decreased.

The SCORE central RVO study included 271 people; 73% had high blood pressure, and 23% had diabetes. After 1 year, 27% of patients in the 1-mg corticosteroid injection group and 26% of patients in the 4-mg group experienced a substantial gain of 3 or more lines of visual acuity.5 These results appeared to last up to 2 years, though the 2-year results included a smaller number of patients. The SCORE branch RVO trial included 411 people; 70% had high blood pressure. After 1 year, 29% of patients in the laser treatment group, 26% of patients in the 1-mg corticosteroid injection group, and 27% of patients in the 4-mg injection group experienced a substantial gain of 3 or more lines of visual acuity.6 These results appeared to last up to 3 years, although the 3-year results included a smaller number of patients.

The dexamethasone intravitreal implant 0.7-mg (Ozurdex, Allergan) is the most recent treatment approved by the US Food and Drug Administration for the treatment of macular edema secondary to RVO. In the pivotal phase 3 trial, GENEVA, which enrolled 1267 patients, there was a visual acuity gain and reduction in macular edema at 2 months in the treatment arm that was not observed in the placebo arm.7 The dexamethasone intravitreal implant is a biodegradable implant that delivers extended release of the corticosteroid after intravitreal insertion.

Ranibizumab was recently FDA-approved for the treatment of macular edema following both BRVO and CRVO, based on the results of the BRAVO8 and CRUISE studies.9

BRAVO randomized 397 patients to 6 monthly injections of ranibizumab, either 0.3 mg or 0.5 mg, or to sham injections. The primary efficacy outcome was mean change from baseline best corrected visual acuity (BCVA) at 6 months. Secondary outcomes included the percentage of patients who gained 3 lines (15 letters) of BCVA at 6 months. The mean gain from baseline at month 6 was 16.6 letters in patients receiving 0.3 mg of ranibizumab, 18.3 letters in those receiving 0.5 mg, and 7.3 in those receiving sham injection. By month 6, most patients in the 2 ranibizumab groups gained at least 3 lines of BCVA (55.2% in the 0.3 mg group and 61.1% in the 0.5 mg group), while most of those in the sham group did not (28.8%). Safety profiles were consistent with those found in other studies of ranibizumab for AMD.

CRUISE randomized 392 patients with visual acuity between 20/40 and 20/320 with CRVO to 0.3-mg ranibizumab, 0.5-mg ranibizumab, or sham injections. The patients all had macular edema secondary to central RVO. BCVA improvements occurred rapidly for those in the ranibizumab groups, averaging 9 letters improvement in 7 days, with around a 440 μm decrease in central foveal thickness as well. Safety profiles were consistent with those found in other studies of ranibizumab for AMD.

The COPERNICUS study evaluated aflibercept for the treatment of macular edema secondary to CRVO. At 6 months, 56.1% of patients receiving monthly 2-mg aflibercept gained at least 15 letters of visual acuity from baseline, compared with 12.3% of patients receiving sham injections (P < .0001).10 Treated patients gained a mean 17.3 letters of visual acuity, compared with a mean loss of 4.0 letters in those receiving sham injections (P < .001). These results were confirmed by the GALILEO trial.11

There has also been a small study evaluating the Iluvien fluocinolone acetonide implant (Alimera Sciences) for CRVO, showing that the implant has a benefit but with the side effects of cataract and IOP.12

  1. 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.
  2. 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.
  3. Argon laser photocoagulation for macular edema in branch vein occlusion. The Branch Vein Occlusion Study Group. Am J Ophthalmol. 1984;98(3):271-282.
  4. 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.
  5. Ip MS, Scott IU, VanVeldhuisen PC, et al; SCORE Study Research Group. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with observation to treat vision loss associated with macular edema secondary to central retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 5. Arch Ophthalmol. 2009;127(9):1101-1114.
  6. Scott IU, Ip MS, VanVeldhuisen PC, et al; SCORE Study Research Group. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss associated with macular Edema secondary to branch retinal vein occlusion: the Standard Care vs Corticosteroid for Retinal Vein Occlusion (SCORE) study report 6. Arch Ophthalmol. 2009;127(9):1115-1128.
  7. 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.
  8. 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.
  9. 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.
  10. Boyer DM. Anti-VEGF therapy for CRVO: COPERNICUS study. Paper presented at: Angiogenesis, Exudation and Degeneration 2011; February 12, 2011; Miami, FL.
  11. Regeneron and Bayer Report Positive Results for VEGF Trap-Eye in Second Phase 3 Study in Central Retinal Vein Occlusion [press release]. Tarrytown, NY, and Berlin: Regeneron Pharmaceuticals, Inc., and Bayer HealthCare; April 27, 2011.
  12. Jain N, Stinnett SS, Jaffe GJ. Prospective study of a fluocinolone acetonide implant for chronic macular edema from central retinal vein occlusion: thirty-six-month results. Ophthalmology. 2012 Jan;119(1):132-137.

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:

  • Recognize various forms of macular edema and inflammation using the latest developments in medical literature and new insights from case-based learning.
  • Understand the new data available on treatments for RVO and how to apply this information in monotherapy and combination therapy treatment schemes.
  • Understand key techniques for administering intravitreal injections of anti-VEGF agents.
  • Comprehend fundamental elements of successful intravitreal implantation of steroids.
  • Differentiate steroids and their effects in the treatment of macular edema and inflammation.
  • Treat various forms of macular edema and inflammation, based on assessment of patient need, latest developments in medical literature, and insights from case-based learning.

MET HOD OF INSTRUCTION

Participants should read the CME activity in its entirety. After reviewing the material, please complete the self assessment test, which consists of a series of multiple choice questions. To answer these questions online and receive real-time 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

Carl D. Regillo, MD, is the Director of the Retina Service of Wills Eye Institute and a Professor of Ophthalmology at Thomas Jefferson University, Philadelphia. He may be reached at +1 800 331 6634; or via email at cregillo@aol.com.

Gaurav K. Shah, MD, is a vitreoretinal specialist and Director of Vitreoretinal Fellowship at The Retina Institute in St. Louis. He is a Professor of Clinical Ophthalmology at Washington University School of Medicine. He may be reached at +1 314 367 1181; fax: +1 314 367-5764; or via email at gkshah1@gmail.com.

FACULTY/STAFF DISCLOSURE DECLARATIONS

Dr. Regillo states that he receives research grant support from Genentech, Regeneron, Inc, and Allergan, Inc.; and is a consultant to Genentech, Regeneron Inc., and Allergan, Inc.

Dr. Shah states that he serves as a consultant for Alcon Laboratories, Inc., Allergan, Inc., Dutch Ophthalmic, USA, Heidelberg Engineering, Inc., Johnson & Johnson, Inc., QLT, Inc., Synergetics USA, Inc., and Thrombogenics, Inc.

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