Fluocinolone Acetonide Implant Improves Outcomes in Eyes with Chronic DME

José María Ruiz-Moreno, PhD

Credit: LinkedIn

Fluocinolone acetonide intravitreal implant (ILUVIEN) was associated with improvement in visual and anatomic outcomes in eyes with diabetic macular edema (DME) insufficiently responsive to prior therapies, according to new research.¹

For eyes with a baseline best-corrected visual acuity (BCVA) ≤70 ETDRS letters, a statistically significant improvement was observed at month 24 after implant; those with baseline BCVA ≥50 letters experienced greater anatomic improvement after treatment.

“These findings clearly suggest a positive benefit to the risk profile in patients treated earlier with the fluocinolone acetonide intravitreal implant,” wrote the investigative team, led by José María Ruiz-Moreno, department of ophthalmology, Castilla La Mancha University in Spain.

Vascular endothelial growth factor (VEGF) inhibitors play a role as the first-line treatment for retinal diseases, including DME. For eyes that do not show adequate response to these therapies or those with contraindications to anti-VEGF agents, intravitreal corticosteroid implants could be a chosen treatment. The fluocinolone acetonide sustained-release intravitreal implant is non-erodible and can deliver a sustained daily 0.2 µg dose of fluocinolone acetonide over a 3-year period.

Multiple studies have indicated a favorable, long-term benefit-risk profile of the implant in eyes with DME who did not achieve an adequate response to other therapies. Data from the ILUVIEN Registry Safety study showed a significant improvement in BCVA, with greater improvement in eyes with a shorter duration of DME, and no unexpected adverse events. The PALADIN study reported significant improvements in both visual and anatomic outcomes, with favorable safety.²

In this phase 4, observational, prospective, non-randomized, multicenter REACT trial, Ruiz-Moreno and colleagues assessed the effectiveness and safety of the fluocinolone-acetonide implant in patients with chronic DME, who did not sufficiently respond to other therapies. The study occurred between September 2017 and February 2022.¹

Patients underwent one screening visit (–14 to 0 days before implant), one baseline visit (administration of implant), and 10 follow-up visits from week 1 to month 24. The primary endpoint for the analysis was the mean change in BCVA from baseline values. Secondary endpoints consisted of the mean changes in central subfield thickness (CST) and macular volume assessed on spectral-domain optical coherence tomography (SD-OCT), the incidence of adverse events, and the results of the VFQ-25 questionnaire.

The analysis included a total of 31 eyes from 31 patients, with a mean age of 68.0 years; only 10 patients (32.3%) were women. Participants had received an average of 5.3 prior DME treatment injections before the start of the study.

From the overall sample, investigators found BCVA improved from 56.1 ± 12.3 ETDRS letters at baseline to 62.4 ± 17.0 ETDRS letters at 24 months, but the improvement was not statistically significant (P = .0510).

In those eyes with baseline BCVA ≤70 ETDRS letters, however, the analysis showed a significant improvement in BCVA, from 53.2 ± 10.2 letters at baseline to 61.5 ± 17.9 letters at month 24 (P = .0165). Compared to baseline measures, the mean BCVA improvement was statistically significant at week 1, month 1, month 3, and month 24 in this population.

Regarding anatomic outcomes, the overall study population experienced a significant reduction in CST from 474.0 ± 135.1 µm at baseline to 333.4 ± 135.6 at month 24 (P <.0001). The analysis also showed a significant reduction in macular volume from 10.7 ± 2.7 mm³ at baseline to 9.6 ± 2.9 mm³ at month 24 (P = .0027).

Among the total study population, 19 eyes (61.3%) required additional treatment for DME, including intravitreal anti-VEGF (n = 15) and an intravitreal corticoid (n = 11). Safety data showed 33 adverse events (AEs) were reported in 17 patients, of which 8 (24.2%) were “possible-definitive” related to the study medication.

Investigators noted a statistically significant increase was observed in mean IOP from 14.6 ± 3.0 mmHg at baseline to 16.8 ± 2.7 mmHg (mean difference, 2.2 ± 2.9 mmHg; 95% CI, 0.6 to 3.9 mmHg; P = .0086) at month 24. Over the study period, 9 (29.0%) eyes required ocular hypotensive medication to control their intraocular pressure (IOP) and 5 (16.1%) eyes required cataract surgery.

The study sample size was originally planned to include 40 eyes, but lockdown measures taken during the COVID-19 pandemic disrupted the delivery of health care and may factor into the lack of statistical significance.

“This could have motivated the lack of statistical significance in the BCVA improvement achieved at 24 months,” investigators wrote.

References

1. Ruiz-Moreno, J.M., Adán, A., Lafuente, M. et al. Effectiveness and safety of fluocinolone acetonide intravitreal implant in diabetic macular edema patients considered insufficiently responsive to available therapies (REACT): a prospective, non-randomized, and multicenter study. Int Ophthalmol (2023). https://doi.org/10.1007/s10792-023-02864-2
2. Iapoce C. PALADIN: Fluocinolone Acetonide Implant Associated with Stable Intraocular Pressure. HCP Live. September 7, 2023. Accessed September 19, 2023. https://www.hcplive.com/view/paladin-fluocinolone-acetonide-implant-stable-intraocular-pressure.