An in vitro study on the compatibility and precipitation of a combination of ciprofloxacin and vancomycin in human vitreous

AIMS: To investigate the precipitation process of a mixture of vancomycin and ciprofloxacin by equilibrium dialysis and its subsequent effect on the level of available free antibiotics. METHODS: Concentrations of vancomycin and ciprofloxacin in an equilibrium dialysis chamber were measured during the equilibrium process by high performance liquid chromatography and fluorescence polarisation immunoassay. Normal saline (NS), balanced salt solution plus (BSS Plus), and vitreous were used separately as the medium of dialysis. RESULTS: Precipitation of ciprofloxacin occurred on incubation at 37 degrees C. It formed precipitate on its own or when mixed with vancomycin in all the three media of NS, BSS Plus, and vitreous. There was more precipitation at higher initial ciprofloxacin concentrations; at 25.0 mg/l about 75% free drug in BSS Plus was lost after 72 hours. The extent of precipitation was similar in both NS and BSS Plus. In the dialysis chambers, 20 mg/l ciprofloxacin dialysed against 125 mg/l vancomycin was reduced to a concentration about 5.0 mg/l after 168 hours. Precipitation of vancomycin was negligible. Ciprofloxacin precipitated in vitreous at body temperature, irrespective of the presence of vancomycin. Even after precipitation, the resultant concentration of ciprofloxacin was still higher than the MIC(90) of the drug against most Gram negative organisms. CONCLUSIONS: Based on this in vitro study, ciprofloxacin precipitated in vitreous at body temperature, irrespective of the presence of vancomycin or the medium for intravitreal injection. The resultant amount of ciprofloxacin was still higher than the MIC(90) of the drug against most Gram negative organisms after precipitation. The authors suggest ciprofloxacin in place of ceftazidime when used in combination with vancomycin for treatment of infective endophthalmitis.     

An in vitro study on the compatibility and concentrations of combinations of vancomycin, amikacin, and dexamethasone in human vitreous

PURPOSE: To investigate the precipitation process of a mixture of vancomycin, amikacin, and dexamethasone by equilibrium dialysis and its subsequent effect on the levels of available-free antibiotics and steroid. METHODS: Concentrations of amikacin, vancomycin, and dexamethasone in an equilibrium dialysis chamber were measured during the equilibrium process by high-performance liquid chromatography and fluorescence polarisation immunoassay. Vitreous were used as the medium of dialysis, with the three medications prepared in normal saline (NS) and balanced salt solution plus (BSS Plus) separately. RESULTS: Amikacin showed no measurable loss in NS or BSS Plus, either alone or when mixed with vancomycin or dexamethasone. Vancomycin showed minimal loss in BSS Plus, either alone or when mixed with amikacin or dexamethasone. Dexamethasone showed a median loss of 16 and 15% when incubated alone in NS and BSS Plus, respectively, at 48 h. When mixed with vancomycin or amikacin in BSS Plus, it showed a median loss of 13 and 12%, respectively, at 48 h. There was no statistically significant difference in the loss of dexamethasone under various conditions. In equilibrium dialysis in vitreous, amikacin, vancomycin, and dexamethasone reached equilibrium within 24 h and with no loss up to 192 h. There was no difference observed when the medications were prepared in NS or BSS Plus. CONCLUSIONS: Both amikacin and vancomycin did not show precipitation or decrease in concentration in NS or BSS Plus. Dexamethasone showed relatively small percentage loss. As a result, treatment of endophthalmitis with vancomycin and amikacin combination is preferred.     

Physicochemical properties and antibacterial activity of the precipitate of vancomycin and ceftazidime: implications in the management of endophthalmitis

OBJECTIVE: To study the physicochemical properties, bioavailability, and microbicidal activity of vancomycin and ceftazidime in the precipitate formed by the drugs in mixture. METHODS: The precipitation of the drugs prepared in buffers in the pH range of 5.8 to 8.9, in normal saline, in balanced salt solution (BSS), and in Ringer lactate, was studied by light scatter analysis. Bioavailability and antibacterial activity of the precipitate and the supernatant were estimated using high-performance liquid chromatography (HPLC) and microbiologic assay respectively. RESULTS: The scatter analysis showed precipitation of vancomycin alone at pH 7.5 and in BSS. When mixed together precipitation was observed in the mixture of the two drugs within the pH range of 6.8 to 8.0 and in all solutions. HPLC of both supernatant and precipitate showed the presence of active drugs and the microbiologic assay confirmed its inhibitory activity against bacteria. The precipitate had greater activity against Gram-positive bacteria while the supernatant showed greater activity against Gram-negative bacteria. CONCLUSIONS: Vancomycin's pH dependent precipitation occurs regardless of the presence of ceftazidime. The precipitate as well as the supernatant retains significant antibacterial activity thus confirming the efficacy of combination therapy with vancomycin and ceftazidime in the management of bacterial endophthalmitis.     

Safety of in vivo pharmacologic vitreolysis with recombinant microplasmin in rabbit eyes

PURPOSE: To investigate the safety of intravitreal microplasmin in rabbits and to confirm previous findings of posterior vitreous detachment (PVD). METHODS: Different doses of microplasmin, from 12.5 microg to 250 microg, in 0.1 mL balanced salt solution (BSS) were injected into the vitreous cavity of rabbit eyes to induce PVD. Fellow eyes were injected with the same volume of BSS. Slit-lamp biomicroscopy, ophthalmoscopic fundus examinations, A- and B-mode ultrasonography, and electroretinography were performed to assess the retina. Electroretinograms (ERGs) were recorded up to 90 days after injection. Morphologic alterations were assessed by light microscopy, scanning electron microscopy (SEM), and transmission (TEM) electron microscopy. RESULTS: A slight aqueous flare and cells were observed in the anterior chamber after microplasmin and BSS injection. A slight inflammatory reaction was also observed transiently in the vitreous cavity. In control eyes, B-mode ultrasonography and SEM examination demonstrated that PVD did not develop after BSS injection. Intravitreal injections of 125 microg or greater of microplasmin induced complete PVD with an internal limiting membrane (ILM) devoid of vitreous collagen fibrils. Eyes injected with 12.5 microg microplasmin had partial PVD, and SEM showed residual fibrils covering the ILM. In all eyes, there was a transient reduction in the a- and b-waves of the ERG on days 2 through 7. The ERGs showed less effect with < 250 microg microplasmin. CONCLUSIONS: Intravitreal injection of recombinant microplasmin in the rabbit induces no ERG or retinal ultrastructural abnormalities. Pharmacologic vitreolysis with this agent may be a useful adjunct to vitreous surgery and could be used to induce PVD without vitreous surgery.     

Prophylaxis of experimental Pseudomonas aeruginosa endophthalmitis after vitrectomy using ceftazidime in the irrigating solution

Purpose: To test the efficacy of ceftazidime in irrigating solution during vitrectomy to prevent experimental Pseudomonas aeruginosa endophthalmitis. Methods: Thirty-two rabbit eyes were divided into 6 groups. Vitrectomy using one of two different irrigating solutions was followed by intravitreal injection of P. aeruginosa: Group 1, balanced salt solution (BSS) followed by 100 colony-forming units (CFU) P. aeruginosa; Group 2, BSS fortified with ceftazidime 175 μg/mL (CBSS) followed by intravitreal injection of 100 CFU P. aeruginosa; Group 3, BSS followed by 500 CFU P. aeruginosa; Group 4, CBSS followed by 500 CFU P. aeruginosa; Group 5, BSS followed by 5000 CFU P. aeruginosa; and Group 6, CBSS followed by 5000 CFU P. aeruginosa. The eyes were examined clinically. Vitreous samples were cultured and histology was performed. Results: Group 1: Three of 5 eyes showed mild to moderate vitreous opacities. Group 2: No vitreous opacities developed. Group 3: All eyes demonstrated endophthalmitis. Group 4: All 6 eyes had clear vitreous with visible fundus. Group 5: Severe endophthalmitis occurred in all 6 eyes. Group 6: Four eyes had clearly visible fundus, 2 eyes had hazy vitreous with red reflex of the fundus. Bacterial growth in groups 3, 4, 5, and 6 was seen in 4/4, 1/6, 6/6, and 0/6 eyes, respectively. Conclusion: When 100-5000 CFU P. aeruginosa were injected after vitrectomy, ceftazidime in the irrigating solution inhibited the signs of intraocular inflammation, and the rate of positive bacterial culture. This revised version was published online in July 2006 with corrections to the Cover Date.     

Vitreous dynamics: vitreous flow analysis in 20-, 23-, and 25-gauge cutters

PURPOSE: To evaluate porcine vitreous flow and balanced saline solution (BSS) flow rates in different vitrectomy systems. METHODS: Porcine vitreous was obtained within 24 hours of slaughter. A high-speed (2 samples/s) balance, precise to 0.01 g, was used. Variable cut rates and vacuum pressures were analyzed in vitreous and BSS. The vitreous was labeled with glass microspheres and triamcinolone acetonide. A high-speed (400 frames/s) camera was used to record cutting for each condition. RESULTS: For all cutters, there was no vitreous flow at zero cut rates (off). In 25-gauge cutters, at 500 mmHg of vacuum, the electric cutter produced higher average flow rates at high cut rates (600 cpm, 0.004 mL/s, and 1500 cpm, 0.013 mL/s) than pneumatic, which demonstrated a decreased flow at speeds higher than 1000 cpm (1000 cpm, 0.015 mL/s, and 1500 cpm, 0.006 mL/s). The percentage of vitreous flow rate/BSS flow rate in different aspiration and cut rates showed an ascending curve. This demonstrates evidence of flow obstruction in 25- (all cut rates), 23- (all cut rates), and 20-gauge (all cut rates). Flow obstruction and surge movements were seen in the high-speed videos. CONCLUSIONS: The vitrectomy systems each illustrate different performances of vitreous removal. The physical characteristics of vitreous resulted in nonuniform flow in all vitreous cutters.     

Experimental prophylaxis of Staphylococcus aureus endophthalmitis after vitrectomy: the use of antibiotics in irrigating solution.

PURPOSE: To test the efficacy of clindamycin and gentamicin in irrigating solution during vitrectomy to prevent experimental Staphylococcus aureus endophthalmitis. MATERIALS AND METHODS: Thirty-six New Zealand white rabbits were divided into six groups. Vitrectomy using two different irrigating solutions was followed by intravitreal injection of S. aureus: Group 1, balanced salt solution (BSS) followed by 1,000 colony-forming units (CFU) S. aureus; Group 2, BSS fortified with clindamycin, 10 microg/mL, and gentamicin, 8 microg/mL (CGBSS), followed by intravitreal injection of 1,000 CFU S. aureus; Group 3, BSS followed by 2,000 CFU S. aureus; Group 4, CGBSS followed by 2,000 CFU S. aureus; Group 5, BSS followed by 4,000 CFU S. aureus; and Group 6, CGBSS followed by 4,000 CFU S. aureus. The eyes were examined clinically after surgery. Vitreous samples were cultured and histologic studies were performed. RESULTS: Severe endophthalmitis developed in all eyes in Groups 1, 3, and 5 (not given antibiotics). No endophthalmitis developed in Group 2. In Group 4, five of the six eyes were normal and one eye had endophthalmitis. In Group 6, one eye had clear vitreous and fundus, three eyes had moderate vitreous haze, and the other four eyes demonstrated severe endophthalmitis. Bacterial growth in Groups 1, 2, 3, 4, 5, and 6 were 4/4, 0/4, 6/6, 1/6, 4/6, and 2/8 eyes, respectively. CONCLUSION: When 1,000 to 2,000 CFU S. aureus were injected after vitrectomy, clindamycin and gentamicin in the irrigating solution significantly diminished the intraocular inflammation and the rate of positive bacterial culture. Clindamycin and gentamicin in the irrigating solution were not significantly effective when 4,000 CFU bacteria was injected; however, the degree of inflammation was less severe than in the control group.     

头孢哌酮/舒巴坦玻璃体腔注射治疗兔铜绿假单胞菌性眼内炎

目的评价头孢哌酮/舒巴坦治疗铜绿假单胞菌眼内炎的疗效。方法青紫蓝兔18只,随机分为3组,右眼注菌后6h分别注入100g/L头孢哌酮/舒巴坦、22.5g/L头孢他啶和生理盐水各0.1mL,观察24h。另取青紫蓝兔12只,随机分为2组。早期注药组注菌后6h注入100g/L头孢哌酮/舒巴坦0.1mL,晚期注药组注菌后20h注入100g/L头孢哌酮/舒巴坦0.1mL,观察1周。结果头孢哌酮/舒巴坦组、头孢他啶组与生理盐水组比较除角膜评分外（P〉0.05）,结膜、前房、玻璃体、视网膜、B型超声检查及组织病理学评分结果差异均有统计学意义（P〈0.05）;头孢哌酮/舒巴坦组与头孢他啶组相比,除虹膜炎症反应评分差异有统计学意义外（P〈0.05）,其他评分差异均无统计学意义（P〉0.05）,但从具体评分来看头孢哌酮/舒巴坦组优于头孢他啶组。早期注药组与晚期注药组相比,1周后结膜、前房、虹膜、玻璃体、视网膜、B型超声检查及组织病理学评分差异均有统计学意义（P〈0.05）。结论 100g/L头孢哌酮/舒巴坦0.1mL玻璃体腔注射治疗早期铜绿假单胞菌眼内炎有效。     

Aqueous and vitreous penetration of linezolid (Zyvox) after oral administration

OBJECTIVE: To investigate the penetration of linezolid, a synthetic oxazolidinone antibiotic, into the aqueous and vitreous humor after oral administration. DESIGN: Noncomparative interventional, prospective case series study, randomized into group 1 (dose, one 600-mg tablet) or group 2 (2 doses of 600 mg given 12 hours apart). PARTICIPANTS: Patients undergoing pars plana vitrectomy between March 2001 and August 2002 at the University of Illinois at Chicago Eye Center who had not had prior vitrectomy surgery. METHODS: Aqueous, vitreous, and plasma samples were obtained and analyzed from 29 patients after oral administration of 1 dose (group 1A, 13 patients [13 eyes] sampled less than 2 hours after administration; group 1B, 9 patients [9 eyes] sampled more than 2 hours after administration) or 2 doses 12 hours apart (group 2, 7 patients [7 eyes]) before surgery. MAIN OUTCOME MEASURES: Aqueous, vitreous, and plasma concentrations of linezolid (micrograms per milliliter). RESULTS: Group 1A achieved mean aqueous, vitreous, and plasma levels of 0.77+/-0.6 microg/mL, 0.3+/-0.3 microg/mL, and 5.0+/-3.3 microg/mL, respectively. Group 1B achieved mean aqueous, vitreous, and plasma levels of 3.8+/-1.2 microg/mL, 2.3+/-1.4 microg/mL, and 7.6+/-2.7 microg/mL, respectively. Group 2 achieved mean aqueous, vitreous, and plasma levels of 6.6+/-2.7 microg/mL, 5.7+/-2.7 microg/mL, and 10.3+/-4.1 microg/mL, respectively. CONCLUSIONS: Mean inhibitory aqueous and vitreous minimum inhibitory concentrations for 90% of isolates (MIC(90)) were achieved against all gram-positive bacteria, including vancomycin-resistant enterococcus, methicillin-resistant Staphylococcus aureus, and streptococcal species after 2 doses given 12 hours apart. Mean MIC(90) were achieved for many gram-positive pathogens after only one dose in many patients after approximately 4 hours.     

Intraocular vancomycin levels after intravitreal injection in post cataract extraction endophthalmitis.

PURPOSE: Intravitreal antibiotics are the mainstay of treatment of endophthalmitis following cataract surgery. The purpose of this study is to determine the range of intraocular vancomycin found after intravitreal therapy and assess the optimum time for repeat injections. METHODS: Aqueous and vitreous vancomycin was assayed at the time of reinjection in 14 patients with endophthalmitis showing a poor clinical response after their primary injection. Nine patients received vancomycin 2 mg and another five received vancomycin 1 mg. In six patients the injection was repeated at 48 hours and in seven at 72 hours. Two patients received three injections. RESULTS: Aqueous vancomycin varied from 8.4 to 170 mg/L and the vitreous vancomycin level ranged from 21.2 to 220 mg/L. CONCLUSIONS: In the current study vitreous vancomycin levels were variable, but well within the therapeutic range for sensitive Gram-positive organisms. At times they exceeded the putative retinotoxic levels (100 mg/L). Higher aqueous levels were found after an injection of 2 mg than after 1 mg. Vancomycin levels were still very high 3 days after injection of 2 mg where results were available. Assay at the time of repeat injection may provide insight into the adequacy of vitreous levels and guide future therapy.     

Bilateral Endophthalmitis as the Initial Presentation of Bacterial Meningitis

To report a case of bilateral endophthalmitis as the initial presentation of bacterial meningitis in a young, immunocompetent Korean patient. A 35-year-old female with a one day history of bilateral swollen eyes, visual disturbance, headache, petechial skin rash, and nausea visited our clinic. She was diagnosed as having endogenous endophthalmitis associated with bacterial meningitis. Intravenous broad spectrum antibiotic therapy was initiated with cefotaxime 3 g and ubacillin 3 g, four times daily. Intravitreal antibiotic (vancomycin 1 mg/0.1 mL and ceftazidime 2 mg/0.1 mL) injections were performed in both eyes. Two weeks post presentation, the best corrected visual acuity in both eyes improved to 0.7, and inflammation of the anterior chamber and vitreous cavity was decreased. We recommend that when endogenous endophthalmitis is suspected along with meningitis, or if it is known to be present, intravitreal and intravenous antibiotics should be promptly administered to preserve vision.     

Usefulness of voriconazole in treatment of Phoma glomerata after penetrating injury

We report the first case of endophthalmitis caused by Phoma glomerata. A 32-year-old man who underwent retinal detachment surgery consecutive to a penetrating globe injury presented with endophthalmitis 7 days after surgery. Anterior chamber tap and intravitreal injection of antibiotics (ceftazidime and vancomycin) were performed systematically. Fungus was observed at microscopic examination of the aqueous humor and treatment with intravitreal injection of amphotericin B was decided. The patient failed to improve with intravitreal amphotericin B but responded clinically to intravitreal voriconazole. The fungus was identified after culture as Phoma glomerata. The MIC for amphotericin B was 1microg/ml, for caspofungin was 2microg/ml, and for itraconazole was 8microg/ml or more. The MIC for voriconazole was up to 8microg/ml. The clinical response after intravitreal injection may be related to the high concentrations reached in the vitreous. Because of severity and ominous prognosis of intraocular fungal infections and posttraumatic Phoma ocular infections, aggressive management is required by intravitreal voriconazole administration.     

Clearance of intravitreal moxifloxacin

PURPOSE: To study the clearance of moxifloxacin after intravitreal injection in rabbits. METHODS: Intravitreal injections of 200 microg/0.1 mL of moxifloxacin were administered to rabbits. Four eyes per time point after injection (1 hour and 6, 12, 24, and 36 hours) and three eyes at 48 hours, respectively, were enucleated and immediately frozen and stored at -80 degrees C. Ocular dissection and isolation of frozen vitreous was performed. Vitreous samples were acquired at the various time intervals after injection. Antibiotic assays were performed with high performance liquid chromatography. RESULTS: The concentration of intravitreal moxifloxacin showed an exponential decay with a half-life of 1.72 hours. The mean vitreous concentration was 120.49 +/- 49.23 microg/mL 1 hour after injection, and declined to 20.23 +/- 5.85 microg/mL at 6 hours and 1.06 +/- 0.81 microg/mL at 12 hours, respectively. CONCLUSIONS: The vitreous concentrations achieved were several orders of magnitude greater than the MIC90 of organisms commonly involved in bacterial endophthalmitis, and therapeutic levels were maintained at 12 hours in uninflamed, phakic rabbit eyes. The pharmacokinetic data suggest that intravitreal moxifloxacin may have a role in the treatment of bacterial endophthalmitis.     

Modified high-performance liquid chromatography technique for detection of vancomycin in human vitreous

PURPOSE: To standardize the technique and methodology for estimating the level of vancomycin in human vitreous using a modified high-performance liquid chromatographic method. METHODS: Sample preparation involved spiking the vitreous with known quantities of the drug followed by a brief treatment with 30% trichloroacetic acid. Samples were analyzed on a C18 reverse-phase column using a mobile phase of 50 mM phosphate buffer (pH 4.0) and 10% acetonitrile. RESULTS: Vancomycin was detected at 198 nm. It showed a retention time of 2.2 min in the vitreous. A linear increase in the area under the peak corresponding to the drug was observed with increase in concentration of vancomycin in the vitreous. The method was applied to detect the vancomycin levels in vitreous of 5 patients with exogenous endophthalmitis, 24-48 h after intravitreal injection of vancomycin 1 mg/0.1 ml. The mean concentration of vancomycin in these samples was 120.022 +/- 59.87 microg/ml (43.859-179.09 microg/ml). The present technique allowed a quantification limit of 1 microg/ml. CONCLUSION: This technique is suitable to estimate vancomycin levels in human vitreous in a variety of clinical and experimental studies. It has the added advantages of being less expensive, simple and rapid.     

Pharmacokinetics of intravitreal 5-fluorouracil prodrugs in silicone oil: experimental studies in pigs

PURPOSE: To examine the in vivo pharmacokinetics of intravitreal 5-Fluorouracil (5-FU) following tamponade with 5-FU prodrug silicone oil formulations. METHOD: Two different alkoxycarbonyl 5-FU prodrugs denoted C12 and C18 were synthesized and formulated as silicone oil suspensions. A total of 26 pigs underwent conventional three-port lens-sparing pars plana vitrectomy. Approximately 1.6 ml of the prodrug-silicone oil formulation was placed in the vitreous cavity. Operated eyes were enucleated between 20 min and 168 hours postoperatively, and analysed for their content of free 5-FU by high performance liquid chromatography. RESULTS: With the C12 prodrug silicone oil formulation, the concentration of free 5-FU in the vitreous water phase 1 hour after surgery was 3.30 +/- 1.62 microg/ml. After 4 hours this concentration had declined to 1 microg/ml. With the C18 prodrug, the concentration of free vitreal 5-FU never reached 1 microg/ml during the 7 days these experiments lasted. A mathematical model is presented that can explain the measured data if the clearance of 5-FU from the vitreous water phase follows first order kinetics with a half-life of 20 min. CONCLUSION: These experiments, and the model analysis, suggest that the elimination half-life of 5-FU in the vitreous cavity of a vitrectomized, silicone oil-filled eye is very fast. The model analysis indicates that an alkoxycarbonyl 5-FU prodrug with a specific release rate constant of 10.7 microg/square root h cm(2) can maintain an intravitreal 5-FU concentration above 1 microg/ml for 5 days in the porcine eye.     

In vitro influence of vancomycin on adhesion of a Staphylococcus epidermidis strain encoding intercellular adhesion locus ica to intraocular lenses

PURPOSE: To assess anti-adhesion and/or bactericidal properties of vancomycin in vitro and to determine when these effects are detectable to estimate its relevance to perioperative antibiotic prophylaxis and analyze the efficacy of a newly designed vancomycin insert prototype for endophthalmitis prevention. SETTING: University research laboratory, Lyon, France. METHODS: Staphylococcus epidermidis clinical strain N890074 containing the intercellular adhesion locus ica was used as the infectious agent. Vancomycin was used at 20 microg/mL. A sterile biocompatible, biodegradable vancomycin insert, releasing 230 microg of antibiotics over 100 minutes, was designed especially for this study. To obtain bacterial killing curves, experiments were first performed in a 103 colony-forming units (CFU/mL) bacterial suspension containing no intraocular lenses (IOL). Then IOLs were incubated in the suspension, and bacterial adherence was determined using bacterial counting with and without antibiotic. RESULTS: Vancomycin (solution and insert) had an anti-adhesion effect after 1 hour and a relevant bactericidal effect after 6 hours of incubation. CONCLUSIONS: Vancomycin used with irrigating solutions does not remain in the anterior chamber long enough to develop bactericidal effect. Even if it initially reduces bacterial adhesion, used at a drug level dropping below the bacterial minimal inhibitory concentration, it could result in a secondary increase of the adhesion of slime-producing bacteria. A sufficiently high concentration was obtained in vitro by the new sustained-release system, thereby overcoming the theoretical drawback of a short half-life within the anterior chamber. Anti-adhesion and bactericidal action of vancomycin inserts remains to be confirmed in clinical studies.     

Clearance of intravitreal voriconazole

Purpose To investigate the elimination rate of voriconazole after intravitreal injection in rabbits. METHODS: Intravitreal injections of 35 microg/0.1 mL voriconazole were administered to rabbits. Vitreous and aqueous humor levels of voriconazole were determined at selected time intervals (1, 2, 4, 8, 16, 24, and 48 hours), and the in vitreous half-life was calculated. Four to six eyes per time point after injection were enucleated and immediately stored at -80 degrees C. Aqueous humor samples were withdrawn before enucleation, and vitreous samples were obtained from ocular dissection and isolation at various time intervals. Voriconazole concentrations in vitreous and aqueous humor were assayed with high-performance liquid chromatography (HPLC). RESULTS: The concentration of intravitreal voriconazole at various time points exhibited exponential decay with a half-life of 2.5 hours. The mean vitreous concentration was 18.912 +/- 2.058 microg/mL 1 hour after intravitreal injection; this declined to 0.292 +/- 0.090 microg/mL at 16 hours. The mean aqueous concentration was much lower and showed a decline from 0.240 +/- 0.051 microg/mL at 1 hour to undetectable levels 8 hours after injection. CONCLUSIONS: Vitreous concentrations achieved during the first 8 hours were greater than the previously reported minimum inhibitory concentrations (MICs) of organisms most involved in fungal endophthalmitis. A rapid decline of intravitreal concentration suggests that supplementation of intraocular voriconazole to maintain therapeutic levels may therefore be required in clinical settings. Further studies are needed to determine the elimination rate of voriconazole after intravitreal injection in humans.     

Real-life comparison of three intravitreal antibiotic drug regimens in endophthalmitis

Purpose:Real-life comparison of three intravitreal drug regimens used in cases of endophthalmitis at a tertiary care center in India.Methods:In this prospective, comparative study, patients of bacterial endophthalmitis were grouped according to intravitreal antibiotic drug regimens into Group 1 (ceftazidime and vancomycin), Group 2 (piperacillin + tazobactam and vancomycin), and Group 3 (imipenem and vancomycin). Forty-eight hours after injection nonresponding/worsening patients underwent vitrectomy. Vitreous samples were subjected to microbiological and pharmacokinetic tests.Results:A total of 64 patients were included and divided into Group 1: 29, Group 2: 20, and Group 3: 15 cases. Also, 75% of patients were post-surgical endophthalmitis, whereas 25% were post-traumatic. Improvement in vision (V_90-0) and vision at 3 months (V₉₀) were comparable between the three groups. Visual recovery was poorer in post-traumatic cases. In post-surgical cases, visual recovery was poorer in those presenting beyond 72 h of onset of symptoms (P = 0.0002). Polymerase chain reaction (PCR) positivity (66%) was higher than BACTEC™ (33%) and culture (14%). Antibiotic resistance was comparable amongst the three groups. Most patients (62/64) further underwent vitrectomy. Ceftazidime and vancomycin achieved vitreous concentrations more than the minimum inhibitory concentration (MIC) at 48 h after the first injection.Conclusion:The choice of antibiotics did not affect the rate of vitrectomy and final vision in a real-life scenario. Ceftazidime and vancomycin can still be used as first-line intravitreal antibiotics owing to their comparable microbial sensitivity profile and adequate ocular bioavailability.     

Visualizing vitreous using Kenalog suspension

We developed and evaluated a method of visualizing vitreous gel in the anterior segment. In this study, 0.2 mL of injectable triamcinolone (Kenalog) 40 mg/mL was captured in a 5 microm filter and rinsed with 2 mL of balanced salt solution (BSS). It was then resuspended in 5 mL of BSS and recaptured to thoroughly remove the preservative. The Kenalog particles were ultimately resuspended in 2 mL of BSS and injected into the anterior chamber through a 27-gauge cannula. Kenalog particles were trapped on and within the vitreous gel, making it clearly visible. The visualization provided direct observation of vitreous behavior in various experimental settings and assisted surgeons intraoperatively in the identification and removal of vitreous in the anterior segment.     

Alpha-tocopherol derivatives and wound healing in an experimental model of filtering surgery

OBJECTIVE: To describe the effect of alpha-tocopherol derivatives (acetate and acid-succinate) on the histopathological characteristics of the surgical fistula in an experimental model of filtering surgery. MATERIALS AND METHODS: Thirty pigmented rabbits were divided into 3 groups. Twenty-four hours before surgery the animals were injected subconjunctivally with 0.5 mL of solution that depended on the group of treatment: Group 1 (n = 10) 0.75% ethanol in balanced salt solution (BSS); Group 2 (n = 10) 100 microg alph-tocopherol-acetate in 0.75% ethanol in BSS; Group 3 (n = 10) 100 microg alpha-tocopheryl-acid-succinate in 0.75% ethanol in BSS. Histological findings were evaluated 30 days after surgery. RESULTS: The groups treated with alpha-tocopherol derivatives showed a higher percentage of persistence of the fistula and better intraocular pressure (IOP) control. CONCLUSIONS: Alpha-tocopherol derivatives showed antiproliferative properties in this experimental model of filtering surgery.