Others and Fluocinolone, Dexamethasone, Triamcinolone, chapCorticosteroids:• 30

A

B

Figure 30.6  (A, B) Dexamethasone (Ozurdex, Allergan, Irvine, CA), currently in phase III clinical trials for the treatment of macular edema delivery system.

and 0.5 g of fluocinolone to the retina, is complete. The FAME study is a double-masked, randomized, multicenter clinical trial involving more than 900 patients in the USA, Canada, Europe, and India. Safety and efficacy will be assessed at 2 years, and patients will be followed for 3 years. Results from the FAME study will help to determine if Medidur FA is effective and capable of reducing the steroid-induced side-effects seen in the Retisert trial.

DEXAMETHASONE DRUG

DELIVERY SYSTEM

A sustained-delivery formulation of dexamethasone (Ozurdex, Allergan, Irvine, CA) is in phase III clinical trials for the treatment of macular edema. The phase III trial employs the new applicator, allowing placement of an extruded, rather than pelleted, form of the dexamethasone delivery system through a small self-sealing puncture (Figure 30.6).

Two doses of dexamethasone were evaluated in a 6-month, phase II, multicenter, randomized clinical trial.61 The 315 patients in the trial had persistent macular edema due to diabetic retinopathy (n = 172), retinal vein occlusion (n = 102), Irvine–Gass syndrome (n = 27), or uveitis (n = 14). In each patient, one eye was randomized to treatment with a 350-g dose of Ozurdex, a 700-g dose of Ozurdex (both inserted into the vitreal cavity via a small pars plana incision) or observation.

Implantation with Ozurdex resulted in a statistically significant increase in patients gaining 2 and 3 lines or more of visual acuity in a dose-dependent fashion at 90 and 180 days compared with observation (P < 0.025). The percentages of patients who gained 2 lines or more of visual acuity 180 days after implantation were 32.4% in the 700-g group, 24.3% in the 350-g group, and 21% in the observation group (P = 0.06). The percentages of patients who gained 3 lines or more of visual acuity 180 days after implantation were 18.1% in the 700-g group, 14.6% in the 350-g group, and 7.6% in the observation group (P = 0.02). The visual acuity improvements achieved with the 700-g implant were consistent across all subgroups at day 90.

In addition, at the primary endpoint, 2% of the patients who were implanted with the 350-g and 700-g dose of Ozurdex had an increase in IOP of 10 mmHg or more from baseline, compared with 1% of patients in the observation arm. All were successfully managed with either observation or topical IOP-lowering medication. Cataracts were present in 15% of the 350-g group, 17.8% of the 700-g group, and 12.4% of the observation group (P < 0.001 versus observation).

SUMMARY AND KEY POINTS

In summary, macular edema occurs when a variety of disease states induce changes to retinal capillaries resulting in a breakdown of the tight junctions that form the blood–retinal barrier, with subsequent increased retinal vascular permeability.1,62 Chronic, low-grade, inflammation of the retinal microvasculature appears to be a significant contributor to this process. The goals of therapy should be to reduce inflammation, restore blood–retinal barrier patency, and interfere with the production or action of VEGF and other proinflammatory cytokines. Corticosteroids are the one class of agents that acts upon most of the multiple processes in the pathophysiology of macular edema. However, despite their significant benefits, the primary ocular adverse effects associated with the use of steroids – IOP rise and cataract – are important issues which may limit their use in certain situations. The need for repeated injections may be offset by the use of long-term sustained-release implants, most of which are in advanced stages of clinical trials. Once approved, the steroid implants may be extremely beneficial in the management of serious retinal diseases.

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Diseases Retinal in Mechanisms and Drugs • 4 section