Vulvar neuroendocrine carcinoma that is independent of merkel cell polyomavirus and human papillomavirus suggests endometrial cancer recurrence: a case report.

BACKGROUND: Vulvar neuroendocrine carcinomas with small cell morphology need an appropriate differential diagnosis with respect to primary Merkel cell carcinomas, primary small cell neuroendocrine carcinomas, and secondary/metastatic carcinomas. Herein, we report a woman with a history of endometrial carcinoma led to neuroendocrine vulvar carcinoma. CASE PRESENTATION: An 82-y-old woman with right vulvar swelling was transferred to our hospital. Computed tomography scan showed a 75 mm irregular mass in her right vulva. Three years ago, she had been diagnosed with endometrial endometrioid carcinoma stage IA and had undergone surgery. Vulvar biopsy revealed neuroendocrine carcinomas with small cell morphology. Immunohistochemical staining showed that the vulvar tumor was positive for CD56 and chromogranin A, but negative for Merkel cell polyomavirus and cytokeratin 20. Incidentally, her endometrial carcinoma was also positive for CD56 and chromogranin A. Human papillomavirus DNA typing analysis of vulvar tumor was negative. Hence, the vulvar tumor seemed to be a recurrence of the endometrial cancer rather than a primary vulvar neuroendocrine carcinoma. The patient died of the disease within a month. CONCLUSION: We report a case of vulvar neuroendocrine carcinoma that is independent of Merkel cell polyomavirus and human papillomavirus, thereby suggesting a recurrence of endometrial cancer. Immunohistochemical and virological analyses helped in the differential diagnosis of the neuroendocrine carcinoma.

Mixed large and small cell neuroendocrine carcinoma and endometrioid carcinoma of the endometrium with high microsatellite instability: A case report and literature review.

A 65-year-old, gravida 3, para 2 Japanese woman was referred to our hospital for symptomatic thickening of the endometrial lining. Endocervical and endometrial cytology revealed an adenocarcinoma. The endometrial biopsy specimen was mixed, with a glandular part diagnosed as endometrioid carcinoma and a solid part diagnosed as high-grade mixed large and small cell neuroendocrine carcinoma (L/SCNEC). She underwent extra-fascial hysterectomy with bilateral salpingo-oophorectomy, complete pelvic and para-aortic lymphadenectomy, and omentectomy (FIGO IIIB, pT3b pN0 M0). She currently has no deleterious germline mutation, but high tumor mutation burden and high microsatellite instability (MSI) were identified. She underwent six cycles of platinum-based frontline chemotherapy and achieved complete remission. Immune checkpoint blockade therapy is a promising second-line therapy for MSI-high solid tumors. However, the MSI or mismatch repair (MMR) status of endometrial L/SCNEC remains unclear in the literature. Universal screening for MSI/MMR status is needed, particularly for a rare and aggressive disease.

Development of a bioanalytical method for an antisense therapeutic using high-resolution mass spectrometry.

Background: Ion-pairing reverse-phase LC coupled with high-resolution mass spectrometry (IP-LC/HRMS) has gained attention in oligonucleotide therapeutic bioanalyses owing to its high sensitivity and selectivity. However, optimization and validation of IP-LC/HRMS-based methods are rare. The objective of this study is the development of a sensitive and reproducible IP-LC/HRMS-based bioanalytical method using clinically approved mipomersen as a model for antisense oligonucleotides. Materials & methods/results: Mipomersen was extracted from rat plasma using Clarity OTX SPE and quantified by IP-LC/HRMS. The calibration range was 0.5-250.0 ng/ml. The developed method met the general regulatory criteria for accuracy, precision, carry-over, selectivity, matrix effect and dilution integrity. Conclusion: A highly sensitive and reliable method for mipomersen measurement with potential antisense oligonucleotide bioanalysis applications has been developed.

A Case of Vaginal Malignant Melanoma Completely Resected by Radical Surgery.

BACKGROUND Primary vaginal malignant melanoma is a rare and aggressive tumor with a high risk of local recurrence and distant metastasis. Although there are several available treatment options, none are considered as standard. Surgical resection is the first treatment choice because of its superior survival benefits. CASE REPORT The patient was a 56-year-old woman with a vaginal mass. At the first visit to our institution, a 20×20 mm black and flat lesion on the lower third of the posterior vaginal wall and a polypoid mass near the vaginal fornix were detected by gynecologic examination. Study of the tumor on the posterior vaginal wall suggested that it did not extend to the uterine cervix. The preoperative diagnosis was vaginal malignant melanoma FIGO stage I (cT1, cN0, cM0). The patient underwent a total vaginectomy, pelvic and inguinal lymphadenectomy, modified radical hysterectomy, and bilateral salpingo-oophorectomy. The tumor cells were arranged in sheets and nests and exhibited nuclear pleomorphism, eosinophilic cytoplasm, brisk mitotic activity, and melanin production. The overlying mucosa was ulcerated. The tumor thickness was 2.5 mm and no residual lesion was found at the surgical margin. No adjuvant therapies were performed. The patient is alive without recurrence 15 months after the initial treatment. CONCLUSIONS This is a case of vaginal malignant melanoma for which complete response was achieved by radical tumor resection, without severe adverse effects and with no observed recurrence 15 months after the surgery.

Sensitivity and specificity of high-resolution wide field fundus imaging for detecting neovascular age-related macular degeneration.

PURPOSE: Early detection and treatment are important management strategies for neovascular age-related macular degeneration (AMD). The purpose of this study was to determine the sensitivity and specificity in detecting neovascular AMD using two wide-field imaging systems: ClarusTM (CLARUS 500™, Carl Zeiss Meditec AG, Jena, Germany) and Optos®(Optos California®, Optos PLC, Dunfermline, United Kingdom), compared to conventional digital fundus photographs. METHODS: We retrospectively analyzed 109 eyes of 73 consecutive patients with neovascular AMD, who underwent standard examination and multimodal imaging, including fundus photography, and optical coherence tomography (OCT). Unmasked graders utilized slit-lamp biomicroscopy and OCT to diagnose neovascular AMD. Masked graders evaluated ClarusTM, Optos®, and digital fundus photograph methods to determine the presence of choroidal neovascularization associated with AMD. Sensitivity and specificity analyses were performed using combined fundoscopy and OCT as the reference standard. RESULTS: Ninety eyes were diagnosed with neovascular AMD and the remaining 19 eyes were normal based on the reference standard. Of these, neovascular AMD was detected using ClarusTM in 94.4% (85/90). The sensitivities of Optos® and digital fundus photographs were 81.1% (73/90) and 87.8% (79/90), respectively. The specificities using ClarusTM, Optos®, and digital fundus photographs were 89.5% (17/19), 94.7% (18/19), and 89.5% (17/19), respectively. CONCLUSION: ClarusTM, with its ability to image high-resolution wide field fundus, was considered superior for diagnosing neovascular AMD with high sensitivity and specificity. It may be a useful screening tool for early detection of neovascular AMD, facilitating prompt referral and treatment.

Comparison of one-year results of photodynamic therapy combined with ranibizumab or aflibercept for treating polypoidal choroidal vasculopathy.

PURPOSE: To compare the 1-year visual outcomes and anatomical responses of patients who received photodynamic therapy (PDT) combined with intravitreal ranibizumab (IVR) injections with those of patients who received PDT combined with intravitreal aflibercept (IVA) injections for treating polypoidal choroidal vasculopathy (PCV). METHODS: We retrospectively studied all treatment-naïve patients with PCV who received PDT combined with either IVR or IVA. Best-corrected visual acuity (BCVA), central macular thickness (CMT), central choroidal thickness (CCT), the number of additional injections, and the presence of polypoidal lesions, as indicated by indocyanine green angiography (ICGA), during 1 year were evaluated. RESULTS: Forty-four eyes were assessed at the 1-year follow-up examination. Of these, 23 were treated with PDT combined with IVR (PDT/IVR group), and 21 were treated with PDT combined with IVA (PDT/IVA group). In both groups, BCVA was shown to be significantly improved 1 year after the initial treatment. CMT and CCT were also significantly decreased after 1 year. There were no significant differences in the changes in BCVA or CMT between the two groups. However, the change in CCT in the PDT/IVA group was significantly larger than that of the PDT/IVR group (P < 0.001). The mean number of additional injections was 0.78 ± 0.21 in the PDT/IVR group and 0.57 ± 0.21 in the PDT/IVA group with no significant difference between the two groups (P = 0.45). The polyp regression rate at 12 months was 78.2% in the PDT/IVR group and 78.9% in the PDT/IVA group with no significant difference between the two groups. CONCLUSIONS: PDT combined with either IVR or IVA was well tolerated and appeared to improve both vision and anatomy in patients with PCV. PDT/IVA may have a more pronounced effect on macular choroidal thickness at 1-year follow-up.

One-year outcome of combination therapy with intravitreal anti-vascular endothelial growth factor and photodynamic therapy in patients with pachychoroid neovasculopathy.

PURPOSE: To identify the functional outcome and evaluate the morphologic changes of patients with pachychoroid neovasculopathy (PNV) undergoing intravitreal anti-vascular endothelial growth factor (VEGF) combined with photodynamic therapy (PDT) at the 1-year follow-up. METHODS: We retrospectively studied all the treatment-naïve PNV patients who were scheduled to undergo combination therapy between September 2017 and November 2018. All the patients received three consecutive monthly injections of 0.5 mg/0.05 mL ranibizumab as loading doses. Full-dose PDT was performed within 1 week of the first injection. Retreatment was allowed if evidence of clinical deterioration or the presence of fluid on spectral-domain optical coherence tomography examination performed at the 1-month follow-up was noted. The best-corrected visual acuity (BCVA) was compared before treatment and at 3, 6, and 12 months after the initial treatment. Changes in the central foveal thickness (CFT), central choroidal thickness (CCT), and retreatment rate during the maintenance phase were also evaluated. RESULTS: Eleven eyes were enrolled in this study. Significantly, better BCVA was observed at 12 months than at baseline (P = 0.010). The mean CFT significantly decreased from 331 ± 93 to 237 ± 72 µm at 12 months (P < 0.001). The mean CCT also significantly decreased from 361 ± 74 to 310 ± 83 µm at 12 months (P < 0.001). The mean number of injections per eye was 3.9 ± 1.3 during the follow-up period. A total of 45.5% (5 /11) of the patients required retreatment during the maintenance phase. CONCLUSION: Anti-VEGF combined with full-dose PDT was well tolerated and appeared to be effective treatment for patients with treatment-naïve PNV. Combination therapy might also reduce the treatment burden with fewer injections in patients with PNV.

Uterine tumor resembling ovarian sex-cord tumor (UTROSCT) with sarcomatous features without recurrence after extended radical surgery: A case report.

RATIONALE: The malignant potential and the appropriate treatment of uterine tumor resembling ovarian sex-cord tumor (UTROSCT) is controversial. Although these tumors generally have benign outcomes, several reports have described recurrences, metastases, and deaths associated with this disease. PATIENT CONCERNS: A 57-year-old Japanese woman (gravida 2, para 2) was referred to our hospital for the evaluation and treatment of uterine fibroids. Magnetic resonance imaging revealed a right ovarian mass and multiple fibroids in the uterine myometrium. DIAGNOSES: The patient was diagnosed with UTROSCT with sarcomatous features. INTERVENTIONS: She initially underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy, followed by second-stage surgery comprising pelvic and para-aortic lymphadenectomy and subtotal omentectomy. OUTCOMES: No postoperative recurrence was observed in the patient in 36 months. LESSONS: In this case, extended radical surgery prevented the development of recurrent disease in a patient with UTROSCT with sarcomatous features. These clinicopathological findings suggest that UTROSCT is associated with several risk factors, including older age, presence of necrosis, lymphovascular invasion, significant nuclear atypia, and significant mitotic activity. This lesion type should be considered malignant and treated with curative intent.

Predictive Factors And Long-Term Visual Outcomes After Anti-Vascular Endothelial Growth Factor Treatment Of Retinal Angiomatous Proliferation.

PURPOSE: To report the results of 9-year follow-up examinations and predictive factors for visual acuity outcome after intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents to treat retinal angiomatous proliferation (RAP). METHODS: We conducted a retrospective observational study of 85 treatment-naïve eyes in 61 patients (21 men, 40 women; age range, 70-95 years; mean age, 84.0 years) treated with intravitreal injections of anti-VEGF agents. All patients received three consecutive monthly injections as an induction treatment. During the maintenance phase, the patients received intravitreal injections as needed or fixed dosing. The primary outcome measures were best-corrected visual acuity (BCVA) during the follow-up period. Furthermore, we investigated potential predictive factors of improvement in visual acuity. The proportion of patients who developed specific complications were also analyzed. RESULTS: The mean BCVA gradually decreased from 0.58 at baseline to 0.70 at 36 months (P = 0.146), 0.82 at 48 months (P = 0.004), and 0.92 at 108 months (P = 0.021). Improvement in visual acuity at the final visits was associated with baseline visual acuity and central foveal thickness. Massive subretinal hemorrhage, fibrotic scars, and macular atrophy developed in 4 (4.7%), 9 (10.6%), and 50 (56.8%) eyes, respectively, at the final visits, and were all significantly associated with final visual acuity (P = 0.013, P < 0.001, and P = 0.001, respectively). CONCLUSION: Long-term stabilization of vision in patients with RAP, regardless of treatment modality, was difficult to achieve by using intravitreal injections of anti-VEGF agents. Earlier detection and treatment are important to maintain visual acuity in patients with RAP.

Health Benefits of Polyphenols and Carotenoids in Age-Related Eye Diseases.

Oxidative stress and inflammation play a critical role in the initiation and progression of age-related ocular abnormalities as cataract, glaucoma, diabetic retinopathy, and macular degeneration. Therefore, phytochemicals with proven antioxidant and anti-inflammatory activities, such as carotenoids and polyphenols, could be of benefit in these diseases. We searched PubMed and Web of Science databases for original studies investigating the benefits of different carotenoids and polyphenols in age-related ophthalmic diseases. Our results showed that several polyphenols (such as anthocyanins, Ginkgo biloba, quercetin, and resveratrol) and carotenoids (such as lutein, zeaxanthin, and mezoxanthin) have shown significant preventive and therapeutic benefits against the aforementioned conditions. The involved mechanisms in these findings include mitigating the production of reactive oxygen species, inhibiting the tumor necrosis factor-α and vascular endothelial growth factor pathways, suppressing p53-dependent apoptosis, and suppressing the production of inflammatory markers, such as interleukin- (IL-) 8, IL-6, IL-1a, and endothelial leucocyte adhesion molecule-1. Consumption of products containing these phytochemicals may be protective against these diseases; however, adequate human data are lacking. This review discusses the role and mechanisms of polyphenols and carotenoids and their possible synergistic effects on the prevention and treatment of age-related eye diseases that are induced or augmented by oxidative stress and inflammation.

Variable response of subretinal hyperreflective material to anti-vascular endothelial growth factor classified with optical coherence tomography angiography.

PURPOSE: To evaluate the prognosis and response of neovascular age-related macular degeneration (AMD) to anti-vascular endothelial growth factor (VEGF), according to the components of subretinal hyperreflective material (SHRM) classified using optical coherence tomography angiography (OCTA), is the aim of this study. METHODS: We retrospectively studied 39 eyes of 39 consecutive patients with SHRM associated with exudative AMD, who underwent standard examination and multimodal imaging, including fundus photography, optical coherence tomography (OCT), and OCTA. We classified SHRM into type 2 neovascularization (NV), fibrosis, subretinal hyperreflective exudation (SHE), and hemorrhage using OCTA. If compound SHRM was found, components in the foveal center were considered. All patients except one with fibrosis received anti-VEGF treatment for more than 12 months. The best-corrected visual acuity (BCVA) values measured before treatment and at 3, 6, and 12 months after the first injection were compared according to the components of SHRM. RESULTS: Using OCTA, 11 eyes with type 2 NV showed abnormal blood flow and 1 eye with fibrosis showed strong surface projection. Both SHE and hemorrhage components showed projection artifact with no intrinsic flow. However, OCTA enabled eyes with SHE (17 eyes) to be distinguished from those with hemorrhage (10 eyes) because hemorrhage showed masking of choriocapillaris flow. Eyes with SHE showed a significant improvement in the mean logMAR BCVA as compared with the value at the baseline, which was sustained throughout the 12-month follow-up period (p < 0.05). In eyes with type 2 NV and hemorrhage, no significant difference in the mean BCVA values was observed at any follow-up time-point (all, p > 0.05). CONCLUSION: OCTA was useful to noninvasively distinguish SHRM components. It may be important to consider the components of SHRM to predict the visual acuity in patients with AMD.

Association between tongue pressure and subclinical carotid atherosclerosis in relation to platelet levels in hypertensive elderly men: a cross-sectional study.

BACKGROUND: Age-related low-grade inflammation causing endothelial disruption influences sarcopenia, hypertension, and atherosclerosis. We reported previously that maintenance of muscle strength in elderly hypertensive men with high platelet levels is positively associated with subclinical atherosclerosis but not in those with low platelet levels. Since reduced tongue pressure is related to sarcopenia, tongue pressure may be associated with subclinical carotid atherosclerosis in hypertensive elderly subjects, and platelet levels may function as an indicator of the association between tongue pressure and subclinical carotid atherosclerosis. METHODS: We conducted a cross-sectional study of 342 hypertensive elderly Japanese men aged 60-89 who participated in an annual health check-up in 2015 and 2016. Subclinical carotid atherosclerosis was defined as a common carotid intima-media thickness (CIMT) of 1.1 mm or more. RESULTS: In the overall study population, 171 subjects demonstrated low platelets (< 21.4 × 104/µL). Tongue pressure was significantly inversely associated with subclinical carotid atherosclerosis in these subjects, but not in subjects with high platelets. The known cardiovascular risk factor adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of subclinical carotid atherosclerosis for a 1 standard deviation (SD) increment in tongue pressure (10.4 kPa) were 0.54 (0.35, 0.85) and 1.31 (0.87, 1.96), respectively. CONCLUSION: Tongue pressure is inversely associated with subclinical carotid atherosclerosis in hypertensive elderly men with low platelet levels, but not in those with high levels. This finding may thus constitute an efficient tool for clarifying the background mechanism of age-related diseases such as sarcopenia, hypertension, and atherosclerosis.

Hepatocyte growth factor and carotid intima-media thickness in relation to circulating CD34-positive cell levels.

BACKGROUND: Hepatocyte growth factor (HGF) may act as a possible biochemical index for vascular damage, although evidence for the association between HGF and carotid intima-media thickness (CIMT) is limited. Since both HGF and circulating CD34-positive cells play an important role in endothelial repair, circulating CD34-positive cell levels may influence the association between HGF and CIMT. METHODS: We conducted a cross-sectional study of 269 elderly Japanese men aged 60-69 years who had undertaken an annual medical checkup from 2014 to 2015. RESULTS: The median value for circulating CD34-positive cells was 0.93 cells/µL. Among the study population, 135 men showed low circulating CD34-positive cell levels (≤ 0.93 cells/µL). By multivariable linear regression analysis, HGF was found to be significantly positively associated with CIMT only to participants with low circulating CD34-positive cell levels, with a multi-adjusted ß of 0.26 (p = 0.005) and 0.002 (0.986) for low and high circulating CD34-positive cell levels, respectively. In addition, a significant interaction was observed between HGF and circulating CD34-positive cell levels (low and high) on CIMT (multivariable p value of 0.049). A positive association exists between HGF and CIMT in elderly Japanese men, limited to participants with low circulating CD34-positive cell levels. CONCLUSION: A positive association exists between HGF and CIMT in community-dwelling elderly Japanese men, which is limited to participants with low numbers of circulating CD34-positive cells. Our findings indicate that circulating CD34-positive cell levels could determine the influence of HGF on CIMT in elderly Japanese men.

Possible mechanism underlying the association between height and vascular remodeling in elderly Japanese men.

Height is reported to be inversely associated with cardiovascular disease. And platelets play an important role in vascular remodeling by supporting CD34-positive cells. To clarify the association between height and platelet, we conducted a cross-sectional study of 219 elderly Japanese men. Since hemoglobin concentration is influenced by vascular remodeling activity, an analysis stratified by hemoglobin level was performed. An inverse association was seen between height and platelet count in subjects with a high hemoglobin concentration (≥ 14.5 g/dL), but not in subjects with a low hemoglobin concentration (< 14.5 g/dL). The standardized parameter estimates (ß) were ß = -0.22, p = 0.019 for subjects with high hemoglobin, and ß = -0.01, p = 0.931 for subjects with low hemoglobin. We also found a positive association between platelets and carotid intima media thickness (CIMT) and circulating CD34-positive cells in subjects with high hemoglobin (partial correlation coefficient (r) = 0.21, p = 0.037 and r = 0.40, p =< 0.001), but not in subjects with low hemoglobin (r = 0.04, p = 0.710 and r = 0.06, p = 0.544). In subjects with a high hemoglobin concentration, platelets were inversely associated with height, and positively associated with CIMT and circulating CD34-positive cells. These results indicate that subjects with a short stature activate vascular remodeling to a much greater extent than subjects with a tall stature.

Validity of maximum isometric tongue pressure as a screening test for physical frailty: Cross-sectional study of Japanese community-dwelling older adults.

AIM: Maximum isometric tongue pressure (MIP) seems to have a diagnostic value for oral phase dysphagia. The present study aimed to examine the association between MIP and frailty, and to assess the screening validity of MIP for physical frailty. METHODS: We carried out a cross-sectional study, and enrolled participants aged ≥60 years from Japanese national medical check-ups in 2015 and 2016. The Fried frailty phenotype model was used. We analyzed odds ratios (OR) and 95% confidence intervals (CI) of physical frailty using one standard deviation increments of tongue pressure. Receiver operating characteristic curves were obtained to predict physical frailty using MIP values. RESULTS: Out of 1603 participants, 968 were categorized as non-frail, 605 as pre-frail and 30 as frail. In logistic regression analysis, one standard deviation increment of MIP significantly differentiated frail and pre-frail: the OR for frail with one standard deviation increment in MIP was 0.37 (95% CI 0.26-0.54, P < 0.001), and the OR for pre-frail was 0.63 (95% CI 0.57-0.70, P < 0.001). The area under the receiver operating characteristic curve for predicting frailty with MIP score was as high as 0.776 (95% CI 0.689-0.862). A point of MIP 35 kPa had a sensitivity of 90.0%, specificity of 40.4%, a positive likelihood ratio of 1.5 and a negative likelihood ratio of 0.2 for predicting frailty. CONCLUSIONS: MIP performance is independently associated with frailty. MIP also can be used as a simple screening tool for frailty. Geriatr Gerontol Int 2018; 18: 240-249.

Serum sodium level within the normal range is associated with maximum voluntary tongue pressure against the palate among community-dwelling older Japanese men.

AIM: Recent geriatric studies have focused on maximum voluntary tongue pressure against the palate (MTP) as a diagnostic value for dysphagia, as dysphagia causes aspiration pneumonia. Dysphagia can also cause water intake difficulties, resulting in hypernatremia by indicating the presence of hyperosmotic dehydration. However, no studies have reported on a possible association between reduced MTP and serum sodium levels. METHODS: To evaluate hyperosmotic dehydration within the normal range as an indicator of reduced MTP, we carried out a cross-sectional study of 655 older Japanese community-dwelling men (age ≥60 years) who undertook a general health check-up from 2015 to 2016. As a high concentration of glucose influences serum osmolarity, which might act as a strong confounding factor on this association, the additional analysis was limited to individuals without diabetes. Reduced MTP is defined as a tongue pressure at or under the 20th percentile of the study population (≤24.0 kPa). RESULTS: Independent of classical cardiovascular risk factors, the adjusted odds ratio of reduced MTP for a 1-standard deviation increment of serum sodium (2.21 mEq/L) was 1.29 (95% confidence interval 1.10-1.52). When the analysis was limited to individuals without diabetes, the association became slightly stronger, with an adjusted corresponding value of 1.59 (95% confidence interval 1.21-2.10). CONCLUSIONS: Serum sodium level within the normal range is independently associated with reduced MTP in older Japanese men. This finding suggests that measuring the MTP is clinically relevant for estimating the pathophysiological values (such as dysphagia risks and aspiration pneumonia risks) in daily clinical practice. Geriatr Gerontol Int 2018; 18: 183-186.

INTRAVITREAL INJECTION OF AFLIBERCEPT IN PATIENTS WITH POLYPOIDAL CHOROIDAL VASCULOPATHY: A 3-YEAR FOLLOW-UP.

PURPOSE: To compare the 3-year follow-up results of intravitreal injections of aflibercept between fixed dosing (FD) regimen and a pro re nata (PRN) regimen after three initial monthly doses for the treatment of polypoidal choroidal vasculopathy and to analyze factors influencing improvement in visual acuity. METHODS: We retrospectively studied all treatment-naive patients with polypoidal choroidal vasculopathy who were scheduled to receive intravitreal aflibercept injections FD or PRN after induction treatment between March 2013 and May 2014. Best-corrected visual acuity was evaluated before treatment and at 4, 12, 24, and 36 months after initial treatment. Factors that influence improvement in visual acuity were also investigated. RESULTS: Thirty-three eyes were assessed at the 3-year follow-up examination. Twenty-three eyes were treated with intravitreal aflibercept injections every 2 months for at least 1 year after three initial monthly doses (FD group), and 10 eyes were treated PRN after loading doses (PRN group). In the FD group, during the follow-up period from 1 to 3 years, quarterly dosing with capped PRN or a treat and extend regimen were selected. The mean number of administered intravitreal aflibercept was 15.3 ± 4.6 in the FD group and 9.0 ± 8.9 in the PRN group, with a significant difference between the two groups (P = 0.004). Significant improvement of the mean logarithm of the minimum angle of resolution values for best-corrected visual acuity was shown at 36 months, as compared to baseline values (P = 0.019). No significant difference in the improvement of best-corrected visual acuity between the two groups was observed at baseline or at 4, 12, 24, and 36 months after treatment (all P > 0.05), although there was a trend toward better results in the FD group. Multiple regression analysis showed that the FD group had better visual acuity at 36 months and greater improvement in visual acuity than the PRN group (P = 0.031 for both comparisons). CONCLUSION: Intravitreal aflibercept was effective in improving the vision of patients with polypoidal choroidal vasculopathy, as evaluated at the 3-year follow-up. Fixed treatment might be an important factor influencing improvement in visual acuity.

Social networks, leisure activities and maximum tongue pressure: cross-sectional associations in the Nagasaki Islands Study.

OBJECTIVES: Social environment is often associated with health outcomes, but epidemiological evidence for its effect on oral frailty, a potential risk factor for aspiration, is sparse. This study aimed to assess the association between social environment and tongue pressure, as an important measure of oral function. The study focused on family structure, social networks both with and beyond neighbours, and participation in leisure activities. DESIGN: A population-based cross-sectional study. SETTING: Annual health check-ups in a rural community in Japan. PARTICIPANTS: A total of 1982 participants, all over 40 years old. Anyone with missing data for the main outcome (n=14) was excluded. OUTCOME MEASURES: Tongue pressure was measured three times, and the maximum tongue pressure was used for analysis. A multivariable adjusted regression model was used to calculate parameter estimates (B) for tongue pressure. RESULTS: Having a social network involving neighbours (B=2.43, P=0.0001) and taking part in leisure activities (B=1.58, P=0.005) were independently associated with higher tongue pressure, but there was no link with social networks beyond neighbours (B=0.23, P=0.77). Sex-specific analyses showed that for men, having a partner was associated with higher tongue pressure, independent of the number of people in the household (B=2.26, P=0.01), but there was no association among women (B=-0.24, P=0.72; P-interaction=0.059). CONCLUSIONS: Having a social network involving neighbours and taking part in leisure activities were independently associated with higher tongue pressure. Marital status may be an important factor in higher tongue pressure in men.