Elsevier

Ophthalmology

Volume 119, Issue 10, October 2012, Pages 2125-2132
Ophthalmology

Original article
Sustained Delivery Fluocinolone Acetonide Vitreous Inserts Provide Benefit for at Least 3 Years in Patients with Diabetic Macular Edema

https://doi.org/10.1016/j.ophtha.2012.04.030Get rights and content

Objective

To assess long-term efficacy and safety of intravitreal inserts releasing 0.2 μg/d (low dose) or 0.5 μg/d (high dose) fluocinolone acetonide (FAc) in patients with diabetic macular edema (DME).

Design

Two randomized, sham injection-controlled, double-masked, multicenter clinical trials.

Participants

Subjects with persistent DME despite ≥1 macular laser treatment were randomized 1:2:2 to sham injection (n = 185), low-dose insert (n = 375), or high-dose insert (n = 393).

Methods

Subjects received study drug or sham injection and after 6 weeks were eligible for rescue laser. Based on retreatment criteria, additional study drug or sham injections could be given after 1 year.

Main Outcome Measures

Percentage of patients with improvement of ≥15 letters from baseline. Secondary outcomes included other parameters of visual function and foveal thickness.

Results

At month 36, the percentage of patients who gained ≥15 in letter score using the last observation carried forward method was 28.7% (low dose) and 27.8% (high dose) in the FAc insert groups compared with 18.9% (P = 0.018) in the sham group, and considering only those patients still in the trial at month 36, it was 33.0% (low dose) and 31.9% (high dose) compared with 21.4% in the sham group (P = 0.030). Preplanned subgroup analysis demonstrated a doubling of benefit compared with sham injections in patients who reported duration of DME ≥3 years at baseline; the percentage who gained ≥15 in letter score at month 36 was 34.0% (low dose; P<0.001) or 28.8% (high dose; P = 0.002) compared with 13.4% (sham). An improvement ≥2 steps in the Early Treatment Diabetic Retinopathy Study retinopathy scale occurred in 13.7% (low dose) and 10.1% (high dose) compared with 8.9% in the sham group. Almost all phakic patients in the FAc insert groups developed cataract, but their visual benefit after cataract surgery was similar to that in pseudophakic patients. The incidence of incisional glaucoma surgery at month 36 was 4.8% in the low-dose group and 8.1% in the high-dose insert group.

Conclusions

In patients with DME FAc inserts provide substantial visual benefit for up to 3 years and would provide a valuable addition to the options available for patients with DME.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found after the references.

Section snippets

Methods

The FAME A and B studies were performed under a single protocol as randomized, double-masked, sham injection-controlled, parallel-group, multicenter studies conducted over a 36-month period. The first, FAME A, was conducted at 49 sites in the United States, Canada, 4 countries in the European Union, and India; FAME B was conducted at 52 sites in the United States, India, and 3 countries in the European Union. The studies adhered to the guidelines of the Declaration of Helsinki and the protocol

Baseline Characteristics and Patient Disposition

There were no imbalances at baseline with respect to age, race, the mean duration of diabetes (range, 16.1–17.1 years), the mean duration of DME (range, 3.5–3.9 years), mean BCVA (range, 52.9–54.7 ETDRS visual acuity score), or FTH (range, 451.3–485.1 μm). The percentage of patients who failed to remain in the study until the month 24 primary endpoint was 19.0% in the high-dose group, 19.9% in the low-dose group, and 22.7% in the sham group, and the percentage that exited before the month 36

Discussion

The primary outcome was met in both FAME trials. The integrated dataset showed that 28% of patients treated with a low- or high-dose FAc insert had an improvement of ≥15 in BCVA letter score at month 24 compared with 16% in the sham injection group. Continued follow-up has shown that those excellent results are maintained through at least 3 years, with roughly 28% of patients in the FAc insert groups still showing improvement of ≥15 in BCVA letter score. Approximately 30% of patients in each of

Acknowledgments

The study was supported by Alimera Sciences, Atlanta, Georgia. The authors thank the Data and Safety Monitoring Board: Frederick L. Ferris, III (Chairman), Stanley Chang, Matthew Davis, Michele Melia, and Richard Parrish for overseeing the trial.

References (4)

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Manuscript no. 2012-67.

Financial Disclosure(s): The authors have made the following disclosures:

Clare Bailey: Travel grant — Novartis UK.

Kathleen Billman: Employee — Stock options, Alimera Sciences.

David Boyer: Consultant — Alimera Sciences; consultant, lecture fees — Genentech; Consultant — Regeneron.

David Brown: Consultant — Alimera Sciences, Allergan, Alcon, Eli Lilly, Novartis, Regeneron.

Peter Campochiaro: Data and safety monitoring committee — Regeneron; consultant — Allergan and LPath.

Sanford Chen: Consultant, travel support — Alimera Sciences; consultant — Genentech, Regeneron, Allergan, Alcon, EyeTech; lecture fees — Genentech, Alcon; travel support — Genentech, Regeneron.

Bruce Garretson: Travel support — Alimera Sciences.

Kenneth Green: Employee, stock options — Alimera Sciences.

Seenu Hariprased: Advisory board — Scimedica; consultant — Alcon, Allergan, Genentech, Regeneron, Ocular Therapeudix, Bayer, Optos, OD-OS; lecture feed — Alcon, Allergan, Genentech; stock options — OD-OS, Ocular Therapeudix. Employee, stock options — Alimera Sciences.

Frances Kane: Employee, stock options — Alimera Sciences

Barry Kapik: Employee, stock options — Alimera Sciences.

Andrew Pearson: Consultant — Alimera Sciences; stock options — pSividia.

Jose Ruiz-Moreno: Advisory board — Bayer, Allergan, Novartis.

Gisele Soubrane: Travel support — Alimera Sciences; advisory board — Allergan, Novartis; consultant — Thea; lecture fees — Allergan.

Supported by Alimera Sciences Inc.

*The complete list of FAME Study Group is available at http://aaojournal.org.

Group members listed online (available at http://aaojournal.org).

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