Ocular coherence tomography-measured changes over time in anterior chamber angle and diurnal intraocular pressure after laser iridotomy: IMPACT study

Importance: The change in the anatomical dimensions over time and the effect on diurnal intraocular pressure following laser peripheral iridotomy is poorly understood. Background: To evaluate change over time in anterior chamber angle anatomy following laser peripheral iridotomy (LPI) in patients with primary angle closure compared to control eyes. Additionally, the effect of LPI on diurnal intraocular pressure (DIOP) fluctuation was investigated. Design: Longitudinal, prospective, double-randomised research study. Participants: Adults with suspected angle closure or angle closure diagnosis referred to hospital services in the United Kingdom. Methods: Thirty-nine patients newly diagnosed with bilateral primary angle closure/suspects (PAC/PACS) received LPI to one eye and changes in angle morphology were measured over 8 sections with swept source AS-OCT. The other eye acted as control with intraocular pressure (IOP) measured hourly. Main outcome measures: Angle opening distance (AOD), trabecular–iris angle (TIA), angle recess area (ARA), and trabecular–iris space area (TISA) at 500 m and 750 m from scleral spur Results: There was an increase in all angle parameters following LPI, which was maintained for 6 months (e.g inferotemporal segment AOD500 0.041mm (p=0.008) at 1 week and 0.039mm (p=0.003) at 6 months) following LPI. Greatest effect at 6 months post-LPI was observed opposite the iridotomy site in the inferior/inferotemporal sections (AOD500 0.039mm, p=0.003 and AOD750 0.075mm, p=0.002). There were no statistically significant differences for the overall DIOP fluctuation values in the treated group at 6 months post-LPI compared to baseline. Conclusions and Relevance: LPI widened all angle sections with maximum effect observed in the site opposite the iridotomy. Angle changes were maintained up to 6 months after LPI treatment without any statistically significant change in DIOP fluctuation

Dissection of a functional interaction between the DNA translocase, FtsK, and the XerD recombinase

Successful bacterial circular chromosome segregation requires that any dimeric chromosomes, which arise by crossing over during homologous recombination, are converted to monomers. Resolution of dimers to monomers requires the action of the XerCD site-specific recombinase at dif in the chromosome replication terminus region. This reaction requires the DNA translocase, FtsK(C), which activates dimer resolution by catalysing an ATP hydrolysis-dependent switch in the catalytic state of the nucleoprotein recombination complex. We show that a 62-amino-acid fragment of FtsK(C) interacts directly with the XerD C-terminus in order to stimulate the cleavage by XerD of BSN, a dif-DNA suicide substrate containing a nick in the ‘bottom’ strand. The resulting recombinase–DNA covalent complex can undergo strand exchange with intact duplex dif in the absence of ATP. FtsK(C)-mediated stimulation of BSN cleavage by XerD requires synaptic complex formation. Mutational impairment of the XerD–FtsK(C) interaction leads to reduction in the in vitro stimulation of BSN cleavage by XerD and a concomitant deficiency in the resolution of chromosomal dimers at dif in vivo, although other XerD functions are not affected

Temporal ocular coherence tomography-measured changes in anterior chamber angle and diurnal intraocular pressure after laser iridoplasty: IMPACT study

Aims: To evaluate temporal change in anterior chamber angle anatomy following argon laser peripheral iridoplasty (ALPI) in eyes with occludable angles postlaser peripheral iridotomy (LPI) compared with control eyes. Additionally, the effect on diurnal intraocular pressure (DIOP) fluctuation (maximum-minimum IOP) was investigated. Methods: Twenty-two patients with bilateral primary angle closure/suspects with gonioscopically occludable anterior chamber angles following LPI were randomised to receive ALPI (n=11) or no further treatment (n=11). Angle opening distance (AOD), trabecular-iris angle, angle recess area and trabecular-iris space area were measured over eight sections with swept-source anterior segment optical coherence tomography and DIOP was measured pre-LPI and repeated at 3 months after ALPI (hourly measures). Results: All angle parameters increased following ALPI. This change was maintained for 3 months in seven of the eight sections (eg, inferotemporal AOD500 increased by 0.063 mm, p=0.004 at 1 day; 0.051 mm, p=0.029 at 1 week; 0.059 mm, p=0.006 at 6 weeks and 0.056 mm, p=0.011 at 3 months). The only exception was in the inferior sector (eg, AOD500 increased by 0.041 mm, p=0.025 at 1 day and by 0.029 mm, p=0.054 at 3 months). DIOP at 3 months was significantly reduced (5.04 mm Hg; ±1.61 mm Hg) compared with controls (6.61 mm Hg; ±1.63 mm Hg). Maximum IOP was significantly greater in the non-ALPI group (1.87 mm Hg, p=0.026). Conclusions: ALPI widened all angle sections in eyes that remained occludable post-LPI. Changes were maintained for 3 months. ALPI decreased DIOP fluctuation in the treated eyes by lowering the maximum IOP value

Dissection of a functional interaction between the XerD recombinase and the DNA translocase FtsK

Successful bacterial circular chromosome segregation requires that any dimeric chromosomes, which arise by crossing over during homologous recombination, are converted to monomers. Resolution of dimers to monomers requires the action of the XerCD site-specific recombinase at dif in the chromosome replication terminus region. This reaction requires the DNA translocase, FtsK(C), which activates dimer resolution by catalysing an ATP hydrolysis-dependent switch in the catalytic state of the nucleoprotein recombination complex. We show that a 62-amino-acid fragment of FtsK(C) interacts directly with the XerD C-terminus in order to stimulate the cleavage by XerD of BSN, a dif-DNA suicide substrate containing a nick in the 'bottom' strand. The resulting recombinase-DNA covalent complex can undergo strand exchange with intact duplex dif in the absence of ATP. FtsK(C)-mediated stimulation of BSN cleavage by XerD requires synaptic complex formation. Mutational impairment of the XerD-FtsK(C) interaction leads to reduction in the in vitro stimulation of BSN cleavage by XerD and a concomitant deficiency in the resolution of chromosomal dimers at dif in vivo, although other XerD functions are not affected.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Dissection of a functional interaction between the XerD recombinase and the DNA translocase FtsK

Successful bacterial circular chromosome segregation requires that any dimeric chromosomes, which arise by crossing over during homologous recombination, are converted to monomers. Resolution of dimers to monomers requires the action of the XerCD site-specific recombinase at dif in the chromosome replication terminus region. This reaction requires the DNA translocase, FtsK(C), which activates dimer resolution by catalysing an ATP hydrolysis-dependent switch in the catalytic state of the nucleoprotein recombination complex. We show that a 62-amino-acid fragment of FtsK(C) interacts directly with the XerD C-terminus in order to stimulate the cleavage by XerD of BSN, a dif-DNA suicide substrate containing a nick in the 'bottom' strand. The resulting recombinase-DNA covalent complex can undergo strand exchange with intact duplex dif in the absence of ATP. FtsK(C)-mediated stimulation of BSN cleavage by XerD requires synaptic complex formation. Mutational impairment of the XerD-FtsK(C) interaction leads to reduction in the in vitro stimulation of BSN cleavage by XerD and a concomitant deficiency in the resolution of chromosomal dimers at dif in vivo, although other XerD functions are not affected.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

A retrospective analysis of long-term outcomes following a single episode of transscleral cyclodiode laser treatment in patients with glaucoma

OBJECTIVES: To investigate the efficacy of a single cyclodiode laser photocoagulation treatment for refractory glaucoma and its effect on visual outcome in patients with good visual potential as well as to evaluate possible predictive factors in establishing optimal treatment parameters. DESIGN: Retrospective observational study. SETTING: Tertiary referral centre. PARTICIPANTS: The notes of 87 patients with refractory glaucoma who underwent cyclodiode photocoagulation as a first surgical intervention over a 7-year period. MAIN OUTCOME MEASURES: Maintenance of intraocular pressure (IOP) reduction, number of medications and visual acuity outcomes post-treatment. RESULTS: The mean IOP after a single treatment decreased from 39.5±1.3 to 17.8±1.5 mm Hg after a 6-week follow-up period (p<0.0001). This reduction in IOP was maintained over a 3-year period. Here, 61.5% of patients were able to reduce the number of medications used, with mean reduction from 2.6 to 1.5 medications (p<0.05). The mean initial visual field loss prior to treatment was 8.74 dB and at 6 months post-treatment was measured at 9.06 dB (p>0.05), suggesting no significant overall change. Visual acuity remained unchanged or improved for 83.6% of patients (p>0.05) with relatively good visual potential (average vision preoperatively was 0.57 logMAR). Hypotony occurred in 5.3% of patients. No patients required enucleation or evisceration. CONCLUSIONS: A single session of cyclodiode laser therapy was associated with significant IOP reduction in a majority of patients with refractory glaucoma. The majority were able to maintain the IOP reduction over a 3-year period without the need for a further surgical intervention. Additionally, over 80% of the patients in our study were able to maintain their baseline visual acuity. These results support the view that a single cyclodiode treatment can be sufficient in achieving long-term IOP control and may be considered in eyes with relatively good visual potential