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PURPOSE: To compare surgical outcomes of phacoemulsification combined with Baerveldt implantation (phaco-tube) or trabeculectomy with mitomycin-C (MMC) (phaco-trab) in patients without prior incisional ocular surgery. DESIGN: Single-center, retrospective, comparative case series. PARTICIPANTS: A total of 90 patients underwent surgical treatment, including 45 patients in the phaco-tube group and 45 patients in the phaco-trab group. METHODS: Eligible patients were identified using current procedural terminology (CPT) codes, and their medical records were retrospectively reviewed. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of surgical failure (IOP ≤5 mmHg or >21 mmHg or reduced <20% from baseline on 2 consecutive study visits after 3 months, reoperations for glaucoma, or experienced loss of light perception vision). Patients who had successful surgical outcomes without use of glaucoma medications were classified as complete successes, while those who used glaucoma medications were classified as qualified successes. Secondary outcome measures were visual acuity (VA), visual field mean deviation (VFMD), intraocular pressure (IOP), glaucoma medication use, and complications. RESULTS: The cumulative probability of failure was 6.7% in the phaco-tube group and 32.8% in the phaco-trab group after 3 years (P = 0.005; Restricted Mean Survival Time = 5.9 months, 95% CI = 1.4-10.4 months). The IOP was 13.1 ± 3.4 mmHg in the phaco-tube group and 13.3 ± 6.2 mmHg in the phaco-trab group at 3 years (P = 0.90), and the number of glaucoma medications was 2.6 ± 1.5 in the phaco-tube group and 1.7 ± 1.3 in the phaco-trab group (P = 0.015). The logarithm of the minimum angle of resolution VA was 0.39 ± 0.58 in the phaco-tube group and 0.43 ± 0.73 in the phaco-trab group at 3 years (P = 0.82), and VFMD was -18.3 ± 9.0 dB in the phaco-tube group and -14.1 ± 7.0 dB in the phaco-trab group (P = 0.16). Postoperative complications developed in 21 patients (47%) in the phaco-tube group and 15 patients (33%) in the phaco-trab group (P = 0.28). CONCLUSIONS: Phaco-tubes had a significantly lower rate of surgical failure compared to phaco-trabs after 3 years of follow-up. However, phaco-trabs used significantly fewer glaucoma medications at multiple postoperative timepoints and had a higher proportion of complete success. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
RESUMEN
Pore-forming toxins (PFTs) are commonly produced by pathogenic bacteria, and understanding them is key to the development of virulence-targeted therapies. Streptococcus agalactiae, or group B Streptococcus (GBS), produces several factors that enhance its pathogenicity, including the PFT ß-hemolysin/cytolysin (ßhc). Little is understood about the cellular factors involved in ßhc pore formation. We conducted a whole-genome CRISPR-Cas9 forward genetic screen to identify host genes that might contribute to ßhc pore formation and cell death. While the screen identified the established receptor, CD59, in control experiments using the toxin intermedilysin (ILY), no clear candidate genes were identified that were required for ßhc-mediated lethality. Of the top targets from the screen, two genes involved in membrane remodeling and repair represented candidates that might modulate the kinetics of ßhc-induced cell death. Upon attempted validation of the results using monoclonal cell lines with targeted disruption of these genes, no effect on ßhc-mediated cell lysis was observed. The CRISPR-Cas9 screen results are consistent with the hypothesis that ßhc does not require a single nonessential host factor to mediate target cell death. IMPORTANCE CRISPR-Cas9 forward genetic screens have been used to identify host cell targets required by bacterial toxins. They have been used successfully to both verify known targets and elucidate novel host factors required by toxins. Here, we show that this approach fails to identify host factors required for cell death due to ßhc, a toxin required for GBS virulence. These data suggest that ßhc may not require a host cell receptor for toxin function or may require a host receptor that is an essential gene and would not be identified using this screening strategy.