In this meta-analysis, seven studies were selected to evaluate the safety and efficacies of DEX implants in treating RVO. DEX could improve visual function and changes in fundus structure during treatment. No difference in the treatment effects on BCVA or CRT 3 months before and after medication and no statistical heterogeneity were found. However, a significant improvement in BCVA was observed 6 months before injecting DEX, with statistical significance. At the same time, the analysis demonstrated that DEX implant could obviously improve BCVA and decrease the CRT after 6 months. However, in the first 3 months, no significant improvement and reduction in BCVA and CRT were observed. This might be related to the slow release of DEX. At first, the concentration of drugs in the vitreous cavity was relatively low. With the extension of time, the drug was released gradually, and the drug concentration reached the peak. At this moment, the medicinal effect was the best. The drug concentration then stabilized as the metabolism in the body gradually decreased [3].
At present, an intravitreal injection of anti-VEGF is considered as the preferred treatment for RVO. The pathogenesis of RVO is still unclear. Some scientists believe that retinal vein blood flow does not cause vascular obstruction, blood stasis in blood vessels, and increase in capillary pressure, resulting in retinal bleeding, exudation, reduction in capillary perfusion, and retinal ischemia caused by the release of a large number of vascular endothelial factors. Hence, it is presumed that macular edema secondary to RVO can be decreased by resisting the release of vascular endothelial factors. Anti-VEGF becomes the main treatment in the short term. However, it has some limitations: monthly injections are required, causing inconvenience; repeated injections lead to some difficulties, for example, wastage of time in treatment, increased risk of infection, intraocular inflammation, and so on[13]; and the treatment is also expensive for most patients. Therefore, another study found that RVO was also related to inflammatory cytokines causing inflammatory diseases, including chemokines, prostaglandins, matrix metalloproteinase, interleukins, selectins, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), angiotensin II, and inflammatory cells (macrophages and neutrophils) [14]. It is believed that RVO can be effectively relieved by controlling the release of inflammatory factors. An intravitreal injection of DEX is an effective way because the drug can be released slowly and continuously in the vitreous cavity for at most 6 months [14]. Glucocorticoid can effectively control inflammation and edema. DEX is useful in treating RVO, decreasing the time of injection and the chance of infection. Thus, DEX implant may be a better way for treating RVO compared with other treatments.
According to some studies, the outcomes, such as BCVA and center retinal thickness, are often considered as important measures of treatment efficacy. The outcome measures in the present study were the same as in other studies.
At present, an intravitreal injection of DEX preparation is increasingly accepted by the majority of patients. The implantation of sustained-release devices in the vitreous cavity is a novel treatment method introduced in clinical practice. Several basic experimental studies have proved that DEX has a good alleviating effect on macular edema secondary to RVO. At present, a number of studies have shown that this disease has an inflammatory response with inflammatory factors. DEX is a corticosteroid hormone that can effectively inhibit inflammatory factors and maintain the pharmaceutical concentration in the vitreous cavity with a long half-life, which solves the inconvenience of patients with repeated injections in the past. At the same time, the drug implant is rod-shaped, about 6 mm long and less than 0.5 mm in diameter, and can be completely degraded without removal. The injection instrument uses 22G precision needles and innovative drug thrusters, which makes the injection easier, effectively reduces the difficulty of surgery, and facilitates surgeons. Therefore, DEX is the most popular ophthalmic treatment at present and is gradually accepted by patients and ophthalmologists.
The cost and convenience also need to be considered when applying therapies. DEX can maintain its effective dose in the vitreous cavity for about 6 months [15], which decreases the time of injection compared with anti-VEGF and reduces the risk of infection. One study analyzed the cost of these therapies. Multiple injections cost a lot of money, and many patients finally chose to give up because they could not afford the high cost. The average number of DEX injections was reduced. Although the cost of a single injection was higher, the long-term cumulative cost was significantly lower than that of anti-VEGF [16].
However, an intravitreal injection of DEX inevitably leads to some common complications. In this meta-analysis, the data demonstrated that SAEs, such as intraocular hypertension and postoperative cataract, could easily happen in the DEX implant, showing statistically significant differences between before and after medication [17]. Some studies reported that previous pars plana vitrectomy, an open/defective lens capsule, and/or iris defects may increase the risk of DEX implant migration into the anterior chamber [15]. Therefore, for patients with a history of vitrectomy, anterior chamber surgery, and lens capsule damage, extreme care is needed when injecting DEX into the vitreous cavity.
Due to the limited number of included studies and other limitations, subgroup analysis on the heterogeneity of studies to find the source of heterogeneity could not be conducted. It was presumed that the heterogeneity of 3-month CRT mainly derived from the small sample size, age of participants, and a higher proportion of females. Further, the CRT was disturbed by many factors, such as individual difference, measurement error, individual sensitivity to medication, and actual dosage of medication administered. The heterogeneity of mean change in the CRT after 12 months was caused by the studies of Chun- Ju Lin et al [8] and Mariacristina et al [9]. In these two studies, some patients were injected more than one time. It increased the doses of DEX, affecting the result of CRT. Many factors, such as age, baseline data, race, dosage, and way of injecting, might affect the heterogeneity. However, some factors could not be removed. Similar to the results of relevant studies, the present study showed a significant decrease in the CRT in patients after DEX injection in the vitreous body for 6 months.
This meta-analysis had some limitations: (1) it included only six studies, and hence the total sample was relatively small. (2) Some studies proceeded for only 3 months, and hence the incidence of postoperative adverse reactions could not be accurately assessed. (3) At the same time, due to the different age range of the participants, it was not possible to accurately assess the preoperative vision and fundus condition of the patients. At the same time, different drug sensitivity of the patients led to greater heterogeneity. (4) The follow-up was performed for only 6 months and hence the efficacy of DEX at a later stage could not be evaluated accurately.