PMC5444334_01
Patient 1 is an 87 year old pseudophakic Caucasian woman with neovascular AMD and active choroidal neovascularization (A, B) who presented with intra- and sub-retinal fluid on OCT (C). She underwent multiple intravitreal ranibizumab and aflibercept injections (>20), but developed persistent fluid despite monthly injections of each and had a BCVA of 20/50 (C, D, E). She underwent dual therapy with intravitreal aflibercept and the dexamethasone intravitreal implant, which resulted in significant improvement of intra- and sub-retinal fluid and improved BCVA to 20/25 (F). She did not have any IOP elevation or injection- related complications.
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Figures 1, 2 and 3 summarize clinical data from three index patients included in the series. The first is an 87 year-old pseudophakic Caucasian woman with nvAMD and active CNV (Figure 1A, B). Following a single dual therapy treatment, there was significant resolution of intraretinal and subretinal fluid and VA improved to 20/25 (Figure 1F).
Patient 2 is an 67 year-old phakic Caucasian man with active neovascular AMD with subfoveal choroidal neovascularization (A, B). Patient had significant intra-retinal fluid with exudate on OCT (C) and underwent intravitreal injection of ranibizumab with minimal response (D) after 1 month. He subsequently received another injection of bevacizumab, but with a similar lack of effect (E) after 1 month. At that time, the eye was treated with a combined injection of intravitreal bevacizumab and the dexamethasone intravitreal implant after which there was a significant decrease in intraretinal fluid and improvement of visual acuity to 20/70 after 1 month (F). There was no elevation of IOP or injection-related complications.
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Figures 1, 2 and 3 summarize clinical data from three index patients included in the series. The second patient is a 67 year-old phakic Caucasian man with recent conversion to nvAMD (Figure 2 A, B) who failed to significantly respond to initial ranibizumab and subsequent bevacizumab intravitreal injections (Figure 2 C-E). However, after one dual therapy treatment with the dexamethasone intravitreal implant combined with bevacizumab, the patient showed significant resolution of intra- and sub-retinal fluid and experienced significant improvement in BCVA to 20/70 from 20/800 (Figure 2F).
Patient 3 is a 74 year-old pseudophakic man with neovascular AMD and active subfoveal CNV with persistent intra-retinal fluid despite multiple bevacizumab (n=15) and aflibercept (n=15) intravitreal injections. Patient underwent injection of intravitreal ranibizumab (A) with minimal change in fluid appearance on OCT after 1 month (B). Then, combined intravitreal ranibizumab and dexamethasone intravitreal implant were given with complete resolution of the intraretinal fluid (C). As a result, no anti-VEGF treatment was given at this visit and patient continued to do well with observation alone at 1 month (D) and 3 months (E) post-combined treatment without anti-VEGF injections. At that time, additional combined intravitreal ranibizumab and dexamethasone intravitreal implant were given, and patient followed at monthly intervals for 1 year with stable visual acuity without requiring additional anti-VEGF or dual therapy re-treatment (F). The best corrected visual acuity remained stable at 20/50.
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Figures 1, 2 and 3 summarize clinical data from three index patients included in the series. He underwent injection of intravitreal ranibizumab with minimal response (Figure 3A, B) before he received a combination treatment of intravitreal ranibizumab and dexamethasone implant. This resulted in complete resolution of the intraretinal fluid (Figure 3C). He was observed monthly without anti-VEGF therapy, without recurrence of fluid (Figure 3D, E), and requiring only a single dual therapy during 12 months of follow up (Figure 3F).
Comparison of mean central foveal thickness (CFT) change in patients with neovascular AMD treated with anti-VEGF agents alone (left, black) and those treated with subsequent combined therapy with dexamethasone intravitreal implant and anti-VEGF agent (grey, right) administered concurrently at the same visit. The mean changes represent treatment effects of the consecutive visits; the last anti- VEGF injection (left graph) and then the subsequent first combined treatment (right graph). The mean difference between the treatments was evaluated using paired t-test with significance level of p<0.05.
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Figures 4 and 5 summarize the mean change in CFT and MCV after dual therapy with the dexamethasone intravitreal implant and anti-VEGF injection compared to anti-VEGF therapy alone.
Comparison of mean macular cube volume (MCV) change in patients with neovascular AMD treated with anti-VEGF agents alone (left, black) with those treated with subsequent combined therapy with the dexamethasone intravitreal implant and an anti-VEGF agent (checkered, right) administered concurrently at the same visit. The mean changes represent treatment effects of the consecutive visits; the last anti-VEGF injection (left graph) and the subsequent first combined treatment (right graph). The mean difference between the treatments was evaluated using paired t-test with significance level of p<0.05.
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Figures 4 and 5 summarize the mean change in CFT and MCV after dual therapy with the dexamethasone intravitreal implant and anti-VEGF injection compared to anti-VEGF therapy alone.
Comparison of best-corrected visual acuities in patients with neovascular AMD treated with anti-VEGF agents alone (left two graphs) and those treated with subsequent combined therapy with the dexamethasone intravitreal implant and an anti-VEGF agent (right two graphs) administered concurrently at the same visit. The mean BCVA represent treatment effects of the consecutive visits; the last anti- VEGF injection (left two plots) and the subsequent first combined treatment (right two plots). The mean differences between the treatments were evaluated using paired ANOVA with multiple comparisons and a significance level of p<0.05 (relevant comparisons shown).
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Figure 6 summarizes the visual acuity data.
Correlation between the number of prior anti-VEGF injections before dual therapy with the dexamethasone intravitreal implant and an anti-VEGF agent and the change in central foveal thickness after the first combined treatment. A best-fitted linear regression curve and Pearson correlation were determined and demonstrated correlation with Pearson correlation coefficient (r=0.375).
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There was mild-moderate correlation between number of prior anti-VEGF injections and the likelihood of CFT reduction in response to dual therapy (Figure 7) with the Pearson correlation coefficient (r=0.375).
Comparison of the treatment burden before and after dual therapy with the dexamethasone intravitreal implant and anti-VEGF agent. The mean total number of anti-VEGF injections in the 6 months after dual therapy (4.25 injections) was significantly decreased compared to the mean during the 6 months prior to dual therapy (5.33 injections) (p=0.0199). The mean injection-free interval during the 6 months following dual therapy (1.75 months) was significantly longer compared to that seen during the 6 months before dual therapy (1. 13 months) (p=0.0312).
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In addition, dual therapy significantly reduced the number of required anti-VEGF injections after combined injections (Figure 8). The mean total number of injections during the 6 months before dual therapy (5.33) was significantly greater than the total number of injections during the 6 months after dual therapy (4.25) with p=0.0199 (Figure 8A). In addition, the mean treatment-free interval between injections before (1.13 months) was significantly extended to 1.74 months as a result of dual therapy (Figure 8B, p=0.0312).