We aimed to examine the benefits and harms of inserting steroids into the eye for treating macular edema secondary to central retinal vein occlusion (CRVO-ME).
Central retinal vein occlusion (CRVO) is a common abnormality of the blood vessels in the retina (back portion of the eye which receives visual images). CRVO usually presents as a painless loss of vision in one eye of people over the age of 40 who often have other health issues such as high blood pressure, diabetes, glaucoma, and blood diseases. Macular edema (ME) is the swelling of the macula (central area of the retina responsible for detailed vision, such as reading and seeing colors). ME is a complication of CRVO and is the primary reason for loss of vision in this condition. Steroids inserted into the eye, either by injection or an implanted device, have been used to treat ME caused by eye disorders other than CRVO. While steroids can lead to improvements in vision, the effect usually lasts only a few months and there is a risk of developing glaucoma, cataracts, and other complications.
The review authors searched the medical literature up to 13 November 2014 and included two randomized controlled trials (GENEVA and SCORE) that had evaluated steroids in 708 participants with CRVO-ME. Both trials included participants with similar baseline characteristics with respect to age, gender, and co-morbidities. GENEVA was conducted in 24 countries across the world and SCORE was conducted in the US. Both trials compared two different doses of steroid, but the investigators of the two trials used different steroidal agents and different methods of delivery (implant versus injection). Both trials received full or partial sponsorship from the manufacturer of the drugs.
Neither trial provided sufficient evidence to determine whether steroids had improved visual acuity after six months of treatment. Due to the limited evidence, we are unable to determine reliably whether steroid implants improved vision in eyes with CRVO-ME. Although the SCORE trial showed that more eyes in the steroid injection groups had improvement in vision compared with eyes in the observation group, participants treated with steroids and those not treated with steroids both lost vision on average at eight months. The GENEVA investigators reported no difference in vision outcomes between participants treated with steroids and those not treated with steroids after six months of treatment; however the GENEVA study was not limited to participants with only CRVO-ME and included participants with other retinal disease. Both trials showed that patients treated with steroids were at increased risk for high eye pressure - requiring additional medications to lower the eye pressure - and developing cataracts.
Quality of the evidence
The overall quality of the evidence was low due to clinical differences between studies, incomplete information available to assess outcomes, and lack of masking which may lead to biased study results.
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.
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.