Intraoperative Dexamethasone Intravitreal Implant (Ozurdex) in Vitrectomy Surgery for Epiretinal Membrane.

Objective: To study the effectiveness and safety of the intravitreal dexamethasone implant 0.7 mg (Ozurdex®) in vitrectomy surgery for epiretinal membrane.Methods: This is a prospective, multicenter, pilot study. Inclusion criteria included visually significant (<20/50) idiopathic epiretinal membrane. All patients underwent 23-gauge pars plana vitrectomy with membrane peeling and Ozurdex implant injection. The primary outcome measure was best corrected visual acuity (BCVA) change at 3 months. Secondary outcomes included BCVA at 6 months and changes in central retinal thickness (CRT). Intraocular (IOP) changes were monitored and cataract progression in phakic patients was documented.Results: 15 patients were enrolled in the study, 12 eyes of 12 patients were included in the analysis. Mean preoperative BCVA was 50.67 ETDRS letters and improved significantly to 63.67 (+12.91 letters, p = .008) at 3 months. Mean CRT improved from 548 to 409 microns (p = .002) at 3 months. The IOP showed mild elevation at months 1 and 2 and returned almost to baseline at month six. There were no complications related to the steroid implant injection procedure in an air-filled eye.Conclusions: Intra-operative injection of Ozurdex® at the conclusion of PPV can be done safely. The peak IOP and lowest CRT after 2 months strengthens the findings of prior studies demonstrating Ozurdex activity up to 3 months in vitrectomized eyes.

Porcine CD38 exhibits prominent secondary NAD(+) cyclase activity.

Cyclic ADP-ribose (cADPR) mobilizes intracellular Ca(2+) stores and activates Ca(2+) influx to regulate a wide range of physiological processes. It is one of the products produced from the catalysis of NAD(+) by the multifunctional CD38/ADP-ribosyl cyclase superfamily. After elimination of the nicotinamide ring by the enzyme, the reaction intermediate of NAD(+) can either be hydrolyzed to form linear ADPR or cyclized to form cADPR. We have previously shown that human CD38 exhibits a higher preference towards the hydrolysis of NAD(+) to form linear ADPR while Aplysia ADP-ribosyl cyclase prefers cyclizing NAD(+) to form cADPR. In this study, we characterized the enzymatic properties of porcine CD38 and revealed that it has a prominent secondary NAD(+) cyclase activity producing cADPR. We also determined the X-ray crystallographic structures of porcine CD38 and were able to observe conformational flexibility at the base of the active site of the enzyme which allow the NAD(+) reaction intermediate to adopt conformations resulting in both hydrolysis and cyclization forming linear ADPR and cADPR respectively.

Spexin Enhances Bowel Movement through Activating L-type Voltage-dependent Calcium Channel via Galanin Receptor 2 in Mice.

A novel neuropeptide spexin was found to be broadly expressed in various endocrine and nervous tissues while little is known about its functions. This study investigated the role of spexin in bowel movement and the underlying mechanisms. In functional constipation (FC) patients, serum spexin levels were significantly decreased. Consistently, in starved mice, the mRNA of spexin was significantly decreased in intestine and colon. Spexin injection increased the velocity of carbon powder propulsion in small intestine and decreased the glass beads expulsion time in distal colon in mice. Further, spexin dose-dependently stimulated the intestinal/colonic smooth muscle contraction. Galanin receptor 2 (GALR2) antagonist M871, but not Galanin receptor 3 (GALR3) antagonist SNAP37899, effectively suppressed the stimulatory effects of spexin on intestinal/colonic smooth muscle contraction, which could be eliminated by extracellular [Ca(2+)] removal and L-type voltage-dependent Ca(2+) channel (VDCC) inhibitor nifedipine. Besides, spexin dramatically increased the [Ca(2+)]i in isolated colonic smooth muscle cells. These data indicate that spexin can act on GALR2 receptor to regulate bowel motility by activating L-type VDCC. Our findings provide evidence for important physiological roles of spexin in GI functions. Selective action on spexin pathway might have therapeutic effects on GI diseases with motility disorders.

Identifying predictive morphologic features of malignancy in eyelid lesions.

OBJECTIVE: To determine features of eyelid lesions most predictive of malignancy, and to design a key to assist general practitioners in the triaging of such lesions. DESIGN: Prospective observational study. SETTING: Department of Ophthalmology at Queen's University in Kingston, Ont. PARTICIPANTS: A total of 199 consecutive periocular lesions requiring biopsy or excision were included. MAIN OUTCOME MEASURES: First, potential features suggestive of malignancy for eyelid lesions were identified based on a survey sent to Canadian oculoplastic surgeons. The sensitivity, specificity, and odds ratios (ORs) of these features were then determined using 199 consecutive photographed eyelid lesions of patients who presented to the Department of Ophthalmology and underwent biopsy or excision. A triage key was then created based on the features with the highest ORs, and it was pilot-tested by a group of medical students. RESULTS: Of the 199 lesions included, 161 (80.9%) were benign and 38 (19.1%) were malignant. The 3 features with the highest ORs in predicting malignancy were infiltration (OR = 18.2, P < .01), ulceration (OR = 14.7, P < .01), and loss of eyelashes (OR = 6.0, P < .01). The acronym LUI (loss of eyelashes, ulceration, infiltration) was created to assist in memory recall. After watching a video describing the LUI triage key, the mean total score of a group of medical students for correctly identifying malignant lesions increased from 46% to 70% (P < .001). CONCLUSION: Differentiating benign from malignant eyelid lesions can be difficult even for experienced physicians. The LUI triage key provides physicians with an evidence-based, easy-to-remember system for assisting in the triaging of these lesions.

Intravitreal injections inducing de quervain tenosynovitis: injector's wrist.

PURPOSE: To describe a case of de Quervain tenosynovitis triggered by the repetitive performance of intravitreal injections. METHODS: Case report of a 32-year-old ophthalmologist. RESULTS: The ophthalmologist experienced de Quervain tenosynovitis while performing 425 intravitreal injections a month. These were predominantly performed in condensed sessions (injection clinics). Symptoms resolved with nonsurgical management. CONCLUSION: The repetitive performance of intravitreal injections may be an unrecognized occupational hazard for ophthalmologists.

Brachial plexus neuropathy secondary to postoperative prone positioning for macular hole surgery.

PURPOSE: To report a case of unilateral brachial plexus neuropathy after prone positioning for macular hole repair. METHODS: Case report. RESULTS: After 7 days of strict prone positioning post-macular hole surgery, a 60-year-old patient developed severe pain and weakness in the left arm. Neurologic examination, imaging, and electromyography showed that the patient developed a unilateral brachial plexus neuropathy. Her strength and pain quickly improved after hospitalization and treatment with intravenous solumedrol, pain control, and physiotherapy. Her best-corrected vision improved from 20/400 to 20/40, however, she was left with frozen shoulder syndrome. CONCLUSION: After macular hole surgery, prone positioning with persistent abduction of the shoulder such that the patient's hands rest above the head may put patients at risk for a brachial plexus neuropathy. However, this risk may be minimized by the use of positioning assistive devices, reducing the duration in the prone position, instituting frequent breaks, and warning patients to look for signs of neuropathy.

Visualization of stochastic Ca2+ signals in the formed somites during the early segmentation period in intact, normally developing zebrafish embryos.

Localized Ca(2+) signals were consistently visualized in the formed somites of intact zebrafish embryos during the early segmentation period. Unlike the regular process of somitogenesis, these signals were stochastic in nature with respect to time and location. They did, however, occur predominantly at the medial and lateral boundaries within the formed somites. Embryos were treated with modulators of [Ca(2+)](i) to explore the signal generation mechanism and possible developmental function of the stochastic transients. Blocking elements in the phosphoinositol pathway eliminated the stochastic signals but had no obvious effect, stochastic or otherwise, on the formed somites. Such treatments did, however, result in the subsequently formed somites being longer in the mediolateral dimension. Targeted uncaging of buffer (diazo-2) or Ca(2+) (NP-ethyleneglycoltetraacetic acid [EGTA]) in the presomitic mesoderm, resulted in a regular mediolateral lengthening and shortening, respectively, of subsequently formed somites. These data suggest a requirement for IP(3) receptor-mediated Ca(2+) release during convergence cell movements in the presomitic mesoderm, which appears to have a distinct function from that of the IP(3) receptor-mediated stochastic Ca(2+) signaling in the formed somites.