Tomoko Sawada

Pharmacokinetics of bevacizumab and its effect on vascular endothelial growth factor after intravitreal injection of bevacizumab in macaque eyes.

PURPOSE To evaluate the pharmacokinetics of intravitreally injected bevacizumab in the systemic circulation and the aqueous humor and its effect on vascular endothelial growth factor (VEGF) in the aqueous humor. METHODS Bevacizumab (1.25 mg/50 microL) was injected into the vitreous cavity of the right eyes of three cynomolgus macaques. Aqueous humor and serum were obtained from the macaques just before injection and on days 1, 3, and 7 and weeks 2, 4, 6, and 8 after injection. The bevacizumab and VEGF concentrations were measured using enzyme-linked immunosorbent assay. RESULTS Aqueous VEGF concentrations ranged from 63.2 to 106 pg/mL (mean, 80.0 +/- 22.6 pg/mL) before injection; decreased to <31.2 pg/mL, the lower limit of detection, in all eyes between 1 and 28 days after injection; and returned to the preinjection concentration at 42 days. Aqueous VEGF concentrations in the fellow eyes did not change throughout the experiment. Aqueous bevacizumab concentrations in the treated eyes reached a mean peak concentration of 49,500 +/- 10,900 ng/mL the day after injection and gradually declined, whereas those in the untreated eyes peaked at 3 days, with a mean concentration of 18.5 +/- 25.5 ng/mL, and declined to below 0.156 ng/mL, the limit of detection at 2 weeks. A maximum mean bevacizumab concentration of 1430 +/- 186 ng/mL was achieved in the serum 1 week after injection. CONCLUSIONS Intravitreal injection of bevacizumab decreased the VEGF concentration in the treated eyes for at least 4 weeks and had no or a minimal effect on the untreated fellow eyes.

Comparison of macular thickness between Cirrus HD-OCT and Stratus OCT.

BACKGROUND AND OBJECTIVE To compare macular thicknesses in healthy subjects measured with spectral domain optical coherence tomography (SD-OCT) (Cirrus; Carl Zeiss Meditec, Inc., Dublin, CA) with measurements using time domain (TD-OCT) (Stratus; Carl Zeiss Meditec, Inc.). PATIENTS AND METHODS Macular thickness was measured five times in the same eye of 10 healthy subjects with both Cirrus and Stratus to assess reliability and then once in the same eye of 50 healthy subjects with both Cirrus and Stratus to compare the average obtained by each device. RESULTS Using TD-OCT, the coefficient of variations (CV) of the macular thicknesses within a 1-mm central area ranged from 0.7% to 3.3% (mean, 1.33%); with SD-OCT, the range was 0.2% to 1.3% (mean, 0.66%). The mean CV with SD-OCT was significantly smaller than with TD-OCT (P < .05). The average macular thicknesses with TD-OCT and SD-OCT were 197.2 +/- 17.8 microm and 257.6 +/- 19.6 microm, respectively. However, the correlation was significant (correlation coefficient, 0.916, P<.001). CONCLUSION Cirrus showed better reliability than Stratus. Using SD-OCT, the macula was 60-microm thicker than when measured with TD-OCT. Attention should be given to comparing data obtained using different OCT machines.

Effect of vitrectomy on aqueous VEGF concentration and pharmacokinetics of bevacizumab in macaque monkeys.

PURPOSE To evaluate the effect of vitrectomy on the concentration of vascular endothelial growth factor (VEGF) and the pharmacokinetics of intravitreally injected bevacizumab in the aqueous humor in cynomolgus macaques. METHODS Pars plana lensectomy and a standard three-port vitrectomy were performed in one eye each of six macaques. After a minimal 12-week healing period, the vitrectomized eyes received an intravitreal injection of bevacizumab (1.25 mg/50 μL). Aqueous humor and venous blood samples were obtained from the macaques just before vitrectomy, just before injection of bevacizumab, on days 1, 3, and 7, and during weeks 2, 4, 6, and 8 after the injection. The bevacizumab and VEGF concentrations were measured by using enzyme-linked immunosorbent assay. RESULTS The VEGF concentrations in the aqueous humor ranged from 52.6 to 113.9 pg/mL (mean ± standard deviation [SD], 81.7 ± 27.0 pg/mL) before vitrectomy and 20.7 to 72.7 pg/mL (mean ± SD, 51.4 ± 20.5 pg/mL) 3 months after vitrectomy, a difference that reached significance (P = 0.03). The aqueous VEGF concentrations decreased to less than 9.0 pg/mL, the lower limit of detection, in all eyes between 1 and 7 days after injection of bevacizumab. The mean half-life of 1.25 mg intravitreally injected bevacizumab was 1.5 ± 0.6 days (range, 1.0-2.4 days) in the aqueous humor. CONCLUSIONS The VEGF concentration in the aqueous humor decreased and the half-life of the intravitreally injected bevacizumab was shorter in vitrectomized eyes.

Serum and Plasma Vascular Endothelial Growth Factor Concentrations Before and After Intravitreal Injection of Aflibercept or Ranibizumab for Age-Related Macular Degeneration

PURPOSE To evaluate serum and plasma vascular endothelial growth factor (VEGF) concentrations in neovascular age-related macular degeneration patients treated bimonthly with an intravitreal injection of aflibercept or ranibizumab. DESIGN Prospective, interventional case series. METHODS This study includes 17 eyes of 17 patients treated with 2 mg aflibercept (the aflibercept group), 15 eyes of 15 patients treated with 0.5 mg ranibizumab (the ranibizumab group), and 12 patients with cataract (the control group). Serum and plasma VEGF concentrations were quantified using the enzyme-linked immunosorbent assay. RESULTS At baseline, mean serum VEGF concentration (in picograms per milliliter) did not differ significantly among the 3 groups (P = .99). In the aflibercept group, it was 28.3 pg/mL at baseline, decreased to below the detectable limit at 1 week (P < .0001), increased to 11.7 pg/mL at 1 month, which was still significantly less than the baseline level (P < .001), and returned to 23.9 pg/mL (P = .35) at 2 months. In the ranibizumab group, there were no significant differences. At baseline, mean plasma VEGF concentration did not differ significantly among the 3 groups (P = .64). In the aflibercept group, it was 16.2 at baseline, decreased to less than the detectable limit at 1 week (P < .01) and at 1 month (P < .05), and returned to 13.6 pg/mL at 2 months (P = .73). In the ranibizumab group, there were no significant differences. CONCLUSIONS Aflibercept significantly decreased serum and plasma VEGF concentrations 1 month after injection; however, ranibizumab had no significant effect on either serum or plasma VEGF level.

Ranibizumab and Aflibercept: Intraocular Pharmacokinetics and Their Effects on Aqueous VEGF Level in Vitrectomized and Nonvitrectomized Macaque Eyes.

PURPOSE We evaluated the pharmacokinetics of intravitreally injected ranibizumab and aflibercept, and their effects on VEGF in the aqueous humor of vitrectomized and nonvitrectomized macaque eyes. METHODS Intravitreal ranibizumab (IVR; 0.5 mg/50 μL) or intravitreal aflibercept (IVA; 2 mg/50 μL) was injected into the previously vitrectomized right eyes of three macaques and nonvitrectomized right eyes of three macaques. The left eyes served as controls (nonvitrectomized, noninjected). Aqueous humor was obtained from both eyes just before injection and on days 1 and 3, and weeks 1 to 8 after IVR and IVA. The ranibizumab, aflibercept, and VEGF concentrations were measured using enzyme-linked immunosorbent assays. RESULTS The half-lives in aqueous humor of nonvitrectomized and vitrectomized eyes were, respectively, 2.3 and 1.4 days for ranibizumab, and 2.2 and 1.5 days for aflibercept. Concentration of VEGF was decreased below the limit of detection (LOD) by IVR for 3 weeks in nonvitrectomized eyes and 1 week in vitrectomized eyes, respectively, and by IVA for 6 weeks in nonvitrectomized eyes and 4 weeks in vitrectomized eyes, respectively. In the untreated control eyes, the ranibizumab and aflibercept concentrations were below the LOD, and the VEGF aqueous concentrations remained unchanged after IVR and decreased for 3 days after IVA. CONCLUSIONS Intravitreally injected ranibizumab and aflibercept have similar half-lives in aqueous humor and shorter half-lives in vitrectomized eyes. Compared to IVR, IVA suppresses VEGF level for a longer time period.

Prospective comparisons of intravitreal injections of triamcinolone acetonide and bevacizumab for macular oedema due to branch retinal vein occlusion

Purpose:  To compare the efficacy of intravitreal injections of triamcinolone acetonide (TA) and that of bevacizumab for macular oedema because of branch retinal vein occlusion (BRVO).

Scleral imbrication combined with vitrectomy and gas tamponade for refractory macular hole retinal detachment associated with high myopia.

Purpose: To evaluate scleral imbrication with vitrectomy and gas tamponade for refractory macular hole retinal detachment associated with high myopia. Methods: We retrospectively reviewed the medical records of eight eyes with macular hole retinal detachment and high myopia treated with temporal scleral imbrication, pars plana vitrectomy, and gas tamponade for refractory macular hole retinal detachment with history of pars plana vitrectomy. Retinal reattachment and macular hole closure were assessed. Postoperative changes in axial length and surgically induced astigmatism were evaluated. Results: The retinas were reattached in all eyes and the macular holes closed in 6 (75%) eyes. The mean baseline logarithm of the minimum angle of resolution best-corrected visual acuity of 1.43 ± 0.48 significantly (P < 0.01) improved to 0.87 ± 0.34 at the final visit (889 ± 173 postoperative days). The mean baseline axial length of 29.5 ± 1.3 mm decreased significantly (P < 0.01) to 27.1 ± 1.9 mm 1 month after scleral imbrication and 28.1 ± 1.7 mm at the final visit (P < 0.05 vs. baseline, P = 0.13 vs. 1 month). The mean 1-month surgically induced astigmatism of 3.6 ± 1.4 diopters (D) after scleral imbrication significantly (P < 0.05) decreased to 2.4 ± 1.5 D at the final visit. Conclusion: Scleral imbrication with vitrectomy and gas tamponade resulted in high reattachment and macular hole closure rates for treating refractory macular hole retinal detachment.

Vascular endothelial growth factor in the aqueous humour in eyes with myopic choroidal neovascularization

Purpose:  To determine the concentration of vascular endothelial growth factor (VEGF) in the aqueous humour of eyes with myopic choroidal neovascularization (mCNV).

Negative correlation between aqueous vascular endothelial growth factor levels and axial length.

PurposeThe aim of this study was to evaluate the relationship between the concentrations of vascular endothelial growth factor (VEGF) in the aqueous humor and axial length.MethodsAqueous humor samples were obtained from 60 eyes of 60 patients without ocular diseases other than cataracts. No patients with diabetes mellitus were included. The VEGF concentration in the aqueous humor was measured using an enzyme-linked immunosorbent assay.ResultsThe VEGF concentrations in the aqueous humor samples ranged from 25 to 241 pg/ml [mean ± standard deviation (SD), 116.6 ± 46.7 pg/ml]. The axial lengths ranged from 20.98 to 31.95 mm (mean ± SD, 24.09 ± 2.06 mm). The VEGF concentrations in the aqueous humor samples were correlated with axial length (Pearson product moment correlation test, ρ = −0.373; P = 0.003).ConclusionsThe concentration of VEGF in the aqueous humor is negatively correlated with axial length.

Aqueous vascular endothelial growth factor after intravitreal injection of pegaptanib or ranibizumab in patients with age-related macular degeneration.

Purpose: The purpose of this study was to evaluate vascular endothelial growth factor (VEGF) concentrations in the aqueous humor of eyes after intravitreal injections of pegaptanib or ranibizumab in patients with age-related macular degeneration. Methods: Aqueous humor samples were obtained from 16 eyes with choroidal neo-vascularization secondary to age-related macular degeneration before and after intravitreal injections of pegaptanib (0.3 mg; 5 eyes) and ranibizumab (0.5 mg; 11 eyes). The VEGF concentration was measured using an enzyme-linked immunosorbent assay using a primary antibody against VEGF121 and VEGF165. Results: The VEGF concentrations in the aqueous humor of eyes with age-related macular degeneration ranged from 35.3 pg/mL to 142.4 pg/mL (mean ± standard deviation, 90.9 pg/mL ± 40.0 pg/mL) before the injection of pegaptanib and increased significantly, ranging from 298.2 pg/mL to 571.3 pg/mL (mean ± standard deviation, 452.0 pg/mL ± 106.4 pg/mL) 6 weeks after the injection (P = 0.005). The VEGF concentrations ranged from 47.2 pg/mL to 307.4 pg/mL (mean ± standard deviation, 125.9 pg/mL ± 77.2 pg/mL) before injection of ranibizumab and decreased to <31 pg/mL, the lower limit of detection, 4 weeks after injection. Conclusion: The VEGF concentrations in the aqueous humor of eyes with age-related macular degeneration decreased after injections of ranibizumab and increased after injections of pegaptanib.