Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Ophthalmology
Published in: BMC Ophthalmology 1/2014

Open Access 01-12-2014 | Research article

Efficacy and safety of widely used treatments for macular oedema secondary to retinal vein occlusion: a systematic review

Authors: Julie Glanville, Jacoby Patterson, Rachael McCool, Alberto Ferreira, Kerry Gairy, Ian Pearce

Published in: BMC Ophthalmology | Issue 1/2014

Login to get access

Abstract

Background

Macular oedema secondary to retinal vein occlusion (RVO) can cause vision loss due to blockage of the central retinal vein (CRVO) or a branch retinal vein (BRVO). This systematic review assessed the efficacies of widely used treatments for macular oedema secondary to RVO and the feasibility of conducting indirect comparisons between these therapies.

Methods

A systematic review was undertaken in November 2010, including a literature search for trials in medical databases and relevant websites. Abstracts, conference presentations and unpublished studies were considered. Studies were data-extracted and quality assessed by two independent researchers. Outcome measures included the mean change in best corrected visual acuity (BCVA) from baseline in the study eye and/or number of patients gaining at least 10 letters from baseline to 6 months or the nearest equivalent time point.

Results

Fourteen unique randomized controlled trials (RCTs) were identified. Ranibizumab 0.5 mg produced greater improvements in BCVA at 6 months than sham in BRVO (mean difference 11.0 letters, 95% confidence interval [CI] 7.83, 14.17) and CRVO (mean difference 14.10 letters, 95% CI 10.51, 17.69) in two double-blind sham-controlled RCTs. Pooled data from two double-blind, sham-controlled RCTs showed that improvements in BCVA were also significantly better for dexamethasone intravitreal (IVT) implant 0.7 mg compared with sham in patients with BRVO or CRVO (mean difference 2.5 letters, 95% CI 0.7, 4.3); the difference was significant for BRVO alone, but not CRVO alone. A significantly greater proportion of patients with BRVO gained ≥15 letters with laser therapy vs. no treatment at 36 months in a large prospective RCT (odds ratio 3.16, 95% CI 1.25, 8.00), whereas no difference was observed at 9 months in a smaller study. Three studies reported no benefit for laser therapy in CRVO. No indirect comparisons with ranibizumab were feasible due to differences in study design and baseline characteristics.

Conclusions

Data from RCTs for ranibizumab and dexamethasone IVT demonstrate that both new agents constitute significant improvements over the previously widely accepted standard of care (laser therapy) for the treatment of BRVO and CRVO. However, head-to-head studies are needed to assess the relative efficacies of licensed therapies for RVO.
Appendix
Available only for authorised users
Literature
1.
Parodi MB, Bandello F: Branch retinal vein occlusion: classification and treatment. Ophthalmologica. 2009, 223 (5): 298-305. 10.1159/000213640.CrossRefPubMed
2.
Hayreh SS, Zimmerman MB, Podhajsky P: Incidence of various types of retinal vein occlusion and their recurrence and demographic characteristics. Am J Ophthalmol. 1994, 117 (4): 429-441.CrossRefPubMed
3.
Wong TY, Scott IU: Clinical practice. Retinal-vein occlusion. N Engl J Med. 2010, 363 (22): 2135-2144. 10.1056/NEJMcp1003934.CrossRefPubMed
4.
5.
Yau JW, Lee P, Wong TY, Best J, Jenkins A: Retinal vein occlusion: an approach to diagnosis, systemic risk factors and management. Intern Med J. 2008, 38 (12): 904-910. 10.1111/j.1445-5994.2008.01720.x.CrossRefPubMed
6.
BVOS: Argon laser photocoagulation for macular edema in branch vein occlusion. The branch vein occlusion study group. Am J Ophthalmol. 1984, 98 (3): 271-282.CrossRef
7.
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, 117 (6): 1113-1123. 10.1016/j.ophtha.2010.01.060. e1115CrossRefPubMed
8.
Awdeh RM, Elsing SH, Deramo VA, Stinnett S, Lee PP, Fekrat S: Vision-related quality of life in persons with unilateral branch retinal vein occlusion using the 25-item national eye institute visual function questionnaire. Br J Ophthalmol. 2010, 94 (3): 319-323. 10.1136/bjo.2007.135913.CrossRefPubMed
9.
Deramo VA, Cox TA, Syed AB, Lee PP, Fekrat S: Vision-related quality of life in people with central retinal vein occlusion using the 25-item national eye institute visual function questionnaire. Arch Ophthalmol. 2003, 121 (9): 1297-1302. 10.1001/archopht.121.9.1297.CrossRefPubMed
10.
CVOS: Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. The central vein occlusion study group. Ophthalmology. 1995, 102 (10): 1425-1433.CrossRef
11.
Varma R, Wu J, Chong K, Azen SP, Hays RD: Impact of severity and bilaterality of visual impairment on health-related quality of life. Ophthalmology. 2006, 113 (10): 1846-1853. 10.1016/j.ophtha.2006.04.028.CrossRefPubMed
12.
13.
14.
15.
Pieramici DJ, Rabena M, Castellarin AA, Nasir M, See R, Norton T, Sanchez A, Risard S, Avery RL: Ranibizumab for the treatment of macular edema associated with perfused central retinal vein occlusions. Ophthalmology. 2008, 115 (10): e47-54. 10.1016/j.ophtha.2008.06.021.CrossRefPubMed
16.
McAllister IL, Vijayasekaran S, Chen SD, Yu DY: Effect of triamcinolone acetonide on vascular endothelial growth factor and occludin levels in branch retinal vein occlusion. Am J Ophthalmol. 2009, 147 (5): 838-846. 10.1016/j.ajo.2008.12.006. e831-832CrossRefPubMed
17.
Leopold IH: Nonsteroidal and steroidal anti-inflammatory agents. Surgical Pharmacology of the Eye. Edited by: Sears ML, Tarkkanen A. 1985, New York: Raven Press, 83-133.
18.
Haller JA, Bandello F, Belfort R, Blumenkranz MS, Gillies M, Heier J, Loewenstein A, Yoon YH, Jacques ML, Jiao J, 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. 10.1016/j.ophtha.2010.03.032. e1133CrossRefPubMed
19.
Koss MJ, Pfister M, Rothweiler F, Michaelis M, Cinatl J, Schubert R, Koch FH: Comparison of cytokine levels from undiluted vitreous of untreated patients with retinal vein occlusion. Acta Ophthalmol. 2012, 90 (2): e98-e103. 10.1111/j.1755-3768.2011.02292.x.CrossRefPubMed
20.
Kuppermann BD, Blumenkranz MS, Haller JA, Williams GA, Weinberg DV, Chou C, Whitcup SM: Randomized controlled study of an intravitreous dexamethasone drug delivery system in patients with persistent macular edema. Arch Ophthalmol. 2007, 125 (3): 309-317. 10.1001/archopht.125.3.309.CrossRefPubMed
21.
Pfister M, Rothweiler F, Michaelis M, Cinatl J, Schubert R, Koch FH, Koss MJ: Correlation of inflammatory and proangiogenic cytokines from undiluted vitreous samples with spectral domain OCT scans, in untreated branch retinal vein occlusion. Clin Ophthalmol. 2013, 7: 1061-1067.CrossRefPubMedPubMedCentral
22.
Wang K, Wang Y, Gao L, Li X, Li M, Guo J: Dexamethasone inhibits leukocyte accumulation and vascular permeability in retina of streptozotocin-induced diabetic rats via reducing vascular endothelial growth factor and intercellular adhesion molecule-1 expression. Biol Pharm Bull. 2008, 31 (8): 1541-1546. 10.1248/bpb.31.1541.CrossRefPubMed
23.
Scott IU, Ip MS, VanVeldhuisen PC, Oden NL, Blodi BA, Fisher M, Chan CK, Gonzalez VH, Singerman LJ, Tolentino M: 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.CrossRefPubMedPubMedCentral
24.
Zhang X, Bao S, Lai D, Rapkins RW, Gillies MC: Intravitreal triamcinolone acetonide inhibits breakdown of the blood-retinal barrier through differential regulation of VEGF-A and its receptors in early diabetic rat retinas. Diabetes. 2008, 57 (4): 1026-1033. 10.2337/db07-0982.CrossRefPubMedPubMedCentral
25.
26.
Center for Reviews and Dissemination: Systemtic Reviews: CRD’s guidance for undertaking reviews in health care. 2009, York: CRD, University of York
27.
Gray S, Rubio R: A phase III, multicenter, randomized, sham injection-controlled study of the efficacy and safety of ranibizumab injection compared with sham in subjects with macular edema secondary to branch retinal vein occlusion [Clinical Study Report]. 2009, Genentech: South San Francisco, CA
28.
Gray S, Rubio R: A phase III, multicenter, randomized, sham injection-controlled study of the efficacy and safety of ranibizumab injection compared with sham in subjects with macular edema secondary to branch retinal vein occlusion [Clinical Study Report Addendum]. 2009, Genentech: South San Francisco, CA
29.
Gray S, Rubio R: A phase III, multicenter, randomized, sham injection-controlled study of the efficacy and safety of ranibizumab injection compared with sham in subjects with macular edema secondary to central retinal vein occlusion [Clinical Study Report]. 2010, Genentech: South San Francisco, CA
30.
Gray S, Rubio R: A phase III, multicenter, randomized, sham injection-controlled study of the efficacy and safety of ranibizumab injection compared with sham in subjects with macular edema secondary to central retinal vein occlusion [Clinical Study Report Addendum]. 2010, Genentech: South San Francisco, CA
31.
32.
33.
34.
35.
36.
Chang TS, Bressler NM, Fine JT, Dolan CM, Ward J, Klesert TR: Improved vision-related function after ranibizumab treatment of neovascular age-related macular degeneration: results of a randomized clinical trial. Arch Ophthalmol. 2007, 125 (11): 1460-1469. 10.1001/archopht.125.11.1460.CrossRefPubMed
37.
Mangione CM, Lee PP, Gutierrez PR, Spritzer K, Berry S, Hays RD: Development of the 25-item national eye institute visual function questionnaire. Arch Ophthalmol. 2001, 119 (7): 1050-1058. 10.1001/archopht.119.7.1050.CrossRefPubMed
38.
Margolis MK, Coyne K, Kennedy-Martin T, Baker T, Schein O, Revicki DA: Vision-specific instruments for the assessment of health-related quality of life and visual functioning: a literature review. Pharmacoeconomics. 2002, 20 (12): 791-812. 10.2165/00019053-200220120-00001.CrossRefPubMed
39.
Csaky KG, Richman EA, Ferris FL: Report from the NEI/FDA ophthalmic clinical trial design and endpoints symposium. Invest Ophthalmol Vis Sci. 2008, 49 (2): 479-489. 10.1167/iovs.07-1132.CrossRefPubMed
40.
NICE: Single technology appraisal (STA). Specification for manufacturer/sponsor submission of evidence. 2009, London: NICE
41.
42.
Brown DM, Campochiaro PA, Singh RP, Li Z, Gray S, Saroj N, Rundle AC, Rubio RG, Murahashi WY: 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. 10.1016/j.ophtha.2010.02.022. e1121CrossRefPubMed
43.
Campochiaro PA, Heier JS, Feiner L, Gray S, Saroj N, Rundle AC, Murahashi WY, Rubio RG: 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. 10.1016/j.ophtha.2010.02.021. e1101CrossRefPubMed
44.
Kinge B, Stordahl PB, Forsaa V, Fossen K, Haugstad M, Helgesen OH, Seland J, Stene-Johansen I: Efficacy 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 (3): 310-314. 10.1016/j.ajo.2010.03.028.CrossRefPubMed
45.
Battaglia Parodi M, Saviano S, Bergamini L, Ravalico G: Grid laser treatment of macular edema in macular branch retinal vein occlusion. Doc Ophthalmol. 1999, 97 (3–4): 427-431.CrossRefPubMed
46.
Laatikainen L, Kohner EM, Khoury D, Blach RK: Panretinal photocoagulation in central retinal vein occlusion: a randomised controlled clinical study. Br J Ophthalmol. 1977, 61 (12): 741-753. 10.1136/bjo.61.12.741.CrossRefPubMedPubMedCentral
47.
May DR, Klein ML, Peyman GA, Raichand M: Xenon arc panretinal photocoagulation for central retinal vein occlusion: a randomised prospective study. Br J Ophthalmol. 1979, 63 (11): 725-734. 10.1136/bjo.63.11.725.CrossRefPubMedPubMedCentral
48.
49.
Moradian S, Faghihi H, Sadeghi B, Piri N, Ahmadieh H, Soheilian M, Dehghan MH, Azarmina M, Esfahani MR: Intravitreal bevacizumab vs. sham treatment in acute branch retinal vein occlusion with macular edema: results at 3 months (Report 1). Graefes Arch Clin Exp Ophthalmol. 2011, 249 (2): 193-200. 10.1007/s00417-010-1440-8.CrossRefPubMed
50.
Russo V, Barone A, Conte E, Prascina F, Stella A, Noci ND: Bevacizumab compared with macular laser grid photocoagulation for cystoid macular edema in branch retinal vein occlusion. Retina. 2009, 29 (4): 511-515. 10.1097/IAE.0b013e318195ca65.CrossRefPubMed
51.
52.
Brown DM, Campochiaro PA, Bhisitkul RB, Ho AC, Gray S, Saroj N, Adamis AP, Rubio RG, Murahashi WY: Sustained benefits from ranibizumab for macular edema following branch retinal vein occlusion: 12-month outcomes of a phase III study. Ophthalmology. 2011, 118 (8): 1594-1602. 10.1016/j.ophtha.2011.02.022.CrossRefPubMed
53.
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, 118 (10): 2041-2049. 10.1016/j.ophtha.2011.02.038.CrossRefPubMed
54.
Haller JA, Bandello F, Belfort R, Blumenkranz MS, Gillies M, Heier J, Loewenstein A, Yoon YH, Jiao J, Li XY, et al: Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results. Ophthalmology. 2011, 118 (12): 2453-2460. 10.1016/j.ophtha.2011.05.014.CrossRefPubMed
55.
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, 119 (4): 802-809. 10.1016/j.ophtha.2011.12.005.CrossRefPubMed
56.
Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S: Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006, 355 (14): 1432-1444. 10.1056/NEJMoa062655.CrossRefPubMed
57.
Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, Ferris FL, Friedman SM, Glassman AR, Miller KM, et al: Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for diabetic macular edema. Ophthalmology. 2010, 117 (6): 1064-1077. 10.1016/j.ophtha.2010.02.031. e1035CrossRefPubMedPubMedCentral
58.
Regillo CD, Brown DM, Abraham P, Yue H, Ianchulev T, Schneider S, Shams N: Randomized, double-masked, sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1. Am J Ophthalmol. 2008, 145 (2): 239-248. 10.1016/j.ajo.2007.10.004.CrossRefPubMed
59.
Aiello LM: Perspectives on diabetic retinopathy. Am J Ophthalmol. 2003, 136 (1): 122-135. 10.1016/S0002-9394(03)00219-8.CrossRefPubMed
60.
Lovestam-Adrian M, Agardh E: Photocoagulation of diabetic macular oedema complications and visual outcome. Acta Ophthalmol Scand. 2000, 78 (6): 667-671. 10.1034/j.1600-0420.2000.078006667.x.CrossRefPubMed
61.
Striph GG, Hart WM, Olk RJ: Modified grid laser photocoagulation for diabetic macular edema. The effect on the central visual field. Ophthalmology. 1988, 95 (12): 1673-1679. 10.1016/S0161-6420(88)32957-X.CrossRefPubMed
62.
Boyer D, Heier J, Brown DM, Clark WL, Vitti R, Berliner AJ, Groetzbach G, Zeitz O, Sandbrink R, Zhu X, et al: Vascular endothelial growth factor Trap-Eye for macular edema secondary to central retinal vein occlusion: six-month results of the phase 3 COPERNICUS study. Ophthalmology. 2012, 119 (5): 1024-1032. 10.1016/j.ophtha.2012.01.042.CrossRefPubMed
63.
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, 155 (3): 429-437. 10.1016/j.ajo.2012.09.026. e427CrossRefPubMed
64.
Holz FG, Roider J, Ogura Y, Korobelnik JF, Simader C, Groetzbach G, Vitti R, Berliner AJ, Hiemeyer F, Beckmann K, et al: VEGF Trap-Eye for macular oedema secondary to central retinal vein occlusion: 6-month results of the phase III GALILEO study. Br J Ophthalmol. 2013, 97 (3): 278-284. 10.1136/bjophthalmol-2012-301504.CrossRefPubMed
65.
Korobelnik JF, Holz FG, Roider J, Ogura Y, Simader C, Schmidt-Erfurth U, Lorenz K, Honda M, Vitti R, Berliner AJ, et al: Intravitreal aflibercept injection for macular edema resulting from central retinal vein occlusion: one-year results of the phase 3 GALILEO study. Ophthalmology. 2013, 121 (1): 202-208.CrossRefPubMed
Metadata
Title
Efficacy and safety of widely used treatments for macular oedema secondary to retinal vein occlusion: a systematic review
Authors
Julie Glanville
Jacoby Patterson
Rachael McCool
Alberto Ferreira
Kerry Gairy
Ian Pearce
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Ophthalmology / Issue 1/2014
Electronic ISSN: 1471-2415
DOI
https://doi.org/10.1186/1471-2415-14-7

Other articles of this Issue 1/2014

BMC Ophthalmology 1/2014 Go to the issue

Research article

Improving adherence to glaucoma medication: a randomised controlled trial of a patient-centred intervention (The Norwich Adherence Glaucoma Study)

Case report

Ocular rhinosporidiosis mimicking conjunctival squamous papilloma in Kenya – a case report

Research article

Preliminary study of the association between corneal histocytological changes and surgically induced astigmatism after phacoemulsification

Research article

Essential infantile esotropia: postoperative motor outcomes and inferential analysis of strabismus surgery

Research article

Computer aided quantification for retinal lesions in patients with moderate and severe non-proliferative diabetic retinopathy: a retrospective cohort study

Research article

Clinical and optic coherence tomography findings of focal choroidal excavation in Chinese patients