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Purpose To assess the structure-function relationship in glaucoma using Humphrey visual field (HVF) perimetry and a three-dimensional neuroretinal rim parameter derived from spectral domain optical coherence tomography (SD-OCT) volume scans. Methods Structure-function correlation was analyzed globally and regionally (four quadrants and four sectors). Structural data included peripapillary retinal nerve fiber layer (RNFL) thickness and minimum distance band (MDB) neuroretinal rim thickness, defined as the shortest distance between the inner cup surface and the outer retinal pigment epithelium/Bruch's membrane complex. Logarithmic regression analyses were performed and Pearson correlation coefficients determined to assess relationship strength. Results The study consisted of 102 open-angle glaucoma patients and 58 healthy subjects. The Pearson correlation coefficient for global MDB thickness (R = 0.585) was higher than for global RNFL thickness (R = 0.492), but the difference was not statistically significant (P = 0.18). The correlation coefficients for regional MDB thicknesses and corresponding HVF sensitivities were higher than those for regional RNFL thicknesses and HVF in six out of eight regions (P = 0.08 to 0.47). In the remaining two out of eight regions, the correlation coefficients were higher for RNFL thickness than for MDB thickness (P = 0.15 to 0.20). Conclusions Three-dimensional MDB neuroretinal rim thickness relates to visual function as strongly as the most commonly used SD-OCT parameter for glaucoma, two-dimensional peripapillary RNFL thickness. Translational relevance This paper illustrates the potential for 3D OCT algorithms to improve in vivo imaging in glaucoma.

Précis: Neuroretinal rim minimum distance band (MDB) thickness is significantly lower in older subjects and African Americans compared with whites. It is similar in both sexes. Purpose: To evaluate the relationship between age, race, and sex with the neuroretinal rim using high-density spectral-domain optical coherence tomography optic nerve volume scans of normal eyes. Methods: A total of 256 normal subjects underwent Spectralis spectral-domain optical coherence tomography optic nerve head volume scans. One eye was randomly selected and analyzed for each subject. Using custom-designed software, the neuroretinal rim MDB thickness was calculated from volume scans, and global and quadrant neuroretinal rim thickness values were determined. The MDB is a 3-dimensional neuroretinal rim band comprised of the shortest distance between the internal limiting membrane and the termination of the retinal pigment epithelium/Bruch’s membrane complex. Multiple linear regression analysis was performed to determine the associations of age, race, and sex with neuroretinal rim MDB measurements. Results: The population was 57% female and 69% white with a mean age of 58.4±15.3 years. The mean MDB thickness in the normal population was 278.4±47.5 µm. For this normal population, MDB thickness decreased by 0.84 µm annually (P

Supplemental Digital Content is available in the text., Precis: In open-angle glaucoma, when neuroretinal rim tissue measured by volumetric optical coherence tomography (OCT) scans is below a third of the normal value, visual field (VF) damage becomes detectable. Purpose: To determine the amount of neuroretinal rim tissue thickness below which VF damage becomes detectable. Methods: In a retrospective cross-sectional study, 1 eye per subject (of 57 healthy and 100 open-angle glaucoma patients) at an academic institution had eye examinations, VF testing, spectral-domain OCT retinal nerve fiber layer (RNFL) thickness measurements, and optic nerve volumetric scans. Using custom algorithms, the minimum distance band (MDB) neuroretinal rim thickness was calculated from optic nerve scans. “Broken-stick” regression was performed for estimating both the MDB and RNFL thickness tipping-point thresholds, below which were associated with initial VF defects in the decibel scale. The slopes for the structure-function relationship above and below the thresholds were computed. Smoothing curves of the MDB and RNFL thickness covariates were evaluated to examine the consistency of the independently identified tipping-point pairs. Results: Plots of VF total deviation against MDB thickness revealed plateaus of VF total deviation unrelated to MDB thickness. Below the thresholds, VF total deviation decreased with MDB thickness, with the associated slopes significantly greater than those above the thresholds (P

PURPOSE. To compare the diagnostic capability of three-dimensional (3D) macular parameters against traditional two-dimensional (2D) retinal nerve fiber layer (RNFL) thickness using spectral domain optical coherence tomography. To determine if manual correction and interpolation of B-scans improve the ability of 3D macular parameters to diagnose glaucoma. METHODS. A total of 101 open angle glaucoma patients (29 with early glaucoma) and 57 healthy subjects had peripapillary 2D RNFL thickness and 3D macular volume scans. Four parameters were calculated for six different-sized annuli: total macular thickness (M-thickness), total macular volume (M-volume), ganglion cell complex (GCC) thickness, and GCC volume of the innermost 3 macular layers (retinal nerve fiber layer + ganglion cell layer + inner plexiform layer). All macular parameters were calculated with and without correction and interpolation of frames with artifacts. The areas under the receiver operating characteristic curves (AUROC) were calculated for all the parameters. RESULTS. The 3D macular parameter with the best diagnostic performance was GCC-volume-34, with an inner diameter of 3 mm and an outer of 4 mm. The AUROC for RNFL thickness and GCC-volume-34 were statistically similar for all regions (global: RNFL thickness 0.956, GCC-volume-34 0.939, P value = 0.3827), except for the temporal GCC-volume-34, which was significantly better than temporal RNFL thickness (P value = 0.0067). Correction of artifacts did not significantly change the AUROC of macular parameters (P values between 0.8452 and 1.0000). CONCLUSIONS. The diagnostic performance of best macular parameters (GCC-volume-34 and GCC-thickness-34) were similar to or better than 2D RNFL thickness. Manual correction of artifacts with data interpolation is unnecessary in the clinical setting.

Purpose To report the long-term visual outcomes and complications after Boston keratoprosthesis type II implantation in the largest single-center case series with the longest average follow-up. Design Retrospective review of consecutive clinical case series. Participants Between January 1992 and April 2015 at the Massachusetts Eye and Ear Infirmary, 48 eyes of 44 patients had keratoprosthesis type II implanted by 2 surgeons (C.H.D. and J.C.). Methods For each eye, data were collected and analyzed on the preoperative characteristics, intraoperative procedures, and postoperative course. Main Outcome Measures Visual acuity outcomes, postoperative complications, and device retention. Results The most common indications for surgery were Stevens–Johnson syndrome in 41.7% (20 of 48 eyes) and mucous membrane pemphigoid in 41.7% (20 of 48 eyes). Mean follow-up duration was 70.2 months (standard deviation, 61.8 months; median, 52 months; range, 6 months to 19.8 years). Almost all patients (95.8%, 46 of 48 eyes) had a preoperative visual acuity of 20/200 or worse. Postoperative visual acuity improved to 20/200 or better in 37.5% (18 of 48 eyes) and to 20/100 or better in 33.3% (16 of 48 eyes) at the last follow-up visit. The most common postoperative complication was retroprosthetic membrane formation in over half (60.4%, 29 of 48 eyes). The most pressing postoperative complication was glaucoma onset or progression in about a third. Preexisting glaucoma was present in 72.9% (35 of 48 eyes). Glaucoma progressed in 27.1% (13 of 48 eyes) and was newly diagnosed in 8.3% (4 of 48 eyes) after surgery. Other postoperative complications were tarsorrhaphy revision in 52.1% (25 of 48 eyes), retinal detachment in 18.8% (9 of 48 eyes), infectious endophthalmitis in 6.3% (3 of 48 eyes), and choroidal detachment or hemorrhage in 8.3% (4 of 48 eyes). Half of eyes retained their initial keratoprosthesis at the last follow-up (50.0%, 24 of 48 eyes). Conclusions The Boston keratoprosthesis type II is a viable option to salvage vision in patients with poor prognosis for other corneal procedures. Retroprosthetic membranes, keratoprosthesis retention, and glaucoma are major challenges in the postoperative period; however, the keratoprosthesis can still provide improved vision in a select group of patients.

PURPOSE. To describe spectral-domain optical coherence tomography (OCT) methods for quantifying neuroretinal rim tissue in glaucoma and to compare these methods to the traditional retinal nerve fiber layer thickness diagnostic parameter. METHODS. Neuroretinal rim parameters derived from three-dimensional (3D) volume scans were compared with the two-dimensional (2D) Spectralis retinal nerve fiber layer (RNFL) thickness scans for diagnostic capability. This study analyzed one eye per patient of 104 glaucoma patients and 58 healthy subjects. The shortest distances between the cup surface and the OCT-based disc margin were automatically calculated to determine the thickness and area of the minimum distance band (MDB) neuroretinal rim parameter. Traditional 150-lm reference surface-based rim parameters (volume, area, and thickness) were also calculated. The diagnostic capabilities of these five parameters were compared with RNFL thickness using the area under the receiver operating characteristic (AUROC) curves. RESULTS. The MDB thickness had significantly higher diagnostic capability than the RNFL thickness in the nasal (0.913 vs. 0.818, P = 0.004) and temporal (0.922 vs. 0.858, P = 0.026) quadrants and the inferonasal (0.950 vs. 0.897, P = 0.011) and superonasal (0.933 vs. 0.868, P = 0.012) sectors. The MDB area and the three neuroretinal rim parameters based on the 150-lm reference surface had diagnostic capabilities similar to RNFL thickness. CONCLUSIONS. The 3D MDB thickness had a high diagnostic capability for glaucoma and may be of significant clinical utility. It had higher diagnostic capability than the RNFL thickness in the nasal and temporal quadrants and the inferonasal and superonasal sectors. © 2016, Association for Research in Vision and Ophthalmology Inc. All rights reserved.

Background/Aims: The presence of a posterior vitreous detachment (PVD) may play a role in the development of severe retinal toxicity following intravitreal melphalan (IVM) injection for vitreous seeding. We aimed to evaluate the incidence of PVD in retinoblastoma eyes and its association with retinal toxicity after IVM. Methods: We reviewed 112 eyes of 81 retinoblastoma patients with B-scan images available for review from 2010 to 2017. A cohort with vitreous seeding treated with IVM was compared to a cohort that did not undergo injection. The primary outcome measure was the presence of PVD at diagnosis and after treatment. Secondary measures included IVM-associated retinal toxicity and other ocular complications. Results: The incidence of PVD was 20% at diagnosis, and in eyes with B-scans available both at diagnosis and after treatment 18% of eyes developed a PVD over the course of therapy, more frequently after IVM (p = 0.05). Of 34 eyes receiving IVM treatment, the incidences of posterior segment toxicity and globe salvage were similar between eyes with and without PVD (p = 0.4015 and 0.52, respectively). Conclusion: In this cohort of patients, there did not appear to be an association with the presence of PVD during IVM and the development of retinal toxicity.

Purpose: To evaluate the effects of age, race, and ethnicity on the optic nerve and peripapillary retina using spectral-domain optical coherence tomography (SD-OCT) three-dimensional (3D) volume scans in normal subjects. Methods: This is a cross-sectional study performed at a single institution in Boston. All patients received retinal nerve fiber layer (RNFL) scans and an optic nerve 3D volume scan. The SD-OCT software calculated peripapillary RNFL thickness, retinal thickness (RT), and retinal volume (RV). Custom-designed software calculated neuroretinal rim minimum distance band (MDB) thickness and area. Results: There were 272 normal subjects, including 175 whites, 40 blacks, 40 Asians, and 17 Hispanics. Rates of age-related decline were 2.3%, 2.0%, 1.7%, 3.3%, and 4.3% per decade for RNFL, RT, RV, MDB neuroretinal rim thickness, and MDB area, respectively. The RNFL was most affected by racial and ethnic variations, with Asians having thicker global, superior, and inferior RNFL, Hispanics having thicker inferior RNFL, and blacks having thinner temporal RNFL, compared to whites. For MDB thickness and area, Asians had smaller nasal values and blacks had smaller temporal values. Peripapillary RT and RV parameters were not influenced by race and ethnicity. Conclusions: All of the parameters exhibited age-related declines. RNFL, MDB thickness, and MDB area demonstrated racial and ethnic variations, while peripapillary RT and RV did not. Translational Relevance: This study demonstrates that both normal aging and ethnicity affect several novel 3D OCT parameters used to diagnose and monitor glaucoma (i.e., RT, RV, and MDB), and this should be factored in when making clinical decisions based on these parameters. © 2018 The Authors.

Purpose To determine the diagnostic capability of peripapillary 3-dimensional (3D) retinal nerve fiber layer (RNFL) volume measurements from spectral-domain optical coherence tomography (OCT) volume scans for open-angle glaucoma (OAG). Design Assessment of diagnostic accuracy. Methods SETTING: Academic clinical setting. STUDY POPULATION: Total of 180 patients (113 OAG and 67 normal subjects). OBSERVATION PROCEDURES: One eye per subject was included. Peripapillary 3D RNFL volumes were calculated for global, quadrant, and sector regions, using 4 different-size annuli. Peripapillary 2D RNFL thickness circle scans were also obtained. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUROC) values, sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios. Results Among all 2D and 3D RNFL parameters, best diagnostic capability was associated with inferior quadrant 3D RNFL volume of the smallest annulus (AUROC value 0.977). Otherwise, global 3D RNFL volume AUROC values were comparable to global 2D RNFL thickness AUROC values for all 4 annulus sizes (P values:.0593 to.6866). When comparing the 4 annulus sizes for global RNFL volume, the smallest annulus had the best AUROC values (P values:.0317 to.0380). The smallest-size annulus may have the best diagnostic potential, partly owing to having no areas excluded for being larger than the 6 × 6 mm2 scanned region. Conclusion Peripapillary 3D RNFL volume showed excellent diagnostic performance for detecting glaucoma. Peripapillary 3D RNFL volume parameters have the same or better diagnostic capability compared to peripapillary 2D RNFL thickness measurements, although differences were not statistically significant. © 2017 Elsevier Inc.

Suboptimal HIV/STI testing uptake has a profound impact on morbidity and mortality. Incentives have been effective in other areas of medicine and may improve HIV/STI testing uptake rates. This study reviewed the effects of incentives on HIV/STI testing uptake. A systematic search of seven databases was undertaken. Testing uptake was defined as test implementation and/or test result retrieval. Incentives were defined as monetary or non-monetary rewards or free-of-charge testing vouchers. Seven studies were included. All seven studies demonstrated higher rates of uptake in an incentivized group. Incentives offered at a non-clinical setting demonstrated more significant differences in uptake rates compared to incentives offered at a clinical setting. Incentivizing HIV/STI testing uptake, especially testing at a non-clinical setting, may be a useful tool to modify health behavior. Further research is needed to understand how incentives could be an effective component within a comprehensive HIV/STI control strategy.

Comprehensive interventions that address both individual and structural determinants associated with HIV/STI risk are gaining increasing attention over the past decade. Microenterprise development offers an appealing model for HIV prevention by addressing poverty and gender equality. This study systematically reviewed the effects of microenterprise development interventions on HIV/STI incidence and sexual risk behaviors. Microenterprise development was defined as developing small business capacity among individuals to alleviate poverty. Seven eligible research studies representing five interventions were identified and included in this review. All of the studies targeted women, and three focused on sex workers. None measured biomarker outcomes. All three sex worker studies showed significant reduction in sexual risk behaviors when compared to the control group. Non-sex worker studies showed limited changes in sexual risk behavior. This review indicates the potential utility of microenterprise development in HIV risk reduction programs. More research is needed to determine how microenterprise development can be effectively incorporated in comprehensive HIV control strategies.

Purpose The aim of this 8-year retrospective review was to determine the clinical significance of gadolinium-enhanced magnetic resonance imaging (MRI) findings in retinoblastoma patients after enucleation, particularly the presence of abnormal contrast enhancement of the transected optic nerve. Design Retrospective chart review. Subjects A review was done on 88 patients with retinoblastoma undergoing 90 enucleations between January 2008 and December 2015. Methods These patients underwent 233 MRI scans: 90 preoperative and 143 postoperative that were included for review. Main Outcome Measure The primary outcome measure assessed was abnormal MRI findings in the preoperative and postoperative MRI scans, specifically enhancement of the optic nerve and correlations between abnormal MRI findings and clinical outcomes for the 88 patients. Results On the preoperative MRI, 4 optic nerves out of 90 scans showed positive enhancement. Fifty orbits had ≥1 postoperative MRI. Overall, 41 of 50 orbits (82%) of enucleated patients demonstrated postoperative contrast enhancement on MRI after enucleation, at a mean interval of 10 months after surgery. The percentage of MRI scans with optic nerve enhancement was 77% from 0 to 6 months after enucleation and 68% at >24 months after surgery. Postenucleation optic nerve enhancement did not correlate with preoperative optic nerve enhancement, chemotherapy administration, or the presence of optic nerve invasion on histopathology. No child required an orbital biopsy. None of the 88 patients were found to have subsequent orbital or metastatic disease at the last clinical follow-up visit (average, 29 months; range, 1–71). Conclusion Optic nerve contrast enhancement on follow-up MRI after enucleation for retinoblastoma seems to be a common, benign radiographic finding; none of the patients in this series developed extraocular tumor relapse. The presence of postenucleation enhancement on MRI did not correlate with preoperative chemotherapy or the presence of optic nerve invasion on histopathology. Based on our findings, intervention for isolated optic nerve enhancement on MRI is not indicated in the absence of other abnormal clinical or radiographic signs. A prospective trial with a validated radiographic grading system would be helpful to clarify the MRI features to differentiate orbital recurrence from benign postoperative enhancement.

Targeting glutamine metabolism via pharmacological inhibition of glutaminase has been translated into clinical trials as a novel cancer therapy, but available drugs lack optimal safety and efficacy. In this study, we used a proprietary emulsification process to encapsulate bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES), a selective but relatively insoluble glutaminase inhibitor, in nanoparticles. BPTES nanoparticles demonstrated improved pharmacokinetics and efficacy compared with unencapsulated BPTES. In addition, BPTES nanoparticles had no effect on the plasma levels of liver enzymes in contrast to CB-839, a glutaminase inhibitor that is currently in clinical trials. In a mouse model using orthotopic transplantation of patient-derived pancreatic tumor tissue, BPTES nanoparticle monotherapy led to modest antitumor effects. Using the HypoxCR reporter in vivo, we found that glutaminase inhibition reduced tumor growth by specifically targeting proliferating cancer cells but did not affect hypoxic, noncycling cells. Metabolomics analyses revealed that surviving tumor cells following glutaminase inhibition were reliant on glycolysis and glycogen synthesis. Based on these findings, metformin was selected for combination therapy with BPTES nanoparticles, which resulted in significantly greater pancreatic tumor reduction than either treatment alone. Thus, targeting of multiple metabolic pathways, including effective inhibition of glutaminase by nanoparticle drug delivery, holds promise as a novel therapy for pancreatic cancer.

BACKGROUND: Health services for men who have sex with men (MSM) are inadequate in many areas around the world. HIV and syphilis test uptake remain suboptimal among MSM in China and many other regions. To inform the development of more comprehensive sexually transmitted disease (STD) testing programs among MSM, we collected descriptive data on MSM testing practices and preferences. METHODS: MSM in two large urban Chinese cities were recruited through community-based organizations and clinics to participate in semi-structured interviews. We purposively sampled MSM across a range of sociodemographic characteristics and testing history, and assessed preferences for HIV and syphilis testing in the context of facilitators and barriers to testing and previous testing experiences. Each interview transcript was coded and thematically analyzed using Atlas.ti 7.0. RESULTS: 35 MSM were interviewed. Confidentiality and privacy were the most important factors influencing participants' decisions about whether and where to get tested. Men preferred rapid testing (results available within 30 minutes) compared to conventional tests where results take several hours or days to return. Participants described concerns about quality and accuracy of rapid tests offered in non-clinical settings such as community-based organizations. Men preferred testing service providers who were MSM-friendly, non-discriminatory, and medically trained. Preferred service center environments included: convenient but discrete location, MSM-friendly atmosphere, and clean/standard medical facilities. CONCLUSION: Our data highlight the need for HIV/syphilis testing services that are confidential and inclusive of MSM. Rapid testing in decentralized (i.e. peripheral health facilities and community-level, non-clinical venues) settings provides an opportunity to reach individuals who have not been tested before, but must be accompanied by quality assurance systems and technical competence. Implementation research could further evaluate HIV/syphilis testing programs responsive to MSM preferences. SHORT SUMMARY: A qualitative study of MSM in South China found that men preferred rapid STD testing at MSM-focused test centers, but were concerned about test quality assurance and confidentiality.

Background UNAIDS has called for greater HIV/syphilis testing worldwide just as local HIV/syphilis testing programs are cut or altered. New models are needed to make HIV/syphilis testing services sustainable while retaining their essential public health function. Social entrepreneurship, using business principles to promote a social cause, provides a framework to pilot programs that sustainably expand testing. Drawing on fieldwork in two South Chinese cities, we examined organizational and financial characteristics of current HIV/syphilis testing systems for men who have sex with men (MSM) in addition to new pilot programs focused on revenue-generation for sustainability. Methods We undertook a qualitative study to explore organizational and financial characteristics of HIV/syphilis testing for MSM. Data were collected from men who have sex with men and policy stakeholders in Guangzhou and Hong Kong. Framework analysis was used to identify themes and then code the data. Results Our qualitative research study included MSM and policy stakeholders (n = 84). HIV/syphilis testing services were implemented at a wide range of organizations which we grouped broadly as independent community-based organizations (CBOs), independent clinics, and hybrid CBO-clinic sites. From an organizational perspective, hybrid CBO-clinic sites offered the inclusive environment of an MSM CBO linked to the technical capacity and trained staff of a clinic. From a financial perspective, stakeholders expressed concern about the sustainability and effectiveness of sexual health services reliant on external funding. We identified four hybrid CBO-clinic organizations that launched pilot testing programs in order to generate revenue while expanding HIV testing. Conclusion Many MSM CBOs are searching for new organizational models to account for decreased external support. Hybrid CBO-clinic organizations create a strong foundation to increase HIV/syphilis testing using social entrepreneurship models in China. Electronic supplementary material The online version of this article (doi:10.1186/s12879-014-0601-5) contains supplementary material, which is available to authorized users.