Concentrations of levofloxacin, ofloxacin, and ciprofloxacin in human corneal stromal tissue and aqueous humor after topical administration

OBJECTIVE: To evaluate the penetration of commercially available levofloxacin 0.5%, ofloxacin 0.3%, and ciprofloxacin 0.3% topical ophthalmic solutions in human corneal stromal and aqueous humor tissues. METHODS: A total of 67 patients scheduled to undergo penetrating keratoplasty for treatment of stromal scar or dystrophy, keratoconus, pellucid marginal degeneration, or endothelial disease were enrolled in this prospective, double-blind, 3-center study. To be considered for inclusion, patients had to have an intact corneal epithelium and minimal or no corneal edema (pachymetry < 650 microm). After informed consent was obtained, patients were randomized to receive 1 drop of levofloxacin 0.5%, ofloxacin 0.3%, or ciprofloxacin 0.3% topical ophthalmic solution at approximately 15 and 10 minutes before surgery. Approximately 0.1 mL of aqueous fluid was aspirated by paracentesis through the trephination wound at the onset of surgery, followed by excision of the affected cornea and removal of its epithelium. Specimens were stored frozen at -70 degrees C until assayed by high-performance liquid chromatography. RESULTS: All 3 fluoroquinolones were well tolerated. A total of 65 corneas and 59 aqueous fluid samples were obtained and assayed. The mean +/- standard deviation corneal concentrations of ciprofloxacin, ofloxacin, and levofloxacin following a 2-drop administration were 9.92 +/- 10.99 microg/g (n = 18), 10.77 +/- 5.90 microg/g (n = 23), and 18.23 +/- 20.51 microg/g (n = 24), respectively. Although corneal stromal levels were highest in the levofloxacin group, the high degree of interpatient variability prevented demonstration of statistically significant differences when compared with ofloxacin (P = 0.377). In contrast, levofloxacin concentrations were approximately twice as high as ciprofloxacin, and this difference reached statistical significance (P = 0.014). The corresponding aqueous humor concentrations of ciprofloxacin, ofloxacin, and levofloxacin were 0.135 +/- 0.231 microg/mL (n = 15), 0.135 +/- 0.111 microg/mL (n = 20), and 0.372 +/- 0.546 microg/mL (n = 24, P < 0.001 versus ciprofloxacin and ofloxacin). CONCLUSION: The topical administration of all 3 agents was well tolerated in patients undergoing penetrating keratoplasty. Two drops of levofloxacin 0.5% solution results in a 1.7- to 2.7-fold greater penetration into human corneal stromal and aqueous humor tissues than ofloxacin 0.3% or ciprofloxacin 0.3%. The mean intracorneal concentrations of all three agents following 2 drops exceeds the MIC90 for the majority of pathogens causing bacterial keratitis. Topical levofloxacin appears to offer pharmacokinetic and pharmacodynamic advantages over ofloxacin and ciprofloxacin in terms of enhanced transcorneal penetration; however, clinical comparative trials are needed to confirm these relative advantages.     

Penetration of topically applied ciprofloxacin and ofloxacin into the aqueous humor and vitreous

PURPOSE: To determine the intraocular penetration of topical drops of 2 antibiotics, ciprofloxacin 0.3% and ofloxacin 0.3%, into the aqueous humor and vitreous and to relate these levels to the miminum inhibitory concentration (MIC(90)) for organisms associated with ocular bacterial infections. SETTING: Department of Ophthalmology, Ankara Hospital, and Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey. METHODS: This prospective randomized clinical trial comprised 18 patients having cataract surgery, all with an intact corneal epithelium. The patients were randomly assigned to receive topical ciprofloxacin 0.3% (n = 10) or topical ofloxacin 0.3% (n = 8) 1 drop every 15 minutes 5 times and every 30 minutes 3 times before surgery. Aqueous and vitreous samples (if vitreous loss occurred during the cataract surgery) were collected 30 minutes after the administration of the last dose. Drug concentrations were determined by high-performance liquid chromatography (HPLC) fluorescence. RESULTS: All patients had detectable drug concentrations in the aqueous humor and vitreous measurable by HPLC. The mean aqueous humor concentration of ciprofloxacin was 1.13 microg/mL +/- 1.90 (SD) and the mean vitreous concentration, 0.23 +/- 0.06 microg/mL. Topical administration of ciprofloxacin yielded 4.9 times more drug concentration in the anterior chamber than in the vitreous. The mean aqueous concentration of ofloxacin was 2.06 +/- 1.06 microg/mL and the mean vitreous concentration, 0.46 +/- 0.10 microg/mL. Topical administration of ofloxacin yielded 4.7 times more drug concentration in the anterior chamber than in the vitreous. Aqueous humor concentrations of ofloxacin and ciprofloxacin were not statistically significantly different (P =.353). Intravitreal concentrations of ofloxacin were statistically significantly higher than those of ciprofloxacin (P =.001). CONCLUSIONS: Topical ofloxacin 0.3% penetrated better than topical ciprofloxacin 0.3% into the anterior chamber and vitreous in noninflamed eyes. Both drugs were above the MIC(90) for most ocular pathogens in the anterior chamber. The mean concentration in the vitreous of topically applied ofloxacin 0.3% was statistically significantly higher than that of ciprofloxacin 0.3%, but it was not sufficiently above the MIC(90) for most ocular pathogens in terms of empirical endopthalmitis therapy.     

Aqueous humor levels of topically applied levofloxacin in human eyes

PURPOSE: To evaluate transcorneal penetration of topically applied 0.5% levofloxacin into the aqueous humor in human eyes. METHODS: Twenty cataract patients (14 females, 6 males) received 3 drops of 0.5% levofloxacin at 15 min intervals from 90 minutes before the surgery. At the beginning of the cataract surgery, 50 microL of aqueous humor was aspirated from the anterior chamber and stored at -80 degrees C until analysis. The drug concentration of the samples was analyzed using high-performance liquid chromatography. RESULTS: A mean aqueous humor level of levofloxacin was 1.00 +/- 0.48 microg/mL (mean +/- standard deviation, n = 20), ranging from 0.30 microg/mL to 2.32 microg/mL. CONCLUSIONS: The mean concentration of levofloxacin in the aqueous humor was higher than the MIC(90) values against some common pathogens of postoperative endophthalmitis, although a great degree of interpatient variability was present.     

Ciprofloxacin iontophoresis for aminoglycoside-resistant pseudomonal keratitis

Studies using ciprofloxacin for the therapy of experimental aminoglycoside-resistant keratitis caused by Pseudomonas aeruginosa were conducted using transcorneal iontophoresis as the drug-delivery system. Corneas infected with P. aeruginosa ATCC 27853/pMG6 were treated 22 hours postinfection with ciprofloxacin delivered by iontophoresis (0.8 mA X 10 min), mock iontophoresis (eyecup with no current), or frequently applied topical drops. Iontophoresis of 10 mg/ml or 25 mg/ml of ciprofloxacin significantly reduced the number of viable bacteria per cornea by more than 5 log units compared with untreated controls (P less than 0.0001). Five hours after the initiation of treatment, mock iontophoresis (10 mg/ml or 25 mg/ml) or 11 applications of topical ciproflaxicin drops (7.5 mg/ml) decreased the viable bacteria relative to the untreated controls by 5 log units (P less than 0.0001). One treatment with an eyecup was as effective as 11 treatments with topical drops (P greater than 0.75). One hour after treatment with iontophoresis or mock iontophoresis of 10 mg/ml of ciprofloxacin, aqueous humor concentrations were 83.75 +/- 8.85 micrograms/ml and 24.87 +/- 4.0 micrograms/ml (mean +/- standard error of the mean), respectively. One hour after the last of five applications of 7.5 mg/ml of ciprofloxacin (every 15 min for 1 hr) the aqueous humor concentration was 4.2 +/- 1.14 micrograms/ml. These results show the value of ciprofloxacin in treating aminoglycoside-resistant infections caused by P. aeruginosa and suggest that ciprofloxacin can be efficiently delivered by iontophoresis.     

Aqueous humor levels of topically applied levofloxacin, norfloxacin, and lomefloxacin in the same human eyes

PURPOSE: To assess the relative penetration of topical eyedrops of 3 fluoroquinolones into the aqueous humor in human eyes. SETTING: Department of Ophthalmology, Sano-Kosei Hospital, Sano, Japan. METHODS: Fifty-nine cataract patients (36 women, 23 men) received 3 drops each of levofloxacin 0.5%, norfloxacin 0.3%, and lomefloxacin 0.3% in the same eye at 15-minute intervals beginning 90 minutes before cataract surgery. At the beginning of surgery, 50 microL of aqueous humor was aspirated from the anterior chamber and stored at -80 degrees C until analyzed. The drug concentrations in the samples were analyzed using high-performance liquid chromatography. RESULTS: Five patients were excluded from the study because their sample volumes were insufficient. Norfloxacin was detected in 3 patients; the mean aqueous humor level was 0.10 microg/mL +/- 0.02 (SD). Levofloxacin was detected in all cases; the mean aqueous humor level was 0.60 +/- 0.28 microg/mL (n = 54). Lomefloxacin was not detected in 10 patients; the mean aqueous humor level was 0.23 +/- 0.11 microg/mL (n = 44). CONCLUSION: Topically applied levofloxacin had better penetration into the aqueous humor than lomefloxacin and norfloxacin.     

Comparison of 2 moxifloxacin regimens for preoperative prophylaxis: prospective randomized triple-masked trial. Part 1: aqueous concentration of moxifloxacin

PURPOSE: To evaluate the aqueous concentration of moxifloxacin following 2 dosing regimens of topically administered moxifloxacin hydrochloride ophthalmic solution 0.5% (Vigamox). SETTING: Iladevi Cataract & IOL Research Centre, Ahmedabad, India. METHODS: In this prospective randomized triple-masked clinical trial, 156 patients having cataract surgery were randomly assigned to 1 of 2 regimens of preoperative prophylaxis. In Group A (n = 76), Vigamox was instilled 4 times a day 1 day before surgery plus 1 drop 2 hours before surgery (total of 5 drops). In Group B (n = 76), Vigamox was first instilled 2 hours before surgery and then every 15 minutes for 1 hour (total of 5 drops). In both groups, aqueous samples (0.1 mL) were collected within 2 hours of the first instillation on the day of surgery and stored at -80 degrees C. The antibiotic concentration in all aqueous aspirates was determined using high-performance liquid chromatography. Data were analyzed using the Kolmogorov-Smirnov t test; 95% confidence intervals (CIs) were calculated. RESULTS: The mean aqueous humor concentration of moxifloxacin was 1.58 microg/mL +/- 0.80 (SD) in Group A and 2.05 +/- 0.72 microg/mL in Group B (P<.0001; 95% CI, -0.72 to -0.22). CONCLUSIONS: Both dosing regimens produced substantially higher aqueous concentrations than the known minimum inhibitory concentration for Staphylococcus epidermidis. Topical moxifloxacin administered 2 hours before surgery achieved significantly higher aqueous concentrations than topical moxifloxacin administered 1 day before surgery with 1 drop given on the day of surgery.     

Human aqueous humor levels of oral ciprofloxacin, levofloxacin, and moxifloxacin

PURPOSE: To evaluate the penetration of ciprofloxacin, levofloxacin, and moxifloxacin into the aqueous humor after oral administration. SETTING: Alcorcon Hospital, Madrid, Spain. METHODS: Forty-two patients having cataract surgery were randomly divided into 3 groups the day before surgery. The first group received 2 oral 500 mg doses of ciprofloxacin at 12-hour intervals. The second group received a single oral 500 mg dose of levofloxacin. The third group received a single oral 400 mg dose of moxifloxacin. At the time of surgery, 0.1 mL aqueous fluid was aspirated from the anterior chamber just before the operation and immediately stored at -80 degrees C. Drug concentrations were measured using a biological assay. RESULTS: The mean aqueous level of ciprofloxacin was 0.50 microg/mL +/- 0.25 (SD); of levofloxacin, 1.50 +/- 0.50 microg/mL; and of moxifloxacin, 2.33 +/- 0.85 microg/mL. The mean aqueous levels of levofloxacin and moxifloxacin were above the 90% minimum inhibitory concentration for most of the common microorganisms that cause endophthalmitis. CONCLUSIONS: Therapeutic concentrations of fluoroquinolones, mainly levofloxacin and moxifloxacin, were reached with oral administration. These antibiotics may be effective for prophylaxis and adjuvant therapy of bacterial endophthalmitis.     

Ocular bioavailability of ciprofloxacin in sustained release formulations.

A novel sustained release delivery system of ciprofloxacin for the eye was developed. The system consists of a viscosity enhancer (carbopol gel or hydroxypropylmethylcellulose solution) plus a penetration enhancer (dodecylmaltoside) to overcome penetration barriers and loss due to wash-out and thus achieve the desired ciprofloxacin ocular absorption. The present studies were designed to assess the ocular penetration and bioavailability of ciprofloxacin in sustained release formulations. In vitro studies in rabbits indicated an approximate 10-fold increase in drug penetration through the rabbit cornea using the penetration enhancer, dodecylmaltoside. In vivo bioavailability studies demonstrate that these formulations provided a long drug duration in the cornea. After administration of a single topical dose of ciprofloxacin (0.3%/30 microL), corneal levels greater than the Minimum Inhibitory Concentration (MIC90) (0.5 microg/g) were observed through eight hours. These sustained release formulations delivered 10-fold more drug into the aqueous humor than the standard solution formulation. Maximum ciprofloxacin concentrations in the aqueous humor (0.5-0.7 microg/mL) were attained between one and two hours after dosing. Using these sustained release formulations, ciprofloxacin can penetrate to the anterior chamber of the eye in concentrations that are inhibitory for most gram-negative and gram-positive organisms. These topical ocular formulations have prophylactic utility for prevention of post-surgical infection, offering greater efficacy and safety than currently available treatments.     

FK506及其纳米粒的房水药代动力学的实验研究

目的探讨FK506及其纳米粒的房水药代动力学特征。方法42只新西兰白兔分为:(1)FK506纳米胶体液滴眼组(18只兔)和注射组(16只兔):双眼结膜囊滴入或结膜下注射10μgFK506的纳米胶体溶液;(2)不含纳米微粒的FK506滴眼组(8只兔):再分为2个亚组,即双眼结膜囊分别滴入20μg和40μg FK506的滴眼液。不同时间点采集房水,酶联免疫法测定房水中FK506含量,计算药代动力学参数。结果含10μg FK506的纳米胶体溶液结膜下注射和滴眼后房水有效药物浓度可分别维持96 h和16 h;结膜下注射后2 h房水浓度为(1.15±0.25)ng/m、l6~96 h房水浓度为(9.62±2.19)~(2.60±0.21)ng/m l,滴眼16 h内房水浓度为(15.50±3.39)~(2.59±0.83)ng/m l;药代动力学参数分别为:达峰时间(Tm ax)(64.00±13.86)h和(1.25±0.50)h,达峰浓度(Cm ax)(10.16±1.37)ng/m l和(15.52±2.37)ng/m l,曲线下面积(AUC0→t)(612.48±54.39)ng.m l-1.h-1和(152.44±16.74)ng.m l-1.h-1,吸收速率常数(Ka)0.040±0.004和3.790±0.730,平均滞留时间(MRT)(58.53±5.42)h和(8.20±1.28)h。房水中FK506质量浓度呈一室模型。不含纳米微粒的FK506(20μg和40μg)液滴眼后房水有效药物浓度维持均≤4 h;其中含20μgFK506液的Tm ax为1 h,Cm ax为(18.93±6.95)ng/m l;含40μg FK506液的Tm ax为2 h;Cm ax为(28.33±1.31)ng/m。l结论采用FK506纳米粒胶体溶液行结膜下注射和滴眼时均可延长FK506药物在房水中的滞留时间,而且结膜下注射能使房水中维持的有效药物浓度相对较低和时间更长     

更昔洛韦原位胶化滴眼液兔眼部药物动力学及生物利用度研究

目的比较0．2％更昔洛韦滴眼液及其原位胶化滴眼液给兔眼滴用后,更昔洛韦在兔眼泪液、房水以及角膜组织中的经时过程及其药物动力学行为。方法采用健康无眼疾白色家兔,按完全随机化方法分为试验组与对照组。试验组每眼结膜囊内单次给更昔洛韦原位胶化滴眼液50山,对照组动物每眼结膜囊单次给更昔洛韦一般滴眼液50μl。两种制剂滴眼后,在不同时间点分别取泪液、房水以及角膜组织,样品经处理后,采用高效液相色谱法（HPLC）测定不同时间的兔眼泪液、房水及角膜组织中更昔洛韦浓度,药物动力学参数采用非线性最小二乘法进行计算机拟合求得。结果在用药后120min内,试验组各时间点房水中和角膜组织中的药物浓度均明显高于对照组。泪液中在5—10min时试验组药物浓度明显高于对照组。试验组的泪液、房水和角膜药物浓度一时间曲线下面积分别是对照组的2．2、5．5和3．4倍,试验组和对照组药物在房水中的t1／2分别为59和43min,在角膜中分别为223和87min。试验组和对照组房水中药物达峰浓度分别为4．79和0．96μg／ml,达峰时间分别为60和45min。结论更昔洛韦原位胶化滴眼液同一般滴眼液相比,明显延长药物在眼部的滞留时间,增加角膜组织和房水中的药物浓度。显著提高更昔洛韦的眼部生物利用度。     

Corneal penetration of fluoroquinolones: aqueous humor concentrations after topical application of levofloxacin 0.5% and ofloxacin 0.3% eyedrops

PURPOSE: To investigate the penetration of topically applied levofloxacin 0.5% and ofloxacin 0.3% eyedrops into the aqueous humor of patients having cataract surgery. SETTING: Hochkreuzklinik Eye Hospital, Bonn, Germany. METHODS: In this randomized, investigator-masked study, 69 patients received 4 drops of either levofloxacin 0.5% or ofloxacin 0.3% eyedrops within 1 hour (60 min, 45 min, 30 min, and 15 min) of elective cataract surgery. Aqueous humor samples of at least 50 muL were drawn from the anterior chamber at the beginning of the cataract operation. The concentrations of the fluoroquinolones in the anterior chambers were measured using high-performance liquid chromatography. To exclude a dilution effect of the anterior chamber (AC), they were related to the AC volumes (measured by 3-dimensional modeling of central Orbscan [Bausch & Lomb] slit-image photos) and AC depths (measured by ultrasound). RESULTS: The mean concentration of levofloxacin (1139.9 ng/mL +/- 717.1 [SD]) in the aqueous humor was significantly higher (P = .0008) than that of ofloxacin (621.7 +/- 368.7 ng/mL). The aqueous humor concentrations correlated negatively with the measured volumes and depths of the ACs. CONCLUSIONS: The new fluoroquinolone, levofloxacin, is more soluble in water enabling the use of higher drug concentrations (0.5%) compared with other currently available fluoroquinolone eyedrops (0.3%). The concentration AC with levofloxacin eyedrops was about 2-fold that reached with ofloxacin eyedrops. The concentration of the antibacterial isomer was approximately 3.5 to 4 times higher when levofloxacin was administered, assuming negligible stereoselective uptake.     

Intraocular penetration and systemic absorption after topical application of dexamethasone disodium phosphate

PURPOSE: To study the dexamethasone concentration in aqueous humor, vitreous, and serum of patients after repeated topical application of dexamethasone disodium phosphate. DESIGN: Prospective nonrandomized comparative trial. PARTICIPANTS: Twenty phakic patients scheduled for a first vitrectomy. METHODS: All participants received dexamethasone disodium phosphate drops according to an application schedule intended to result in steady-state drug concentrations. Starting on the preoperative day, they received 1 drop of dexamethasone disodium phosphate (0.1%) every 1 hours until the time of vitrectomy (total, 10 or 11 drops). At night, ointment containing dexamethasone (0.3 mg/g) and gentamicin (5 mg/g) was administered once. From 7 AM on, the drop application schedule was resumed. At the start of the vitrectomy, samples were taken from the aqueous humor, vitreous, and blood. MAIN OUTCOME MEASURES: The dexamethasone concentrations in the aqueous humor, vitreous, and serum measured by radioimmunoassay. RESULTS: The mean dexamethasone concentrations in the aqueous humor, vitreous, and serum were 30.5 ng/ml (range, 7.1-57.7; standard deviation [SD] 15.0), 1.1 ng/ml (range, 0.0-1.6; SD 0.4), and 0.7 ng/ml (range, 0.0-1.2; SD 0.4), respectively. CONCLUSIONS: Compared with previously tested administration routes (peribulbar or subconjunctival injection or oral administration), the penetration of dexamethasone into the vitreous after repeated drop application is negligible. Despite the frequent dosing schedule, the dexamethasone concentration in the aqueous humor is far lower than after a subconjunctival injection with dexamethasone disodium phosphate. Systemic uptake is low.     

Comparative penetration of moxifloxacin and gatifloxacin in rabbit aqueous humor after topical dosing

PURPOSE: To evaluate the aqueous penetration of the fourth-generation fluoroquinolones moxifloxacin and gatifloxacin. SETTING: University of Arizona, Tucson, Arizona, USA. METHODS: Forty eyes of 20 New Zealand white rabbits were divided into 2 experimental groups. In Experiment I rabbits (20 eyes), a commercial preparation of topical gatifloxacin 0.3% was administered to 9 eyes and moxifloxacin 0.5% to 9 eyes; 2 eyes served as a control. Eyes were dosed according to a keratitis protocol; ie, every 15 minutes for 4 hours. The aqueous humor was sampled 10 minutes after the last dose. Experiment II rabbits (20 eyes) were dosed according to a cataract prophylaxis protocol; ie, 4 times a day for 10 days. The aqueous humor was sampled 1 hour after the last dose of antibiotic in 12 eyes and 24 hours after the last dose in 8 eyes. High-performance liquid chromatography was used to determine the fluoroquinolone concentration. RESULTS: In the keratitis dosing protocol, the mean concentration of moxifloxacin in the aqueous (n=9) was 11.057 microg/mL (range 7.66 to 18.87 microg/mL), which was significantly higher than the mean concentration of gatifloxacin (n=8) (7.570 microg/mL [range 4.75 to 10.86 microg/mL]) (P=.030). In the cataract prophylaxis dosing protocol, the mean aqueous concentration of moxifloxacin (n=6) was 1.745 microg/mL (range 0.92 to 3.87 mg/mL). The mean concentration of gatifloxacin (n=6) was 1.207 microg/mL (range 0.44 to 2.44 microg/mL). The difference was not statistically significant (P=.359). CONCLUSIONS: Higher mean levels (x1.46) of aqueous penetration were achieved with moxifloxacin than with gatifloxacin in the keratitis-dosing model. There was no statistically significant difference between the 2 drugs in the cataract prophylaxis dosing model. Both antibiotics had aqueous levels in excess of the minimum inhibitory concentration for most pathogenic organisms in both models.     

Decrease of pigment epithelium-derived factor in aqueous humor with increasing age

PURPOSE: To determine whether the level of pigment epithelium-derived factor (PEDF) in the aqueous humor is altered with age. DESIGN: Observational case series. METHODS: The PEDF concentration in the aqueous humor was measured by enzyme-linked immunosorbent assay in 152 eyes of 121 patients who underwent cataract surgery. RESULTS: The mean aqueous level of PEDF was 0.86 +/- 0.04 microg/ml (mean +/- standard error, 70.7 +/- 1.0 years). The PEDF levels decreased with increasing age, and the decrease was significantly correlated with age (Pearson product moment correlation coefficient, r = - 0.22, P =.006). The mean PEDF level in the men (0.76 +/- 0.06 microg/ml, 53 eyes, 71.5 +/- 2.0 years) was significantly lower than that in women (0.91 +/- 0.04 microg/ml, 99 eyes, 70.2 +/- 1.1 year, P =.03). CONCLUSIONS: The negative correlation of PEDF level and age should be considered in age-related eye diseases, especially those associated with angiogenesis.     

Aqueous humor levels of topically applied bupivacaine 0.75% in cataract surgery

PURPOSE: To measure the intraocular levels of bupivacaine 0.75% topically applied before phacoemulsification and to develop standards for topical anesthesia in cataract surgery. SETTING: Department of Ophthalmology, University Hospitals of Leicester, Leicester, United Kingdom. METHODS: Forty eyes having phacoemulsification for senile cataract under topical anesthesia without sedation were randomly assigned to 1 of 2 preoperative topical anesthesia regimens. Bupivacaine 0.75% was applied in 0.1 mL drops 3 times in the 30 minutes before surgery in 18 eyes and 6 times in the 60 minutes before surgery in 22 eyes. Aqueous humor and serum samples were taken at the start of surgery and the bupivacaine levels measured. A visual analog pain score scale was used to indicate intraoperative pain. RESULTS: The mean aqueous humor level of bupivacaine was 5.9 microg/mL +/- 4.3 (SD) after 3 drops and 5.7 +/- 4.0 microg /mL after 6 drops. The blood levels were less than 1.0 microg/mL. There was no statistically significant difference in the intraocular level of bupivacaine between the 2 groups. There was no difference in the age or sex distribution between the 2 groups, although there was an increase in the intraocular level of bupivacaine with age (approximately 1.4 microg/mL per decade; P =.048). There was no clear pattern associating the pain score with age, sex, or intraocular level of bupivacaine. CONCLUSIONS: A 3-drop regimen of bupivacaine 0.75% in the half hour before cataract surgery penetrated the eye as effectively as 6 drops in the 1 hour before surgery and provided good analgesia for phacoemulsification. Bupivacaine 0.75% penetrated the eye increasingly effectively with increasing age.     

Penetration of ofloxacin and ciprofloxacin in aqueous humor after topical administration.

BACKGROUND AND OBJECTIVE: To compare the aqueous humor levels of 0.3% ofloxacin and 0.3% ciprofloxacin containing eyedrops in patients with healthy cornea. PATIENTS AND METHODS: Fifty patients with cataract were randomly assigned to have 0.3% ofloxacin containing eyedrop (25 patients) or 0.3% ciprofloxacin containing eyedrop (25 patients). Both drugs were repetitively instilled to each patient for 6 hours before the surgery. Aqueous samples were collected after penetrating the anterior chamber during cataract extraction and assayed by high-performance liquid chromatography method. RESULTS: The aqueous humor level of ofloxacin (1.43 +/- 0.26 microg/ml, mean +/- SEM) was significantly higher than that of ciprofloxacin (0.35 +/- 0.07 microg/ml) following the topical application (P < .0002). CONCLUSION: Aqueous humor penetration of topical ofloxacin is about 4 times higher than that of topical ciprofloxacin when the drugs are applied as described above.     

Heparin drug delivery system for prevention of posterior capsular opacification in rabbit eyes

BACKGROUND: The aim of this study was to investigate the safety and efficacy of a heparin drug delivery system (HEP DDS) for prevention of posterior capsular opacification (PCO) in rabbits. METHODS: Fifty New Zealand albino rabbits (50 eyes) undergoing phacoemulsification were equally divided into five groups receiving normal saline eye drops (group A), a carrier DDS implanted into the posterior chamber (group B), 5% heparin eye drops (group C), a HEP DDS implanted subconjunctivally (group D) and a HEP DDS implanted into the posterior chamber (group E). All the 50 eyes were examined by slit-lamp microscopy. The heparin levels in blood and aqueous humor were measured, and the wet posterior capsules were weighed. RESULTS: All eyes in groups A and B had PCO at 5-7 days, much earlier than in groups C, D and E. Two eyes in group C, three eyes in group D and six eyes in group E showed no signs of PCO throughout the 12-week study. The mean weight of wet posterior capsules from groups A-E was 157.919 mg, 160.091 mg, 81.114 mg, 71.827 mg and 19.984 mg respectively. The mean aqueous humor heparin level in groups C, D and E was 10.279 microg/ml, 13.246 microg/ml and 25.964 microg/ml respectively. Cell proliferation of the posterior capsules in group E was not active. The conjunctiva, cornea, iris, ciliary body and retina remained intact, and no significant toxic reactions were observed. No intraocular hemorrhage occurred during the follow-up. CONCLUSION: Implantation of a HEP DDS into the posterior chamber of experimental animals significantly maintained a higher heparin level in aqueous humor for a relatively long period of time. The findings indicate potential prevention of PCO with minimum toxic and side effects.     

Decreased levels of pigment epithelium-derived factor in eyes with neuroretinal dystrophic diseases

PURPOSE: To determine the concentration of pigment epithelium-derived factor (PEDF) in the aqueous humor of eyes with neuroretinal dystrophy. DESIGN: Observational case series. METHODS: Aqueous humor was obtained from patients during cataract surgery, and the PEDF concentration in the aqueous humor was measured by enzyme-linked immunosorbent assay. The primary diagnosis was cataract in 162 eyes; of these there were five eyes with retinitis pigmentosa, nine eyes with advanced glaucoma, and 148 eyes with cataract alone. RESULTS: The mean levels of PEDF in eyes with retinitis pigmentosa (0.24 +/- 0.04 microg/ml, mean +/- SE, P =.0004) and advanced glaucoma (0.46 +/- 0.08 microg/ml, P =.003) were significantly lower than that in eyes with cataract alone (0.86 +/- 0.04 microg/ml). CONCLUSION: The lower levels of PEDF in eyes with neuroretinal dystrophy may be related to the loss of the retinal ganglion cells or retinal pigment epithelium cells that synthesize PEDF.     

兔眼局部应用盐酸川芎嗪滴眼液的前房穿透性研究

目的:探讨兔眼局部应用盐酸川芎嗪滴眼液后前房穿透性。方法:18只白兔随机分为6组,并于各组白兔结膜囊内滴入50μL盐酸川芎嗪滴眼液,分别于5、15、30、60、120、180min取房水,采用高效液相色谱法进行测定。色谱柱为DiamonsilCl8不锈钢柱(250mm×4.6mm,5μm);流动相为甲醇:水=62:38;流速:0.9mL/min;检测波长为280nm。结果:5、15、30、60、120、180min各组的房水浓度分别为(15.785±2.988)μg/mL,(11.900±1.743)μg/mL,(8.286±1.182)μg/mL,(2.745±0.807)μg/mL,(0.379±0.091)μg/mL,(0.049±0.038)μg/mL,其中5min为最高峰,然后逐渐下降,180min后房水浓度已降到很低。结论:盐酸川芎嗪滴眼液滴眼后房水穿透性良好,这一结果为盐酸川芎嗪滴眼液局部应用后治疗眼前部疾病提供了实验依据。     

Penetration of topically applied levofloxacin into eyes with thin-wall filtering bleb after trabeculectomy

PURPOSE: To investigate the comparative penetration of 0.3% levofloxacin eye drops into the aqueous humour between cataract patients with or without (control) thin-wall filtering blebs. METHODS: One drop of 0.3% levofloxacin was administered to the eyes at 30-min intervals for 3.5 h before phacoemulcification for both groups. Aqueous humour samples (0.1-0.2 ml) were aspirated during surgery. The concentration of levofloxacin in the aqueous humour was determined by high-performance liquid chromatography. The Student's t-test, Pearson correlation, and chi(2) test were used to compare the data of the two groups. A P<0.05 was required for results to be considered statistically significant. RESULTS: The levofloxacin concentration in the aqueous humour was significantly increased (P<0.0001) in the bleb (mean+SD: 3.7+/-2.3 microg/ml) vscontrol group (0.4+/-0.2 microg/ml). Intraocular pressure and the bleb area were not correlated with levofloxacin concentration. CONCLUSION: The presence of thin-wall filtering blebs increases intraocular penetration of topically administered levofloxacin.