Evaluation of Optic Nerve Head Microcirculation in Open-Angle Glaucoma Patients with Unilateral Visual Field Defect.

INTRODUCTION: Microcirculation of optic nerve head (ONH) in open-angle glaucoma (OAG) patients with unilateral visual field (VF) loss has yet to be fully investigated, especially the perimetrically unaffected fellow eyes. METHODS: Thirty-eight OAG patients with VF defect in one eye and normal VF in the other eye, and thirty-one healthy participants were analyzed. All participants underwent laser speckle flowgraphy (LSFG), spectral-domain optical coherence tomography (SD-OCT) imaging, and VF test for further analyses. LSFG measurements included mean blur rate in all area of ONH (MA), big vessel area of ONH (MV), and tissue area of ONH (MT). SD-OCT parameters included circumpapillary retinal nerve fiber layer (cpRNFL) thickness and macula thicknesses. The difference of LSFG and SD-OCT indices between glaucoma patients and healthy controls were compared. The diagnostic accuracy was analyzed with the areas under the receiver operating characteristic curves (AROCs). RESULTS: Global cpRNFL thickness and macular thickness in unaffected eyes of OAG patients were higher than their fellow eyes and lower than healthy eyes. MA and MV in healthy eyes and unaffected eyes were significantly higher than in affected eyes. MT in unaffected eyes of OAG patients was higher than in their fellow affected eyes but lower than in healthy eyes. The AROCs were highest for cpRNFL (0.925), followed by macular thickness (0.838), and MT (0.834). CONCLUSIONS: ONH microcirculation in perimetrically unaffected fellow eyes was decreased in OAG patients with unilateral VF loss. LSFG can detect changes of ONH in high-risk eyes before detectable VF damage, which may reflect the vascular pathophysiology for glaucoma.

The severity of visual field defect and the defective angles of localized retinal nerve fiber layer using a novel approach.

BACKGROUND/PURPOSE: A modified novel analytical method for evaluating photographic retinal nerve fiber layer defect (RNFLD) was developed for the purpose of estimating the severity of early glaucomatous eyes. This new method was then compared with the original method, as described below, in relation to the visual field defect severity. METHODS: The clinical records of 47 glaucomatous eyes with qualified photographs were obtained from a prior retrospective study. The reference point of the angle was set at the center of the optic disc center (COD group) and the central vessel trunk (COV group). Angle α was the angular width between the fovea and the proximity of RNFLD, while angle ß (+c) was the sum of the angular width(s) of localized RNFLD. The correlation between the visual field parameters and the angles of RNFLD in the above two groups were analyzed. RESULTS: There were significant differences in angle α (p = 0.001) and angle ß (+c) (p = 0.016) between the two groups. Angle ß (+c) showed significant correlation with MD (p = 0.012), PSD (p = 0.035), VFI (p = 0.042) and MD (p = 0.016), PSD (p = 0.035), VFI (p = 0.031) in the COD and COV group, respectively. No correlation was found between angle α and the presence of central scotoma in both groups. CONCLUSION: Our novel method was more convenient in a clinical setting and noninferior to the original method.

Defective angles of localized retinal nerve fiber layer reflect the severity of visual field defect- a cross-sectional analysis.

BACKGROUND: In order to detect glaucomatous optic nerve damages early on and evaluate the severity of glaucoma, a previously developed analytic method based on photographic retinal nerve fiber layer (RNFL) angle defect was proposed. However, the correlation between these defective angles and the severity of visual field defect has not been verified. This study aimed to confirm the correlation described above. METHODS: We reviewed a total of 227 glaucomatous eyes (38 enrolled, 189 excluded) during an interval of 5 years. The angles of all eyes were measured on RNFL photograph, of which angle α is the angular width between the macula center and the proximity of RNFL defect, and angle ß (+c) is the sum of angular width(s) of localized RNFL defect. The severity of visual field defect was determined by mean deviation (MD), pattern standard deviation (PSD), and visual field index (VFI). Correlation analysis was performed on angle α and angle ß (+c) with the presence of central scotoma and visual field defect parameters, respectively. RESULTS: Angle ß (+c) showed significant correlation with MD (P = 0.007), PSD (P = 0.02), VFI (P = 0.03), and average RNFL thickness (P = 0.03). No correlation was found between angle α and the presence of central scotoma. CONCLUSIONS: In conclusion, measuring the angular width of localized RNFL defect is a viable method for determining the severity of visual field defect.

The difference of surgical outcomes between manifest exotropia and esotropia.

PURPOSE: To determine the factors that affect ocular alignment and binocular sensory functions after strabismus surgery and compare surgical outcomes between manifest exotropia (XT) and esotropia (ET). METHODS: In a retrospective study, 41 XT and 17 ET patients who had undergone strabismus surgery were recruited. Information on type and duration of strabismus, age at onset of deviation and surgery, pre- and postoperative strabismus deviation angles, and binocular sensory functions including stereoacuity and macular fusion capacity was recorded. RESULTS: In all patients, the ocular alignment and binocular sensory functions improved with time following surgery. Residue strabismus deviation angles (≦ 10 prism diopters) at postoperative 1 month determined the final successful ocular alignment. In patients with final excellent binocular sensory functions, XT group restored macular fusion capacity and stereoacuity at postoperative 1 month, but ET group regained macular fusion capacity at postoperative 1 month and then restored stereoacuity at postoperative 3 months. Though XT patients showed better pre- and postoperative stereoacuity than ET patients, patients with successful ocular alignment had an odd of 4.5 in XT group and 22.5 in ET group to achieve excellent and fair binocular sensory functions. CONCLUSION: Surgical correction of strabismus could improve ocular alignment and binocular sensory functions in patients with manifest strabismus, regardless of onset age, strabismus duration, or type. Postoperative 1-month status may help to predict the final motor and sensory outcomes. ET patients would benefit more final successful ocular alignment and excellent binocular sensory functions from early surgery and maintaining postoperative small deviation angle than XT patients.

Macular Diagnostic Ability in OCT for Assessing Glaucoma in High Myopia.

PURPOSE: To compare the diagnostic abilities of spectral-domain optical coherence tomography (SD-OCT; Spectralis OCT) and time-domain OCT (TD-OCT; Stratus OCT). Changes in macular parameters in highly myopic eyes of glaucoma patients and highly myopic eyes of glaucoma suspects were evaluated and compared. METHODS: We collected data from 72 highly myopic eyes (spherical equivalent, ≤-6.0D). Forty-one eyes had perimetric glaucoma and 31 eyes were suspected to have glaucoma (control group). All eyes underwent SD-OCT and TD-OCT imaging. Area under the receiver operating characteristic (AUROC) curve and sensitivity were examined on macular volume and thickness parameters at a fixed specificity and compared between groups. RESULTS: The highest TD-OCT AUROC curves were found using outer inferior sector macular thickness (AUROC curve, 0.911) and volume (AUROC curve, 0.909). The highest SD-OCT AUROC curves were found using outer inferior region thickness (AUROC curve, 0.836) and volume (AUROC curve, 0.834). The difference between the two imaging modalities was not statistically significant (thickness, p = 0.141; volume, p = 0.138). The sensitivity of TD-OCT macular outer inferior average thickness was highest and was 88.2%, with a specificity of 80.4%. The sensitivity of TD-OCT average volume measurements in this same region was 76.5%, with a specificity of 91.3%. The SD-OCT average thickness measurements also had the highest sensitivity in this region, which was 78.6%, with a specificity of 82.1%. The SD-OCT volume measurements had a sensitivity of 67.9%, with a specificity of 92.3%. CONCLUSIONS: Both SD-OCT and TD-OCT measurements of outer inferior macular thickness and volume can differentiate between eyes of glaucoma patients and glaucoma suspects with high myopia. These independent predictors all had good sensitivity. Based on our results, SD-OCT and TD-OCT have similar diagnostic abilities. These parameters may provide useful additional data in highly myopic eyes to complement standard glaucoma diagnosis tools.

The role of Atg5 gene in tumorigenesis under autophagy deficiency conditions.

Autophagy is a self-recycling machinery to maintain cellular homeostasis by degrading harmful materials in the cell. Autophagy-related gene 5 (Atg5) is required for autophagosome maturation. However, the role of Atg5 in tumorigenesis under autophagy deficient conditions remains unclear. This study focused on the autophagy-independent role of Atg5 and the underlying mechanism in tumorigenesis. We demonstrated that knockout of autophagy-related genes including Atg5, Atg7, Atg9, and p62 in mouse embryonic fibroblast (MEF) cells consistently decreased cell proliferation and motility, implying that autophagy is required to maintain diverse cellular functions. An Atg7 knockout MEF (Atg7-/- MEF) cell line representing deprivation of autophagy function was used to clarify the role of Atg5 transgene in tumorigenesis. We found that Atg5-overexpressed Atg7-/-MEF (clone A) showed increased cell proliferation, colony formation, and migration under autophagy deficient conditions. Accordingly, rescuing the autophagy deficiency of clone A by overexpression of Atg7 gene shifts the role of Atg5 from pro-tumor to anti-tumor status, indicating the dual role of Atg5 in tumorigenesis. Notably, the xenograft mouse model showed that clone A of Atg5-overexpressed Atg7-/- MEF cells induced temporal tumor formation, but could not prolong further tumor growth. Finally, biomechanical analysis disclosed increased Wnt5a secretion and p-JNK expression along with decreased ß-catenin expression. In summary, Atg5 functions as a tumor suppressor to protect the cell under normal conditions. In contrast, Atg5 shifts to a pro-tumor status under autophagy deprivation conditions.

Revealing potential Rab proteins participate in regulation of secretory autophagy machinery.

Autophagy can be classified as degradative and secretory based on distinct functions. The small GTPase proteins Rab8a and Rab37 are responsible for secretory autophagy-mediated exocytosis of IL-1ß, insulin, and TIMP1 (tissue inhibitor of 54 metalloproteinase 1). Other Rab family members participating in secretory autophagy are poorly understood. Herein, we identified 26 overlapped Rab proteins in purified autophagosomes of mouse pancreatic ß-cell "Min-6" and human lung cancer cell "CL1-5-Q89L" with high secretory autophagy tendency by LC-MS/MS proteomics analysis. Six Rab proteins (Rab8a, Rab11b, Rab27a, Rab35, Rab37, and Rab7a) were detected in autophagosomes of four cell lines, associating them with autophagy-related vesicle trafficking. We used CL1-5-Q89L cell line model to evaluate the levels of Rab proteins colocalization with autophagy LC3 proteins and presence in purified autophagosomes. We found five Rab proteins (Rab8a, Rab11b, Rab27a, Rab35, and Rab37) are highly expressed in the autophagosome compared to the normal control by immunoblotting under active secretion conditions. However, only Rab8a, Rab35, and Rab37 showing high colocalization with LC3 protein by cofocal microscopy. Despite the discrepancy between the image and immunoblotting analysis, our data sustains the speculation that Rab8a, Rab11b, Rab27a, Rab35, and Rab37 are possibly associated with the secretory autophagy machinery. In contrast, Rab7a shows low colocalization with LC3 puncta and low level in the autophagosome, suggesting it regulates different vesicle trafficking machineries. Our findings open a new direction toward exploring the role of Rab proteins in secretory autophagy-related cargo exocytosis and identifying the cargoes and effectors regulated by specific Rab proteins.

The Prevalence of Optical Coherence Tomography Artifacts in High Myopia and its Influence on Glaucoma Diagnosis.

PRCIS: Optical coherence tomography (OCT) artifacts occur much more frequently in highly myopic eyes compared with non-highly myopic eyes. A longer axial length is predictive of having OCT artifacts. PURPOSE: To investigate the types and prevalence of artifacts on OCT scans in patients with and without high myopia. MATERIALS AND METHODS: Patients were divided into 4 groups based on whether they had glaucoma and/or high myopia. All peripapillary retinal nerve fiber layer (RNFL) scan images were individually inspected for the presence of artifacts. RESULTS: Two hundred twenty-six patients were enrolled. The prevalence of OCT artifacts was 18.6% in non-high myopes and 51.9% in high myopes ( P <0.001). Outer RNFL border misidentification was the most common type of artifact for non-high myopes, whereas retinal pathology-related artifact was the most common in high myopes. Univariable regression analysis showed that a longer axial length [odds ratio (OR) 1.815, P <0.001], a higher pattern standard deviation (OR 1.194, P <0.001), and thinner RNFL (OR 0.947, P <0.001) were predictive factors for the presence of OCT artifacts. The diagnostic capability of global RNFL thickness before and after manual correction of segmentation errors did not differ for both non-high myopes [area under the receiver operating curve 0.915-0.913 ( P =0.955)] and high myopes [area under the receiver operating curve 0.906-0.917 ( P =0.806)]. CONCLUSION: The prevalence of OCT artifacts was the highest in patients with both high myopia and glaucoma. The most common type of OCT artifact is different for non-high myopes and high myopes. Physicians need to be aware of a higher likelihood of OCT artifacts, particularly in those with a longer axial length, worse visual field, and thinner RNFL thickness.

Homocysteine Levels in Severe OSA Patients Before and After TORS-OSA Surgery.

OBJECTIVE: The increased risk of cardiovascular diseases owing to a high level of serum homocysteine has been widely reported. Literature has demonstrated that patients with obstructive sleep apnea/hypopnea syndrome (OSA) had a higher homocysteine level than control group. This study aimed to investigate the alteration of serum homocysteine levels in severe OSA patients receiving transoral robotic surgery (TORS). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic medical center. METHODS: Data of polysomnography (PSG) and serum homocysteine levels before and at least 3 months after the surgery were collected and analyzed via paired t tests. A subgroup analysis based on the preoperative homocysteine level (≥15 mcmol/L, as hyperhomocysteinemia group) was conducted to compare the intergroup differences of homocysteine decrease. Pearson's correlation was used to survey the relationships between the changes of major PSG parameters and the levels of homocysteine decrease at baseline and after TORS-OSA surgery. RESULTS: Two hundred sixty-one patients with severe OSA were enrolled. There were significant improvements in major PSG parameters after TORS-OSA surgery. Homocysteine levels significantly decreased from 12.1 ± 3.9 to 11.4 ± 3.7 mcmol/L (difference = -0.7 ± 2.8 mcmol/L, p = .001) postoperatively, which was shown in the hyperhomocysteinemia group (difference = -2.9 ± 4.7 mcmol/L, p = .007) to a greater extent. Pearson's correlation revealed that ΔODI (oxygen desaturation index/h) was the predominant estimate with a positive association with Δhomocysteine (r = 0.525, p = .012). CONCLUSION: TORS-OSA surgery could decrease homocysteine levels in OSA patients. The effects were more relevant in severe OSA patients with abnormal preoperative homocysteine levels.

Decreased Peripapillary and Macular Vascular Densities in Patients with Moderate/Severe Obstructive Sleep Apnea/Hypopnea Syndrome.

Purpose: To compare peripapillary and macular vascular densities (PVDs and MVDs) between patients with obstructive sleep apnea/hypopnea syndrome (OSA) and control subjects with symptoms of sleep-related breathing disorders only by swept-source optical coherence tomography angiography (OCTA). Participants and Methods: In this prospective study, 192 participants underwent a full-night polysomnography to determine OSA severity and subsequently received OCTA measurements as well as AngioTool software analysis. Results: A total of 146 patients with OSA (51 mild, 43 moderate, 52 severe) and 24 control subjects (apnea/hypopnea index, AHI <5) were enrolled. PVDs and MVDs in the superficial and choroidal layers were significantly different among the four groups. When participants with simple snoring/mild OSA (AHI <15) were grouped together and compared with moderate/severe OSA (AHI ≥15), PVDs were significantly lower for the latter group in the superficial layer (p = 0.0003), deep layer (p = 0.004), and choroidal layer (p = 0.003). MVDs were also lower for the moderate/severe OSA group in the superficial (p = 0.012) and choroidal layer (p = 0.004). Negative correlations were identified between AHI and PVDs in the superficial layer (ρ = -0.257, p = 0.0007), deep layer (ρ = -0.197, p = 0.0102) and choroidal layer (ρ = -0.220, p = 0.0039) and between AHI and MVDs in the superficial layer (ρ = -0.199, p = 0.0094) and choroid layer (ρ = -0.186, p = 0.0152). Conclusion: PVDs and MVDs were significantly lower in patients with moderate/severe OSA as compared to subjects with simple snoring/mild OSA. Furthermore, decreased PVDs and MVDs significantly correlated with OSA severity.

Formosanin C suppresses cancer cell proliferation and migration by impeding autophagy machinery.

Formosanin C (FC) is a natural compound extracted from Paris formosana Hayata with anticancer activity. FC induces both autophagy and apoptosis in human lung cancer cells. FC-induced depolarization of mitochondrial membrane potential (MMP) may trigger mitophagy. In this study, we clarified the effect of FC on autophagy, mitophagy, and the role of autophagy in FC-related cell death and motility. We found FC caused the continuous increase of LC3 II (representing autophagosomes) from 24 to 72 h without degradation after treatment of lung and colon cancer cells, indicating that FC blocks autophagic progression. In addition, we confirmed that FC also induces early stage autophagic activity. Altogether, FC is not only an inducer but also a blocker of autophagy progression. Moreover, FC increased MMP accompanied by overexpression of COX IV (mitochondria marker) and phosphorylated Parkin (p-Parkin, mitophagy marker) in lung cancer cells, but no colocalization of LC3 with COX IV or p-Parkin was detected under confocal microscopy. Moreover, FC could not block CCCP (mitophagy inducer)-induced mitophagy. These results imply that FC disrupts mitochondria dynamics in the treated cells, and the underlying mechanism deserves further exploration. Functional analysis reveals that FC suppresses cell proliferation and motility through apoptosis and EMT-related pathway, respectively. In conclusion, FC acts as an inducer as well as a blocker of autophagy that results in cancer cell apoptosis and decreased motility. Our findings shed the light on the development of combined therapy with FC and clinical anticancer drugs for cancer treatment.

Inflammatory biomarkers of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in 563 severe OSA patients before and after surgery.

BACKGROUND: Evidence has proved that high neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were risk factors for cardiovascular comorbidities. The alterations of NLR and PLR following obstructive sleep apnea (OSA) treatment were under studied and thus should be investigated. This study aimed to evaluate the changes of inflammatory biomarkers including NLR and PLR in severe OSA patients after surgical interventions of the upper airway, and their relationships with improvements in polysomnographic (PSG) parameters. METHODS: This retrospective cohort study included 563 consecutive severe OSA patients at a tertiary academic medical center who received OSA surgery, as well as underwent pre- and post-operative polysomnographic (PSG) examinations and blood tests. The changes of major PSG estimates, NLR, and PLR before and at least 3 months after OSA surgery were analyzed using paired t-tests with subgroup analyses. Pearson's correlations were performed to discover which PSG parameter contributed to the improvement of the values. RESULTS: After OSA surgery, the major PSG estimates, NLR and PLR dropped significantly in the overall population. In those with a higher preoperative NLR (pre-operative NLR≧3) and PLR (pre-operative PLR≧150), the mean (SD) difference of NLR (- 0.8 [1.6], 95% CI - 1.5 to - 0.2) and PLR (- 41.6 [40], 95% CI - 52.8 to - 30.5) were even more substantial. The changes of the "apnea, longest (r = 0.298, P = .037)" and "hypopnea, longest (r = 0.321, P = .026)" were found significantly related to the improvement of PLR. CONCLUSION: NLR and PLR did significantly drop in severe OSA patients following OSA surgery, and this could be related to the alterations of sleep indices. The findings could possess clinical importance for severe OSA patients after OSA surgeries in reducing possible OSA-associated cardiovascular comorbidities.

Temporal transition trends of cord blood lead levels in various human development index countries and in the Taipei metropolitan area.

Since low-level lead exposure is still of concern for neonates, it is worth further characterizing the temporal transition trends of cord blood lead levels (CBLLs) globally and locally in Taipei, Taiwan, after the cessation of leaded gasoline use. A literature review on CBLLs around the world was performed by searching three databanks, i.e., PubMed, Google Scholar and Web of Science, with the search keywords "cord blood" combined with "lead" or "Pb" for studies published from 1975 to May 2021. In total, 66 articles were included. Linear regressions for the reciprocal of sample size weighed CBLLs against calendar year presented a high r2 value (0.722) for the very high Human Development Index (HDI) countries and a moderate r2 value (0.308) for the combined high and medium HDI countries. The predicted CBLLs in 2030 and 2040 were 6.92 (95% CI: 6.02-7.81) µg/L and 5.85 (95% CI: 5.04-6.66) µg/L, respectively, for the very high HDI countries and 13.10 (95% CI: 7.12-19.09) µg/L and 10.63 (95% CI: 5.37-15.89) µg/L, respectively, for the combined high and medium HDI countries. To characterize the CBLL transitions in the Great Taipei metropolitan area, data from five studies conducted from 1985 to 2018 were employed. Although the results of the early four studies indicated that the Great Taipei metropolitan area did not reach the pace in CBLL reduction among the very high HDI countries, the CBLLs of the latest study during 2016-2018 were pretty low (8.1 ± 4.5 µg/L), approximately 3 years in advance of the very high HDI countries as one group to reach this low CBLL. In conclusion, further effective reduction in environmental lead exposure is challenging and must be based on the efforts from the aspects reflected by the HDI index compositions, i.e., economics, education and health, mostly implying health disparity and inequality.

High G9a Expression in DLBCL and Its Inhibition by Niclosamide to Induce Autophagy as a Therapeutic Approach.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is a malignant lymphoid tumor disease that is characterized by heterogeneity, but current treatment does not benefit all patients, which highlights the need to identify oncogenic genes and appropriate drugs. G9a is a histone methyltransferase that catalyzes histone H3 lysine 9 (H3K9) methylation to regulate gene function and expression in various cancers. METHODS: TCGA and GTEx data were analyzed using the GEPIA2 platform. Cell viability under drug treatment was assessed using Alamar Blue reagent; the interaction between G9a and niclosamide was assessed using molecular docking analysis; mRNA and protein expression were quantified in DLBCL cell lines. Finally, G9a expression was quantified in 39 DLBCL patient samples. RESULTS: The TCGA database analysis revealed higher G9a mRNA expression in DLBCL compared to normal tissues. Niclosamide inhibited DLBCL cell line proliferation in a time- and dose-dependent manner, reducing G9a expression and increasing p62, BECN1, and LC3 gene expression by autophagy pathway regulation. There was a correlation between G9a expression in DLBCL samples and clinical data, showing that advanced cancer stages exhibited a higher proportion of G9a-expressing cells. CONCLUSION: G9a overexpression is associated with tumor progression in DLBCL. Niclosamide effectively inhibits DLBCL growth by reducing G9a expression via the cellular autophagy pathway; therefore, G9a is a potential molecular target for the development of therapeutic strategies for DLBCL.

Alterations of Ocular Surface and Tear Film in Patients with Obstructive Sleep Apnea/Hypopnea Syndrome.

Purpose: Obstructive sleep apnea/hypopnea syndrome (OSA) results in repeated oxygen desaturation, repeated arousals, and episodic nocturnal activation of sympathetic nervous system during sleep. Untreated OSA is strongly associated with an increase of cardio- and cerebrovascular disorders, as well as the damages of ophthalmological microstructures. However, previous literature only simply studied the association between the ophthalmic disorders and OSA. In the present study, we first investigated the alterations of ocular surface and tear film non-invasively with the innovated corneal topographer in untreated OSA patients and normal control subjects. Furthermore, we analyzed in depth whether the correlations between OSA severity and ocular surface exams exist. Participants and Methods: Participants underwent a full-night polysomnography to determine OSA occurrence and severity. All participants subsequently received Ocular Surface Disease Index questionnaire and comprehensive ocular exams, including floppy eyelid syndrome (FES) assessment, oculus scan for tear meniscus height, non-invasive keratograph tear film breakup time (NIKBUT), and ocular surface redness, endothelial cell density, and corneal fluorescein staining. Results: One hundred eighty-one participants were prospectively enrolled in the study. FES was found in 11.5% of the normal control group and 60.0% of the severe OSA group (p=0.0005). There were significant differences in the first-NIKBUT (F-NIKBUT) (p < 0.0001), average-NIKBUT (A-NIKBUT) (p = 0.0007), and redness scores over the nasal bulbar (p = 0.032), temporal bulbar (p < 0.0001), nasal limbal (p = 0.014), and temporal limbal (p < 0.0001) areas among the four groups. F-NIKBUT and A-NIKBUT were significantly shorter in the moderate/severe OSA group (apnea/hypopnea index (AHI) ≥15) than in the normal/mild OSA group (AHI <15) (both p < 0.0001). The redness scores over the temporal bulbar (p < 0.0001) and temporal limbal (p < 0.0001) areas were also significantly different in these two OSA groups. Moreover, F-NIKBUT and A-NIKBUT negatively correlated with AHI. Nasal bulbar redness, temporal bulbar redness, nasal limbal redness, and temporal limbal redness positively correlated with AHI. Conclusion: OSA patients had higher occurrence of FES. The NIKBUT was significantly shorter, and the temporal conjunctival redness scores over bulbar and limbal areas were higher in the moderate/severe OSA group than in the normal/mild OSA group. NIKBUT and conjunctival hyperemia significantly correlated with the severity of untreated OSA.

Effects of TORS-OSA Surgery on Lower Urinary Tract Symptoms, Overactive Bladder Symptoms, and Nocturia in Male Patients with Obstructive Sleep Apnea/Hypopnea Syndrome.

Objective: To determine the presence of lower urinary tract symptoms (LUTS), and overactive bladder (OAB) symptoms in men with obstructive sleep apnea/hypopnea syndrome (OSA) and the effects of transoral robotic surgery (TORS) for the treatment of OSA on these conditions. Materials and Methods: One hundred twenty-three patients with a diagnosis of OSA were prospectively enrolled. The evaluations of LUTS and OAB symptoms were based on self-administered questionnaires containing international prostate symptom score (IPSS) and OAB symptom score (OABSS), respectively. Men with an OABSS urgency score of ≥2 and sum score of ≥3 were considered to have OAB. The therapeutic outcomes were assessed at baseline, and 12 weeks after TORS-OSA Surgery. Results: There were significant differences in IPSS, and OABSS according to OSA severity. After TORS-OSA surgery, significant improvements on OSA severity, daytime quality of life (QoL) and nighttime sleep quality were observed. TORS-OSA surgery was also associated with a statistically significant improvement of LUTS, LUTS QoL score, and OAB symptoms (IPSS 22.1% decrease; IPSS QoL score 21.1% decrease; OABSS17.4% decrease) at post-operative 3 months' follow-up. The presence of OAB, and severe nocturia was significantly reduced from 22.8% to 11.4% (p=0.001), 5.7% to 0.8% (p=0.031) after TORS-OSA surgery. There were no patients who had acute airway compromise or massive bleeding peri- or post-operatively. Conclusion: TORS upper airway surgery could improve LUTS and OAB symptoms on male patients with OSA in addition to improvement of major parameters of sleep study and sleep-related QoL.

Systematic review and updated meta-analysis of multi-level surgery for patients with OSA.

OBJECTIVES: To perform an updated systematic review for determining the surgical success rate of multilevel upper airway surgery for patients with obstructive sleep apnea/hypopnea syndrome (OSA). METHODS: A systematic review was performed to identify English-language studies that evaluated the treatment of adult OSA patients with multilevel OSA surgery up to January, 2018. We used polysomnography as a metric of treatment success. Articles were only included if the surgery intervention involved at least two of the frequently involved anatomic sites: nose, oropharynx and hypopharynx. Eighty-seven studies fit the inclusion criteria and a meta-analysis was performed to determine the overall success. RESULTS: The meta-analysis included 3931 subjects with a mean age of 46.1 years. The originally reported success rate in the included literature was 59.9%. A meta-analysis was performed to redefine the success rate to be consistent with the commonly agreed upon criteria - namely "a reduction in apnea/hypopnea index (AHI, /hr.) of 50% or more and an AHI of less than 20". The recalculated success rate was 60.2%. Standard meta-analytic techniques for combining p-values between studies after weighting for sample size found significant improvements in AHI, apnea index, % of rapid eye movement sleep, lowest saturation of oxygen (%), and Epworth Sleepiness Scale. CONCLUSION: This study shows the significant improvement of treatment outcomes with multilevel surgery for OSA patients.

OSA Treatment on Cardio- and Cerebrovascular Comorbidities: A Long-term Nationwide Cohort Study.

OBJECTIVE: To compare the cardio- and cerebrovascular outcomes and survival rates of surgical and nonsurgical interventions for patients with obstructive sleep apnea (OSA) based on a national population-based database. STUDY DESIGN: Retrospective cohort study. SETTING: Taiwan National Health Insurance Research Database. METHODS: We analyzed all cases of OSA among adults (age >20 years and confirmed with ICD-9-CM) from January 2001 to December 2013. We compared the patients with OSA who received upper airway surgery with age-, sex-, and comorbidity index-matched controls with continuous positive airway pressure (CPAP) treatment. The risk of myocardial infarction (MI) or stroke after treatment of OSA-related surgery versus CPAP was investigated. RESULTS: During follow-up, 112 and 92 incident cases of MI occurred in the OSA surgery and CPAP treatment groups, respectively (rates of 327 and 298 per 100,000 person-years). Furthermore, 50 and 39 cases were newly diagnosed with stroke in the OSA surgery and CPAP treatment groups (rates of 144 and 125 per 100,000 person-years). Cox proportional hazard regressions showed that the OSA treatment groups (OSA surgery vs CPAP) were not significantly related to MI (hazard ratio, 1.03 [95% CI, 0.781-1.359]; P = .833) and stroke (hazard ratio, 1.12 [95% CI, 0.736-1.706]; P = .596) at follow-up, after adjustment for sex, age at index date, days from diagnosis to treatment, and comorbidities. CONCLUSION: Our study demonstrated that there was no difference of cardio- and cerebrovascular results between CPAP and surgery for patients with OSA in a 13-year follow-up. LEVEL OF EVIDENCE: 3.

Targeted activation of androgen receptor signaling in the periosteum improves bone fracture repair.

Low testosterone level is an independent predictor of osteoporotic fracture in elderly men as well as increased fracture risk in men undergoing androgen deprivation. Androgens and androgen receptor (AR) actions are essential for bone development and homeostasis but their linkage to fracture repair remains unclear. Here we found that AR is highly expressed in the periosteum cells and is co-localized with a mesenchymal progenitor cell marker, paired-related homeobox protein 1 (Prrx1), during bone fracture repair. Mice lacking the AR gene in the periosteum expressing Prrx1-cre (AR-/Y;Prrx1::Cre) but not in the chondrocytes (AR-/Y;Col-2::Cre) exhibits reduced callus size and new bone volume. Gene expression data analysis revealed that the expression of several collagens, integrins and cell adhesion molecules were downregulated in periosteum-derived progenitor cells (PDCs) from AR-/Y;Prrx1::Cre mice. Mechanistically, androgens-AR signaling activates the AR/ARA55/FAK complex and induces the collagen-integrin α2ß1 gene expression that is required for promoting the AR-mediated PDCs migration. Using mouse cortical-defect and femoral graft transplantation models, we proved that elimination of AR in periosteum of host mice impairs fracture healing, regardless of AR existence of transplanted donor graft. While testosterone implanted scaffolds failed to complete callus bridging across the fracture gap in AR-/Y;Prrx1::Cre mice, cell-based transplantation using DPCs re-expressing AR could lead to rescue bone repair. In conclusion, targeting androgen/AR axis in the periosteum may provide a novel therapy approach to improve fracture healing.

Decreased retinal nerve fiber layer thickness in patients with obstructive sleep apnea/hypopnea syndrome.

BACKGROUND: To compare parameters for retinal nerve fiber layer (RNFL) thickness, optic nerve head (ONH) measurements, and macular thickness in patients with different severities of obstructive sleep apnea/hypopnea syndrome (OSAHS) versus normal controls. METHODS: Patients presenting with snoring and daytime sleepiness who underwent overnight polysomnography to determine OSAHS severity were recruited, and subsequently referred for ophthalmologic evaluation. Optical coherence tomography was used to evaluate the retinal nerve fiber layer (RNFL), optic nerve head topography, and macular thickness for early detection of glaucoma. Patients determined not to have OSAHS were included as controls. RESULTS: A total of 127 subjects were recruited, including 105 patients with OSAHS and 22 normal control subjects. RNFL thickness was significantly lower for the severe OSAHS group than for the control and mild OSAHS groups in the average (p < 0.0001) and in the superior quadrant (p = 0.0007). When subjects without OSAHS or with mild disease (AHI < 15) were grouped together and compared with patients with moderate/severe OSAHS (AHI ≧ 15), RNFL thickness measurements for the latter group were significantly lower in the average (p < 0.0001), and in the superior (p = 0.001), inferior (p = 0.029), and temporal (p = 0.007) quadrants. Positive correlations were identified between lowest oxygenation saturation on PSG and RNFL thickness in the average (r = 0.260), superior (r = 0.200) and nasal (r = 0.156) quadrants. CONCLUSIONS: Compared to patients without OSAHS or those with mild disease, RNFL thickness was lower in patients with moderate/severe OSAHS. Lowest saturation of oxygen in the moderate/severe OSAHS group correlated with decreased RNFL thickness. Patients with moderate and severe OSAHS are at increased risk for glaucoma.