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.

A positive feedback between p53 and miR-34 miRNAs mediates tumor suppression.

As bona fide p53 transcriptional targets, miR-34 microRNAs (miRNAs) exhibit frequent alterations in many human tumor types and elicit multiple p53 downstream effects upon overexpression. Unexpectedly, miR-34 deletion alone fails to impair multiple p53-mediated tumor suppressor effects in mice, possibly due to the considerable redundancy in the p53 pathway. Here, we demonstrate that miR-34a represses HDM4, a potent negative regulator of p53, creating a positive feedback loop acting on p53. In a Kras-induced mouse lung cancer model, miR-34a deficiency alone does not exhibit a strong oncogenic effect. However, miR-34a deficiency strongly promotes tumorigenesis when p53 is haploinsufficient, suggesting that the defective p53-miR-34 feedback loop can enhance oncogenesis in a specific context. The importance of the p53/miR-34/HDM4 feedback loop is further confirmed by an inverse correlation between miR-34 and full-length HDM4 in human lung adenocarcinomas. In addition, human lung adenocarcinomas generate an elevated level of a short HDM4 isoform through alternative polyadenylation. This short HDM4 isoform lacks miR-34-binding sites in the 3' untranslated region (UTR), thereby evading miR-34 regulation to disable the p53-miR-34 positive feedback. Taken together, our results elucidated the intricate cross-talk between p53 and miR-34 miRNAs and revealed an important tumor suppressor effect generated by this positive feedback loop.