導讀：Used in combination with antivascular endothelial growth factor (Anti-VEGF) therapy, dexamethasone implants (0.7 mg Ozurdex, Allergan) may help some patients with neovascular age-related macular degeneration (nAMD) that is resistant to anti-VEGF monotherapy, researchers say.

        Used in combination with antivascular endothelial growth factor (anti-VEGF) therapy, dexamethasone implants (0.7 mg Ozurdex, Allergan) may help some patients with neovascular age-related macular degeneration (nAMD) that is resistant to anti-VEGF monotherapy, researchers say.

        In a group of patients with a disappointing response to anti-VEGF treatment, the implants improved anatomical signs of disease, reduced the number of injections needed, and showed a trend toward improved visual acuity, say Bozho Todorich, MD, PhD, from Associated Retinal Consultants in Royal Oak, Michigan, and colleagues.

        "Earlier treatment with dual therapy may be beneficial to maximize anatomic and visual outcomes in these patients," the researchers write in an article published in the January/February issue of the Journal of VitreoRetinal Diseases.

        Although injections with the anti-VEGF treatments bevacizumab (Avastin, Genentech), ranibizumab (Lucentis, Genentech), and aflibercept (Eylea, Regeneron) improve the eyesight of most patients with nAMD, some do not respond.

        Corticosteroids may suppress inflammatory processes involved in the disease, stabilizing vascular tight junctions and decreasing leakage, producing apoptosis of peripheral T-cells and eosinophils, and possibly blocking fibroblast activation and proliferation, Dr Todorich and colleagues write. In addition, glucocorticoids directly inhibit VEGF production, they add.

        Dexamethasone is a potent steroid, but it clears rapidly from the vitreous cavity. In contrast, an intravitreal implant, Ozurdex, emits dexamethasone steadily during a period of up to 6 months.

        The US Food and Drug Administration has approved the implant for the treatment of diabetic macular edema, cystoids, macular edema associated with retinal vein occlusion, and noninfectious uveitis.

        Therefore, Dr Todorich and colleagues wanted to see whether the implant combined with an anti-VEGF treatment could benefit patients whose nAMD had not responded well to anti-VEGF treatment alone.

        They recruited 18 consecutive of patients with a mean age of 81.5 years who were diagnosed with nAMD with active subfoveal choroidal neovascularization and best-corrected visual acuity of 20/30 to 20/800.

        All the patients had shown resistance after receiving at least 2 anti-VEGF injections with a minimum follow-up of 3 months. They had received a mean of 26.3 anti-VEGF injections (range, 2 - 56).

        The researchers defined treatment resistance as persistent intraretinal or subretinal fluid despite monthly injections, no improvement in central foveal thickness and macular cube volume in response to anti-VEGF therapy, and new or worsening subretinal hemorrhage despite monthly anti-VEGF injections.

        Two patients had undergone photodynamic therapy, and two had tried intravitreal triamcinolone acetonide.

        With a mean follow-up of 8.2 months (range, 4 - 14.2 months), the patients tolerated the dexamethasone implant well. Two patients developed transient elevation in intraocular pressure, which was successfully treated with topical glaucoma drops. One patient with preexisting cataract underwent treatment for it.

        The treatment appeared to improve central foveal thickness. Whereas patients had averaged an increase of 29.9 μm after their last anti-VEGF treatment, they averaged a decrease of 126.3 μm after their first combined treatment (P = .0017).

        Likewise, macular cube volume decreased by an average of 0.85 mm3 after the dual therapy. In comparison, this measurement grew by 0.19 mm3 after the last monotherapy treatment with an anti-VEGF (P = .0014).

        Best-corrected visual acuity improved by at least one line in six of the patients, but the overall change did not reach statistical significance (P = .92).

        The six patients who improved had a lower mean number of prior anti-VEGF injections, "which may suggest that earlier treatment is beneficial." Those with the fewest injections also improved most in central foveal thickness.

        Finally, the mean number of injections decreased from 5.33 before the dual therapy to 4.25 after (P = .0199), and the mean treatment-free interval lengthened from 1.13 to 1.74 months (P = .0312).

        The researchers acknowledged that the study was limited by its retrospective design, small sample size, and lack of a control group. As well, they note, the patient population had a heterogeneous treatment history, but were almost all Caucasian.

        The study follows other attempts to treat nonresponders with different protocols of anti-VEGF therapy and alternative medications, Neil Finnen, MD, an associate professor at Loma Linda University in California, told Medscape Medical News.

        However, most of these have proved disappointing, including phase 3 results with pegpleranib (Fovista, Ophthotech), an antiplatelet-derived growth factor, as the company announced in December. The drug had looked promising in earlier studies, as reported by Medscape Medical News.

        "There have been a lot of attempts, and I think this is an interesting option," Dr Finnen said. "There is definitely some good scientific rationale for doing this."

        However, this study does not establish a clear role for Ozurdex, he said. "It didn't have a significant impact on their vision, and in the end of the day, that's what the patients are interested in."

        In addition, reducing the number of anti-VEGF injections might not make much difference to patients because they had to get an additional injection for the Ozurdex, he said.

        Still, further research might identify a subgroup of people who get clear benefits from the combined treatment, and a multicenter, randomized clinical trial is worth pursuing, Dr Finnen concluded.

        The study authors have disclosed several relevant financial relationships, including serving as a consultant or advisory board member for one or more of the following companies: Alimera, Allergan, Arctic Dx, Genentech, Novartis, Regeneron, and Intelligent Retinal Imaging Systems. Dr Finnen reported research relationships with Ophthotech and Alcon.

        J Vitreoretinal Disease. 2017;1:65-74. Abstract