Randomized Trial of Endoscopist-Controlled vs. Assistant-Controlled Wire-Guided Cannulation of the Bile Duct.

OBJECTIVES: Biliary cannulation is frequently the most difficult component of endoscopic retrograde cholangiopancreatography (ERCP). Techniques employed to improve safety and efficacy include wire-guided access and the use of sphincterotomes. However, a variety of options for these techniques are available and optimum strategies are not defined. We assessed whether the use of endoscopist- vs. assistant-controlled wire guidance and small vs. standard-diameter sphincterotomes improves safety and/or efficacy of bile duct cannulation. METHODS: Patients were randomized using a 2 × 2 factorial design to initial cannulation attempt with endoscopist- vs. assistant-controlled wire systems (1:1 ratio) and small (3.9Fr tip) vs. standard (4.4Fr tip) sphincterotomes (1:1 ratio). The primary efficacy outcome was successful deep bile duct cannulation within 8 attempts. Sample size of 498 was planned to demonstrate a significant increase in cannulation of 10%. Interim analysis was planned after 200 patients-with a stopping rule pre-defined for a significant difference in the composite safety end point (pancreatitis, cholangitis, bleeding, and perforation). RESULTS: The study was stopped after the interim analysis, with 216 patients randomized, due to a significant difference in the safety end point with endoscopist- vs. assistant-controlled wire guidance (3/109 (2.8%) vs. 12/107 (11.2%), P=0.016), primarily due to a lower rate of post-ERCP pancreatitis (3/109 (2.8%) vs. 10/107 (9.3%), P=0.049). The difference in successful biliary cannulation for endoscopist- vs. assistant-controlled wire guidance was -0.5% (95% CI-12.0 to 11.1%) and for small vs. standard sphincerotome -0.9% (95% CI-12.5 to 10.6%). CONCLUSIONS: Use of the endoscopist- rather than assistant-controlled wire guidance for bile duct cannulation reduces complications of ERCP such as pancreatitis.

Modified release from lipid bilayer coated mesoporous silica nanoparticles using PEO-PPO-PEO triblock copolymers.

Triblock copolymers comprised of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO, or trade name Pluronic) interact with lipid bilayers to increase their permeability. Here we demonstrate a novel application of Pluronic L61 and L64 as modification agents in tailoring the release rate of a molecular indicator species from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) bilayer-coated superparamagnetic Fe3O4/mesoporous silica core-shell nanoparticles. We show there is a direct relationship between the Pluronics' concentration and the indicator molecule release, suggesting Pluronics may be useful for the controlled release of drugs from lipid bilayer-coated carriers.

Reduction of orbital inflammation following decompression for thyroid-related orbitopathy.

PURPOSE: Thyroid-related orbitopathy (TRO) is associated with inflammation, expansion of orbital fat, enlargement of extraocular muscles, and optic neuropathy (ON). We examined the effects of orbital decompression on the inflammatory and congestive signs of TRO in patients who underwent emergent orbital decompression. METHODS: This retrospective, consecutive study included patients with ON from TRO who underwent orbital decompression. Pre- and postoperative orbital inflammatory signs in the operated and nonoperated, contralateral eyes were graded with the 10-item clinical activity score (CAS). RESULTS: Thirty-one orbits were included. Postoperatively, 22 patients and 29 orbits had resolution of ON while the remaining 2 patients had improvement in visual acuity. Mean preoperative CAS was 9.5 ± 0.4. At 12 months, postoperative CAS was 2.1 ± 0.6 (P < 0.01) in the operated eye and 3.2 ± 0.5 (P < 0.05) in the nonoperated, contralateral eye. CONCLUSION: In our series, 94% of orbits had resolution of ON. There was also a statistically significant postoperative reduction in the CAS in both the operated and nonoperated, contralateral eyes. This phenomenon may be due to lowered venous congestion, decreased intraorbital pressure, and diminution in inflammatory factors.

Semiautomated quantification of ß-zone parapapillary atrophy using blue light fundus autofluorescence.

PURPOSE: To evaluate the reproducibility of measurements of area of ß-zone parapapillary atrophy (ß-PPA) using blue laser fundus autofluorescence (FAF) and confocal scanning laser ophthalmoscopy reflectance (CSLO) measurements and to assess agreement between the two imaging modalities. METHODS: Sixty-five eyes of 45 patients (mean age, 68.2 ± 11.3 years) with established or suspected glaucoma from the Diagnostic Innovations in Glaucoma Study (DIGS) were prospectively included. FAF scans were obtained with the Spectralis HRA+OCT and CSLO reflectance images with the HRTII (both from Heidelberg Engineering, Heidelberg, Germany). Two masked graders independently measured ß-PPA area on 3 consecutive scans using the semi-automated BluePeak RegionFinder software (BPRF) and on CSLO reflectance images using the optic disc contour line. Reproducibility of ß-PPA area measurements was assessed using intraclass correlation coefficients (ICC). RESULTS: Intragrader reproducibility was 0.997 (95% CI, 0.996-0.998) and 0.995 (95% CI, 0.992-0.996) for grader 1 and 2, respectively, using FAF-BPRF, and by CSLO, it was 0.991 (95% CI, 0.986-0.994) and 0.988 (95% CI, 0.982-0.992). Intergrader agreement (ICC) was 0.53 (95% CI, 0.331-0.685) for FAF-BPRF and 0.404 (95% CI, 0.149-0.601) for CSLO (comparison between ICC, p = 0.368). Agreement (ICC) between the two devices was worse for grader 1 (0.356; 95% CI, 0.129-0.549) than grader 2 (0.856; 95% CI, 0.774-0.910) (p < 0.001). CONCLUSIONS: Despite excellent intragrader reproducibility for ß-PPA measurements with FAF-BPRF and CSLO, intergrader reproducibility is low to moderate. Measurements of ß-PPA area obtained with the two instruments are of moderate agreement and, therefore, are not interchangeable.

Twenty-four-hour effects of bimatoprost 0.01% monotherapy on intraocular pressure and ocular perfusion pressure.

OBJECTIVES: To investigate the 24 h effects of bimatoprost 0.01% monotherapy on intraocular pressure (IOP) and ocular perfusion pressure (OPP). DESIGN: Prospective, open-label experimental study. SETTING: Single tertiary ophthalmic clinic. PARTICIPANTS: Sixteen patients with diagnosed primary open-angle glaucoma (POAG) or ocular hypertension (ages, 49-77 years). INTERVENTIONS: Baseline data of 24 h IOP in untreated patients were collected in a sleep laboratory. Measurements of IOP were taken using a pneumatonometer every 2 h in the sitting and supine body positions during the 16 h diurnal/wake period and in the supine position during the 8 h nocturnal/sleep period. After baseline measurements were taken, patients were treated with bimatoprost 0.01% one time per day at bedtime for 4 weeks, and then 24 h IOP data were collected under the same laboratory conditions. PRIMARY AND SECONDARY OUTCOME MEASURES: Diurnal and nocturnal IOP and OPP means under bimatoprost 0.01% treatment were compared with baseline. RESULTS: The diurnal and nocturnal IOP means were significantly lower under the bimatoprost 0.01% treatment than baseline in both the sitting and supine positions. The diurnal and nocturnal OPP means were significantly higher under treatment than baseline in both the sitting and supine positions. CONCLUSION: Bimatoprost 0.01% monotherapy significantly lowered IOP and increased OPP during the 24 h period.

The man who could not see what he could not eat.

A 55-year-old Hispanic man born in New Mexico presented with progressively worsening bilateral upper eyelid ptosis and dysphagia. External levator advancement 5 years before did not improve his ptosis. A thorough systemic workup for myasthenia gravis was negative, but electromyography suggested a myopathic process. Molecular genetic testing was positive for oculopharyngeal muscular dystrophy.

Central projections of melanopsin-expressing retinal ganglion cells in the mouse.

A rare type of ganglion cell in mammalian retina is directly photosensitive. These novel retinal photoreceptors express the photopigment melanopsin. They send axons directly to the suprachiasmatic nucleus (SCN), intergeniculate leaflet (IGL), and olivary pretectal nucleus (OPN), thereby contributing to photic synchronization of circadian rhythms and the pupillary light reflex. Here, we sought to characterize more fully the projections of these cells to the brain. By targeting tau-lacZ to the melanopsin gene locus in mice, ganglion cells that would normally express melanopsin were induced to express, instead, the marker enzyme beta-galactosidase. Their axons were visualized by X-gal histochemistry or anti-beta-galactosidase immunofluorescence. Established targets were confirmed, including the SCN, IGL, OPN, ventral division of the lateral geniculate nucleus (LGv), and preoptic area, but the overall projections were more widespread than previously recognized. Targets included the lateral nucleus, peri-supraoptic nucleus, and subparaventricular zone of the hypothalamus, medial amygdala, margin of the lateral habenula, posterior limitans nucleus, superior colliculus, and periaqueductal gray. There were also weak projections to the margins of the dorsal lateral geniculate nucleus. Co-staining with the cholera toxin B subunit to label all retinal afferents showed that melanopsin ganglion cells provide most of the retinal input to the SCN, IGL, and lateral habenula and much of that to the OPN, but that other ganglion cells do contribute at least some retinal input to these targets. Staining patterns after monocular enucleation revealed that the projections of these cells are overwhelmingly crossed except for the projection to the SCN, which is bilaterally symmetrical.