We appreciate the comment of Fingerhut and associates regarding our study of photodynamic therapy (PDT) with or without intravitreal bevacizumab for polypoidal choroidal vasculopathy (PCV). They raise the question of the timing of the intravitreal bevacizumab injection in the combination therapy for PCV. We address this issue herein.
Combination therapy of PDT and anti–vascular endothelial growth factor drugs is one of the treatment choices of PCV. Several studies have shown that combination therapy results in favorable visual and anatomic outcomes in patients with PCV. However, currently there is no consensus regarding the intervention regimen of the sequence of PDT and intravitreal anti–vascular endothelial growth factor drug injection either for age-related macular degeneration or PCV. Intravitreal injection could be carried out before, on the same day of, and even after PDT. Kaiser and associates reported the results of combination intravitreal bevacizumab and PDT in 1196 patients with age-related macular degeneration. In their study, the treatment regimens were divided into 3 groups—treatment at same day, PDT first, and bevacizumab injection first—and there were no significant differences in the visual outcomes among the groups. Furthermore, the intervals between PDT and intravitreal anti–vascular endothelial growth factor drug injection are still controversial. Sawa and associates compared the different treatment intervals between bevacizumab injection and PDT combination therapy in 184 patients with exudative macular degeneration in 100 eyes (54%) with age-related macular degeneration and 84 eyes (46%) with PCV. Their 1-year results demonstrated that the 7-day treatment interval between bevacizumab injection the PDT had better visual acuity gain than a 1-day interval. Fingerhut and associates contend that the half-life of bevacizumab in nonvitrectomized eyes is only 4.32 days and that 1 week between the 2 treatments may result in too much bevacizumab being wash out and a decrease in treatment effect. However, in the study by Bakri and associates, a peak concentration of 400 μg/mL was achieved in the vitreous 1 day after intravitreal injection of 1.25 mg bevacizumab, the vitreous concentration of bevacizumab declined in a monoexponential fashion, and concentrations of more than 10 μg/mL bevacizumab could be maintained in the vitreous even after 30 days. In a monkey eye study, Heiduschka and associates found that even after 14 days after intravitreal injection, positive staining of bevacizumab could be detected in the outer segment of the photoreceptor and choroidal vessels. These data indicate that after a single intravitreal injection of bevacizumab, the anti-VEGF effect could last more than 1 week.
The purpose of our study was to compare the long-term effect of PDT with or without intravitreal bevacizumab for patients with PCV. However, other factors, including initial visual acuity, lesion size, and location of lesion, are more significant than treatment method in influencing the long-term outcomes. We agree with the suggestion of Fingerhut and associates that further investigation into the timing sequence of the combination therapy is needed to optimize the efficacy in treating PCV.