Precision medicine in diabetic macular edema: Expert consensus on the efficacy and safety of the 0.19-mg fluocinolone acetonide implant

(Image Credit: ©ipuwadol - Adobe.Stock.com)

Consensus statements offer valuable guidance in the constantly evolving landscape of patient care, providing insights into current clinical practice patterns and disease pathophysiology. Recently, Kolomeyer et al published results of an expert consensus that sought to gain understanding about the role of inflammation in diabetic macular edema (DME) pathophysiology and the efficacy and safety of the 0.19-mg fluocinolone acetonide (FAc) intravitreal implant Iluvien (Alimera Sciences).¹

Results from expert surveys provide snapshots of our understanding of DME and shed light on where the 0.19-mg FAc implant stands in the current standard of care. They also highlight the general beliefs of retinal physicians regarding the benefits and considerations of using this therapy. The survey included 56 retinal physicians across the US, with 12 consensus statements. The physicians indicated their level of agreement or disagreement to each statement, except for the 2 that were multiple-choice, multiple-answer questions.¹

Out of the 10 consensus statements using the modified Likert scale, 7 reached the consensus threshold of greater than 80% agreement. These statements covered topics such as the role of inflammation in DME pathophysiology, injection burden, retinal thickness variability, and the efficacy and safety of Iluvien.

Physicians broadly agreed that poor glycemic control leads to the production of inflammatory cytokines that cause retinal inflammation and drive diabetic retinopathy (DR) and DME pathogenesis, leading to retinal neurodegeneration. They also agreed that steroids have broad, nonspecific anti-inflammatory properties that can downregulate pathological cytokine levels, including VEGF.¹

Regarding the current standard of care, physicians concurred that the high injection burden required by short-acting therapies leads to patient fatigue and nonadherence. As a result, nonadherence to therapy limits treatment efficacy and can result in increased amplitude and frequency of retinal thickness fluctuations, which may lead to irreversible vision loss.¹

Physicians agreed that the 0.19-mg FAc implant can minimize retinal thickness fluctuations while reducing treatment burden compared with the current standard of care. As for IOP elevations, a common adverse effect of corticosteroid use in the eye, physicians agreed that these elevations were manageable in most cases through topical IOP-lowering medications.¹

The 2 multiple-choice, multiple-answer statements were aimed at understanding when steroid use as baseline therapy is justified and which steroid delivery routes satisfy the corticosteroid challenge specified in the label of the 0.19-mg FAc implant. Among the surveyed physicians, 55% believed that corticosteroids as baseline therapy could be beneficial for any patient with DME, but 7% disagreed, stating it was not appropriate at all. However, a majority of 73% agreed that pseudophakic patients were the best fit for this treatment approach. As for the steroid challenge, 100% of the respondents considered intravitreal steroid delivery as the most appropriate method, with 73% indicating subtenon/periocular administration and 57% favoring topical delivery.¹

Though 7 out of 10 statements reached consensus, 3 statements did not achieve the predefined greater than 80% agreement. These revolved around the use of the 0.19-mg FAc implant and the steroid challenge required by its label. Physicians did not reach consensus that the implant can delay DR progression or reduce the DR severity score. They also did not find consensus that the implant represents a viable treatment option to establish baseline control of chronic inflammation in both DR and DME. Additionally, consensus was not found that the corticosteroid challenge reduces the risk of IOP-related events with the 0.19-mg FAc implant.¹

Supportive data comes from one trial, PALADIN (NCT02424019), a phase 4 open-label observational study that investigated the real-world safety of the 0.19-mg FAc implant for DME.² Results of the study provided evidence that the corticosteroid challenge mitigates the risk of potential IOP events when compared with rates from the registration trial, FAME (NCT00344968).³

Looking beyond steroid treatment as a second-line therapy, the NEW DAY (NCT04469595) trial, recently fully enrolled, will assess the benefit of early inflammatory control in DME. It aims to evaluate the 0.19-mg FAc implant as first-line therapy and compare the number of supplemental aflibercept injections required with each the 0.19-mg FAc implant arm and the aflibercept-only arm. The study will shed further light on the role of long-acting steroid therapy in eyes with DME by assessing the ability of the 0.19-mg FAc implant to delay DR progression and reduce the DR severity score, among other end points.

References:

1. Kolomeyer AM, Eichenbaum DA, Kiernan DF, Suñer IJ, Hariprasad SM. The 0.19-mg fluocinolone acetonide implant for the treatment of diabetic macular edema: an expert consensus. Ophthalmic Surg Lasers Imaging Retina. 2023;54(3):166-173. doi:10.3928/23258160-20230215-01

2. Singer MA, Sheth V, Mansour SE, Coughlin B, Gonzalez VH. Three-year safety and efficacy of the 0.19-mg fluocinolone acetonide intravitreal implant for diabetic macular edema: the PALADIN STUDY. Ophthalmology. 2022;129(6):605-613. doi:10.1016/j.ophtha.2022.01.015

3. Campochiaro PA, Brown DM, Pearson A,
   et al; FAME Study Group. Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema. Ophthalmology. 2012;119(10):2125-2132. doi:10.1016/j.ophtha.2012.04.030

Mark R. Barakat, MD

Barakat is a retinal surgeon at Retinal Consultants of Arizona, director of the Retinal Research Institute, vice chair of clinical research at American Vision Partners, medical director of Spectra Eye Surgery Center, and a clinical assistant professor of ophthalmology at University of Arizona College of Medicine in Phoenix. Barakat is a consultant for Alimera Sciences.