Taichiro Miyake

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.

Subcutaneous inoculation of a whole virus particle vaccine prepared from a non-pathogenic virus library induces protective immunity against H7N7 highly pathogenic avian influenza virus in cynomolgus macaques

Development of H7N7 highly pathogenic avian influenza virus (HPAIV) vaccines is an urgent issue since human cases of infection with this subtype virus have been reported and most humans have no immunity against H7N7 viruses. We made an H7N7 vaccine combining components from an influenza virus library of non-pathogenic type A influenza viruses. Antibody and T cell recall responses specific against the vaccine strain were elicited by subcutaneous inoculation with the whole virus particle vaccine with or without alum as an adjuvant in cynomolgus macaques. No significant difference was observed in magnitude of antibody responses between vaccination with alum and vaccination without alum, though vaccination with alum induced longer recall responses of CD8(+) T cells than did vaccination without alum. After challenge with a subtype of H7N7 HPAIV, the virus was detected in nasal swabs of unvaccinated macaques for 8 days but only for 1 day in the animals vaccinated either with or without alum, although the macaques vaccinated with alum showed elevated body temperature more briefly after infection. These findings demonstrated that this H7N7 HPAIV strain is pathogenic to macaques and that the vaccine conferred protective immunity to macaques against H7N7 HPAIV infection.

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.

Amelioration of pneumonia with Streptococcus pneumoniae infection by inoculation with a vaccine against highly pathogenic avian influenza virus in a non-human primate mixed infection model

Background  Highly pathogenic avian influenza virus (HPAIV) infection has a high mortality rate in humans. Secondary bacterial pneumonia with HPAIV infection has not been reported in human patients, whereas seasonal influenza viruses sometimes enhance bacterial pneumonia, resulting in substantial morbidity and mortality. Therefore, if HPAIV infection were accompanied by bacterial infection, an increase in mortality would be expected. We examined whether a vaccine against HPAIV prevents severe morbidity caused by mixed infection with HPAIV and bacteria.

Comparison of pneumatic displacement for submacular hemorrhages with gas alone and gas plus tissue plasminogen activator.

Purpose: To retrospectively evaluate efficacy, safety, and visual outcomes of pneumatic displacement for submacular hemorrhages (SMHs) with or without tissue plasminogen activator (tPA). Methods: Sixty-eight eyes with fresh SMHs underwent pneumatic displacement. Thirty eyes received intravitreal injection of pure C3F8 gas alone and 38 eyes received gas with tPA (25 &mgr;g). The visual analog scale was used to evaluate displacement. The main outcome measures were the visual analog scale score and best-corrected visual acuity 1 month after treatment. The efficacy and safety of tPA were evaluated. Results: The visual analog scale score was 4.9 ± 2.5 in the gas group and 5.9 ± 2.9 in the gas plus tPA group. Sixteen eyes (53.3%) in the gas group and 15 eyes (39.5%) in the gas plus tPA group had best-corrected visual acuity improvements. In the gas group, complications included retinal detachment (n = 1, 3.3%), vitreous opacity (n = 7, 23.3%), and rebleeding (n = 1, 3.3%). In the gas plus tPA group, vitreous opacity (n = 6, 15.8%) was the only complication. Overall, both groups had similar displacement of SMH, visual improvement, and complication rates at 1 month. Conclusion: Intravitreal injection of pure C3F8 gas displaced SMHs and improved best-corrected visual acuity in eyes with SMHs. No adjuvant effect or adverse reactions of tPA were found.

A simple muscle transposition procedure for abducens palsy without tenotomy or splitting muscles.

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Comparison between One Injection and Three Monthly Injections of Intravitreal Bevacizumab for Myopic Choroidal Neovascularization

Aim: To compare the effects of one intravitreal bevacizumab (IVB) injection with three monthly injections for myopic choroidal neovascularization. Methods: Group A included 13 patients treated with one IVB injection; group B included 19 patients treated with three monthly 1.25-mg IVB injections. All patients were followed monthly for 12 months with additional injections performed as needed. The best-corrected visual acuity (BCVA) and the central foveal thickness (CFT) on optical coherence tomography were evaluated before and after treatment. Results: The mean logMAR BCVA improved from 0.59 to 0.49 at 12 months in group A (p = 0.21) and from 0.65 to 0.29 in group B (p < 0.001); the improved logMAR BCVA differed significantly between the groups (p < 0.05). The mean CFT decreased from 231 µm at baseline to 150 µm at 12 months in group A (p < 0.05) and from 279 to 156 µm in group B (p < 0.001). During the follow-up, 6 of 13 eyes in group A and 5 of 19 eyes in group B received additional injections. Conclusions: Treatment starting with three monthly IVB injections may achieve better functional outcomes with fewer retreatments compared with treatment starting with one IVB injection.

Intranasal administration of a live non-pathogenic avian H5N1 influenza virus from a virus library confers protective immunity against H5N1 highly pathogenic avian influenza virus infection in mice: comparison of formulations and administration routes of vaccines.

Outbreaks of highly pathogenic avian influenza viruses (HPAIVs) would cause disasters worldwide. Various strategies against HPAIVs are required to control damage. It is thought that the use of non-pathogenic avian influenza viruses as live vaccines will be effective in an emergency, even though there might be some adverse effects, because small amounts of live vaccines will confer immunity to protect against HPAIV infection. Therefore, live vaccines have the advantage of being able to be distributed worldwide soon after an outbreak. In the present study, we found that intranasal administration of a live H5N1 subtype non-pathogenic virus induced antibody and cytotoxic T lymphocyte responses and protected mice against H5N1 HPAIV infection. In addition, it was found that a small amount (100 PFU) of the live vaccine was as effective as 100 microg (approximately 10(10-11) PFU of virus particles) of the inactivated whole particle vaccine in mice. Consequently, the use of live virus vaccines might be one strategy for preventing pandemics of HPAIVs in an emergency.

Comparison of single injection and three monthly injections of intravitreal bevacizumab for macular edema associated with branch retinal vein occlusion

Purpose Our aim was to compare the 1 year efficacy and safety results of intravitreal bevacizumab (IVB) in two prospective, consecutive groups of patients with macular edema (ME) following branch retinal vein occlusion (BRVO). Patients and methods Twenty-five eyes with ME after BRVO received one IVB injection (single-injection group) and 27 eyes received three monthly IVB injections (three-injection group). Both groups were followed monthly for 12 months. The best-corrected visual acuity (BCVA) and the central foveal thickness (CFT) on optical coherence tomography were evaluated before and after treatment. Patients were eligible to receive an IVB injection if the mean CFT increased 100 μm or more or the BCVA decreased 0.1 logarithm of the minimum angle of resolution (logMAR) unit or more compared with values measured on the last visit. Results The mean logMAR BCVA and CFT, respectively, improved from 0.56 to 0.33 and from 598 μm to 348 μm in the single-injection group (P<0.001) and from 0.55 to 0.26 and from 514 μm to 293 μm in the three-injection group (P<0.001). During the study period, the mean total number of injections was significantly smaller in the single-injection group than in the three-injection group (2.1 and 4.3, respectively, P<0.001). No serious complications related to the IVB injections developed in either group. Conclusion The single-injection group achieved similar visual outcomes for ME secondary to BRVO with fewer injections compared with the three-injection group.