Dina Gewaily, Karthikeyan Muthuswamy, Paul B Greenberg

Central retinal vein occlusion (CRVO) is a common retinal vascular abnormality associated with conditions such as hypertension, diabetes, glaucoma, and a wide variety of hematologic disorders. Macular edema (ME) represents an important vision-threatening complication of CRVO. Intravitreal steroids (IVS), such as triamcinolone acetonide, have been utilized to treat macular edema stemming from a variety of etiologies and may be a treatment option for CRVO-ME. To explore the effectiveness and safety of intravitreal steroids in the treatment of CRVO-ME. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014 Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2014), EMBASE (January 1980 to November 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 November 2014. For all included primary studies, we used The Science Citation Index (3 December 2014) and manually reviewed reference lists to identify other possible relevant trials. We included randomized controlled trials (RCTs) that compared intravitreal steroids, of any dosage and duration of treatment of at least six months, with observation for the treatment of CRVO-ME. Two review authors independently screened titles and abstracts identified from the electronic searches and assessed full-text articles from potentially eligible trials. Two review authors independently assessed trial characteristics, risk of bias, and extracted data from included trials. We contacted investigators of included trials for desired data not provided in the trial reports. We included two RCTs that enrolled a total of 708 participants with CRVO-ME. SCORE compared triamcinolone acetonide intravitreal injections (n = 165) with observation (n = 72); GENEVA compared dexamethasone intravitreal implants (n = 290) with sham injections (n = 147). We observed characteristics indicative of high risk of bias due to incomplete outcome data in SCORE and selective outcome reporting in GENEVA. Loss to follow-up was high with 10% in the steroid groups and almost twice as much (17%) in the observation group. GENEVA enrolled participants with both branch and central retinal vein occlusion, but did not present subgroup data for the CRVO-ME population. A qualitative assessment of the results from GENEVA indicated that the dexamethasone implant was not associated with improvement in visual acuity after six months among participants with CRVO-ME. Although the SCORE investigators reported that participants treated with 1 mg (n = 82) or 4 mg (n = 83) triamcinolone intravitreal injections were five times more likely to have gained 15 letters or more in visual acuity compared with participants in the observation group (1 mg; risk ratio (RR): 5.27; 95% confidence interval (CI) 1.62 to 17.15; 4 mg RR 4.92; 95% CI 1.50 to 16.10) by the eighth-month follow-up examination, the average visual acuity decreased in all three groups. However, eyes treated with triamcinolone lost fewer letters than participants in the observation group at 8 months (1 mg mean difference (MD): 8.70 letters, 95% CI 1.86 to 15.54; 4 mg MD: 9.80 letters, 95% CI 3.32 to 16.28). A higher incidence of adverse events was noted with IVS therapy when compared with observation alone. As many as 20% to 35% of participants experienced an adverse event in the IVS groups compared with 8% of participants in the observation group of the SCORE study. The GENEVA investigators reported 63% in the treatment arm versus 43% in the observation arm experienced an adverse event. The most commonly encountered adverse events were elevated intraocular pressure, progression of cataracts, and retinal neovascularization. We graded the quality of evidence as low due to study limitations, imprecision of treatment estimates, and selective outcome reporting. The two RCTs reviewed herein provide insufficient evidence to determine the benefits of IVS for individuals with CRVO-ME. The improvement in visual acuity noted in the SCORE trial should be interpreted with caution as outcome data were missing for a large proportion of the observation group. Adverse events were observed more often with IVS treatment compared with observation/no treatment.