A single-shot vaccine approach for the universal influenza A vaccine candidate M2e.

SignificanceAlthough the need for a universal influenza vaccine has long been recognized, only a handful of candidates have been identified so far, with even fewer advancing in the clinical pipeline. The 24-amino acid ectodomain of M2 protein (M2e) has been developed over the past two decades. However, M2e-based vaccine candidates have shortcomings, including the need for several administrations and the lack of sustained antibody titers over time. We report here a vaccine targeting strategy that has the potential to confer sustained and strong protection upon a single shot of a small amount of M2e antigen. The current COVID-19 pandemic has highlighted the importance of developing versatile, powerful platforms for the rapid deployment of vaccines against any incoming threat.

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.

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.

Display of Native Antigen on cDC1 That Have Spatial Access to Both T and B Cells Underlies Efficient Humoral Vaccination.

Follicular dendritic cells and macrophages have been strongly implicated in presentation of native Ag to B cells. This property has also occasionally been attributed to conventional dendritic cells (cDC) but is generally masked by their essential role in T cell priming. cDC can be divided into two main subsets, cDC1 and cDC2, with recent evidence suggesting that cDC2 are primarily responsible for initiating B cell and T follicular helper responses. This conclusion is, however, at odds with evidence that targeting Ag to Clec9A (DNGR1), expressed by cDC1, induces strong humoral responses. In this study, we reveal that murine cDC1 interact extensively with B cells at the border of B cell follicles and, when Ag is targeted to Clec9A, can display native Ag for B cell activation. This leads to efficient induction of humoral immunity. Our findings indicate that surface display of native Ag on cDC with access to both T and B cells is key to efficient humoral vaccination.

Lifetime survival and medical costs of lung cancer: a semi-parametric estimation from South Korea.

BACKGROUND: It is essential to have information on the disease burden of lung cancer at an individual level throughout the life; however, few such results have been reported. Thus, this study aimed to assess the lifetime disease burden in patients with lung cancer by assessing various factors, such as survival, years of life lost (YLL) and medical expenditure in South Korea based on real-world data and extrapolation. METHODS: Newly diagnosed lung cancer patients (n = 2919) in 2004-2010 were selected and observed until the end of 2015 using nationwide reimbursement claim database. The patients were categorised into the Surgery group, Chemo and/or Radiotherapy group (CTx/RTx), and Surgery+CTx/RTx according to their treatment modality. Age- and sex-matched control subjects were selected from among general population using the life table. The survival and cost data after diagnosis were analysed by a semi-parametric method, the Kaplan-Meier analysis for the first 100 months and rolling extrapolation algorithm for 101-300 months. YLL were derived from the difference in survival between patients and controls. RESULTS: Lifetime estimates (standard error) were 4.5 (0.2) years for patients and 14.5 (0.1) years for controls and the derived YLL duration was 10.0 (0.2) years. Lifetime survival years showed the following trend: Surgery (14.2 years) > Surgery+CTx/RTx (8.5 years) > CTx/RTx group (3.0 years), and YLL were increased as lifetime survival years decreased (2.3, 8.7, 12.2 years, respectively). The mean lifetime medical cost was estimated at 30,857 USD/patient. Patients in the Surgery group paid higher treatment cost in first year after diagnosis, but the overall mean cost per year was lower at 4359 USD compared with 7075USD of Surgery+CTx/RTx or 7626USD of CTx/RTx group. CONCLUSIONS: Lung cancer has resulted in about 10 years of life lost in overall patients. The losses were associated with treatment modality, and the results indicated that diagnosing lung cancer in patients with low stage disease eligible for surgery is beneficial for reducing disease burden in terms of survival and treatment cost per year throughout the life.

Choroidal Microvasculature Dropout Is Associated with Progressive Retinal Nerve Fiber Layer Thinning in Glaucoma with Disc Hemorrhage.

OBJECTIVE: We used OCT angiography (OCT-A) to investigate parapapillary choroidal microvasculature dropout (MvD) in glaucomatous eyes with or without disc hemorrhage (DH), and the association with changes in retinal nerve fiber layer (RNFL) thickness. DESIGN: An observational case-control study. PARTICIPANTS: Eighty-two open-angle glaucoma (OAG) eyes with DH and 68 OAG eyes without DH that underwent at least 4 serial OCT examinations were included. METHODS: MvD was defined as complete loss of microvasculature within the choroidal layer of the parapapillary region, as revealed by standardized assessment of OCTA-derived density maps of the vessels of the optic nerve head. The circumferential extent of MvD was measured on OCT-A images. The RNFL thinning rate was calculated using a linear mixed model. Kaplan-Meier survival analysis and the log-rank test were used to compare the cumulative risk ratio of progression between groups stratified by DH and MvD. MAIN OUTCOME MEASURES: MvD detection rate, the extent of MvD as measured by the MvD angle, and RNFL thinning rate. RESULTS: MvD was found in 38 (46.3%) eyes with DH at the prior DH site, which was found in only 20 (29.4%) eyes without DH, which was significantly different between the 2 groups (P = 0.025). Patients with progressive glaucoma exhibited significantly more MvD than the stable patients in both DH and no-DH groups. There were statistically significant differences between groups subdivided by the presence of DH and MvD as assessed by Kaplan-Meier analysis (log-rank test, P < 0.001). The angle of MvD was significantly greater in eyes with recurrent DH compared with eyes with single DH. Presence of DH, recurrent DH, and presence of MvD were factors associated with progressive RNFL thinning. CONCLUSIONS: We found that MvD was frequent in progressive OAG eyes on the choroidal map of OCT-A, which was more frequently found at the prior DH locations in eyes with DH. This means that observing the presence of MvD using OCT-A may provide a biomarker for glaucoma progression, especially in eyes with DH.

Combined Fractional Treatment of Acne Scars Involving Non-ablative 1,550-nm Erbium-glass Laser and Micro-needling Radiofrequency: A 16-week Prospective, Randomized Split-face Study.

An optimized therapeutic regimen involving a non-ablative fractionated laser or radiofrequency therapy for acne scars has not yet been established. To evaluate whether the combination of a non-ablative fractional laser (NAF) and fractional micro-needling radiofrequency (FMR) has clinical advantages for the treatment of atrophic acne scars compared with NAF alone, a 16-week prospective, randomized split-face study was performed. Each facial side of a patient was treated with 3 sessions of either NAF with FMR or NAF alone, with a 4-week interval between each session. Although both sides demonstrated significant decreases in the échelle d'évaluation clinique des cicatrices d'acné (ECCA) score, the facial side treated using the combination regimen demonstrated greater improvement in ECCA score regarding degree and onset time than the NAF-treated side. Histopathological and immunohistochemical results confirmed the clinical findings. This study demonstrated that a combination regimen involving NAF and FMR could be a viable option with satisfactory efficacy.

Association between Corneal Deformation Amplitude and Posterior Pole Profiles in Primary Open-Angle Glaucoma.

PURPOSE: To investigate the relationships between corneal deformation amplitude and posterior pole profiles, including ß-zone parapapillary atrophy (ßPPA), optic disc tilt ratio, torsion degree, and disc-foveal angle, in patients with glaucoma. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 107 patients with glaucoma. METHODS: Each patient underwent measurement of deformation amplitude with Corvis ST (Oculus Optikgeräte GmbH, Wetzlar, Germany), color optic disc photography, red-free retinal nerve fiber layer photography, axial length measurement, and 24-2 standard automated perimetry. From fundus photographs, the ßPPA area, optic disc tilt ratio, torsion degree, and disc-foveal angle were obtained. Pearson's correlation was used to determine the relationships between deformation amplitude and posterior pole profiles. To determine the factors associated with the posterior pole profiles, univariate and multivariate regression analyses were performed. MAIN OUTCOME MEASURES: Deformation amplitude, ßPPA area, optic disc tilt ratio, torsion degree, and disc-foveal angle. RESULTS: The study included 50 men (46.7%) and 57 women (53.3%). The mean age was 55.38±14.14 years. The mean tilt ratio, torsion degree, and disc-foveal angle were 1.16±0.14, 10.26±7.63°, and 7.60±3.64°, respectively. The mean ßPPA area was 18 211.00±28 725.53 pixels. The ßPPA (r = 0.391, P < 0.001) and tilt ratio (r = 0.408, P < 0.001) had significant relationships with deformation amplitude after adjusting for intraocular pressure (IOP). Torsion degree and disc-foveal angle showed no significant relationship with deformation amplitude. The ßPPA area was associated with deformation amplitude and axial length in both univariate (P = 0.008 and 0.006, respectively) and multivariate (P = 0.035 and <0.001, respectively) regression analyses. The tilt ratio was associated with deformation amplitude in univariate regression analysis (P = 0.002), but not in multivariate regression analysis. Axial length was significantly associated with the tilt ratio in both univariate (P < 0.001) and multivariate (P < 0.001) regression analyses. CONCLUSIONS: Deformation amplitude was associated with PPA area and tilt ratio in patients with glaucoma, although in our data set ßPPA area and tilt ratio were not associated with visual field mean deviation.

Alterations of the Lamina Cribrosa Are Associated with Peripapillary Retinoschisis in Glaucoma and Pachychoroid Spectrum Disease.

PURPOSE: To describe the findings of enhanced depth imaging (EDI) optical coherence tomography (OCT) of the lamina cribrosa (LC) in glaucoma and pachychoroid spectrum diseases associated with peripapillary retinoschisis. DESIGN: Retrospective, observational case series. PARTICIPANTS: A total of 16 patients from 1 institution. METHODS: Detailed medical case histories, optic disc and retinal imaging with EDI using the Spectralis OCT (Heidelberg Engineering, Heidelberg, Germany), and clinical course were reviewed for patients with peripapillary retinoschisis without a known predisposing condition. MAIN OUTCOME MEASURES: Clinical features and findings of the EDI OCT. RESULTS: Among the 16 eyes with peripapillary retinoschisis that had abnormal findings on EDI of the LC, 8 had glaucoma and 8 had pachychoroid spectrum diseases, including chronic central serous chorioretinopathy (CSC) (6 eyes), small pigment epithelium detachment (1 eye), and polypoidal choroidal vasculopathy (PCV) (1 eye). The abnormal LC findings were central or peripheral focal LC defects in eyes with glaucoma and LC disinsertions or peripheral focal LC defects in eyes with pachychoroid spectrum diseases. Central LC defects were related to inner layer retinoschisis, whereas LC disinsertions and peripheral LC defects were related to outer layer retinoschisis. The peripapillary retinoschisis did not show a topographic association with the underlying chronic CSC- or PCV-associated lesions. In 6 treated eyes with pachychoroid, peripapillary retinoschisis resolved along with subretinal fluid after anti-vascular endothelial growth factor injection in 4 eyes, whereas retinoschisis persisted after the resolution of subretinal fluid in 2 eyes. CONCLUSIONS: Enhanced depth imaging OCT of the LC demonstrated alterations associated with peripapillary retinoschisis, pachychoroid spectrum diseases, and glaucoma.

Prescribed drugs and polypharmacy in healthcare service users in South Korea: an analysis based on National Health Insurance Claims data.

OBJECTIVE: This study was conducted to analyze and compare the exposure to individually prescribed drugs and the prevalence of polypharmacy according to age group and concomitant disease in South Korea. METHODS: The use of prescribed drugs was evaluated according to average numbers of prescription drugs used daily during a year or month, using the Korean Health Insurance Claims Database, which is representative of over 90% of citizens, in 2010 and 2011. The use of prescribed drugs was also analyzed according to concomitant diseases and age. Polypharmacy was defined as the use of 5 or more drugs daily during a specific observation period, and proportions of polypharmacy users were calculated according to comorbidity and age group. RESULTS: The annual average numbers of daily used prescription drugs in 2010 and 2011 were 0.3 (SD = 0.5), 0.4 (SD = 0.7), 1.2 (SD = 1.5), and 2.3 (SD = 2.0) for people aged < 20 years, 20-49 years, 50-64 years, and ≥ 65 years, respectively. Proportions of individuals demonstrating polypharmacy increased with age and were 9.5% and 44.1% for elderly individuals in the year- and month-based analyses, respectively. The annual average number of daily medications used increased by ~2 drugs in the concomitant disease group, and the higher mortality group used a higher number of prescribed drugs than the lower mortality group. CONCLUSIONS: The results highlight the elevated burden of multi-medication in elderly patients, and the study found that prescribed drug use increased with age and the number of concomitant diseases.

Neuronal cell death in the inner retina and the influence of vascular endothelial growth factor inhibition in a diabetic rat model.

To inhibit vascular changes in diabetic retinopathy, inhibiting vascular endothelial growth factor (VEGF) has become a mainstay of the treatment of diabetic retinopathy. However, its effects on neuronal cells remain to be elucidated. We aimed to evaluate the effect of VEGF inhibition on neuronal cells in a streptozotocin-induced diabetic rat retina. VEGF inhibition was performed by intravitreal VEGF-A antibody injection. After anti-VEGF treatment, apoptosis in retinal ganglion cells (RGCs) increased, and novel apoptosis in amacrine and bipolar cells of the inner nuclear layer was observed by TUNEL staining. Phosphorylated Akt expression was significantly higher in RGCs but was decreased in neuronal cells of the inner nuclear layer after anti-VEGF treatment by Western blot analysis and immunohistochemical staining. These results demonstrate that VEGF inhibition significantly increased RGC apoptosis and neuronal cell apoptosis in the inner nuclear layer of a diabetic retina, which seems to consist primarily of amacrine and bipolar cells. The phosphorylated Akt pathway, which plays a neuroprotective role via VEGF, was significantly affected by VEGF inhibition in the inner nuclear layer, suggesting that neurotrophic factor deprivation is the main mechanism for neuronal cell death after inhibiting VEGF. The results of this study show that inhibiting VEGF may have detrimental effects on the apoptosis of neuronal cells in the inner layers of the diabetic retina.

Evolution of B cell responses to Clec9A-targeted antigen.

The response of B cells to Ag targeted to Clec9A on dendritic cells was followed using the hapten nitrophenol (NP) conjugated to rat Ig carrier. Injection of small amounts of NP conjugated to anti-Clec9A in the absence of adjuvants gave high and very prolonged Ab responses, approaching those obtained by high doses of nontargeted NP-protein conjugates with alum adjuvant. The response to NP-anti-Clec9A included the transient formation of germinal centers, maturation of Ab affinity, and some memory B cell formation. Serum Ab titers remained high 35 wk postimmunization, well after the initial follicular response had faded. The results suggest Clec9A-targeting strategies for improving Ab responses to vaccine Ags.

VEGF induces TGF-ß1 expression and myofibroblast transformation after glaucoma surgery.

Subconjunctival fibrosis at the surgical site determines the outcome of glaucoma surgery. Myofibroblast transformation has a significant role in fibrosis, and vascular endothelial growth factor (VEGF) is reported to trigger myofibroblast transformation by inducing transforming growth factor (TGF)-ß1. In the present study, we used IHC, Western blot analysis, enzyme-linked immunosorbent assay, and electron microscopy to determine the contribution of VEGF to myofibroblast transformation in subconjunctival fibrosis after glaucoma surgery. A rabbit trabeculectomy model was generated, and VEGF stimulation or VEGF inhibition was performed during surgery. VEGF stimulation induced TGF-ß1 expression in a dose-dependent manner. Down-regulation of epithelial markers (E-cadherin and ß-catenin) and up-regulation of mesenchymal marker (α-smooth muscle actin) were observed in the subconjunctival layers after trabeculectomy with VEGF stimulation. Up-regulations of Smad and Snail, which play a central role in myofibroblast transformation, were observed in the conjunctival and subconjunctival layers at the site of trabeculectomy. Electron microscopy revealed changes of the conjunctival epithelial cells, especially the presence of myofilaments and increased rough endoplasmic reticulum in the cytoplasm. Myofibroblast transformation was activated by VEGF stimulation and decreased by VEGF inhibition. These findings suggest that VEGF potentially affected the TGF-ß1/Smad/Snail pathway, thereby triggering myofibroblast transformation. Therapeutic approaches modulating VEGF may control myofibroblast transformation and reduce subconjunctival fibrosis after glaucoma surgery.

Glaucoma diagnostic ability of ganglion cell-inner plexiform layer thickness differs according to the location of visual field loss.

OBJECTIVE: To determine whether the ganglion cell-inner plexiform layer (GCIPL) or circumpapillary retinal nerve fiber layer (cpRNFL) is better at distinguishing eyes with early glaucoma from normal eyes on the basis of the the initial location of the visual field (VF) damage. DESIGN: Retrospective, observational study. PARTICIPANTS: Eighty-four patients with early glaucoma and 43 normal subjects were enrolled. The patients with glaucoma were subdivided into 2 groups according to the location of VF damage: (1) an isolated parafoveal scotoma (PFS, N = 42) within 12 points of a central 10 degrees in 1 hemifield or (2) an isolated peripheral nasal step (PNS, N = 42) within the nasal periphery outside 10 degrees of fixation in 1 hemifield. METHODS: All patients underwent macular and optic disc scanning using Cirrus high-definition optical coherence tomography (Carl Zeiss Meditec, Dublin, CA). The GCIPL and cpRNFL thicknesses were compared between groups. Areas under the receiver operating characteristic curves (AUCs) were calculated. MAIN OUTCOME MEASURES: Comparison of diagnostic ability using AUCs. RESULTS: The average and minimum GCIPL of the PFS group were significantly thinner than those of the PNS group, whereas there was no significant difference in the average retinal nerve fiber layer (RNFL) thickness between the 2 groups. The AUCs of the average (0.962) and minimum GCIPL (0.973) thicknesses did not differ from that of the average RNFL thickness (0.972) for discriminating glaucomatous changes between normal and all glaucoma eyes (P =0.566 and 0.974, respectively). In the PFS group, the AUCs of the average (0.988) and minimum GCIPL (0.999) thicknesses were greater than that of the average RNFL thickness (0.961, P =0.307 and 0.125, respectively). However, the AUCs of the average (0.936) and minimum GCIPL (0.947) thicknesses were lower than that of the average RNFL thickness (0.984) in the PNS group (P =0.032 and 0.069, respectively). CONCLUSIONS: The GCIPL parameters were more valuable than the cpRNFL parameters for detecting glaucoma in eyes with parafoveal VF loss, and the cpRNFL parameters were better than the GCIPL parameters for detecting glaucoma in eyes with peripheral VF loss. Clinicians should know that the diagnostic capability of macular GCIPL parameters depends largely on the location of the VF loss.

Glaucoma diagnostic accuracy of optical coherence tomography parameters in early glaucoma with different types of optic disc damage.

PURPOSE: To compare the initial visual field (VF) defect pattern and the spectral-domain optical coherence tomography (OCT) parameters and investigate the effects of distinct types of optic disc damage on the diagnostic performance of these OCT parameters in early glaucoma. DESIGN: Retrospective, observational study. PARTICIPANTS: A total of 138 control eyes and 160 eyes with early glaucoma were enrolled. The glaucomatous eyes were subdivided into 4 groups according to the type of optic disc damage: focal ischemic (FI) group, myopic (MY) group, senile sclerotic (SS) group, and generalized enlargement (GE) group. METHODS: The values of total deviation (TD) maps were analyzed, and superior-inferior (S-I) differences of TD were calculated. The optic nerve head (ONH) parameters, peripapillary retinal nerve fiber layer (pRNFL), and ganglion cell-inner plexiform layer (GCIPL) thicknesses were measured. MAIN OUTCOME MEASURES: Comparison of diagnostic ability using area under the receiver operating characteristic curves (AUCs). RESULTS: The S-I and central S-I difference of the FI group were larger than those of the GE group. The rim area of the SS group was larger than those of the 3 other groups, and the vertical cup-to-disc ratio (CDR) of the GE group was larger than that of the MY group. In addition, the minimum and inferotemporal GCIPL thicknesses of the FI group were smaller than those of the GE group. The AUC of the rim area (0.89) was lower than that of the minimum GCIPL (0.99) in the SS group, and the AUC of the vertical CDR (0.90) was lower than that of the minimum GCIPL (0.99) in the MY group. Furthermore, the AUCs of the minimum GCIPL thicknesses of the FI and MY group were greater than those of the average pRNFL thickness for detecting glaucoma, as opposed to the SS and GE. CONCLUSIONS: The OCT parameters differed among the 4 groups on the basis of the distinct optic disc appearance and initial glaucomatous damage pattern. Clinicians should be aware that the diagnostic capability of OCT parameters could differ according to the type of optic disc damage in early glaucoma.

Macular ganglion cell-inner plexiform layer thinning in patients with visual field defect that respects the vertical meridian.

The aim of this work is to compare the thinning patterns of the ganglion cell inner-plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) as measured using Cirrus high-definition optical coherence tomography (HD-OCT) in patients with visual field (VF) defects that respect the vertical meridian. Twenty eyes of 11 patients with VF defects that respect the vertical meridian were enrolled retrospectively. The thicknesses of the macular GCIPL and pRNFL were measured using Cirrus HD-OCT. The 5 and 1% thinning area index (TAI) was calculated as the proportion of abnormally thin sectors at the 5 and 1% probability level within the area corresponding to the affected VF. The 5 and 1% TAI were compared between the GCIPL and pRNFL measurements. The color-coded GCIPL deviation map showed a characteristic vertical thinning pattern of the GCIPL, which is also seen in the VF of patients with brain lesions. The 5 and 1% TAI were significantly higher in the GCIPL measurements than in the pRNFL measurements (all p < 0.01). Macular GCIPL analysis clearly visualized a characteristic topographic pattern of retinal ganglion cell (RGC) loss in patients with VF defects that respect the vertical meridian, unlike pRNFL measurements. Macular GCIPL measurements provide more valuable information than pRNFL measurements for detecting the loss of RGCs in patients with retrograde degeneration of the optic nerve fibers.

Effect of Bromfenac on Reducing Neuroinflammation in an Ischemia-Reperfusion Glaucoma Model.

In the context of glaucoma, intraocular pressure (IOP) and age are recognized as the primary factors contributing to its onset and progression. However, significant reductions in IOP fail to completely halt its advancement. An emerging body of literature highlights the role of neuroinflammation in glaucoma. This study aimed to explore Bromfenac's anti-inflammatory properties in mitigating neuroinflammation associated with glaucoma using an ischemia-reperfusion (IR) glaucoma model. Bromfenac's impact on microglia and astrocytes under pressure was assessed via Western blotting and an enzyme-linked immunosorbent assay. Immunohistochemical staining was used to evaluate glial activation and changes in inflammatory marker expression in the IR model. Bromfenac led to the downregulation of inflammatory markers, which were elevated in the conditions of elevated pressure, and necroptosis markers were downregulated in astrocytes. In the IR model, elevated levels of GFAP and Iba-1 indicated glial activation. Following Bromfenac administration, levels of iNOS, COX-2, and PGE2-R were reduced, suggesting a decrease in neuroinflammation. Furthermore, Bromfenac administration in the IR model resulted in the improved survival of retinal ganglion cells (RGCs) and preservation of retinal function, as demonstrated by immunohistochemical staining and electroretinography. In summary, Bromfenac proved effective in diminishing neuroinflammation and resulted in enhanced RGC survival.

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 Staging of Prostaglandin-Associated Periorbitopathy Syndrome in Glaucoma: A Review from Asia.

PURPOSE: Topical prostaglandin analogues are commonly used to treat patients with glaucoma, but may cause periocular and periorbital complications known as prostaglandin-associated periorbitopathy syndrome (PAPS). METHODS: A literature review was conducted on PAPS. Given the lack of consensus on grading PAPS, glaucoma specialists from Asia convened to evaluate current PAPS grading systems and propose additional considerations in grading PAPS. RESULTS: Existing grading systems are limited by the lack of specificity in defining grades and consideration for patients' subjective perception of symptoms. Patient-reported symptoms (e.g., via a self-assessment tool) and additional clinical assessments (e.g., exophthalmometry, lid laxity, differences between tonometry results, baseline measurements, and external ocular photographs) would be beneficial for grading PAPS systematically. CONCLUSIONS: Effective management of PAPS could be facilitated by a common clinical grading system to consistently and accurately diagnose and characterise symptoms. Further research is required to validate specific recommendations and approaches to stage and monitor PAPS.

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.