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To the Editor:
We thank Drs. Dan and Mihai Călugăru for their interest in our study.1 They had several queries which we will attempt to answer.
Drs. Călugăru enquired about the lesion type and the presence of subretinal atrophy and scarring. The study excluded eyes with retinal angiomatous proliferation and polypoidal choroidopathy. All patients had minimally classic/occult lesions. Seven of 19 eyes (37%) had retinal pigment epithelial detachment and 9 eyes (47%) had retinal pigment epithelial atrophy to varying degrees. Subretinal and sub–retinal pigment epithelial scarring was present in five eyes (26%). As for the presence of subretinal and intraretinal fluid, this information is already described in the article with 13 eyes having only intraretinal fluid, 4 eyes with only subretinal fluid and 2 eyes with both intraretinal and subretinal fluid.
Drs. Călugăru raises the issue of sufficient washout of the anti-vascular endothelial growth factor (anti-VEGF) agents from the eye and resistance to treatment. We included only patients with treatment-naive neovascular age-related macular degenerations who commenced treatment at our clinics with bevacizumab. These patients were considered for enrollment if they had persistent intraretinal or subretinal macular fluid on optical coherence tomography despite continuous and uninterrupted monthly intravitreal anti-VEGF injections since initiation of therapy. We excluded patients who demonstrated at any time resolution of macular fluid on optical coherence tomography with either bevacizumab or ranibizumab and those with a nondurable response whereby the anti-VEGF treatment resulted in fluid-free macula for less than 4 weeks. Based on this, we cannot label these patients as exhibiting tachyphylaxis or tolerance since they never responded with complete drying of the macula on optical coherence tomography after a mean of more than 10 injections. The fact that macular thickness decreased significantly one week after the dexamethasone implant only in eyes with intraretinal fluid makes one suspect that it is due to the dexamethasone. Of course, we cannot not definitely rule out a “carryover effect” but at least we should have seen a fluid-free macula at some point with monthly anti-VEGF injections before the dexamethasone implant to truly suspect such a phenomenon. Switching to aflibercept is an excellent suggestion in these eyes; however, this agent was not available at the time of the study. Needless to say, even after switching to aflibercept, some eyes continue to have persistent fluid on optical coherence tomography.2,3
Given that dexamethasone implant was and still not approved as treatment for neovascular age-related macular degeneration, we could not in good conscience withhold standard-of-care treatment (i.e., intravitreal ranibizumab) for the sake of the study. This is, also, why we did not allow a longer “washout” nor stop the intravitreal ranibizumab altogether. We believe that dexamethasone may be sufficient to clear intraretinal fluid but may be less effective compared with anti-VEGF agents in controlling the growth of the choroidal neovascular membrane. Therefore, both intravitreal corticosteroids and anti-VEGF agents may work synergistically to control the disease. We agree with Drs. Călugăru that earlier intervention in neovascular age-related macular degeneration leads to better functional outcome and that a single dexamethasone implant is not sufficient over the span of 6 months. However, the dexamethasone implant was administered within the confines of the study and budgeting did not allow for more than one injection per patient. We need to stress this was only an exploratory pilot study. Future studies can enroll patients earlier in the course of their disease and allow for more than one injection over 6 months.
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