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.     

Corneal penetration of simultaneously applied topical levofloxacin, norfloxacin and lomefloxacin in human eyes

PURPOSE: This study was performed to assess the corneal penetration of three topically applied fluoroquinolones (levofloxacin, norfloxacin and lomefloxacin) in corneal buttons obtained from patients undergoing penetrating keratoplasty. METHODS: Fourteen patients received three drops each of 0.5% levofloxacin, 0.3% norfloxacin and 0.3% lomefloxacin (the standard clinically available preparations) over a 30-min interval beginning 90 mins before their scheduled keratoplasty. Corneal samples obtained from excised buttons at the time of surgery were stored at - 80 degrees until analysis. The concentration of the administered fluoroquinolones was measured using high-performance liquid chromatography. RESULTS: The mean corneal concentration of levofloxacin (4.6 +/- 3.5 microg/g, mean +/- standard deviation) was significantly higher than that of lomefloxacin (2.7 +/- 1.8 microg/g, p = 0.0018) and norfloxacin (1.3 +/- 1.2 microg/g, p = 0.00012). CONCLUSION: Levofloxacin achieves a higher mean corneal concentration than norfloxacin and lomefloxacin in the human cornea.     

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.     

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.     

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 gatifloxacin eye drops into the aqueous humor in humans

The authors topically administered gatifloxacin (GFLX) into the eye before cataract surgery and measured the concentrations of this agent to determine its penetration into aqueous humor. Seventy-seven patients with age-related cataracts who underwent cataract surgery were enrolled in this study. They received 0.3% GFLX ophthalmic solution 4 times at 30-min intervals, beginning 2 h before surgery. Aqueous humor was aspirated from the anterior chamber and assayed for GFLX concentration using high-performance liquid chromatography. The mean intraoperative GFLX concentration in aqueous humor was 0.485 +/- 0.328 microg/mL. GFLX level was 0.573 +/- 0.367 microg/mL in elderly patients, at least 70 years of age, and was significantly higher than that (0.322 +/- 0.135 microg/mL) in the patients less than 70 years old. This concentration was close to or higher than the minimum inhibitory concentrations required to inhibit the growth of 90% of major pathogens of endophthalmitis (MIC90), such as Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecalis associated with poor prognosis, other than Staphylococcus epidermidis, Pseudomonas aeruginosa, and MRSA (methicillin-resistant S. aureus) in vitro. The GFLX concentrations found in aqueous humor samples were sufficient to kill bacteria other than S. epidermidis, P. aeruginosa, and MRSA in vitro.     

Aqueous humor penetration of gatifloxacin and moxifloxacin eyedrops given in different concentrations in a wick before cataract surgery

PURPOSE: To determine whether the penetration into the aqueous humor of gatifloxacin (Zymar) and moxifloxacin (Vigamox) eyedrops was affected by altering their concentrations in the dilating mixture in which the wick used to dilate the pupil before cataract surgery was soaked. SETTING: Pasqua Hospital, Regina, Saskatchewan, Canada. METHODS: This prospective randomized open-label study comprised 65 women and 35 men who were divided into 2 main groups. One group received 1 mL of the antibiotic in the dilating mixture and the other, 2 mL. Each group was divided into 2 subgroups, 1 for gatifloxacin and 1 for moxifloxacin. At the beginning of surgery, 0.1 mL of aqueous humor was aspirated, frozen, and couriered to the provincial laboratory for analysis by high-performance liquid chromatography. RESULTS: In the first group, the mean concentration of gatifloxacin in the aqueous humor was 0.30 microg/mL +/- 0.21 (SD) and of moxifloxacin, 0.97 +/- 0.63 microg/mL. When the volume of the antibiotic in the dilating mixture was doubled, the mean concentration increased to 0.34 +/- 0.25 microg/mL and 1.37 +/- 0.79 microg/mL, respectively. Only the increased penetration of moxifloxacin was statistically significant. CONCLUSIONS: Moxifloxacin penetrated the aqueous humor better than gatifloxacin when given in a wick soaked in the dilating mixture before cataract surgery. Only the penetration of moxifloxacin increased significantly when the volume of the antibiotic in the dilating mixture was doubled. In both groups, only moxifloxacin reached and exceeded the minimum inhibitory concentration levels for the most common ocular pathogens causing endophthalmitis.     

Ocular penetration of cefepime following systemic administration in humans

OBJECTIVE: To investigate the penetration of cefepime (a fourth generation cephalosporin) into the aqueous humor after single-dose intravenous administration in humans. PATIENTS AND METHODS: Before receiving cataract surgery, 30 patients received randomly 1 g (group 1, 15 patients) and 2 g (group 2, 15 patients) single intravenous injection of cefepime before surgery. Samples of aqueous humor and serum were obtained at 0.5, 1, 2, 4, and 12 hours after injection. Three patients were sampled each time for 1 g and 2 g of cefepime. Samples were assayed for cefepime concentrations with high performance liquid chromatography (HPLC). RESULTS: All the patients had detectable cefepime in their aqueous humor and serum measurable by HPLC. A mean peak aqueous humor level was 5.16 +/- 0.88 microg/mL in group 1 and 5.87 +/- 1.64 microg/mL in group 2 at 0.5 hour after injection. The mean level of cefepime in aqueous humor decreased after 0.5-hour measurements in both groups and was measured as 0.82 +/- 0.21 microg/mL in group 1 and 2.04 +/- 0.30 microg/mL in group 2 at 12 hours after injection. CONCLUSION: Aqueous humor levels of cefepime after single IV injection were above the minimum inhibitory concentration (MIC90) for most ocular pathogens, but the duration of exposure to an antibiotic was not sufficient for therapeutic effect.     

Flomoxef sodium and levofloxacin concentrations in aqueous humor

AIMS: We intravenously administered flomoxef sodium (FMOX) 120 minutes before cataract surgery, topically administered levofloxacin (LVFX) into the eyes four times at 30-minute intervals before surgery, and measured the aqueous humor concentrations of these agents to investigate their penetration into the aqueous humor and their efficacy in the prevention of postoperative endophthalmitis. METHODS: Sixty-eight patients who underwent cataract surgery at the Department of Ophthalmology, Yokohama City University School of Medicine, or its affiliate, Kanazawa Hospital, Yokohama, were enrolled in this study. They received one or both of the following: 1.0 g FMOX via a 20-minute intravenous drip and LVFX ophthalmic solution applied four times at 30-minute intervals, both beginning two hours before the operation. Aqueous humor was aspirated from the anterior chamber and assayed for FMOX and LVFX concentrations using high-performance liquid chromatography (HPLC). RESULTS: The mean intraoperative FMOX and LVFX concentrations in the patients' aqueous humor were 1.21 +/- 0.63 microg/ml and 0.69 +/- 0.47 microg/ml, respectively. These concentrations sufficiently exceeded the MIC90 values against Staphylococcus epidermidis, S. aureus, and Propionibacterium acnes. CONCLUSIONS: The FMOX and LVFX concentrations in the aqueous humor sampling were adequate to kill bacteria in vitro. These drugs may have efficacy in the prevention of postoperative endophthalmitis in patients undergoing cataract surgery.     

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.     

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 and vitreous penetration of levofloxacin after topical and/or oral administration

PURPOSE: To investigate the aqueous and vitreous penetration of levofloxacin, the drug was administered topically and/or orally to patients undergoing vitrectomy. METHODS: Thirty-six patients undergoing initial vitrectomy with phacoemulsification and aspiration (PEA) were enrolled, and were divided randomly into three groups. Group 1 was treated with topical application of levofloxacin (three times on the day before surgery and seven times on the day of surgery), Group 2 received oral administration of levofloxacin (200 mg twice on the day before surgery and 200 mg at 3 hours before surgery), and Group 3 received both topical and oral levofloxacin according to the above schedules. The concentration of levofloxacin was measured in aqueous humor and vitreous fluid samples obtained during surgery. RESULTS: In Groups 1, 2, and 3, the mean levofloxacin concentration in aqueous humor was 0.765+/-0.624 micro g/mL, 1.279+/-0.440 micro g/mL, and 1.823+/-0.490 micro g/mL, respectively, while the mean levofloxacin concentration in vitreous fluid was <0.02 micro g/mL, 1.455+/-0.445 micro g/mL, and 1.369+/-0.530 micro g/mL, respectively. CONCLUSIONS: Oral administration of levofloxacin at a dose of 400 mg/day was sufficient for the prophylaxis of ocular infections, because the drug concentrations in both aqueous humor and vitreous fluid were higher than the MIC90 values for major ocular pathogens. Topical application of levofloxacin achieved adequate drug levels in aqueous humor, but not in vitreous fluid, while combined topical and oral administration had an additive effect on the drug concentration in aqueous humor.     

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.     

Preoperatively administered flomoxef sodium concentration in aqueous humor

PURPOSE: We intravenously administered flomoxef sodium (FMOX) 0.5-3.5 hours before cataract surgery and measured the concentration of the agent in the aqueous humor to investigate its penetration into the aqueous humor and its efficacy in the prevention of postoperative endophthalmitis. METHODS: 56 patients who underwent cataract surgery were enrolled in this study. They received 1 g FMOX via a 20-minute intravenous drip beginning 0.5-3.5 hours before the operation. Aqueous humor was aspirated from the anterior chamber and assayed for FMOX concentration using high-performance liquid chromatography. RESULTS: The mean intraoperative FMOX concentrations in the patients' aqueous humor were 0.79 +/- 0.24 microg/ml (administered 3.5 hours before surgery)--1.47 0.79 microg/ml (administered 1.5 hours before surgery). These concentrations administered 0.5-3.0 hours before surgery sufficiently exceeded the minimum inhibitory concentration (MIC) 90 values against Staphylococcus epidermidis, Staphylococcus aureus and Propionibacterium acnes, but did not achieve the MIC90 values against Enterococcus faecalis and Pseudomonas aeruginosa. CONCLUSIONS: The FMOX concentrations in the aqueous humor sampling were adequate to kill bacteria in vitro. This drug may be efficacious in the prevention of postoperative endophthalmitis in patients undergoing cataract surgery.     

Effect of gatifloxacin ophthalmic solution 0.3% on human corneal endothelial cell density and aqueous humor gatifloxacin concentration

PURPOSE: To evaluate the effect of gatifloxacin ophthalmic solution 0.3% (Zymar, Allergan, Inc., Irvine, CA, USA) on corneal endothelial cell density and morphology and to measure gatifloxacin penetration into aqueous humor. METHODS: This was a single-center, open-label clinical study. Ten patients undergoing standard cataract surgery and 20 nonsurgical subjects instilled gatifloxacin 0.3% four times per day for 2 days, then every 10 min for 1 hr on the third day (the surgery day for the cataract patients). Corneal endothelial cells were counted using noncontact specular microscopy. Anterior chamber fluid was withdrawn from the surgical patients, and the gatifloxacin concentration was quantified by high-pressure liquid chromatography. RESULTS: Baseline endothelial cell counts (mean +/- SD) were 2400 +/- 442 in the surgical group and 2520 +/- 212 in the nonsurgical group. The mean differences from baseline 1 hr after the last dose of gatifloxacin 0.3% were -51 +/- 213 (p = 0.23) in the surgical group and -7 +/- 150 (p = 0.42) in the nonsurgical group. In the nonsurgical group, the mean difference from baseline 3 weeks after the last dose was 18 +/- 147 (p = 0.71). The mean concentration (+/- SD) of gatifloxacin in aqueous humor was 1.26 +/- 0.55 microg/ml. CONCLUSIONS: A preoperative, prophylactic course of gatifloxacin 0.3% ophthalmic solution did not significantly affect endothelial cell density or morphology, while meaningful drug concentration was achieved in the aqueous humor.     

Penetration of betaxolol HCL ionic suspension 0.25% and betaxolol HCL solution 0.50% into the aqueous humor

PURPOSE: To determine the intraocular penetration of topical drops of betaxolol HCl 0.25% suspension and betaxolol HCl 0.50% solution into the aqueous humor. METHODS: Fifteen patients were randomly assigned to receive topical betaxolol HCl 0.25% suspension (n=7) or topical betaxolol HCl 0.50% solution (n=8) the day before cataract surgery. Aqueous samples were collected 2 hours after the administration of the morning dose during cataract surgery. Drug concentrations were determined by high-performance liquid chromatography with fluorescence detection. RESULTS: The mean aqueous humor concentration of topical betaxolol HCl 0.25% suspension was 275.1+/-168.8 micro g/mL (range 570-70 micro g/mL) and the mean aqueous humor concentration of topical betaxolol HCl 0.50% solution was 195.4+/-102.4 micro g/mL (range 334-50 micro g/mL) (p=0.281). CONCLUSIONS: The mean aqueous humor concentration of betaxolol 0.25% suspension was higher than betaxolol 0.50% solution; however, the difference was not statistically significant. With twofold reduced concentration and similar anterior chamber penetration, betaxolol 0.25% suspension could be first choice for Beta 1 selective blocker therapy when considered for patients with glaucoma.     

Penetration of norfloxacin into the aqueous humor of the human eye.

Forty six patients received a topical application of a 0.3% norfloxacin (Zoroxin; MSD, Austria) solution into the lower fornix at different time intervals and frequencies before undergoing planned extracapsular cataract extraction. Aqueous humor was sampled at the beginning of surgery and assayed for the level of the antibiotic with high performance liquid chromatography. The highest aqueous humor level observed 30 min after the administration of the last drop in four patients who received five drops of norfloxacin into the lower fornix was 660.25 +/- 378.2 ng/ml. These concentrations are above the minimum inhibitory concentration of norfloxacin for 90% (MIC90) of most of the gram-negative microorganisms, but below the MIC90 of most of the staphylococci (coagulase negative Staph. and Staphylococcus aureus range between 0.25-1 mg/ml).     

Intraocular penetration of topical lidocaine 4%.

PURPOSE: To evaluate the intraocular penetration of lidocaine 4% topically applied before phacoemulsification. SETTINGS: Institute of Ophthalmology, University of Verona, and Department of Medical Pharmacology, University of Padua, Italy. METHODS: Thirty eyes having phacoemulsification for senile cataract were anesthetized by topical application of lidocaine 4%. The drug was applied 3 times in 30 minutes in 15 eyes and 6 times in 60 minutes in 15 eyes. At the beginning of surgery, aqueous humor samples were obtained to measure the lidocaine levels. Blood samples were obtained in 6 patients 30 and 60 minutes after aqueous humor collection. The aqueous humor levels were compared with the amount of pain perceived by patients during surgery. RESULTS: Mean aqueous humor lidocaine concentration was 8.68 micrograms/mL +/- 2.43 (SD) after 3 instillations and 23.21 +/- 8.87 micrograms/mL after 6 instillations. Blood levels of lidocaine were negligible. Patients whose intraocular level was below 12 micrograms/mL perceived more pain during surgery. Only 2 eyes had these low levels after 6 instillations. CONCLUSIONS: Topically applied lidocaine 4% effectively penetrates the eye, providing analgesia for phacoemulsification. We suggest at least 6 instillations in the hour preceding surgery. In this study, pain during surgery was primarily related to poor intraocular levels of the anesthetic agent.     

Vascular endothelial growth factor is increased in aqueous humor of glaucomatous eyes

PURPOSE: To assess the concentrations of vascular endothelial growth factor (VEGF) in aqueous humor in eyes with and without glaucoma. METHODS: Concentrations of VEGF were measured using a sandwich ELISA kit in aqueous humor aspirates taken during anterior segment surgery from 87 patients, of whom 54 had glaucoma (27 primary open-angle glaucoma, 8 angle-closure glaucoma, 16 exfoliative glaucoma) and 33 had cataract only. RESULTS: Vascular endothelial growth factor was detected in all samples. The concentration in eyes with cataract only without glaucoma was 102.4 +/- 29.7 pg/mL (mean +/- SD), which was significantly lower than that from eyes with glaucoma (146.7 +/- 51.8 pg/mL). There were no significant differences between primary open-angle glaucoma (140.4 +/- 51.0 pg/mL), angle-closure glaucoma (142.8 +/- 40.2 pg/mL), and exfoliative glaucoma (158.6 +/- 58.9 pg/mL). An unusually high VEGF concentration was detected in one eye with neovascular glaucoma (759 pg/mL) and two eyes with uveitic glaucoma (322 pg/mL). No effect of age, gender, or previous history of medical, laser, or surgical treatment of the aqueous humor VEGF concentration could be detected ( > 0.05). Aqueous humor and plasma VEGF concentrations were measured and compared in 46 patients. The aqueous humor VEGF concentration (144.2 +/- 107.9 pg/mL) was significantly higher ( < 0.01) than the plasma concentration (79.2 +/- 46.1 pg/mL). No significant correlation was found between aqueous humor and plasma VEGF concentrations. CONCLUSION: Aqueous VEGF concentration is increased in eyes with glaucoma.     

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.