Prostaglandin E2 inhibition and aqueous concentration of ketorolac 0.4% (acular LS) and nepafenac 0.1% (nevanac) in patients undergoing phacoemulsification

PURPOSE: To determine the prostaglandin E(2) (PGE(2)) levels and aqueous concentrations achieved with ketorolac 0.4% (Acular LS; Allergan, Inc, Irvine, California, USA) and nepafenac 0.1% (Nevanac; Alcon Laboratories, Inc, Fort Worth, Texas, USA). DESIGN: Single-center, randomized, double-masked study. METHODS: One hundred and thirty-two patients received ketorolac or nepafenac four times daily for two days before cataract extraction. Aqueous samples obtained at surgery were analyzed for PGE(2) levels (competitive enzyme immunoassay) and drug concentrations. RESULTS: More ketorolac eyes than nepafenac eyes had PGE(2) levels less than the level of detection (<100 pg/ml; 26/42 [61.9%] and 7/40 [17.5%], respectively; P < .001). Mean PGE(2) levels in ketorolac eyes were lower than that in nepafenac eyes (159.5 +/- 114.66 pg/ml and 322 +/- 197.8 pg/ml, respectively; P < .001). The mean aqueous level was 1079.1 +/- 881.5 ng/ml with ketorolac and 353.4 +/- 126.0 ng/ml with amfenac. The nepafenac eyes exhibited 588.4 +/- 394.6 ng/ml of the inactive nepafenac molecule (P < .001 vs ketorolac). CONCLUSIONS: Ketorolac 0.4% inhibited PGE(2) and penetrated into aqueous significantly more than nepafenac 0.1%.     

In vivo pharmacokinetics and in vitro pharmacodynamics of nepafenac, amfenac, ketorolac, and bromfenac

PURPOSE: To evaluate the aqueous humor concentrations and cyclooxygenase (COX) inhibitory activities of nepafenac, amfenac, ketorolac, and bromfenac after topical ocular administration of Nevanac (nepafenac 0.1%), Acular LS (ketorolac 0.4%), or Xibrom (bromfenac 0.09%). SETTING: Five private ophthalmology practices throughout the United States. METHODS: Patients requiring cataract extraction were randomized to 1 of 3 treatment groups: Nevanac, Acular LS, or Xibrom. Patients were administered 1 drop of the test drug 30, 60, 120, 180, or 240 minutes before cataract surgery. At the time of paracentesis, an aqueous humor sample was collected and later analyzed for drug concentration. In addition, COX-1 (homeostatic) and COX-2 (inducible) inhibitory activities of nepafenac, amfenac, ketorolac, and bromfenac were determined via the in vitro measurement of prostaglandin E(2) (PGE(2)) inhibition. RESULTS: Seventy-five patients participated in the study. The prodrug nepafenac had the shortest time to peak concentration and the greatest peak aqueous humor concentration (C(max)). The C(max) of nepafenac was significantly higher than that of the other drugs (P<.05), including the higher-concentration ketorolac (0.4%). The area under the curve (AUC) of nepafenac was significantly higher (P<.05) than the AUCs of amfenac, ketorolac, and bromfenac. The combined AUCs of nepafenac and amfenac were the highest of all drugs tested (P<.05). Ketorolac showed the most potent COX-1 inhibition, whereas amfenac was the most potent COX-2 inhibitor. The PGE(2) aqueous humor levels of each study medication were highly variable; as a result, meaningful interpretation of the data was not possible. CONCLUSION: Nepafenac showed significantly greater ocular bioavailability and amfenac demonstrated greater potency at COX-2 inhibition than ketorolac or bromfenac.     

Preoperative ketorolac tromethamine 0.4% in phacoemulsification outcomes: pharmacokinetic-response curve

PURPOSE: To assess the clinical benefit, relative efficacy, and pharmacokinetic-response curve of preoperative and postoperative ketorolac tromethamine 0.4% (Acular LS) to improve outcomes during and after cataract surgery. SETTING: Private clinical practice. METHODS: One hundred patients were randomized in a double-masked fashion to 4 groups of 25 to receive ketorolac for 3 days, 1 day, or 1 hour or a placebo before phacoemulsification. All treatment groups received ketorolac 0.4% for 3 weeks postoperatively; the placebo group received vehicle. Outcomes measures were preservation of preoperative mydriasis, phacoemulsification time and energy, operative time, corneal clarity, endothelial cell counts, postoperative inflammation, intraoperative and postoperative discomfort, complications, and incidence of clinically significant cystoid macular edema (CME). RESULTS: Maintenance of pupil size with 3-day ketorolac dosing was significantly better than with 1-day dosing (P<.01), which was significantly better than with 1-hour or placebo dosing (P<.01). Both 3-day and 1-day dosing were superior to 1-hour or placebo dosing. No patient receiving ketorolac 0.4% for 1 or 3 days developed CME compared with 12% of patients in the control (placebo) group and 4% in the 1-hour group. Three-day and 1-day dosing of ketorolac reduced surgical time, phacoemulsification time and energy, and endothelial cell loss and improved visual acuity in the immediate postoperative period compared with 1-hour predosing and the placebo (P<.05). CONCLUSION: The preoperative use of ketorolac tromethamine 0.4% for 3 days followed by 1-day of predosing provided optimum efficacy and superior outcomes relative to 1-hour pretreatment and a placebo.     

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.     

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.     

Hepatocyte growth factor is increased in the aqueous humor of glaucomatous eyes.

PURPOSE: To assess the concentrations of hepatocyte growth factor (HGF) in the aqueous humor of eyes with glaucoma compared with control eyes with cataract only. METHODS: Concentrations of HGF were measured in aqueous humor aspirates taken during anterior segment surgery from 84 patients, of whom 72 had glaucoma (38 cases of primary open-angle glaucoma, 17 angle-closure glaucoma, and 17 exfoliative glaucoma) and 12 had cataract only, using a sandwich enzyme-linked immunosorbent assay kit. RESULTS: Hepatocyte growth factor was detected in all samples. The concentration in eyes with cataract only was 563.3 +/- 178.8 pg/mL (mean +/- standard deviation), which was significantly lower than that in eyes with glaucoma (967.1 +/- 514.7 pg/mL, P < 0.01). Eyes with exfoliative glaucoma had significantly higher HGF concentrations (1,425.5 +/- 586.7 pg/mL) than did eyes with primary open-angle glaucoma (855.0 +/- 341.5 pg/mL) and angle-closure glaucoma (759.4 +/- 511.4 pg/mL) (P < 0.01). There was no effect of age, sex, or history of medical, laser, or surgical treatment on the aqueous humor HGF concentration (P > 0.05). Aqueous humor and plasma HGF concentrations were measured and compared in 28 patients. The aqueous humor HGF concentration (908 +/- 586.2 pg/mL) was significantly higher (P < 0.01) than the plasma concentration (521.3 +/- 183.1 pg/mL). No significant correlation could be found between aqueous humor and plasma HGF concentrations. CONCLUSIONS: The relatively high concentration of HGF in human aqueous humor suggests that HGF may play an important role in ocular physiology and disease. The higher concentration in patients with glaucoma may indicate a response to injury.     

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.     

Evaluation of 0.4% ketorolac tromethamine ophthalmic solution versus 0.5% ketorolac tromethamine ophthalmic solution after phacoemulsification and intraocular lens implantation.

PURPOSE: The aim of this study was to compare the effectiveness and patient tolerance of 0.4% ketorolac tromethamine ophthalmic solution and 0.5% ketorolac tromethamine ophthalmic solution after routine phacoemulsification and lens implantation. Setting: The setting for this study was the Storm Eye Institute and Magill Research Center for Vision Correction, Medical University of South Carolina (Charleston, SC). METHODS: This work was a prospective, double-masked study that included 40 eyes of 40 patients randomly assigned to receive topical treatment with 0.4% ketorolac or 0.5% ketorolac, starting 15 min prior to routine phacoemulsification and foldable posterior chamber intraocular lens implantation. Following the procedure, patients were instructed to use the assigned treatment agent 4 times a day after surgery for 1 week and twice a day for 3 weeks, when drops were discontinued. Slit-lamp examination, intraocular pressure (IOP), laser cell and flare measurements, and subjective patient tolerance were evaluated postoperatively at 1, 7, and 30 d. Comparisons between the 2 groups were made at each visit, as well as comparisons to baseline. A P=value less than .05 was considered statistically significant. RESULTS: At day 1, a higher percentage of patients (70% vs. 40%) reported symptoms (mainly foreign body sensation and stinging/burning) in the 0.5% ketorolac group, compared to the 0.4% ketorolac group. No significant differences were found between the 2 groups over time regarding best-corrected visual acuity (BCVA), IOP, slit-lamp assessment of cells, and cell and flare measured using the laser cell/flare meter. CONCLUSIONS: Treatment with 0.4% ketorolac tromethamine ophthalmic solution is as effective as 0.5% ketorolac tromethamine ophthalmic solution in reducing inflammation after routine cataract surgery. Patients reported less discomfort using 0.4% ketorolac.     

Bromfenac ophthalmic solution 0.09 %: human aqueous humor concentration detected by high-performance liquid chromatography

The purpose of this study was to evaluate the aqueous humor concentrations of bromfenac ophthalmic solution 0.09 % in patients undergoing phacoemulsification. Patients requiring cataract extraction received one drop (50 µL) of bromfenac 0.09 % solution in the eye to be operated, before bedtime the day before surgery or the morning of the surgery. The last administration was recorded. At the time of paracentesis, an aqueous humor sample was collected with a 30-gauge needle attached to a TB syringe and was later analyzed by high-performance liquid chromatography for drug concentration. 188 treated volunteers and 48 control, untreated, subjects were included in the study. The mean aqueous concentration of bromfenac in the treated group was 37.60 ± 68.86 and 0 nM (nmol/L) in the control group (p < 0.0001). Correlation coefficient in bromfenac group between time elapsed from instillation and drug concentration was ?0.16 (p not significant). Bromfenac showed properties of good penetration and stable concentration in aqueous humor up to about 12 h after instillation.     

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.     

VEGF、IL-6的水平与糖尿病视网膜病变关系的研究

目的:检测2型糖尿病患者眼房水中血管内皮生长因子(Vascular endothelial growth factor,VEGF)和白细胞介素-6(Interleukin-6,IL-6)的含量,并探讨其临床意义.方法:在白内障手术过程中获取66例2型糖尿病患者的房水,采用双抗体夹心酶联免疫吸附(ELISA)法测定VEGF和IL-6的含量.根据手术后散瞳眼底检查和眼底荧光素血管造影检查确定糖尿病视网膜病变的分期.实验组分为:无糖尿病视网膜病变组(NDR)21例、单纯型糖尿病性视网膜病变组(BDR)26例、增生型糖尿病性视网膜病变组(PDR)19例,正常对照组为健康的老年性白内障患者20例.结果:NDR组、BDR组、PDR组的房水VEGF含量分别为(240.30±26.15)pg/ml、(292.27±58.91)pg/ml、(477.41±91.01)pg/ml,IL-6含量分别为(160.83±33.41)pg/ml、(238.60±62.23)pg/ml、(389.13±90.35)pg/ml,对照组房水VEGF含量为(140.58±26.27)pg/ml、IL-6含量为(82.72±21.53)pg/ml,对照组与实验组比较差异均有统计学意义(F=113.67,P＜0.01;F=106.53,P＜0.01).实验组房水中的VEGF与IL-6含量有相关性(r=0.995,P＜0.01);糖尿病患者的病程与房水中VEGF(r=0.792,0.826,0.841均P＜0.01)、IL-6(r=0.829,0.817,0.896均P＜0.01)含量有相关性.结论:VEGF、IL-6在糖尿病视网膜病变的形成过程中有重要作用,且两者之间有相关性.     

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.     

Prostaglandin E2 Levels of Aqueous and Vitreous Humor in Ketorolac 0.4% and Nepafenac 0.1% Administered Healthy Rabbits

Purpose: To compare the lowering effects of ketorolac 0.4% and nepafenac 0.1% on aqueous and vitreous humor prostaglandin E₂ (PGE₂) levels in rabbits.

Methods: Ketorolac and nepafenac ophthalmic solutions were administered to the right eyes of 24 healthy rabbits after randomized division into two groups. The left eyes of these rabbits were considered as controls for the two groups. On the 4th day of the experiment, the samples were taken from the aqueous and vitreous humors of the rabbits bilaterally, and PGE₂ levels were measured by an enzyme immune assay kit.

Results: Ketorolac and nepafenac achieved a statistically significant decrease (p<0.001, for each) in PGE₂ levels in the aqueous (11.75 ± 6.15 and 14.75 ± 7.60 pg/mL, respectively) and the vitreous humor (6.58 ± 4.62 and 9.83 ± 4.55 pg/mL, respectively).

Conclusions: Both ketorolac and nepafenac inhibited PGE₂ levels in both the aqueous and vitreous humors of rabbits. Although PGE₂-lowering effects were similar in the aqueous humor, nepafenac seemed to be more potent than ketorolac in the vitreous humor.     

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.     

Efficacy and safety of indomethacin 0.1% eye drops compared with ketorolac 0.5% eye drops in the management of ocular inflammation after cataract surgery

Purpose: To determine whether indomethacin 0.1% eye drops are at least as effective as ketorolac 0.5% eye drops in treating ocular inflammation following cataract surgery. Methods: Prospective, multicenter, investigator‐masked, parallel‐group, randomized, active‐controlled clinical trial. Cataract patients were randomized in a 1:1 ratio to receive indomethacin or ketorolac administered QID for 3 weeks beginning 1 day before surgery. The primary end‐point was aqueous flare measured by laser flare meter at postoperative Days 1 and 7. Secondary end‐points included retinal thickness, slit lamp and funduscopic examinations and postsurgical pain ratings. Safety and tolerability were also assessed. Results: A total of 86 patients were included in the per protocol population (n = 43 per treatment group). Indomethacin was found non‐inferior to ketorolac for comparison of aqueous flare at postoperative Days 1 and 7 (Day 1: 95% CI: ?2.37, 5.50; non‐inferiority upper margin, 15 ph/ms and Day 7: 95% CI: ?7.83, ?0.94; non‐inferiority upper margin, 8 ph/ms) and statistically better than ketorolac at Day 7 (p = 0.013). There were no significant between‐group differences in aqueous flare and change from baseline in retinal thickness at postoperative Days 30 and 90. Indomethacin showed a higher subjective tolerance rating than ketorolac at postoperative Days 7 and 30 (p ≤ 0.044). Conclusion: Indomethacin 0.1% was at least as effective as ketorolac 0.5% at Day 1 and more effective than ketorolac 0.5% at Day 7 in treating ocular inflammation after uncomplicated cataract surgery. Indomethacin was better tolerated than ketorolac. There were no clinically meaningful safety concerns with either treatment.     

Higher concentration of transforming growth factor-beta in aqueous humor of glaucomatous eyes and diabetic eyes

PURPOSE: Diabetic retinopathy and glaucoma are the primary causes of acquired blindness. Cytokines including transforming growth factor (TGF)-beta may be involved in these diseases. We therefore collected aqueous humor samples from patients with glaucoma and/or diabetes who were undergoing surgery, and determined the concentration of TGF-beta. METHODS: Aqueous humor samples were collected from 80 patients (84 eyes), including 19 eyes with primary open-angle glaucoma (POAG), 22 eyes with diabetes, and 18 eyes with diabetes complicated with POAG. Twenty-five eyes with cataract served as controls. The concentration of TGF-beta1 or TGF-beta2 was measured by enzyme-linked immunosorbent assay. RESULTS: The concentration of TGF-beta1 was less than 0.1 pg/mL in all of the groups. In contrast to controls who had 1001.4 +/- 444.1 pg/mL, the concentration of total TGF-beta2 in the diabetes group was 1715.6 +/- 882.1 pg/mL, and that in the diabetes complicated with POAG group was 1692.9 +/- 361.9 pg/mL. These were significantly higher than that in controls. In contrast to the controls who had 321.2 +/- 197.9 pg/mL, the concentration of mature TGF-beta2 with POAG was 822.5 +/- 484.4 pg/mL, and that of diabetes complicated with POAG was 1058.9 +/- 648.4 pg/mL. These were significantly higher than that in the controls. The eyes with diabetes complicated with POAG also had a significantly higher concentration than the eyes with diabetes alone. CONCLUSION: Total TGF-beta2 and mature TGF-beta2 in high concentration may correlate with progression of POAG, diabetes, and diabetes complicated with POAG.     

The systemic safety of bromfenac ophthalmic solution 0.09%.

STUDY OBJECTIVE: The aim of this study was to evaluate the systemic safety of a commercially available bromfenac ophthalmic solution 0.09% for the treatment of postoperative inflammation and reduction of ocular pain in subjects who have undergone cataract extraction. DESIGN: Two phase III, multicenter, randomized, double-masked, parallel, placebo-controlled, clinical trials were conducted under a common protocol. These data were pooled for analysis. SETTING: The setting for this study was a series of multicentered, private, and university-affiliated ophthalmology clinics in the United States. SUBJECTS: A total of 527 subjects were sequentially assigned, according to a computer-generated randomization list (2:1) to either bromfenac (n = 356) or placebo (n = 171). Potential subjects were excluded if using nonsteroidal anti-inflammatory drugs (NSAIDs), steroids, anticoagulants, or with uncontrolled ocular or systemic disease, preexisting ocular inflammation, surgical complications, or liver chemistry values of > or =Grade 1 according to World Health Organization Common Toxicity Criteria scoring. Intervention: Subjects who underwent cataract surgery without prior anti-inflammatory treatment and had a postsurgical Summed Ocular Inflammation Score (SOIS) of > or =3 were treated with either bromfenac or placebo. Subjects self-instilled 1 drop of the assigned test agent twice-daily for 14 days and were followed for an additional 14 days for safety evaluation. MAIN OUTCOME MEASURES: Safety data were collected and the results for systemic safety are reported in this paper. RESULTS: Five hundred and twenty-seven (527) subjects comprised the safety population. A total of 290 of 356 bromfenac and 93 of 171 placebo subjects received 28 doses of test agent. No clinically significant treatment-related systemic adverse effects or changes in liver chemistries were observed. CONCLUSIONS: Bromfenac ophthalmic solution 0.09% demonstrated neither treatment-related systemic adverse events nor evidence of hepatic toxicity.     

Effect of bromfenac ophthalmic solution on ocular inflammation following cataract surgery

Purpose: This study compared the post‐cataract surgery anti‐inflammatory effects of topical treatment with 0.1% bromfenac, 0.1% betamethasone or both on postoperative anterior chamber inflammation and corneal swelling. Methods: Seventy‐two patients with no eye disease other than cataract were enrolled in a prospective, randomized study to undergo phacoemulsification combined with intraocular lens implantation. After cataract surgery, patients were randomized to treatment with bromfenac, betamethasone or both agents. Twenty‐five eyes were assigned to bromfenac, 23 to betamethasone and 24 to the combined treatment group. Inflammatory reactions in the anterior chamber were measured with laser flare photometry preoperatively and at 1 and 3 days, 1 and 2 weeks, and 1 and 2 months postoperatively. Intraocular pressure (IOP) and corneal thickness were measured at the same time‐points. Best corrected visual acuity (BCVA) was measured preoperatively and at 2 days, 1 and 2 weeks, and 1 and 2 months postoperatively. Specular microscope endothelial photography of the central region of the cornea was performed preoperatively and at 3 months after surgery. Results: There were no significant differences among the bromfenac, betamethasone and combined treatment groups in BCVA, IOP, aqueous flare or corneal thickness. Cystoid macular oedema was present in one eye treated with betamethasone. Conclusions: There were no significant differences in anti‐inflammatory effects among the three treatments. These findings suggest that bromfenac is as effective as betamethasone in minimizing inflammatory reactions after cataract surgery.     

Increased melatonin levels in aqueous humor of patients with proliferative retinopathy in type 2 diabetes mellitus

AIM: To report the association between melatonin levels in aqueous humor and serum, and diabetic retinopathy (DR) grade in type 2 diabetic patients. METHODS: Aqueous humor and plasma samples from 26 patients with DR (in nonproliferative and proliferative stages) and 14 control subjects were collected during cataract surgery after 6 p.m. Melatonin concentrations were determined using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Melatonin levels were significantly higher in the aqueous humor of patients with proliferative diabetic retinopathy (PDR) [18.57±2.67 pg/mL (range 15.20-23.06) vs 13.63±2.71 pg/mL (range 10.20-20.20), P=0.0001], but not in those with nonproliferative retinopathy (NPDR) [13.79±2.56 pg/mL (range 9.80-20.10) vs 13.63±2.71 pg/mL (range 10.20-20.20), P=0.961] compared to controls. There was decrement in the plasma melatonin level of patients with PDR, but no significant differences between the plasma melatonin levels of the study groups [5.37±1.74 pg/mL (range 2.85-8.65) vs 6.11±1.90 pg/mL (range 3.13-9.41), P=0.293], or between control and DR groups [NPDR 6.11±1.90 pg/mL (range 3.13-9.41) vs control 6.15±1.91 pg/mL (range 2.18-9.86); PDR (5.37±1.74 pg/mL (range 2.85-8.65) vs control 6.15±1.91 pg/mL (range 2.18-9.86), P=0.808, P=0.264]. CONCLUSION: Elevated melatonin levels in aqueous humor in PDR may indicate the level to be associated with DR severity.     

Comparison of the efficacy and safety of ketorolac tromethamine 0.5% and prednisolone acetate 1% after cataract surgery.

PURPOSE: To compare the anti-inflammatory and analgesic efficacy and safety of ketorolac tromethamine 0.5% ophthalmic solution with those of prednisolone acetate 1% in patients having cataract surgery. SETTING: Shawnee Mission Eye Care, Shawnee Mission, Kansas, USA. METHODS: This double-blind, randomized, single-site study comprised 59 healthy men and women with a clinical diagnosis of routine ocular cataract requiring surgical removal. All patients had extracapsular cataract extraction and posterior chamber intraocular lens implantation. After surgery, patients were randomized to receive ketorolac tromethamine 0.5% or prednisolone acetate 1%, self-instilled in the treated eye, according to the following schedule: 1 to 2 drops 4 times daily (week 1); 3 times daily (week 2); 2 times daily (week 3); once daily (week 4). Patients were examined postoperatively on days 1, 7, and 28. Intraocular anti-inflammatory efficacy was assessed by lid edema, lid injection, conjunctival injection, corneal edema, ciliary flush, and anterior chamber cells. Analgesic efficacy was assessed by patient self-rated pain severity, pain frequency, total symptom sum, and overall global improvement. RESULTS: Both treatments produced comparable reductions in intraocular inflammation and pain after cataract surgery and were well tolerated by patients. No adverse events were reported, and there were no significant changes in intraocular pressure in either group. Improvements in visual acuity were also similar in both groups. CONCLUSION: Ketorolac tromethamine 0.5% ophthalmic solution was as effective and well-tolerated as prednisolone acetate 1% solution in controlling postoperative inflammation and pain after cataract surgery.