PALADIN: Fluocinolone Acetonide Implant Associated with Stable Intraocular Pressure

Daniel B. Roth, MD

Credit: NJRetina

New research suggests 0.19-mg fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN) was associated with relatively stable intraocular pressure (IOP) in patients with diabetic macular edema (DME) over a 36-month period.¹

A secondary analysis of the phase 4 PALADIN study showed those with IOP elevations >30 mmHg or those who required IOP-lowering medication or procedure generally experienced stable best-corrected visual acuity post-FAc implant.

“These data provide a valuable contribution to the understanding of the use of the 0.19-mg FAc implant, supporting the idea that long-term low-dose steroid delivery can provide meaningful stabilization of DME disease status,” wrote the investigative team, led by Daniel B. Roth, MD, a clinical associate professor in the department of ophthalmology at Rutgers University Robert Wood Johnson Medical School.

Intravitreal anti-vascular endothelial growth factor (VEGF) agents are the current standard of care in treating DME. With the need for frequent injections, however, issues arise with adherence and may lead to worse outcomes, particularly in real-world clinical practice. Corticosteroids are a potential therapeutic strategy to reduce treatment burden but are still used as a second-line therapy due to observed increases in IOP and cataract formation.

The non-randomized, open-label, observational PALADIN study included 202 eyes from 159 patients with DME who received the 0.19-mg FAc implant after a successful prior steroid challenge, per the US label indication.

Initial results from PALADIN suggest anatomical and functional benefits of FAc implants due to reduced macular thickness, improved best-corrected visual acuity (BCVA), and a reduced number of yearly treatments. However, many of these DME eyes had IOP elevations over 30 mmHg and required IOP-lowering medications or IOP-lowering surgeries.²

In this analysis, the predictive value described the probability of an IOP response after FAc implantation remaining at ≤25 mmHg if the prior corticosteroid IOP response was also ≤25 mmHg. IOP levels of each eye before and after FAc implantation were grouped into 2 categories: ≤25 mmHg and >25 mmHg.¹

Among eyes that had IOP response ≤25 mmHg after a previous steroid challenge, the analysis showed 77.95% remained stable over 36 months post-FAc. The mean IOP was found to increase post-FAc, with the highest difference of 2.12 mmHg (P <.05) at 9 months.

However, investigators noted overall IOP values remained relatively stable without significant differences at 36 months post-FAc compared with baseline.

At 36 months post-FAc, eyes showed a 32.5% probability of an IOP elevation to >25 mmHg and a 15.6% probability of an IOP elevation to >30 mmHg, according to Kaplan-Meier analysis. However, only 15 of 202 eyes (7.4%) had an IOP >30 mmHg during a study visit and most (60%) exceeded the threshold only a single time.

The probability of needing IOP-lowering medication at any point by month 36 was reported as 38.3%. In most eyes (78%), IOP remained at ≤25 mmHg at any point over the 36-month period, while approximately 97% of eyes had an IOP value ≤25 mmHg at the last visit if the prior steroid challenge reported similar values.

These data suggest IOP increases related to the 0.19-mg FAc implant can be predictable and manageable in eyes with DME that have received an appropriate steroid challenge, ultimately leading to improved visual outcomes.

“These data point to future research into the effect of the 0.19-mg FAc implant on retinal structure post-FAc, such as retinal thickness fluctuations, as well as patient-related outcomes, including post-FAc changes in activities of daily living,” investigators wrote.

References

1. Roth DB, Eichenbaum D, Malik D, et al. 0.19-mg fluocinolone acetonide intravitreal implant for diabetic macular edema: intraocular pressure-related effects over 36 months [published online ahead of print, 2023 Aug 14]. Ophthalmol Retina. 2023;S2468-6530(23)00373-1. doi:10.1016/j.oret.2023.08.004
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