JW Seo and IW Park. INTRAVITREAL BEVACIZUMAB FOR TREATMENT OF DME with pegaptanib had better visual acuity outcomes, were more likely to have reduction in central retinal thickness, and were less likely to need additional photocoagulation therapy at follow-up.12 In light of this information, intravitreal beva- cizumab injection is expected to have good efficacy in the treatment of DME. Recently, Haritoglou et al.28 published a prospective, noncomparative case series of patients with DME treated with 1.25 mg bevacizumab. There was a significant reduction in macular thickness at 2 weeks (p=0.002) and although mean visual acuity improved significantly at 6 weeks (p=0.02), this was not sustained at 12 weeks. In the present investigation, however, we found that significant improvement in both visual acuity and retinal thickness was achieved soon after intra- vitreal bevacizumab injection, and the beneficial effects lasted for 3 months. The mean BCVA improved from 0.73±0.36 logMAR at baseline to 0.63±0.41 logMAR at 1- week follow-up (p=0.02), and the mean central retinal thickness as measured by OCT also decreased significantly from 498.96±123.99 µm at baseline to 359.06±105.97 µm at 1-week follow-up (p<0.001). At 1 month after the injection of bevacizumab, this beneficial effect on BCVA and central retinal thickness appeared to be most prominent in the current study. Thirteen (43%) of 30 eyes showed an improve- ment in BCVA by 2 or more lines, and only 1 eye (3%) decreased ≥2 lines on BCVA at 1-month follow-up. In addition, the central retinal thickness showed a considerable reduction (33%): from 498.96±123.99 µm at baseline to 334.40±121.76 µm at 1 month. Although the duration of action of intravitreal bevacizumab is unknown, recent electro- physiologic and retinal penetration studies have reported that full thickness retinal penetration is present at 24 hours.24 This may explain the earlier clinical effects of intravitreal bevaci- zumab observed in the current study. A recent report from the Pan-American Collaborative Retina Study Group showed a significant decrease of DME one month after intravitreal injection of bevacizumab, and those decreased levels were kept for up to six months.29 In our study, the reduction of central retinal thickness and the improvement of BCVA were observed at 1 week, and these results were maintained for up to 3 months. However, at 3-month follow-up, a slight decrease in visual acuity and an increase in retinal thickness were observed as compared with the 1-month follow-up. The central retinal thickness increased significantly from 334.40±121.76 µm at 1 month to 421.40± 192.76 µm at 3 months (p=0.044). This slight reduction in the improvement of visual acuity and central retinal thickness at 3-month follow-up suggests that repeated intravitreal beva- cizumab injections may be necessary within 3 months to maintain a beneficial effect. In this study, 6 (20%) of 30 eyes received the second injection at a mean of 3.8 months. Re-treatment was done only in cases of BCVA deterioration and increased macular edema on OCT. It is possible that a different dosing schedule, such as a series of injections every 3 months for an extended period, may be superior to the method used in this study. However, we chose to re-treat the recurrent cases only, because data concerning toxicity and duration of action of intravitreal bevacizumab were not sufficient at the beginning of the study. The breakdown of endothelial tight junctions and loss of the blood-retina barrier that lead to DME can be associated with both nonproliferative diabetic retinopathy and PDR. The present study demonstrates a comparable population of PDR and NPDR patients with macular edema. The results of the present study indicate that intravitreal bevacizumab in- jections may have a beneficial effect on retinal thickness and visual acuity, independent of the type of diabetic retinopathy. In addition, previous treatments, such as focal laser treatment, panretinal photocoagulation, or IVTA injection, did not influence the results of the study, except in the case of previous vitrectomy. Previously vitrectomized eyes showed no increase in visual acuity, and this finding is consistent with a previous study that found there was no change in BCVA or foveal thickness after intravitreal bevacizumab injection for DME in previously vitrectomized eyes.30 This outcome may be attributable to rapid clearance of intravitreal bevacizumab and insufficient sustained therapeutic levels in vitrectomized eyes. Further studies are warranted due to the relatively small number of participants in this study. In conclusion, intravitreal bevacizumab injection appears to result in significant improvement in BCVA and reduction in central retinal thickness as early as 1 week after injection, and this beneficial effect was shown to persist for up to 3 months. However, the slight reduction in improvement in visual acuity and central retinal thickness at 3-month follow- up suggests that repeated bevacizumab injections might be necessary within 3 months to maintain its effect, as the drug is well tolerated and there are no safety concerns. To evaluate the long-term safety and efficacy of this new treatment, further prospective randomized controlled clinical trials will be needed, with scheduled re-injection and longer follow-up. References 1. Ferris FL 3rd, Patz A. Macular edema: a complication of diabetic retinopathy. Surv Ophthalmol 1984;28:452-61. 2. Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 1. Early Treatment Diabetic Retinopathy Study Research Group. Arch Ophthalmol 1985;103:1796-806. 3. Jonas JB, Kreissig I, Sofker A, Degenring RF. Intravitreal injection of triamcinolone for diffuse diabetic macular edema. Arch Ophthalmol 2003;121:57-61. 4. Martidis A, Duker JS, Greenberg PB, et al. Intravitreal triamcinolone for refractory diabetic macular edema. Am J Ophthalmol 2002;109:920-7. 5. Jonas JB, Kreissig I, Degenring RF. Intraocular pressure after intravitreal injection of triamcinolone acetonide. Br J Ophthalmol 2003;87:24-7. 6. Patelli F, Fasolino G, Radice P, et al. Time course of changes in retinal thickness and visual acuity after intravitreal triamcinolone acetonide for diffuse diabetic macular edema with and without previous macular laser treatment. Retina 2005;26:840-5. 21