In 2011, the DEX implant was approved for the treatment of posterior non-infectious uveitis based on a prospective randomized clinical trial by the HURON Study group [4]. In their study, 47% of the eyes achieved the primary outcome measure of a vitreous haze score of 0 at 8 weeks [4]. The DEX implant, however, has remained off-label for the treatment of macular edema in non-infectious uveitis. Macular edema is one of the leading causes of blindness and accounts for up to one-third of blindness and visual impairment in chronic non-infectious uveitis [9]. Two studies have been conducted regarding the use of multiple DEX implants in macular edema caused by non-infectious uveitis [10, 11]. In both of these studies, there was a statistically significant decrease in CRT on OCT at 1 month and up to 6 months from the first injection, with a median time to re-injection of 6 months [10, 11]. Only one of the studies compared the effect of multiple implants to the first implant, and no significant difference in effect was observed [11].

We demonstrated that the DEX implant, when used in conjunction with systemic corticosteroids, improved BCVA and reduced CRT in patients with CME secondary to non-infectious uveitis in our previous 2017 publication [6]. A literature review was conducted to search for previous studies assessing the use of the DEX implant as a monotherapy and we were unable to find any such studies. Monotherapy would avoid the use of concomitant systemic immune suppression and also avoid side-effects from systemic corticosteroid treatment, while maintaining adequate vision. In our study, the etiology of uveitis in the majority of the patients was attributed to idiopathic uveitis. The etiologies may result in varying responses to the implant and this may be a confounding variable in the results analysis. This study shows that the DEX implant, used as a monotherapy without concomitant or recent prior systemic treatment to effectively treat macular edema in non-infectious uveitis, with these results showing a statistically significant improvement in both BCVA and CRT over the course of 12 months. BCVA improved on average from 0.285 logMAR units to 0.175 logMAR units. From a practical perspective, the difference in logMAR is an improvement in patient vision from 20/40 to 20/32.

CRT decreased from 392 μm to 318 μm during the same time period. Between 1 month post-operatively and 12 months, there was no statistically significant difference in CRT reduction, showing that improvement in CRT occurred within one month and was unchanged thereafter. It was noted at month four that CRT returned close to baseline levels as the implant is expected to last 4–6 months. The rise in CRT at 4 months may reflect the nine eyes (9/39, 23%) who had recurrence of macular edema and then required a second implant.

A Kaplan–Meier survival analysis was conducted to study the survival of the treatment during the 12-month analysis period. A 77% success between 4 to 7 months and 46% beyond 10 months was demonstrated, providing strong evidence for the DEX implant as treatment for macular edema in uveitis. There were 5 eyes that had a successful improvement in BCVA and only one eye that had a successful improvement in CRT but not in BCVA.

Furthermore, only one of the eyes developed a cataract and none of the patients required systemic corticosteroid treatment. IOP may be elevated in patients with ocular implants and this is often treated by topical therapy [6], however, our study demonstrated that despite initial increases in IOP at one month post-implant, the pressure dropped significantly 4 months post-implant. These pressure values even returned to normal after 10 months and were sustained thereafter (Table 3). Patients did not receive any systemic corticosteroid or immunosuppressive therapy; nine of the 39 (23%) eyes required a second implant over a study period of 12 months. The data suggests that either patients did not have aggressive uveitis, or the dexamethasone implant was effective. This provides preliminary evidence to support the hypothesis that DEX implants can be used as monotherapy for macular edema in uveitis, however, keeping in mind that the patient’s underlying inflammatory disease would need to be addressed with other systemic treatments.

The current standard of care for posterior non-infectious uveitis involves systemic corticosteroids or the use of any of the following local treatments: intravitreal and periocular steroid injections, topical steroids and intravitreal anti-VEGF agents [12]. In situations when patients have adverse reactions or treatment-resistant uveitis, managing this condition presents as a significant challenge. This retrospective study displayed a significant reduction in CRT and improvement in BCVA, similar to previous studies which have been published regarding the use of the 0.7 mg dexamethasone implant for this condition [12,13,14].

The study's limitations include data collection from a single centre, referral bias to a tertiary care centre, and small cohort size. A confounding variable is the prior use of topical corticosteroids, which was not controlled or standardized among patients. The idiopathic etiology of uveitis was disproportionately high with most patients having idiopathic uveitis. The group of patients enrolled in this study had inflammatory posterior segment disease; one had retinal vasculitis and none had occlusive vasculopathy. Treatment outcomes could be impacted, and future studies may include controlling for the etiology of the uveitis. Long term studies of the effects of single versus multiple implants and a direct comparison to systemic corticosteroids would reveal if the DEX implant is equivalent to systemic corticosteroid in patients with posterior segment non-infectious uveitis. Lastly, data points at each time point decreased progressively; the results presented in this study, however, can be interpreted to assess trends, showing a significant decrease in CRT and increase in BCVA, thereby demonstrating that the implant can lead to both anatomical and visual improvements for patients.

This study has provided initial evidence with statistical significance that the DEX implant can successfully be used as monotherapy to treat uveitic macular edema.