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Use of medical devices represents a unique opportunity to facilitate scale-up of early infant male circumcision (EIMC) across sub-Saharan Africa. The ShangRing, a circumcision device prequalified by WHO, is approved for use in adults and adolescents and requires topical anaesthesia only. We aimed to investigate the safety and efficacy of the ShangRing versus the Mogen clamp for EIMC in infants across eastern sub-Saharan Africa.In this multicentre, non-inferiority, open-label, randomised controlled trial, we enrolled healthy male infants (aged60 days), with a gestational age of at least 37 weeks and a birthweight of at least 2·5 kg, from 11 community and referral centres in Kenya, Tanzania, and Uganda. Infants were randomly assigned (1:1) by a computer-generated text message service to undergo EIMC by either the ShangRing or the Mogen clamp. The primary endpoint was safety, defined as the number and severity of adverse events (AEs), analysed in the intention-to-treat population (all infants who underwent an EIMC procedure) with a non-inferiority margin of 2% for the difference in moderate and severe AEs. This trial is registered with Clinical.gov, NCT03338699, and is complete.Between Sept 17, 2018, and Dec 20, 2019, a total of 1420 infants were assessed for eligibility, of whom 1378 (97·0%) were enrolled. 689 (50·0%) infants were randomly assigned to undergo EIMC by ShangRing and 689 (50·0%) by Mogen clamp. 43 (6·2%) adverse events were observed in the ShangRing group and 61 (8·9%) in the Mogen clamp group (p=0·078). The most common treatment-related AE was intraoperative pain (Neonatal Infant Pain Scale score ≥5), with 19 (2·8%) events in the ShangRing and 23 (3·3%) in the Mogel clamp group. Rates of moderate and severe AEs were similar between both groups (29 [4·2%] in the ShangRing group vs 30 [4·4%] in the Mogen clamp group; difference -0·1%; one-sided 95% CI upper limit of 1·7%; p=0·89). No treatment-related deaths were reported.Use of the ShangRing device for EIMC showed safety, achieved high caregiver satisfaction, and did not differ from the Mogen clamp in other key measures. The ShangRing could be used by health systems and international organisations to further scale up EIMC across sub-Saharan Africa.BillMelinda Gates Foundation.

Varicoceles are dilated veins within the spermatic cord and a relatively common occurrence in men. Fortunately, the large majority of men are asymptomatic, however, a proportion of men with varicoceles can suffer from infertility and testosterone deficiency. Sperm and testosterone are produced within the testis, and any alteration to the testicular environment can negatively affect the cells responsible for these processes. The negative impact of varicoceles on testicular function occurs mainly due to increased oxidative stress within the testicular parenchyma which is thought to be caused by scrotal hyperthermia, testicular hypoxia, and blood-testis barrier disruption. Management of varicoceles involves ligation or percutaneous embolization of the dilated veins. Repair of varicoceles can improve semen parameters and fertility, along with serum testosterone concentration. In this review, we discuss the pathophysiology of varicoceles, their impact on testicular function, and management.

Purpose To evaluate the burden of incisional glaucoma surgery (trabeculectomy and glaucoma drainage device implantation) after laser trabeculoplasty (LTP) in the United States. Design Retrospective, matched, case-comparison study. Participants Medicare beneficiaries who underwent LTP between January 2012 and December 2014 were identified using the 5% Medicare Current Beneficiary Survey. Methods Subjects aged 35 years or older at the time of LTP with ocular hypertension, suspected glaucoma, or mild open-angle glaucoma (OAG) were matched to a comparison group without LTP on the basis of age, gender, race, geographic region, and glaucoma diagnosis codes. Survival analysis and Cox proportional hazard analysis were performed. Main Outcome Measures Primary analysis included risk of incisional glaucoma surgery. Secondary analysis included risk of conversion to moderate or severe OAG based on billing data. Results The mean age of study participants was 75.0 ± 8.9 years. After 2 years, 40 of 2435 eyes required incisional glaucoma surgery after LTP, and 51 of 2435 eyes required glaucoma surgery in the comparison group (P = 0.27, adjusted for covariates). Regardless of intervention, Black Americans were more likely to require glaucoma surgery (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.13–3.17). Patients with a diagnosis of OAG were more likely to require surgery than glaucoma suspects (HR, 2.03; 95% CI, 1.12–3.69). Black Americans were also more likely to require surgery or convert to more severe glaucoma (HR, 3.21; 95% CI, 1.92–5.37) versus White Americans. Conclusions Laser trabeculoplasty did not alter the need for subsequent incisional glaucoma surgery among glaucoma suspects or patients with mild OAG. Regardless of treatment with LTP, African heritage and OAG diagnosis status were risk factors for requiring glaucoma surgery.

Introduction: The main aim of this article was to study the retinal peripapillary and macular vascular structures in eyes with primary angle-closure suspects (PACS) using optical coherence tomography angiography (OCTA). Methods: In this cross-sectional study, control and PACS subjects were recruited from a community screening. Only one eye per subject was used for analysis. All participants underwent a questionnaire survey, physical and ophthalmic examinations, ocular biometry measurements, and OCTA. We compared basic demographics and vessel structure parameters between control and PACS eyes. Univariate and multivariate linear regression analyses were performed to investigate factors associated with vascular parameters in both groups. Results: Data from 254 subjects including 155 PACS and 99 controls were analyzed. In the peripapillary region, PACS eyes showed similar retina nerve fiber layer (RNFL) and vessel densities (VDs) including and excluding large vessels compared to control eyes. Compared to control eyes, all macular OCTA parameters showed significant differences in PACS eyes, including decreased superficial VD (p = 0.006) and deep VD (p = 0.004), larger fovea avascular zone (FAZ) area (p = 0.006), and longer FAZ perimeter (p = 0.004). Gender (p = 0.039), age (p < 0.001), and Garway-Heath superior hemisphere RNFL (p < 0.001) were risk factors influencing optic disc VD excluding large vessels. Axial length was the major factor affecting macula superficial and deep VDs (p = 0.004 and 0.001 respectively), while PACS was an independent factor associated with larger FAZ perimeter (p = 0.046). Conclusion: While PACS and control eyes have comparable RNFL and vascular structure around the optic nerve head, macular vascular structures are significantly different.

PRCIS The multiplicity of treatment options for lowering intraocular pressure (IOP) is both a blessing and a challenge. Some attention to cost-analysis might assist in choosing an optimal therapy, especially in a cost-constrained, international setting. PURPOSE The aim of this study was to quantify and to analyze the relative cost of various glaucoma surgical procedures and selective laser trabeculoplasty surgery per mm Hg IOP reduction ($/mm Hg) since standard cost-utility methods are not well suited to the study of glaucoma which characteristically only claims visual acuity in its end stages. METHODS Published glaucoma treatment studies were reviewed to quantitate the reduction of mean IOP and glaucoma medications for a given treatment modality. A US perspective was adopted, using Medicare allowable costs were used to calculate a newly introduced parameter-cost per mm Hg IOP reduction-at 1 year postoperatively. RESULTS The cost per mm Hg IOP reduction after 1 year of treatment ranged from $190/mm Hg for trabeculectomy to $1376/mm Hg for iStent. For reference, the cost of selective later trabeculoplasty surgery was $121/mm Hg. After the first year, cost/mm Hg ranged from $12 to $61/mm Hg. CONCLUSIONS Conventional glaucoma surgeries and selective laser trabeculoplasty surgery were the most cost-efficient surgical methods to lower IOP compared with the various minimally invasive glaucoma surgeries options. They may be more appropriate management when cost is an important issue.

Reporting treatment outcomes of slow coagulation transscleral cyclophotocoagulation (TSCPC) as an initial surgical intervention in pseudophakic patients with glaucoma.Retrospective case series.This single academic center study reviewed 74 pseudophakic patients who had a diagnosis of glaucoma and no previous glaucoma surgeries (mean age 82.6 ± 12.5 years; mean follow-up 18.7 ± 9.1 months). The intervention used was slow coagulation continuous wave TSCPC (1250-mW power and 4-second duration). The primary outcome measure was surgical success defined as an intraocular pressure (IOP) of 6-21 mm Hg with a ≥20% reduction from baseline, no reoperation for glaucoma, and no loss of light-perception vision. Secondary outcome measures included glaucoma medication use, visual acuity (VA), and complications.IOP decreased from 27.5 ± 9.8 mm Hg preoperatively to 16.1 ± 6.3 mm Hg postoperatively (P.001). The preoperative number of glaucoma medications was 4.1 ± 0.9 and 3.1 ± 1.3 post-TSCPC (P.001). The cumulative probabilities of success at 1 and 2 years were 60.6 % and 58.5%, respectively. When patients were divided into 2 groups based on their baseline IOP being21 mm Hg (high group) or ≤21 mm Hg (low group), success rates at 2 years were 64.9% and 45.5%, respectively (P = .144). The mean logarithm of the minimum angle of resolution VA changed from 0.70 ± 0.64 to 1.04 ± 0.87 at the last follow-up visit (P = .01). No serious complications were observed and most of the complications were mild and transient.Slow coagulation TSCPC has good efficiency, especially in patients with baseline IOP21 mm Hg, and safety profile as an initial surgical intervention in pseudophakic patients with glaucoma.

To report treatment outcomes of primary transscleral cyclophotocoagulation (TSCPC) in glaucomatous eyes.Retrospective noncomparative study.Forty-eight eyes with a diagnosis of glaucoma and no previous incisional ocular surgery.Continuous-wave TSCPC was applied to the ciliary body.The primary outcome measure was surgical success defined as an IOP ≤ 21 mmHg and reduced by 20% or more from baseline, IOP5 mmHg, no reoperation for glaucoma, and no loss of light perception vision. Secondary outcome measures included visual acuity (VA) and complications.Glaucoma eyes were stratified into 2 groups: (1) those with pretreatment IOP21 mmHg (high group) and (2) those with pretreatment IOP ≤ 21 mmHg (low group). Mean ± standard deviation (SD) IOP at baseline was 30.6 ± 6.3 mmHg in the high group and 16.2 ± 2.8 mmHg in the low group. Mean ± SD number of glaucoma medications at baseline was 4.1 ± 0.8 in the high group and 3.6 ± 1.1 in the low group. Based on our success criteria, the cumulative probability of success during the first year of follow-up was 58.3% in the high group and 28.1% in the low group (P = 0.052). Postoperative mean IOP was significantly lower than baseline IOP in the high group at 1-, 3-, 6-, 12-, and 18-month postoperative visits (P0.05). No significant change was observed in IOP at follow-up visits after 1 month in the low IOP group. Throughout the first year of follow-up, both groups required fewer glaucoma medications compared with baseline at the 1-, 3-, 6-, and 12-month postoperative visits (P0.05). The most frequent cause of postoperative decrease in VA was cataract in 9 eyes. Decrease in vision resulting from glaucoma was observed in 3 eyes. Complications included prolonged inflammation (11 eyes), iris neovascularization (2 eyes), cystoid macular edema (4 eyes), and hyphema (1 eye). No severe or long-term complications were observed.Continuous-wave TSCPC was effective in lowering IOP in glaucoma patients without prior incisional ocular surgery whose disease was recalcitrant to medical therapy, particularly those with baseline IOP of more than 21 mmHg.

Novel minimally invasive therapies like the prostatic urethral lift are among the many endoscopic options for the treatment of benign prostatic enlargement and lower urinary tract symptoms (BPE/LUTS). To further understand the relative uptake, complications and retreatment rates of contemporary endoscopic procedures for BPE/LUTS across diverse practice types, we performed a retrospective study of inpatient and ambulatory surgery encounters in the Premier Healthcare database.We included men who underwent endoscopic procedures for BPE/LUTS between 2000 and 2018. We determined the utilization of endoscopic therapies for BPE/LUTS, 30-day and 90-day readmission rates, and retreatment rate. Multivariable logistic regression was used to assess the association of procedure type with outcomes for the 3 most commonly performed procedures.We identified 175,150 men treated with endoscopic surgery for BPE/LUTS. The annual percent utilization of the prostatic urethral lift increased from1% in 2014 to 10.4% in 2018. Compared to transurethral resection of the prostate and prostate photovaporization, prostatic urethral lift was associated with a lower odds of readmission at 30 (OR 0.58, p0.01) and 90 (OR 0.55, p0.01) days and a higher odds of retreatment within 2 years of followup (OR 1.78, p0.01).Providers have rapidly adopted prostatic urethral lift which accounted for more than 1 in 10 endoscopic procedures captured for BPE/LUTS in 2018. Men treated with prostatic urethral lift are readmitted less within 30 and 90 days but are more likely to be retreated within 2 years of their index procedure as compared to men treated with transurethral resection of the prostate or prostate photovaporization.

Objective To determine whether the academic achievement of Department Chairperson (DC) and Research Director (RD), when present, is associated with increased scholarly productivity and National Institutes of Health (NIH) funding of faculty members in academic urology departments. Materials and Methods We identified the DC, RD and faculty members of 145 academic urology departments. The scholarly productivity and NIH funding for each individual faculty member was assessed from 2018 to 2019 using an h-index extrapolated from the Scopus database and the NIH RePORTER tool, respectively. The Spearman correlation coefficient was employed to define the correlation of these parameters. Hypothesis testing was conducted using the Mann-Whitney U test. Results After excluding 13 departments due to missing faculty listing, our final sample included 132 departments and 2227 faculty members. In 2018, the NIH provided $55,243,658 in urology research grants to 24.2% of departments and 4.0% of faculty members. Of departments with NIH funding, 68.8% employed a RD. DC and RD h-index were positively correlated with departmental h-index. DC h-index positively correlated with department NIH funding. Moreover, NIH funding was significantly higher for departments with a RD vs those without a RD ($1,268,028 vs $62,941, P Conclusion Academic success of a DC and RD was associated with urology departmental scholarly productivity and NIH funding. The presence of a RD, funded or unfunded, was associated with increased departmental NIH funding.

Overactive bladder syndrome is a prevalent condition impacting quality of life, activities of daily living, work productivity, physical and psychological health, sleep, and sexuality. Published guideline recommendations and effective behavioral, pharmacologic, and neuromodulatory therapies exist; however, adherence can be poor. Clinicians have important roles educating patients, setting treatment expectations, and providing follow-up. Determining patient goals, routinely assessing and adjusting therapy, and combining treatment strategies may improve outcomes. We review the benefits and challenges of overactive bladder treatments and propose approaches to improve patient management, with the goals of initiating therapy earlier and achieving better patient satisfaction, functioning, and quality of life.

Aim Female urethral stricture disease is rare and has several surgical approaches including endoscopic dilations (ENDO), urethroplasty with local vaginal tissue flap (ULT) or urethroplasty with free graft (UFG). This study aims to describe the contemporary management of female urethral stricture disease and to evaluate the outcomes of these three surgical approaches. Methods This is a multi-institutional, retrospective cohort study evaluating operative treatment for female urethral stricture. Surgeries were grouped into three categories: ENDO, ULT, and UFG. Time from surgery to stricture recurrence by surgery type was analyzed using a Kaplan-Meier time to event analysis. To adjust for confounders, a Cox proportional hazard model was fit for time to stricture recurrence. Results Two-hundred and ten patients met the inclusion criteria across 23 sites. Overall, 64% (n = 115/180) of women remained recurrence free at median follow-up of 14.6 months (IQR, 3-37). In unadjusted analysis, recurrence-free rates differed between surgery categories with 68% ENDO, 77% UFG and 83% ULT patients being recurrence free at 12 months. In the Cox model, recurrence rates also differed between surgery categories; women undergoing ULT and UFG having had 66% and 49% less risk of recurrence, respectively, compared to those undergoing ENDO. When comparing ULT to UFG directly, there was no significant difference of recurrence. Conclusion This retrospective multi-institutional study of female urethral stricture demonstrates that patients undergoing endoscopic management have a higher risk of recurrence compared to those undergoing either urethroplasty with local flap or free graft.

A minimum number of index procedures is required for graduation. Without thresholds for surgical technique, it is unclear if robotic and open learning is balanced. We assessed the distribution of robotic and open surgeries performed by residents upon graduation.Voluntary Accreditation Council for Graduate Medical Education resident case logs from 11 institutions were de-identified and trends in robotic and open major surgeries were compared using Wilcoxon rank sum and 2-sample t-tests.A total of 89,199 major cases were recorded by 209 graduates from 2011 to 2017. The median proportion of robotic cases increased from 2011 to 2017 in reconstruction (4.7% to 15.2%), oncology (27.5% to 54.2%) and pediatrics (0% to 10.9%) (all values p0.001). Robotic and open cases remained most divergent in reconstruction, with a median of 12 robotic (IQR 9-19) to 70 open cases (IQR 55-106) being performed by residents in 2017. Similar observations occurred in pediatrics. In oncology the number of robotic procedures superseded that of open in 2016 and rose to a median of 148 robotic (IQR 108-214) to 121 open cases (IQR 90-169) in 2017, with the driver being robotic prostatectomy. Substantial differences in surgical technique were observed between institutions and among graduates from the same institution.Although robotic volume is increasing, the balance of surgical technique and the pace of change differ in reconstruction, oncology and pediatrics, as well as among individual institutions and graduates themselves. This raises questions about whether more specific guidelines are needed to ensure equity and standardization in training.

Overactive bladder (OAB) is a widely prevalent urinary condition affecting women of all ages, with increasing incidence in advancing age. A primary care provider is likely to encounter a significant proportion of women experiencing lower urinary tract symptoms (LUTS). This review serves primary care physicians as a thorough reference for a common condition causing LUTS in women. Most emerging data addressing overactive bladder relates to the different treatment modalities available. The side effect profile of antimuscarinic drugs remains an ongoing concern among OAB patients, especially with recent data linking the use of this class of drugs with Alzheimer’s and future development of dementia. In addition, it was recently demonstrated that individuals taking medications of medium-to-high anticholinergic activity had reduced brain glucose metabolism and increased brain atrophy. Combination treatments seem to be more efficacious than monotherapies, as has been proven when using mirabegron with antimuscarinics. Many studies have also validated the use of neuromodulation as a safe and effective treatment for OAB. Overactive bladder is a widely prevalent urinary condition affecting women of all ages. It is regarded as multifactorial with several proposed theories to explain its occurrence. Several tests are available to aid in diagnosing OAB. Symptom severity and patient-related factors including patient preferences drive treatment.

Although glial scar formation has been extensively studied after optic nerve injury, the existence and characteristics of traumatic optic nerve fibrotic scar formation have not been previously characterized. Recent evidence suggests infiltrating macrophages are involved in pathological processes after optic nerve crush (ONC), but their role in fibrotic scar formation is unknown. Using wild-type and transgenic mouse models with optic nerve crush injury, we show that macrophages infiltrate and associate with fibroblasts in the traumatic optic nerve lesion fibrotic scar. We dissected the role of hematogenous and resident macrophages, labeled with Dil liposomes intravenously administered, and observed that hematogenous macrophages (Dil

Purpose To report the outcomes of slow-coagulation continuous-wave transscleral cyclophotocoagulation (CW-TSCPC) in post-keratoplasty glaucoma refractory to medical therapy. Methods Medical records of 47 patients (mean age of 70.7 ± 15.7 years and follow-up of 13.9 ± 7.1 months) were retrospectively enrolled. All patients had the diagnosis of secondary glaucoma after penetrating keratoplasty (PKP; n = 28) or Descemet's stripping automated endothelial keratoplasty (DSAEK; n = 19) with no previous history of incisional glaucoma or TSCPC surgeries. Study participants underwent slow-coagulation CW-TSCPC (1250-milliwatt power and 4-second duration). Results A statically significant reduction of IOP from 31.8 ± 8.0 mmHg preoperatively to 16.9 ± 9.0 mmHg postoperatively was noted ( p Conclusions Our study suggests that slow-coagulation TSCPC may be a safe and efficient surgical glaucoma treatment modality in patients with medically uncontrolled post-keratoplasty glaucoma.

Purpose To compare the long-term safety and efficacy of amniotic membrane–umbilical cord (AM–UC) and pericardium patch grafts in reducing glaucoma shunt tube exposure. Design Multicenter, prospective, randomized clinical trial. Participants Adults with uncontrolled glaucoma undergoing glaucoma drainage device (GDD) implantation. Methods Patients were randomized to receive GDD with either AM-UC or pericardium patch grafts to cover GDD tubes. Patients were followed up clinically with anterior segment (AS) OCT to assess patch graft stability and host–tissue integration prospectively. Main Outcome Measures Tube exposure, graft thinning, and graft-related complications. Results A total of 81 eyes of 81 patients (50 women, 31 men) with a mean age of 67±13 years underwent GGD implantation using Baerveldt (n = 72) or Ahmed valve (n = 9). Tubes were inserted in the anterior chamber (n = 71), sulcus (n = 6), or pars plana (n = 4). Tube ligation was performed with Baerveldt GDD along with fenestration (n = 51) or orphan trabeculectomy (n = 21). Tubes were covered with AM–UC (n = 41) or pericardium (n = 40). The mean follow-up time was 29±8 months (range, 13–40 months). Tube exposure occurred in 1 eye (2%) in the AM–UC group at 3 months and in 2 eyes (5%) in the pericardium group at 2 and 6 months (P = 0.54). Sequential AS OCT showed better host–tissue integration and significantly less graft thinning in the AM–UC group. Early graft thinning (≤3 months) occurred in 5 eyes (12%) in the AM–UC group and in 17 eyes (43%) in the pericardium group (P = 0.002). Late thinning occurred in 2 eyes (5%) and 11 eyes (28%) in the AM–UC and pericardium groups, respectively (P = 0.007). Graft translucency and cosmetic appearance of the AM–UC graft were superior to those of the pericardium graft. No evidence of graft rejection or infection was associated with the patch grafts in either group. Conclusions Amniotic membrane–umbilical cord grafts are well tolerated and offer an alternative to pericardium for safe and stable tube shunt coverage. Its high-tensile strength, low immunogenicity, and excellent host–tissue integration significantly reduced graft thinning.

Therapies for genetic disorders caused by mutated mitochondrial DNA are an unmet need, in large part due barriers in delivering DNA to the organelle and the absence of relevant animal models. We injected into mouse eyes a mitochondrially targeted Adeno-Associated-Virus (MTS-AAV) to deliver the mutant human NADH ubiquinone oxidoreductase subunit I (hND1/m.3460 G A) responsible for Leber's hereditary optic neuropathy, the most common primary mitochondrial genetic disease. We show that the expression of the mutant hND1 delivered to retinal ganglion cells (RGC) layer colocalizes with the mitochondrial marker PORIN and the assembly of the expressed hND1 protein into host respiration complex I. The hND1-injected eyes exhibit hallmarks of the human disease with progressive loss of RGC function and number, as well as optic nerve degeneration. We also show that gene therapy in the hND1 eyes by means of an injection of a second MTS-AAV vector carrying wild-type human ND1 restores mitochondrial respiratory complex I activity, the rate of ATP synthesis and protects RGCs and their axons from dysfunction and degeneration. These results prove that MTS-AAV is a highly efficient gene delivery approach with the ability to create mito-animal models and has the therapeutic potential to treat mitochondrial genetic diseases.

Purpose The HGF/MET pathway is involved in cell motility, angiogenesis, proliferation, and cancer invasion. We assessed the clinical utility of plasma HGF level as a prognostic biomarker in patients with MIBC. Methods We retrospectively analyzed 565 patients with MIBC who underwent radical cystectomy. Logistic regression and Cox regression models were used, and predictive accuracies were estimated using the area under the curve and concordance index. To estimate the clinical utility of HGF, DCA and MCID were applied. Results Plasma HGF level was significantly higher in patients with advanced pathologic stage and LN metastasis (p = 0.01 and p p p p p Conclusion Preoperative HGF identified MIBC patients who harbored features of clinically and biologically aggressive disease. Plasma HGF could serve, as part of a panel, as a biomarker to aid in preoperative treatment planning regarding intensity of treatment in patients with clinical MIBC.

Testicular torsion (TT) is a common urologic emergency that can occur at any age. It is most common in newborns and during puberty. Prompt evaluation and management is required to salvage the testis following an episode of torsion. TT brings about damage to testicular tissue and spermatogenesis through various hypothesized mechanisms; however there is a consensus that the effects of ischemia, ischemia-reperfusion injury, and oxidative stress account for the most destructive effects. Numerous studies have examined the effects of various agents and therapies in limiting the effects of TT on the testis.

There have been significant advancements in male infertility microsurgery over time, and there continues to be significant promise for new and emerging techniques, technologies, and methodologies. In this review, we discuss the history of male infertility and the evolution of microsurgery, the essential role of education and training in male infertility microsurgery, and new technologies in this space. We also review the potentially important role of artificial intelligence (AI) in male infertility and microsurgery.

PurposeCommon LOXL1 protein-altering variants are significant genetic risk factors for exfoliation syndrome (XFS) and the related secondary glaucoma (XFG). A rare LOXL1 missense allele has been associated with protective effects in a Japanese cohort, suggesting that other rare alleles may also exhibit protective effects. The goal of this study was to assess the contributions of rare LOXL1 variants to XFS/XFG risk in cases and controls from the United States.MethodsLOXL1 rare (minor allele frequency less than 1%) variants were identified from Humanexome BeadArray (Illumina) data for 1118 XFS/XFG cases and 3661 controls. Distribution of rare variants, haplotypes (defined using IMPUTE2) and diplotypes were examined using the Fisher’s exact test. Rare variant allele distribution was confirmed in an independent set of primary open angle glaucoma (POAG) controls and multi-ethnic datasets. Correlation of LOXL1 common allele homozygosity with disease risk used data from gnomAD (gnomad.broadinstitute.org/) and an existing multi-ethnic meta-analysis.ResultsFour rare LOXL1 missense alleles were identified, and all were more common in controls (combined P= 7.6E-4), with two of these located in a LOXL1 intrinsic disordered region (IDR) known to be involved in LOXL1 aggregation. Haplotypes that included the rare or minor variants were more common in controls compared to cases (OR= 0.33, P=1.7E-8). Heterozygous diplotypes were significantly associated with reduced risk overall (OR= 0.45 P= 1.7 E-89) with the largest effects observed for diplotypes with more than one heterozygous genotype (OR= 0.05, P= 1.0E-39). A homozygous diplotype was associated with increased disease risk (OR= 6.8, P= 4.7E-157) and homozygosity was correlated with disease risk for common LOXL1 variants across multi-ethnic populations (Pearson= 0.92, PConclusionsUsing exome array data from XFS/XFG cases and controls from the United States, we identify 4 rare protective LOXL1 missense variants and show that the distribution of the corresponding haplotypes and diplotypes are associated with reduced risk of XFS/XFG. The diplotype results also demonstrate that LOXL1 allelic heterozygosity is protective while homozygosity is associated with increased disease risk. These results suggest that LOXL1 minor allele frequency variation among populations, with corresponding variation in genotype heterozgyosity and homozygosity, determines the XFS/XFG association effects and that genotypic effects may also impact protein aggregation involving intrinsic disordered regions.

Pseudoexfoliation syndrome (PEX) is characterized by the production of white extracellular fluffy clumps of microfibrillar material that aggregates in various organs throughout the body but is known to cause disease in the eye. The accumulation of PEX material (PEXM) in the anterior segment ocular structures is believed to cause an increase in intraocular pressure (IOP) resulting in pseudoexfoliation glaucoma (PEXG). The onset of PEXG is often bilateral but asymmetric-one eye often presents with glaucoma prior to the other eye. Proteomics has been used to identify key proteins involved in PEXM formation with the end goal of developing effective treatments for PEX and PEXG which may act through inhibiting the formation of the PEX aggregates. To date, a variety of proteins with various molecular functions have been identified from extracted anterior segment structures and fluids, such as aqueous humor (AH) and blood serum of patients affected by PEX. From past studies, some proteins identified in AH, lens capsule epithelium, iris tissue, and blood serum samples include vitamin D binding protein (GC), apolipoprotein A4 (APOA4), lysyl oxidase like-1 (LOXL1), complement C3, beta-crystalline B1, and B2, and antithrombin-III (SERPINC1). Each of these proteins have been observed in eyes with PEX at varying levels within the different eye structures. In this review, we further examine the anterior segment ocular proteomics of PEXM from past studies to better understand the mechanism of PEX and PEXG development. Both genetic and environmental risk factors have been implicated to be involved in the development of PEX and PEXG. This field is at an early stage of investigation identifying how these factors modify proteins both at the expression and functional level to cause changes leading to the pathophysiology of PEX glaucoma.

AimsTo report treatment outcomes of slow-coagulation continuous-wave transscleral cyclophotocoagulation (TSCPC) as an initial surgical intervention in patients with neovascular glaucoma (NVG).MethodsA retrospective study including 53 patients (mean age of 69.6±16.6 years and mean follow-up of 12.7±8.9 months) with a diagnosis of NVG and no previous incisional glaucoma or cyclophotocoagulation surgeries. All patients underwent slow-coagulation continuous-wave TSCPC (1250-milliwatt power and 4-second duration).Primary outcome measure was surgical success defined as an intraocular pressure (IOP) from 6 to 21 mm Hg with a reduction ≥20% from baseline, no reoperation for glaucoma and no loss of light perception vision. Secondary outcome measures include IOP, glaucoma medications, visual acuity (VA) and complications.ResultsIOP decreased from 40.7±8.6 mm Hg preoperatively to 18.4±12.2 mm Hg postoperatively (pConclusionsSlow-coagulation TSCPC is an effective and relatively safe initial surgical intervention in medically uncontrolled NVG.

The present study aims to investigate the effect of temporary cerebrospinal fluid pressure (CSFP) reduction on optic nerve head (ONH) and macular vessel density (VD) using optical coherence tomography angiography. Forty-four eyes of 44 adults with diagnostic lumbar puncture and CSFP reduction were recruited. Thirty-two eyes of 32 healthy volunteers were controls. ONH and macular VD images were evaluated differences between baseline and after CSFP reduction. The results showed that the mean CSFP decreased from (11.6±2.1) mmHg to (8.2±3.4) mmHg (P 0.05). In the study group, decreased VD in the macular parainferior region was associated with CSFP reduction (R2=0.192, P=0.003), the reduction of macular VD in parafoveal (R2=0.098, P=0.018), parainferior (R2=0.104, P=0.021), parasuperior (R2=0.059, P=0.058), paranasal (R2=0.057, P=0.042), paratemporal (R2=0.079, P=0.026) was associated with mean ocular perfusion pressure decrease following CSFP reduction. ONH vessel density did not differ after CSFP reduction (all P>0.05). In conclusion, macular vessel density decreased in association with CSFP reduction. Retinal vessel density in the macular region is more sensitive than that in peripapillary region after CSFP reduction.

This labeled quantitative proteomics dataset was collected from a transgenic channel rhodopsin mouse model (Chr2) subjected to light stimulation after traumatic optic nerve crush (ONC). Protein extraction was performed by careful mincing of the tissue in extraction buffer (TEAB, NaCl and SDS). Protein amounts were normalized across samples using dot blot densitometry and ImageJ software. Samples were labeled for quantification using a modified TMTpro™ 16plex Label Reagent Set (Thermo Scientific™) after performing an overnight trypsin digestion. Untargeted liquid chromatography-mass spectrometry was performed on an Easy-nLC 1000 liquid chromatograph coupled to a Q Exactive mass spectrometer (LC-MS/MS). Data analysis was performed using Proteome Discoverer™ 2.5 (Thermo Scientific™). This data has been deposited to the ProteomeXchange (PX) and is available through PRIDE with the identifier PXD032788.

Objective: To investigate the effect of interview format changes (in-person to virtual, one-to-one to multiple-to-one) necessitated by the COVID-19 travel restrictions on candidate ranking variabilities.Method: In 2018/2019, the glaucoma fellowship interviews were conducted in-person and one-to-one, whereas in 2020, interviews were virtual and multiple (interviewers)-to-one (candidate). We compared ranking ranges of interviewers within the same virtual room (WSR) and not within the same virtual room (NWSR) to assess the effect of this change on ranking variabilities. We also compared ranking categories (“accept,” “alternate,” and “pass”) agreements between in-person and virtual interviews to assess the effect of this change on ranking variabilities.Results: NWSR and WSR mean rankings differed by 1.33 (95% confidence interval difference 0.61 to 2.04, p = 0.0003), with WSR interviewers having less variability than NWSR pairs. The variability of in-person interviews and later virtual interviews showed no differences (weighted Kappa statistic 0.086 for 2018, 0.158 for 2019, and 0.101 for 2020; p < 0.05 for all years). The overall least attractive candidate has the lowest variability; the most attractive candidate has the second lowest variability.Conclusion: Grouping interviewers decreased ranking variabilities, while a change from in-person to virtual interview format did not increase the ranking variabilities.

Objective To provide a conceptual framework to guide investigations into burdens of noncancerous genitourinary conditions (NCGUCs), which are extensive and poorly understood. Methods The National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop of diverse, interdisciplinary researchers and health professionals to identify known and hidden burdens of NCGUCs that must be measured to estimate the comprehensive burden. Following the meeting, a subgroup of attendees (authors of this article) continued to meet to conceptualize burden. Results The Hidden Burden of Noncancerous Genitourinary Conditions Framework includes impacts across multiple levels of well-being and social ecology, including individual (ie, biologic factors, lived experience, behaviors), interpersonal (eg, romantic partners, family members), organizational/institutional (eg, schools, workplaces), community (eg, public restroom infrastructure), societal (eg, health care and insurance systems, national workforce/economic output), and ecosystem (eg, landfill waste) effects. The framework acknowledges that NCGUCs can be a manifestation of underlying biological dysfunction, while also leading to biological impacts (generation and exacerbation of health conditions, treatment side effects). Conclusion NCGUCs confer a large, poorly understood burden to individuals and society. An evidence-base to describe the comprehensive burden is needed. Measurement of NCGUC burdens should incorporate multiple levels of well-being and social ecology, a life course perspective, and potential interactions between NCGUCs and genetics, sex, race, and gender. This approach would elucidate accumulated impacts and potential health inequities in experienced burdens. Uncovering the hidden burden of NCGUCs may draw attention and resources (eg, new research and improved treatments) to this important domain of health.

Male circumcision (MC) is one of the oldest surgical procedures still completed today. Medical indications for MC include phimosis, recurrent balanitis, cosmesis, and infection prevention. In this review, we mainly focus on the role of MC in the prevention of human immunodeficiency virus, human papillomavirus, herpes simplex virus, gonorrhea, chlamydia, chancroid, and syphilis, and the subsequent impact of these genitourinary infections on male fertility. Overall, many compelling data support that MC may play an essential role in both genitourinary infection prevention and male fertility.

Mohamed M Khodeiry,1,2 Xiangxiang Liu,1,3 Mohamed S Sayed,1 Raquel Goldhardt,1 Giovanni Gregori,1 Thomas A Albini,1 Richard K Lee1 1Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA; 2Research Institute of Ophthalmology, Department of Ophthalmology, Giza, 12557, Egypt; 3Beijing Eye Institute, Beijing Tongren Eye Center, Beijing Tongren Eye Hospital, Capital Medical University, Beijing, 100730, People’s Republic of ChinaCorrespondence: Richard K LeeBascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, 900 NW 17 th Street, Miami, FL 33136, USATel +1 305 326-6400Fax +1 305 547-3658Email rlee@med.miami.eduPurpose: Peripapillary halos (PPH) are peripapillary changes observed surrounding the optic nerve head in normal eyes and eyes with different disorders. Recognizing the microstructure and mechanism of development of these halos will help clinicians understand the different associated retinal and optic nerve head pathologies. We describe the in vivo histological characteristics of PPH in birdshot chorioretinopathy (BSCR).Patients and Methods: This was a prospective observational case-series in a single tertiary referral center. Six eyes of three patients with PPH associated with BSCR were determined through clinical examination, fundus photography, and fundus autofluorescence (FAF). Patients underwent swept-source optical coherence tomography (SS-OCT) imaging of the optic nerve head and peripapillary region.Results: In SS-OCT B-scans across the area of PPH, we observed thinning and interruption of retinal pigment epithelium (RPE)-Bruch’s membrane complex. These halos are a circumferential form of alpha zone RPE-associated crescentic peripapillary atrophy (PPA), unlike the PPH observed with myopia and normal aging.Conclusion: PPH in BSCR patients may be a sign of prior inflammatory optic neuropathy.Keywords: birdshot chorioretinitis, optical coherence tomography, optic nerve head, peripapillary halo, peripapillary atrophy

To evaluate the burden of incisional glaucoma surgery (trabeculectomy and glaucoma drainage device implantation) after laser trabeculoplasty (LTP) in the United States.Retrospective, matched, case-comparison study.Medicare beneficiaries who underwent LTP between January 2012 and December 2014 were identified using the 5% Medicare Current Beneficiary Survey.Subjects aged 35 years or older at the time of LTP with ocular hypertension, suspected glaucoma, or mild open-angle glaucoma (OAG) were matched to a comparison group without LTP on the basis of age, gender, race, geographic region, and glaucoma diagnosis codes. Survival analysis and Cox proportional hazard analysis were performed.Primary analysis included risk of incisional glaucoma surgery. Secondary analysis included risk of conversion to moderate or severe OAG based on billing data.The mean age of study participants was 75.0 ± 8.9 years. After 2 years, 40 of 2435 eyes required incisional glaucoma surgery after LTP, and 51 of 2435 eyes required glaucoma surgery in the comparison group (P = 0.27, adjusted for covariates). Regardless of intervention, Black Americans were more likely to require glaucoma surgery (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.13-3.17). Patients with a diagnosis of OAG were more likely to require surgery than glaucoma suspects (HR, 2.03; 95% CI, 1.12-3.69). Black Americans were also more likely to require surgery or convert to more severe glaucoma (HR, 3.21; 95% CI, 1.92-5.37) versus White Americans.Laser trabeculoplasty did not alter the need for subsequent incisional glaucoma surgery among glaucoma suspects or patients with mild OAG. Regardless of treatment with LTP, African heritage and OAG diagnosis status were risk factors for requiring glaucoma surgery.

Context In recent years, new technologies have been developed to treat benign prostatic enlargement (BPE). Three of these devices may be utilized in office and are promising additions. Objective To systematically review all clinical trials investigating prostatic urethral lift (PUL), water vapor thermal therapy (WVTT), and temporary implantable nitinol device (TIND), with emphasis on clinical efficacy and complications. Evidence acquisition We performed a systematic review of PubMed/Medline database in November 2020 according to Preferred Reporting Items for Systematic Review and Meta-analysis guidelines. Evidence synthesis Of 168 articles identified, 18 met the inclusion criteria. Evidence consisted of few randomized controlled trials, and multiple single-arm prospective and retrospective studies. Among the three modalities, PUL demonstrates rare occurrence of serious complications but higher retreatment rates at short- and long-term follow-up. WVTT offers lower retreatment rates with a similar safety profile. TIND studies report varying rates of retreatment and complications. All technologies offer low rates of erectile and ejaculatory dysfunction, although the risk appears to be highest for WVTT ( Conclusions Among the emerging technologies introduced to treat BPE, the in-office PUL, WVTT, and TIND systems are valuable additions to the current surgical options. These systems offer unique advantages that should be considered in the shared decision-making process. Patient summary In this report, we identified all clinical trials reporting on the efficacy and safety of the in-office prostatic urethral lift (PUL), water vapor thermal therapy (WVTT), and temporary implantable nitinol device (TIND) systems for the treatment of benign prostatic enlargement. We found that PUL and WVTT demonstrate acceptable outcomes in terms of functional improvement, retreatment, and complications. More data with longer follow-up are required to further evaluate TIND, but early results are promising.

Pseudoexfoliation syndrome (PEX) is characterized by the production of white extracellular fluffy clumps of microfibrillar material that aggregates in various organs throughout the body but is known to cause disease in the eye. The accumulation of PEX material (PEXM) in the anterior segment ocular structures is believed to cause an increase in intraocular pressure (IOP) resulting in pseudoexfoliation glaucoma (PEXG). The onset of PEXG is often bilateral but asymmetric-one eye often presents with glaucoma prior to the other eye. Proteomics has been used to identify key proteins involved in PEXM formation with the end goal of developing effective treatments for PEX and PEXG which may act through inhibiting the formation of the PEX aggregates. To date, a variety of proteins with various molecular functions have been identified from extracted anterior segment structures and fluids, such as aqueous humor (AH) and blood serum of patients affected by PEX. From past studies, some proteins identified in AH, lens capsule epithelium, iris tissue, and blood serum samples include vitamin D binding protein (GC), apolipoprotein A4 (APOA4), lysyl oxidase like-1 (LOXL1), complement C3, beta-crystalline B1, and B2, and antithrombin-III (SERPINC1). Each of these proteins have been observed in eyes with PEX at varying levels within the different eye structures. In this review, we further examine the anterior segment ocular proteomics of PEXM from past studies to better understand the mechanism of PEX and PEXG development. Both genetic and environmental risk factors have been implicated to be involved in the development of PEX and PEXG. This field is at an early stage of investigation identifying how these factors modify proteins both at the expression and functional level to cause changes leading to the pathophysiology of PEX glaucoma.

Testicular torsion (TT) is a common urologic emergency that can occur at any age. It is most common in newborns and during puberty. Prompt evaluation and management is required to salvage the testis following an episode of torsion. TT brings about damage to testicular tissue and spermatogenesis through various hypothesized mechanisms; however there is a consensus that the effects of ischemia, ischemia-reperfusion injury, and oxidative stress account for the most destructive effects. Numerous studies have examined the effects of various agents and therapies in limiting the effects of TT on the testis.

PURPOSE: To compare the outcomes of standard pop-titrated transscleral cyclophotocoagulation (TSCPC) and slow-coagulation TSCPC in the treatment of glaucoma. DESIGN: Retrospective case series SUBJECTS: This study included 78 eyes with glaucoma of any type or stage that underwent TSCPC as part of their treatment course METHODS: This study compared 52 eyes treated with slow coagulation TSCPC to 26 eyes treated with standard pop-titrated TSCPC. Patient demographics, treatment course, surgical techniques, settings and outcomes were assessed. MAIN OUTCOME MEASURES: The main outcome measures were visual acuity (VA), intraocular pressure (IOP) and post-surgical complications. RESULTS: The initial LogMAR VA was 1.94 (0.73) [mean (SD)] in the slow coagulation TSCPC group and 1.71 (0.90) in the standard TSCPC group (p=0.507). Initial IOP was 37 (13) mm Hg in the slow coagulation group and 39 (13) mm Hg in the standard group (p=0.297). The follow-up periods were 16.36 months and 24.68 months for the slow coagulation and standard groups (p=0.124). VA remained better than light-perception in 71.1% of slow coagulation treated patients and 65.0% of standard TSCPC treated patients (p=0.599). IOP remained below 20 mm Hg in 46% of slow coagulation treated patients and 44% of standard TSCPC treated patients (p=0.870). The mean number of complications was higher in the standard group [1.46 (1.24)] versus the slow coagulation group [0.62 (0.75)] (p=0.002). The incidence of the need for a second procedure (slow coagulation- 28.8%, standard- 23.1%, p=0.588) and maximum number of medications needed to control IOP postoperatively (p=0.771) were similar between the two groups. CONCLUSIONS: In this case series, slow coagulation TSCPC and standard pop-titrated TSCPC resulted in similar VA and IOP outcomes in the treatment of glaucomatous eyes. The complication profiles of the techniques were also comparable, although standard TSCPC had a higher incidence of prolonged inflammation postoperatively. This study suggests that slow coagulation TSCPC may achieve equivalent control of IOP while reducing the incidence of prolonged post-operative inflammation—a feared complication of TSCPC—when compared to standard “pop-titrated” TSCPC.

Background To investigate the distribution of peripheral anterior chamber depth (ACD) and the relationship between peripheral ACD and gonioscopy compared to other ocular parameters for primary angle closure disease (PACD) screening. We performed a population-based survey in Pudong New District of Shanghai, China, in 2011. Methods Cross-sectional study. Adults 50 and older were enrolled from a population-based study using cluster random sampling in Pudong New District, Shanghai. Remote ocular screening was performed with digital anterior eye structure photography. Van Herrick measurements were used to evaluate the peripheral ACD, the depth of the peripheral anterior chamber, and corneal thickness (CT), and the ACD to CT ratio was calculated. Subjects with peripheral ACD less than 0.5 CT were made follow-up appointments for clinical examination with gonioscopy. Receiver operating characteristic curves (ROC) were generated to show the performance of different tests in screening for primary angle closure disease (PACD). Results Two thousand five hundred twenty-eight adults participated in the study with 91 patients diagnosed with PACD. Two thousand four hundred sixty-three subjects had valid data in the right eye available for analysis. The mean peripheral ACD values for men and women were significantly different: 1.04 ± 0.46 (range 0.11–2.93) CT and 0.87 ± 0.41 (range 0.12–2.96) CT respectively (t = − 4.18; PP P P Conclusions Peripheral ACD measurement is recommended for PACD screening in community elderly Chinese.

Traumatic optic neuropathy leads to bidirectional degeneration of retinal ganglion cells and axons and results in optic nerve scaring, which inhibits the regeneration of damaged axons. Compared with its glial counterpart, the fibrotic response causing nerve scar tissue is poorly permissive to axonal regeneration. Using collagen1α1-GFP reporter mice, we characterize the development of fibrotic scar formation following optic nerve crush injury. We observe that perivascular collagen1α1 cells constitute a major cellular component of the fibrotic scar. We demonstrate that extracellular molecules and monocytes are key factors contributing to the pathogenesis of optic nerve fibrotic scar formation, with a previously unrecognized encapsulation of this scar. We also characterize the distribution of collagen1α1 cells in the retina after optic nerve crush injury based on in vivo and whole-mount retinal imaging. Our results identify collagen1α1 cells as a major component of fibrotic scarring following ONC and are a potential molecular target for promoting axonal regeneration after optic nerve injury.

Benign prostatic hyperplasia (BPH), a nonmalignant enlargement of the prostate, is among the most common diseases affecting aging men, but the underlying molecular features remain poorly understood, and therapeutic options are limited. Here we employ a comprehensive molecular investigation of BPH, including genomic, transcriptomic and epigenetic profiling. We find no evidence of neoplastic features in BPH: no evidence of driver genomic alterations, including low coding mutation rates, mutational signatures consistent with aging tissues, minimal copy number alterations, and no genomic rearrangements. At the epigenetic level, global hypermethylation is the dominant process. Integrating transcriptional and methylation signatures identifies two BPH subgroups with distinct clinical features and signaling pathways, validated in two independent cohorts. Finally, mTOR inhibitors emerge as a potential subtype-specific therapeutic option, and men exposed to mTOR inhibitors show a significant decrease in prostate size. We conclude that BPH consists of distinct molecular subgroups, with potential for subtype-specific precision therapy., Benign prostatic hyperplasia (BPH) is one of the most common diseases affecting aging men with limited therapeutic options. In this study, the authors describe the molecular characterization of BPH performing genomic, transcriptomic and epigenetic analysis of 18 BPH cases.