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Background: Bullous pemphigoid is an autoimmune bullous disease that frequently affects a large skin surface area, but it can also present in localized areas. It has been hypothesized that bullous pemphigoid affects the systemic functioning of different organs because inflammatory cells and cytokines circulate throughout numerous organs. Results: Recent clinical and experimental studies have revealed an association between bullous pemphigoid and systemic organ disorders. To avoid the emergence of systemic organ diseases, the significance of systemic treatment in cases of severe bullous pemphigoid should be emphasized. Conclusions: Here, we discuss the specific molecular processes underlying typical systemic organ inflammatory diseases associated with bullous pemphigoids.

Abstract is missing (Short communication)

Abstract Pyoderma gangrenosum is a rare inflammatory skin disease classified within the group of neutrophilic dermatoses, and clinically characterised by painful, rapidly evolving cutaneous ulcers with undermined, irregular, erythematous‐violaceous edges. Underlying diseases include rheumatoid arthritis, inflammatory bowel disease, haematopoietic malignancy, and aortitis syndrome. However, there was a limited number of cases of concomitant pyoderma gangrenosum and IgA vasculitis. Herein, we report a case presenting persistent large skin wounds as a diagnosis of pyoderma gangrenosum in the setting of IgA cutaneous vasculitis, which was successfully treated by a TNF‐α inhibitor. A 67‐year‐old obese female presented palpable purpura on her lower extremities. A skin biopsy taken from the purpuric eruption showed leukocytoclastic vasculitis with IgA and C3 depositions in the vessel walls of the upper dermis, leading to the diagnosis of IgA vasculitis. Small skin ulcers rapidly expanded in several days, eventually developing perforating skin ulcers with irregular erythematous and violaceous edges on both lower extremities following the tapered oral prednisolone at a dose of 25 mg per day. Based on the clinical manifestation and histological analysis, we diagnosed her skin wound as pyoderma gangrenosum. After the adalimumab administration, the spreading ulceration was dampened, leading to the acceleration of wound epithelialisation.

Abstract We present a case of myasthenia gravis that occurred after alopecia areata and evaluate the literature on the comorbidity of alopecia and myasthenia gravis. A 41‐year‐old male noticed hair loss on his scalp 4 months ago, and his hair loss progressed with drooping of both upper eyelids and diplopia. Physical and laboratory examination identified the comorbidity of myasthenia gravis and alopecia areata. Prednisolone 10 mg/day and tacrolimus 3 mg/day were administered for 7 days following hospitalization, which served to improve diplopia and ptosis. Following methylprednisolone therapy, hair loss in alopecia areata improved without the enlargement of bald areas. Based on the literature review, a total of 29 cases with alopecia and myasthenia gravis including our case have been reported. Among them, seven cases of myasthenia gravis developed after alopecia. The average time for the onset of myasthenia gravis after alopecia was 16.6 months. Four cases showed other autoimmune disease comorbidity, such as vitiligo, lichen planus, cutaneous lupus erythematosus, and pemphigus foliaceus, suggesting the involvement of Th1‐significant immunological states in these patients.

Abstract Biological agents targeting inflammatory skin diseases have dramatically overcome many of the limitations of older oral therapeutic options. Among the various biological agents, ixekizumab is a humanised monoclonal antibody that blocks the biological activity of IL‐17A, which exhibited high efficacy against psoriasis. Although there are a limited number of cutaneous adverse reactions, biologic‐induced type I allergic reactions are rare. Herein, we report a case of ixekizumab‐induced urticaria.

Abstract The coronavirus disease 2019 (COVID‐19) vaccine is positively changing the health crises of this pandemic and is currently essential to overcome the COVID‐19 pandemic. The vaccine shows high efficacy against the infection and impairs the severity of symptoms. However, this vaccination is associated with concerns, such as vaccine‐associated adverse reactions, which are currently highlighted issues for clinicians. We experienced two cases of mild cutaneous adverse reaction following COVID‐19 vaccine administration, which was successfully controlled by prior administration of the antihistamine agent fexofenadine 3 days before COVID‐19 vaccination for 7 days.

Abstract Mycosis fungoides is recognized as an indolent cutaneous malignant T-cell lymphoma. In contrast, there are few therapeutic options for advanced forms of mycosis fungoides. Since immunotherapy is desirable as an alternative therapeutic option, identifying candidate molecules is an important goal for clinicians. Although tumor-derived negative immunomodulatory molecules, such as PD-1/PD-L1, have been identified in various malignancies, the useful positive immunological drivers of mycosis fungoides are largely unknown. We found that the stimulator of interferon (IFN) genes (STING) was highly upregulated in early-stage mycosis fungoides. Immunohistochemical examination revealed different STING staining patterns in patients with mycosis fungoides. Although there were no significant differences in clinical factors’ characteristics, STING expression was associated with the survival of patients with mycosis fungoides. The survival rate was significantly poor in patients with low STING-expressing mycosis fungoides. Univariate and multivariate analyses revealed that low STING expression was associated with an increased hazard ratio. Our results indicate that STING expression independently influences the prognosis of mycosis fungoides.

The skin, the outermost layer of the human body, is exposed to various external stimuli that cause inflammatory skin reactions. These external stimulants trigger external epithelial cell damage and the release of intracellular substances. Following cellular damage or death, intracellular molecules are released that enhance tissue inflammation. As an important substance released from damaged cells, the S100 protein is a low-molecular-weight acidic protein with two calcium-binding sites and EF-hand motif domains. S100 proteins are widely present in systemic organs and interact with other proteins. Recent studies revealed the involvement of S100 in cutaneous inflammatory disorders, psoriasis, and atopic dermatitis. This review provides detailed information on the interactions among various S100 proteins in inflammatory diseases.

Abstract Psoriasis is a chronic inflammatory skin disease that involves various systemic organs and tissues and is characterized by scaly erythematous skin. Among the different types of psoriasis, psoriatic arthritis (PsA) is frequently reported, and occasionally develops into severe arthritis leading to joint dysfunction. There are various tools, especially questionnaires, to identify the presence of PsA in European and American populations; however, little is known about the utility of these tools in the Asian population. In this study, we investigated the utility of a representative tool, the psoriasis epidemiology screening tool (PEST) questionnaire, to identify PsA among Japanese patients with psoriasis. A total of 143 patients with psoriasis were enrolled in this study. Among them, 29 patients were diagnosed with PsA. The frequency of PsA was significantly increased in patients with PEST scores > 3, with a sensitivity of 93.1% and a specificity of 78.9%. Among the questions in the PEST questionnaire, “Have you ever had a swollen joint?” showed the highest frequency to answer “Yes” among patients with PsA. Univariate and multivariate analyses revealed that high PEST scores (> 3) was an independent variable in PsA patients. Taken together, our study suggests that the PEST questionnaire is a useful tool to identify PsA among Japanese patients with psoriasis.

Abstract Telaprevir used as a protease inhibitor against hepatitis C virus is frequently associated with cutaneous adverse reactions. To explore a histological biomarker of cutaneous adverse events induced by telaprevir, we systematically searched for genes that were dysregulated by telaprevir in normal human epidermal keratinocytes (NHEKs). Microarray analysis and real-time polymerase chain reaction (PCR) revealed the significant increase in the expression of S100 calcium-binding protein A2 (S100A2) gene following treatment of NHEKs with telaprevir. Immunohistochemical analysis demonstrated that the expression of S100A2 was dominant in the spinous layer of the epidermis in patients with telaprevir-mediated severe-type drug eruptions and limited to the basal layer of the epidermis in healthy subjects. Furthermore, S100A2 expression increased after treatment with trichloroethylene and other medications, and the degree of S100A2 expression correlated with the severity of cutaneous adverse events. S100A2 expression also significantly increased in the skin of patients with atopic dermatitis and psoriasis. Taken together, S100A2 is highly expressed in the epidermis under inflammatory conditions and drug eruptions and may serve as a marker for keratinocyte damage in response to any inflammatory or toxic condition.

Abstract To investigate nasal displacement of central retinal vessel (CRV) on the optic nerve head (ONH) in glaucoma in association with its passage through lamina cribrosa (LC). This cross-sectional study included 113 eyes with glaucoma and 60 normal eyes. Horizontal spectral-domain optical coherence tomography (SD-OCT) scans of the ONH were acquired, and point where CRV emerged on the ONH surface was defined as the position of the CRV. Next, radial scans of the ONH were acquired, and angle of the CRV passing through the LC was measured. These parameters were compared between glaucomatous and normal eyes by t-test, and their relationship with possible confounders was assessed by multiple regression analyses. In glaucoma, CRV was significantly more nasally displaced than it was in normal eyes (66.0 ± 8.6 vs. 54.3 ± 9.5, P

Abstract Background Although endoscopic interventions for chronic pancreatitis are highly developed, surgery for severe complicated cases such as the coexistence of bile duct, duodenum, and portal vein stenosis is a challenging issue for surgeons. In such instances, pancreaticoduodenectomy could lead to massive intraoperative bleeding due to severe collateral veins. A surgical drainage procedure, instead of pancreatic resection, may be a reasonable and safer option in such cases, but the literature on a surgical drainage technique to resolve all obstructions of the pancreatic duct, bile duct, and duodenum at once is limited. We devised a new surgical drainage method for such cases with consideration for a possible future second surgery for newly developed pancreatic cancer because chronic pancreatitis is a well-known high-risk factor for pancreatic cancer in the long term. Here, we report this surgical procedure. Case presentation A 55-year-old man was diagnosed with alcoholic chronic pancreatitis 15 years ago. Before surgery, he underwent regular endoscopic pancreatic stenting for pancreatic ductal stenosis for 3 years. Three months before surgery, his duodenal stenosis worsened, and he was referred to our department for surgery. Preoperative imaging revealed pancreatic and bile duct stenosis, duodenal stenosis, and portal vein stenosis. To avoid intraoperative bleeding caused by the development of collateral veins, we performed a triple drainage procedure: longitudinal pancreaticojejunostomy with coring-out of the pancreatic head, hepaticojejunostomy, and gastrojejunostomy. The patient did not develop postoperative complications, and he was discharged from the hospital on postoperative day 14. For 5 years after surgery, no abdominal pain or recurrent pancreatitis was observed. Conclusion Our triple drainage procedure seems effective and minimally invasive for patients complicated with bile duct stenosis, duodenal stenosis, and portal vein stenosis.

It is understood that the skin is a peripheral lymphoid tissue that defends against external environmental stimuli. Continuous activation from these factors, on the other hand, promotes persistent inflammation at the local location and, occasionally, tissue damage. Hidradenitis suppurativa (HS) is a typical inflammatory skin disease and becomes a source of numerous inflammatory cytokines due to the chronic intractable repeated inflamed tissues. Because inflammatory cells and cytokines circulate throughout the body from the inflamed organ, it has been hypothesized that HS-mediated skin inflammation impacts the systemic functioning of numerous organs. Recent updates to clinical and experimental investigations revealed that HS has a significant connection with systemic inflammatory disorders. We provide the details and comprehensive molecular mechanisms associated with systemic inflammatory illnesses due to HS.

S100 proteins are a family of low-molecular-weight proteins characterized by two calcium-binding sites with a helix-loop-helix (“EF-hand-type”) domain. The S100 family of proteins is distributed across various organs and can interact with diverse molecules. Among the proteins of the S100 family, S100 calcium-binding protein A2 (S100A2) has been identified in mammary epithelial cells, glands, lungs, kidneys, and prostate gland, exhibiting various physiological and pathological actions in human disorders, such as inflammatory diseases and malignant tumors. In this review, we introduce basic knowledge regarding S100A2 regulatory mechanisms. Although S100A2 is a tumor suppressor, we describe the various influences of S100A2 on cancer and inflammatory diseases.

Humans are exposed to various external environmental factors. Food intake is one of the most influential factors impacting daily lifestyle. Among nutrients obtained from foods, omega-3 polyunsaturated fatty acids (PUFAs) have various beneficial effects on inflammatory diseases. Furthermore, omega-3 PUFA metabolites, including resolvins, are known to demonstrate strong anti-inflammatory effects during allergic and inflammatory diseases; however, little is known regarding the actual impact of these metabolites on skin diseases. In this review, we focused on metabolites that have strong anti-inflammatory actions in various inflammatory diseases, as well as those that present antitumor actions in malignancies, in addition to the actual effect of omega-3 PUFA metabolites on various cells.

Atypical lipomatous tumor (ALT) has been defined as a well-differentiated liposarcoma exhibiting a higher frequency of a local recurrence after surgical resection. ALT is mainly classified into deep type and superficial type. Compared with deep type ALT, superficial type ALT is rarely observed. One of the most important issues is that little has been known about superficial type ALT and it is not easy to predict the presence of superficial type ALT before surgical resection. To clarify the clinical manifestations of superficial type ALT, we examined 15 cases with superficial type ALT and 118 cases with benign lipoma, and analyzed their differences in clinical characteristics and the findings of MRI test. In clinical characteristics, the tumor size of superficial type ALT was significantly greater than that of benign lipoma, and superficial type ALT showed a significantly higher frequency of the tumor size of more than 4 cm. Superficial type ALT exhibited poor tumor mobility and hardness with elastic soft. In addition, a significantly higher frequency of tumor location of superficial type ALT was observed in extremities. Among tumor sites at the trunk, buttocks, and shoulder were high frequent location in superficial type ALT. In an MRI examination, superficial type ALT exhibited a significantly higher frequency of the septal structures compared with benign lipoma. The combinations of clinical characteristics, including physical examinations, MRI, and histological examinations, are helpful for the diagnosis of superficial type ALT.

Abstract Background Medullary carcinoma of the pancreas (MCP) is a rare malignant pancreatic tumor. The World Health Organization classification defines the tumor as a subtype of pancreatic ductal carcinomas. MCP is histologically characterized as having highly pleomorphic cells with syncytial morphology, expansive tumor growth, and necrosis. The pathogenesis and clinical course of MCP are largely unknown. Herein, we report an unusual case of MCP that was radiologically followed up for 9 years prior to surgical intervention. Case presentation A 73-year-old Japanese woman with a nonspecific disease history was found to have an asymptomatic cyst in the pancreatic duct by abdominal ultrasonography. Thorough radiological investigation suggested it was not an aggressive neoplasm, and she received periodic check-ups under a clinical diagnosis of “a cystic pancreatic lesion of uncertain malignancy.” Nine years after initial presentation, she experienced acute pancreatitis and underwent thorough re-evaluation. Dynamic computed tomography revealed no cyst; rather, a solid tumor was detected. Cytology of the pancreatic duct suggested adenocarcinoma. Pancreatoduodenectomy with D2 lymph node dissection was performed. The resected tumor was a non-mucinous, solid mass measuring 22 × 10 mm. Microscopically, the tumor had a well-demarcated pushing border. Lymphocytic infiltration was abundant, and stromal component was sparse. The tumor cells were composed of highly pleomorphic cells, proliferating in sheets without glandular formation. Neither lymphovascular invasion nor lymph node metastasis was detected. The histopathologic diagnosis was MCP, pT1aN0M0. The tumor carried a KRAS mutation, and MLH-1, MSH-2, MSH-6, and PMS-2 immunostaining results were normal, suggesting microsatellite stability. The patient has remained free of disease for 29 months following surgical intervention. Conclusion A review of 20 previously reported cases plus the present case suggests that subsets of MCPs have genetic aberrations such as KRAS mutation and high microsatellite instability. MCP has been suggested to have a better prognosis than common ductal adenocarcinoma; however, 15 of 20 previously reported cases died from disease. Whether the asymptomatic cyst observed over 9 years contributed to the development of MCP in this patient is a subject for future study.

Abstract The anti-inflammatory effect of omega 3 polyunsaturated fatty acids has been confirmed in various inflammatory disease models. Maresin-1 (MaR1) is a lipid mediator derived from the omega-3 fatty acid docosahexaenoic acid (DHA) that has displayed strong anti-inflammatory effects in various inflammatory disease models. However, the effect of topical MaR1 on cutaneous inflammation remains unclear. Therefore, we initially examined the anti-inflammatory effects of topical Maresin-1 using an imiquimod (IMQ)-induced psoriasis-like mouse model of inflammation. Topical MaR1 reduced the ear swelling response as seen in histological findings. RT-PCR and flow cytometry analyses revealed MaR1 had no inhibitory effect on IL-23, but MaR1 suppressed IL-17A production by γδTCRmid+ and CD4+ cells in the skin. These inhibitory effects were also observed in a subcutaneous IL-23-injected psoriasis model. MaR1 downmodulated IL-23 receptor (IL-23R) expression by suppressing retinoic acid-related orphan receptor γt (RORγt) expression and internalization in a clathrin-dependent manner in γδTCRmid+ and CD4+ cells. These results lead to assumptions that topical MaR1 may be a new therapeutic agent for psoriasis and other IL-17-mediated cutaneous inflammatory diseases.

Dietary nutrition intake is essential for human beings and influences various physiological and pathological actions in the human body. Among various nutritional factors, dietary intake of omega-3 polyunsaturated fatty acids (PUFAs) has been shown to have various beneficial effects against inflammatory diseases. In addition to their therapeutic potency against inflammation, omega-3 PUFAs have also been shown to have anti-tumor effects via various mechanisms, such as cell arrest and apoptosis. To date, limited information is available on these effects in cutaneous malignancies. In this review, we focused on the effect of omega-3 PUFAs on skin cancers, especially malignant melanoma, basal cell carcinoma, lymphoma, and squamous cell carcinoma and discussed the detailed molecular mechanism of the omega-3 PUFA-mediated anti-tumor response. We also explored the molecular mechanisms mediated by epigenetic modifications, cell adhesion molecules, and anti-tumor immune responses.

Summary: Type I interferons (IFNs) play important roles in antitumor immunity. We generated IFN-α-producing cells by genetically engineered induced pluripotent stem cell (iPSC)-derived proliferating myeloid cells (iPSC-pMCs). Local administration of IFN-α-producing iPSC-pMCs (IFN-α-iPSC-pMCs) alters the tumor microenvironment and propagates the molecular signature associated with type I IFN. The gene-modified cell actively influences host XCR1+ dendritic cells to enhance CD8+ T cell priming, resulting in CXCR3-dependent and STING-IRF3 pathway-independent systemic tumor control. Administration of IFN-α-iPSC-pMCs in combination with immune checkpoint blockade overcomes resistance to single-treatment modalities and generates long-lasting antitumor immunity. These preclinical data suggest that IFN-α-iPSC-pMCs might constitute effective immune-stimulating agents for cancer that are refractory to checkpoint blockade. : Tsuchiya et al. demonstrate that local administration of iPSC-derived myeloid cells producing interferon-α suppresses local, as well as distant, tumors. The efficacy depends on the tumor-reactive T cell response mediated by the activation of host XCR1+ dendritic cells. The concomitant use of a PD-1/PD-L1 inhibitor yields a superior antitumor effect. Keywords: cancer immunotherapy, induced pluripotent stem cells, type I interferon, XCR1, dendritic cells, cross-presentation, checkpoint blockade, PD-1, STING, CXCR3

Extramammary Paget’s disease is recognized as an apocrine-origin cutaneous tumor and is localized in the intraepithelial skin lesion. However, its advanced form is intractable, and there is currently no therapeutic option with a satisfactory level of clinical outcome. Therefore, it is of great importance to identify a potential biomarker to estimate tumor advancement in extramammary Paget’s disease. Dermcidin is an antimicrobial peptide derived from the eccrine gland and is identified as a biomarker in various malignancies. To investigate the potential of dermcidin in extramammary Paget’s disease, we investigated dermcidin expression in tumors using the immunostaining technique. Although previous studies have reported that extramammary Paget’s disease has no positive staining against dermcidin, 14 out of 60 patients showed positive staining of dermcidin in our study. To clarify the characteristics of positive dermcidin in extramammary Paget’s disease, we investigated the clinical characteristics of positive dermcidin extramammary Paget’s disease patients. Positive dermcidin patients showed a significantly high frequency of lymph node metastasis. We next investigated the impact of positive dermcidin on overall survival. Univariate analysis identified that positive dermcidin showed a significantly increased hazard ratio in overall survival, suggesting that dermcidin might be a prognostic factor for extramammary Paget’s disease.

Cell adhesion molecular 1 (CADM1) is a multifunctional cell adhesion molecule belonging to the immunoglobulin superfamily, which suppresses malignant solid tumor development. However, the correlation between CADM1 expression and prognosis in cutaneous squamous cell carcinoma (cSCC) patients remains unclear. In a retrospective analysis of 88 patients diagnosed with cSCC at our institution between January 2006 and December 2016, the degree of CADM1 expression in tumor cells was evaluated by immunostaining. Fifty-five and 33 patients had tumors with high and low CADM1 expression, respectively. Low CADM1 expression on the tumor was associated with poor differentiation, whereas the Kaplan–Meier curve and log-lank test indicated a favorable prognosis with high CADM1 expression. Multivariate analysis excluding the effect of the degree of differentiation and clinical stages showed that the hazard ratio (HR) of survival was significantly increased with low CADM1 expression. Thus, CADM1 expression is an independent prognostic factor for cSCC patients.

Purpose: The clinical efficacy of cancer peptide vaccine therapy is insufficient. To enhance the anti-tumor effect of peptide vaccine therapy, we combined this therapy with an anti-CD4 mAb (GK1.5), which is known to deplete CD4+ cells, including regulatory T cells (Tregs). Methods: To determine the treatment schedule, the number of lymphocyte subsets in the peripheral blood of mice was traced by flow cytometry after administration of anti-CD4 mAb. The ovalbumin (OVA)257–264 peptide vaccine was injected intradermally and anti-CD4 mAb was administered intraperitoneally into C57BL/6 mice at different schedules. We evaluated the enhancement of OVA peptide-specific cytotoxic T lymphocyte (CTL) induction in the combination therapy using the ELISPOT assay, CD107a assay, and cytokine assay. We then examined the in vivo metastasis inhibitory effect by OVA peptide vaccine therapy in combination with anti-CD4 mAb against OVA-expressing thymoma (EG7) in a murine liver metastatic model. Results: We showed that peptide-specific CTL induction was enhanced by the peptide vaccine in combination with anti-CD4 mAb and that the optimized treatment schedule had the strongest induction effect of peptide-specific CTLs using an IFN-γ ELISPOT assay. We also confirmed that the CD107a+ cells secreted perforin and granzyme B and the amount of IL-2 and TNF produced by these CTLs increased when the peptide vaccine was combined with anti-CD4 mAb. Furthermore, metastasis was inhibited by peptide vaccines in combination with anti-CD4 mAb compared to peptide vaccine alone in a murine liver metastatic model. Conclusion: The use of anti-CD4 mAb in combination with the OVA peptide vaccine therapy increased the number of peptide-specific CTLs and showed a higher therapeutic effect against OVA-expressing tumors. The combination with anti-CD4 mAb may provide a new cancer vaccine strategy.

We have previously conducted a phase I trial to test the efficacy of a glypican-3 (GPC3) peptide vaccine in patients with advanced hepatocellular carcinoma (HCC); however, its immunological mechanism of action remains unclear. Here, we report a pilot study conducted to evaluate the immunological mechanisms of action of this GPC3 peptide vaccine (UMIN-CTR number 000005093). Eleven patients with advanced HCC were vaccinated with the GPC3 peptide in this trial. The primary end point was GPC3 peptide-specific immune response induced by the GPC3 peptide vaccination. The secondary endpoints were clinical and biologic outcomes. We demonstrated that the present vaccine induced GPC3 peptide-specific cytotoxic T lymphocytes (CTLs), which were found to infiltrate into the tumor. Moreover, we established GPC3 peptide-specific CTL clones from a biopsy specimen: these cells exhibited GPC3 peptide-specific cytokine secretion and cell cytotoxicity. The plasma GPC3 level tended to decrease temporarily at least once during the follow-up period. The GPC3-specific CTL frequency after vaccination was correlated with overall survival. The degree of skin reactions at the injection site correlated with the GPC3 peptide-specific CTLs. Furthermore, we sequenced the T cell receptors (TCRs) of tumor-infiltrating lymphocyte (TIL) clones, and confirmed the existence of this TCR repertoire in both tumor tissue and PBMCs. In response to these data, we are developing TCR-engineered T cell therapy using TCR sequences obtained from GPC3 peptide-specific CTL clones for improved efficacy in patients with advanced HCC.

The influence of myopia on glaucoma progression remains unknown, possibly because of the multifactorial nature of glaucoma and difficulty in assessing a solo contribution of myopia. The purpose of this study is to investigate the association of myopia with visual field (VF) progression in glaucoma using a paired-eye design to minimize the influence of confounding systemic factors that are diverse among individuals.This retrospective study evaluated 144 eyes of 72 subjects with open-angle glaucoma, with similar intra-ocular pressure between paired eyes, spherical equivalent (SE) ≤ -2 diopter (D), and axial length ≥ 24 mm. Paired eyes with faster and slower VF progression were grouped separately, according to the global VF progression rate assessed by automated pointwise linear regression analysis. The SE, axial length, tilt ratio and torsion angle of optic discs, Bruch's membrane (BM) opening area, and gamma zone parapapillary atrophy (PPA) width were compared between the two groups. Factors associated with faster VF progression were determined by logistic regression analysis.The mean follow-up duration was 8.9 ± 4.4 years. The mean value of SE and axial length were -6.31 ± 1.88 D and 26.05 ± 1.12 mm, respectively. The mean global visual field progression rate was -0.32 ± 0.38 dB/y. Tilt ratio, BM opening area, and gamma zone PPA width were significantly greater in the eyes with faster VF progression than those with slower progression. In multivariate analysis, these factors were significantly associated with faster VF progression (all P < 0.05), while SE and axial length were not associated with it.In myopic glaucoma subjects, tilt of the optic disc and temporal shifting and enlargement of the BM opening were associated with faster rate of VF progression between paired eyes. This suggests that myopia influences VF progression in glaucomatous eyes via optic disc deformations rather than via refractive error itself.

To examine the association of myopia with the visual field (VF) defects in open-angle glaucoma (OAG) using paired eyes to eliminate the effect of unknown confounding factors that are diverse among individuals.One hundred eighteen eyes of 59 subjects with myopia (spherical equivalent [SE] ≥ -2 diopter [D] and axial length ≥ 24.0 mm) whose intra-ocular pressure between paired eyes was similar and the mean deviation (MD) of the Humphrey VF test differed by more than 6 dB were included. Refractive errors (SE, axial length) and parameters associated with the papillary and parapapillary myopic deformation (tilt ratio, torsion angle, and β-zone parapapillary atrophy [PPA] area without Bruch's membrane) were measured in each eye. The paired eyes were divided into worse and better eyes according to the MD of the VF, and parameters were compared between them. Further, multiple linear regression analysis was performed to examine the correlation of the difference in various parameters with the MD difference between paired eyes.The SE of all eyes was -6.39 ± 2.15 D (mean ± standard deviation) and axial length was 26.42 ± 1.07 mm. MD of the worse and better VF eyes were -13.56 ± 6.65 dB and -4.87 ± 5.32 dB, respectively. Eyes with worse VFs had significantly greater SE, axial length, tilt ratio, and PPA area without Bruch's membrane than those with better VFs (all P < 0.05). In multiple linear regression analysis, the difference of the MD between paired eyes was significantly correlated with the difference in the tilt ratio and PPA area without Bruch's membrane.The myopic papillary and parapapillary deformations, but not refractive error itself, were related to the worse VF in paired eyes with OAG. This suggests that myopia influences the severity of the glaucomatous VF defects via structural deformation.

Cholinergic urticaria (CU) has clinically characteristic features, and has been frequently described in the literature. However, despite its comparatively old history, the pathogenesis and classification remains to be clarified. CU patients are occasionally complicated by anhidrosis and/or hypohidrosis. This reduced-sweat type should be included in the classification because the therapeutic approaches are different from the ordinary CU. It is also well-known that autologous sweat is involved in the occurrence of CU. More than half of CU patients may have sweat hypersensitivity. We attempt to classify CU and address the underlying mechanisms of CU based on the published data and our findings. The first step for classification of CU seems to discriminate the presence or absence of hypersensitivity to autologous sweat. The second step is proposed to determine whether the patients can sweat normally or not. With these data, the patients could be categorized into three subtypes: (1) Cu with sweat hypersensitivity; (2) CU with acquired anhidrosis and/or hypohidrosis; (3) idiopathic CU. The pathogenesis of each subtype is also discussed in this review.

Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population, and the prevalence of the disease increases exponentially with every decade after the age of 50 years. While VEGF inhibitors are promising drugs for treating patients with ocular neovascularization, there are limitations to their potential for improving vision in AMD patients. Thus, future therapies are required to have the potential to improve visual outcomes. This paper will summarize the future strategies and therapeutic targets that are aimed at enhancing the efficacy and duration of effect of antiangiogenic strategies.