Reactive Vapor-Phase Inhibitors for Area-Selective Depositions at Tunable Critical Dimensions.

Area-selective depositions (ASD) take advantage of the chemical contrast between material surfaces in device fabrication, where a film can be selectively grown by chemical vapor deposition on metal versus a dielectric, for instance, and can provide a path to nontraditional device architectures as well as the potential to improve existing device fabrication schemes. While ASD can be accessed through a variety of methods, the incorporation of reactive moieties in inhibitors presents several advantages, such as increasing thermal stability and limiting precursor diffusion into the blocking layer. Alkyne-terminated small molecule inhibitors (SMIs)─propargyl, dipropargyl, and tripropargylamine─were evaluated as metal-selective inhibitors. Modeling these SMIs provided insight into the binding mechanism, influence of sterics, and complex polymer network formed from the reaction between inhibitors consisting of alkene, aromatic, and network branchpoints. While a significant contrast in the binding of the SMIs on copper versus a dielectric was observed, residual amounts were detected on the dielectric surfaces, leading to variable ALD growth rates dependent on pattern-critical dimensions. This behavior can be controlled and utilized to direct film growth on patterns only above a critical threshold dimension; below this threshold, both the dielectric and metal features are protected. This method provides another design parameter for ASD processes and may extend its application to broader-ranging device fabrication schemes.

Comparison of Outcomes Following Glaucoma Drainage Tube Surgery Between Primary and Secondary Glaucomas, and Between Phakic and Pseudophakic eyes.

PURPOSE: To report outcomes of glaucoma drainage device (GDD) surgery based on primary or secondary glaucoma diagnosis and lens status. DESIGN: Single-center, retrospective, consecutive cohort study. METHODS: University of Florida patients aged 18 to 93 years who underwent nonvalved GDD surgery between 1996 and 2015 with a minimum of 1-year follow-up were examined. Of the 186 eyes of 186 patients enrolled, 108 had a primary glaucoma and 78 a secondary glaucoma diagnosis. Excluding 13 aphakic patients, 57 eyes were phakic and 116 pseudophakic. Mean intraocular pressure (IOP), mean number of medications, visual acuity (VA), surgical complications, and failure (IOP ≥18 mm Hg, IOP <6 mm Hg, reoperation for glaucoma, or loss of light perception) were the main outcome measures. RESULTS: No significant difference was noted in mean IOP and mean medication use (12.8 ±â€Š4.5 and 13.0 ±â€Š6.6 mm Hg on 2.0 ±â€Š1.2 and 1.5 ±â€Š1.1 medication classes, respectively), mean VA (1.08 ±â€Š0.98 and 0.94 ±â€Š0.89, respectively), failure, or numbers of complications and reoperations (P > 0.05) between eyes with primary and secondary glaucomas at up to 5 years postoperatively. Comparison of phakic and pseudophakic eyes showed a statistically significant higher success rate for the pseudophakic patient group at the ≥18 mm Hg upper limit and <6 mm Hg lower limit (P = 0.01), and significantly fewer eyes required reoperation to lower IOP (6.9% vs 23%). CONCLUSIONS: GDD surgery appears equally effective for secondary glaucomas as for primary glaucomas, and has a better outcome for pseudophakic eyes than phakic eyes.

Bilateral anterior segment dysgenesis and persistent fetal vasculature associated with terminal 10q26 deletion.

Deletion of the 26q position on chromosome 10 results in a syndrome with well-documented systemic phenotypes. There are few reports of ophthalmic manifestations in terminal 10q26 deletion. We report a 4-week-old boy with terminal 10q26 deletion who had extensive ophthalmic abnormalities, including bilateral anterior segment dysgenesis and bilateral persistent fetal vasculature, with microphthalmia, microcornea, iris corectopia, congenital cataracts, and posterior embryotoxon.

Astrocytic IP3Rs: Beyond IP3R2.

Astrocytes are sensitive to ongoing neuronal/network activities and, accordingly, regulate neuronal functions (synaptic transmission, synaptic plasticity, behavior, etc.) by the context-dependent release of several gliotransmitters (e.g., glutamate, glycine, D-serine, ATP). To sense diverse input, astrocytes express a plethora of G-protein coupled receptors, which couple, via Gi/o and Gq, to the intracellular Ca2+ release channel IP3-receptor (IP3R). Indeed, manipulating astrocytic IP3R-Ca2+ signaling is highly consequential at the network and behavioral level: Depleting IP3R subtype 2 (IP3R2) results in reduced GPCR-Ca2+ signaling and impaired synaptic plasticity; enhancing IP3R-Ca2+ signaling affects cognitive functions such as learning and memory, sleep, and mood. However, as a result of discrepancies in the literature, the role of GPCR-IP3R-Ca2+ signaling, especially under physiological conditions, remains inconclusive. One primary reason for this could be that IP3R2 has been used to represent all astrocytic IP3Rs, including IP3R1 and IP3R3. Indeed, IP3R1 and IP3R3 are unique Ca2+ channels in their own right; they have unique biophysical properties, often display distinct distribution, and are differentially regulated. As a result, they mediate different physiological roles to IP3R2. Thus, these additional channels promise to enrich the diversity of spatiotemporal Ca2+ dynamics and provide unique opportunities for integrating neuronal input and modulating astrocyte-neuron communication. The current review weighs evidence supporting the existence of multiple astrocytic-IP3R isoforms, summarizes distinct sub-type specific properties that shape spatiotemporal Ca2+ dynamics. We also discuss existing experimental tools and future refinements to better recapitulate the endogenous activities of each IP3R isoform.

NMDARs, Coincidence Detectors of Astrocytic and Neuronal Activities.

Synaptic plasticity is an extensively studied cellular correlate of learning and memory in which NMDARs play a starring role. One of the most interesting features of NMDARs is their ability to act as a co-incident detector. It is unique amongst neurotransmitter receptors in this respect. Co-incident detection is possible because the opening of NMDARs requires membrane depolarisation and the binding of glutamate. Opening of NMDARs also requires a co-agonist. Although the dynamic regulation of glutamate and membrane depolarization have been well studied in coincident detection, the role of the co-agonist site is unexplored. It turns out that non-neuronal glial cells, astrocytes, regulate co-agonist availability, giving them the ability to influence synaptic plasticity. The unique morphology and spatial arrangement of astrocytes at the synaptic level affords them the capacity to sample and integrate information originating from unrelated synapses, regardless of any pre-synaptic and post-synaptic commonality. As astrocytes are classically considered slow responders, their influence at the synapse is widely recognized as modulatory. The aim herein is to reconsider the potential of astrocytes to participate directly in ongoing synaptic NMDAR activity and co-incident detection.

Comparison of Outcomes of Glaucoma Drainage Implant Surgery With or Without Prior Failed Trabeculectomy.

PRECIS: A comparison of 186 glaucoma patients with mixed diagnoses who underwent nonvalved glaucoma drainage device (GDD) implant surgery showed similar long-term intraocular pressure (IOP), medication, and visual acuity (VA) outcomes between those with prior failed trabeculectomy surgery versus those without. PURPOSE: The purpose of this study was to evaluate whether prior failed trabeculectomy adversely affects the outcome of glaucoma tube surgery. PATIENTS AND METHODS: A total of 186 eyes of 186 patients who underwent a nonvalved GDD implant surgery by a single surgeon between 1996 and 2015 at a University practice were included. Patients were of mixed diagnoses and over 18 years old. Before the GDD surgery, 65 had a previous failed glaucoma filtering surgery and 121 had no prior glaucoma surgery. Demographic information, preoperative and postoperative IOP, medication, VA, and complications were collected from chart review. RESULTS: No significant difference was noted in mean IOP and mean medication use (13.0 and 12.6 mm Hg on 2.0 and 1.7 medication classes at 5 y postoperatively, respectively), mean VA and change in VA from baseline, or numbers of complications (P>0.05), between eyes that had a prior failed filtration surgery and those that had not. Kaplan-Meier plots for failure over 5 years using a lower limit of <5 mm Hg and an upper limit of ≥18, ≥15, or ≥12 mm Hg did not show a significant difference between groups. Subanalyses were performed to examine only primary glaucoma eyes and results were similar. Further group subanalyses comparing those with baseline IOP ≥25 or <25 mm Hg, age 65 and above or below 65 years and those specifically with Baerveldt 350 mm2 implants also did not show significant differences. CONCLUSION: Prior failed filtration surgery does not appear to affect the outcome of future GDD surgery.

A new, minimally invasive procedure for dogs with encapsulated Ahmed drainage implants and elevated intraocular pressures: A case series.

OBJECTIVE: To describe a novel, minimally invasive method for re-establishing aqueous humor outflow in dogs with refractory glaucoma after fibrous encapsulation of their Ahmed drainage implants. PROCEDURE: Three dogs (4 eyes) underwent trans-capsular implantation of an Alcon EX-PRESS® glaucoma filtration device under sedation (2 dogs) or general anesthesia (1 dog). After rotating the eye downwards, a 2 mm incision was made in the conjunctiva/Tenon's capsule overlying the encapsulated Ahmed plate, and later closed with absorbable suture. All eyes received subconjunctival mitomycin-C 0.02 mg. RESULTS: Mean post-operative follow-up was 341 days (range: 77-530). All eyes were hypertensive pre-operatively (mean IOP: 31.25 ± 7.14 mmHg) despite receiving topical latanoprost (4/4), timolol (4/4), carbonic anhydrase inhibitors (4/4), and demecarium bromide (2/4). Two eyes (dogs 1 and 2) were visual pre-operatively, while 2 eyes (dog 3) displayed equivocal or no vision. Post-operatively, all eyes received timolol and a carbonic anhydrase inhibitor. Other anti-hypertensive medications were discontinued. Immediately following surgery, all eyes were mildly hypotensive (mean IOP: 5.75 ± 1.71 mm Hg). Two of 4 eyes were normotensive and visual until days 90 (dog 2) and 530 (dog 1) (IOP range: 10-16 mm Hg). One eye (dog 3) was normotensive for approximately 150 days, and then hypertension returned. One eye (dog 3) from the start displayed severe uveitis, hypertensive episodes, and was phthisical by the end of follow-up. CONCLUSIONS: Trans-capsular EX-PRESS® implantation is a minimally invasive procedure for treatment of refractory glaucoma in dogs with encapsulated Ahmed drainage implants, and further investigation is warranted.

Attaining Intraocular Pressure of ≤10 mm Hg: Comparison of Tube and Trabeculectomy Surgery in Pseudophakic Primary Glaucoma Eyes.

PURPOSE: The aim of this study is to evaluate whether trabeculectomy with antimetabolites or glaucoma drainage device (GDD) surgery is more likely to achieve an intraocular pressure (IOP) ≤10 mm Hg. DESIGN: Retrospective, nonrandomized, cohort study of pseudophakic, primary glaucoma patients. METHODS: 53 pseudophakic patients underwent trabeculectomy and 65 received GDD at the University of Florida by one surgeon between 1993 and 2015. The main outcome measures were mean IOP and percentage of patients obtaining an IOP ≤10 mm Hg for up to 5 years postoperatively. A subgroup undergoing a first time glaucoma surgery was also analyzed because there were more redo glaucoma procedures in the GDD group. RESULTS: Over 5 years, the mean annual IOP for the trabeculectomy eyes was between 6.9 and 7.8 mm Hg on an average of 0.2 medications, and that for GDD eyes was between 11.4 and 12.1 mm Hg on a mean of 1.6 to 1.9 medications (P < 0.002). A significantly higher percentage of trabeculectomy eyes than GDD eyes achieved a pressure of ≤10 mm Hg, for years 1 to 4 (P < 0.05). Visual acuity (VA) change was not statistically different between the groups, both for mean logMAR acuity and percentage of patients that lost ≥2 Snellen lines. Complication rates were similar between the groups. Postoperative VA change was similar for eyes achieving low IOP ≤5 mm Hg and those eyes with an IOP ≥10 mm Hg. CONCLUSIONS: Trabeculectomy provided significantly lower IOP for 5 years postoperatively in pseudophakic primary glaucoma patients, and was more likely to achieve an IOP ≤10 mm Hg.

Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid.

AIM: The aim of this study is to assess the effectiveness of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor (HDI) with a broad spectrum epigenetic activity, in improving filtration bleb survival as an adjunct therapy to glaucoma filtration surgery (GFS) in the rabbit model. MATERIALS AND METHODS: Eighteen New Zealand White rabbits underwent GFS in the left eye and were randomized to receive either a subconjunctival (SC) injection of 0.1 mL SAHA (9.25 µg/mL) or balanced saline solution (BSS) at the end of surgery, or a 3-minute intraoperative topical application of 0.4 mg/mL mitomycin-C (MMC). Bleb survival and histology were compared. RESULTS: Blebs of rabbits receiving injections of SAHA survived an average (mean ± SD) of 23.2 ± 2.7 days. SAHA rabbits showed a nonsignificant improvement over rabbits that received an injection of BSS, which had a mean survival time of 19.7 ± 2.7 days (p = 0.38) according to a one-way analysis of variance (ANOVA). Eyes receiving intraoperative topical MMC survived an average of 32.5 ± 3.3 days, which is significantly longer than both the control group treated with BSS (p = 0.01) and the experimental group treated with the SAHA (p = 0.0495). SAHA was well tolerated and showed no significant avascularity, necrosis, or conjunctival thinning. CONCLUSION: Although it was well tolerated, a single intraoperative injection of SAHA did not significantly prolong bleb survival in the rabbit model. CLINICAL SIGNIFICANCE: Epigenetic adjuncts hold promise for improving GFS outcome; however, future studies must continue to examine different administration protocols and dosages to substantiate their efficacy. HOW TO CITE THIS ARTICLE: Rodgers CD, Lukowski ZL, et al. Modulating Ocular Scarring in Glaucoma Filtration Surgery Using the Epigenetic Adjunct Suberoylanilide Hydroxamic Acid. J Curr Glaucoma Pract 2019;13(1):37-41.

Astroglial CB1 Receptors Determine Synaptic D-Serine Availability to Enable Recognition Memory.

Bidirectional communication between neurons and astrocytes shapes synaptic plasticity and behavior. D-serine is a necessary co-agonist of synaptic N-methyl-D-aspartate receptors (NMDARs), but the physiological factors regulating its impact on memory processes are scantly known. We show that astroglial CB1 receptors are key determinants of object recognition memory by determining the availability of D-serine at hippocampal synapses. Mutant mice lacking CB1 receptors from astroglial cells (GFAP-CB1-KO) displayed impaired object recognition memory and decreased in vivo and in vitro long-term potentiation (LTP) at CA3-CA1 hippocampal synapses. Activation of CB1 receptors increased intracellular astroglial Ca2+ levels and extracellular levels of D-serine in hippocampal slices. Accordingly, GFAP-CB1-KO displayed lower occupancy of the co-agonist binding site of synaptic hippocampal NMDARs. Finally, elevation of D-serine levels fully rescued LTP and memory impairments of GFAP-CB1-KO mice. These data reveal a novel mechanism of in vivo astroglial control of memory and synaptic plasticity via the D-serine-dependent control of NMDARs.

Intracellular rupture, exocytosis and actin interaction of endocytic vacuoles in pancreatic acinar cells: initiating events in acute pancreatitis.

KEY POINTS: Giant trypsin-containing endocytic vacuoles are formed in pancreatic acinar cells stimulated with inducers of acute pancreatitis. F-actin envelops endocytic vacuoles and regulates their properties. Endocytic vacuoles can rupture and release their content into the cytosol of acinar cells. Endocytic vacuoles can fuse with the plasma membrane of acinar cells and exocytose their content. ABSTRACT: Intrapancreatic activation of trypsinogen is an early event in and hallmark of the development of acute pancreatitis. Endocytic vacuoles, which form by disconnection and transport of large post-exocytic structures, are the only resolvable sites of the trypsin activity in live pancreatic acinar cells. In the present study, we characterized the dynamics of endocytic vacuole formation induced by physiological and pathophysiological stimuli and visualized a prominent actin coat that completely or partially surrounded endocytic vacuoles. An inducer of acute pancreatitis taurolithocholic acid 3-sulphate and supramaximal concentrations of cholecystokinin triggered the formation of giant (more than 2.5 µm in diameter) endocytic vacuoles. We discovered and characterized the intracellular rupture of endocytic vacuoles and the fusion of endocytic vacuoles with basal and apical regions of the plasma membrane. Experiments with specific protease inhibitors suggest that the rupture of endocytic vacuoles is probably not induced by trypsin or cathepsin B. Perivacuolar filamentous actin (observed on the surface of ∼30% of endocytic vacuoles) may play a stabilizing role by preventing rupture of the vacuoles and fusion of the vacuoles with the plasma membrane. The rupture and fusion of endocytic vacuoles allow trypsin to escape the confinement of a membrane-limited organelle, gain access to intracellular and extracellular targets, and initiate autodigestion of the pancreas, comprising a crucial pathophysiological event.

The impact of conjunctival flap method and drainage cannula diameter on bleb survival in the rabbit model.

PURPOSE: To examine the effect of cannula diameter and conjunctival flap method on bleb survival in rabbits undergoing cannula-based glaucoma filtration surgery (GFS). METHODS: Twelve New Zealand White rabbits underwent GFS in both eyes. The twenty-four eyes were divided into four groups. Two of the four groups (N = 12) received limbus-based conjunctival flaps (LBCF), and the other two (N = 12) received fornix-based conjunctival flaps (FBCF). Six FBCF rabbit eyes were implanted with 22-gauge drainage tubes, and the other six were implanted with 26-gauge tubes. Likewise, six LBCF rabbits received 22-gauge drainage tubes and six received 26-gauge tubes. Filtration blebs were evaluated every three days by a masked observer. Bleb failure was defined as the primary endpoint in this study and was recorded after two consecutive flat bleb evaluations. RESULTS: Group 1 (LBCF, 22- gauge cannula) had a mean bleb survival time (Mean ± SD) of 18.7 ± 2.9 days. Group 2 (LBCF, 26-gauge cannula) also had a mean bleb survival time of 18.7 ± 2.9 days. Group 3 (FBCF, 22-gauge cannula) had a mean bleb survival time of 19.2 ± 3.8 days. Group 4 (FBCF, 26-gauge cannula) had a mean bleb survival time of 19.7 ± 4.1 days. A 2-way analysis of variance showed that neither surgical approach nor cannula gauge made a statistically significant difference in bleb survival time (P = 0.634 and P = 0.874). Additionally, there was no significant interaction between cannula gauge and conjunctival flap approach (P = 0.874), suggesting that there was not a combination of drainage gauge and conjunctival flap method that produced superior bleb survival. CONCLUSION: Limbus and fornix-based conjunctival flaps are equally effective in promoting bleb survival using both 22 and 26-gauge cannulas in the rabbit model. The 26-gauge drainage tube may be preferred because its smaller size facilitates the implantation process, reducing the risk of corneal contact.

Comparing glaucomatous disc change using stereo disc viewing and the MatchedFlicker programme in glaucoma experts and trainees.

BACKGROUND/AIMS: The objective of this study is to evaluate the accuracy and speed of trainees and experienced glaucoma specialists using the MatchedFlicker software against the manual examination of stereoscopic disc photographs for detecting glaucomatous optic disc change. METHODS: Three experienced glaucoma specialists, two resident ophthalmologists and one glaucoma fellow from multiple institutions independently evaluated the same 140 image pairs from 100 glaucomatous/ocular hypertensive eyes using a handheld stereo viewer and the MatchedFlicker programme. Fifty had progression to glaucoma as determined by the Ocular Hypertension Treatment Study (OHTS) Optic Disc Reading Group and endpoint committee, and 50 more were negative controls for progression with photos taken a few minutes apart. Twenty photo pairs from each of the two groups were duplicated for reviewer variability analysis. The initial viewing method was randomised and then alternated for each group of 70 image pairs. Reviewer accuracy and evaluation time for each method were measured. RESULTS: Evaluators averaged 8.6 s faster per image pair (26%) with the MatchedFlicker programme than with the stereo viewer (p=0.0007). Evaluators correctly identified more image pairs when using the MatchedFlicker software over the stereo viewer (p=0.0003). There was no significant difference between the expert and trainee group in speed or overall accuracy for either method. Experts were significantly more consistent than trainees with the duplicate image pairs (p=0.029). Trainees appeared more reluctant to designate eyes as showing glaucoma progression than experts. CONCLUSIONS: Both expert glaucoma specialists and ophthalmologists in various stages of training had greater accuracy and speed with the MatchedFlicker programme than with a handheld stereoscopic viewer.

Hyperconnected molecular glass network architectures with exceptional elastic properties.

Hyperconnected network architectures can endow nanomaterials with remarkable mechanical properties that are fundamentally controlled by designing connectivity into the intrinsic molecular structure. For hybrid organic-inorganic nanomaterials, here we show that by using 1,3,5 silyl benzene precursors, the connectivity of a silicon atom within the network extends beyond its chemical coordination number, resulting in a hyperconnected network with exceptional elastic stiffness, higher than that of fully dense silica. The exceptional intrinsic stiffness of these hyperconnected glass networks is demonstrated with molecular dynamics models and these model predictions are calibrated through the synthesis and characterization of an intrinsically porous hybrid glass processed from 1,3,5(triethoxysilyl)benzene. The proposed molecular design strategy applies to any materials system wherein the mechanical properties are controlled by the underlying network connectivity.

Retrospective Comparison of Intermediate-term Efficacy of 350 mm2 Glaucoma Drainage Implants and Medium-sized 230-250 mm2 Implants.

AIM: To compare the intermediate-term efficacy of a large surface area Baerveldt 350 mm2 glaucoma drainage device (GDD) with medium surface area implants (Baerveldt 250 mm2 and Molteno 3, 230, or 245 mm2). DESIGN: This is a retrospective, nonrandomized comparative trial. MATERIALS AND METHODS: A total of 94 eyes of 94 patients of mixed glaucoma diagnoses without any prior glaucoma surgical procedures and who had undergone a glaucoma drainage implant surgery with either a large Baerveldt 350 mm2 GDD or a medium-sized GDD (Baerveldt 250 mm2 or Molteno 230 or 245 mm2) were reviewed for intraocular pressure (IOP), number of glaucoma medications, and visual acuity (VA) preoperatively, and at 1, 2, and 3 years postprocedure. RESULTS: No significant differences were found in mean IOP, number of glaucoma medications used, and VA at 1, 2, and 3 years postoperatively. The rate of additional glaucoma procedures was similar between the two groups. CONCLUSION: There is no clear evidence that a larger implant surface area beyond 230 to 250 mm2 is advantageous in providing intermediate-term IOP control. CLINICAL SIGNIFICANCE: It may be technically easier to surgically place a GDD that does not need to have its wings placed underneath the recti muscles, and the IOP results are similar. HOW TO CITE THIS ARTICLE: Meyer AM, Rodgers CD, Zou B, Rosenberg NC, Webel AD, Sherwood MB. Retrospective Comparison of Intermediate-term Efficacy of 350 mm2 Glaucoma Drainage Implants and Medium-sized 230-250 mm2 Implants. J Curr Glaucoma Pract 2017;11(1):8-15.

Relationship between Glaucoma Drainage Device Size and Intraocular Pressure Control: Does Size Matter?

There is ambiguity in the literature regarding whether a larger glaucoma drainage device (GDD) achieves a lower long-term intraocular pressure (IOP). There is some evidence on both sides, but overall there seems to be an optimal surface area of approximately 200-250 mm2 beyond which there may be little advantage to increasing the plate size for most patients. HOW TO CITE THIS ARTICLE: Rodgers CD, Meyer AM, Sherwood MB. Relationship between Glaucoma Drainage Device Size and Intraocular Pressure Control: Does Size Matter? J Curr Glaucoma Pract 2017;11(1):1-2.

Astrocytic IP3 Rs: Contribution to Ca2+ signalling and hippocampal LTP.

Astrocytes regulate hippocampal synaptic plasticity by the Ca2+ dependent release of the N-methyl d-aspartate receptor (NMDAR) co-agonist d-serine. Previous evidence indicated that d-serine release would be regulated by the intracellular Ca2+ release channel IP3 receptor (IP3 R), however, genetic deletion of IP3 R2, the putative astrocytic IP3 R subtype, had no impact on synaptic plasticity or transmission. Although IP3 R2 is widely believed to be the only functional IP3 R in astrocytes, three IP3 R subtypes (1, 2, and 3) have been identified in vertebrates. Therefore, to better understand gliotransmission, we investigated the functionality of IP3 R and the contribution of the three IP3 R subtypes to Ca2+ signalling. As a proxy for gliotransmission, we found that long-term potentiation (LTP) was impaired by dialyzing astrocytes with the broad IP3 R blocker heparin, and rescued by exogenous d-serine, indicating that astrocytic IP3 Rs regulate d-serine release. To explore which IP3 R subtypes are functional in astrocytes, we used pharmacology and two-photon Ca2+ imaging of hippocampal slices from transgenic mice (IP3 R2-/- and IP3 R2-/- ;3-/- ). This approach revealed that underneath IP3 R2-mediated global Ca2+ events are an overlooked class of IP3 R-mediated local events, occurring in astroglial processes. Notably, multiple IP3 Rs were recruited by high frequency stimulation of the Schaffer collaterals, a classical LTP induction protocol. Together, these findings show the dependence of LTP and gliotransmission on Ca2+ release by astrocytic IP3 Rs. GLIA 2017;65:502-513.

Porosity of Bleb Capsule declines rapidly with Fluid Challenge.

INTRODUCTION: The porosity of the fibrous capsule around a glaucoma drainage device (GDD) may be the most important functional attribute. The factors that determine capsular porosity are not well understood. Failed GDD surgeries are usually associated with thick impervious capsules and components of aqueous have been implicated in this process. PURPOSE: In this study, we interrogated the effect of passage of nonaqueous fluid on capsular porosity in mature (but aqueous naïve) blebs in a previously reported GDD model (the "Center for Eye Research Australia Implant"). MATERIALS AND METHODS: The study was performed at two centers using 17 New Zealand White (NZW) rabbits. An experimental GDD was implanted into the subconjunctival space but without connection to the anterior chamber. After 28 days, balanced salt solution (BSS) was passed through the implant for 30 to 40 minutes at 12 mm Hg. Capsular porosity was measured as flow (µL/min) at a constant pressure. Porosity of the capsule was retested at 3 and 6 days. RESULTS: There was a marked reduction in capsular porosity within 3 days of exposure to BSS (fluid challenge). Even though the baseline porosity was significantly different in the two groups (3.00 ± 0.5 µL/min and 29.67 ± 12.12 µL/min, p < 0.001), the effect of passage of BSS was similar. Capsular porosity fell by approximately 80% in both groups from baseline after single BSS challenge. Capsular thickness was significantly less in Advanced Eye Center (AEC) rabbits at baseline. There was no change in the capsular thickness before and after single fluid challenge. CONCLUSION: Passage of BSS at physiological pressures for under 40 minutes caused marked reduction in the porosity of the fibrous capsule within 3 days. This was not associated with any significant thickening of the fibrous capsule within this time frame. HOW TO CITE THIS ARTICLE: Pandav SS, Ross CM, Thattaruthody F, Nada R, Singh N, Gautam N, Beirne S, Wallace GG, Sherwood MB, Crowston JG, Coote M. Porosity of Bleb Capsule declines rapidly with Fluid Challenge. J Curr Glaucoma Pract 2016;10(3):91-96.

Mid-term Clinical Results of CO2 Laser-assisted Sclerectomy Surgery (CLASS) for Open-Angle Glaucoma Treatment.

PURPOSE: To evaluate the efficacy and safety of CO2 Laser-assisted Sclerectomy Surgery (CLASS) in primary and pseudoexfoliative open-angle glaucoma. MATERIALS AND METHODS: Single-arm, open-label study included data from 9 medical centers located in 7 countries. Subjects underwent nonpenetrating CLASS procedure with a CO2 laser system (IOPtiMate). Intraocular pressure (IOP) and number of medications were measured at baseline, 1, 2, 4, and 6 weeks, and 3, 6, 12, 24, and 36 months. Complete success was defined as 5≤IOP≤18 mm Hg and at least 20% IOP reduction with no medications, and qualified success as the same with or without medications at 12, 24, and 36 months. RESULTS: A total of 111 consecutive eyes were enrolled in the study, 14 were excluded from the study due to protocol deviation or operator error. The mean age was 69.3±12.8 and 73.9% were whites. Percent change in IOP from baseline at 1, 2, and 3 years was, respectively, 45.1%, 46.8%, and 42.5% (P<0.001). Complete success rates after 12, 24, and 36 months were 60.2%, 57.9%, and 47.8%, respectively. Qualified success rates after 12, 24, and 36 months were 79.6%, 91.2%, and 84.8%, respectively. Number of medications dropped from 2.39±1.24 to 0.47±0.84, 0.53±0.75, and 0.71±0.89 at 12, 24, and 36 months, respectively (P<0.001). CONCLUSIONS: The CLASS procedure may be a simple and effective treatment for open-angle glaucoma providing extended relief of elevated IOP.