Real-world study of the fluocinolone acetonide implant show its benefits for treating DME

January 11, 2019

A retrospective chart review study of patients who received the fluocinolone acetonide 0.19 mg implant (Iluvien, Alimera Sciences) for diabetic macular edema shows its efficacy and safety when patients are selected per the FDA-approved indication. Compared with the pre-implant period, visual acuity was maintained or improved and there were reductions in both treatment burden and the amplitude of retinal thickness fluctuation.

In the United States, the fluocinolone acetonide (FAc) 0.19 mg implant (Iluvien, Alimera Sciences) is indicated for the treatment of diabetic macular edema (DME) in patients who were previously treated with a course of corticosteroids and did not have a clinically significant rise in IOP. Results from a real-world retrospective study show that patients treated with the FAc implant for DME per the US FDA approved indication had a low treatment burden and a marked reduction in the IOP signal compared to that observed in the pivotal Fluocinolone Acetonide in Macular Edema (FAME) study, reported Alexander M. Eaton, MD.

“The results from use of the FAc implant in the United States raises the question of whether before using the implant to treat recurrent DME, European retina specialists should consider a trial with a corticosteroid in order to mitigate an IOP effect,” said Dr. Eaton, Founder and Director, Retina Health Center, Fort Myers and Naples, FL.

“Based on the positive results from the US study, it also seems reasonable to ask whether we are approaching treatment for DME backward and if it is time for a paradigm shift where the FAc implant would be first-line therapy and supplemented with anti-VEGF injections as needed. More data are needed, but the efficacy, safety, and treatment burden outcomes in the US real-world study makes the FAc implant a lot more appealing than it was before the results were available.”

Known as USER (US Retrospective Chart Review in Patients Receiving Iluvien), the US real-world study included data from 160 eyes of 130 patients treated across four US centers. All patients had DME that persisted or recurred and therefore had persistent DME. Mean duration of DME was 4.4 years. All received the FAc implant before January 1, 2016, and had at least 1 year of follow-up after the injection. 

The 130 patients included in the outcomes analysis had a mean age of approximately 70 years and a mean duration of diabetes of 24 years. Mean HbA1c was 7.07%, nearly 90% of patients were white and had type 2 diabetes, and approximately 70% of the patients were pseudophakic. Mean duration of follow-up was 899 days before the FAc implant and 403 days after it was placed. 

Mean visual acuity (VA) analyzed for visits at 3-month intervals from 36 months prior to receipt of the FAc implant through 24 months after showed that VA remained stable, but visual function was maintained in the cohort with a significantly reduced treatment burden (once every 2.9 months before the FAc implant to once every 14.3 months after; P<.001).

Approximately two-thirds of patients required no additional treatment after getting the FAc implant; 17.4% of patients received anti-VEGF injections, 7.5% received additional corticosteroid, and 6.0% were treated with laser.

An analysis with patients divided into four groups according to baseline VA (<20/200, 20/200 to <20/100, 20/100 to <20/40, and ≥20/40) showed a significant reduction in need for treatment across all groups. Before getting the FAc implants, patients in all four groups were being treated approximately every 2 to every 3 months. After getting the FAc implant, treatment frequency across the four groups ranged from a maximum of about once every 7 months to a low of once every 22 months.

“Patients with better VA at baseline needed less frequent treatment after getting the FAc implant. They also had had little room for improvement in VA, but patients who had the worst VA at baseline benefited with improvement after getting the FAc implant,” Dr. Eaton said.

Mean retinal thickness trended downward from the beginning of the study, but the improvement was greater after patients received the FAc implant. Fluctuation in retinal thickness, evaluated by analyzing the maximum range of the retinal thickness fluctuations as derived from the difference of minimum and maximum central subfield thickness, decreased by more than 50% after patients received the FAc implant, from approximately 225 microns to less than 100 microns (P<.001). Subgroup analyses showed the statistically significant benefit for reduced retinal thickness fluctuation after FAc implant injection was present regardless of baseline VA.

“Consistent with other evidence, we found a poor correlation between retinal thickness and VA in our patients with DME. There was a stronger correlation between the amplitude of fluctuation and VA. This finding suggests that mitigating the amplitude of the fluctuation of retinal thickness might translate into beneficial effects on vision, and that certainly makes sense theoretically,” said Dr. Eaton.

Proper patient selection mitigates IOP response

Mean IOP was stable throughout the follow-up period prior to FAc implantation and elevated slightly after patients received the FAc implant. Mean IOP was 14.6 mmHg at the time of injection and reached a maximum of 16.2 mmHg at 15 months, but declined thereafter, which was explained by initiation of treatment for IOP-lowering.

Dr. Eaton reported that most IOP elevations were controlled with topical medications. Twenty-eight (17.5%) eyes were receiving IOP-lowering medication on the day of the FAc implant injection and 24.4% were receiving IOP-lowering medication after its administration during the follow-up. Two eyes underwent incisional IOP-lowering surgery after FAc administration, which was the same number that had incisional IOP-lowering surgery in the period before receiving the implant, Dr. Eaton said.

Disclosures:

Alexander M. Eaton, MD 
ame@retinahealthcenter.com
This article is based on a presentation given by Dr. Eaton at the 18th EURETINA Congress in Vienna, Austria. Dr. Eaton receives grant/research support, is on the speaker bureau for, has patents with, and/or is a shareholder for Alimera Sciences and other companies that market or are developing treatments for DME.