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PURPOSE To investigate baseline characteristics of patients undergoing additional anti-vascular endothelial growth factor (VEGF) injections for residual or recurrent diabetic macular edema (DME) in the first year after 0.19 mg fluocinolone acetonide (FAc) implant. DESIGN Prospective cohort study METHODS: Ninety-four eyes of 66 patients received FAc implant. Eyes with persistent or recurrent DME were managed with pro-re-nata anti-VEGF agents. Demographic data and medical history were collected at baseline. Best-corrected visual acuity(BCVA) and central macular thickness(CMT) were measured every 2 months. Three outcomes explored:1) risk factors for administration of additional anti-VEGF agents;2) interval from FAc to first anti-VEGF injection;3) number of anti-VEGF doses required to maintain regression of DME. RESULTS Eighteen eyes(19.1%) of 13 patients received 1.3±0.6 anti-VEGF injections. These eyes had significantly thicker CMT at baseline and over entire follow-up(p<0.001); BCVA was similar at every time-point to eyes not receiving extra DME treatments. Eyes without preexistent panretinal photocoagulation(PRP) had higher risk to undergo supplemental treatments(HR:1.5;95%CI:1.1-2.5, p=0.03). The interval between FAc implant and the first anti-VEGF had significant linear positive relationship with the number of dexamethasone implant before FAc implant(p=0.002, R2=0.47).No association was found between baseline factors and the number of injections given. CONCLUSION Anti-VEGF agents are efficient treatment to maintain visual acuity in residual/recurrent DME after FAc. Patients with higher baseline CMT and with no previous PRP are more likely to require additional treatments to control DME.