jurnal OVR

7/27/2019 jurnal OVR

1/25

T h e n e w e n g l a n d j o u r n a l o f m e d i c i n e

clinical pr actice

Retinal-Vein Occlusion

Tien Y. Wong, M.D., Ph.D., and Ingrid U. Scott, M.D., M.P.H.

This Journal feature begins with a case vignette highlighting a common clinical problem.

Evidence supporting various strategies is then presented, followed by a review of formal

guidelines, when they exist. The article ends with the authors clinical recommendations.

A 69-year-old man, a former smoker with a history of hypertension and hyperlipidemia,

presents with acute visual loss in his right eye of 2 weeks duration. Examina- tion of the eye

reveals a visual acuity of 20/60 and a sectoral area of retinal hemorrhages, cotton-wool

spots, and swelling in the center of the retina (macular edema). A diagnosis of right-branch

retinal-vein occlusion is made. How should he be treated?

T h e C l i n i c a l Pr o b l e m

Retinal-vein occlusion is a common cause of vision loss in older persons, and the second

most common retinal vascular disease after diabetic retinopathy. There are two distinct types,

classif ied according to the site of occlusion.1 In branch retinal- vein occlusion, the occlusion

is typically at an arteriovenous intersection (Fig. 1); in central retinal-vein occlusion, the

occlusion is at or proximal to the lamina cribrosa of the optic nerve, where the central retinal

vein exits the eye (Fig. 2).

Retinal-vein occlusion has a prevalence of 1 to 2% in persons older than 40 years of age2,3

and affects 16 million persons worldwide.4 Branch retinal-vein occlusion is four times as

common as central retinal-vein occlusion.4 In a population-based cohort study, the 10-year

incidence of retinal-vein occlusion was 1.6%.5


2/25

Bilateral retinal-vein occlusion is uncommon (occurring in about 5% of cases), although in

10% of patients with retinal-vein occlusion in one eye, occlusion de- velops in the other eye

over time.6 Both branch retinal-vein occlusion and central retinal-vein occlusion are further

divided into the categories of perfused (non- ischemic) and nonperfused (ischemic), each

of which has implications for prognosis and treatment.

Pathogenesis and Risk Factors

The pathogenesis of retinal-vein occlusion is believed to follow the principles of Virchows

triad for thrombogenesis, involving vessel damage, stasis, and hypercoagulability. Damage

to the retinal-vessel wall from atherosclerosis alters rheologic properties in the adjacent

vein, contributing to stasis, thrombosis, and thus occlusion. Inf lammatory disease may

also lead to retinal-vein occlusion by means of these mechanisms. However, evidence of

hypercoagulability in patients with retinal- vein occlusion is less consistent. Although

individual studies have reported associations between retinal-vein occlusion andhyperhomocysteinemia,7 factor V Leiden mutation,8 def iciency in protein C or S,8

prothrombin gene mutation,9 and anticardiolipin antibodies,10,11 a meta-analysis of 26

studies suggested that only hyperho- mocysteinemia and anticardiolipin antibodies have

signif icant independent associations with retinal-vein occlusion.11

From the Singapore Eye Research Insti- tute, Singapore National Eye Centre, Na- tional

University of Singapore, Singapore (T.Y.W.); the Centre for Eye Research Aus- tralia,

University of Melbourne, Mel- bourne, VIC, Australia (T.Y.W.); and Penn State College of

Medicine, Penn State Hershey Eye Center, Hershey, PA (I.U.S.). Address reprint requests

to Dr. Wong at the Singapore Eye Research Institute, Singapore National Eye Centre, 11

Third Hospital Ave., Singapore 168751, Singa- pore, or at [email protected].

N Engl J Med 2010;363:2135-44.

Copyright 2010 Massachusetts Medical Society.

An audio version of this article


3/25

is available at

NEJM.org

n engl j med 363;22 nejm.org november 25, 2010

2135

The New England Journal of Medicine

Downloaded from nejm.org on September 8, 2013. For personal use only. No other uses

without permission.Copyright 2010 Massachusetts Medical Society. All rights reserved.


A B

C D


4/25

Figure 1. Branch Retinal-Vein Occlusion in the Superotemporal Quadrant of the Right Eye.

A fundus photograph (Panel A) shows a sectoral area of dilated veins, retinal hemorrhages

(white arrows), cotton- wool spots (black arrows), and retinal edema, and a fluorescein

angiogram (Panel B) reveals blockage (white arrows) and leakage of dye (yellow arrows).

Optical-coherence tomographic scans (horizontal scan in Panel C and vertical scan in PanelD) show retinal thickening (white arrows), as compared with normal retinal thickness (black

arrow), and macular edema (yellow arrows). NT denotes a nasal-to-temporal cut of the

retinal scan, and IS an inferior- to-superior cut.

The strongest risk factor for branch retinal- vein occlusion is hypertension,12-15 but

associations have been reported for diabetes mellitus,13-15 dyslipidemia,15 cigarette

smoking,2 and renal disease.16 For central retinal-vein occlusion, an additional ocular

risk factor is glaucoma or elevated intraocular pressure, which may compromise retinal

venous outf low.2

Natural History and Complications

Macular edema, with or without macular nonperfusion, is the most frequent cause of vision

loss in patients with retinal-vein occlusion.17-21

Vision loss may also be due to neovascularization, leading to vitreous hemorrhage, retinal

detach- ment, or neovascular glaucoma.


5/25

The natural history of branch retinal-vein occlusion is variable.22 Many patients with

branch retinal-vein occlusion have a good prognosis,

with one study showing that half have a return to 20/40 vision or better within 6 months,

without treatment.23 Nevertheless, many patients con- tinue to have poor vision in the

affected eye. Among participants enrolled in the Branch Vein Occlusion Study, a randomizedtrial of the effects of laser treatment for branch retinal-vein occlusion, only a third of

untreated eyes with macular edema and presenting vision of 20/40 or worse improved to

better than 20/40 after 3 years.17

Retinal neovascularization developed in one third of untreated eyes.17

The visual prognosis is generally worse for patients with central retinal-vein occlusion, par-

ticularly when nonperfused, than in patients with branch retinal-vein occlusion.6 A

systematic review suggested that neovascularization may de- velop in 20% of eyes and

neovascular glaucoma in 60% when nonperfused central retinal-vein oc-

2136



Downloaded from nejm.org on September 8, 2013. For personal use only. No other useswithout permission.

Copyright 2010 Massachusetts Medical Society. All rights reserved.

clinic a l pr ac tice

A B


6/25

C D

Figure 2. Nonperfused Central Retinal-Vein Occlusion in the Left Eye.

A fundus photograph (Panel A) shows scattered retinal hemorrhages (white arrows), cotton-

wool spots (black arrows), optic-disk edema and hyperemia, and venous dilatation andtortuosity (yellow arrow), and a f luorescein angiogram (Panel B) reveals areas of capillary

nonperfusion (white arrows) and disk leakage (yellow arrow). Optical-coherence

tomographic scans (horizontal scan in Panel C and vertical scan in Panel D) show marked

retinal thickening (white arrows) and edema (yellow arrows). NT denotes a nasal-to-

temporal cut of the retinal scan, and IS an inferior-to- superior cut.

clusion is present.6 In addition, in one third of eyes initially classif ied as having perfusedcen- tral retinal-vein occlusion, the occlusion may be- come nonperfused within the f irst


7/25

year.21 Visual acuity at the time of presentation is a strong indicator of the ultimate

quality of the patients vision. In the Central Vein Occlusion Study, a randomized trial of

the use of laser treatment for central retinal-vein occlusion, 65% of patients eyes

maintained 20/40 vision or better if acuity at the time of presentation was 20/40 or better, but

only 1% achieved this level if acuity was initially 20/200 or worse.19,21,24

Despite its associations with vascular risk factors, retinal-vein occlusion does not appear to

be an independent risk factor for death from cardiovascular causes.25-27 In a pooled

analysis of two population-based studies, retinal-vein occlusion was not independently

associated with in-

creased cardiovascular mortality,27 although a post hoc analysis revealed an association

among persons younger than 70 years of age.

S t r a t e g i e s a n d E v i d e n c e

Diagnosis and Assessment

Patients with retinal-vein occlusion typically present with sudden, unilateral, painless loss

of vision. The degree of vision loss depends on the extent of retinal involvement and on

macular- perfusion status. Some patients with branch retinal-vein occlusion report only a

peripheral visual-f ield defect.

Retinal-vein occlusion has a characteristic appearance on fundus examination. In branch

retinal-vein occlusion, there is a wedge-shaped area in which retinal vascular signs (hemor-rhages, cotton-wool spots, edema, and venous


2137



without permission.



dilatation and tortuosity) arise from an arteriovenous crossing, usually in thesuperotemporal quadrant (Fig. 1A). In central retinal-vein occlusion, extensive retinal


8/25

signs, with dilated and tortuous veins, are seen in all quadrants, often along with optic-disk

edema (Fig. 2A).

The diagnosis of retinal-vein occlusion is usually made on the basis of the clinical examina-

tion alone. Nonperfused central retinal-vein occlusion is suggested by vision that is worse

than

20/200, a relative afferent pupillary defect, and the presence of cotton-wool spots and large,

con- f luent hemorrhages.28 Fundus f luorescein angiography (Fig. 1B and 2B) is

commonly performed to assess the severity of macular edema and perfusion status. Optical-

coherence tomography is a noninvasive imaging technique used to quantify macular

edema and assess treatment response (Fig. 1C, 1D, 2C, and 2D).

Evaluation of patients with retinal-vein occlusion should include a detailed history taking,

clinical assessment, and laboratory investigations to check for the presence of cardiovascular

risk factors (Table 1). Although evidence is lacking to

show that treatment of hypertension and other conditions associated with cardiovascular

disease can alter the visual prognosis for patients with retinal-vein occlusion, this condition

should be considered end-organ damage,29 with appropriate risk-management strategies

routinely instituted. Tests for coagulation abnormalities (Table 1) are commonly performed in

selected patients, such as those younger than 50 years of age or those with bilateral retinal-

vein occlusion, although evidence is lacking to indicate that coagulation disorders are more

common in these patients.

ManagementUntil recently, laser photocoagulation was the only treatment supported by data from high-

quality randomized trials30-32; data are now also available from several trials assessing the

use of intraocular glucocorticoids and agents inhibiting vascular endothelial growth factor

(VEGF). These more recent treatment options are increasingly being used in clinical

practice. (For summaries of the recommendations for the management of branch retinal-vein

occlusion and central retinal-

Table 1. Assessment of Cardiovascular Risk in Patients with Retinal-Vein Occlusion.

History and clinical assessment

Hypertension Diabetes mellitus Dyslipidemia

Cardiovascular disease (e.g., stroke, coronary artery disease, peripheral artery disease)

Medications (e.g., oral contraceptives, diuretics)

Hypercoagulable states and hyperviscosity syndromes (e.g., leukemia, polycythemia vera)

Routine investigations


9/25

Complete blood count

Renal function (levels of serum electrolytes, urea, creatinine) Fasting serum levels of glucose

and glycated hemoglobin Fasting levels of lipids

Additional investigations (consider in select cases, such as in patients who are younger than

50 years of age, who have bilateral retinal-vein occlusion, or who may have thrombophilic or

coagulation disorders)

Homocysteine levels

Levels of functional protein C and protein S Antithrombin III levels

Antiphospholipid antibodieslupus anticoagulant, anticardiolipin antibodies

Activated protein C resistancepolymerase-chain-reaction assay for factor V Leiden

mutation (R506Q) Factor XII

Prothrombin gene mutation (G20210A)

2138




without permission.



Table 2. Recommendations for the Management of Branch Retinal-Vein Occlusion.

Intervention Guidelines

Evidence* Comments

Macular grid laser photocoagulation

Associated with reduced macular edema and improved vision in patients with macular edemaand visual acuity 20/40


10/25

A-I May not be effective in presence of macular ischemia

Scatter laser photocoagulation Recommended for treatment of ischemic retina if retinal or

disk neovascularization is also present

A-I

Intravitreal injection of triamcinolone acetonide

Intravitreal injection of ranibizumab

Intravitreal dexamethasone implant

No more effective than macular grid laser photocoagulation in improving visual acuity in

patients with macular edema from branch retinal-vein occlusion and associated with a higher

risk of adverse events

Associated with greater improvement in visual acuity, as compared with sham injection, over

12-mo period in patients with macular edema from branch retinal-vein occlusion

Associated with more rapid improvement in visual acuity than sham implant in patients with

macular edema from branch retinal-vein occlusion

A-I

A-II May be administered monthly in

0.5-mg doses, depending on per- sistence or recurrence of macular edema

B-II May be administered in 0.7-mg doses every 6 mo, depending on persis- tence orrecurrence of macular edema; contraindicated in patients with advanced glaucoma

Hemodilution Not recommended for routine use to improve visual acuity

or prevent neovascularization

B-III

Pars plana vitrectomy with adventitial sheathotomy

Not routinely recommended to improve visual acuity or prevent neovascularization

B-III


11/25

Ticlopidine, troxerutin Not routinely recommended to improve visual acuity or

prevent neovascularization

B-III

* For the ranking of the importance of the recommendation with respect to the clinical

outcome, A denotes most important or critical for a good clinical outcome and B moderately

important; for the strength of the evidence, I denotes strong evidence in support of the

recommendation, II strong evidence in support of the recommendation but lacking in some

respects (e.g., longer-term efficacy or safety uncertain),

and III insufficient evidence to provide support for or against the recommendation.

vein occlusion, see Tables 2 and 3, respectively. For the outcomes of trials conducted to

gauge the effects of various treatments on each condition, see the Supplementary Appendix,

available with the full text of this article at NEJM.org.)

Branch Retinal-Vein Occlusion

Laser Treatment

Grid laser photocoagulation is used for the treatment of macular edema resulting from

branch retinal-vein occlusion, and scatter laser photocoagulation is used for the prevention

and treatment of neovascularization. In the Branch Vein Occlusion Study,17,18 which

included patients with branch retinal-vein occlusion and macular edema in one or both eyes

(a total of 139 eyes were studied), eyes treated with grid laser photocoagulation were

almost twice as likely as untreated eyes to enable patients to read two additional lines on an

eye chart at 3 years (65% vs. 37%).17 However, in some patients, poor vision persisted

despite treatment; vision in 40% of treated eyes was

worse than 20/40 and that in 12% of treated eyes was worse than 20/200 at 3 years. In eyes

with extensive nonperfusion, scatter laser photocoagulation markedly reduced the risks

of retinal neovascularization (12%, vs. 22% in controls) and vitreous hemorrhage (29% vs.60%).18

Glucocorticoids

Case series have suggested that intravitreal injection of triamcinolone acetonide may be

useful for the treatment of macular edema in patients with branch retinal-vein occlusion.33

However, the use of this treatment was not supported by the Stan- dard Care versus

Corticosteroid for Retinal Vein Occlusion (SCORE) Study, a randomized trial in which 411

patients with branch retinal-vein occlusion and vision loss from macular edema were treated

with intravitreal injection of preservative- free triamcinolone acetonide (1 mg or 4 mg, in-


12/25

jected as frequently as every 4 months) or standard care (grid laser treatment of eyes

without dense macular hemorrhage).34 From baseline to


2139



without permission.



Table 3. Recommendations for the Management of Central Retinal-Vein Occlusion.

Intervention Guidelines

Evidence* Comments

Scatter laser photocoagulation Not recommended for patients without neovascularization

unless regular follow-up is not possible

Recommended for patients with anterior-segment neovascularization

A-I

A-I

Macular grid laser photo- coagulationIntravitreal injection of triamcinolone acetonide

Intravitreal injection of ranibizumab

Intravitreal dexamethasone implant


13/25

Not recommended for treatment of macular edema from central retinal-vein occlusion

Associated with greater improvement in visual acuity, as compared with observation, in

patients with macular edema from central retinal-vein occlusion

Associated with greater improvement in visual acuity, as compared with sham injection, over

12-mo period in patients with macular edema from central retinal-vein occlusion

Associated with more rapid improvement in visual acuity, as compared with sham implant, in

patients with macular edema from central retinal-vein occlusion

A-I

A-I May be administered every 4 mo in

1-mg doses, depending on persis- tence or recurrence of macular edema

A-II May be administered every mo in

0.5-mg doses, depending on per- sistence or recurrence of macular edema

B-II May be administered in 0.7-mg doses every 6 mo depending on persis- tence or

recurrence of macular edema; contraindicated in patients with advanced glaucoma

Laser-induced chorioretinal anastomosis

May improve visual acuity in patients with nonperfused central retinal-vein occlusion but

may be associated with significant ocular complications

B-II

Hemodilution May improve visual outcome in some patients if per-

formed as inpatient procedure following a protocol with a statistically relevant clinical

outcome

B-II Difficult to generalize recommendation due to variations in protocols (e.g., inpatient

and outpatient) and use of different agents

Ticlopidine, troxerutin, epo- prostenol

Not routinely recommended to improve visual acuity or prevent neovascularization

B-III

* For the ranking of the importance of the recommendation with respect to the clinical

outcome, A denotes most important or critical for a good clinical outcome and B moderately

important; for the strength of the evidence, I denotes strong evidence in support of the

recommendation, II strong evidence in support of the recommendation but lacking in some

respects (e.g., longer-term efficacy or safety uncertain),and III insufficient evidence to provide support for or against the recommendation.


14/25

1 year, the rate of the primary outcomethe proportion of eyes with an improvement in

visual acuity that enabled patients to read 15 or more additional letters (or 3 lines) on an eye

chartwas similar among the three groups (27% in the group treated with the 4-mg dose of

triamcinolone, 26% in the group treated with the 1-mg dose, and 29% in the control

group). Adverse eventsprincipally, elevated intraocular pressure and progression of

cataractswere more frequent in the groups treated with triamcinolone. The percentage

of eyes treated with glaucoma medications was 41% in the group receiving

4 mg of triamcinolone, 8% in the group receiving

1 mg, and 2% in the control group; for cataract progression, the percentages were 35%, 25%,

and

13%, respectively.

An alternative glucocorticoid, dexamethasone, was evaluated in a randomized trial

involving

1267 patients who had vision loss owing to macular edema caused by branch retinal-vein

occlusion or central retinal-vein occlusion.35 The primary end point the time required

to achieve a visual-acuity gain of 3 lines or more on an eye chartwas signif icantly shorter

among patients receiving dexamethasone (in a dose of

0.7 mg or 0.3 mg) than among patients who received a sham injection. The proportion

of eyes with this degree of improvement was also signif icantly higher in bothdexamethasone groups than in the placebo group at 1 month and 3 months but not at the

prespecif ied time point of 6 months. Dexamethasone showed similar benef its in preplanned

subgroup analyses of branch and central retinal-vein occlusion, although details on the

extent of improvement in visual acuity at 3 and 6 months were not provided. However,

the proportion of eyes in

2140




without permission.




15/25

which elevated intraocular pressure developed was higher with dexamethasone treatment

than with the sham injection (4% for both dexamethasone doses vs. 0.7%, P


16/25

Chorioretinal Venous Anastomosis Chorioretinal venous anastomosis, a procedure in which a

bypass for the venous obstruction is cre- ated with the use of laser therapy, has been sug-

gested for patients with perfused central retinal- vein occlusion.44 In a randomized trial

comparing the use of laser-induced chorioretinal venous anastomosis with conventionalcare in 113 patients with perfused central retinal-vein occlusion, visual acuity did not

change in laser-treated eyes, but in conventionally treated eyes, there was a loss of 8 letters

(nearly 2 lines) from baseline at

18 months (P = 0.03). However, laser-related neovascularization developed in 20% of laser-

treated eyes, and vitrectomy for vitreous hemorrhage was performed in 10%. Thus, the

potential bene- f it of chorioretinal anastomosis in perfused central retinal-vein occlusion

must be weighed against the risk of clinically signif icant ocular complications.

Glucocorticoids

Intravitreal injection of triamcinolone was evaluated in the SCORE Study in 271 patients

with central retinal-vein occlusion and vision loss due to macular edema.45 At 1 year,

improvement in visual acuity, def ined as the ability to read an additional 15 letters (3

lines) or more on an eye chart, occurred in 27% of patients receiving 1 mg of triamcinolone,

26% of those receiving 4 mg, and 7% of controls (P = 0.001 for both compari- sons with

controls). Rates of adverse events were similar to those among the patients with branch

retinal-vein occlusion in the SCORE Study.34 The study of intravitreal injection of

dexamethasone through an implant was associated with a shorter time to achieve a gain in

acuity of 15 letters on an eye chart in patients with central retinal- vein occlusion, as well asin those with branch retinal-vein occlusion, as discussed above.35 In both the triamcinolone

and dexamethasone stud-


2141



without permission.




17/25

ies, elevated intraocular pressure was a significant adverse event for patients receiving these

drugs.

Anti-VEGF Agents

Ranibizumab and bevacizumab are widely used in the treatment of central retinal-vein

occlusion, as well as in the treatment of branch retinal-vein occlusion.41,42,46 In the

Ranibizumab for the Treatment of Macular Edema after Central Reti- nal Vein Occlusion

(CRUISE) trial, which included

392 patients with central retinal-vein occlusion and macular edema, the proportion of

patients with clinically signif icant improvement in visual acuity was higher in the

ranibizumab groups than in the sham-injection group (46% of patients receiving 0.3 mg

of ranibizumab and 48% of those receiving 0.5 mg vs. 17% of those under- going sham

injection).47 Like the BRAVO trial,43 which assessed the same ranibizumab intervention

in patients with branch retinal-vein occlusion and in those with central retinal-vein occlu-

sion, the CRUISE study showed no signif icant between-group differences in the

incidence of systemic vascular events among the patients with central retinal-vein occlusion,

and the vision gain with ranibizumab treatment was maintained at

12 months.47

A r e a s o f U n c e r t a i n t y

Although retinal-vein occlusion is much more common in persons older than 50 years of age,

it can also arise in younger persons with no identi- f iable risk factors.48 In younger patients,

retinal- vein occlusion may have a different pathogenesis, but it is not clear whether systemic

coagulation abnormalities are more common in such patients.

Trials of treatments with intraocular glucocorticoid and anti-VEGF agents have had

relative- ly short periods of follow-up. Longer-term trials are needed to determine whether

visual gains will be maintained after 1 year, to establish optimal dosing regimens, and to

ascertain the risks of these therapies. In some trials, treatment was delayed to allow for

spontaneous improvement; thus, it is not clear how different treatments would compare ifused earlier in the course of disease.

In post hoc analyses of two trials addressing neovascular age-related macular

degeneration,36,37 rates of nonocular hemorrhage, including cere- bral hemorrhage, were

higher among patients

treated for 2 years with monthly intravitreal injections of ranibizumab than among

controls (7.8% vs. 4.2%, P = 0.01).49 Although an increased rate of vascular events was not

identified in trials of intraocular anti-VEGF agents, more data are needed to assess whether

anti-VEGF treatment increases the risk of cardiovascular events, par- ticularly stroke, in

patients with retinal-vein occlusion.50


18/25

Data are lacking from randomized trials comparing glucocorticoids and anti-VEGF

therapies head to head and assessing the effects of various combination therapies (e.g., laser

plus anti-VEGF therapy). Most trials have largely excluded patients with poor visual

acuity and nonperfused retinal-vein occlusion, and it is unclear what type of treatment is

appropriate for these patients.

Other systemic therapies have been tried (e.g., hemodilution, streptokinase, and

anticoagulants such as troxerutin and ticlopidine), as have surgical approaches (e.g., radial

optic neurotomy, performed to improve venous outf low at the optic disc, and vitrectomy

with arteriovenous sheathotomy, performed to relieve venous compression at the

arteriovenous junctions),30-32 but these treatments have not been rigorously studied.

Surgical procedures are increasingly being replaced by intraocular injections, which can be

given in a physicians off ice.

G u i d e l i n e s f r o m Pr o f e s s i o n a l

S o c i e t i e s

The United Kingdom Royal College of Ophthal- mologists has published guidelines for the

management of retinal-vein occlusion,51 but these guidelines do not take into account

data from recent clinical trials.

C o n c l u s i o n s a n d

R e c o m m e n d a t i o n s

The patient described in the vignette has a superotemporal branch retinal-vein occlusion

with macular edema. We recommend a thorough ocular evaluation, including the use of

fundus f luorescein angiography to assess macular perfusion and leakage and optical

coherence tomography to quantify macular edema. Systemic evaluation by the patients

general physician and appropriate management of modif iable cardiovascular risk factors

(e.g., hypertension and hyperlipidemia) are

2142



19/25



without permission.



indicated. We do not recommend further workup for coagulation abnormalities in this patient.

We would discuss with the patient the risks and potential benef its of grid laser photoco-

agulation or intraocular injections of anti-VEGF agents. The advantages of using grid laser

for f irst-line treatment of branch retinal-vein occlusion include the availability of longer-

term data from clinical trials showing improvement in visual acuity, lower rates of adverseeffects, and lower costs with this treatment than with anti- VEGF therapy. In selected cases

(e.g., dense macular hemorrhage that precludes the use of laser therapy), we would

consider intraocular injection of an anti-VEGF agent for f irst-line treatment;

we would inform the patient of the increased risk of arterial thromboembolic events. Treat-

ment with a dexamethasone implant is another option, but evidence is lacking to demonstrate

an improvement in visual acuity beyond 3 months. The patient should be monitored closely

for signs of neovascularization (e.g., new vessels or vitreous hemorrhage), which would

require scatter laser photocoagulation.

Dr. Wong reports receiving consulting fees from Allergan, Novartis, and Pf izer and

speaking fees and grant support from Allergan; and Dr. Scott reports receiving consulting

fees from Genentech. No other potential conf lict of interest relevant to this article was

reported.

Disclosure forms provided by the authors are available with the full text of this article at

NEJM.org.

Reference s

1. Hayreh SS. Prevalent misconceptions about acute retinal vascular occlusive disorders.

Prog Retin Eye Res 2005;24:493-

519.

2. Mitchell P, Smith W, Chang A. Preva- lence and associations of retinal vein occlusion

in Australia: the Blue Mountains Eye Study. Arch Ophthalmol 1996;114:

1243-7.

3. Klein R, Klein BE, Moss SE, Meuer SM. The epidemiology of retinal vein occlusion:the Beaver Dam Eye Study. Trans Am Ophthalmol Soc 2000;98:133-41.


20/25

4. Rogers S, McIntosh RL, Cheung N, et al. The prevalence of retinal vein occlusion:

pooled data from population studies from the United States, Europe, Asia, and Australia.

Ophthalmology 2010;117(2):

313.e1-319.e1.

5. Cugati S, Wang JJ, Rochtchina E, Mitchell P. Ten-year incidence of retinal vein occlusion

in an older population: the Blue Mountains Eye Study. Arch Ophthal- mol 2006;124:726-32.

6. McIntosh RL, Rogers SL, Lim L, et al. Natural history of central retinal vein occlusion:

an evidence-based systematic review. Ophthalmology 2010;117(6):1113. e15-1123.e15.

7. Chua B, Kif ley A, Wong TY, Mitchell P. Homocysteine and retinal vein occlusion: a

population-based study. Am J Oph- thalmol 2005;139:181-2.

8. Greiner K, Hafner G, Dick B, Peetz D, Prellwitz W, Pfeiffer N. Retinal vascular

occlusion and deficiencies in the protein C pathway. Am J Ophthalmol 1999;128:69-

74.

9. Incorvaia C, Lamberti G, Parmeggiani F, et al. Idiopathic central retinal vein occlusion

in a thrombophilic patient with the heterozygous 20210 G/A prothrombin ge- notype. Am J

Ophthalmol 1999;128:247-8.

10. Lahey JM, Tun M, Kearney J, et al. Laboratory evaluation of hypercoagulable states in

patients with central retinal vein

occlusion who are less than 56 years of age. Ophthalmology 2002;109:126-31.

11. Janssen MC, den Heijer M, Cruysberg JR, Wollersheim H, Bredie SJ. Retinal vein

occlusion: a form of venous thrombosis or a complication of atherosclerosis? A meta-

analysis of thrombophilic factors. Thromb Haemost 2005;93:1021-6.

12. Rath EZ, Frank RN, Shin DH, Kim C. Risk factors for retinal vein occlusions: a case-

control study. Ophthalmology 1992;

99:509-14.

13. Hayreh SS, Zimmerman B, McCarthy MJ, Podhajsky P. Systemic diseases associated

with various types of retinal vein occlusion. Am J Ophthalmol 2001;131:61-

77.

14. Elman MJ, Bhatt AK, Quinlan PM, Enger C. The risk for systemic vascular diseases

and mortality in patients with central retinal vein occlusion. Ophthal- mology

1990;97:1543-8.

15. Wong TY, Larsen EK, Klein R, et al. Cardiovascular risk factors for retinal vein

occlusion and arteriolar emboli: the Atherosclerosis Risk in Communities & Cardiovascular

Health studies. Ophthal- mology 2005;112:540-7.


21/25

16. Cheung N, Klein R, Wang JJ, et al. Traditional and novel cardiovascular risk factors for

retinal vein occlusion: the Multi- ethnic Study of Atherosclerosis. Invest Ophthalmol Vis Sci

2008;49:4297-302.

17. The Branch Vein Occlusion Study Group. Argon laser photocoagulation for macular

edema in branch vein occlusion. Am J Ophthalmol 1984;98:271-82.

18. Idem. Argon laser scatter photocoagulation for prevention of neovascularization and

vitreous hemorrhage in branch vein occlusion: a randomized clinical trial. Arch Ophthalmol

1986;104:34-41.

19. The Central Vein Occlusion Study Group. Baseline and early natural history report:

the Central Vein Occlusion Study. Arch Ophthalmol 1993;111:1087-95.

20. Idem. A randomized clinical trial of early panretinal photocoagulation for ischemic

central vein occlusion: the Central Vein Occlusion Study Group N report. Ophthalmology1995;102:1434-44.

21. Idem. Natural history and clinical management of central retinal vein occlusion. Arch

Ophthalmol 1997;115:486-91. [Erra- tum, Arch Ophthalmol 1997;115:1275.]

22. Rogers SL, McIntosh RL, Lim L, et al. Natural history of branch retinal vein occlusion:

an evidence-based systematic review. Ophthalmology 2010;117(6):1094. e5-1101.e5.

23. Finkelstein D. Ischemic macular edema: recognition and favorable natural history in

branch vein occlusion. Arch Ophthalmol 1992;110:1427-34.

24. The Central Vein Occlusion Study Group. Evaluation of grid pattern photo-coagulation for macular edema in central vein occlusion: the Central Vein Occlusion Study

Group M report. Ophthalmology

1995;102:1425-33.

25. Tsaloumas MD, Kirwan J, Vinall H, et al. Nine year follow-up study of mor- bidity and

mortality in retinal vein occlusion. Eye (Lond) 2000;14:821-7.

26. Christoffersen N, Gade E, Knudsen L, Juel K, Larsen M. Mortality in patients with

branch retinal vein occlusion. Oph- thalmology 2007;114:1186-9.

27. Cugati S, Wang JJ, Knudtson MD, et al. Retinal vein occlusion and vascular mortality:

pooled data analysis of 2 population-based cohorts. Ophthalmology 2007;

114:520-4.

28. Hayreh SS, Rojas P, Podhajsky P, Mon- tague P, Woolson RF. Ocular neovascular-

ization with retinal vascular occlusion. III. Incidence of ocular neovascularization with

retinal vein occlusion. Ophthal- mology 1983;90:488-506.

29. Wong TY, Mitchell P. Hypertensive retinopathy. N Engl J Med 2004;351:2310-7.

30. McIntosh RL, Mohamed Q, Saw SM,


22/25


2143



without permission.



Wong TY. Interventions for branch retinal vein occlusion: an evidence-based systematic

review. Ophthalmology 2007;114:835-

54.

31. Mohamed Q, McIntosh RL, Saw SM, Wong TY. Interventions for central retinal vein

occlusion: an evidence-based systematic review. Ophthalmology 2007;114:507-

19.

32. Lazo-Langner A, Hawel J, Ageno W, Kovacs MJ. Low molecular weight heparin for the

treatment of retinal vein occlusion: a systematic review and meta-analysis of randomized

trials. Haematologica

2010;95:1587-93.

33. Jonas JB, Akkoyun I, Kamppeter B, Kreissig I, Degenring RF. Branch retinal vein

occlusion treated by intravitreal triamcinolone acetonide. Eye (Lond) 2005;

19:65-71.

34. Scott IU, Ip MS, VanVeldhuisen PC, et al. A randomized trial comparing the eff icacy

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;127:1115-

28. [Erratum, Arch Ophthalmol 2009;127:

1655.]

35. 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.e3-1146.e3.


23/25

36. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporf in for

neovascular age-related macular degeneration. N Engl J Med 2006;355:1432-44.

37. Rosenfeld PJ, Brown DM, Heier JS,

et al. Ranibizumab for neovascular age- related macular degeneration. N Engl J Med

2006;355:1419-31.

38. Aiello LP, Avery RL, Arrigg PG, et al. Vascular endothelial growth factor in ocular f

luid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med

1994;331:1480-7.

39. Campochiaro PA, Haf iz G, Shah SM, et al. Ranibizumab for macular edema due to

retinal vein occlusions: implication of VEGF as a critical stimulator. Mol Ther

2008;16:791-9.

40. Spaide RF, Chang LK, Klancnik JM, et al. Prospective study of intravitreal ranibizumab

as a treatment for decreased visual acuity secondary to central retinal vein occlusion. Am J

Ophthalmol 2009;

147:298-306.

41. Wu L, Arevalo J, Berrocal MH, et al. Comparison of two doses of intravitreal

bevacizumab as primary treatment for macular edema secondary to central retinal vein

occlusion: results of the Pan Amer- ican Collaborative Retina Study Group at

24 months. Retina 2010;30:1002-11.

42. Prager F, Michels S, Kriechbaum K, et al. Intravitreal bevacizumab (Avastin) for macularoedema secondary to retinal vein occlusion: 12-month results of a prospective clinical trial.

Br J Ophthalmol

2009;93:452-6.

43. 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.e1-1112.e1.

44. McAllister IL, Gillies ME, Smithies LA, et al. The Central Retinal Vein Bypass Study: atrial of laser-induced chorioretinal venous anastomosis for central retinal

vein occlusion. Ophthalmology 2010;117:

954-65.

45. Ip MS, Scott IU, VanVeldhuisen PC, et al. A randomized trial comparing the eff icacy

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;127:1101-

14. [Erratum, Arch Ophthalmol 2009;127:


24/25

1648.]

46. Kinge B, Stordahl PB, Forsaa V, et al. Eff icacy of ranibizumab in patients with macular

edema secondary to central retinal vein occlusion: results from the sham- controlled ROCC

study. Am J Ophthalmol

2010;150:310-4.

47. 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.e1-1133.e1.

48. Rouhani B, Mandava N, Olson JL. Central retinal vein occlusion after in- tense

exercise in healthy patients. Retinal Cases Brief Rep 2010;4:105-8.

49. Gillies MC, Wong TY. Ranibizumab for neovascular age-related macular de-

generation. N Engl J Med 2007;356:748-9.

50. Wong TY. Age-related macular degeneration and cardiovascular disease in the era of

anti-vascular endothelial growth factor therapies. Am J Ophthalmol 2009;

148:327-9.

51. Retinal vein occlusion (RVO) interim guidelines. London: The Royal College of

Ophthalmologists, February 2009. (http:// www.rcophth.ac.uk.)

Copyright 2010 Massachusetts Medical Society.

specialties and topics at nejm.org

Specialty pages at the Journals Web site (NEJM.org) feature articles in cardiology,

endocrinology, genetics, infectious disease, nephrology, pediatrics, and many other medical

specialties. These pages, along with collections of articles on clinical and nonclinical topics,

offer links to interactive and multimedia content and feature recently published articles aswell as material from the NEJM archive (18121989).


25/25

2144




without permission.


Documents

jurnal OVR