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Central Retinal Vein Occlusion

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Last updated: February 6th, 2022

Summary of Evidence
Evidence
References
Comments

Summary of Evidence

Treatment of Macular Edema

Intravitreal anti-VEGF injections

Intravitreal ranibizumab provides rapid, effective treatment for macular oedema following CRVO at 6 months.(CRUISE, 2010). {Brown DM, Campochiaro PA, Singh RP, Li Z, Gray S, Saroj N, Rundle AC, Rubio RG, Murahashi WY; CRUISE Investigators. Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010 Jun;117(6):1124-1133.e1.}

Intravitreal Aflibercept provided significant functional and anatomic benefits at 1 year vs sham in patients with Macular oedema secondary to CRVO, with improvements after 6 monthly doses maintained at 1 year on a PRN dosing.(GALILEO, 2014). {Korobelnik JF, Holz FG, Roider J, Ogura Y, Simader C, Schmidt-Erfurth U, Lorenz K, Honda M, Vitti R, Berliner AJ, Hiemeyer F, Stemper B, Zeitz O, Sandbrink R; GALILEO Study Group. Intravitreal Aflibercept Injection for Macular Edema Resulting from Central Retinal Vein Occlusion: One-Year Results of the Phase 3 GALILEO Study. Ophthalmology. 2014 Jan;121(1):202-208.}

Intravitreal Bevacizumab was non-inferior to Aflibercept in 6-month visual outcomes in macular oedema secondary to central/hemi-RVO.(SCORE2, 2017). {Scott IU, VanVeldhuisen PC, Ip MS, Blodi BA, Oden NL, Awh CC, Kunimoto DY, Marcus DM, Wroblewski JJ, King J; SCORE2 Investigator Group. Effect of Bevacizumab vs Aflibercept on Visual Acuity Among Patients With Macular Edema Due to Central Retinal Vein Occlusion: The SCORE2 Randomized Clinical Trial. JAMA. 2017 May 23;317(20):2072-2087.}

Mean change in vision were similar with Aflibercept and Ranibizumab in macular oedema due to CRVO. Vision change with Bevacizumab vs Ranibizumab was inconclusive.(LEAVO, 2019). {Hykin P, Prevost AT, Vasconcelos JC, Murphy C, Kelly J, Ramu J, Hounsome B, Yang Y, Harding SP, Lotery A, Chakravarthy U, Sivaprasad S; LEAVO Study Group. Clinical Effectiveness of Intravitreal Therapy With Ranibizumab vs Aflibercept vs Bevacizumab for Macular Edema Secondary to Central Retinal Vein Occlusion: A Randomized Clinical Trial. JAMA Ophthalmol. 2019 Nov 1;137(11):1256-1264.}

Laser Photocoagulation (Macular laser)

Macular grid photocoagulation is not recommended for macular oedema secondary to CRVO.(CVOS, 1995). {Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. The Central Vein Occlusion Study Group M report. Ophthalmology. 1995 Oct;102(10):1425-33.}

Intravitreal triamcinolone

Intravitreal triamcinolone is superior to observation for treating macular edema secondary to CRVO.(SCORE, 2009). {Ip MS, Scott IU, VanVeldhuisen PC, Oden NL, Blodi BA, Fisher M, Singerman LJ, Tolentino M, Chan CK, Gonzalez VH; 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 Sep;127(9):1101-14.}

Treatment of Neovascularization

Laser panretinal photocoagulation

Prophylactic PRP does not totally prevent iris/angle neovascularisation (CVOS definition). The study authors recommend careful close observation initially and prompt PRP of eyes in which iris/angle neovascularisation develops.(CVOS, 1995). {A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion. The Central Vein Occlusion Study Group N report. Ophthalmology. 1995 Oct;102(10):1434-44. PMID: 9097789.}

Evidence

1 Background

Review

2018 Khayat et.al.

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2018
Review

Review of ischemic retinal vein occlusion: definition, diagnosis, epidemiology, risk factors and pathogenesis, the structural and functional effects of this disease in the eye and its complications, natural history, and outcomes after treatment. {Khayat M, Williams M, Lois N. Ischemic retinal vein occlusion: characterizing the more severe spectrum of retinal vein occlusion. Surv Ophthalmol. 2018 Nov-Dec;63(6):816-850.}

Review

2011 London & Brown

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2011
Review

1.1 Epidemiology

Meta-analysis

2019 Song et.al.

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2019
Meta-analysis

The prevalence of any RVO, branch RVO (BRVO) and central RVO (CRVO) all increased with advanced age, but didn’t differ significantly between sexes. In 2015, the global prevalence of any RVO, BRVO and CRVO in people aged 30-89 years was 0.77%, 0.64% and 0.13%. For any RVO, the pooled five-year cumulative incidence was 0.86% and the pooled ten-year cumulative incidence was 1.63%. Hypertension was the strongest risk factor for any RVO, with a meta- odds ratio (OR) of 2.82. {Song P, Xu Y, Zha M, Zhang Y, Rudan I. Global epidemiology of retinal vein occlusion: a systematic review and meta-analysis of prevalence, incidence, and risk factors. J Glob Health. 2019 Jun;9(1):010427.}

Review

2010 Rogers et.al.

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2010
Review

The age- and sex-standardized prevalence was 5.20 per 1000. Prevalence varied by race/ethnicity and increased with age, but did not differ by gender. {Rogers S, McIntosh RL, Cheung N, Lim L, Wang JJ, Mitchell P, Kowalski JW, Nguyen H, Wong TY; International Eye Disease Consortium. The prevalence of retinal vein occlusion: pooled data from population studies from the United States, Europe, Asia, and Australia. Ophthalmology. 2010 Feb;117(2):313-9.e1.}

Pooled analysis of the prevalence of retinal vein occlusion from studies in the United States, Europe, Asia, and Australia using individual population-based data.

1.2 Natural history

Systematic review

2010 McIntosh et.al.

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2010
Systematic review

Systematic review of 53 studies of CRVO showed that visual acuity was generally poor at baseline (<20/40) and decreased further over time. Up to 34% of eyes with nonischemic CRVO converted to ischemic CRVO over a 3-year period. In ischemic CRVO cases, neovascular glaucoma developed in at least 23% of eyes within 15 months. In nonischemic CRVO cases, macular edema resolved in approximately 30% of eyes over time, and subsequent neovascular glaucoma was rare. {McIntosh RL, Rogers SL, Lim L, Cheung N, Wang JJ, Mitchell P, Kowalski JW, Nguyen HP, Wong TY. Natural history of central retinal vein occlusion: an evidence-based systematic review. Ophthalmology. 2010 Jun;117(6):1113-1123.e15.}

2 Treatment of Macular Oedema

2.1 Laser photocoagulation (Macular laser)

2.1.1 Laser vs control

Clinical Trial

1995 CVOS Group

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1995
Clinical Trial

Macular grid photocoagulation is not recommended for macular oedema secondary to CRVO. {Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. The Central Vein Occlusion Study Group M report. Ophthalmology. 1995 Oct;102(10):1425-33.}

Randomized controlled trial of Macular grid photocoagulation vs control in CRVO with Macular oedema (155 patients)
Findings (3-years):
- There was no difference in visual acuity between treated and untreated eyes at any point during the follow-up period.

2.2 Anti-VEGF intravitreal injection

Cohort study

2021 Hogg et.al.

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2021
Cohort study

Visual acuity in CRVO complicated by macular oedema improves following anti-VEGF treatment but real-world gains are more modest than those from clinical trials. {Hogg HDJ, Talks SJ, Pearce M, Di Simplicio S. Real-World Visual and Neovascularisation Outcomes from anti-VEGF in Central Retinal Vein Occlusion. Ophthalmic Epidemiol. 2021 Feb;28(1):70-76.}

2.2.1 Ranibizumab

Clinical Trial

2012 Heier et.al. (HORIZON)

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2012
Clinical Trial

In the extension trial of CRUISE, vision in CRVO patients declined with 3 monthly reviews and intravitreal ranibizumab injection PRN. {Heier JS, Campochiaro PA, Yau L, Li Z, Saroj N, Rubio RG, Lai P. Ranibizumab for macular edema due to retinal vein occlusions: long-term follow-up in the HORIZON trial. Ophthalmology. 2012 Apr;119(4):802-9.}

Extension study of CRUISE, a randomized controlled trial of intravitreal ranibizumab vs sham in CRVO with Macular oedema (304 patients)
Findings (1-year):
- Vision in BRVO patients remained stable, while CRVO had a decline in vision. This could be due to reduced follow up and fewer ranibizumb injections in the second year of treatment.

	BRVO	CRVO
Mean no. of injections	2-2.4	2.9-3.8
Change in BCVA score (letter)	-2.3 to +0.9	-5.2 to -4.1

Clinical Trial

2011 Campochiaro et.al. (CRUISE)

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2011
Clinical Trial

Intravitreal ranibizumab PRN from months 6 to 11 maintained benefits achieved by 6 monthly ranibizumab injections in patients with macular oedema following CRVO. {Campochiaro PA, Brown DM, Awh CC, Lee SY, Gray S, Saroj N, Murahashi WY, Rubio RG. Sustained benefits from ranibizumab for macular edema following central retinal vein occlusion: twelve-month outcomes of a phase III study. Ophthalmology. 2011 Oct;118(10):2041-9.}

Randomized controlled trial of intravitreal ranibizumab vs sham in CRVO with Macular oedema (392 patients)
Findings (1-year):

Outcomes	Time point	RAN 0.3mg	RAN 0.5mg	Sham (RAN after 6mo)
Mean BCVA change (letter)	6 months	12.7	14.9	0.8
	12 months	13.9	13.9	7.3
Gained ≥15 letters in BCVA	6 months	46.2%	47.7%	16.9%
	12 months	47.0%	50.8%	33.1%
BCVA ≥20/40	6 months	43.9%	46.9%	20.8%
Reduction in CFT	6 months	434um	452um	168um

Campochiaro et.al. (CRUISE)
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Clinical Trial

2010 Brown et.al. (CRUISE)

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2010
Clinical Trial

Intravitreal ranibizumab provides rapid, effective treatment for macular oedema following CRVO at 6 months. {Brown DM, Campochiaro PA, Singh RP, Li Z, Gray S, Saroj N, Rundle AC, Rubio RG, Murahashi WY; CRUISE Investigators. Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology. 2010 Jun;117(6):1124-1133.e1.}

Randomized controlled trial of intravitreal ranibizumab vs sham in CRVO with Macular oedema (392 patients)
Findings (1-year):

Outcomes	Time point	RAN 0.3mg	RAN 0.5mg	Sham (RAN after 6mo)
Mean BCVA change (letter)	6 months	12.7	14.9	0.8
	12 months	13.9	13.9	7.3
Gained ≥15 letters in BCVA	6 months	46.2%	47.7%	16.9%
	12 months	47.0%	50.8%	33.1%
BCVA ≥20/40	6 months	43.9%	46.9%	20.8%
Reduction in CFT	6 months	434um	452um	168um

2.2.2 Aflibercept

Clinical Trial

2014 Ogura et.al. (GALILEO)

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2014
Clinical Trial

Improvements by 12 months were maintained at 18 months in patients with Macular oedema secondary to CRVO reviewed 8-weekly and intravitreal Aflibercept given PRN. {Ogura Y, Roider J, Korobelnik JF, Holz FG, Simader C, Schmidt-Erfurth U, Vitti R, Berliner AJ, Hiemeyer F, Stemper B, Zeitz O, Sandbrink R; GALILEO Study Group. Intravitreal aflibercept for macular edema secondary to central retinal vein occlusion: 18-month results of the phase 3 GALILEO study. Am J Ophthalmol. 2014 Nov;158(5):1032-8.}

Randomized controlled trial of intravitreal aflibercept vs sham in CRVO with Macular oedema (177 patients)
Findings (18-months):

Outcome	Time point	AFLI	Sham
Gained ≥15 letters	Week 24	60.2%	22.1%
	Week 52	60.2%	32.4%
	Week 76	57.3%	29.4%

Clinical Trial

2014 Korobelnik et.al. (GALILEO)

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2014
Clinical Trial

Intravitreal Aflibercept provided significant functional and anatomic benefits at 1 year vs sham in patients with Macular oedema secondary to CRVO, with improvements after 6 monthly doses maintained at 1 year on a PRN dosing. {Korobelnik JF, Holz FG, Roider J, Ogura Y, Simader C, Schmidt-Erfurth U, Lorenz K, Honda M, Vitti R, Berliner AJ, Hiemeyer F, Stemper B, Zeitz O, Sandbrink R; GALILEO Study Group. Intravitreal Aflibercept Injection for Macular Edema Resulting from Central Retinal Vein Occlusion: One-Year Results of the Phase 3 GALILEO Study. Ophthalmology. 2014 Jan;121(1):202-208.}

Randomized controlled trial of intravitreal aflibercept vs sham in CRVO with Macular oedema (177 patients)
Findings (1-year):

Outcome	Time point	AFLI	Sham
Gained ≥15 letters	Week 24	60.2%	22.1%
	Week 52	60.2%	32.4%
	Week 76	57.3%	29.4%

Korobelnik et.al. (GALILEO)
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Clinical Trial

2014 Brown et.al. (COPERNICUS)

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2014
Clinical Trial

Benefits achieved after monthly dosing through week 24 and PRN dosing with monthly monitoring from weeks 24 to 52 were diminished after continued PRN dosing with a reduced monitoring frequency from weeks 52 to 100. {Heier JS, Clark WL, Boyer DS, Brown DM, Vitti R, Berliner AJ, Kazmi H, Ma Y, Stemper B, Zeitz O, Sandbrink R, Haller JA. Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study. Ophthalmology. 2014 Jul;121(7):1414-1420.e1.}

Randomized controlled trial of intravitreal aflibercept vs sham in CRVO with Macular oedema (188 patients)
Findings (1-year):

Outcomes	Time point	AFLI + AFLI PRN/Sham	Sham + AFLI PRN
Gained ≥15 letters	Week 24	56.1%	12.3%
	Week 52	55.3%	30.1%
	Week 100	49.1%	23.3%
BCVA change from baseline	Week 24	+17.3	-4.0
	Week 52	+16.2	+3.8
	Week 100	+13.0	+1.5

Brown et.al. (COPERNICUS)
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Clinical Trial

2013 Brown et.al. (COPERNICUS)

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2013
Clinical Trial

Monthly injections of intravitreal aflibercept for patients with macular edema secondary to CRVO resulted in significant improvement in visual acuity at week 24, which was largely maintained through week 52 with PRN dosing. {Brown DM, Heier JS, Clark WL, Boyer DS, Vitti R, Berliner AJ, Zeitz O, Sandbrink R, Zhu X, Haller JA. Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study. Am J Ophthalmol. 2013 Mar;155(3):429-437.e7.}

Randomized controlled trial of intravitreal aflibercept vs sham in CRVO with Macular oedema (188 patients)
Findings (1-year):

Outcomes	Time point	AFLI + AFLI PRN/Sham	Sham + AFLI PRN
Gained ≥15 letters	Week 24	56.1%	12.3%
	Week 52	55.3%	30.1%
	Week 100	49.1%	23.3%
BCVA change from baseline	Week 24	+17.3	-4.0
	Week 52	+16.2	+3.8
	Week 100	+13.0	+1.5

Brown et.al. (COPERNICUS)
Journal full text Archive Metrics

2.2.3 Bevacizumab

Clinical Trial

2017 Scott et.al. (SCORE2)

Article link | Archive link | Metrics

2017
Clinical Trial

Intravitreal Bevacizumab was non-inferior to Aflibercept in 6-month visual outcomes in macular oedema secondary to central/hemi-RVO. {Scott IU, VanVeldhuisen PC, Ip MS, Blodi BA, Oden NL, Awh CC, Kunimoto DY, Marcus DM, Wroblewski JJ, King J; SCORE2 Investigator Group. Effect of Bevacizumab vs Aflibercept on Visual Acuity Among Patients With Macular Edema Due to Central Retinal Vein Occlusion: The SCORE2 Randomized Clinical Trial. JAMA. 2017 May 23;317(20):2072-2087.}

Randomized controlled trial of intravitreal aflibercept vs intravitreal bevacizumab in CRVO with Macular oedema (362 patients)
Findings (6-months):
- Mean VA letter score improvement was similar between both groups (18.6 vs 18.9); Bevacizumab was non-inferior to Aflibercept.

2.2.4 Ranibizumab vs Aflibercept vs Bevacizumab

Clinical Trial

2019 Hykin et.al. (LEAVO)

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2019
Clinical Trial

Mean change in vision were similar with Aflibercept and Ranibizumab in macular oedema due to CRVO. Vision change with Bevacizumab vs Ranibizumab was inconclusive. {Hykin P, Prevost AT, Vasconcelos JC, Murphy C, Kelly J, Ramu J, Hounsome B, Yang Y, Harding SP, Lotery A, Chakravarthy U, Sivaprasad S; LEAVO Study Group. Clinical Effectiveness of Intravitreal Therapy With Ranibizumab vs Aflibercept vs Bevacizumab for Macular Edema Secondary to Central Retinal Vein Occlusion: A Randomized Clinical Trial. JAMA Ophthalmol. 2019 Nov 1;137(11):1256-1264.}

Randomized controlled trial of intravitreal ranibizumab vs aflibercept vs bevacizumab in CRVO with Macular oedema (463 patients)
Findings (2-years):

	RAN	AFLI	BEV
BCVA gain (letters)	+12.5	+15.1	+9.8
Mean injections	11.8	10.0	11.5

2.3 Intravitreal Triamcinolone

2.3.1 Triamcinolone vs observation

Clinical Trial

2009 Ip et.al. (SCORE)

Article link | Archive link

2009
Clinical Trial

Intravitreal triamcinolone is superior to observation for treating macular edema secondary to CRVO. {Ip MS, Scott IU, VanVeldhuisen PC, Oden NL, Blodi BA, Fisher M, Singerman LJ, Tolentino M, Chan CK, Gonzalez VH; 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 Sep;127(9):1101-14.}

Randomized controlled trial of intravitreal triamcinolone vs observation in CRVO with Macular oedema (271 patients)
Findings (1-year):

	Observation	IVTA 1mg	IVTA 4mg
VA gain ≥ 15 letters from baseline	7%	27%	26%

2.3.2 Corticosteroid vs Laser

Refer to 2.1.2 above

3 Treatment of Neovascularization

Cohort study

2021 Hogg et.al.

Article link | Metrics

2021
Cohort study

Neovascularisation following CRVO can be substantially delayed by anti-VEGF treatment and so if individuals who have received IVIs are to be effectively screened for neovascularisation long-term surveillance is necessary. {Hogg HDJ, Talks SJ, Pearce M, Di Simplicio S. Real-World Visual and Neovascularisation Outcomes from anti-VEGF in Central Retinal Vein Occlusion. Ophthalmic Epidemiol. 2021 Feb;28(1):70-76.}

3.1 Laser photocoagulation (PRP)

Clinical Trial

1995 CVOS Group

Article link | Archive link | Metrics

1995
Clinical Trial

Prophylactic PRP does not totally prevent iris/angle neovascularisation (CVOS definition). The study authors recommend careful close observation initially and prompt PRP of eyes in which iris/angle neovascularisation develops. {A randomized clinical trial of early panretinal photocoagulation for ischemic central vein occlusion. The Central Vein Occlusion Study Group N report. Ophthalmology. 1995 Oct;102(10):1434-44. PMID: 9097789.}

Randomized controlled trial of immediate prophylactic PRP vs observation in ischaemic CRVO (181 patients)
Findings
- 2 clock hours of iris neovascularization or any angle neovascularization (TC-INV/ANV) developed less often in prophylactically treated than untreated eyes, but the difference was not statistically significant.

Central Retinal Vein Occlusion

Summary of Evidence

Evidence

1 Background

1.1 Epidemiology

Details

1.2 Natural history

2 Treatment of Macular Oedema

2.1 Laser photocoagulation (Macular laser)

2.1.1 Laser vs control

Details

2.2 Anti-VEGF intravitreal injection

2.2.1 Ranibizumab

Details

Details

Details

2.2.2 Aflibercept

Details

Details

Details

Details

2.2.3 Bevacizumab

Details

2.2.4 Ranibizumab vs Aflibercept vs Bevacizumab

Details

2.3 Intravitreal Triamcinolone

2.3.1 Triamcinolone vs observation

Details

2.3.2 Corticosteroid vs Laser

Refer to 2.1.2 above

3 Treatment of Neovascularization

3.1 Laser photocoagulation (PRP)

Details

References

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