Clinical utility of intravitreal fluocinolone acetonide (Iluvien^®) implant in the management of patients with chronic diabetic macular edema: a review of the current literature

Abstract

The first-line therapy for patients with center-involving diabetic macular edema (DME) is with intravitreal anti-vascular endothelial growth factor (VEGF) agents, with or without adjunctive macular laser treatment. However, a significant proportion of patients have persistent and recurrent edema despite repeated anti-VEGF injections. The fluocinolone acetonide (FA) 190 μg intravitreal implant has been shown in pivotal clinical trials to be efficacious for the treatment of DME and has been approved in many countries for use in patients who have not responded to first-line therapy. In this report, we have collated the latest data from the increasing number of studies to illustrate the pattern of usage of the Iluvien FA implant for DME during the current anti-VEGF era. We have shown that there is now a wealth of published evidence from real-world studies to support the clinical utility of the FA implant in achieving further resolution of edema and improving visual acuity outcomes in this challenging group of patients.

<p>Early adoption of the fluocinolone acetonide (FAc) intravitreal implant in patients with persistent or recurrent diabetic macular edema (DME)</p>

“…Such evidence has shown improvements in visual acuity following injection of the FAc implant, compared with worsening in fellow eyes,14,15 as well as larger improvements in central foveal thickness,14,15,18 improvements in visual acuity in patients with pseudophakia and bilateral persistent or recurrent DME,12 and improvements in visual acuity and foveal thickness in patients with vitrectomized and nonvitrectomized eyes 17,18. Increases with IOP in real-world cases have not been notable or have been significant but small and managed successfully,8,12–18 although tests and risk factors for IOP such as ocular hypertension and glaucoma should be taken into account when deciding whether to use the FAc implant 8. A retrospective cost–analysis study in the UK found that switching to the FAc implant in patients with refractory DME was cost- and time-saving without any reduction in efficacy 19…”

“…Corticosteroids act on inflammatory cytokines and pathogenic mechanisms in addition to those associated with VEGF 5,8. They inhibit edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation, leading to visual gain and reduction of DME 5.…”

“…In the absence of head-to-head studies of the FAc implant and anti-VEGF drugs for the treatment of DME, case reports and case series from clinical practice offer additional evidence for the implant’s role in the real-life setting 8,12–17. Such evidence has shown improvements in visual acuity following injection of the FAc implant, compared with worsening in fellow eyes,14,15 as well as larger improvements in central foveal thickness,14,15,18 improvements in visual acuity in patients with pseudophakia and bilateral persistent or recurrent DME,12 and improvements in visual acuity and foveal thickness in patients with vitrectomized and nonvitrectomized eyes 17,18.…”

Advanced implantable drug delivery technologies: transforming the clinical landscape of therapeutics for chronic diseases

“…This implant is not the first line of therapy but is only approved for DME eyes that did not respond to laser therapy and anti-VEGF therapy (Elaraoud et al 2016a;Figueira et al 2017;Massin et al 2016). Realworld results indicate the efficacy of ILUVIEN®, demonstrating improved best corrected visual acuity and central foveal thickness (Alfaqawi et al 2017;Amoaku et al 2015;Bailey et al 2017;Bertelmann et al 2013;Bertelmann and Schulze 2015;Cunha-Vaz et al 2014;Elaraoud et al 2016b, c;El-Ghrably et al 2017;Fusi-Rubiano et al 2018;Gonçalves et al 2017;Mourtzoukos 2017;Quhill and Quhill 2016;Saedon et al 2017;Schmit-Eilenberger 2015;Syed 2017;Veritti et al 2017;Yang et al 2015). Another implant, Vetrisert®, was FDA-approved for the treatment of cytomegalovirus retinitis but was later discontinued.…”

Evolution of intravitreal therapy for retinal and macular disorders

“… 50 – 53 In 2014, Iluvien (intravitreal implant releasing fluocinolone acetonide for 36 months), developed by Alimera, received FDA approval for DMO and has been shown to be effective for patients who have persistent or recurrent macular oedema, despite previous multiple and frequent anti-VEGF injections. 54 , 55 Recently, brolucizumab, a new anti-VEGF agent for the treatment of wet AMD (developed by Alcon Laboratories, Inc.), has been found to be comparable to aflibercept, with better anatomical results. 56 Larger studies in this field, especially regarding the efficacy of the newer anti-VEGF drug, brolucizumab, are expected with great interest.…”