Medline ® Abstracts for References 3-8
of 'Retinal vein occlusion: Treatment'
Anti-vascular endothelial growth factor for macular edema secondary to central retinal vein occlusion.
Braithwaite T, Nanji AA, Greenberg PB
Cochrane Database Syst Rev. 2010;
BACKGROUND: Central retinal vein occlusion (CRVO) is a common retinal vascular disorder in which macular edema (ME) may develop, with a consequent reduction in visual acuity. The visual prognosis in CRVO-ME is poor in a substantial proportion of patients, especially those with the ischemic subtype, and until recently there has been no treatment of proven benefit. Macular grid laser treatment is ineffective, and whilst a few recent randomized controlled trials (RCTs) suggest short-term gains in visual acuity with intravitreal steroids for patients with non-ischemic CRVO-ME, there is no established treatment for ischemic CRVO-ME. Anti-vascular endothelial growth factor (anti-VEGF) agents have been used to treat ME resulting from a variety of causes and may represent a treatment option for CRVO-ME.
OBJECTIVES: To investigate the effectiveness and safety of intravitreal anti-VEGF agents in the treatment of CRVO-ME.
SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2010, Issue 8), MEDLINE (January 1950 to August 2010), EMBASE(January 1980 to August 2010), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2010), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to August 2010), OpenSIGLE (January 1950 to August 2010), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (www.clinicaltrials.gov). There were no language or date restrictions in the search for trials. The electronic databases were last searched on 10 August 2010.
SELECTION CRITERIA: We considered RCTs that compared intravitreal anti-VEGF agents of any dose or duration to sham injection or no treatment. We focused on studies that included individuals of any age or gender with unilateral or bilateral disease and a minimum of six months follow up. Secondarily, we considered non-randomized studies with the same criteria, but did not conduct a separate electronic search for these.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data.
MAIN RESULTS: We found two RCTs that met the inclusion criteria after independent and duplicate review of the search results. These RCTs utilized different anti-VEGF agents which cannot be assumed to be directly comparable. We, therefore, performed no meta-analysis. Evidence from these trials and from other non-randomized case series is summarized in this review.
AUTHORS' CONCLUSIONS: Ranibizumab and pegaptanib sodium have shown promise in the short-term treatment of non-ischemic CRVO-ME. However, effectiveness and safety data from larger RCTs with follow up beyond six months are not yet available. There are no RCT data on anti-VEGF agents in ischemic CRVO-ME. The use of anti-VEGF agents to treat this condition therefore remains experimental.
Moorfields Eye Hospital NHS Foundation Trust, 162 City Road, London, UK, EC1V 2PD.
Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study.
Brown DM, Campochiaro PA, Singh RP, Li Z, Gray S, Saroj N, Rundle AC, Rubio RG, Murahashi WY, CRUISE Investigators
Ophthalmology. 2010;117(6):1124. Epub 2010 Apr 9.
PURPOSE: To assess the efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after central retinal vein occlusion (CRVO).
DESIGN: Prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trial.
PARTICIPANTS: A total of 392 patients with macular edema after CRVO.
METHODS: Eligible patients were randomized 1:1:1 to receive monthly intraocular injections of 0.3 or 0.5 mg of ranibizumab or sham injections.
MAIN OUTCOME MEASURES: The primary efficacy outcome measure was mean change from baseline best-corrected visual acuity (BCVA) letter score at month 6. Secondary outcomes included other parameters of visual function and central foveal thickness (CFT).
RESULTS: Mean (95% confidence interval [CI]) change from baseline BCVA letter score at month 6 was 12.7 (9.9-15.4) and 14.9 (12.6-17.2) in the 0.3 mg and 0.5 mg ranibizumab groups, respectively, and 0.8 (-2.0 to 3.6) in the sham group (P<0.0001 for each ranibizumab group vs. sham). The percentage of patients who gained>or =15 letters in BCVA at month 6 was 46.2% (0.3 mg) and 47.7% (0.5 mg) in the ranibizumab groups and 16.9% in the sham group (P<0.0001 for each ranibizumab group vs. sham). At month 6, significantly more ranibizumab-treated patients (0.3 mg = 43.9%; 0.5 mg = 46.9%) had BCVA of>or = 20/40 compared with sham patients (20.8%; P<0.0001 for each ranibizumab group vs. sham), and CFT had decreased by a mean of 434 microm (0.3 mg) and 452 microm (0.5 mg) in the ranibizumab groups and 168 microm in the sham group (P<0.0001 for each ranibizumab group vs. sham). The median percent reduction in excess foveal thickness at month 6 was 94.0% and 97.3% in the 0.3 mg and 0.5 mg groups, respectively, and 23.9% in the sham group. The safety profile was consistent with previous phase III ranibizumab trials, and no new safety events were identified in patients with CRVO.
CONCLUSIONS: Intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid improvement in 6-month visual acuity and macular edema following CRVO, with low rates of ocular and nonocular safety events.
Retina Consultants of Houston, The Methodist Hospital, Houston, Texas 77030, USA. email@example.com
Sustained benefits from ranibizumab for macular edema following central retinal vein occlusion: twelve-month outcomes of a phase III study.
Campochiaro PA, Brown DM, Awh CC, Lee SY, Gray S, Saroj N, Murahashi WY, Rubio RG
Ophthalmology. 2011 Oct;118(10):2041-9. Epub 2011 Jun 29.
PURPOSE: Assess the 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after central retinal vein occlusion (CRVO).
DESIGN: Prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trial.
PARTICIPANTS: We included 392 patients with macular edema after CRVO.
METHODS: Eligible patients were randomized 1:1:1 to receive 6 monthly intraocular injections of 0.3 mg or 0.5 mg of ranibizumab or sham injections. After 6 months, all patients with BCVA≤20/40 or central subfield thickness≥250μm could receive ranibizumab.
MAIN OUTCOME MEASURES: Mean change from baseline best-corrected visual acuity (BCVA) letter score at month 12,additional parameters of visual function, central foveal thickness (CFT), and other anatomic changes were assessed.
RESULTS: Mean (95% confidence interval) change from baseline BCVA letter score at month 12 was 13.9 (11.2-16.5) and 13.9 (11.5-16.4) in the 0.3 mg and 0.5 mg groups, respectively, and 7.3 (4.5-10.0) in the sham/0.5 mg group (P<0.001 for each ranibizumab group vs. sham/0.5 mg). The percentage of patients who gained≥15 letters from baseline BCVA at month 12 was 47.0% and 50.8% in the 0.3 mg and 0.5 mg groups, respectively, and 33.1% in the sham/0.5 mg group. On average, there was a marked reduction in CFT after the first as-needed injection of 0.5 mg ranibizumab in the sham/0.5 mg group to the level of the ranibizumab groups, which was sustained through month 12. No new ocular or nonocular safety events were identified.
CONCLUSIONS: On average, treatment with ranibizumab as needed during months 6 through 11 maintained the visual and anatomic benefits achieved by 6 monthly ranibizumab injections in patients with macular edema after CRVO, with low rates of ocular and nonocular safety events. After sham injections for 6 months, treatment with ranibizumab as needed for 6 months resulted in rapid reduction in CFT in the sham/0.5 mg group to a level similar to that in the 2 ranibizumab treatment groups and an improvement in BCVA, but not to the same level as that in the 2 ranibizumab groups. Intraocular injections of ranibizumab provide an effective treatment for macular edema after CRVO.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
Departments of Ophthalmology and Neuroscience, The Johns Hopkins School of Medicine, Baltimore, MD 21287-9277, USA. firstname.lastname@example.org
Intravitreal pharmacotherapy: applications in retinal disease.
Prasad AG, Schadlu R, Apte RS
Compr Ophthalmol Update. 2007;8(5):259.
Intravitreal pharmacotherapies have been used with increasing frequency in the treatment of retinal disease. Indications for their use include choroidal neovascular membranes, diabetic macular edema, ischemic neovascularization, inflammatory and infectious processes, and neoplasia. Complications of intravitreal therapies include cataract formation, glaucoma, and endophthalmitis. Recent developments of pharmacologic agents administered intravitreally and the new applications of systemic medications in retinal disease present the practitioner with expanded treatment options. Current and emerging data will help guide therapy in order to maximize the benefits and limit the systemic and ocular complications of these new treatment options.
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA.
Pegaptanib sodium for macular edema secondary to central retinal vein occlusion.
Wroblewski JJ, Wells JA 3rd, Adamis AP, Buggage RR, Cunningham ET Jr, Goldbaum M, Guyer DR, Katz B, Altaweel MM, Pegaptanib in Central Retinal Vein Occlusion Study Group
Arch Ophthalmol. 2009;127(4):374.
OBJECTIVES: To assess the safety and efficacy of intravitreous pegaptanib sodium for the treatment of macular edema following central retinal vein occlusion (CRVO).
DESIGN: This dose-ranging, double-masked, multicenter, phase 2 trial included subjects with CRVO for 6 months' or less duration randomly assigned (1:1:1) to receive pegaptanib sodium or sham injections every 6 weeks for 24 weeks (0.3 mg and 1 mg, n=33; sham, n=32).
MAIN OUTCOME MEASURE: Visual acuity at week 30.
RESULTS: In the primary analysis at week 30, 12 of 33 (36%) subjects treated with 0.3 mg of pegaptanib sodium and 13 of 33 (39%) treated with 1 mg gained 15 or more letters from baseline vs 9 of 32 (28%) sham-treated subjects (P= .48 for 0.3 mg and P= .35 for 1 mg of pegaptanib sodium vs sham). In secondary analyses, subjects treated with pegaptanib sodium were less likely to lose 15 or more letters (9% and 6%; 0.3-mg and 1-mg pegaptanib sodium groups, respectively) compared with sham-treated eyes (31%; P= .03 for 0.3 mg and P= .01 for 1 mg of pegaptanib sodium vs sham) and showed greater improvement in mean visual acuity (+7.1 and +9.9, respectively, vs -3.2 letters with sham; P= .09 for 0.3 mg and P= .02 for 1 mg of pegaptanib sodium vs sham). By week 1, the mean central retinal thickness decreased in the 0.3-mg and 1-mg pegaptanib sodium groups by 269 microm and 210 microm, respectively, vs 5 microm with sham (P<.001).
CONCLUSIONS: Based on this 30-week study, intravitreous pegaptanib sodium appears to provide visual and anatomical benefits in the treatment of macular edema following CRVO.
APPLICATION TO CLINICAL PRACTICE: Benefits accrued with intravitreous pegaptanib sodium treatment of macular edema following CRVO suggest a role for vascular endothelial growth factor in the pathogenesis of this condition.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00088283.
Cumberland Valley Retina Consultants, Hagerstown, Maryland 21740, USA. email@example.com
Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study.
Brown DM, Heier JS, Clark WL, Boyer DS, Vitti R, Berliner AJ, Zeitz O, Sandbrink R, Zhu X, Haller JA
Am J Ophthalmol. 2013 Mar;155(3):429-437.e7. Epub 2012 Dec 4.
PURPOSE: To evaluate intravitreal aflibercept injections (IAI; also called VEGF Trap-Eye) for patients with macular edema secondary to central retinal vein occlusion (CRVO).
DESIGN: Randomized controlled trial.
METHODS: This multicenter study randomized 189 patients (1 eye/patient) with macular edema secondary to CRVO to receive 6 monthly injections of either 2 mg intravitreal aflibercept (IAI 2Q4) (n = 115) or sham (n = 74). From week 24 to week 52, all patients received 2 mg intravitreal aflibercept as needed (IAI 2Q4 + PRN and sham + IAI PRN) according to retreatment criteria. The primary endpoint was the proportion of patients who gained≥15 ETDRS letters from baseline at week 24. Additional endpoints included visual, anatomic, and quality-of-life NEI VFQ-25 outcomes at weeks 24 and 52.
RESULTS: At week 24, 56.1% of IAI 2Q4 patients gained≥15 letters from baseline compared with 12.3% of sham patients (P<.001). At week 52, 55.3% of IAI 2Q4 + PRN patients gained≥15 letters compared with 30.1% of sham + IAI PRN patients (P<.001). At week 52, IAI 2Q4 + PRN patients gained a mean of 16.2 letters of vision vs 3.8 letters for sham + IAI PRN (P<.001). The most common adverse events for both groups were conjunctival hemorrhage, eye pain, reduced visual acuity, and increased intraocular pressure.
CONCLUSIONS: Monthly injections of 2 mg intravitreal aflibercept for patients with macular edema secondary to CRVO resulted in a statistically significant improvement in visual acuity at week 24, which was largely maintained through week 52 with intravitreal aflibercept PRN dosing. Intravitreal aflibercept injection was generally well tolerated.
Retina Consultants of Houston, The Methodist Hospital, Houston, TX, USA.