Aqueous shunts for glaucoma.

BACKGROUND: Aqueous shunts are employed for intraocular pressure (IOP) control in primary and secondary glaucomas that fail medical, laser, and other surgical therapies. OBJECTIVES: This review compares aqueous shunts for IOP control and safety. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, PubMed, EMBASE, NRR all in January 2006, LILACS to February 2004 and reference lists of included trials. SELECTION CRITERIA: We included all randomized and quasi-randomized trials in which one arm of the study involved shunts. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data for included studies and a third adjudicated discrepancies. We contacted investigators for missing information. We used fixed-effect models and summarized continuous outcomes using mean differences. MAIN RESULTS: We included fifteen trials with a total of 1153 participants with mixed diagnoses. Five studies reported details sufficient to verify the method of randomization but only two had adequate allocation concealment. Data collection and follow-up times were variable.Meta-analysis of two trials comparing Ahmed implant with trabeculectomy found trabeculectomy resulted in lower mean IOPs 11 to 13 months later (mean difference 3.81 mm Hg, 95% CI 1.94 to 5.69 mm Hg). Meta-analysis of two trials comparing double-plate Molteno implant with the Schocket shunt was not done due to substantial heterogeneity. One study comparing ridged with standard double-plate Molteno implants found no clinically significant differences in outcome. Two trials investigating the effectiveness of adjunctive mitomycin (MMC) with the Molteno and Ahmed implants found no evidence of benefit with MMC. Two trials that investigated surgical technique variations with the Ahmed found no benefit with partial tube ligation or excision of Tenon's capsule. One study concluded there were outcome advantages with a double versus a single-plate Molteno implant and one trial comparing the 350 mm(2) and 500 mm(2) Baerveldt shunts found no clinically significant advantage of the larger device but neither of these trials included all patients randomized. One study suggested improved clinical outcome when MMC was employed with a newly described shunt including ultrasound supporting the conclusion. One small study did not demonstrate an outcome advantage to systemic steroid use postoperatively with single-plate Molteno shunts. One study comparing endocyclophotocoagulation (ECP) with Ahmed implant in complicated glaucomas found no evidence of better IOP control with Ahmed implant over ECP. AUTHORS' CONCLUSIONS: Relatively few randomized trials have been published on aqueous shunts and methodology and data quality among them is poor. To date there is no evidence of superiority of one shunt over another.

Changes in axial length following trabeculectomy and glaucoma drainage device surgery.

AIM: This study examines the changes in axial length (AL) after trabeculectomy and glaucoma drainage device (GDD) surgery and enabled an equation to be derived allowing prediction of AL change after filtering surgery. METHODS: This was a prospective, interventional case series from the Glaucoma Service of the Doheny Eye Institute. PATIENT POPULATION: One eye of 39 patients undergoing trabeculectomy and 22 undergoing Baerveldt tube shunt implantation for uncontrolled glaucoma. INTERVENTION: These patients had AL measurements by non-contact, partial coherence interferometry preoperatively, at 1 week, 1 month, and >3 months after surgery. MAIN OUTCOME MEASURES: Axial length and intraocular pressure were compared at preoperative and postoperative visits. Postoperative intraocular pressure (IOP) was categorised as hypotonous (0-4 mm Hg), low (5-9), normal (10-17), and high (18 or more). RESULTS: There was a statistically significant reduction in IOP after 3 months of -12.8 (SD 1.5) mm Hg following trabeculectomy (p<0.001), and -10.7 (1.9) mm Hg after GDD (p<0.001). There was a statistically significant reduction in AL, which was similar after trabeculectomy and GDD at all time points (p<0.001), of -0.15 (0.03) and -0.21 (0.04) mm (1 week), -0.18 (0.02) and -0.10 (0.02) mm (1 month), and -0.16 (0.03) and -0.15 (0.03) mm (3 months). At 3 months or later the AL reduction was related to postoperative IOP and to the amount of IOP reduction (p<0.05, stepwise multiple regression). 10.2% (4/39) of trabeculectomy patients had hypotony after 3 months, with a mean AL reduction (-0.39 (0.11)) that was statistically significantly lower (p<0.01) than the other trabeculectomy eyes (-0.14 (0.15)). CONCLUSIONS: There is a small but statistically significant decrease in AL after both trabeculectomy and GDD surgery, greater in eyes that are hypotonous after surgery. The authors suggest that AL reduction can be predicted after 3 months by the formula: AL reduction (mm) = -199+0.006 x IOP reduction+0.008 x final IOP.

Comparing the fixed combination dorzolamide-timolol (Cosopt) to concomitant administration of 2% dorzolamide (Trusopt) and 0.5% timolol -- a randomized controlled trial and a replacement study.

PURPOSE: To compare the intraocular pressure (IOP) lowering effect of concomitant administration of 0.5% timolol and 2% dorzolamide and a fixed combination dorzolamide-timolol (Cosopt) To critically evaluate discrepancies between phase 3 clinical trials and prior replacement studies. DESIGN: A prospective, randomized, controlled clinical trial and a prospective, non-randomized comparative replacement trial. PARTICIPANTS/INTERVENTIONS: In a national multicentre trial, 131 patients were randomized to dorzolamide-timolol or a topical carbonic anhydrase inhibitor (CAI) and non-selective beta-blocker following a 1-month run-in using the separate components. Peak (maximal drug effect) and trough (minimal drug effect) IOPs were measured at baseline and 1 month after treatment. The replacement therapy study enrolled 404 consecutive glaucoma patients using a non-selective beta-blocker and dorzolamide and changed treatment to the fixed combination. Mean IOPs at the same time of day were compared before and 1 month after changeover. MAIN OUTCOME MEASURE: The main outcome measure was IOP, comparing baseline and on-therapy measurements at study conclusion between the two arms of the randomized trial and before and after switching therapy in the replacement trial. RESULTS: In the randomized trial, the mean baseline peak and trough IOPs were 18.4 and 21.0 mmHg in the group randomized to combination therapy and 17.6 and 19.8 mmHg in the dual drug group. After randomization and treatment for four weeks, the peak and trough IOPs were 17.6 and 19.5 mmHg in the combination group and 17.3 and 19.0 mmHg in the concomitant group. The percentage change in IOP was -3.2% at peak and -6.5% at trough for the combination and -0.3 and -3.2% for the concomitant group. These differences did not show statistical significance. In the replacement study, mean baseline IOP was 19.4 mmHg. Four weeks after initiation of treatment on the fixed combination, a significant additional IOP reduction of 1.7 mmHg (-8.8%) was observed (P < 0.0001). Overall, 81% of eyes exhibited equal or lower IOP on the fixed combination compared with concomitant therapy. CONCLUSION: The results of the randomized trial indicate that the fixed combination dorzolamide-timolol (Cosopt) was as effective as its components in controlling IOP, confirming results seen in phase 3 clinical trials. However, in the replacement study, utilization of the combination drug offered a statistically significant additional IOP reduction (P < 0.0001), which duplicates results from previous replacement studies.

Characteristics of glaucoma drainage implants during dynamic and steady-state flow conditions.

OBJECTIVE: This study aimed to ascertain whether the Optimed, Krupin, and Ahmed drainage devices function as valves that vary resistance depending on flow conditions to maintain pressure within a desired range. STUDY DESIGN: Experimental study. INTERVENTION: The three devices and a control cannula were submerged in fluid and perfused with balanced salt solution using a computer-driven apparatus that continuously monitors flow (Q) and pressure (P). In one set of experiments, the flow rates were maintained at 2, 5, 10, 25, or 50 microliters/min until steady-state pressures were achieved. In another set of experiments, the flow rate was increased linearly from 0 to 100 microliters/min over 15 to 20 minutes. MAIN OUTCOME MEASURES: The resistance of each implant was calculated from the first set of experiments by dividing the change in pressure (P) by the change in flow (Q) between successive perfusion rates. Flow-pressure curves were plotted from the experiments in which perfusion rate was increased linearly. RESULTS: Resistance remained relatively constant for the cannula (0.18-0.24 mmHg/microliter/min), the Krupin (0.09-0.25 mmHg/microliter/min), and the Optimed implants (0.04-0.08) throughout the tested flow rates. For the Ahmed device, conversely, resistance decreased proportionally (2.86-0.05 mmHg/microliter/min) to the increase in flow. When flow rate was increased linearly from 0 to 100 microliters/min, the Optimed and Krupin devices as well as the cannula generated a linear pressure response with a constant slope. The pressure in the two devices increased at a rate of 0.11 mmHg/microliter compared to 0.23 mmHg/microliter/min for the cannula. The flow-pressure curve for the Ahmed implant was distinct with a steep initial pressure rise and an essentially constant pressure of 12 mmHg thereafter. CONCLUSION: The Optimed and Krupin devices displayed resistance and pressure responses to various flow conditions that were similar to those of a cannula or flow resistor. In these devices, resistance remained relatively stable and pressure increased linearly with flow. The Ahmed device, conversely, functioned as a valve that closely regulated pressure within a desired range by decreasing or increasing resistance as a function of flow.

The cellular basis of aqueous outflow regulation.

This review begins with an introduction to the concept of the cellular regulation of aqueous outflow, current methods used for its study, and the cell types that are known to participate in this process. Current research in the field is divided into work on cell properties, cell products and extracellular matrix, cytoskeletal and structural changes, and drug interactions.

Particle size and drug interactions of injectable corticosteroids used in ophthalmic practice.

PURPOSE: The aim of this study is to compare the particle sizes of commercially available corticosteroids for intralesional injection to manufacturers' specifications and to evaluate changes in size when mixed with other steroids and other commonly used solutions. METHODS: The particle sizes of dexamethasone sodium phosphate, methylprednisolone acetate, triamcinolone acetonide, and betamethasone sodium phosphate and beta-methasone acetate were measured with the Coulter counter. Each steroid was mixed with each of the others, lidocaine, and lidocaine with epinephrine, then measured immediately and after 1 hour to determine the effect on particle size. RESULTS: All steroids showed accurate manufacturer specifications. Dexamethasone showed an increase in particle size when mixed with lidocaine alone, immediately and after 1 hour. Triamcinolone showed an increase in particle size only after 1 hour after mixture with lidocaine alone. Triamcinolone, dexamethasone, and methylprednisolone particles increased in size when mixed with lidocaine and epinephrine. Dexamethasone and triamcinolone showed an additional increase in size when allowed to sit for 1 hour after mixture with lidocaine and epinephrine. Mixing steroids caused no increase in particle size. CONCLUSION: Because an increase in the number of particles greater than 20 microns in a solution also increases the likelihood of vascular occlusion, the authors urge care in the mixing of these drugs, especially with lidocaine and epinephrine. If mixture is necessary, the authors recommend that injection take place immediately subsequent.

Ion trap and quadrupole mass spectra of lignin pyrolysates: how well do they compare?

Lignin samples from wheat straw, orchard grass, red clover and a synthetic lignin were subjected to pyrolysis gas chromatography/mass spectrometry using both quadrupole (QMS) and ion-trap detector (ITD). ITD mass spectra were comparable with those presented in the National Bureau of Standards (NBS) library and with those obtained by QMS as evaluated by discrepancy factors. Computer-assisted library searches for ITD spectra were successful for 22 of 47 compounds. The other 25 compounds were not present in the library. A typical program and mass spectra are shown. Statistical data are discussed.

Magnetic resonance imaging of orbital lymphangioma with and without gadolinium contrast enhancement.

BACKGROUND: Lymphangioma is a vascular tumor of the orbit with a propensity for recurrent hemorrhage. These tumors may be difficult to diagnose in young patients who present with sudden proptosis due to hemorrhage into a previously unrecognized lesion. Magnetic resonance imaging (MRI) should be ideally suited for evaluating lymphangioma due to the unique ability of MRI to characterize hemorrhage because of the paramagnetic qualities of hemoglobin. METHODS: The authors performed T1-, T2-, and proton density-weighted MRI on 12 patients with orbital lymphangioma. Six patients underwent MRI with gadolinium-DTPA contrast enhancement. The MRI studies were performed using a 1.5 Tesla super-conducting magnetic resonance unit, except for 3 early studies performed with a 0.5 Tesla unit. All studies were performed with orbital surface coil imaging. Computed tomography (CT) was performed in 10 patients. RESULTS: Tumor was visible on MRI in all 12 patients. Magnetic resonance imaging delineated clearly the internal structure of subacute and chronic hemorrhagic cysts, and differentiated between these tumors because of the different paramagnetic qualities of subacute hemorrhage compared to chronic hemorrhage. In two patients, MRI detected large tumor feeding vessels by the flow void phenomenon unique to MRI. Computed tomography did not detect these vessels. Gadolinium-contrasted T1-weighted MRI did not further delineate or characterize the tumor. CONCLUSION: Magnetic resonance imaging is the modality of choice for imaging orbital lymphangioma because of its unequalled differentiation of hemorrhagic cysts, and its unique ability to detect tumor feeding vessels by the flow void phenomenon.