Both 0.19-mg (Iluvien®) and 0.18-mg (Yutiq®) FA implants are intravitreally injected through the pars plana with a preloaded applicator with a 25-gauge needle in an office-based setting. Both are designed to release FA over a 3-year period at a rate of 0.2 μg/day, progressively decreasing to 0.1 μg/day.
The three-year results of the prospective, randomized, sham injection-controlled clinical trial analysing the recurrence rate of uveitis in adults with a diagnosis of NIPU treated with intravitreal 0.18-mg Fai compared to the standard of care have been recently published [
23,
24]. The recurrence rate of uveitis was statistically lower in the implant group compared to the sham group at 6 months (27.6% vs. 90.5% respectively), 12 months (37.9% vs. 97.6%) and 36 months (65.5% vs. 97.6%), as well as was the mean number of recurrences per eye (0.7 vs. 2.5 at 12 months and 1.7 vs. 5.3 at 36 months, respectively). A significant higher proportion of eyes in the FAi group had no recurrences compared to the sham group (34.5% vs. 2.4%, respectively), or had only one recurrence in 36 months (33.3% vs. 11.9%, respectively). Median time to first recurrence was significantly longer in the implant group than in the sham group (378 vs. 70.5 days at 12 months and 657.0 vs. 70.5 days at 36 months, respectively). A decrease in BVCA of ≥15 letters from baseline was less common in the FAi group compared to the sham group (14% vs. 31% at 12 months and 1.4% vs. 8.8% at 36 months, respectively), as well as was an increase in BVCA of ≥15 letter from baseline (33.3% vs. 14.7% at 36 months, respectively). Mean central subfield thickness (CST) decreased more in the FAi group than in the sham-injected eyes at day 28 (− 61.3 vs. -7.5 μm, respectively), and a higher proportion of FAi-treated patients had no macular oedema at 12 months compared to patients treated with sham injections (71% vs. 48%, respectively). Although not statistically significant, fewer eyes in the FAi-treated group had persistent macular oedema at 36 months compared to sham-treated eyes (13.0% vs. 27.3%, respectively). A similar percentage of eyes in the FAi- and sham-treated groups had no VH or anterior chamber cells at month 36; however, the control of intraocular inflammation was achieved more rapidly in the FAi-treated eyes. There was a statistically significant difference in the proportion of patients receiving adjunctive systemic corticosteroids or immunosuppressants among the two study groups (19% FAi group vs. 40% sham group at 12 months and 57.5% vs 97.6% at 36 moths, respectively). Regarding the safety, mean change from baseline IOP was slightly greater at 12 months in the FAi group (+ 1.3 mmHg) than in the sham injection (+ 0.2 mmHg) eyes. FAi treated patients had a higher rate of IOP ≥ 25 mmHg compared to the sham group (17% vs. 5%, respectively), or of IOP increase > 5 mmHg over baseline (42% vs. 14%, respectively). At 36 months, a higher proportion of FAi-treated eyes received IOP-lowering medication compared to the sham-treated eyes (42.5% vs. 33.3%, respectively), while surprisingly, the proportion of eyes that underwent IOP-lowering surgery was lower in the FAi-treated group then in the sham group (5.7% vs. 11.9%, respectively). This was explained by the use of rescue therapy with other forms of local steroids predominantly in the sham arm of the study. Cataract surgery was more frequently required in the FAi-treated group compared to the sham-treated group (73.8% vs. 23.8% of eyes, respectively) [
23,
24]. To summarize, the study demonstrated that 0.2 μg/day intravitreal sustained-release of FA is a safe and effective treatment for chronic and recurrent NIPU, being associated with a substantial lower recurrence rate and number of recurrences, and longer recurrence-free time compared to the standard of care. This results in less retinal structural and functional damages, less frequent examinations, higher patient’s adherence to therapy and better quality of life [
25]. Furthermore, the use of a lower dose of FA compared to the initial dose of 0.59-mg allows a reduction in the risk of IOP elevation.
Given the lack of comparative trials between low-dose FA and DEX implants and long-term studies on repeated injections of DEX implants, it is difficult to draw conclusions about which implant is better in terms of efficacy and safety in the treatment of NIU [
5,
24]. It is important to stress that these implants have been licensed with different indications, especially, the FA implant is indicated with the objective of preventing relapses and not to treat active inflammation, different from the DEX implant. The longer anti-inflammatory effect of low-dose FAi compared to DEX implant makes FAi more effective in the prevention of relapses.