Impact of silicone oil tamponade on intravitreally injected vancomycin pharmacokinetics in cynomolgus monkey eyes.

Intravitreal injections of vancomycin (VCM) and ceftazidime (CAZ) are commonly used to treat infectious endophthalmitis. When patient cases require retinal detachment with silicone oil (SO) tamponade, the antibiotic doses are empirically reduced to 25 %. Currently, there is no scientific evidence for these empirical dose reductions. The purpose of the present study is to determine the quantitative impact that SO tamponades have on intraocular VCM pharmacokinetics. Because of high invasiveness of frequent sampling of intraocular VCM concentrations in human, this pharmacokinetic study was performed in cynomolgus monkey's eyes. Population pharmacokinetic modeling and simulation were performed using 75 different intraocular VCM concentrations obtained from 8 male cynomolgus monkeys. A one-compartment model with a first-order diffusion rate was used as a structural pharmacokinetic model. From the covariate analysis, SO tamponade significantly decreased the volume of distribution while pars plana vitrectomy with lensectomy (PPV) significantly increased the clearance and diffusion rate constants. From the Monte Carlo simulation (n = 1,000), the median time above minimum inhibitory concentration (T>MIC, a therapeutic effect index) durations of SO and normal eyes at clinical doses of 1,000 µg were 2.6 and 11.0 days, respectively. Using intravitreal injections of VCM with SO tamponade or PPV may reduce the therapeutic effect.

Systemic adverse events after screening of retinopathy of prematurity with mydriatic.

PURPOSE: To evaluate systemic adverse events after screening for retinopathy of prematurity (ROP) performed with mydriatic. METHODS: This was a retrospective case series study. Medical records of consecutive patients who underwent screening for ROP with 0.5% phenylephrine and 0.5% tropicamide eyedrops were retrospectively reviewed. The score of abdominal distention (0-5), volume of milk sucked and volume of stool, along with systemic details (pulse and respiration rates, blood pressure and number of periods of apnea) were collected at 1 week and 1 day before ROP examination, and at 1 day after examination. Results were compared between the days before and after examination. Correlation between body weight at the time of examination and the score of abdominal distention was examined. The numbers of infants with abdominal and/or systemic adverse events were compared between pre- and post-examination periods. RESULTS: Eighty-six infants met the inclusion criteria. The score of abdominal distention increased from 2.0 at 1 day before examination to 2.3 at 1 day after examination (p = 0.005), and the number of infants who had worsened abdominal distension increased after examination (p = 0.01). Infants with lower body weight had a higher score of abdominal distention (p < 0.0001, r = -0.57). The number of infants with reduced milk consumption increased after examination (p = 0.0001), as did the number of infants with decreased pulse rate (p = 0.0008). CONCLUSIONS: Screening for ROP with mydriatic may have adverse effects on systemic conditions. Infants should be carefully monitored after ROP screening with mydriatic.

Pharmacokinetics of Intravitreal Vancomycin and Ceftazidime in Silicone Oil-Filled Macaque Eyes.

Purpose: This study evaluated the pharmacokinetics of intravitreal vancomycin and ceftazidime in the aqueous humor of macaque eyes filled with silicone oil in the vitreous cavity. Methods: Intravitreal vancomycin (1 mg/0.1 mL) and ceftazidime (2 mg/0.1 mL) were injected into four normal macaque eyes, four vitrectomized aphakic macaque eyes, and four previously vitrectomized aphakic macaque eyes filled with silicone oil (silicone oil-filled eyes). Aqueous humor samples (0.1 mL) were obtained just before injection and at 2 and 5 hours and 1, 2, 3, 5, 7, and 10 days after injection. In each group, corneal endothelial cell density (ECD) measurements and electroretinogram (ERG) recordings were obtained before injection and after 1 month. Results: The half-lives of vancomycin in the aqueous humor of normal, vitrectomized, and silicone oil-filled eyes were 29.4, 21.1, and 6.8 hours, respectively, and those of ceftazidime were 20.4, 5.2, and 3.1 hours, respectively. The maximum vancomycin aqueous humor concentrations of normal, vitrectomized, and silicone oil-filled eyes were 151.4, 205.6, and 543.5 µg/mL, respectively, and the maximum ceftazidime aqueous humor concentrations are 64.6, 260.0, and 1176.3 µg/mL, respectively. There was no change in ECD, and ERG was not declined after intravitreal injection in all groups. Conclusions: The half-lives of vancomycin and ceftazidime in the aqueous humor were shorter in silicone oil-filled eyes than in normal and vitrectomized eyes. High antibiotic concentrations in silicone oil-filled eyes seemed to be well tolerated. Translational Relevance: This study aids in estimating how often an antibiotic should be intravitreally injected for endophthalmitis of silicone oil-filled eyes.

Short-Term Changes in Intraocular Pressure After Intravitreal Injection of Bevacizumab for the Treatment of Retinopathy of Prematurity.

PURPOSE: To evaluate short-term changes in intraocular pressure after intravitreal injection of bevacizumab for retinopathy of prematurity. PATIENTS AND METHODS: This study was a prospective case-series. Consecutive infants underwent intravitreal injection with bevacizumab for type 1 retinopathy of prematurity at a university hospital. Intraocular pressure was measured with tonometer at baseline, at 1 min, and at 3, 10, 30 and 60 mins after injection. RESULTS: Five patients (four boys) were enrolled in this study. Mean (± standard deviation) intraocular pressure was 8.0 ± 2.4 mmHg (range: 6-11.5 mmHg) just before the intravitreal injection, and the pressures were 19.8 ± 2.8 mmHg (16.4-23.9 mmHg), 14.6 ± 4.4 mmHg (7.6-18.4 mmHg), 11.2 ± 4.2 mmHg (6.4-16.5 mmHg), 9.3 ± 3.5 mmHg (5.8-13.2 mmHg), and 8.2 ± 1.4 mmHg (6.9-10.0 mmHg) at 1 min, 3, 10, 30 and 60 mins after the injection, respectively. Mean intraocular pressure after 1 min was significantly higher than intraocular pressure before injection (p = 0.02). Pressures decreased between 1 min and 3 mins after intravitreal injection, although there was no statistically significant difference between the pressures at those time-points. Intraocular pressures after 3, 10, 30 and 60 mins were not significantly different from the pressure before injection. CONCLUSION: Intraocular pressure elevation after intravitreal injection of bevacizumab for neonatal infants may be mild, so there may be a limited risk due to intraocular pressure after intraocular injection of bevacizumab for retinopathy of prematurity.