MEDICAL RETINA FEATURE STORY

Treatment of Retinal
Vein Occlusion
Individualized therapy is crucial to good patient outcomes.
BY GAURAV K. SHAH, MD

Retinal vein occlusion (RVO) is a restriction of the flow found that up to 34% of nonischemic CRVO converted to
of blood leaving the retina. The resulting pressure can ischemic CRVO over a 3-year period. I consider CRVO
cause fluid and blood to leak, resulting in macular edema, worse than BRVO because it affects a greater area of the
macular ischemia, or neovascularization that can lead to retina, so for CRVO I proceed more aggressively.
vitreous hemorrhage and retinal detachment. My approach also depends on the type of disease that
The most common reason for loss of vision is macular I am treating. For a patient with ischemic CRVO, I am fairly
edema, and for patients who have macular edema second- aggressive in my approach, using anti-VEGF agents and
ary to RVO our treatment options include observation, steroids in combination for those patients, and possibly
laser, anti-vascular endothelial growth factor (anti-VEGF) laser therapy for areas of ischemia. Because most cases of
therapy, and bolus intravitreal or sustained-release ischemic CRVO do not improve without treatment, by
steroids. Our treatment is guided by past trials in this area. treating I am trying to decrease the risk of neovasculariza-
The Branch Vein Occlusion Study (BVOS) showed that tion of the iris and glaucoma.
laser photocoagulation can significantly lessen the devel- For BRVO, I observe in order to allow spontaneous reso-
opment of neovascularization and the occurrence of vitre- lution. If BRVO does not resolve, I initiate therapy. I typical-
ous hemorrhage in a patient with branch retinal vein ly start with anti-VEGF therapy, either ranibizumab
occlusion (BRVO).1 The Central Vein Occlusion Study (Lucentis, Genentech) or bevacizumab (Avastin,
(CVOS) did not show that laser treatment was beneficial Genentech). It is not yet known which is better for RVO,
in patients with central retinal vein occlusion (CRVO).2 but we will soon begin enrolling patients in a new study,
The Standard Care vs Corticosteroid for Retinal Vein Bevacizumab Versus Ranibizumab in Treatment of
Occlusion (SCORE) Study found that for BRVO3 laser Macular Edema From Vein Occlusion (CRAVE), which will
treatment is preferred to an injection of intravitreal triam- compare the 2 compounds in a randomized fashion. I ini-
cinolone (IVTA) because it is safer and as effective, but tially treat the patient with at least 2 injections of anti-
that for CRVO the previous standard treatment of obser- VEGF therapy, and if the patient responds I continue that
vation should be replaced with an IVTA injection.4 A treatment. If the patient does not respond or has a subop-
phase 3, multicenter, randomized, sham injection-con- timal response, meaning vision does not improve and/or
trolled study of the efficacy and safety of ranibizumab fluid is seen on optical coherence tomography (OCT),
injection compared with sham in patients with macular then I consider using steroids. It is important to obtain a
edema secondary to BRVO (BRAVO) and a phase 3, multi- fluorescein angiogram for nonresponders because some of
center, randomized, sham injection-controlled study of the these patients may have ischemia that is causing macular
efficacy and safety of ranibizumab injection compared edema. For these patients I often use supplemental ther-
with sham in patients with macular edema secondary to mal laser.
CRVO (CRUISE) showed that injections of ranibizumab are
effective treatments for BRVO and CRVO, respectively.5,6 CUSTOMIZED TRE ATMENT
It is likely that, as we gain more experience treating RVO
DECIDING HOW TO TREAT with the expanded range of therapies, we will find that few
Part of the decision of how to treat RVO depends on or no treatments are standalone. The choices of treatment
whether a patient has CRVO or BRVO. McIntosh et al7 include laser, anti-VEGF agents, and steroids, and it is
describe the natural history of CRVO as presenting with important to use the therapy that is most effective for
poor visual acuity (<20/40) that worsens over time. They each individual, often in combination with one another.

70 I RETINA TODAY I MARCH 2012

It should be noted that if therapy is applied and does steroids should be avoided. For those who are candidates
not produce the desired response, this does not mean that for either bolus injection or the sustained-release implant,
therapy should be completely abandoned for a particular informed consent is important. Most cases of IOP eleva-
patient. Rather, it is a reasonable strategy to switch to tion with the dexamethasone intravitreal implant can be
another mode of treatment or to a combination managed with topical glaucoma drops.
approach. For example, if a patient is treated with an anti-
VEGF agent and the response is less than satisfactory, the LOOKING AHE AD
therapy may be switched to steroids. If some fluid persists, The CRAVE trial will hopefully provide answers as to
it may be effective to reapply anti-VEGF therapy. It is the comparative efficacy and safety of ranibizumab vs
important to remember that, in a different setting, the ini- bevacizumab in the setting of newly diagnosed RVO.
tial treatment may be effective. More information regarding CRAVE enrollment criteria
When choosing a steroid, I consider the patient’s history. and contact information can be found on the Web at:
In a patient with intraocular pressure (IOP) issues, a history http://1.usa.gov/v5KMqg. Additionally, results from the
of glaucoma, or who is taking medicine for glaucoma, I will phase 3 COPERNICUS study evaluating aflibercept
use a steroid in an extended-release delivery mechanism (Eylea, Regeneron) for CRVO have been released,
that is less likely to raise IOP, such as the dexamethasone demonstrating significant gains in vision at 6 months
intravitreal implant (Ozurdex, Allergan, Inc.). If they do not with aflibercept vs sham.8
have any issues of glaucoma or IOP, and they have not had As our treatment armamentarium for RVO expands, it
problems in the past, then I may administer an intravitreal will be crucial to use the tools, both medical and surgical,
injection of triamcinolone acetonide (Kenalog, Bristol- that we have at our disposal to individualize therapy. As
Myers Squibb). There are certain high-risk groups, particu- we are learning, patients respond differently to treatments,
larly black patients, who have other vasculopathic factors and the response also appears to be dependent upon
and therefore may be at increased risk of having IOP eleva- when in the disease state treatments are applied. ■
tion after intravitreal triamcinolone acetonide injection.
Gaurav K. Shah, MD, is a vitreoretinal spe-
VITRECTOMY cialist and Director of Vitreoretinal Fellowship
Most patients, after receiving a combination of thera- at The Retina Institute in St.Louis, MO. He is a
pies including laser, anti-VEGF agent, and steroids, will Professor of Clinical Ophthalmology at
have some level of response. The question then is whether Washington University School of Medicine. Dr.
that response is acceptable or suboptimal. In patients who Shah states that he serves as a consultant for QLT, Dutch
are not satisfied with the results, surgery may be an option. Ophthalmic, Alcon, Heidelberg Engineering, Allergan,
If a patient has vitreous traction that may be causing mac- Thrombogenics, Synergetics,
ular edema, for example, I may decide to perform vitrecto- and Johnson & Johnson. He may be reached at
my and internal limiting membrane (ILM) removal. +1 314 367 1181; fax: +1 314 367-5764; or via email at
However, I save the option of surgery until after I have [email protected].
applied medical therapy because subsequent anti-VEGF
1. Branch Vein Occlusion Study Group. Argon laser scatter photocoagulation for prevention of
and intravitreal steroid injections will not work as well in neovascularization and vitreous hemorrhage in branch vein occlusion. A randomized clinical
that eye due to faster drug clearance after vitrectomy. For trial. Arch Ophthalmol. 1986;104:34-41.
2. The Central Vein Occlusion Study Group. Evaluation of grid pattern photocoagulation for
patients who have undergone a previous vitrectomy and macular edema in central vein occlusion. The Central Vein Occlusion Study Group M Report.
who have RVO with macular edema, the best option will Ophthalmology. 1995;102(10):1425-1433.
3. The SCORE Study Research Group. SCORE Study Report 6. A randomized trial comparing
most likely be the dexamethasone intravitreal implant the efficacy and safety of intravitreal triamcinolone with standard care to treat vision loss associ-
because of its durability. ated with macular edema secondary to branch retinal vein occlusion. Arch Ophthalmol.
2009;127:1115-1128.
4. The SCORE Study Research Group. SCORE Study Report 5. A randomized trial comparing
COMPLICATIONS the efficacy and safety of intravitreal triamcinolone with observation to treat vision loss associ-
ated with macular edema secondary to central retinal vein occlusion. Arch Ophthalmol.
Complications of any intravitreal injection can include 2009;127:1101-1114.
iris neovascularization and vitreous hemorrhage, which 5. Campochiaro PA, Heier JS, Feiner L, et al; BRAVO Investigators. Ranibizumab for macular
edema following branch retinal vein occlusion: six-month primary end point results of a phase
can be managed with laser photocoagulation. The long- III study. Ophthalmology. 2010;117:1102-1112.e1. Epub 2010 Apr 15.
term use of steroids can result in cataract formation, so it 6. Brown DM, Campochiaro PA, Singh RP, et al. Ranibizumab for macular edema following cen-
tral retinal vein occlusion: six-month primary end point results of a phase III study.
is important to advise patients of this so that they can Ophthalmology. 2010;117:1124-1133.e1. Epub 2010 Apr 9.
weigh the risks against the benefits of treatment. The most 7. McIntosh RL, Rogers SL, Lim L, et al. Natural history of central retinal vein occlusion: an evi-
dence-based systematic review. Ophthalmology. 2010;117:1113-1123.e15.
significant concerns with any use of a steroid are IOP 8. Boyer DM. Anti-VEGF therapy for CRVO: COPERNICUS study. Paper presented at:
spikes and glaucoma, and so for patients who are at risk Angiogenesis, Exudation and Degeneration 2011; February 12, 2011; Miami, FL.

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