Outcome of primary rhegmatogenous retinal detachment surgery in a tertiary referral centre in Northern Ireland - A regional study.

PURPOSE: To report the primary and final success, functional outcome and complication rates of patients with primary rhegmatogenous retinal detachment (RRD) who underwent retinal detachment surgery in a tertiary referral centre in Northern Ireland. VENUE: Vitreoretinal service, Royal Victoria Hospital, Belfast, Northern Ireland. METHODS: This is a retrospective case series of all patients who underwent primary RRD repair between 1st of January 2013 and 31st of December 2013. Charts were reviewed. Patients' demographics, overall primary and final success, functional outcome, complication rates were identified and recorded. Subgroup analysis according to lens status and foveal attachment was also performed. RESULTS: A total of 212 cases of primary RRD were included. Mean age at time of surgery was 56.6 years (range 9-90 years); 175(82.5%) had pars plana vitrectomy (PPV), 27 (12.5%), scleral buckle (SB) repair and 10 (5%) pneumatic retinopexy (PR). Overall primary and final success rate were 86% and 95.6% respectively. Overall mean visual acuity improved from 1.1 to 0.4 LogMAR postoperatively after a mean follow-up of 9 months. There was no significant difference in the primary success rate in relation to the baseline lens status (χ2 = 3.4, P = 0.2) and to the baseline macular status (χ2 = 0.6, P = 0.7). Presence of proliferative vitreoretinopathy (PVR) negatively affected the primary success rate (χ2=7.2, P = 0.03). Poor prognostic factors for success were PVR at presentation, inferior breaks and increasing number of detached quadrants. CONCLUSIONS: This study demonstrates a success rate comparable with other centres with a low rate of final failure. Despite sub-specialism and the great advances in VR surgery, the biology of RRD dictates a failure rate. New therapies may improve results in the future.

A one-piece 3D printed flexure translation stage for open-source microscopy.

Open source hardware has the potential to revolutionise the way we build scientific instruments; with the advent of readily available 3D printers, mechanical designs can now be shared, improved, and replicated faster and more easily than ever before. However, printed parts are typically plastic and often perform poorly compared to traditionally machined mechanisms. We have overcome many of the limitations of 3D printed mechanisms by exploiting the compliance of the plastic to produce a monolithic 3D printed flexure translation stage, capable of sub-micron-scale motion over a range of 8 × 8 × 4 mm. This requires minimal post-print clean-up and can be automated with readily available stepper motors. The resulting plastic composite structure is very stiff and exhibits remarkably low drift, moving less than 20 µm over the course of a week, without temperature stabilisation. This enables us to construct a miniature microscope with excellent mechanical stability, perfect for time-lapse measurements in situ in an incubator or fume hood. The ease of manufacture lends itself to use in containment facilities where disposability is advantageous and to experiments requiring many microscopes in parallel. High performance mechanisms based on printed flexures need not be limited to microscopy, and we anticipate their use in other devices both within the laboratory and beyond.

Commercial air travel after intraocular gas injection.

Passengers with intraocular gas are at risk of profound visual loss when exposed to reduced absolute pressure within the cabin of a typical commercial airliner. Information provided on the websites of the world's 10 largest airlines offer a considerable range of opinion as to when it might be safe to fly after gas injection. Physicians responsible for clearing pseassengers as 'fit to fly' should be aware modern retinal surgical techniques increasingly employ long-acting gases as vitreous substitutes. The kinetics of long-acting intraocular gases must be considered when deciding how long after surgery it is safe to travel. It is standard practice to advise passengers not to fly in aircraft until the gas is fully resorbed. To achieve this, it may be necessary to delay travel for approximately 2 wk after intraocular injection of sulfur hexafluoride (SF6) and for 6 wk after injection of perfluoropropane (C3F8).

Cartwheel retinopathy.

A case of Valsalva retinopathy is presented, with a discussion of treatment options.

Cdk5rap2 exposes the centrosomal root of microcephaly syndromes.

Autosomal recessive primary microcephaly (MCPH) is characterized by small brain size as a result of deficient neuron production in the developing cerebral cortex. Although MCPH is a rare disease, the questions surrounding its etiology strike at the core of stem cell biology. The seven genes implicated in MCPH all encode centrosomal proteins and disruption of the MCPH gene Cdk5rap2 in mice revealed its role in neural progenitor proliferation and in maintaining normal centriole replication control. We discuss here the impact that centrosome regulation has upon neural progenitors in the developing brain. We integrate the impact of centriole replication defects with the functions of Cdk5rap2 and other MCPH proteins, propose mechanisms for progenitor loss in MCPH, and discuss links to two other microcephaly syndromes.

Melatonin sensitizes human myometrial cells to oxytocin in a protein kinase C alpha/extracellular-signal regulated kinase-dependent manner.

CONTEXT: Studies have shown that labor occurs primarily in the night/morning hours. Recently, we identified the human myometrium as a target for melatonin (MEL), the neuroendocrine output signal coding for circadian night. OBJECTIVE: The purpose of this study was to determine the signaling pathway underlying the effects of MEL on contractility and the contractile machinery in immortalized human myometrial cells. DESIGN: To ascertain the signaling pathway of MEL leading to its effects on myometrial contractility in vitro, we performed gel retraction assays with cells exposed to iodo-MEL (I-MEL) with or without oxytocin and the Rho kinase inhibitor Y27632. I-MEL effects on inositol trisphosphate (IP(3))/diacylglycerol (DAG)/protein kinase C (PKC) signaling were also investigated. Additionally, we assayed for caldesmon phosphorylation and ERK1/2 activation. RESULTS: I-MEL was found to activate PKC alpha via the phospholipase C/IP(3)/DAG signaling pathway, which was confirmed by PKC enzyme assay. I-MEL did not affect myosin light chain phosphatase activity, and its effects on contractility were insensitive to Rho kinase inhibition. I-MEL did increase phosphorylation of ERK1/2 and caldesmon, which was inhibited by the MAPK kinase inhibitor PD98059 or the PKC inhibitor C1. CONCLUSIONS: MEL sensitizes myometrial cells to subsequent procontractile signals in vitro through activation of the phospholipase C/IP(3)/DAG signaling pathway, resulting in specific activation of PKC alpha and ERK1/2, thereby phosphorylating caldesmon, which increases actin availability for myosin binding and cross-bridging. In vivo, this sensitization would provide a mechanism for the increased nocturnal uterine contractility and labor that has been observed in late-term human pregnancy.

The incidence and rate of rhegmatogenous retinal detachment seven years after cataract surgery in patients with high myopia.

BACKGROUND: Cataract extraction is the most commonly performed surgery in the National Health Service. Myopia increases the risk of postoperative rhegmatogenous retinal detachment (RRD). The aim of this study was to determine the incidence and rate of RRD seven years after cataract extraction in highly myopic eyes. METHODS: Retrospective review was performed of notes of all high myopes (axial length 26.0 mm or more) who underwent cataract extraction during the study period in one centre. RESULTS: 84 eyes met the study criteria. Follow-up time from surgery was 93 to 147 months (median 127 months). The average axial length was 28.72 mm (sd 1.37). Two eyes developed post-operative RRD; the incidence was 2.4% and the rate one RRD per 441.6 person-years. The results of 15 other studies on the incidence of RRD after cataract extraction in high myopia were pooled and combined with our estimate. CONCLUSION: Both patients in our study who developed RRD had risk factors for this complication as well as high myopia. Risk factors are discussed in the light of our results and the pooled estimate. Our follow-up time is longer than most. Future case series should calculate rates to allow meaningful comparison of case series.

Melatonin synergizes with oxytocin to enhance contractility of human myometrial smooth muscle cells.

CONTEXT: Studies have shown that labor occurs primarily in the night/morning hours. Recently, we identified the human myometrium as a target for melatonin (MEL), the neuroendocrine output signal coding for circadian night. OBJECTIVE: The purpose of this study was to determine the effects of MEL on contractility and the contractile machinery in telomerase-immortalized human myometrial cells. DESIGN: To ascertain the effect of MEL on myometrial contractility in vitro, we performed gel retraction assays with cells exposed to iodomelatonin +/- oxytocin (OT). The effects of iodomelatonin on gap junctions were also investigated. Additionally, expression levels of the type 2 MEL receptor (MT2R) were assessed in myometrial biopsies from term pregnant women with or without labor. RESULTS: MEL was found to synergistically enhance OT-induced contractility via the MT2R, which is coupled to a protein kinase C-dependent increase in phosphorylation of the myosin light chain protein. MT2R expression was markedly elevated in samples from pregnant women who had entered labor, as compared to matched nonlaboring pregnant women. MEL increased expression of the gap junction protein, connexin 43. In vitro dye spread assays showed that MEL-treated cells displayed substantially increased intercellular coupling. Increases in connexin 43 mRNA and cell to cell coupling were also found to be mediated via the MT2R in a protein kinase C-dependent manner. CONCLUSIONS: MEL synergizes with OT to promote myometrial cell contractions and to facilitate gap junction activity in vitro. Such a synergy in vivo would promote coordinated and forceful contractions of the late term pregnant uterus necessary for parturition.

Transcriptional inhibition of oxytocin receptor expression in human myometrial cells by melatonin involves protein kinase C signaling.

CONTEXT: Our laboratory recently characterized the expression of the melatonin receptors in the human myometrium and showed that the expression of these receptors is suppressed during late pregnancy. OBJECTIVE: In an effort to understand better the significance of melatonin in the human myometrium, we explored the mechanisms through which this hormone influences the expression of the oxytocin receptor in vitro. DESIGN: The stable melatonin analog iodomelatonin was presented to cultured telomerase-immortalized myometrial cells of the human telomerase reverse transcriptase line under physiological doses and durations. Pharmacological inhibitors of melatonin binding, gene transcription, phospholipase C, and protein kinase C signaling were used to define the mechanism of melatonin action. RESULTS: Our results reveal that melatonin significantly inhibits oxytocin receptor mRNA expression primarily via the melatonin 2 receptor. The melatonin-dependent decrease in oxytocin receptor transcripts involves suppression of gene transcription rather than enhanced rates of transcript degradation. Melatonin effects were abolished by pretreating the cells with the phospholipase C inhibitor U73122 or the protein kinase C inhibitor C1. CONCLUSIONS: Melatonin, like oxytocin, can negatively regulate oxytocin receptor transcription in human myometrial cells via modulation of protein kinase C signaling. This is consistent with the hypothesis that the reduced melatonin receptor expression during late pregnancy, which occurs at a time when oxytocin receptors are up-regulated, may be physiologically important for the subsequent timing of labor.