Clinical Significance of Recurrent Disc Hemorrhage and Choroidal Microvasculature Dropout on Optical Coherence Tomography Angiography in Glaucoma.

Purpose: The purpose of this study was to investigate the clinical significance of recurrent disc hemorrhage (DH) and choroidal microvasculature dropout (MvD). Methods: A retrospective cohort study was conducted of 181 eyes with open-angle glaucoma. The clinical characteristics of patients with nonrecurrent and recurrent DH with and without MvD were investigated. Results: Fifty-eight patients (32.0%) had a single, nonrecurrent DH, and 63 (34.8%) had more than one DH. Sixty eyes (33.1%) with no history of DH were presented as a control group. MvD was more frequent in the recurrent DH group (44.4%) than in the nonrecurrent DH group (27.6%, P = 0.041). The recurrent DH with MvD group experienced more frequent central visual field (VF) progression (71.4%) than the recurrent DH without MvD group (17.1 %, P < 0.001). The recurrent DH without MvD group had a higher frequency of DH recurrence at different locations (42.9%) and more vascular symptoms (37.1%) than the recurrent DH with MvD group (14.3% and 7.1%, P = 0.013 and P = 0.005, respectively). Presence of DH, presence of MvD, vascular symptoms, and DH recurrence at different locations were the factors associated with central VF progression in multivariate analysis. Conclusions: DH occurrence and the presence of MvDs constitute critical parameters associated with central VF progression. In the presence of MvD, recurrent DH was more likely to recur at the same location as the MvD, whereas recurrent DH without MvD was related to vascular symptoms and recurred at other locations. When eyes present with recurrent DH and MvD, closer follow-up and more aggressive treatment are required to prevent the progression of central VF.

Clinical Characteristics and Associated Factors to the Development of Glaucoma in Eyes With Myopic Optic Neuropathy.

PURPOSE: To observe the development of glaucoma in myopic eyes with and without myopic optic neuropathy (MON) and analyze associated factors to the development of typical glaucomatous damage. DESIGN: A prospective, observational, cohort study. METHODS: A total of 233 myopic eyes with no definite evidence of glaucomatous damage were included. Myopic patients without any retinal nerve fiber layer (RNFL) or visual field (VF) abnormalities were classified as myopic eyes without MON. Myopic patients with decreased RNFL at the superonasal (SN) or nasal area, and with corresponding VF defects either in the temporal or inferotemporal (IT) region were classified as myopic eyes with MON. Myopic eyes that developed glaucoma were defined by the presence of glaucomatous VF in the SN region including defects in Bjerrum area, or a new localized RNFL defect in the IT region. Disc morphological features and optic nerve head (ONH) parameters of two groups were compared. RESULTS: Myopic eyes with MON had a thinner average peripapillary RNFL thickness (P < 0.001), worse MD of the VF (P = 0.031), a higher percentage of IT VF defects (P < 0.001), smaller torsion degree (P = 0.047), and greater LCD (P = 0.022). Myopic eyes with MON who developed glaucoma had a thinner average peripapillary RNFL thickness (P = 0.009), greater PPA area (P = 0.049), greater LCD (P < 0.001), and thinner LCT (P < 0.001). Thinner baseline temporal RNFL thickness (HR, 0.956; 95% CI, 0.928-0.986; P = 0.004), greater baseline LCD (HR, 1.003; 95% CI, 1.000-1.005; P = 0.022), and greater PPA area (HR, 1.000; 95% CI, 1.000-1.003; P = 0.050) were significantly associated factors with glaucoma development. CONCLUSIONS: Myopic eyes with MON have a greater risk to develop glaucoma compared to myopic eyes without MON. Structural weakness due to myopia, especially at the temporal side of the ONH and the peripapillary sclera, increases the risk of glaucoma in myopic eyes with MON.

Effect of a Pericardium Graft Inserted Adjacent to the Endplate in the Ahmed Glaucoma Valve Implantation.

The surface area of encapsulation around the Ahmed glaucoma valve (AGV) endplate is a critical factor in the surgical outcome as it is associated with the degree of IOP reduction. We investigated the surgical outcome of AGV implantation with an additional pericardium graft inserted adjacent to the endplate, with the intent of expanding the surface area of encapsulation. We enrolled 92 patients (92 eyes) who underwent AGV implantation. Of them, 50 patients underwent conventional surgery (termed the without-expansion group), and 42 received an additional an 8 × 6 mm pericardium graft inserted adjacent to the AGV endplate at the sub-Tenon's space (with-expansion). The hypertensive phase was classified as mild (>21 mmHg), moderate (>25 mmHg), and severe (>30 mmHg). Six months post-surgery, the with-expansion group exhibited a lower IOP (14.90 ± 4.27 mmHg) and lower peak IOP (22.29 ± 4.95 mmHg) than the without-expansion group (17.56 ± 4.88 mmHg and 25.06 ± 6.18 mmHg, p = 0.008 and p = 0.021, respectively). The with-expansion group exhibited a relatively low rate of moderate (16.7%) and severe (4.8%) hypertensive phases compared to the without-expansion group (40.0% and 20.0%, with p = 0.014 and p = 0.031, respectively). The additional pericardium graft was associated with a reduced occurrence of moderate hypertensive phase in both univariate and multivariate analysis logistic regression analyses (p = 0.017 and p = 0.038, respectively). Endplate surface area expansion using an additional pericardium graft reduced the occurrence of moderate and severe hypertensive phases, and lower postoperative 6-month IOP could be achieved.

Importance of Pattern Standard Deviation of Humphrey 10-2 Visual Field to Evaluate Central Visual Function in Patients with Early-Stage Glaucoma.

To explore various parameters that can evaluate the central visual impairment in patients with early-stage glaucoma, we included patients into a study with central visual impairments with an MD value greater than -6.0 dB on the 24-2 VF test. A possible association between structural parameters acquired by OCT and functional parameters of VF and PERG was determined. A total of 70 eyes of patients with suspected glaucoma or NTG underwent VF, OCT, and PERG examinations. The patients were classified into two groups according to the MD of the 24-2 VF test. We used Pearson correlation analysis to evaluate the relationships between GCIPL thickness/RNFL thickness and visual functional parameters, such as PERG and perimetry. Linear regression analyses were conducted to evaluate the significant factors affecting the PSD of VF 10-2. In the low MD group, the P50 amplitude presented significant correlations (r = 0.346, p = 0.048) with GCIPL thickness. In the correlation analysis of the high MD group, it was found that only the PSD of 10-2 uniquely presented borderline significant correlations with GCIPL thickness (r = -0.327, p = 0.055), and no other functional parameter showed significant correlation. Univariate and multivariate analyses revealed that GCIPL thickness was significantly associated with a PSD of 10-2 VF (p < 0.001 and 0.013, respectively). Among various parameters, the P50 amplitude and 10-2 PSD demonstrated statistically borderline significant structure-function relationships with GCIPL thickness in early-stage glaucoma.

Deviated Saccadic Trajectory as a Biometric Signature of Glaucoma.

Purpose: To investigate whether the trajectories of saccadic eye movements (SEMs) significantly differ between glaucoma patients and controls. Methods: SEMs were recorded by video-based infrared oculography in 53 patients with glaucoma and 41 age-matched controls. Participants were asked to bilaterally view 24°-horizontal, 14°-vertical, and 20°-diagonal eccentric Goldmann III-sized stimuli. SEMs were evaluated with respect to the saccadic reaction time (SRT), the mean velocity, amplitude, and two novel measures: departure angle (DA) and arrival angle (AA). These parameters were compared between the groups and the associations of SEM parameters with glaucoma parameters and integrated visual field defects were investigated. Results: Glaucoma patients exhibited increased mean SRT, DA, and AA values compared with controls for 14°-vertical visual targets (P = 0.05, P < 0.01, and P < 0.01, respectively). The SRT, DA, and AA were significantly associated with the mean and pattern standard deviations of perimetry and with the mean RNFL thickness by OCT (all P < 0.001). Glaucoma was associated with the AA (P = 0.05) and both the SRT (P = 0.01) and DA (P = 0.04) were associated with integrated visual field defects. Conclusions: The saccadic trajectories of glaucoma patients depart in an erroneous path and compensate the disparity by deviating the trajectory at arrival. Translational Relevance: The initial deviation that we observed (despite continuous exposure to the stimulus) suggests the disoriented spatial perception of glaucoma patients which may be relevant to difficulties encountered daily.

Factors Associated with Vascular Changes at the Level of Retinal Ganglion Cell Axon versus Soma/Dendrite in Glaucoma Patients.

Superficial and deep macular vessel density (VD) is decreased in eyes with glaucoma. Superficial VD comprises both the retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GC/IPL), and various terms have been used previously to describe the layers of macular VD. In our study, we readjusted the macular segmentation. We obtained RNFL and GC/IPL VDs separately to evaluate VD changes of axon versus soma/dendrite of the retinal ganglion cells (RGCs) in detail. We included 66 eyes of normal tension glaucoma patients with inferior localized RNFL defects solely impacting the inferior hemiretina. Macular VD was measured as RNFL VD and GC/IPL VD. VD ratio was calculated by dividing the VD from the affected hemiretina by the VD from the unaffected hemiretina. RNFL VD ratio was related to RNFL and GC/IPL thicknesses (p = 0.005, p = 0.001), whereas GC/IPL VD ratio was not (p = 0.596, p = 0.783). A lower GC/IPL VD ratio was associated with lower RNFL VD (p = 0.017) and systemic hypertension (p = 0.03) in multivariate analysis. Patients with a reduced GC/IPL VD ratio were more prone to poor visual field defects (p = 0.022) and paracentral scotoma (p = 0.046) and more likely to be on treatment for systemic hypertension (p = 0.024). Therefore, glaucoma patients on systemic hypertension treatment and reduced GC/IPL VD require cautious management.

Cost-Effectiveness of All-Oral Regimens for the Treatment of Multidrug-Resistant Tuberculosis in Korea: Comparison With Conventional Injectable-Containing Regimens.

BACKGROUND: Regimens for the treatment of multidrug-resistant tuberculosis (MDR-TB) have been changed from injectable-containing regimens to all-oral regimens. The economic effectiveness of new all-oral regimens compared with conventional injectable-containing regimens was scarcely evaluated. This study was conducted to compare the cost-effectiveness between all-oral longer-course regimens (the oral regimen group) and conventional injectable-containing regimens (the control group) to treat newly diagnosed MDR-TB patients. METHODS: A health economic analysis over lifetime horizon (20 years) from the perspective of the healthcare system in Korea was conducted. We developed a combined simulation model of a decision tree model (initial two years) and two Markov models (remaining 18 years, six-month cycle length) to calculate the incremental cost-effectiveness ratio (ICER) between the two groups. The transition probabilities and cost in each cycle were assumed based on the published data and the analysis of health big data that combined country-level claims data and TB registry in 2013-2018. RESULTS: The oral regimen group was assumed to spend 20,778 USD more and lived 1.093 years or 1.056 quality-adjusted life year (QALY) longer than the control group. The ICER of the base case was calculated to be 19,007 USD/life year gained and 19,674 USD/QALY. The results of sensitivity analyses showed that base case results were very robust and stable, and the oral regimen was cost-effective with a 100% probability for a willingness to pay more than 21,250 USD/QALY. CONCLUSION: This study confirmed that the new all-oral longer regimens for the treatment of MDR-TB were cost-effective in replacing conventional injectable-containing regimens.

Fluctuation of Intraocular Pressure and Vascular Factors Are Associated With the Development of Epiretinal Membrane in Glaucoma.

PURPOSE: To identify factors associated with the development of epiretinal membranes (ERM) in glaucoma patients. DESIGN: Multicenter, propensity-score matched, case-control study. METHODS: One hundred ninety-two eyes of 192 patients with glaucoma from the Catholic Medical Center Glaucoma Suspect Cohort Study were analyzed. We identified 64 eyes who developed ERM from the cohort, and 128 eyes without ERM were selected by propensity score matching (1:2) according to baseline age and mean deviation (MD) of the visual field (VF). Demographic, systemic, and ocular characteristics were determined at baseline. Intraocular pressure (IOP) was measured, including baseline, mean IOP, and IOP fluctuation. Early-stage ERM, defined as translucent membrane with no underlying retinal distortion, was detected by fundus photography and optical coherence tomography. Central VF progression was considered when new VF defets developed in one either or both hemifields or when there was an increase of 3 or more abnormal points within 12 points of central 10° fixation. Autonomic nervous system status was evaluated by heart rate variability. RESULTS: Patients who developed ERM were more frequently receiving medication for systemic hypertension and had higher systolic blood pressure, greater IOP fluctuation, more frequent disc hemorrhage (DH), worse VF MD, and a higher rate of central VF progression than patients without ERM. Additionally, patients with early glaucoma who developed ERM had higher rate of autonomic imbalance while patients with moderate-to-advanced glaucoma who developed ERM had greater baseline and peak IOP and worse MD of the last follow-up VF (MD < 6.0 dB). Older age (P = .048), medication for systemic hypertension (P < .001), IOP fluctuation (P < .001), presence of DH (P < .001), and worse last MD of VF (P = .033) were significantly associated with ERM in Cox proportional hazard analysis. CONCLUSIONS: Early stage of ERMs in glaucomatous eyes are significantly associated with glaucoma progression, medication of systemic hypertension, presence of DH, and IOP fluctuation. These suggest that glaucoma patients who develop early stage of ERMs should be carefully monitored in terms of IOP fluctuation, vascular factors, and glaucoma progression.

Harnessing dendritic cell diversity in cancer immunotherapy.

Dendritic cells (DCs) are ubiquitous immune cells endowed with a unique capacity to initiate antigen-specific immunity and tolerance. Owing to their unique functional attributes, DCs have long been considered ideal candidates for the induction of effective antitumour responses. At the forefront of the cancer-immunity cycle, attempts to harness DC natural adjuvant properties in the clinic have resulted so far in suboptimal antitumour responses. A better understanding of the heterogeneity of the DC network and its dynamics within the tumour microenvironment will provide a blueprint to fully capitalise on their functional properties to achieve more effective antitumour responses. In this review, we will briefly summarise the origin and heterogeneity of the DC network, their roles in shaping antitumour immunity and in modulating the response to immune checkpoint blockade therapies.

Factors Affecting Visual Acuity and Central Visual Function in Glaucoma Patients With Myopia.

PURPOSE: To investigate associated factors including structural parameters of myopia and vessel density (VD) using optical coherence tomography angiography (OCT-A) to visual acuity (VA) and central visual function in glaucoma patients with myopia. DESIGN: Retrospective cross-sectional study. METHODS: Sixty-five eyes of 60 glaucoma patients with myopia and without media opacity and retinal lesions were included. Both Swedish interactive thresholding algorithm (SITA) 24-2 and 10-2 visual field (VF) testing were performed. Superficial and deep VD in the peripapillary and macular regions were evaluated using OCT-A; retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL) thicknesses were measured. ß-zone peripapillary atrophy (PPA) area, disc torsion, disc-fovea distance, and peripapillary choroidal thickness were measured. Decreased VA was defined as best-corrected VA <20/25. RESULTS: The worse mean deviation of SITA 24-2, thinner GCIPL thickness, and lower deep peripapillary VD were associated with the presence of central VF damage in glaucoma patients with myopia. Thinner GCIPL thickness, lower deep peripapillary VD, and longer disc-fovea distance were associated with decreased VA in logistic regression analysis. Thinner GCIPL thickness, lower deep peripapillary VD, and larger ß-zone PPA area were associated with lower VA in linear regression analysis. Deep peripapillary VD showed a positive correlation with GCIPL thickness, whereas there was no relationship between deep peripapillary VD and RNFL thickness. CONCLUSION: Decreased VA in glaucoma patients with myopia was associated with lower deep peripapillary VD and papillomacular bundle damage. Lower deep peripapillary VD was independently associated with decreased VA along with thinner GCIPL thickness. Therefore, it could be stated that decreased VA in glaucoma patients is related to the damage location and the status of blood flow in the optic nerve head.

Angiotensin II-Related Activation of Scleral Fibroblasts and Their Role on Retinal Ganglion Cell Death in Glaucoma.

We identify the angiotensin II (AngII)-associated changes in the extracellular matrix (ECM) and the biomechanical properties of the sclera after systemic hypotension. Systemic hypotension was induced by administering oral hydrochlorothiazide. AngII receptor levels and ECM components in the sclera and biomechanical properties were evaluated based on the stress-strain relationship after systemic hypotension. The effect of inhibiting the AngII receptor with losartan was determined in the systemic hypotensive animal model and the cultured scleral fibroblasts from this model. The effect of losartan on retinal ganglion cell (RGC) death was evaluated in the retina. Both AngII receptor type I (AT-1R) and type II (AT-2R) increased in the sclera after systemic hypotension. Proteins related to the activation of fibroblasts (transforming growth factor [TGF]-ß1 and TGF-ß2) indicated that transformation to myofibroblasts (α smooth muscle actin [SMA]), and the major ECM protein (collagen type I) increased in the sclera after systemic hypotension. These changes were associated with stiffening of the sclera in the biomechanical analysis. Administering losartan in the sub-Tenon tissue significantly decreased the expression of AT-1R, αSMA, TGF-ß, and collagen type I in the cultured scleral fibroblasts and the sclera of systemic hypotensive rats. The sclera became less stiff after the losartan treatment. A significant increase in the number of RGCs and decrease in glial cell activation was found in the retina after the losartan treatment. These findings suggest that AngII plays a role in scleral fibrosis after systemic hypotension and that inhibiting AngII could modulate the tissue properties of the sclera, resulting in the protection of RGCs.

Normotensive Glaucoma in the Fellow Eye of Patient with Unilateral Pseudoexfoliation.

PURPOSE: To investigate the characteristics of normotensive glaucoma (NTG) in the fellow eye of patients with unilateral pseudoexfoliation syndrome (PXS). METHODS: This study is a retrospective chart review. We included 313 patients with NTG. Using the 1:1 matched propensity score, only 94 well-matched patients were selected. A total of 47 NTG patients who had PXS in their contralateral eye (PXS group) and 47 NTG patients who did not (control group) were compared. The propensity score was matched based on age, mean intraocular pressure (IOP), baseline retinal nerve fiber layer (RNFL) thickness and baseline mean deviation (MD) of visual field (VF) score. The diagnosis of NTG was based on the presence of glaucomatous optic nerve head injury with VF defect, intraocular pressure less than 22 mmHg, open angles and no pseudoexfoliation material. RESULTS: The PXS group had a higher ratio of males (34.0%) than the control group (17.0%). No significant differences were observed between the two groups in terms of CCT, axial length, untreated baseline IOP, baseline PSD of VF, systemic blood pressure and follow-up duration. The rate of RNFL thinning was significantly faster in the PXS group (-1.88 ± 2.83 µm/year) compared with the control group (-0.27 ± 5.29 µm/year) (p = 0.02). The progression rate of VF MD was slightly faster in PXS than in the control group, but there was no statistically significant difference (PXS group, -0.33 ± 0.90 dB/year; control group, -0.11 ± 0.84 dB/year; p = 0.236). CONCLUSIONS: NTG eyes with PXS showed faster RNFL thinning than did control NTG eyes.

Incidence and risk factors of tuberculosis in patients following gastrectomy or endoscopic submucosal dissection: a cohort analysis of country-level data.

BACKGROUND: Gastric cancer adversely affects nutrition and immunity, while increasing the risk of tuberculosis (TB). This study investigated the incidence and risk factors for TB in gastric cancer patients who had undergone gastrectomy or endoscopic submucosal dissection (ESD). METHODS: This retrospective cohort study was conducted using Korean national insurance claims data. We defined three study groups (total gastrectomy, subtotal gastrectomy, and ESD) of patients diagnosed with gastric cancer plus a cancer-free control group. The latent TB infection (LTBI) screening status, TB incidence, and potential confounders in each cohort were analyzed, and the risk of TB was analyzed using a Cox proportional hazard model. RESULTS: LTBI tests were performed in less than 1% of all patients, and the TB incidence rates were 473.8, 287.4, 199.4, 111.1 events/100,000 person-years in the total gastrectomy, subtotal gastrectomy, ESD, and control cohorts, respectively. Compared to the control cohort, the total gastrectomy cohort showed the highest hazard ratio (HR) for TB incidence (HR: 2.896, 95% CI: 2.559-2.337), while the ESD cohort showed a significantly increased risk (HR: 1.578, 95% CI: 1.957-1.980). Age, body mass index, and lack of exercise were risk factors in all cohorts. Comorbidities were also considered risk factors, depending on the cohort type. CONCLUSIONS: Patients who underwent gastrectomy or ESD had an increased risk of TB, and this risk was correlated with the scope of gastrectomy. Considering the low rate of LTBI diagnostic tests and increased risk of TB in the study cohorts, more specific and practical guidelines for TB management are required for gastric cancer patients.

Factors Contributing to the Development of Choroidal Microvasculature Dropout in Glaucoma Suspects and Patients with Glaucoma.

We aimed to characterize and compare the occurrence of peripapillary microvasculature dropout (MvD) between glaucoma suspects and patients with glaucoma. In addition, the factors related to the development of parapapillary MvD in glaucoma suspects and patients with glaucoma were investigated. Of a total 150 eyes, 68 eyes of glaucoma suspects and 82 eyes of glaucoma patients were analyzed in this study. Univariate and multivariate logistic regression analyses were used to identify factors associated with MvD development. The classification of glaucoma patients or glaucoma suspects was not significantly associated with MvD development (beta 1.368, 95% CI, 0.718-2.608, p = 0.341). In the regression analysis of the glaucoma suspect group, greater axial length (beta 1.520, 95% CI, 1.008-2.291, p = 0.046) and baseline cup volume (beta 3.993, 95% CI, 1.292-12.345, p = 0.035) among the baseline factors and the slope of ganglion cell-inner plexiform layer (GCIPL) thickness (beta 0.027, 95% CI, 0.072-0.851, p = 0.027) and central visual field (VF) progression (beta 7.040, 95% CI, 1.781-16.306, p = 0.014) among follow-up factors were significantly associated with MvD development. In the glaucoma group, central VF progression (beta 5.985, 95% CI, 1.474-24.083, p = 0.012) and ONH depression (beta 3.765, 95% CI, 1.301-10.895, p = 0.014) among follow-up elements were observed as significant factors and the baseline factor had little relationship. MvD appears not only as a result of the progression of axonal loss of RGC in glaucoma but may also be developed due to structural changes and mechanical susceptibility of the ONH associated with baseline characteristics. Analyzing the structural susceptibility of the ONH can predict the occurrence of MvD, which can be helpful in predicting the progression of glaucoma.

Real-world association of adherence with outcomes and economic burden in patients with tuberculosis from South Korea claims data.

Objectives: We analyzed tuberculosis (TB)-related costs according to treatment adherence, as well as the association between treatment adherence, treatment outcomes, and costs related to drug-susceptible TB in South Korea. Methods: Patients who had newly treated TB in South Korea between 2006 and 2015 were selected from nationwide sample claims data and categorized into adherent and non-adherent groups using the proportion of days TB drugs covered. Patients were followed-up from the initiation of TB treatment. The mean five-year cumulative costs per patient were estimated according to adherence. Moreover, we evaluated the relative ratios to identify cost drivers such as adherence, treatment outcomes, and baseline characteristics using generalized linear models. Four treatment outcomes were included: treatment completion, loss to follow-up, death, and the initiation of multidrug-resistant TB treatment. Results: Out of the 3,799 new patients with TB, 2,662 were adherent, and 1,137 were non-adherent. Five years after initiating TB treatment, the mean TB-related costs were USD 2,270 and USD 2,694 in the adherent and non-adherent groups, respectively. The TB-related monthly cost per patient was also lower in the adherent than in the non-adherent (relative ratio = 0.89, 95% CI 0.92-0.98), while patients who were lost to follow-up spent more on TB-related costs (2.52, 2.24-2.83) compared to those who completed the treatment. Conclusion: Non-adherent patients with TB spend more on treatment costs while they have poorer outcomes compared to adherent patients with TB. Improving patient adherence may lead to effective treatment outcomes and reduce the economic burden of TB. Policymakers and providers should consider commitment programs to improve patient's adherence.

Factors Associated with Elevated Tumor Necrosis Factor-α in Aqueous Humor of Patients with Open-Angle Glaucoma.

Tumor necrosis factor-alpha (TNF-α) is an important modulator of neuroinflammation, secreted from activated glial cells in response to intraocular stress. The purpose of this study was to investigate the clinical factors associated with elevated TNF-α and its level in aqueous humor of patients with open-angle glaucoma (OAG). Aqueous humor was collected from 73 OAG eyes, and TNF-α level was analyzed using the singleplex bead immunoassay method. Patients were divided into TNF-α-positive and TNF-α-negative groups according to the TNF-α level of 10 pg/mL, and baseline clinical characteristics were compared. The TNF-α-positive group showed higher baseline IOP, greater IOP fluctuation, and higher systolic blood pressure than the TNF-α-negative group (p = 0.007, p < 0.001, and p = 0.009, respectively). In the multivariate logistic regression analysis, IOP fluctuation (p = 0.037) and systolic blood pressure (p = 0.016) were all independently associated with positive TNF-α level. In normal-tension glaucoma (NTG) patients, presence of central scotoma (p = 0.029) was significantly associated with positive TNF-α level. In conclusion, positive TNF-α level in OAG patients was associated with greater IOP fluctuation and higher systolic blood pressure. In NTG patients, positive TNF-α level was associated with the presence of central scotoma. IOP factors and vascular factors, including blood pressure and presence of central scotoma, may indicate glaucoma pathogenesis related to TNF-α elevation in OAG patients.

Microvasculature Dropout and Development of Normal Tension Glaucoma in Glaucoma Suspects: The Normal Tension Glaucoma Suspect Cohort Study.

PURPOSE: To investigate the contribution of vessel parameters to identify normal tension glaucoma (NTG) suspects at risk of NTG development. DESIGN: Multicenter prospective cohort study. SUBJECTS: A total of 307 eyes of 307 NTG suspects having intraocular pressure within the normal range; a suspicious optic disc, but without definite localized retinal nerve fiber layer (RNFL) defects; and a normal visual field (VF). METHODS: To measure laminar vessel density (VD), the VD was measured in the intradisc region from images of the deep vascular layers of optical coherence tomography angiography (OCT-A). Conversion to NTG was defined either by a new localized RNFL defect in the superotemporal or inferotemporal region, or the presence of a glaucomatous VF defect on 2 consecutive tests according to the pattern deviation plots. MAIN OUTCOME MEASURE: Conversion to NTG. RESULTS: In total, 73 (23.8%) of the 307 NTG suspects converted to NTG during the follow-up period of 59.84 ± 12.44 months. Detection rate of microvasculature dropout (MvD) was significantly higher in NTG suspects who progressed to NTG (50.7%) than in those who did not (6.4%; P < .001). The macular deep VD (P = .006) and laminar deep VD (P = .004) were significantly lower in NTG suspects who progressed to NTG. The presence of MvD (P < .001) and lower laminar deep VD (P = .006) were significantly associated with NTG conversion. CONCLUSIONS: NTG suspects with baseline MvD or a lower laminar deep VD on OCT-A had a higher risk of conversion.

Predicting Visual Field Progression by Optical Coherence Tomography Angiography and Pattern Electroretinography in Glaucoma.

PRCIS: Reduced P50-N95 amplitude on pattern electroretinography (PERG) and the presence of microvasculature dropout (MvD) on optical coherence tomography angiography (OCT-A) at baseline were significant factors associated with visual field (VF) progression in predominantly normal tension glaucoma (NTG) patients. OBJECTIVE: We investigated the baseline demographics and ocular characteristics that predict future progression in glaucoma patients, including PERG and OCT-A parameters. METHODS: One Hundred forty eyes with open angle glaucoma that were prospectively enrolled and followed up for at least 3 years, and underwent at least 5 serial VF tests were included. Baseline PERG was performed, and N35, P50, and N95 latencies and amplitudes were obtained. Superficial vessel density at the macula and complete loss of microvasculature within the deep retinal layer of the parapapillary region (MvD) were evaluated from baseline OCT-A images. Eyes with a glaucomatous VF defect in either both hemifields within 24 points of a central 10 degrees of fixation, and with no VF abnormality in the nasal periphery outside 10 degrees of fixation, were considered to have isolated central scotoma. During follow-up, detected disc hemorrhage (DH) was recorded. Parameters associated with VF progression were determined using linear regression analysis of the mean deviation (MD) values, in combination with an event-based analysis using the Glaucoma Progression Analysis (GPA) software from the Humphrey Field Analyzer. "Likely progression" using GPA was considered to have glaucoma progression. RESULTS: Of the 140 eyes, 107 (76.4%) were NTG and 57 (40.7%) exhibited glaucoma progression as defined by Humphrey VF GPA. The MD slopes were -0.43±1.11 dB/y in the progressors and 0.59±1.27 dB/y in the nonprogressors ( P <0.001). Glaucoma patients with progression showed frequent MvD on OCT-A, isolated central scotoma, frequent DH, and reduced baseline P50-N95 amplitude compared with patients without progression. Age at diagnosis ( P =0.038) and baseline P50-N95 amplitude ( P =0.019) showed significant associations with the MD slope. The presence of MvD on OCT-A ( P <0.001) and baseline P50-N95 amplitude ( P =0.037) were significantly associated with VF progression on GPA. CONCLUSIONS: The presence of MvD and retinal ganglion cell dysfunction by PERG at baseline, DH or central scotoma were significant factors associated with VF progression in predominantly NTG patients. These patients should be monitored more closely.

TGFß and CIS Inhibition Overcomes NK-cell Suppression to Restore Antitumor Immunity.

Antibodies targeting "immune checkpoints" have revolutionized cancer therapy by reactivating tumor-resident cytotoxic lymphocytes, primarily CD8+ T cells. Interest in targeting analogous pathways in other cytotoxic lymphocytes is growing. Natural killer (NK) cells are key to cancer immunosurveillance by eradicating metastases and driving solid tumor inflammation. NK-cell antitumor function is dependent on the cytokine IL15. Ablation of the IL15 signaling inhibitor CIS (Cish) enhances NK-cell antitumor immunity by increasing NK-cell metabolism and persistence within the tumor microenvironment (TME). The TME has also been shown to impair NK-cell fitness via the production of immunosuppressive transforming growth factor ß (TGFß), a suppression which occurs even in the presence of high IL15 signaling. Here, we identified an unexpected interaction between CIS and the TGFß signaling pathway in NK cells. Independently, Cish- and Tgfbr2-deficient NK cells are both hyperresponsive to IL15 and hyporesponsive to TGFß, with dramatically enhanced antitumor immunity. Remarkably, when both these immunosuppressive genes are simultaneously deleted in NK cells, mice are largely resistant to tumor development, suggesting that combining suppression of these two pathways might represent a novel therapeutic strategy to enhance innate anticancer immunity.

Comparison between frequency-doubling technology perimetry and standard automated perimetry in early glaucoma.

This study aimed to find out the significance of the difference between frequency-doubling technology perimetry (FDT) and standard automated perimetry (SAP) in terms of the detected visual field (VF) damage, and evaluate associated factors to SAP-FDT difference in early glaucoma. Glaucoma patients in early stage (MD better than - 6.0 decibel, 96 eyes) were included in this cross-sectional study. We subtracted mean deviation (MD) and pattern standard deviation (PSD) of FDT from those of SAP, respectively. Additionally, we counted significantly depressed points of P < 5% and P < 1% on the pattern deviation probability plot of both FDT and SAP and defined eyes with significant SAP-FDT difference when the number of abnormal points were greater than 4 points on FDT. We measured lamina cribrosa depth (LCD) and lamina cribrosa curvature index (LCCI) for structural parameters of the optic nerve head from images using enhanced depth imaging of the optical coherence tomography (OCT). Peripapillary vessel density (VD) and presence of microvasculature dropout (MvD), the complete loss of choriocapillaris in localized regions of parapapillary atrophy, was evaluated using deep layer map of OCT angiography (OCT-A) for vascular parameters. Peripheral nasal step (PNS) group had an isolated glaucomatous VF defect within nasal periphery outside 10° of fixation. Parafoveal scotoma (PFS) group had an isolated glaucomatous VF defect within 12 points of a central 10˚ radius. Eyes with significant SAP-FDT difference showed higher detection of MvD on deep layer map of OCT-A, greater LCD, and greater LCCI (all P < 0.05, respectively). In logistic regression analysis, frequent presence of MvD, less presence of disc hemorrhage, and greater LCD were significantly associated with significant SAP-FDT difference. Sub-analysis was performed in eyes with PNS (50 eyes) and PFS (46 eyes). SAP-FDT difference of MD value showed positive association with peripapillary VD on deep layer of OCT-A, which was significant in eyes with PFS compared to eyes with PNS. SAP-FDT difference of PSD value showed negative association with LCCI and LCD, which was significant in eyes with PNS compared to eyes with PFS. Glaucomatous eyes classified by the difference of the detected VF damage on FDT versus SAP showed different clinical features. Greater SAP-FDT difference was significantly associated with structural parameters such as LCD and LCCI. Less SAP-FDT difference was associated with presence of disc hemorrhage and lower deep layer peripepillary VD. There is possibility to use the difference of SAP and FDT to identify associated risk factors in glaucoma patients.