Early Conversion to Aflibercept for Persistent Diabetic Macular Edema Results in Better Visual Outcomes and Lower Treatment Costs.

PURPOSE: To evaluate the functional and anatomic outcomes, as well as cost-effectiveness, of the timing of conversion to intravitreal aflibercept (IVA) in patients with treatment-resistant diabetic macular edema (DME). METHODS: Thirty consecutive eyes (25 patients) were identified that were treated with ≥3 intravitreal bevacizumab (IVB) and/or ranibizumab (IVR) injections prior to treatment with ≥3 IVA injections. Eyes that received ≤6 IVB and/or IVR injections (early-switch) were compared to those that received ≥7 injections (late-switch) prior to conversion to IVA. Treatment effectiveness was measured in quality-adjusted life years (QALYs). A micro-simulation model examined the impact of treatment duration on outcomes. RESULTS: Early- (n=18) and late- (n=12) switch eyes had similar vision prior to conversion to IVA. Despite improvements in retinal thickness, only the early-switch eyes maintained vision gains after conversion to IVA through the end of follow-up (p=0.027). Early switch saved $22,884/eye and produced an additional 0.027 QALYs. CONCLUSION: Early conversion to IVA optimizes vision outcomes and results in lower overall treatment expenditures.

Changes in flare after intravitreal injection of three different anti-vascular endothelial growth factor medications.

PURPOSE: To compare the change in anterior chamber flare after intravitreal injection of the anti-vascular endothelial growth factor agents bevacizumab, aflibercept, and ranibizumab. METHODS: Sixty-one eyes of 53 patients underwent intravitreal injection with anti-vascular endothelial growth factor medications for exudative age-related macular degeneration, diabetic macular edema, or retinal vein occlusion. There were a total of 26 eyes injected with bevacizumab, 14 eyes injected with aflibercept, and 21 eyes injected with ranibizumab. Anterior segment flare was measured with a laser flare meter (Kowa) before intravitreal injection and 1 day after injection. The change in flare was analyzed. RESULTS: The mean change in flare after 1 day was +2.5 photons per millisecond in patients who received bevacizumab, 0.0 photons per millisecond for aflibercept, and -0.2 photons per millisecond for ranibizumab. There was a statistically significant difference between the 3 medications (P = 0.006). Pairwise analysis of the change in flare showed a statistically significant difference between bevacizumab and ranibizumab (P = 0.002). The change in flare in patients who received aflibercept was not different from that in those who received bevacizumab (P = 0.08) or ranibizumab (P = 0.99). CONCLUSION: There was a statistically significant increase in flare after bevacizumab injection compared with ranibizumab. This difference was small and is not believed to be clinically significant. There was no statistical difference in the change in flare between aflibercept and the other medications, although the number of eyes in the aflibercept group was small.

Randomized trial of anesthetic methods for intravitreal injections.

PURPOSE: To compare the effectiveness of four different anesthetic methods for intravitreal injection. METHODS: Twenty-four patients each received four intravitreal injections using each of four types of anesthesia (proparacaine, tetracaine, lidocaine pledget, and subconjunctival injection of lidocaine) in a prospective, masked, randomized block design. Pain was graded by the patient on a 0 to 10 scale for both the anesthesia and the injection. RESULTS: The average combined pain scores for both the anesthesia and the intravitreal injection were 4.4 for the lidocaine pledget, 3.5 for topical proparacaine, 3.8 for the subconjunctival lidocaine injection, and 4.1 for topical tetracaine. The differences were not significant (P = 0.65). There were also no statistical differences in the individual anesthesia or injection pain scores. Subconjunctival lidocaine injection had the most side effects. CONCLUSION: Topical anesthesia is an effective method for limiting pain associated with intravitreal injections.

Potential future targets for treating ocular neovascularization.

A wide variety of mediators likely contribute to ocular NV and these can serve as potential targets for the treatment of ocular NV. Several targets have already been validated in preclinical models and are being explored in clinical studies. In addition, targeting other processes besides angiogenesis, such as inflammation and apoptosis, may be beneficial in the treatment of ocular NV. Combined approaches with the use of several angiogenesis inhibitors or anti-inflammatory agents may show synergistic effects in treating ocular NV.