The DEX implant is practical for treating uveitis and uveitic macular edema, and its ease of delivery and favorable risk profile is preferable compared to systemic corticosteroids. This literature review combines data from pediatric and adult cases to assess the effect of the DEX implant. Most of the data comes from retrospective reviews and are reliable sources when analyzed against the OCEMLEC . The HURON trial (Lowder et al.) is the only RCT done with the DEX implant and its data mirrors the retrospective reviews. According to the OCEMLEC our study would rank at the “3a” level as we mostly combined data from case control studies .
Central retinal thickness
The DEX implant almost unanimously reduced retinal thickness apart from the case reported by Arcinue et al.; the DEX implant was shown to have reduced macular thickness by an average of 42.7% (range 9.9 to 85.4%) from baseline across all studies. As cystoid macular edema is common sequelae of uveitis, the DEX implant is an effective option for treating posterior segment uveitis with macular edema.
Overall, the studies have shown that the DEX implant is effective at improving vision. Except for the study by Lei and Lam, there was a significant improvement in logMAR visual acuity, ranging from 21.1–85.0% improvement (Fig. 2). The study which showed deterioration in visual acuity only showed a mild decrease in visual acuity of 0.013 logMAR (2.1%). The HURON trial by Lowder et al. showed a 10.8 letter improvement in BCVA in the 0.7 mg the DEX implant group. The average improvement was 0.38 log scores or a 43.1% improvement from baseline.
After treatment, 40 eyes (13.7%) had an anterior chamber cell score of ≤ 0.5+ and/or vitreous haze ≤ 1+. In all the trials, except the review by Tomkins-Netzer et al., the DEX implant successfully reduced inflammation. Since the number of eyes achieving a score of 0.5+ and 0+ was almost always grouped together, it was not possible to demonstrate improvement in eyes from an anterior cell score of 0.5+ to 0+. The magnitude of effect of the DEX implant on reducing inflammation is undermined by this ceiling effect. The data shows the DEX implant to be effective in reducing the concomitant inflammation in noninfectious uveitis.
Cataracts and PSCO were the most common adverse events occurring in 47 cases (11.0%). This is an expected finding, as local ocular steroid treatment results in cataract formation; however, it is not clear whether cataract was due to steroid treatment or associated with uveitis. Nonetheless, patients should be monitored for lens opacities. Subconjunctival hemorrhage was the second most common side effect occurring in 24 cases (5.4%).
A concern with intraocular implants and steroid usage is secondary glaucoma; our review confirmed this to be a tangible risk. A total of 102 eyes (23.1%) had elevated IOP; therefore, it is imperative to monitor the IOP of patients receiving the DEX implant. Endophthalmitis, retinal detachment, and subretinal fluid were very rare adverse events (0.5%). Implant migration to the anterior chamber occurred in seven cases (1.6%); most of these patients were aphakic (5/7 or 71.4%). The studies by Adan et al. and Ragam et al. do not specify whether their patients were aphakic or not. A study by Kang et al. found implant migration into the anterior chamber in four of their patients (0.4%) . It is important to inform patients of this risk as corneal edema and severe visual disturbances can occur, or the implant could be deferred until after a secondary intraocular lens implant is placed in aphakic patients. Vitreous hemorrhage and hypotony were rare complications having a prevalence of 1.6% and 1.8%, respectively. Eye pain and ocular discomfort were relatively rare complications occurring at 8 (1.8%) and 10 cases (2.3%). This suggests that the DEX implant does not significantly impair a patient’s quality of life.
Endophthalmitis and retinal detachments
The higher than expected prevalence of endophthalmitis and retinal detachments may be due to injection technique or the DEX implant. Because placing an intravitreal implant uses a similar techniques to injecting anti-VEGF medications, to determine whether complications are due to the intravitreal injection or due to the DEX implant, we looked at the prevalence rates of these complications in patients receiving anti-VEGF medications. The rates of endophthalmitis and retinal detachment were lower in anti-VEGF patients; in a meta-analysis by van der Reiss et al., endophthalmitis had an incidence rate of 0.09–0.11% and retinal detachment had an incidence of 0.01–0.08% . The higher rates of endophthalmitis in the DEX implant patients could be explained by the fact that the 22-gauge (inner diameter 0.413 mm) DEX implantation device has a larger bore compared with the 30-gauge (inner diameter 0.159 mm) intraocular needles. This creates a larger needle tract in the globe which may have a higher probability of developing endophthalmitis.
Conducting a pars plana vitrectomy and DEX implantation simultaneously
Following vitrectomy surgery, medications have a shorter half-life in the vitreous and patients may receive more frequent intravitreal injections. One of the studies analyzed the effectiveness of the DEX implant in vitrectomized and non-vitrectomized eyes. Vitrectomized eyes had a 49.1% reduction in CRT, whereas non-vitrectomized eyes had a 32.0% reduction in CRT . Vitrectomized eyes had a greater improvement in visual acuity improving it by 71.6% compared to non-vitrectomized eyes at 62.1% . Vitreous haze improvement was the same between both groups . It is clear that vitrectomized eyes fair better outcomes compared with non-vitrectomized eyes; however, the improvement is only slight and non-vitrectomized eyes still have significantly favorable outcomes.
The use of different endpoints
As Table 2 shows, there is variation in the duration of each of the studies. The DEX implant varies in effectiveness for different severities of uveitis. In the typical onset and course of uveitis, a single DEX implant begins working around 6–8 weeks and can last for about 6 months. In more severe uveitis, a single dose could have a lifetime of 4 months. Variable end points would explain the findings from Lowder et al. and Ragam et al. which had low IOP adverse events (7.3% and 0%, respectively) at their 6-month endpoints, while Latronico et al. found at the end of 5 weeks, 50% of their eyes had elevated IOP.
Monotherapy or adjunct therapy
The DEX implant has been used as a monotherapy in clinical practice; however, there is currently no literature analyzing the benefits of the DEX implant in such a manner. In this review, 61.5% of all the study participants had previous immunomodulatory therapy (IMT) and 64.8% of all participants were treated with IMT and the DEX implant. Whether the DEX implant is effective as a monotherapy versus adjunctive therapy remains unknown and further research is needed.
In our review, 8/20 studies (40%) did not report data on changes in inflammatory score despite the DEX implant’s indication for treating posterior uveitis. To date, there has been only one RCT (Lowder et al.) studying the DEX implant. More RCTs need to be conducted to investigate the DEX implant as an effective treatment. Although this systematic review was able to study the prevalence of ocular pain and discomfort, many other factors on quality of living that are still unknown. A useful tool to measure the quality of life with ocular mediations is the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25). Further research measuring the NEI VFQ-25 score changes would shed more light onto the effects of the DEX implant and patient quality of life.