One of the strengths of Iluvien (fluocinolone acetonide intravitreal implant 0.19 mg, Alimera Sciences), our newest treatment option for patients with diabetic macular edema (DME), is how it can be used to ease the treatment burden on our patients. The implant is designed to deliver a continuous microdose of fluocinolone to the eye for 36 months. Few cases illustrate this benefit as clearly as that of my patient, a 60-year-old female diagnosed with diabetes in 1983 and DME in both eyes in 2004. Her case also illustrates how corticosteroid medications may be the best option for saving sight in patients whose DME is refractory to anti-VEGF agents.

More than a Decade of Repeat Treatments

In addition to diabetic eye disease, this patient, who is pseudophakic, also has bilateral mixed mechanism glaucoma — due, in part, to the multiple steroid treatments she’d received for more than a decade. The glaucoma was brought under control with a trabeculectomy in 2009 and continued use of topical dorzolamide HCL/timolol maleate, brimonidine, and latanoprost in both eyes. For the glaucoma in the left eye, the patient also underwent selective laser trabeculoplasty in 2014. For DME or proliferative diabetic retinopathy OS, she received 15 intravitreal steroid injections between 2004 and 2014, three focal laser treatments between 2006 and 2012, and panretinal photocoagulation in 2008. In 2012 ranibizumab (Genentech) was approved for treating DME, so in 2013 she received three ranibizumab injections, which had no effect on the macular edema. Also in 2013, the patient underwent pars plana vitrectomy and membrane peel OS.

Since 2004, the pattern for this patient had been the same. The DME would respond well to intravitreal steroid injections but repeatedly recur. In an effort to reduce the number of treatments necessary to keep the retina dry, the left eye received a dexamethasone intravitreal implant (Allergan) in January 2015 and another in April 2015.

Iluvien for the Left Eye

By the time the patient returned for her July 8, 2015 follow-up visit, 3 months after the second dexamethasone intravitreal implant OS, the effects of the implant were waning. Central subfield thickness (CST) as measured by OCT had increased to 281 µm and visual acuity (VA) had declined to 20/50+2 (Figure 1). At the next visit, Aug. 26, 2015, CST and VA further worsened to 392 µm and 20/60 and Iluvien was implanted (Figure 2).

The FDA labeling of Iluvien states that it should be used only for patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in IOP. I appreciate this labeling not only because it clarifies who should receive the implant but also because it leaves the individual retina specialist to decide how to identify steroid responders and how to define a clinically significant steroid challenge and a clinically significant IOP response. This patient in fact did have a clinically significant steroid response prior to Iluvien. However, the resultant glaucoma was treated with trabeculectomy and kept controlled with topical medications, rendering it no longer clinically significant. The benefit of steroids in this case — effectively treating DME and preventing the associated vision loss, along with eliminating the treatment burden of monthly anti-VEGF injections — outweighed the risks. Furthermore, the intermittent steroid dosing that had been employed left the retina vulnerable to recurrent periods of DME, associated reduction in visual acuity, and the increased treatment burden of steroid injections every 3 to 5 months.

At the patient’s first follow-up visit, 1 week after Iluvien implantation OS, Sept. 2, 2015, the retinal anatomy had normalized and VA improved to 20/40-1 (Figure 3). With the patient still using three IOP-lowering medications, intraocular pressure remained unchanged since before the implant at 14 mmHg. IOP remained stable at the next visit on Oct. 28, 2015, and VA further improved to 20/30+1 (Figure 4). While I’d typically recommend that this patient see me every 3 months, she also sees a glaucoma specialist. We’ve scheduled the visits so that she sees each of us every 6 months, but she’s examined every 3 months. I continue to measure IOP at every visit. Today, more than a year after Iluvien was placed in the left eye, the patient’s vision is consistently better than it had been in more than a decade, and we’re both thrilled that she’s been able to carry on with her busy real estate business on a much easier office visit schedule than she had been enduring.

Potential for Paradigm Shift

As this case illustrates, DME is a multifactorial disease, involving both VEGF and cytokines other than VEGF, which means when it comes to treatment, there’s no one right answer for all patients. Treatment must be individualized based on each patient’s clinical fact pattern, which may include such factors as appearance on fluorescein angiography and duration of disease. Iluvien represents an opportunity for retina specialists to move out of the mode of giving an anti-VEGF injection every month for a patient’s lifetime and move toward something efficacious that can break the disease cycle. As experience with Iluvien increases, we may learn that a low-dose steroid is preferable to higher-dose steroids in many instances. We may also gain confidence in turning to steroid therapy earlier than we were previously accustomed. In the meantime, Iluvien is an invaluable option in DME cases such as the one described here, where laser isn’t an option, anti-VEGF agents are ineffective, the edema is persistent, and steroids have been shown to work. •

Dr. Riemann is a vitreoretinal specialist with Cincinnati Eye Institute in Ohio, a member of the volunteer faculty at the University of Cincinnati, and director of the combined vitreoretinal fellowship at both institutions.