Intraocular pharmacokinetics of intravitreal vascular endothelial growth factor-Trap in a rabbit model.

PURPOSE: To determine intraocular pharmacokinetic properties of intravitreally injected vascular endothelial growth factor (VEGF)-Trap in a rabbit model. METHODS: VEGF-Trap was intravitreally injected in 18 rabbit eyes. Eyes were enucleated 1 h and 1, 2, 5, 14, and 30 days after injections and immediately frozen at -80 °C. Concentration of VEGF-Trap in vitreous, aqueous humor, and retina/choroid was determined using an indirect enzyme-linked immunosorbent assay and analyzed to obtain pharmacokinetic properties. RESULTS: Maximum concentration of VEGF-Trap was achieved at 1 h in all three tissues. A one-compartment model of distribution was selected as the final model for all tissues studied. Estimated half-life of VEGF-Trap in vitreous, aqueous humor, and retinal/choroid was 87.1, 36.8, and 35.0 h, respectively, and estimated mean residence time was 125.7, 53.1, and 50.5 h, respectively. Area under the curve from time 0 to the end point was 10009.8, 3945.1, and 1189.3, respectively. Total exposure of the aqueous humor and retina/choroid to VEGF-Trap was 39.4% and 11.9% of vitreous exposure, respectively. CONCLUSION: The vitreous half-life of VEGF-Trap is 3.63 days. This is shorter than that of bevacizumab (6.99 days) and longer than that of ranibizumab (2.51 days), as shown in studies using the same experimental settings. The concentration of VEGF-Trap peaked at 1 h after injections in all eye tissues studied.

Visual and anatomic outcomes of golf ball-related ocular injuries.

AIMS: To investigate the characteristics and prognoses of golf ball-related ocular injuries (GROIs) using standardized terminology, classification, and scoring systems. METHODS: Twenty-two GROI patients were assessed using the Birmingham Eye Trauma Terminology, Ocular Trauma Classification Group (OTCG) classification, and Ocular Trauma Score. Globe preservation and final visual acuity (FVA) were assessed according to the injury severity categorical designation. RESULTS: Fourteen patients were injured on golf courses and eight on driving ranges. Nine patients (40.9%) had open-globe injuries (five ruptures (22.7%), four penetrating injuries (18.2%)). All rupture cases required enucleation, whereas penetrating injury cases did not (the FVA ranged from 20/100 to no light perception). In open-globe injuries, wearing glasses protected against rupture (P=0.008). Thirteen patients sustained closed-globe injuries that were accompanied by lens subluxation (38.5%), choroidal rupture (30.8%), macular commotio retinae (38.5%), and traumatic optic neuropathy (7.7%). Twelve (54.5%) patients had orbital wall fractures. The mean number of related surgeries required was 1.5±1.7 across all patients. CONCLUSION: Eyes with GROIs had devastating FVA and globe preservation status, especially those with open-globe injuries. Observing golf rules and improving driving-range facilities are essential for preventing GROIs. Protective eyewear may reduce ocular damage from GROIs, especially globe rupture.

Comparison of postoperative intraocular pressure changes between 23-gauge transconjunctival sutureless vitrectomy and conventional 20-gauge vitrectomy.

PURPOSE: To compare the intraocular pressure (IOP) after 23-gauge transconjunctival sutureless vitrectomy (TSV) and conventional 20-gauge vitrectomy for various vitreoretinal diseases. METHODS: This was a retrospective interventional case series including 338 cases of 23-gauge TSV and 476 cases of 20-gauge vitrectomy with minimum follow-up period of 1 month. Postoperative 1 day, 1 week and 1 month IOPs were compared. Multiple regression analysis to assess the actual effect of gauge of vitrectomy on postoperative IOP was performed including intraoperative and postoperative factors influencing postoperative IOP as covariates. RESULTS: The mean IOP of 20-gauge vitrectomy was significantly higher than that of 23-gauge TSV (20.6 ± 8.02 mm Hg vs 12.8 ± 4.48 mm Hg, P<0.001) at postoperative day 1, but the differences were not significant at postoperative 1 week and 1 month. The IOP pattern of 23-gauge TSV demonstrated more stable course than that of 20-gauge vitrectomy. At 1 day post vitrectomy, the incidence of hypertony was higher in 20-gauge, whereas that of hypotony was higher in 23-gauge. Among risk factors, the 20-gauge vitrectomy showed the strongest association with postoperative 1 day IOP rise. CONCLUSION: Twenty-three-gauge TSV has stable and lower IOP in the early postoperative period than the 20-gauge vitrectomy. In patients whose retina and optic nerves are vulnerable to higher or fluctuating IOP, 23-gauge TSV may be more beneficial.

A co-twin study of the relative effect of birth weight and gestational age on retinopathy of prematurity.

PURPOSE: To determine the relative effect of birth weight and gestational age on retinopathy of prematurity (ROP) using preterm twin pairs discordant for birth weight. METHODS: This study was a retrospective cohort study including 55 consecutive twin pairs of 110 preterm infants (gestational age ≤33 weeks). The outcomes of ROP including occurrence (any stage), severe ROP (stage 3 or more), and clinically significant ROP requiring laser treatment were compared between twins with the lower birth weight from each pair and their co-twins with the higher birth weight. Using twin pairs having different birth weight and identical gestational age, the independent effects of prematurity and intrauterine growth on ROP could be evaluated. Other perinatal morbidities related to prematurity were also compared between twin pairs. RESULTS: No significant differences in ROP between larger and smaller infants were observed in the twin-paired analysis while analysis on individual infants showed strong association between small birth weight and ROP outcomes. However, in both the larger and smaller infant groups, gestational age of <28 weeks was significantly associated with ROP outcomes. No differences were found between twin pairs regarding other perinatal morbidities including bronchopulmonary dysplasia, respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage, and periventricular leukomalacia. CONCLUSIONS: Birth weight is not associated with ROP, while gestational age is in the twin-paired study, suggesting that gestational age is a better predictor of ROP than birth weight. This indicates that maturity is more important in the pathogenesis of ROP than intrauterine growth.

Surgically induced astigmatism after 23-gauge transconjunctival sutureless vitrectomy.

PURPOSE: To evaluate surgically induced astigmatism (SIA) after 23-gauge transconjunctival sutureless vitrectomy (23GTSV). METHODS: We studied 56 patients (56 eyes) who underwent 23GTSV between January 2006 and December 2007 and who underwent preoperative and 1- and 3-4-months postoperative corneal topography. Fifteen of the 56 patients underwent combined 23GTSV and cataract surgery. SIA was evaluated with Naeser's polar method using the simulated keratometric values obtained with corneal topography. Preoperative and postoperative KP and DeltaKP values were compared in the 23GTSV only group and the combined 23GTSV and cataract surgery group. RESULTS: There were no significant serial changes between the preoperative and postoperative Sim K astigmatism or KP values in the 23GTSV only group. In the 23GTSV only group, the DeltaKP (90) was negative (-0.10+/-0.78) at 1 month postoperatively, but it became positive (0.13+/-0.85) at 3-4 months postoperatively. The DeltaKP (135) showed serially decreasing negative values, -0.02+/-0.80 at 1 month postoperatively and -0.08+/-0.60 at 3-4 months postoperatively. In the combined cataract surgery group, the 1- and 3-4-month postoperative DeltaKP (135) values were -0.64+/-0.50 and -0.71+/-0.48, respectively, which represented a significant decrease compared with the 23GTSV only group (P<0.001, Mann-Whitney U-test). Although statistically insignificant, the DeltaKP (135) value was more negative in the sclerotomy-sutured group (n=6) than the sclerotomy non-sutured group (n=35) at 1 month postoperatively (-0.67+/-1.19 vs 0.09+/-0.67, P=0.110, Mann-Whitney U-test). CONCLUSION: The 23GTSV does not induce significant SIA in the early postoperative period.

Serratia marcescens endophthalmitis associated with intravitreal injections of bevacizumab.

PURPOSE: To report two cases of Serratia marcescens endophthalmitis related to presumed aliquot drug contamination, and to determine the incidence of acute endophthalmitis after intravitreal injection of bevacizumab. METHODS: A retrospective chart review of 2020 consecutive intravitreal bevacizumab injection (IVBI) cases at the three affiliated hospitals of Seoul National University (A, B, and C) was carried out between 12 October 2006, and 31 January 2008. Bevacizumab was retrieved multiple times from a single original vial as needed and then discarded on the same day at hospital A and C, or prepared as a single dose aliquot vial at a compounding pharmacy in the hospital B. RESULTS: The incidence of endophthalmitis after IVBI was 2/2020 (0.099%). Two patients receiving IVBI on the same day, but by different surgeons in different sites in hospital B, developed acute endophthalmitis. S. marcescens was isolated from the vitreous sample of the two patients. Molecular typing with pulsed field gel electrophoresis showed that the organisms were of the same strain, which suggested that the drug was contaminated at the pharmacy. CONCLUSIONS: Endophthalmitis is a rare complication after IVBI and can be caused by contaminated aliquot drug. Serratia is one of the causative organisms of acute endophthalmitis, which can have devastating consequences, despite the treatment. A compounding pharmacy in a hospital might not be able to guarantee that aliquoted drug is free of contamination for the IVBI.

Investigation of the association between 677C>T and 1298A>C 5,10-methylenetetra- hydrofolate reductase gene polymorphisms and normal-tension glaucoma.

PURPOSE: Homozygous polymorphism of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and resultant hyperhomocysteinaemia have been established as an independent risk factor for vascular diseases. There are evidences that vascular abnormalities are involved in the pathogenesis and progression of normal-tension glaucoma (NTG). In the present study, we were to find out the associations between 677C>T and 1298A>C polymorphisms of the MTHFR gene and NTG. METHODS: This was a retrospective, case-controlled study enrolling 78 NTG patients and 100 controls. DNA from peripheral blood lymphocytes was extracted and the genotypes of polymorphisms (677C>T and 1298A>C) in the MTHFR gene were determined using PCR followed by restriction enzyme digestion. The frequencies of the polymorphic genotypes in the patients with NTG and controls were compared. RESULTS: The frequencies of the polymorphisms of the MTHFR gene (677C>T and 1298A>C) in the NTG patients were not significantly different from those of controls. But the younger NTG patients (age at diagnosis < or = 45 years) showed significantly higher prevalence of 677C>T polymorphism than the older NTG patients (age at diagnosis > 45 years) (TT genotype, 38.9 vs 11.9%, P=0.006, OR=4.71, 95% CI=1.49-14.9) and than the younger control subgroup (TT genotype, 38.9 vs 6.1%, P=0.001, OR=9.86, 95% CI=2.23-42.4). CONCLUSIONS: The 677C>T polymorphism was significantly associated with NTG in the younger patients, while 1298A>C polymorphism was not. This suggests that 677C>T polymorphism of the MTHFR gene can be a genetic risk factor of NTG in Korean population.

Phases of atom-molecule vortex matter.

We study ground state vortex configurations in a rotating atom-molecule Bose-Einstein condensate. It is found that the coherent coupling between the atomic and molecular condensates can render a pairing of atomic and molecular vortices into a composite structure that resembles a carbon dioxide molecule. Structural phase transitions of vortex lattices are also explored through different physical parameters including the rotational frequency of the system.

A suprachoroidal electrical retinal stimulator design for long-term animal experiments and in vivo assessment of its feasibility and biocompatibility in rabbits.

This article reports on a retinal stimulation system for long-term use in animal electrical stimulation experiments. The presented system consisted of an implantable stimulator which provided continuous electrical stimulation, and an external component which provided preset stimulation patterns and power to the implanted stimulator via a paired radio frequency (RF) coil. A rechargeable internal battery and a parameter memory component were introduced to the implanted retinal stimulator. As a result, the external component was not necessary during the stimulation mode. The inductive coil pair was used to pass the parameter data and to recharge the battery. A switch circuit was used to separate the stimulation mode from the battery recharging mode. The implantable stimulator was implemented with IC chips and the electronics, except for the stimulation electrodes, were hermetically packaged in a biocompatible metal case. A polyimide-based gold electrode array was used. Surgical implantation into rabbits was performed to verify the functionality and safety of this newly designed system. The electrodes were implanted in the suprachoroidal space. Evoked cortical potentials were recorded during electrical stimulation of the retina. Long-term follow-up using OCT showed no chorioretinal abnormality after implantation of the electrodes.

Clinical characteristics of cyclodeviation.

PURPOSE: To retrospectively evaluate the incidence of cyclodeviation among patients with diplopia and analyse the causative diseases and clinical manifestations of cyclodeviation. METHODS: The medical records of 266 consecutive patients of 15 years of age or older presenting with diplopia, who had undergone the Lancaster red-green test (LRGT) from January 2001 to December 2002, were retrospectively reviewed. The presence of cyclodeviation on LRGT, predisposing conditions, causative diseases, and clinical manifestations of cyclotropia were analysed. Cyclodeviation on the LRGT were compared with those from the Maddox double-rod test (MDRT) and fundus photography. RESULTS: A total of 63 (24%) out of 266 patients exhibited cyclodeviation on LRGT. Eight out of 63 patients with cyclodeviation on the LRGT complained of torsional diplopia. Superior oblique palsy (SOP) was the most common causative disease (42 patients), followed by skew deviation (six) and thyroid orbitopathy (three). Excyclodeviation was found in 57 patients and incyclodeviation in four patients on the LRGT. The spontaneous recovery rate was 83% in patients of vascular origin and 17% of traumatic origin. Cyclodeviation with the MDRT and fundus photography showed good correlation with those obtained from the LRGT. There was no association of the amount of cyclotropia with the presence of torsional diplopia as well as with its recovery. CONCLUSION: In spite of the rare complaint of torsional diplopia, 24% of the patients with diplopia showed cyclodeviation on the LRGT. SOP was the most common causative disease. Most of the patients with cyclodeviation of a vascular origin showed spontaneous improvement.

Excitation spectroscopy of vortex lattices in a rotating Bose-Einstein condensate.

Excitation spectroscopy of vortex lattices in rotating Bose-Einstein condensates is described. We numerically obtain the Bogoliubov-de Gennes quasiparticle excitations for a broad range of energies and analyze them in the context of the complex dynamics of the system. Our work is carried out in a regime in which standard hydrodynamic assumptions do not hold, and includes features not readily contained within existing treatments.

Tkachenko waves in rapidly rotating Bose-Einstein condensates.

We present a mean-field theory numerical study of Tkachenko waves of a vortex lattice in trapped atomic Bose-Einstein condenstates. Our results show remarkable qualitative and quantitative agreement with recent experiments at the Joint Institute for Laboratory Astrophysics. We extend our calculations beyond the conditions of the experiment, probing deeper into the incompressible regime where we find excellent agreement with analytical results. In addition, bulk excitations observed in the experiment are discussed.

Comparison of localised nerve fibre layer defects in normal tension glaucoma and primary open angle glaucoma.

AIM: To compare the pattern of localised nerve fibre layer (NFL) defects in normal tension glaucoma (NTG) and primary open angle glaucoma (POAG). METHODS: 50 NTG eyes and 36 POAG eyes, all with localised NFL defects, were enrolled. On retinal NFL photography, the proximity of the defect to the centre of the fovea (angle alpha) and the sum of the angular width of the defects (angle beta) were determined. Angle alpha was the angle made by a line from the centre of the fovea to the disc centre and a line from the disc centre to the disc margin, where the nearest border of the defect met. The patterns of localised NFL defects in NTG and POAG were compared with angles alpha and beta. Independent t test was used for statistical analysis. RESULTS: Angle alpha in NTG (35.1 (SD 20.0) degrees ) was significantly smaller than that of POAG (45.9 (21.9) degrees ) (p=0.02), while angle beta in NTG (49.0 (31.9) degrees ) was significantly larger than that of POAG (33.1 (23.9) degrees ) (p=0.01). CONCLUSIONS: The pattern of NFL defects in NTG was different from that in POAG. Localised NFL defects in NTG were closer to the fovea and wider in width than those in POAG.

Stability, blood partition, and protein binding of a chemoprotective agent, 2-(allylthio)pyrazine.

The stability of 2-AP, a chemoprotective agent, in various pH solutions and human gastric juice, the blood partition of 2-AP between plasma and blood cells, and the factors influencing the binding of 2-AP to 4% human serum albumin (HSA) were evaluated. 2-AP was stable in human gastric juice and pH solutions ranging from 1 to 12, however, 2-AP was unstable in pH 13 solution; the disappearance rate constant was 0.00759/h. 2-AP reached equilibrium rapidly between plasma and blood cells of rabbit blood. The equilibrium plasma/blood cells partition ratios were independent of initial rabbit blood concentrations of 2-AP, 1, 5, and 10 micrograms/ml; the values were in the range of 5.99-11.8. Binding of 2-AP to 4% HSA was dependent on HSA concentration, incubation temperature, 'the buffer' pH, and addition of acetylsalicylic acid. The binding of 2-AP was independent of buffers containing various concentrations of chloride ion, heparin, and alpha-1-acid glycoprotein.

Determination of a chemoprotective agent, 2-(allylthio)pyrazine, in plasma, urine and tissue homogenates by high-performance liquid chromatography.

A high-performance liquid chromatographic method was developed for the determination of a chemoprotective agent, 2-(allylthio)pyrazine (I), in human plasma and urine, and in rat blood and tissue homogenate using diazepam as an internal standard. The sample preparation was simple; 2.5 volumes of acetonitrile were added to the biological sample to deproteinize it. A 50-100 microl aliquot of the supernatant was injected onto a C18 reversed-phase column. The mobile phase employed was acetonitrile-water (55:45, v/v), and it was run at a flow-rate of 1.5 ml/min. The column effluent was monitored using an ultraviolet detector at 330 nm. The retention times for I and the internal standard were 4.0 and 5.1 min, respectively. The detection limits of I in human plasma and urine, and in rat tissue homogenate (including blood) were 20, 20 and 50 ng/ml, respectively. The coefficients of variation of the assay (within-day and between-day) were generally low (below 6.1%) in a concentration range from 0.02 to 10 microg/ml for human plasma and urine, and for rat tissue homogenate. No interferences from endogenous substances were found.

Pharmacokinetics of a chemoprotective agent, 2-(allylthio)pyrazine, after intravenous administration to rabbits.

The pharmacokinetics of 2-(allylthio)pyrazine (2-AP) were evaluated after intravenous administrations of the drug to rabbits. The reason for the multiple peaks in the plasma concentration of 2-AP after intravenous administration of the drug to rabbits were also investigated. After intravenous administration of 2-AP, 10, 20, and 50 mg/kg, to rabbits, the pharmacokinetic parameters of 2-AP, such as the total area under the plasma concentration-time curve from time 0 to 12 h (261, 672, and 1190 micrograms min/ml), the total body clearance (38.3, 42.0, 44.6 ml/min/kg), and the percentages of intravenous dose of 2-AP excreted in 24 h as unchanged drug (0.0306, 0.0252, and 0.0492%), were independent of the dose ranges studied. Since the amount of 2-AP excreted in 12-h bile as unchanged drug after intravenous administration of 2-AP, 20 mg/kg, was only 0.0241 +/- 0.00156%, and some of 2-AP excreted in gastrointestinal tract as unchanged drug was reabsorbed, the reason for the appearance of multiple peaks after intravenous administration of 2-AP could be at least partly due to gastrointestinal excretion of the drug.