Penetration of ciprofloxacin, norfloxacin and ofloxacin into the aqueous humor using different topical application modes

 · Background: A prospective study was undertaken to determine the transcorneal penetration of three topically applied fluoroquinolones into aqueous humor. · Methods: Cataract patients (n=224) preoperatively received topically applied gyrase inhibitors (0.3% ciprofloxacin, 0.3% norfloxacin, 0.3% ofloxacin) in two different application modes. In application mode I, patients received on the day before operation 3×1 eye drop at 2-h intervals, and on the day of operation 3 drops at 1-h intervals. In application mode II, patients received 9 drops at 15-min intervals on the day of operation only. Just before cataract surgery 50–100 μl aqueous humor was aspirated and stored at –80 °C. The HPLC method was used for measuring the concentration. · Results: The highest concentrations of all tested antibiotics were measured after the mode of application in which one drop was given every 15 min between 06:00 and 08:00 hours before operation. In this mode, ciprofloxacin achieved a mean aqueous level of 379.8±327.8 μg/l (range 33–1388 μg/l), norfloxacin 182.1±118.1 μg/l (range 38–480 μg/l) and ofloxacin 563.9±372.1 μg/l (range 64–1455 μg/l). These mean concentration are all above the MIC₉₀ of gram-negative bacteria like Proteus mirabilis and Escherichia coli. In some cases the concentrations of ciprofloxacin and ofloxacin, but never norfloxacin, reached therapeutic values above the MIC₉₀ of Staphylococcus aureus and Staphylococcus epidermidis · Conclusions: The mean concentration value of 0.3% ciprofloxacin and of 0.3% ofloxacin in the aqueous humor reached the MIC₉₀ values of the frequently occurring gram-positive and gram-negative bacteria. Of the currently available topical fluoroquinolones, ofloxacin achieved the highest aqueous humor concentration. Considering the higher antimicrobial activity of ciprofloxacin, both ciprofloxacin and ofloxacin may be useful ophthalmic agents in antibacterial management, but they are not efficient against Streptococcus pneumoniae and Pseudomonas aeruginosa. Received: 8 September 1997 Revised version received: 19 March 1998 Accepted: 8 April 1998     

Ascorbic acid concentration is reduced in the secondary aqueous humour of glaucomatous patients

Background: We aimed to evaluate the ascorbic acid concentration in secondary aqueous humour (AH) from glaucomatous patients and to compare it with primary AH from primary open‐angle glaucoma patients and non‐glaucomatous patients. Methods: Primary AH samples were prospectively obtained from clinically uncontrolled primary open‐angle glaucoma patients and senile cataract patients (controls) prior to trabeculectomy and cataract surgery. Secondary AH samples were obtained from eyes with previous intraocular surgery, prior to trabeculectomy or cataract surgery. AH (0.1 mL) was aspirated by inserting a 26‐gauge needle into the anterior chamber just before surgery and then immediately stored at ?80°C. The ascorbic acid concentration was determined in a masked fashion by high‐pressure liquid chromatography. Results: A total of 18 patients with senile cataract, 16 glaucomatous patients with primary AH (no previous intraocular surgery) and 11 glaucomatous patients with secondary AH (previous intraocular surgery) were included. There was no difference in mean age between groups (P = 0.15). The mean ± standard deviation concentration of ascorbic acid in the secondary AH from glaucomatous patients (504 ± 213 µmol/L [95% confidence interval {CI}, 383–624]) was significantly lower than the concentration of ascorbic acid found in the primary aqueous of primary open‐angle glaucoma (919 ± 427 µmol/L [95% CI, 709–1128]) and control patients (1049 ± 433 µmol/L [95% CI, 848–1249]; P < 0.01, Kruskal‐Wallis test). Conclusions: The ascorbic acid concentration in secondary AH of glaucomatous patients was approximately twofold lower in comparison with primary AH of glaucomatous and cataract patients. The implications of a reduced concentration of ascorbic acid in the secondary AH deserve further investigation.     

Increased anterior chamber penetration of topical levofloxacin 0.5% after pulsed dosing in cataract patients

Purpose: This study aimed to investigate the rise in aqueous humour (AH) levels of levofloxacin after a specific perioperative pulsed topical drop regimen. Methods: Thirty patients undergoing phacoemulsification surgery were administered two preoperative drops of levofloxacin 0.5%, 30 mins apart, and three pulsed drops postoperatively, 5 mins apart. Aqueous humour levels of levofloxacin were measured at the start of surgery and from 5 mins to 90 mins after the last postoperative drop. Samples from individual patients were collected at the time of surgery and at one additional sampling interval by aqueous tap, and analysed using a high‐performance liquid chromatography assay. Results: Aqueous humour levels of levofloxacin continued to rise gradually, reaching a mean peak level (C_max) of 4.4 μg/ml (± 2.5) at 60 mins after the last postoperative drop was administered. This level exceeded the minimum inhibitory concentration of common ocular pathogens at least fourfold. At 90 mins after the last drop, mean AH levels remained > 3 μg/ml. Conclusions: This is the first study to measure AH levels of levofloxacin after postoperative pulsed dosing in humans. Higher AH levels were found than in previously reported studies in which only preoperative drops were given and levels were measured at the time of surgery. Levels of levofloxacin continued to rise for 60 mins after administration of the last postoperative drop, demonstrating that delivery and maintenance of effective antibiotic levels may be achievable with alternative dosing schedules.     

Plasma and aqueous humour levels of ghrelin in open-angle glaucoma patients

Background: To compare aqueous humour and plasma levels of ghrelin, a peptide recently identified in human eyes, in patients with open‐angle glaucoma and controls. Design: Cross‐sectional, controlled, hospital‐based study. Participants: Twenty‐four open‐angle glaucoma (17 primary open‐angle and 7 pseudo‐exfoliation glaucoma) patients and 30 controls were included. All participants were patients scheduled for cataract or glaucoma surgery. Patients with other ocular pathology, previous ocular surgery or diabetes were excluded. Methods: Blood samples were collected before elective surgery. Aqueous humour was aspirated from the anterior chamber through a paracentesis with a 27‐G needle under sterile conditions before any tissue manipulation. Ghrelin quantification was performed with commercially available Radioimmunoassay kits. Main Outcome Measure: Ghrelin levels in aqueous humour and plasma. Results: Plasma levels of ghrelin were 490.5 ± 156.0 pg/mL in the open‐angle glaucoma and 482.2 ± 125.4 pg/mL in the control group (Mann–Whitney test, P = 0.897). Aqueous humour levels of ghrelin were 85.5 ± 15.4 and 123.4 ± 25.5 pg/mL in the respective groups (P < 0.001). The ratio of plasma/aqueous humour ghrelin concentration was higher in the open‐angle glaucoma versus the control group (5.75 ± 1.92 vs. 4.00 ± 1.04, P < 0.001). There was no difference in aqueous humour levels of ghrelin between primary open‐angle glaucoma and pseudo‐exfoliation glaucoma patients (P = 0.494). Conclusions: Aqueous humour levels of ghrelin were significantly lower in open‐angle glaucoma patients, compared with controls. This difference may manifest a role of ghrelin in the disease process or a consequence of antiglaucoma treatment.     

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.     

静脉用环丙沙星在开放性眼外伤眼内渗透性研究

目的 探讨在开放性眼外伤患者单剂量静脉滴注环丙沙星的眼内渗透性.方法 选择16例非化脓开放性眼外伤和12例住院白内障手术为正常对照的患者,单次静脉滴注环丙沙星注射液200mg后1h抽取少许房水和玻璃体,采用高效液相色谱法检测眼内环丙沙星浓度,双缩脲法检测房水蛋白含量. 结果正常对照组的房水蛋白含量是(0.067±0.037)g/L,开放性眼外伤组是(6.482±2.981)g/L,开放性眼外伤组的房水蛋白含量明显高于正常对照组,P<0.05.在对照组房水中环丙沙星浓度是(0.158±0.035)μg/ml,开放性眼外伤组房水中环丙沙星浓度是(0.175±0.142)μg/ml,开放性眼外伤组与对照组相比P>0.05,浓度差异无统计学意义.开放性眼外伤组玻璃体中环丙沙星浓度(0.082±0.022)μg/ml,环丙沙星在眼内不能达到眼内炎常见致病菌的体外90%最小抑菌浓度((MIC90).结论 在开放性外伤眼的血房水屏障破坏,但环丙沙星眼内渗透性并没有增强,单剂量静脉滴注后不能在眼内达到有效的抑菌浓度,在围手术期用药不能达到预期的抗菌效果.     

Penetration of cefotaxime into the aqueous humour of the human eye after intravenous application

The penetration of cefotaxime, a new semi-synthetic cephalosporin, into human aqueous humour was investigated. Doses of 1 g (17 patients) and 2 g (19 patients) were administered intravenously at time intervals varying from 45 min to 4 h prior to routine cataract surgery. After the 2 g dosage the average concentration of cefotaxime in the aqueous humour was higher (P < 0.05) and lasted longer than after the 1 g dosage. The highest average concentration in the aqueous humour after the 1 g dosage was 1.85 μg/ml, 3.95 μg/ml after the 2 g dosage. Therapeutic levels were consistently found in both groups for the organisms most commonly responsible for bacterial endophthalmitis, except forPseudomonas aeruginosa andStaphylococcus epidermidis. Presented in part at the 12th International Congress of Chemotherapy, Florence, Italy 1981     

Monocyte chemoattractant protein-1 in the aqueous humour of patients with age-related macular degeneration

Background: To investigate the role of inflammation in age‐related macular degeneration by measuring the levels of cytokines in the aqueous humour. Methods: Samples of aqueous humour were collected from 34 patients with age‐related macular degeneration and 16 age‐matched control subjects undergoing cataract surgery. Age‐related macular degeneration stage was determined clinically, before surgery. Levels of cytokines were measured using Luminex X‐MAP technology, and positive results were verified by Western blot. Results: Age‐related macular degeneration was moderate in 18 patients and advanced in 16. The advanced age‐related macular degeneration group was further divided into patients with active choroidal neovascularization (n = 7), disciform scar (n = 7) or central geographic atrophy (n = 2). Higher‐than‐normal levels of monocyte chemoattractant protein‐1 in the aqueous humour were associated with advanced age‐related macular degeneration (200 ± 140 pg/mL vs. 100 ± 61 pg/mL; P = 0.03), especially active choroidal neovascularization (255 ± 155 pg/mL; P = 0.02), Western blot analysis verified the monocyte chemoattractant protein‐1 findings. Patients with disciform scar showed a trend of abnormally high levels of interleukin‐12 (p70) (1.7 ± 2.4 pg/mL vs. 0.2 ± 1 pg/mL; P = 0.07), tumour necrosis factor‐α (1.8 ± 2.4 pg/mL vs. 0.3 ± 1 pg/mL; P = 0.06) and interleukin‐12 (4.7 ± 6.4 pg/mL vs. 1.2 ± 2.1 pg/mL; P = 0.08). Conclusion: Elevated levels of inflammation‐related cytokines in the aqueous humour in various stages of age‐related macular degeneration may suggest a pathogenic role of inflammation. Monocyte chemoattractant protein‐1 may be indicative of the angiogenic phase. Further corroborative studies are required.     

Ocular penetration of topical ciprofloxacin and norfloxacin drops and their effect upon eyelid flora.

A double blind, prospective study was undertaken to compare aqueous humour penetration of topical 0.3% norfloxacin and 0.3% ciprofloxacin and their effect upon normal eyelid flora in 39 patients undergoing cataract surgery. Lid swabs were taken before and after six 1 hourly applications of single drops of ciprofloxacin or norfloxacin given before surgery. Aqueous humour was aspirated at surgery and antibiotic concentration assayed using high performance liquid chromatography. The mean aqueous humour concentrations were: ciprofloxacin 220 ng ml-1, norfloxacin 140 ng ml-1. Although this difference was not statistically significant (p = 0.112) the trend demonstrated may be relevant clinically, especially considering the greater activity of ciprofloxacin. Both coagulase negative staphylococcal (p = 0.004) and total bacterial (p = 0.019) lid counts dropped sixfold after ciprofloxacin treatment but the smaller reductions noted after norfloxacin application did not achieve statistical significance (p > 0.1). The reduction of external eye flora experienced with ciprofloxacin suggests that this may be a useful presurgical prophylactic agent.     

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 topically applied diclofenac and ketorolac into the aqueous humour and subretinal fluid: randomized clinical trial

Objective: To determine the level of intraocular penetration of diclofenac sodium and ketorolac tromethamine into the aqueous humour and subretinal fluid.Design: Prospective randomized clinical trial.Participants: Twenty eyes scheduled for retinal detachment surgery and 17 eyes scheduled for cataract surgery.Methods: Patients with retinal detachment were randomly assigned to receive either topical ketorolac (n = 11) or topical diclofenac (n = 9). Subretinal fluid samples were collected 30–60 minutes after the administration of the last dose. In addition, 17 patients with cataract were randomly assigned to receive topical ketorolac (n = 9) or topical diclofenac (n = 8). The aqueous humour samples were collected 30 minutes after the administration of the last dose. Drug concentrations were determined by high-performance liquid chromatography fluorescence.Results: The mean diclofenac concentration in the subretinal fluid was 42.31 (SD 24.89) ng/μL. Ketorolac was undetectable in the subretinal fluid in all patients who received it because ketorolac tromethamine levels were under the limit of detection. In the aqueous humour, mean diclofenac concentration was 4.98 (SD 4.56) ng/μL, and mean ketorolac concentration was 20.17 (SD 12.21) ng/μL. Topical administration of diclofenac sodium yielded 8.4 times greater drug concentration in the subretinal fluid than in the aqueous humour. Aqueous humour concentrations of ketorolac were higher than those of diclofenac (p = 0.019).Conclusions: The concentration in the subretinal fluid of topically applied diclofenac was higher than that of ketorolac; and topical ketorolac penetrated into the aqueous humour better than diclofenac did. This suggests that diclofenac can be used more effectively in events related to posterior segment and ketorolac in anterior segment events.     

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.     

Analysis of aqueous humour proteins in patients with retinoblastoma

Background: To investigate aqueous humour protein composition from retinoblastoma patients. Design: Prospective, hospital‐based study. Participants: Eighteen retinoblastoma patients (Reese–Ellsworth stage V or ABC classification group E RB) undergoing ocular enucleation, and 10 normal subjects undergoing cataract surgery. Five of 18 patients presented with associated secondary glaucoma whereas 13 had no secondary glaucoma; 5 of 13 patients with no secondary glaucoma received chemotherapeutical treatment with melphalan. Methods: Aqueous humour samples were collected by limbal paracentesis of the anterior chamber after ocular enucleation in patients and after the stab peripheral corneal incision in controls. Total protein concentration according to Bradford method and sodium dodecyl sulphate‐polyacrylamide gel electrophoresis of the samples were performed. Main Outcome Measure: Aqueous humour protein concentration. Results: Aqueous humour protein concentration was significantly higher in retinoblastoma patients than controls (P < 0.01); patients with secondary glaucoma presented the highest values (P < 0.05 vs. controls); patients treated with melphalan presented a significant decrease (P < 0.01) versus non‐treated; controls did not significantly differ from treated patients. Sodium dodecyl sulphate‐polyacrylamide gel electrophoresis pattern in retinoblastoma patients who did not receive any treatment was very different either from treated or from controls. Conclusion: This study represents a preliminary step towards a more accurate two dimensional electrophoresis (2DE) pattern, which will be combined with mass spectrometry analysis to clarify the potential role of specific proteins in tumour development and progression; although these results suggest that aqueous humour protein pattern in retinoblastoma is characteristic, several aspects of the study are still under investigation.     

Geldanamycin is effective in the treatment of herpes simplex virus epithelial keratitis in a rabbit model

Background: To evaluate the efficacy of geldanamycin eye drops against herpes simplex virus epithelial keratitis in a rabbit model. Methods: New Zealand white rabbits were randomized into four groups and infected with herpes simplex virus type 1; geldanamycin topical eye drops was initiated 24 h after the infection and maintained for 12 consecutive days. Four groups of rabbits received 5 µg/mL geldanamycin, 10 µg/mL geldanamycin, 0.1% acyclovir and escipient (a kind of artificial tears), respectively. The severity of herpes simplex virus type 1 epithelial keratitis was measured by slit‐lamp and scored for statistics analysis. The virus shedding in eye swabs was isolated, and tissue culture infective dose (TCID₅₀) was determined. Results: Geldanamycin (10 µg/mL) treatment reduced significantly the severity of herpes simplex virus type 1 epithelial keratitis than the other three groups. Geldanamycin (5 µg/mL) was as effective as acyclovir (0.1%) treatment. The effect of geldanamycin against herpes simplex virus type 1 epithelial keratitis correlated with accelerated clearance of virus of the rabbits. Conclusion: Geldanamycin is a promising treatment option against herpes simplex virus type 1 epithelial keratitis. Geldanamycin (10 µg/mL) is better than acyclovir and geldanamycin (5 µg/mL) in the rabbit model. The optimal concentration of this drug in human is still to be determined.     

Penetration of topical and oral ciprofloxacin into the aqueous and vitreous humor in inflamed eyes.

PURPOSE: To assess the aqueous and vitreous penetration of ciprofloxacin after topical and combined topical and oral administration and investigate the effects of inflammation on drug penetration. METHODS: A standardized penetrating injury was made in the right eyes of 16 rabbits. Intraocular inflammation was induced by intravitreal injection of a suspension of Staphylococcus aureus in these eyes. The animals were divided into two groups according to treatment methodology: topical and topical-oral. The intact left eyes of the animals were maintained as controls. In the topical treatment group, two drops of ciprofloxacin 0.3% were instilled to both eyes every 30 minutes for 4 hours. In the topical-oral treatment group, animals were given two oral 40 mg/kg doses of ciprofloxacin at 12-hour intervals. After the last oral dose, the protocol of the topical group was applied to these eyes. Half an hour after the last drop, 100-microL samples were taken from aqueous and vitreous humor of all eyes. Drug concentrations were measured using high-pressure liquid chromatography. RESULTS: Mean aqueous levels of ciprofloxacin in control eyes were 2.31 microg/mL (range, 1.02-6.27 microg/mL) in the topical group and 5.88 microg/mL (1.52-17.81) in the topical-oral group. Mean aqueous levels in inflamed eyes were 7.36 microg/mL (2.34-17.15) in the topical group and 14.43 microg/mL (2.18-18.66) in the topical-oral group. Mean vitreous levels in control eyes were 0.77 microg/mL (0.09-1.93) in the topical group and 1.01 microg/mL (0.49-1.57) in the topical-oral group. Mean vitreous levels in inflamed eyes were 0.95 microg/mL (0.18-1.27) in the topical group and 1.98 microg/mL (0.51-3.34) in the topical-oral group. There was no significant difference among the groups (P > 0.05). Mean aqueous levels in all eyes and mean vitreous levels in the combined topical and oral group of inflamed eyes were above the 90% minimum inhibitory concentration for most of the common microorganisms causing endophthalmitis. CONCLUSION: There is an increase in both aqueous and vitreous humor concentrations with inflammation and with oral and topical administrations, as opposed to topical only, of ciprofloxacin. Using oral as well as topical treatment may be a beneficial method of antibiotic prophylaxis in ocular trauma once a patient has received intravenous or intravitreal therapy.     

Vascular endothelial growth factor in Coats’ disease

Purpose: To examine whether vascular endothelial growth factor (VEGF) as one of the most important intraocular cytokines for angiogenesis and increased vascular permeability is associated with Coats’ disease. Methods: The clinical interventional study included 28 patients with Coats’ disease and seven control patients with congenital cataract. During intraocular surgery, we obtained aqueous humour samples in which the VEGF concentration was measured by double‐antibody sandwich enzyme‐linked immunosorbent assay (ELISA). Coats’ disease was graded into four stages. Results: The mean aqueous VEGF level was significantly higher in the Coats’ study group than in the control group (158 ± 88 versus 97 ± 21 pg/ml; p = 0.002). The VEGF concentrations increased significantly (p < 0.001) from 91 ± 32 pg/ml in Coats’ disease stage 2 to 100 ± 37 pg/ml in stage 3A1, 185 ± 56 pg/ml in stage 3A2 to 256 ± 93 pg/ml in patients with stage 3B. Vascular endothelial growth factor concentrations in Coats’ stage 2 and 3A1 did not differ significantly from the values in the control group. Parallel to the association with the stage of the diseases, the VEGF concentrations were significantly (p < 0.001) correlated with extent of exudative retinal detachment. Conclusions: Increasing severity of Coats’ disease is significantly associated with intraocular VEGF concentrations. These results favour the intravitreal application of anti‐VEGF drugs as medical therapy of Coats’ diseases.     

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.     

Relationship between the concentration of copper and iron in the aqueous humour and intraocular pressure in rabbits treated with topical steroids

Purpose: To evaluate the concentration of copper and iron in the aqueous humour of steroid‐treated eyes, particularly to study the concentration of these metals in relation to steroid‐induced increases in intraocular pressure (IOP). Methods: Adult rabbits of both sexes were selected in order to study the effect of steroids on the concentrations of copper and iron in the aqueous humour and on IOP. The rabbits were acclimatised for 2 weeks prior to the instillation of various drugs into the eyes. Then a steroid (dexamethasone, betamethasone or fluoromethalone) was instilled in both eyes of the rabbits, for about 1 month. Intraocular pressure was measured twice a week. When IOP was significantly increased, the animals were killed. The aqueous humour was collected and analysed for copper and iron using atomic absorption spectrophotometry coupled with graphite furnace. Results: After about 30 days of steroid treatment the mean (± SD) IOP in dexamethasone, betamethasone and fluoromethalone treated groups was 17.5 (± 4.81) mmHg, 18.48 (± 4.5) mmHg and 21.8 (± 5.7) mmHg, respectively. These values were significantly higher compared to the control group where the mean IOP was 11.6 (± 2.2) mmHg. The concentration of copper in the aqueous humour of steroid‐treated rabbits was significantly lower (P < 0.001) compared to the control group. However, the concentration of iron was not significantly different between the control and steroid treated rabbits. Conclusion: A greater increase in IOP was observed in the fluoromethalone‐treated group compared to the dexa­methasone and betamethasone‐treated groups, but the difference was not significant. The lower concentrations of copper in aqueous humour in steroid‐treated eyes may play an important role in the maintenance of IOP. The concentration of iron was not significantly different compared to the control group. These results may help to explain the role of these metals in the pathogenesis of open angle glaucoma.     

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.     

The effect of colchicine on the rate of formation of aqueous humour and the gross outflow facility in the albino rabbit

Colchicine, a naturally occurring plant alkaloid which prevents the polymerisation of cytoplasmic microtubules, lowers the intraocular pressure after topical administration or intravitreal injection. In this study wer have examined the effect of topically administered colchicine on the rate of formation of aqueous humour and the gross outflow facility in the albino rabbit eye. The disappearance of [¹⁴C]inulin from the anterior chamber was measured to calculate the rate of aqueous humour formation and in a separate group of animals the gross outflow facility determined using a constant pressure perfusion technique.Topically administered colchicine (10, 20 and 40 μg/eye) inhibited the rate of aqueous humour formation dose-dependently. The mean rate of formation in control eyes was 3·68 ± 0·09 μl/min (n = 16) decreasing to 1·8 μl/min (n = 9) in eyes treated with 40 μg colchicine. Furthermore, the gross outflow facility of colchicine treated (10 μg/eye) eyes (0·49 ± 0·03 μl/min/mmHg) was significantly greater (P < 0·05) than that of contralateral control eyes (0·39 ± 0·03 μl/min/mmHg).The pharmacological evidence available indicates that colchicine is acting via mechanisms of microtubule disruption to produce an ocular hypotensive response, suggesting that microtubules may be involved in the formation of aqueous humour and possibly the maintainance of cell shape and form in the outflow vessels of the anterior chamber.