Spanning 36 months, a sustained-delivery intravitreal corticosteroid (0.19 mg fluocinolone acetonide) implant improved best-corrected visual acuity (BCVA), reduced central subfield thickness and treatment burden, and maintained a favorable safety profile in patients with diabetic macular edema (DME). The findings from the PALADIN study were published in Ophthalmology.

PALADIN (ClinicalTrials.gov Identifier: NCT02424019) was a 3-year, phase 4, non-randomized, open-label observation study conducted at 41 sites in the United States evaluating safety and efficacy of the 0.19 mg fluocinolone acetonide implant in patients treated according to the US Food and Drug Administration (FDA) label — patients with DME who were previously treated with a course of ocular corticosteroids and did not have a clinically significant rise in intraocular pressure (IOP). 

The investigators evaluated patients at baseline and observed safety-, visual-, anatomical-, and treatment burden-related outcomes for up to 36 months. The primary safety outcomes included changes in IOP and interventions to manage elevation of IOP, and the secondary outcomes included changes in BCVA, central subfield thickness, and adjunctive DME treatment frequency.


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“As a strategy to reduce treatment burden and improve patient adherence in DME treatment, utilization of a sustained-delivery intravitreal corticosteroid implant may offer longer-lasting treatment effects when compared to those of short-term, intermittent injections (ie, anti-VEGF therapy),” investigators report.

The 0.19 mg fluocinolone acetonide implant releases submicrogram doses of the corticosteroid into the vitreous for up to 36 months, and because fluocinolone acetonide has low water solubility, it preferentially enters the ocular tissue following implantation. 

A total of 202 eyes of 159 patients (mean age, 67.00±9.13 years; 51.5% women and 48.5% men) were included in the study. Of those, 94 eyes completed 36 months of study. They had a mean baseline IOP of 15.05±3.87 mm Hg, mean baseline BCVA of 62.3±15.78 letters, and mean baseline central subfield thickness of 386.10±134.50 µm. Among patients who completed all 36 months, the mean follow-up duration post-implantation was 35.52 months.

At 36 months post-implantation, patients’ study eyes had a mean BCVA increase of 3.61 letters (P <.0222) and mean central subfield thickness decrease of 60.69 µm (P <.0001) relative to baseline. They also found that the implant led to a treatment burden reduction of 67.6%; the median treatment frequency decreased from 3.4 treatments/year in the 36 months prior to implantation to 1 treatment/year in the 36 months following implantation, with 25.53% of eyes remaining treatment free. 

The mean IOP remained stable in the overall population throughout the study, according to the investigators. They observed IOP increases to more than30 mm Hg in 10.89% of all eyes and in 12.77% of 36-month completer eyes. IOP-related procedures included incisional IOP-lowering surgery in 2.97% of all eyes and 5.32% of 36-month completer eyes (with 3 cases due to neovascular glaucoma), and trabeculoplasty in 1.98% of all eyes and 1.6% of 36-month completer eyes. 

The researchers also demonstrate that an IOP response below 25 mmHg after the steroid challenge predicted that 96.92% of eyes would have a similar outcome to 0.19 mg fluocinolone acetonide implant at the last visit.

“Along with previous studies of the 0.19-mg [fluocinolone acetonide] implant, PALADIN demonstrates that continuous microdosing with [fluocinolone acetonide] is associated with improved visual outcomes, reduced macular edema, and a low incidence of IOP-related safety concerns,” concluded the authors. “Ultimately, the benefit-risk profile of the 0.19 mg [fluocinolone acetonide] implant remains positive for long-term use in real-world populations with DME.”

Disclosure: This research was supported by Alimera Sciences. Multiple authors declared affiliations with the biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

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. Ophthalmol. Published online January 18, 2022. doi:10.1016/j.ophtha.2022.01.015