Acute endophthalmitis after cataract surgery at a referral centre in Northern Taiwan: review of the causative organisms, antibiotic susceptibility, and clinical features.

PURPOSES: The aims of this study were to describe the bacterial isolates and treatment outcomes of endophthalmitis after cataract surgery at a referral centre in Northern Taiwan. METHODS: This was a retrospective, interventional, and observational series. Medical records were review of patients with clinical diagnosed, and/or culture-proven bacterial endophthalmitis at a tertiary referral centre in Northern Taiwan from January 2002 to December 2008. Treatment generally conformed to standard guidelines. Main outcome measurements were results of organism culture, antibiotic susceptibility of isolated bacteria, and visual acuity (VA) outcome. RESULTS: Thirty-four patients had positive cultures. A total of 55.9% of the culture-positive isolates were Gram negative and 44.1% were Gram positive. Pseudomonas aeruginosa was the most commonly isolated organism. Eighteen patients had final VA better than 5/200, and 41 had final VA worse than 5/200. In multiple linear regression analysis, female gender, presence of hypopyon, and worse baseline VA were significant independent predictors of worse visual outcome. CONCLUSIONS: It was found that at a referral centre in Northern Taiwan, the majority of bacterial isolates were Gram negative in acute postoperative bacterial endophthalmitis after cataract surgery and P. aeruginosa was the most common bacterial isolate.

Intermediate outcomes of Ahmed glaucoma valve surgery in Asian patients with intractable glaucoma.

OBJECTIVE: To evaluate the efficacy and safety of Ahmed glaucoma valve (AGV) implantation in Asian patients with refractory glaucoma. METHODS: The study was a retrospective interventional case series conducted at a single institution between January 2004 and January 2006. The study population included 91 patients (91 eyes). RESULTS: A total of 70 patients were successfully treated (74.5%). Postoperatively, the median intraocular pressures declined significantly to 13 mm Hg (interquartile range: 10-20 mm Hg) on day 1 (P<0.001) and 17 mm Hg (interquartile range: 12-19 mm Hg) at the last follow-up examination (P<0.001). The cumulative probability of success according to Kaplan-Meier life-table analysis was 74% at 12 months and 43% at 2 years. Hazard of failure increased slightly with age, HR: 1.03 (95% confidence interval (CI)=1.00-1.05; P=0.044). The most common complication was hyphaemia at 12.77%. There were no serious complications involving loss of visual acuity or sight. CONCLUSIONS: AGV implantation is an acceptable treatment for refractory glaucoma in high-risk patients with few additional options.

Sweet hyperopia: refractive changes in acute hyperglycemia.

PURPOSE: A prospective study was performed to evaluate refractive and ocular biometric changes in acute hyperglycemic status in patients with diabetes mellitus. METHODS: From January to August 2002, 48 eyes of 24 patients with persistent diabetes and a plasma glucose level>or=17 mmol/L or HbA1c>or=10.0% on admission were enrolled in this prospective study. Upon admission to Tri-Service General Hospital in Taipei, Taiwan, these patients underwent intensive glycemic control. The basic ophthalmic examinations, including visual acuity, intraocular pressure measurement, slit lamp, and fundus examinations, were conducted. The ocular parameters including refraction, anterior chamber depth, lens thickness, axial length, mean keratometry, and thinnest corneal thickness were evaluated by A-mode scan and Orbscan II. Each patient underwent clinical follow-up visits at 1, 2, and 4 weeks after the acute hyperglycemic episode. RESULTS: Of the 24 patients, 18 were male and 6 were female. The mean age of the patients was 55 years (range: 38 to 69). Comparing the refractive status on admission and at week 4, the authors found that 8 cases (16 eyes, 33%) showed hyperopia during hyperglycemia (+1.9+/-0.8 D), but in the other 16 cases (32 eyes, 67%), there were no significant changes. In addition, there were also no significant changes in anterior chamber depth, lens thickness, axial length, thinnest corneal thickness, or mean keratometry in the follow-up period. CONCLUSIONS: Transitory hyperglycemia produces hyperopia. The alteration in refractive index in the lens may contribute to the hyperopic change, but no change of ocular biometrics in lens or cornea is observed.

Immunohistochemical distinction between primary adenocarcinoma of the bladder and secondary colorectal adenocarcinoma.

Primary adenocarcinoma of the urinary bladder sometimes causes a diagnostic dilemma because it can be indistinguishable morphologically from adenocarcinoma of colorectal origin secondarily involving the bladder by metastasis or direct extension. It is much less well studied than conventional urothelial carcinoma and colorectal adenocarcinoma because of its rarity. The current study was specifically designed to investigate whether an important mechanism involved in the pathogenesis of colorectal adenocarcinoma, beta-catenin dysregulation, was also important for the development of primary bladder adenocarcinoma and whether these two morphologically similar tumors could be distinguished immunohistochemically. Formalin-fixed, paraffin-embedded tissues from 17 primary adenocarcinomas of the urinary bladder, 16 colorectal adenocarcinomas involving the bladder, and 10 conventional urothelial (transitional) carcinomas were included in this study. Thirteen of the primary bladder adenocarcinomas were moderately to well differentiated (enteric type) and morphologically indistinguishable from colorectal cancers. The remaining four primary tumors were poorly differentiated (two cases) or of clear cell type (two cases). Immunohistochemical studies using a panel of monoclonal antibodies demonstrated positive nuclear staining for beta-catenin expression in 13 of the 16 (81%) colorectal adenocarcinomas secondarily involving the bladder but in none of the primary adenocarcinomas or the urothelial carcinomas. Instead, positive membranous (and some cytoplasmic) staining was present in all primary bladder tumors with the exception of two poorly differentiated adenocarcinomas where no beta-catenin staining was detected. All secondary colorectal adenocarcinomas stained negatively for CK7 and thrombomodulin (TM), whereas positivity for CK20 was observed in 15 (94%) cases. All urothelial carcinomas stained positively for CK7 and TM, and four of them also for CK20. Primary adenocarcinomas of the bladder showed mixed staining patterns for CK7, CK20, and TM with a positive rate of 65%, 53%, and 59%, respectively. These data indicate that dysregulation of beta-catenin, an important aberration seen in colorectal carcinogenesis, does not appear to play a role in the pathogenesis of the bladder adenocarcinoma. In addition, our data demonstrate that a panel of immunostains, including CK7, CK20, TM, and beta-catenin, is of diagnostic value in differentiating primary bladder adenocarcinoma from secondary adenocarcinoma of colorectal origin.

The changes of vitreous pH values in an acute glaucoma rabbit model.

The changes of vitreous pH values under acute glaucoma status have never been reported. In this study, we measured the changes of vitreous pH values in an acute glaucoma rabbit model. Under ketamine and xylazine anesthesia, the anterior chamber of the right eye of New Zealand white rabbits was cannulated and connected to a polygraph for continuous intraocular pressure (IOP) monitoring and a mini-pump for persistent injection of viscoelastic substance, Healon GV. The measurement of vitreous pH was done by inserting a pH probe via a third opening through the sclera into the vitreous. Different IOP levels were maintained by varied amounts of Healon GV injections into the anterior chamber. The changes of vitreous pH values following the intracameral injections were recorded and evaluated. The changes of vitreous pH values were minimal when IOPs were maintained at lower than 35 mmHg. Vitreous pH values decreased significantly from 7.32 to less than 7.03, when the IOPs were kept at 70 mmHg or higher. However, the decrease of pH values was reversible if IOP was held at 70 mmHg for less than 10 minutes and then reduced to normal level at once. In addition, with MTT viability assay, it was noted that the decrease in vitreous pH was associated with a higher percentage of retinal cell death.

Formulation factors for preparing ocular biodegradable delivery system of 5-fluorouracil microparticles.

Microparticles containing 5-fluorouracil (5-FU) were prepared using poly(DL-lactide-co-glycolide) with an oil-in-oil emulsion/solvent extraction technique. Particle characteristics including size distribution, 5-FU loading efficiencies, in vitro release and degradation were investigated. The dispersed phase was composed of PLG dissolved in dichloromethane, and the continuous phase was paraffin oil containing lecithin. 5-FU was successfully entrapped in the microparticles with trapping efficiencies up to 76%, loading level 10% w/v, and particle size 3 microm. Release profiles of 5-FU loaded microparticles were determined to follow a first-order-time relationship. An optimized preparation of 5-FU microparticles was achieved and was capable of controlling the release of 5-FU over 21 days with an in vitro delivery rate of 0.4 microg 5-FU/mg particles/day in the study. Preliminary animal studies indicated that the 5-FU loaded microparticles as an ocular delivery system showed no ocular toxicity and no significant inflammatory response in rabbits for 2 months. The 5-FU loaded microparticles approach, with PLG, might be a potential for the application of long-term delivery of hydrophilic drugs in the eye.

Adrenergic supersensitivity of rabbit choroidal blood vessels after sympathetic denervation.

PURPOSE: To demonstrate the phenomenon of adrenergic denervation supersensitivity in rabbit choroidal blood vessels after superior cervical ganglionectomy. METHODS: Twenty four albino rabbits of both sexes weighing 2-3 kg were randomly separated into two groups. Twelve rabbits received bilateral superior cervical sympathectomy 2 weeks prior to the study (group s). The other 12 rabbits served as controls (group n). Four different concentrations of 0.1 ml phenylephrine, 0.05%, 0.025%, 0.013%, and 0.007% were slowly injected into the vitreous body near the retinal surface in group (n) and (s) rabbits (n = 6 in each group). The choroidal blood flow (PF), blood volume (CMBC), and velocity (V) were measured simultaneously by laser Doppler flowmetry (Perimed, PF 4001). RESULTS: The PF showed similar decreases in group (n) and (s) rabbits after injection of 0.05%, 0.025%, and 0.013% phenylephrine. With 0.007% phenylephrine, the PF remained unchanged in group (n) rabbits, but decreased significantly in group (s) rabbits (p = 0.0007). Velocity decreased similarly in both group (n) and (s) rabbits except for the 0.007% phenylephrine, concentration in which velocity decreased significantly in group s rabbits (p = 0.0001). There was no statistical difference in CMBC between group n and s rabbits at any of the test concentrations. CONCLUSIONS: The difference in PF decrease between group (n) and (s) rabbits with 0.007% phenylephrine demonstrated the existence of choroidal blood vessel denervation supersensitivity. The decrease in PF was achieved mainly through a decrease in blood cell velocity.

The use of autologous fibrinogen concentrate in treating ocular hypotony after glaucoma filtration surgery.

Antimetabolite therapy with 5-fluouracil (5-FU) or mitomycin-C (MMC) has significantly improved the success rate of glaucoma filtration surgery. However, in some eyes, when filtration is excessive, persistent hypotony may develop. In this study, we describe the experience of using autologous fibrinogen concentrate (AFC) to treat patients with persistent hypotony after glaucoma filtration surgery. Among seven MMC-augmented trabeculectomy patients who developed persistent postoperative hypotony, the effects of AFC intrableb injections were evaluated. Under a microscope, 0.2 ml AFC and bovine thrombin were injected into the blebs of the patients from both sides of the filtering blebs. Postoperative best-corrected visual acuity, anterior chamber status, intraocular pressure (IOP) and fundus examination were followed and compared with those preoperative. On the second day, the mean IOP of seven eyes elevated from preoperative 3.4 +/- 2.1 mmHg to 12.6 +/- 4.2 mmHg, and the anterior chamber became deep without obvious inflammatory response. Within two weeks, macular edema and visual acuity were noted to improve in six eyes (85.7%). In addition, after a mean follow-up of 25 months, the trabeculectomy procedure remained successful in all eyes. AFC appears to be safe and effective in the treatment of ocular hypotony after glaucoma filtration surgery.

Phenomenological theory on refrigeration effect of practical type-I superconductor.

In accordance with the phenomenological theory of thermodynamics, we discussed the Magnetocaloric effect of type-I superconductors, which are exposed to a varying magnetic field. It is concluded theoretically that the refrigeration effect is closely associated with demagnetization effect for practical specimens, which is different from the situation for ideal superconductor sample having no demagnetization effect. From the thermodynamic formulation of superconductivity, we deduced the integrating function of the thermal effect. By numerical calculation, we found a quantitative relation between the refrigeration effect and the demagnetizing factor which is determined by the shape of the sample.

In vitro and in vivo evaluation of an ocular delivery system of 5-fluorouracil microspheres.

Solvent evaporation technique with O/O (oil/oil) emulsion was used to prepare 5-FU (5-fluorouracil) biodegradable microspheres with a polymer of poly(dl-lactide-co-glycolide) combining lecithin as an emulsifier. In vitro drug release was conducted in phosphate buffer with pH 7.4 at 37 degrees C. For in vivo studies, 10 mg of 5-FU microspheres (containing 1 mg of 5-FU) were implanted in the conjunctival area of the rabbit eye. Rabbits were sacrificed at certain time intervals within 7 days after drug application. Samples of aqueous humor and sclera were prepared and analyzed by the high performance liquid chromatography (HPLC) method. The tested 5-FU microsphere contained 10% drug with a mean particle size of 4.4 +/- 0.6 microm. The microsphere had a burst release initially (64.9 +/- 1.5%), followed by a sustained release; the cumulative release at time points of 1, 10 and 21 days were 71.9 +/- 1.9%, 80.1 +/- 2.1% and 89.8 +/- 2.3%, respectively. For in vivo studies, aqueous humor levels showed a peak at the first sampling point (2 hr), then maintained low levels of 5-FU with a range 0.2-1 microg/mL. Scleral levels were 20-80 microg/mL during a 7-day study. Our results indicate that the prepared 5-FU microsphere provided a long-term release for more than 1 week. The preparation showed no irritation and low toxicity (< 100 microg/mL). For application to the eye, it might be potentially useful as a complement drug system in glaucoma filtration surgery.

Aqueous humor nitric oxide levels differ in patients with different types of glaucoma.

Nitric oxide (NO) has effects on the regulation of aqueous humor dynamics, but the exact mechanism is not yet established. To investigate the possible roles of NO in glaucoma, we determined NO levels in aqueous humor and plasma in glaucoma patients and a control group, cataract patients. The study is an open trial with purposed sampling. One hundred fifty-two patients, including 87 glaucoma patients and 65 cataract patients from two medical centers, were recruited. NO levels in the samples were measured by a chemiluminescence assay. We found that, although the mean aqueous humor NO level (mean +/- SEM) was higher in the glaucoma patients than in the cataract patients (39.7 +/- 1.5 microM vs. 35.5 +/- 1.3 microM, p < 0.05), NO levels varied significantly in different types of glaucoma. The juvenile glaucoma patients had the lowest mean NO level (8.4 +/- 0.9 microM), while the acute angle-closure glaucoma and neovascular glaucoma patients had the highest mean NO levels (64.8 +/- 7.6 microM, 67.3 +/- 8.2 microM). In comparison, the mean plasma NO level in the glaucoma patients was not statistically different from that in the cataract patients (14.1 +/- 1.2 microM vs. 13.9 +/- 1.1 microM, p = 0.91). Our data may provide information for applying NO-mimicking nitrovasodilators in the treatment of glaucoma.

The short-term effect of pentoxifylline on rabbit choroidal blood flow.

This study evaluates the effect of different doses ofpentoxifylline on rabbit choroidal blood flow (CBF). Sixteen albino rabbits of both sexes, weighing 2.0-3.0 kg, were randomly separated into four groups. The first group of rabbits received 2 ml normal saline injection through the ear vein. They served as the control group (group n). Three different doses of pentoxifylline, 1 mg/kg, 5 mg/kg, and 10 mg/kg, were injected intravenously to groups p1, p5 and p10, respectively. By means of a laser Doppler flowmeter, the blood cell flux (PF), velocity, and the concentration of moving blood cells (CMBC) were recorded simultaneously. The laser probe was advanced through the pars plana and positioned near the retinal surface. The mean arterial pressure was recorded at the same time. There was a significant increase in PF at 1, 5 and 10 min in group p10 rabbits compared with the control group (p=0.0005, 0.0416, and 0.0087, respectively). The velocity increased at 5 min in group p5 rabbits (p=0.0082) and at 1, 5 and 10 min in group p10 rabbits (p=0.0188, 0.0080, and 0.0207, respectively) as compared with the controls. The CMBC decreased after injection of pentoxifylline and reached statistical significance at 5 and 10 min in group p5 rabbits (p=0.0019 and 0.0046, respectively) and at 5 min in group p10 rabbits (p=0.0447). These results show that larger doses of pentoxifylline (10 mg/kg) increased the CBF of rabbits. This effect was achieved primarily by an increase in blood cell velocity.

Bilateral superior cervical ganglionectomy increases choroidal blood flow in the rabbit.

In this study, we evaluate the effect of bilateral superior cervical ganglionectomy on albino rabbit choroidal blood flow (CBF) in changes of perfusion pressure (PP). Twenty albino rabbits of either sex weighing between 2.0 and 3.0 kg were randomly divided into two groups. The experimental group (group S) included 10 rabbits (20 eyes) that received bilateral superior cervical ganglionectomy one week prior to the study. The other 10 rabbits (20 eyes) served as a control (group N): each received the same procedure as group S except that the superior cervical ganglion was preserved. By means of a laser Doppler flowmeter (Perimed PF4001), blood cell flux (PF), velocity (V), and concentration of moving blood cells (CMBC) were recorded simultaneously while intraocular pressure was increased linearly by a syringe pump. Blood pressure and intraocular pressure were continuously monitored. The laser beam focused on the posterior pole away from major retinal vessels. When PP decreased from 75 to 0 mm Hg, in group N, PF, V and CMBC decreased from 100% to 6.94+/-0.91%, 8.41+/-0.87%, and 19.38+/-1.11%; in group S, it was 17.75+/-2.58%, 16.78+/-1.48%, and 34.58+/-4.42%, respectively. Group S poses higher PF, V, and CMBC than group N while PP decreased gradually. These results indicate that the superior cervical ganglion plays a role in CBF regulation. Bilateral sympathectomy led to a higher PF in the group S rabbits, indicating increased CBF. PF, V, and CMBC remained constant until PP <55 mm Hg demonstrated the existence of CBF autoregulation within a limited perfusion range in both groups. This autoregulation did not change after sympathectomy.

The application of water drinking test on the evaluation of trabeculectomy patency.

The water drinking test (WDT) was once frequently used as a diagnostic tool for glaucoma, but not so often nowadays. In this study, we investigated the potential use of the WDT on the evaluation of trabeculectomy patency. Twenty age-matched volunteers and thirty-six glaucoma patients who were to receive trabeculectomy procedure were enrolled in this study. The WDT was given to the volunteers once and to all glaucoma patients before undergoing trabeculectomy and at certain intervals after the procedure. The WDT was performed in a standard manner. We defined four parameters after performing the WDT: Initial Pressure [IP, intraocular pressure (IOP) level before the WDT]; Slope of Ascending Trend (SOAT, the slope between baseline IOP and the highest IOP level); Peak Pressure (PP, the highest IOP level during the WDT); and End Pressure (EP, the IOP level after the WDT). It was found that the results of the WDT and trabeculectomy patency were strongly correlated. The four parameters in success and failure cases were significantly different at the last follow up: IP: (15.2 +/- 3.6 vs. 25.3 +/- 6.4, p<0.01); SOAT: (0.9 +/- 0.3 vs. 1.8 +/- 1.2, p<0.01); PP: (19.2 +/- 6.4 vs. 39.5 +/- 12.2, p<0.01); EP: (15.5 +/- 4.8 vs. 29.4 +/- 8.2, p<0.01). Thus, it was observed in this study that WDT was not only easy and safe to perform, but also valuable in evaluating the patency of trabeculectomy.

Wound modulation after trabeculectomy by different formulations of antimetabolites in rabbits.

A prospective, randomized study was performed to examine the effects of subconjunctival retention of 5-fluorouracil (5-FU) microparticles or 5-FU microparticles combined with mitomycin-C (MMC) on the success of trabeculectomy procedure in 32 New Zealand white rabbits. Drug-loaded microparticles were prepared using a biodegradable polymer, 50:50 ploy (D,L-lactide-co-glycolide) (50:50, PLG, MW 9000), by an oil-in-oil emulsification/solvent extraction technique. Each rabbit underwent trabeculectomy on both eyes, then one of the 5-FU and/or MMC preparations was placed at the site of the filtering surgery intraoperatively in the right eye, while the left eye was used as a control. The rabbits were randomly allocated to one of four treatment groups: group 1 rabbits received 5% 5-FU microparticles 10 mg; group 2 rabbits received 10% 5-FU microparticles 10 mg; group 3 rabbits received 10% 5-FU microparticles 5 mg and MMC 0.01 mg (5-FU/MMC); and group 4 rabbits received MMC 0.02 mg. Postoperatively, intraocularpressure (IOP), bleb survival, complications and IOP dynamics were compared during a follow-up period of 42 days. The results showed that IOPs were significantly lower in the eyes that received groups 3 and 4 treatments, while the eyes that received low concentrations of 5-FU microparticles resulted in no difference in IOPs as compared with those of controls. At 42 days, blebs were present in 100% of the eyes treated with 5-FU/MMC and MMC, but 0% of the eyes treated with 5-FU microparticles. The blebs in the eyes treated with MMC 0.02 mg were thinner, and significant complications (endophthalmitis, transient corneal opacification and neovascularization) occurred. In addition, the IOP dynamics study revealed that the eyes treated with 5-FU/MMC and MMC resulted in less IOP spikings after intravenous infusion of 0.9% NaCl solution. Our study suggested that the use of 5-FU microparticles in promoting the success of trabeculectomy in rabbits is dose-dependent, and its effect is less potent than a single intraoperative application of MMC.

Origin of innervation in the feline ophthalmic artery.

In this study, we investigate the innervation to the feline ophthalmic artery by the horseradish peroxidase (HRP) tracing method. Five adult cats with body weights ranging between 2.0 and 3.0 kg were used. Under microscopic dissection, the ophthalmic artery was identified and isolated. A gelfoam (Upjohn Co.), 1 x 3 mm in size, containing 0.1 ml of HRP was applied to the prepared artery segment for 2 h. The cat was sacrificed 3 days later. The trigeminal, stellate, superior cervical, middle cervical and nodal ganglia, and oculomotor, trochlear and abducens nuclei were removed, sectioned and stained for HRP-positive cells. HRP-labeled neurons were found in the ipsilateral trigeminal (TRG) and superior cervical ganglia (SCG). The middle cervical, stellate, Edinger-Westphal, trochlear and abducens nuclei were all deemed negative for HRP-labeled cells. In the TRG, HRP-labeled neurons ranged from 21 to 250 (mean +/- SE = 93.8 +/- 42.5/ganglion). The labeled neurons were distributed primarily in the ophthalmic branch. In the SCG, the HRP-labeled neurons were distributed evenly in the ganglion, ranging from 6 to 180 (mean +/- SE = 91.6 +/- 31.5/ganglion). Two additional cats having received a sham operation revealed a negative finding. The feline ophthalmic artery is innervated by the ipsilateral TRG and SCG. Such innervation may play a role in regulating blood flow to the optic nerve.

Subconjunctival retention of C3F8 gas increased success rates of trabeculectomy in rabbits.

The effect of subconjunctival retention of perfluoropropane (C3F8) gas on rabbit trabeculectomy was evaluated in this study to determine if this maneuver would increase the success rate of the surgery. Sixteen New Zealand white rabbits underwent trabeculectomy in the right eyes and trabeculectomy with subconjunctival retention of 0.3 mL C3F8 gas in the left eyes were used as animal models. One week and six weeks after the operations, the intraocular pressure (IOP) dynamics were compared between the two eyes after intravenous infusion of 0.9% NaCl sterile solution. The results showed that the average retention time of C3F8 gas within the subconjunctival space in the rabbits was 9.5 +/- 2.3 days. There were four parameters available in comparing IOP dynamics: Time Needed to Reach Peak IOP (TNRPI); Ascending Slope (AS); Peak IOP (PI) and Time Needed to Return to the Original IOP (TNROI). It was noted that at the 7th day after the operations, the IOPs in both eyes of the rabbits were not significantly increased after intravenous infusion of 0.9% NaCl solution. At the 42nd day, after 0.9% NaCl intravenous infusion, the eyes that had undergone trabeculectomy and subconjunctival retention of C3F8 gas had less IOP spiking than eyes that had undergone trabeculectomy alone (TNRPI: 6.7 +/- 2.2 vs. 4.2 +/- 2.9, p = 0.01, AS: 0.5 +/- 0.3 vs. 2.8 +/- 2.7, p = 0.002, PI: 24.4 +/- 9.6 vs. 18.7 +/- 7.4, p = 0.07 and TNROI: 6.8 +/- 5.8 vs. 14.7 +/- 11, p = 0.02). Our study suggested that subconjunctival retention of C3F8 gas increased the success rate of trabeculectomy in rabbits in the short-term follow-up period.

A comparison of trabeculectomy with topically applied timolol in a rabbit ocular hypertension model.

The difference in intraocular pressure (IOP) dynamics between trabeculectomy and topical instillation of timolol was compared in a rabbit ocular hypertension model. Twenty New Zealand white rabbits trabeculectomized with subconjunctival retention of 0.3 mL C3F8 gas in the right eyes were used as animal models. One week and three weeks after the operation, the left eyes of the rabbits were given three drops of 0.5% timolol, and IOP dynamics were compared between the two fellow eyes after intravenous infusion of 0.9% NaCl sterile solution. There were four parameters available in comparing IOP dynamics: Time Needed to Reach Peak IOP (TNRPI); Ascending Slope (AS); Peak IOP (PI); and Time Needed to Return to the Original IOP (TNROI). By this method, it was noted that, at the 7th day after the operation, the eyes trabeculectomized with subconjunctival retention of C3F8 gas had lower IOPs than the eyes that received topical instillation of timolol (baseline IOP: 14.7 +/- 4.2 vs. 19.5 +/- 2.5, p < 0.001, PI: 16.4 +/- 5.2 vs. 26.2 +/- 9.3, p < 0.001). In addition, at the 21st postoperative day, after intravenous infusion of 0.9% NaCl solution, the operated eyes showed less IOP spiking than the eyes that received topical instillation of timolol (TNRPI: 5.7 +/- 2.1 vs. 3.9 +/- 2.3, p = 0.014; AS: 0.8 +/- 0.5 vs. 2.7 +/- 2.6, p = 0.003; PI: 21.2 +/- 7.8 vs. 27.9 +/- 8.6, p = 0.014; and TNROI: 8.4 +/- 6.5 vs. 12.6 +/- 7.3, p = 0.06). These results suggested that trabeculectomy, rather than topical timolol, yielded better protection against IOP spiking in a transient rabbit ocular hypertension model.

Intraocular pressure lowering effects of novel arylpiperazine derivatives.

Arylpiperazine derivatives were synthesized and investigated in this study. Two animal models, including an intraocular pressure (IOP) recovery method and an alpha-chymotrypsin-induced glaucoma model, were used to determine the ocular pharmacological effects of the arylpiperazine derivatives. In the IOP recovery method, New Zealand rabbits with normal IOP were instilled with 50 microliters of 0.5% eye drops, then 10% sodium chloride solution was infused through the ear marginal vein. The relative percent of IOPs were calculated, then delta IOPt% was obtained from the difference of IOPt% between the treated and controlled eye. In the alpha-chymotrypsin-induced glaucoma model, the induced glaucoma rabbits were topically instilled with 0.5% arylpiperazines onto the eyes, and then the IOP changes were calculated to evaluate the effect of eye drops. Our results showed that in the IOP recovery method, BG31 and YCT2-2 demonstrated a very significant effect for reducing IOP; delta IOPt% were -27.6 and -25.5 for BG31 and YCT2-2, respectively. Two other compounds, C219 and C220 also lowered IOP, but the effects were less significant. In alpha-chymotrypsin-induced glaucoma, the maximum effect of YCT2-2 on the IOP was found at 5 hrs. The delta IOP and delta delta IOP were -12.5 +/- 1.7 and -5.8 +/- 1.1 mmHg (p < 0.01), respectively. For BG-31 and C220, there existed a trend to increase IOP with time. In the study, we found that YCT2-2 with higher solubility in the acidic condition was correlated to the significant IOP lowering effect.