Short-Term Outcomes of Xen-45 Gel Stent Ab Interno Versus Ab Externo Transconjunctival Approaches.

PRCIS: Ab externo transconjunctival placement of the Xen-45 gel stent offers a faster surgical approach and more rapid visual recovery with similar pressure-lowering and complication rates when compared with implantation by the ab interno approach. PURPOSE: Compare outcomes of closed conjunctival Xen-45 implantation techniques: ab interno versus ab externo transconjunctival. MATERIAL AND METHODS: Single-center, retrospective study of 70 patients undergoing Xen-45 implantation between 2017 and 2020. Group 1 (n=29) had ab interno placement, Group 2 (n=41) had transconjunctival ab externo placement. Primary outcome measures were intraocular pressure (IOP) and medication use. Secondary measures were bleb revision rates, surgical time, time to return to baseline visual acuity, and complication rates. RESULTS: Group 1, preoperative IOP was 22.8±7.5 mmHg on 3.8±0.9 IOP-lowering medications and the postoperative IOP at last follow-up was 11.6±2.8 mmHg on 1.6±1.3 medications. Group 2, preoperative IOP was 25.6 mmHg±7.8 mmHg on 3.7±1.1 medications and the postoperative IOP at last follow-up was 12.4±3.6 mmHg on 1.5±1.3 medications. There was no difference in postoperative IOP or medications between the 2 groups ( P <0.05). The average surgical time for Group 2 was 25±6.5 minutes to 37±7.3 minutes for Group 1 ( P <0.001). Group 2 showed 88% of patients returning to baseline visual acuity at week 2 compared with 66% in Group 1 ( P <0.05). Bleb revision rates, failure rates, and complication rates were comparable between both groups ( P >0.05). CONCLUSION: IOP, medication use, complications, bleb revision rates, and failure rates were similar between ab interno and ab externo transconjunctival approaches. The ab externo group had faster surgical times and postoperative visual recovery despite higher number of patients with previous glaucoma procedures.

Clinical Outcomes of Ab Interno Placement versus Ab Externo Placement of XEN45 Gel Stents.

PURPOSE: To compare the effectiveness of ab interno versus ab externo placement of XEN45 gel stents in patients with open-angle glaucoma. DESIGN: Single-center, noncontrolled, retrospective, comparative case series. PARTICIPANTS: Eighty-nine eyes of 89 patients with open-angle glaucoma who underwent XEN45 gel stent implantation. METHODS: Patients underwent either ab interno (group 1) or ab externo (group 2) placement of a XEN45 stent between 2017 and 2020 by a single surgeon. Outcomes were recorded at each follow-up visit from postoperative day 1 up to 24 months, with median follow-up lengths of 12 months and 8 months for groups 1 and 2, respectively. MAIN OUTCOME MEASURES: The primary outcome measure was the surgical success rate at 8 months. Secondary measures were postoperative intraocular pressure (IOP) and medication usage, complication rates, and bleb revision rates. RESULTS: Success rates at 8 months were 72% in group 1 (n = 29) and 74% in group 2 (n = 60). There was no difference in the median time to failure between groups (P = 0.98). The mean baseline IOPs were 22.8 ± 7.5 on 3.8 ± 0.9 medications in group 1 and 25.3 ± 10.7 on 3.7 ± 1 medications in group 2. At the last follow-up among eyes with surgical success, the mean IOPs were 12.5 ± 3.8 on 2.2 ± 1.4 medications in group 1 and 12.2 ± 2.1 on 1.8 ± 1.3 medications in group 2. The adjusted mean IOPs and numbers of medications used were significantly lower after XEN45 stent implantation at all postoperative time points compared with baseline in both groups (P < 0.05). There were no significant differences in postoperative adjusted mean IOPs or medications used between the groups at any of the follow-up time points. Complication rates and bleb revision rates were comparable between both groups (P > 0.05). CONCLUSIONS: The ab externo approach of XEN45 stent placement demonstrates comparable effectiveness to the ab interno approach in patients with open-angle glaucoma, although this study was underpowered to detect a difference in success rates between groups.

Mutated KCNJ5 activates the acute and chronic regulatory steps in aldosterone production.

Somatic and germline mutations in the inward-rectifying K(+) channel (KCNJ5) are a common cause of primary aldosteronism (PA) in aldosterone-producing adenoma and familial hyperaldosteronism type III, respectively. Dysregulation of adrenal cell calcium signaling represents one mechanism for mutated KCNJ5 stimulation of aldosterone synthase (CYP11B2) expression and aldosterone production. However, the mechanisms stimulating acute and chronic production of aldosterone by mutant KCNJ5 have not been fully characterized. Herein, we defined the effects of the T158A KCNJ5 mutation (KCNJ5(T158A)) on acute and chronic regulation of aldosterone production using an adrenal cell line with a doxycycline-inducible KCNJ5(T158A) gene (HAC15-TRE-KCNJ5(T158A)). Doxycycline incubation caused a time-dependent increase in KCNJ5(T158A) and CYP11B2 mRNA and protein levels. Electrophysiological analyses confirm the loss of inward rectification and increased Na(+) permeability in KCNJ5(T158A)-expressing cells. KCNJ5(T158A) expression also led to the activation of CYP11B2 transcriptional regulators, NURR1 and ATF2. Acutely, KCNJ5(T158A) stimulated the expression of total and phosphorylated steroidogenic acute regulatory protein (StAR). KCNJ5(T158A) expression increased the synthesis of aldosterone and the hybrid steroids 18-hydroxycortisol and 18-oxocortisol, measured with liquid chromatography-tandem mass spectrometry (LC-MS/MS). All of these stimulatory effects of KCNJ5(T158A) were inhibited by the L-type Ca(2+) channel blocker, verapamil. Overall, KCNJ5(T158A)increases CYP11B2 expression and production of aldosterone, corticosterone and hybrid steroids by upregulating both acute and chronic regulatory events in aldosterone production, and verapamil blocks KCNJ5(T158A)-mediated pathways leading to aldosterone production.