The Impact of Interval between Recurrence and Reinjection in Anti-VEGF Therapy for Diabetic Macular Edema in Pro Re Nata Regimen

Background: Pro re nata (PRN) regimen using anti-vascular endothelial growth factor (VEGF) agent is popular for the treatment of diabetic macular edema (DME). We investigated the influence of waiting time (WT) and interval between the date of recurrence of edema and re-injection on treatment efficacy. Methods: This retrospective study conducted at 7 sites in Japan enrolled patients who received intravitreal injection of ranibizumab (IVR) and aflibercept (IVA) in 1+PRN regimen. Enrolled patients were divided into 2 groups: prompt group (less than 1 week) and deferred group (3 weeks or more). Central retinal thickness (CRT) and best corrected visual acuity (BCVA) were measured every month for 1 year. Results: CRT in the deferred group was significantly higher than that in the prompt group at 2, 5, 6, 7, and 12 months (p < 0.05). BCVA in the prompt group was significantly better than that in the deferred group at 7, 10, and 12 months (p < 0.05). Conclusion: The prompt group was superior in anatomical and functional improvement of DME in anti-VEGF therapy than the deferred group. Our data suggests that shorter WT is recommended for better visual prognosis in the treatment for DME.

Real-world outcomes of combined therapy of photodynamic therapy with anti-vascular endothelial growth factor for polypoidal choroidal vasculopathy

Objectives To describe the real-world outcomes of photodynamic therapy (PDT) as a rescue therapy in eyes with polypoidal choroidal vasculopathy (PCV) refractory to anti-vascular endothelial growth factor (VEGF) monotherapy in a British cohort of patients. Methods This is a retrospective chart review of 53 eyes with PCV. Based on the timing of PDT, the eyes were stratified into two groups (9 in the Initial-PDT group, 44 in the Deferred group). The number of anti-VEGF injections/year and the best corrected visual acuity (BCVA) before and after PDT were analysed. Multivariate regression model was created to identify factors predictive of visual outcome and treatment burden after PDT. Results The Deferred group received a mean of 9.4 injections/year but significantly reduced to 7.2 after PDT (p < 0.001). The Initial-PDT group required significantly fewer injections after PDT compared to the Deferred group (p = 0.004). The Deferred group experienced improvement in BCVA from 58.7 letters at baseline to 63.8 at 18-months follow-up (p < 0.001), but no significant increase was observed in the Initial-PDT group (p = 0.310). Better baseline BCVA is associated with higher likelihood of achieving good BCVA ≥ 70 letters after PDT (Odd Ratio=1.12, 95% CI: 1.03–1.21, p = 0.006), while increased number of anti-VEGF injections/year before PDT reduces the likelihood of easing treatment burden to ≥12 weeks apart between each injection after PDT (Odd Ratio=0.724, 95% CI: 0.58–0.91, p = 0.006). Conclusions PDT as a rescue therapy is beneficial in the long-term management of PCV, particularly in eyes that had experienced a significant period of prior exposure to anti-VEGF monotherapy.

P5616Risk stratification of cardiovascular events among patients with functionally non-significant coronary stenosis

Introduction Deferral of percutaneous coronary intervention (PCI) of a functionally non-significant stenosis is associated with a favorable long-term clinical prognosis. However, to date, there has been limited evidence to stratify the risk for the development of cardiovascular (CV) adverse events in patients who were deferred of PCI due to a greater fractional flow reserve (FFR) than 0.80 at the target lesion. Purpose We aimed to stratify the risk of CV events in patients with functionally significant and non-significant coronary stenosis. Methods This observational study included 458 patients who were proven angiographically intermediate coronary stenoses and were measured FFR, of whom 298 deferred patients with FFR>0.80 and 160 intervened patients with FFR<0.80. The primary endpoint was the incidence of major adverse cardiac and cerebrovascular events (MACCE) including any death, non-fatal myocardial infarction, hospitalization due to heart failure, ischemic stroke and any unplanned revascularization. ROC curve for MACCE indicated the cut-off point of FFR as 0.85 and 0.76 in deferred patients and intervened patients, respectively. Results During the observation period, 27 MACCE (9.1%) in the Deferred group, and 33 MACCE (20.6%) in Intervened group were occurred. Kaplan-Meier curves showed a higher MACCE rate in the Intervened group than Deferred group (hazard ratio (HR): 2.19, 95% confidence interval (CI): 1.29–3.71, Figure A). However, even among patients in the Deferred group, the population with “intermediate” FFR (0.81–0.85) had a significantly higher MACCE rate than those with higher FFR (>0.85) (HR 2.55, 95% CI 1.14–5.69, Figure B). This rate was comparable to that of the Intervened group at the remote phase (at 4-year: 32.0% vs. 35.8%). Conversely, in the Intervened group, there was no statistically significant difference in MACCE rate between patients with higher FFR (0.76–0.80) and those with lower FFR (<0.76) (Log-rank: p=0.21, Figure C). Conclusion The population with relatively low FFR in patients who were deferred PCI by FFR>0.80 had comparable MACCE rate to patients with FFR<0.80. Close observation after the FFR evaluation should be considered in those population.

Treatment of Diabetic Macular Edema with Intravitreal Antivascular Endothelial Growth Factor and Prompt versus Deferred Focal Laser during Long-Term Follow-Up and Identification of Prognostic Retinal Markers

Purpose. Long-term follow-up of patients with diabetic macular edema (DME) treated with intravitreal antivascular endothelial growth factor (anti-VEGF) combined focal laser and identification of prognostic morphological characteristics. Methods. Prospective clinical trial (50 treatment-naive eyes) with DME randomized 1 : 1 receiving intravitreal ranibizumab (0.5 mg/0.05 ml) and prompt grid laser compared with ranibizumab and deferred laser. Morphological characteristics potentially relevant for prognosis were assessed at baseline, month 6, month 9, and years 1, 2, 3, 4, and 5 of follow-up. Results. Although functional results were slightly higher in the prompt group at week 12 (0.5; 20/40 Snellen (SD = 0.04, 0.3 logMAR) versus 0.4; 20/50 Snellen (SD = 0.04, logMAR: 0.4), p=0.4) and month 9 (prompt group: 0.5; 20/40 Snellen (SD = 0.03, 0.3 logMAR) versus deferred group: 0.4; 20/50 Snellen (SD = 0.04, 0.4 logMAR), p=0.4), these were statistically insignificant. There was no significant benefit regarding functionality during long-term follow-up in the prompt group compared to the deferred group. BCVA in the eyes with clusters of hyperreflective foci in the central macular region was inferior compared with the eyes without these alterations at year 5 (0.39; 20/50 Snellen, (SD = 0.25, 0.4 logMAR) versus 0.63; 20/80 Snellen (SD = 0.22, 0.2 logMAR), p<0.01). Conclusion. Grid laser and ranibizumab therapy are effective in DME management during the long-term follow-up. Intraretinal hyperreflective material in SD-OCT is negatively related to BCVA.