Utility of Liquid-Based Cytology and Cell Block Procedure Obtained by Vitrectomy to Diagnose Ocular Sarcoidosis-The Significance of Epithelioid Granuloma and Epithelioid Cells.

Purpose: The eyes are one of the most frequently involved organs in sarcoidosis in Asia, including Japan. Sarcoid uveitis is the major complaint of ocular sarcoidosis. The detection of epithelioid granuloma (EG) requires histological biopsy of the uvea for the precise diagnosis of sarcoid uveitis, because it is challenging to diagnose sarcoid uveitis without a history of systemic sarcoidosis. To diagnose sarcoid uveitis, we have established novel methods. Patients and Methods: In this study, we included 30 eyes of 21 patients with granulomatous uveitis diagnosed via slit-lamp examinations, gonioscopy, fundus photography, and fluorescein angiography. Vitrectomy was performed to remove the vitreous opacity with vision loss. To examine vitreous cell components, we used liquid-based cytology (LBC). To detect EG in an intraocular irrigating solution, we collected vitreous cell components, and then the cell pellets were embedded in the cell block procedure. Results: Here, we demonstrated the usefulness of the histological detection of EG and epithelioid cells (ECs) in LBC from vitreous body specimens and in the cell block procedure from vitreous cell components in an intraocular irrigating solution. Our results showed that the detection rates of EG were 6.3% (1/16) in LBC and 9.1% (1/11) in the cell block procedure in the sarcoid uveitis-suspected group and 7.7% (1/13) in LBC and 28.6% (2/7) in the cell block procedure in the sarcoidosis group. We would discuss the specificity of the EG/EC detection of ocular sarcoidosis. Conclusion: Our methods are helpful in the precise diagnosis of ocular sarcoidosis and the control of the development of systemic sarcoidosis.

Ten-year longitudinal investigation of astigmatism: The Yamagata Study (Funagata).

Despite numerous investigations into ocular or corneal astigmatism, the dynamic nature of astigmatism remains poorly understood. To reveal potential associations between age and astigmatism, 264 Japanese participants who underwent systemic and ophthalmological examinations in Funagata Town (Yamagata Prefecture, Japan) were evaluated over a 10-year period. Astigmatism was evaluated with regard to the cylinder power, cylinder axis, and vector analyses. Whereas the refractive cylinders showed age-related increases in patients in their 40s to 60s, the corneal cylinders did not change over 10 years. Nevertheless, cylindrical axis of the cornea demonstrated a continuous shift toward against-the-rule (ATR) astigmatism. Vector analyses revealed that the astigmatic shift toward ATR progressed continually after patients reached their 40s, although the shift did not accelerate with age. These novel insights may pave the way for the development of potential strategies for vision correction, including refractive surgeries, and vision-quality maintenance in the elderly.

Outcomes and prognostic factors in canine epitheliotropic and nonepitheliotropic cutaneous T-cell lymphomas.

Canine cutaneous lymphoma is an uncommon lymphoma in dogs. Most canine cutaneous lymphoma cases have a T-cell origin. Canine cutaneous T-cell lymphoma (CTCL) is classified into epitheliotropic and nonepitheliotropic cutaneous lymphomas, and each type of lymphoma is subclassified into several histological subtypes. Limited information is available regarding the prognostic significance of clinical variables and histopathological subtypes in dogs with CTCL. This retrospective study aimed to investigate the influence of clinical variables and histopathological subtypes on the prognosis of dogs with CTCL. Forty-six dogs diagnosed with CTCL by histopathological examination were included. Histopathological specimens were reexamined and classified into CTCL subtypes. The influence of the type of skin lesion, histopathological subtype, haematological examination results and treatment response on the overall survival time (OS) was examined. Thirty-one dogs were diagnosed with epitheliotropic CTCL (mycosis fungoides in 28 dogs; pagetoid reticulosis in 3 dogs) and 15 dogs were diagnosed with nonepitheliotropic CTCL (anaplastic large T-cell lymphoma in 6 dogs; peripheral T-cell lymphoma, not otherwise specified, in 9 dogs). The OS of dogs diagnosed with epitheliotropic CTCL (141 days) was significantly shorter than that of dogs diagnosed with nonepitheliotropic CTCL (374 days). As clinical variables, the presence of neoplastic lymphocytes in peripheral blood, thrombocytopenia and initial chemotherapeutic response was related to prognosis. Our results demonstrated that histopathological subtype and several clinical variables were found to influence the prognosis of dogs with CTCL.

Renin-Angiotensin-Aldosterone System Inhibitors Prevent the Onset of Oxaliplatin-Induced Peripheral Neuropathy: A Retrospective Multicenter Study and in Vitro Evaluation.

Oxaliplatin (OXA) is used in chemotherapy for various cancer types and is associated with acute and chronic neurotoxicity. However, a preventive strategy for OXA-induced peripheral neuropathy (OIPN) and its underlying mechanism remain unclear. We examined the effects of renin-angiotensin-aldosterone system inhibitors (RAASIs) on OIPN by performing a retrospective multicenter study and an in vitro assay. We retrospectively evaluated electronic medical records of 976 patients who underwent one or more courses of OXA-containing regimens at Ehime, Okayama, and Tokushima University Hospitals. The primary endpoint was the incidence of OIPN during or after OXA administration. The effects of RAASIs and OXA on the neurite length in PC12 cells were determined. The combined administration of an OXA-containing regimen and RAASI significantly inhibited the cumulative incidence grade-2 or higher OIPN (log-rank test; p = 0.0001). RAASIs markedly suppressed the development of both acute and chronic OIPN (multivariate analysis; p = 0.017 and p = 0.011). In an in vitro assay, 10 µM OXA suppressed the neurite length; treatment with 1 µM aliskiren, spironolactone, 10 µM candesartan, and enalapril significantly restored neurite length to the control level. Moreover, 1 µM SCH772984 (a selective inhibitor of extracellular signal-regulated kinase, ERK1/2) and 500 µM SQ22536 (a cell-permeable adenylate cyclase (AC) inhibitor) markedly abolished neurite-extending effects of candesartan and enalapril. These results indicate that RAASIs possess preventive or therapeutic effects in acute and chronic OIPN, candesartan and enalapril may increase in the activity of ERK1/2 and AC in PC12 cells.

Hepcidin in Kawasaki disease: upregulation by acute inflammation in patients having resistance to intravenous immunoglobulin therapy.

Hepcidin is an iron metabolism inhibitor that increases with chronic inflammation. However, it is unclear whether hepcidin indicates acute inflammatory response in Kawasaki disease (KD), which is an acute systemic vasculitis. In this study, we examined the serum hepcidin levels before and after intravenous immunoglobulin (IVIG) therapy in responders and non-responders to IVIG. This was a pilot prospective observational study at a university hospital. All KD patients were initially administered 2 g/kg of IVIG as the first IVIG therapy (IVIG1) on day 4 to day 7 after onset. Non-responders to IVIG1 were additionally treated with the second IVIG therapy (IVIG2) using 1 g/kg of IVIG. All KD patients were also treated with aspirin. We measured serum hepcidin levels before IVIG1, after IVIG1, and during the recovery period. Among the 31 KD patients, 21 patients and 5 patients improved after IVIG1 (responders-1) and IVIG2 (responders-2), respectively, but 5 patients did not improve after IVIG2 (non-responders). Serum hepcidin levels before IVIG1 were significantly higher in responders-2 (159.0 ng/mL) and non-responders (240.0 ng/mL), compared to responders-1 (103.0 ng/mL). Serum hepcidin levels after IVIG1 were significantly higher in non-responders (163.0 ng/mL), compared to responders-1 (43.4 ng/mL) and responders-2 (54.6 ng/mL). Serum hepcidin levels of non-responders to IVIG were higher before IVIG and remained high after IVIG. Erythrocyte-related indexes, including hemoglobin, reticulocytes, iron, and ferritin before IVIG1, were not significantly different among the three groups. Serum hepcidin might be excessively upregulated by acute inflammation in KD patients having resistance to IVIG. Key Points • Hepcidin, an iron metabolism inhibitor in chronic inflammation, increases during the acute phase of Kawasaki disease. • Hepcidin levels before IVIG of non-responders were higher than those of responders in Kawasaki disease. • Hepcidin might be excessively upregulated by acute inflammation in KD patients having resistance to IVIG.

Surgical Outcomes of Rhegmatogenous Retinal Detachment with Different Peripheral Vitreous-Shaving Procedures.

PURPOSE: To compare the surgical outcomes of vitreous surgery for rhegmatogenous retinal detachment (RRD) after two different peripheral vitreous-shaving techniques are performed. METHODS: We reviewed 269 eyes with RRD that were treated with a 25-gauge vitrectomy by a single surgeon between June 2015 and May 2020. The exclusion criteria for the proposed air tamponade selection were as follows: more than two weeks since RRD onset, giant retinal tears, a history of complications following cataract surgery, high myopia, and proliferative vitreoretinopathy classified as grade C or higher. We examined the differences in the therapeutic effect between shaving under slit lamp microscope illumination (group A) and shaving under a wide-angle viewing system (group B). RESULTS: A total of 269 eyes were included in this study, with 146 eyes in group A and 123 eyes in group B. The primary anatomical success rates did not differ between group A (97.3%; 142/146 eyes) and group B (97.6%; 120/123 eyes; P = 0.102). However, the surgical time was significantly longer in group A (60.2 ± 17.1 min) than that in group B (46.9 ± 12.6 min) (P < 0.001). The multiple linear regression analysis revealed that surgical time was significantly correlated with using the wide-angle noncontact viewing system for vitreous shaving (adjusted R 2 = 0.248; beta [standard partial regression coefficient] = -0.447, P < 0.001), the number of retinal breaks (beta = 0.182, P = 0.001), and the quadrant of retinal detachment (beta = 0.205, P < 0.001). CONCLUSION: The surgical outcomes were similar regardless of the shaving procedure performed, and the surgical time was shortened by using the wide-angle noncontact viewing system for vitreous shaving.

Intraoperative Observation of a Macular Holes Using Optical Coherence Tomography.

PURPOSE: This study aimed to observe intraoperative changes in macular hole (MH) form using intraoperative optical coherence tomography (iOCT). METHODS: A total of 10 eyes from 10 patients with MH who underwent vitrectomy using iOCT from May 2015 to October 2015 at the Yamagata University Hospital were retrospectively evaluated. Accordingly, 25-gauge pars plana vitrectomy using iOCT with internal limiting membrane (ILM) peeling and sulfur hexafluoride gas tamponade was performed on each patient. During surgery, MHs were observed using iOCT over four points, namely, before posterior vitreous detachment (PVD) formation, after PVD formation, after ILM peeling, and after fluid-gas exchange. Thereafter, basal MH diameter and minimum aperture MH diameter were postoperatively analyzed. RESULTS: Before PVD formation, after PVD formation, after ILM peeling, and after fluid-gas exchange, the mean basal MH diameters were 690.7 ± 268.4, 683.3 ± 274.2, 683.7 ± 269.5, and 668.3 ± 261.4 µm, while the mean minimum aperture MH diameters were 278.3 ± 165.2, 283.0 ± 170.2, 257.0 ± 127.8, and 188.0 ± 105.0 µm, respectively. The mean minimum aperture MH diameter decreased significantly after fluid-gas exchange (one-way repeated measures ANOVA, p < 0.05). None of the patients exhibited intraoperative closure of the MHs. However, MH closure was confirmed in all patients after the surgery. CONCLUSION: None of the patients demonstrated intraoperative MHs closure. Accordingly, the minimum aperture MH diameter was the first change formation to close after fluid-gas exchange.

Peripheral Cystoid Degeneration Finding Using Intraoperative Optical Coherence Tomography in Rhegmatogenous Retinal Detachment.

PURPOSE: The interaction between the peripheral vitreous and retina is closely associated with the pathogenesis of rhegmatogenous retinal detachment (RRD). This study was conducted to examine the peripheral vitreous and retina in patients with RRD using intraoperative optical coherence tomography (iOCT). METHODS: This retrospective study included 50 eyes of 50 patients (mean age 59.42 ± 10.80 years) that underwent vitrectomy using iOCT for treating RRD at the Yamagata University Hospital between September 2015 and September 2016. Each patient underwent 25-gauge pars plana vitrectomy that was performed by a single surgeon. During vitreous shaving with ocular indentation, the iOCT findings of the peripheral vitreous and retina were recorded and analyzed postoperatively. RESULTS: In all patients, iOCT was able to detect the peripheral retina and vitreous around the vitreous base. Peripheral cystoid degeneration was detected on the peripheral retina of 27 eyes (54%). Furthermore, cystoid degeneration was detected around the retinal tear (5 patients), at the detached retinal area (8 patients), and at the attached retinal area (14 patients). CONCLUSION: iOCT enabled the evaluation of peripheral cystoid degeneration in patients with RRD. Cystoid degeneration might be associated with the pathogenesis of RRD.

Quantification of the peripheral vitreous after vitreous shaving using intraoperative optical coherence tomography.

OBJECTIVE: To evaluate the technique of peripheral vitreous shaving during vitrectomy, we measured the residual peripheral vitreous using intraoperative optical coherence tomography (iOCT). METHODS AND ANALYSIS: This retrospective study included 44 eyes that underwent 25-gauge pars plana vitrectomy with iOCT by a single surgeon. In all cases, the surgery was performed via ocular indentation. Cases in group A were treated with vitreous shaving under slit lamp microscope illumination, whereas cases in group B were treated with vitreous shaving under a wide-angle viewing system. Residual peripheral posterior vitreous-cortex detachment (PVD) was quantified by iOCT. RESULTS: iOCT image analysis enabled the visualisation of the angle formed between the retina and peripheral PVD around the vitreous base in all cases. After the completion of vitreous shaving, the mean length of the peripheral PVD was shorter in group A (961.7±214.7 µm) compared with group B (1925.3.7 ± 626.1 µm; p<0.01). CONCLUSION: iOCT enabled the quantification of the residual peripheral vitreous after vitreous shaving. The quantification of the residual peripheral vitreous after different shaving procedures will be important for advocating appropriate vitreous shaving in future.

Metastatic Orbital Tumor From Breast Ductal Carcinoma With Neuroendocrine Differentiation Initially Presenting as Ocular Symptoms: A Case Report and Literature Review.

Background: Orbital metastases from cancers of various organs can arise via the hematogenous route, and many originate from breast, prostate, and lung cancers. Such metastatic orbital tumors may be diagnosed before the primary tumor. We have encountered a case of breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and responded to chemotherapy, with improvement in visual function. Case Presentation: A woman in her fifties visited our ophthalmology department with a chief complaint of foreign body sensation and exophthalmos in her right eye. An elastic soft mass was palpated from the lateral orbit to the temporal region. A systemic examination revealed breast cancer and a metastatic orbital tumor. Excisional biopsy of the breast revealed a diagnosis of invasive ductal carcinoma with neuroendocrine differentiation, and immunohistochemical examination was negative for cytokeratin 7, making the case unusual. Chemotherapy was remarkably effective, and the tumor size decreased, resulting in improvement of visual function. Her general condition and quality of life are still good at present. We searched the PubMed English language literature focusing on metastatic orbital tumors from breast cancer in which ocular symptoms had been the initial presenting sign. No previous reports have documented neuroendocrine differentiation or cytokeratin 7 expression in isolated orbital metastases from breast cancer. Although it is not possible to be certain from this case alone, we speculated that some such cases might involve cytokeratin 7-negative invasive breast cancer with neuroendocrine differentiation. Conclusion: We have described our experience of a very rare case of cytokeratin 7 negative breast ductal carcinoma with neuroendocrine differentiation that metastasized to the orbit and formed a solitary giant tumor initially manifesting as ocular symptoms.

Age-Related Changes in Astigmatism and Potential Causes.

Astigmatism causes deterioration of the retinal image and affects vision quality. Maintenance and improvement of visual function requires an understanding of the prevalence, age-related changes, and mechanisms of astigmatism. In this article, we discuss the findings of studies that investigated astigmatism. Some of these studies showed that the prevalence of high degrees of astigmatism in childhood typically decreases with emmetropization. With-the-rule astigmatism occurs most commonly in young adults. With age, the prevalence of astigmatism increases, and the axis shifts from a predominance of with-the-rule astigmatism to a predominance of against-the-rule astigmatism. This age-related change is caused by alterations in corneal curvature. Although the cause of this change is not fully understood, alterations in the position and tension of the eyelid, corneal stromal collagen fibrils, Descemet membrane, and extraocular muscles may influence the shape of the cornea. Furthermore, genetic factors may contribute to the development of astigmatism. Technological advances in ophthalmology are expected to improve our understanding of the etiology of astigmatism and enable the maintenance of quality of vision.

Age-related variations in corneal geometry and their association with astigmatism: The Yamagata Study (Funagata).

To investigate how aging affects corneal geometry in Japanese adults, and the association between corneal geometry and astigmatism.We included 421 participants who had undergone systemic and ophthalmological examinations in 2015 in Funagata town, Yamagata, Japan. Corneal topographic data were obtained using anterior-segment optical coherence tomography (CASIA SS-1000). Astigmatism was evaluated using power vector analyses where J0 represents the power of the orthogonal astigmatism. Positive values of J0 indicate with-the-rule astigmatism, while negative values indicate against-the-rule (ATR) astigmatism.Regarding age-related variations in corneal geometry, the anterior elevations at axis 0° and 180° decreased, and those at axis 90° and 270° increased with increasing age in linear regression analyses, demonstrating horizontal steepening and vertical flattening of the corneal surface. There were no significant age-related variations in posterior elevations and pachymetry findings, including central corneal thickness. Regarding age-related variations in orthogonal astigmatism, the mean values of J0 and corneal J0 (cJ0) decreased by -0.014 and -0.015 per year of increase in age, indicating astigmatic shift toward ATR. Regarding the correlation between corneal geometry and astigmatism, the shift toward ATR was positively correlated with horizontal steepening and vertical flattening, in accordance with the age-related corneal variations. In addition, the posterior surface of the cornea also has an association with this shift to some extent.The results of our population-based study demonstrated that the age-related variation in astigmatism is associated with geometrical changes in the cornea, especially those in the anterior surface of the cornea.

Preventive Effects of Renin-angiotensin System Inhibitors on Oxaliplatin-induced Peripheral Neuropathy: A Retrospective Observational Study.

PURPOSE: Oxaliplatin-induced peripheral neuropathy has remained an unresolved issue in clinical practice. Our previous study hypothesized that inhibition of the renin-angiotensin system (RAS) may produce a preventive effect on oxaliplatin-induced neuropathy. The aim of this study was to clarify whether RAS inhibitors prevent oxaliplatin-induced peripheral neuropathy. METHODS: This study retrospectively analyzed data from cancer patients who had received chemotherapy including oxaliplatin and were treated with or without RAS inhibitors. This retrospective observational study was conducted at Ehime University Hospital using electronic medical records from May 2009 to December 2016. The primary end point was the incidence of severe peripheral neuropathy during or after oxaliplatin treatment, according to the Common Terminology Criteria for Adverse Events, version 4.0. A multivariate Cox proportional hazards model analysis was used to identify risk factors. FINDINGS: A total of 150 patients were included in the study. The estimated incidence of peripheral neuropathy was 36.9% and 91.7% in the RAS inhibitor group and the non-RAS inhibitor group, respectively. The multivariate analysis using a Cox proportional hazards model showed that the RAS inhibitor group was slightly associated with a decreased risk of neurotoxicity (adjusted hazard ratio, 0.42 [95% CI, 0.18-0.99]; P = 0.048). IMPLICATIONS: The present findings suggest that RAS inhibitors have the ability to prevent oxaliplatin-induced peripheral neuropathy.

Cross-Sectional and Longitudinal Investigation of the Power Vector in Astigmatism: The Yamagata Study (Funagata).

PURPOSE: To investigate how age and other factors affect astigmatism in Japanese adults over a period of 5 years. METHODS: We included 512 Japanese participants who had undergone systemic and ophthalmological examinations both in 2005-2007 and in 2010-2012 in Funagata town, Yamagata, Japan. Astigmatism was evaluated using power vector analyses, where J0 represents the power of orthogonal astigmatism. Positive values of J0 indicate with-the-rule astigmatism, whereas negative values indicate against-the-rule (ATR). RESULTS: In this cross-sectional investigation, J0 represented the power of orthogonal astigmatism, and multivariate regression revealed that both J0 and corneal J0 (cJ0) declined with increasing age (both P < 0.001). In a longitudinal investigation spanning 5 years, the mean amounts of change (Δ) in J0 and ΔcJ0 were -0.045 ± 0.308 and -0.072 ± 0.278, respectively. This confirmed an ATR shift with increasing age in most individuals. The age-divided distribution of the magnitude of differences indicated that older age was associated with a larger astigmatic change over a 5-year period in both the cornea and the entire eye. Using multivariate logistic regression, we observed that older age at baseline was a risk factor for low ΔJ0, indicating a large shift toward ATR astigmatism. CONCLUSIONS: We confirmed that a refractive and keratometric shift toward ATR astigmatism occurs with aging. Older age at baseline was also associated with a larger magnitude of astigmatic changes over the subsequent 5 years.

Age-Related Changes in Ocular Aberrations and the Yamagata Study (Funagata).

Human vision quality is influenced by ocular aberrations, including astigmatism and higher-order aberrations (HOAs), in combination with other optical factors. In this study, we introduce the results and perceptions of previous studies investigating these aberrations. We also introduce our results obtained as part of the Yamagata Study (Funagata), a population-based epidemiologic study. To investigate the astigmatic change with age, researchers have used the power vector analysis, allowing incorporation of the magnitude and axis of astigmatism into statistical analyses. It was found that the axes of refractive astigmatism shift from with-the-rule toward against-the-rule with aging. It was demonstrated that the change in corneal curvature causes this shift. It was further reported that HOA increase is associated with deterioration of visual function. Some authors described that HOA increases with age in adults and that aging disrupts compensation between corneal and internal aberrations. Our study confirmed these results after considering possible confounding factors. HOA decreased from childhood to early adulthood and then increased with age, as modeled by a second-order polynomial regression. It is possible that the reduction in HOA is involved in emmetropization. In addition to age, HOA is known to be influenced by several factors, including pupil diameter, accommodation, and pupil shift. Although HOA increases with aging, the increase may be compensated by decreasing the pupil diameter. Better understanding of the causes of optical alterations with aging will improve the maintenance of vision quality.

Increased interleukin-1ß and basic fibroblast growth factor levels in the cerebrospinal fluid during human herpesvirus-6B (HHV-6B) encephalitis.

Human herpesvirus 6B (HHV-6B) causes exanthema subitum in infants and is known to be mildly pathogenic. However, HHV-6B infection can induce febrile seizures in a high percentage of patients, and in rare cases, result in encephalitis. We detected higher levels of interleukin (IL)-1ß and basic fibroblast growth factor (bFGF) in the cerebrospinal fluid (CFS) of patients with HHV-6B encephalitis when compared to those in patients with non-HHV-6B-induced febrile seizures. In vitro, IL-1ß and bFGF enhanced HHV-6B gene expression in infected U373 astrocytes during the initial and maintenance phases of infection, respectively. These findings indicated that IL-1ß and bFGF contribute to HHV-6B growth and the onset of encephalitis.

Corneal vesicles accumulate collagen VI associated with tissue remodeling in apolipoprotein a-I deficiency: a case report.

BACKGROUND: Apo A-I deficiency clinically shows low serum levels of HDL cholesterol and corneal opacity at a young age. Histopathological evaluations of affected corneas are not enough, and the mechanism of corneal opacity is still unclear. CASE PRESENTATION: A 61-year-old woman suffered from blurred vision with a corneal opacity. She had significantly reduced serum levels of high-density lipoprotein cholesterol and Apo A-I, stenosis of the coronary arteries, and ischemic heart failure. On genetic examination, a homozygous mutation of Apo A-ITsukuba was identified. Histopathological examination of the corneal button after PKP showed numerous vesicles in the corneal stroma, which were more prominent in the deep stroma than in the shallow stroma. Collagen VI was observed in some of those vesicles. CONCLUSION: We experienced a rare case of corneal opacity due to Apo A-I deficiency. Our histopathological findings indicated that structural changes in corneal collagen fibrils contribute to the formation of stromal vesicles.

Factors Contributing to the Clinical Effectiveness of the DPP-4 Inhibitor Sitagliptin in Patients With Type 2 Diabetes.

PURPOSE: Treatment with dipeptidyl peptidase 4 (DPP-4) inhibitors may have responders or nonresponders. However, agreement on the effects of patient background and/or contributory factors that have a negative effect on the efficacy of DPP-4 inhibitors is lacking. The aim of the present study was to investigate the effect of resistance factors on the clinical efficacy of sitagliptin (SITA) for patients with type 2 diabetes. METHODS: We performed a retrospective study based on the medical records of patients who were treated with SITA alone (SITA-A; n = 16), a combination of a sulfonylurea (SU) without a change in dose and add-on SITA (SU + SITA; n = 29), SITA alone after the discontinuation of premedication with antidiabetic agents (SITA-AD; n = 18), or a combination of an SU with a dose reduction and SITA (L-SU + SITA; n = 17). Multivariate logistic regression analysis was employed to estimate the influence of resistance factors on hemoglobin (Hb) A1c lowering by SITA treatment for 3 months. FINDINGS: The HbA1c levels were significantly lower after 3-month treatment with SITA-A (6.3% [0.2%]), SU + SITA (7.1% [0.2%]), and L-SU + SITA (6.6% [0.2%]), but not with SITA-AD (6.3% [0.2%]), than baseline levels before treatment. Multivariate logistic regression analysis established that a decreased efficacy of SITA was markedly related to baseline HbA1c levels of ≥7.5% and dyslipidemia. IMPLICATIONS: These results suggest that checking for the presence or absence of resistance factors, including elevated HbA1c levels and dyslipidemia, may contribute to the appropriate usage of SITA.