Retinal vein occlusions (RVOs) affect approximately 160 000 people in the United States per year. Most patients (~80%;) have branch RVO (BRVO), and of those with central RVO (CRVO; ~20%), about 30% have ischemic CRVO and about 70% have nonischemic CRVO.1

The long-term visual outcomes in BRVO suggest that approximately onethird of patients may do well with observation, but we do not know who these patients are, so it may be advantageous to treat rather than wait with the result of further loss of visual acuity.1 Patients who have CRVO with poor visual acuity, ie, 20/60, do not tend to do well without treatment.1

The veins most commonly involved in RVO are the branch retinal and central retinal veins; both BRVO and CRVO are characterized by the presence of intraretinal hemorrhage, tortuous and dilated retinal veins, and, on occasion, optic disc edema.

Macular edema is a frequent cause of loss of visual acuity. Macular edema from venous occlusive disease results from the initial insult of thrombus formation at the lamina cribrosa or an arteriovenous crossing (Figure 1).

BVOS: Standard of Care

Risk factors for BRVO include advancing age, hypertension, glaucoma, cardiovascular disease, and increased body mass index. The first study to evaluate treatment (laser) for BRVO was the BVOS. The BVOS determined that if patients with BRVO did not show signs of improvement (vision better than 20/40) after an observation period of 3 months, then light grid pattern laser should be applied to the involved retina. In the study, the eyes that received laser treatment gained an average of 1.33 lines of vision, and eyes treated with laser were more likely to gain vision.2 Based on these results, the standard of care became waiting for 3 months, and if there were no signs of improvement, laser should be applied.

CVOS: Standard of Care

Risk factors for CRVO include hypertension, diabetes, and glaucoma. When younger patients present with CRVO, however, they should be checked for blood clotting issues because they are more prone to retinal hemorrhaging.

The CVOS evaluated laser vs observation for CRVO and found that although grid laser appeared to reduce macular edema, there was no significant improvement in visual acuity. Because of this, the recommended standard of care was observation to spontaneous resolution.3

Steroids for Macular Edema Secondary to CRVO

To address the fact that no treatment existed for CRVO, several studies evaluated the use of intravitreal injection of triamcinolone for macular edema secondary to CRVO. Ip et al4 and Jonas et al5 demonstrated that triamcinolone acetonide injection decreased macular edema and improved visual acuity in patients with macular edema secondary to CRVO, with greater effects seen in nonischemic than in ischemic CRVO.

Williamson et al,6 Oh et al,7 Chen et al,8 Moschos et al,9 and Gregori et al10 further found that the duration of improvement in visual acuity after a single 4-mg dose of intravitreal triamcinolone acetonide may range from less than 3 months to 6 months, indicating that repeated injections may be necessary for sustainability, which could have deleterious effects. It is well known that intravitreal triamcinolone acetonide is associated with several side effects. Complications include elevated IOP, in some cases requiring surgical intervention, cataract formation, and sterile endophthalmitis, although there are studies that implicate the vehicle and specific formulations of drug (particle size) in this devastating complication.11

SCORE

The SCORE study was actually 2 studies: SCOREBRVO and SCORE-CRVO. Both studies evaluated the standard of care (laser for BRVO and observation for CRVO) compared with either 1-mg or 4-mg triamcinolone acetonide injection.

In SCORE-BRVO,12 the 4-mg triamcinolone acetonide produced better visual acuity results; however, after 1 year, there was no significant difference between laser and steroids (Figures 2 and 3). Additionally, the side effect profile with steroids was elevated (41% of patients in the 4-mg triamcinolone acetonide group required medications to lower intraocular pressure [IOP], and cataract formation was almost universal in the steroid groups). Based on these findings, the standard of care of laser after 3 months of observation from the BVOS was upheld.12

The SCORE-CRVO study13 tested steroid vs observation using the same doses as in the BRVO study—1 mgand 4-mg triamcinolone acetonide. The mean loss of vision in the standard of care group was 8 letters over 6 months and 10 letters at 2 years. Steroids showed a benefit in both the 1-mg and 4-mg groups (Figures 4 and 5). These data led to a recommendation from the study authors that observation be replaced as the standard of care by 1-mg triamcinolone acetonide, due to the better safety profile of a lower dose of steroid.13

Another Option for Steroid Delivery

The dexamethasone implant (Ozurdex, Allergan, Inc.) is an injectable, biodegradable intravitreal implant containing 0.7-mg preservative-free dexamethasone in a solid polymer drug delivery system. The drug delivery system (Novadur, Allergan, Inc.) contains a poly(D,Llactide- co-glycolide) biodegradable polymer matrix and provides sustained medication release.

The version of the implant that was tested in phase 2 clinical trials was surgically inserted in the OR through a 20-gauge incision. The doses of dexamethasone that were tested in phase 2 were 0.35 mg and 0.70 mg. In phase 2b clinical trials, the 2 doses were delivered in an office setting via a 23-gauge biplanar injection.

The next article, by Carl Regillo, MD, will discuss the results of the phase 3 clinical trials with the dexamethasone implant for RVO and compare the results of this study (GENEVA) with the ranibizumab (BRAVO and CRUISE) phase 3 clinical trials for BRVO and CRVO.

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. Dr. Shah states that he serves as a consultant for Allergan, Inc., Alcon Laboratories, Inc., Dutch Ophthalmic USA, Heidelberg Engineering, Inc., Johnson & Johnson, Inc., QLT, Inc., Synergetics USA, Inc., and Thrombogenics, Inc. He can be reached at +1 314 367 1181; fax: +1 314 367-5764; or via email at gkshah1@gmail.com.

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  2. Branch Vein Occlusion Study Group: Argon laser photocoagulation for macular edema in branch vein occlusion. Am J Ophthalmol. 1984;98: 271-282.
  3. The Central Vein Occlusion Study Group: Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. The CVOS Group M Report. Ophthalmology. 1995;102:1425-1433.
  4. Ip MS, Gottlieb JL, Kahana A, et al. Intravitreal triamcinolone for the treatment of macular edema associated with central retinal vein occlusion. Arch Ophthalmol. 2004;122(8):1131-1136.
  5. Jonas JB, Akkoyun I, Kamppeter B, Kreissig I, Degenring RF. Intravitreal triamcinolone acetonide for treatment of central retinal vein occlusion. Eur J Ophthalmol. 2005;15(6):751-758.
  6. Williamson TH, O'Donnell A. Intravitreal triamcinolone acetonide for cystoid macular edema in nonischemic central retinal vein occlusion. Am J Ophthalmol. 2005;139(5):860-866.
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  9. Moschos MM, Brouzas D, Loukianou E, Apostolopoulos M, Moschos M.Intraocular triamcinolone acetonide for macular edema due to CRVO. A multifocal-ERG and OCT study. Doc Ophthalmol. 2007;114(1):1-7.
  10. Gregori NZ, Rosenfeld PJ, Puliafito CA, et al. One-year safety and efficacy of intravitreal triamcinolone acetonide for the management of macular edema secondary to central retinal vein occlusion. Retina. 2006;26(8):889-895.
  11. Jonas JB, Kreissig I, Spandau UH, Harder B. Infectious and noninfectious endophthalmitis after intravitreal high-dosage triamcinolone acetonide. Am J Ophthalmol. 2006;141(3):579-580.
  12. 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.
  13. 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.