Fluocinolone Implant Slows Diabetic Retinopathy in Patients With Macular Edema

Laird Harrison

January 19, 2017

Fluocinolone implants can slow diabetic retinopathy and delay proliferation in patients with diabetic macular edema, researchers say.

Compared with antivascular endothelial growth factor (anti-VEGF) treatments, the steroid "may be a viable strategy to decrease treatment burden and improve patient access to care," write Charles C. Wykoff, MD, PhD, from Houston Methodist Hospital in Texas, and colleagues.

They published their post hoc analysis of data from the Fluocinolone Acetonide in Diabetic Macular Edema (FAME) trial in Ophthalmology.

Anti-VEGF treatments for diabetic macular edema have achieved impressive results in reducing the rate of progression to proliferative diabetic retinopathy. For example, in the RIDE/RISE trials, the probability of diabetic retinopathy progressing was 11.2% in patients receiving monthly ranibizumab injections compared with 33.8% in patients receiving a sham treatment (Arch Ophthalmol.  2012;130[9]:1145-1152).

The intravitreal 0.19-mg fluocinolone acetonide implant is designed to provide long-acting, consistent, low-dose steroid exposure after a single injection.

In the FAME trial, 956 patients with persistent diabetic macular edema who had undergone at least one prior macular laser photocoagulation treatment were randomly assigned to either the fluocinolone implant or a sham injection. The implants delivered either 0.2 or 0.5 µg/day of fluocinolone.

After 3 years, 27.8% to 28.7% of patients treated with fluocinolone showed significant improvements in visual function compared with 18.9% of those who received sham injections.

To understand better how the treatment affected the progression of diabetic retinopathy, Dr Wykoff and colleagues analyzed data from the FAME trial on changes in Early Treatment Diabetic Retinopathy Study (ETDRS) diabetic retinopathy severity grades.

They classified eyes as having experienced a proliferative event if they met at least one of these criteria: progressed to diabetic proliferative retinopathy based on the grading of fundus photographs, received laser photocoagulation specifically related to diabetic retinopathy, or underwent victrectomy related to diabetic retinopathy.

The patients treated with fluocinolone were less likely to experience this type of event during the 3 year follow-up.

Percent With Proliferative Event in 3 Years

Sham 0.2 µg/day fluocinolone, n = 376 0.5 µg/day fluocinolone, n = 395
All patients 28.6 16.2 17.2
Patients receiving panretinal photocoagulation 14.1 8.9 7.2
Patients receiving pars plana vitrectomy 1.6 1.9 1.5


Fluocinolone also significantly slowed the time to the first proliferative event compared with the sham treatment (P < .001). The effect was particularly strong among patients with baseline retinal nonperfusion.

Regardless of the dose, patients treated with the fluocinolone implant showed significant improvements in mean diabetic retinopathy severity at 6, 12, and 18 months. Those on the lower dose also showed improvement at week 36.

The fluocinolone implants appeared most effective in patients with chronic diabetic macular edema.

The rate of progression to proliferation in this study was similar to the rate seen with anti-VEGF treatments, but with fewer injections. In this study, patients had a mean of 1.3 to 1.4 injections over 3 years. By comparison, patients in the Diabetic Retinopathy Clinical Research Network (DRCR.net) Protocol T trial needed 15 to 16 intravitreal injections in 20 clinical visits over 2 years.

It's hard for some people to get to the clinic that often, the researchers point out. "Injection frequency has also been demonstrated to affect quality of life and aspects of treatment burden, such as injection anxiety and work absences," they write.

However, the fluocinolone implants in this study did not appear as effective in reducing diabetic retinopathy severity as monthly anti-VEGF injections, the authors say. They speculate that their study population's prior exposure to macular laser could be a factor explaining the difference.

Perhaps more important, steroid use can raise intraocular pressure (IOP) and accelerate the risk for cataract. In the FAME trials, 18.4% to 22.9% of patients receiving the steroid had IOPs higher than 30 mmHg compared with 4.3% of patients receiving sham treatment.

The study provides some assurance that treating a patient's diabetic macular edema with fluocinolone could at least delay the need for laser treatment, said J. Michael Jumper, MD, of West Coast Retina and California Pacific Medical Center in San Francisco.

Clinicians can now choose between anti-VEGF treatments and a steroid in these patients, said Dr Jumper, who was not involved with the study. "Sometimes patients who do not benefit from anti-VEGF injections do benefit from fluocinolone," he said. "For someone who has diabetic macular edema plus proliferative diabetic retinopathy, try anti-VEGF treatment, and if that doesn't work, go with a steroid therapy such as fluocinolone."

He cautioned that patients treated with steroids in this way need constant monitoring in case they develop glaucoma or cataracts.

For patients with this profile who seem unlikely to return after the initial appointment, laser treatment might be the most practical approach, he said.

Alimera Sciences funded the study and paid all the authors. Dr Wykoff and several coauthors report grants, personal fees, and/or stockholdings for one or more of these companies: Acucela, Allegro Ophthalmics, Ampio Pharmaceuticals, Apellis Pharmaceuticals, DRCR network/NEI, Iconic Therapeutics, Ophthotech, Pfizer, Santen, pSivida, Tyrogenex, XOMA, Alcon Laboratories, Inc, Allergan, Clearside Biomedical, Inc, Genentech/Roche, Regeneron Pharmaceuticals, ThromboGenics, Inc; Alimera Sciences, Bayer, DORC International, ONL Therapeutics, AbbVie, Genzyme, GlaxoSmithKline, Applied Genetic Technologies, Intrexon, Merck, Aerpio, AsclepiX, Regenxbio, Graybug, Novartis, Gene Signal, Precision Ocular Ltd, Sanofi-Aventis, Vifor Pharma, and Carl Zeiss Meditec. One author reports being an employee and stockholder in Alimera Sciences.

Dr Jumper reported serving as an investigator for Acucela Inc; Alcon Laboratories, Inc; Allergan, Inc; and Ophthotech Corporation; holding stocks or receiving royalties from Covalent Medical, LLC; serving as an advisory board member and speaker and receiving honoraria from Dutch Ophthalmic Research Center; and serving as an investigator and speaker for and receiving grants from Genentech, Inc.

Ophthalmology. Published online January 9, 2017. Abstract


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