Search

Wataru Matsumiya,1 Sentaro Kusuhara,1 Noriyuki Sotani,1 Kyung Woo Kim,1 Ryuto Nishisho,1 Rei Sotani,1 Hisanori Imai,1 Akihito Uji,2 Makoto Nakamura1 1Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe, Japan; 2Department of Ophthalmology, Kyoto University Graduate School of Medicine, Kyoto, JapanCorrespondence: Wataru Matsumiya, Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan, Tel +81-78-382-6048, Fax +81-78-382-6059, Email ytkmatsu@med.kobe-u.ac.jpPurpose: To evaluate the characteristics of posterior vitreous cells in patients with uveitis on the classification basis using spectral domain optical coherence tomography (SD-OCT).Methods: In this retrospective chart review, all eyes were classified into three groups: infectious uveitis (IFU, n=7), noninfectious granulomatous uveitis (NIGU, n=13), and noninfectious nongranulomatous uveitis (NINGU, n=13). We measured the size, number, and density of vitreous hyperreflective particles in the posterior vitreous area that was defined as the space between the vitreous top and the internal limiting membrane on OCT. The correlations between vitreous haze and vitreous particles were also evaluated.Results: Thirty-three eyes from 23 patients with active posterior uveitis were included. IFU had significantly more particles than NIGU and NINGU (P=0.03 and P< 0.001, respectively). The vitreous particle density was higher in IFU than in NIGU and NINGU (P=0.03 and P=0.003, respectively). The mean largest particle size was greater in IFU and NIGU than in NINGU (P=0.01 and P=0.03, respectively). The median vitreous haze of 2+ in IFU, 1+ in NIGU and NINGU showed no significant difference among three groups (P=0.21). Conversely, the correlation of the largest particle size with vitreous haze was significant at ρ= 0.44 (P=0.01).Conclusion: SD-OCT may be useful for assessing ocular inflammation based on morphological characteristics of vitreous particles on the uveitis classification basis.Keywords: optical coherence tomography, OCT, vitreous cell, cell, hyperreflective particles, uveitis

Satoshi Igawa,1 Masashi Kasajima,1 Taihei Ono,1 Takahiro Ozawa,1 Mikiko Kakegawa,1 Seiichiro Kusuhara,1 Takashi Sato,1 Yoshiro Nakahara,1 Tomoya Fukui,1 Masanori Yokoba,2 Masaru Kubota,2 Hisashi Mitsufuji,3 Jiichiro Sasaki,4 Katsuhiko Naoki1 1Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara-city, Kanagawa, Japan; 2School of Allied Health Sciences, Kitasato University, Sagamihara-city, Kanagawa, Japan; 3Kitasato University School of Nursing, Sagamihara-city, Kanagawa, Japan; 4Kitasato University School of Medicine, Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara-city, Kanagawa, JapanCorrespondence: Satoshi IgawaDepartment of Respiratory Medicine, Kitasato University School of Medicine, 1-15-1, Kitasato, Minami-ku, Sagamihara-city, Kanagawa, 252-0374, JapanTel +81-42-778-8506Fax +81-42-778-6412Email igawa@kitasato-u.ac.jpBackground: The clinical outcomes of elderly patients with EGFR-mutated non-small cell lung cancer (NSCLC) who are treated with osimertinib have not been sufficiently evaluated. This study aimed to assess the efficacy and safety of osimertinib in elderly chemotherapy-naive patients with NSCLC harboring sensitive EGFR mutations.Patients and Methods: We assessed the clinical effects of osimertinib as a first-line treatment for elderly NSCLC patients (≥ 75 years of age) with an exon 19 deletion or exon 21 L858R mutation in EGFR. All patients were administered 80 mg/day osimertinib as initial treatment.Results: Forty-three patients (24 women and 19 men) with adenocarcinoma who were treated between August 2018 and July 2021 were included in this study; their median age was 79 years (range, 75– 90 years). The overall objective response rate was 60.5%. The median progression-free survival (PFS) and time to treatment failure (TTF) of the entire patient population were 22.1 months and 14.6 months, respectively. The most common adverse event was rash acneiform (42%), followed by diarrhea (33%) and paronychia (28%); none of these were grades ≥ 3. Interstitial lung disease developed in 8 patients (18.6%); however, no treatment-related deaths occurred. Multivariate analysis identified performance status and disease stage as predictors of PFS and TTF.Conclusion: Considering the findings of this study and despite an observed discordance between PFS and TTF, osimertinib appears to be an effective and safe treatment option in elderly patients with advanced NSCLC harboring sensitive EGFR mutations. To obtain conclusive results, further studies in a larger elderly population are warranted.Keywords: non-small cell lung carcinoma, chemotherapy-naïve patients, efficacy

Sentaro Kusuhara, Makoto Nakamura Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Kobe 650-0017, JapanCorrespondence: Sentaro KusuharaDepartment of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, JapanTel +81-78-382-6048Fax +81-78-382-6059Email kusu@med.kobe-u.ac.jpAbstract: Reduction of intraocular pressure (IOP) is the only reliable treatment for glaucoma that maintains the patient’s visual function throughout life, and IOP-lowering eyedrops are the mainstay of therapy. Ripasudil hydrochloride hydrate (brand name: Glanatec ophthalmic solution 0.4%; Kowa Company, Ltd., Japan) is a Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor that lowers IOP by increasing conventional aqueous outflow. Since the approval of ripasudil eyedrops in 2014, a large store of clinical data has been amassed in Japan. With regard to safety, conjunctival hyperemia is the most common adverse drug reaction (ADR) and is usually transient and mild. Blepharitis and allergic conjunctivitis are other major local ADRs. Systemic ADRs are rare, but we should be wary of allergic reactions. With regard to efficacy, ripasudil is expected to lower IOP in almost all glaucoma subtypes (including primary open-angle glaucoma, secondary glaucoma, and primary angle-closure glaucoma) and in all patterns of treatment initiation (monotherapy, combination therapy, switching therapy, and add-on therapy). However, the status of the trabecular meshwork may affect the IOP-lowering effect of ripasudil. In patient selection, current evidence-based information on the safety and efficacy of ripasudil should be fully considered. As irreversible damage to the trabecular meshwork would considerably affect efficacy, it may be better to start ripasudil treatment during an early stage of glaucoma.Keywords: ripasudil, glaucoma, intraocular pressure, efficacy, safety

Satoshi Igawa,1 Taihei Ono,1 Masashi Kasajima,1 Mikiko Ishihara,1 Yasuhiro Hiyoshi,1 Seiichiro Kusuhara,1 Noriko Nishinarita,1 Tomoya Fukui,1 Masaru Kubota,1 Jiichiro Sasaki,2 Mitsufuji Hisashi,3 Masanori Yokoba,4 Masato Katagiri,4 Katsuhiko Naoki11Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara-city, Kanagawa, Japan; 2Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara-city, Kanagawa, Japan; 3Kitasato University School of Nursing, Sagamihara-city, Kanagawa, Japan; 4School of Allied Health Sciences, Kitasato University, Sagamihara-city, Kanagawa 252-0373, JapanPurpose: A T790M of the epidermal growth factor receptor (EGFR) is the most frequently encountered mutation conferring acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). The aim of this study was to assess the differential clinical outcomes of osimertinib therapy in NSCLC patients with T790M according to the type of activating EGFR mutation, ie, exon 19 deletion or L858R point mutation.Patients and methods: A prospective observational cohort study was conducted to evaluate the efficacy and safety of osimertinib in patients with a major EGFR mutation and T790M-positive advanced NSCLC who had disease progression after first-line EGFR-TKI therapy. The efficacy of osimertinib was evaluated according to the type of EGFR mutation.Results: A total of 51 patients were included in this study. An objective response was obtained in 29 patients, indicating an objective response rate of 58.8%. The response rate was 69.7% in patients with exon 19 deletion and 38.9% in patients with L858R point mutation, indicating a statistically significant difference (P=0.033). The median progression-free survival (PFS) and overall survival (OS) of the entire patient population were 7.8 and 15.5 months, respectively. The median PFS in the exon 19 deletion and L858R point mutation groups was 8.0 months and 5.2 months, respectively, indicating a statistically significant difference (P=0.045). Median OS in the exon 19 deletion and L858R point mutation groups was significantly different at 19.8 months and 12.9 months, respectively (P=0.0015). Multivariate analysis identified the exon 19 deletion as a favorable independent predictor of PFS and OS.Conclusion: Investigators should consider the proportions of sensitive EGFR mutation types as a stratification factor in designing or reviewing clinical studies involving osimertinib.Keywords: EGFR genotype, non-small cell lung carcinoma, osimertinib, efficacy

Atsuko Katsuyama,1 Sentaro Kusuhara,1 Ryuto Nishisho,1 Wataru Matsumiya,1 Atsushi Azumi,2 Makoto Nakamura1 1Department of Surgery, Division of Ophthalmology, Kobe University Graduate School of Medicine, Chuo-ku, Kobe 650-0017, Japan; 2Department of Ophthalmology, Kobe Kaisei Hospital, Nada-ku, Kobe 657-0068, Japan Purpose: This study aimed to evaluate the long-term efficacy and safety of infliximab (IFX) and cyclosporine (CsA) combination therapy for refractory uveoretinitis in Behçet’s disease (BD). Patients and methods: The study involved a retrospective review of the medical records of 11 patients with Behçet’s uveoretinitis refractory to conventional treatment who had been treated with IFX+CsA combination therapy. The frequency of ocular inflammatory attacks and a Behçet’s disease ocular attack score 24 (BOS24) were used as indices for the evaluation of efficacy during each 6-month period prior to and following initiation of therapy. For the assessment of safety, adverse events (AEs) were recorded throughout the treatment period. Results: The patients had received IFX+CsA combination therapy for 5.6±2.3 years. The frequency of ocular attacks per 6-month period decreased markedly from 2.9±1.6 during the baseline period to 0.6±0.9 during months 1–6, 0.5±0.9 during months 7–12, 0.3±0.5 during months 13–18, 0.3±0.7 during months 19–24, and 0.0±0.0 thereafter (P=0.003). The BOS24 score per ocular attack significantly decreased from 5.2±2.4 during the baseline period to 1.5±2.1 during months 1–6, 1.7±3.1 during months 7–12, 1.6±2.9 during months 13–18, and 0.4±1.0 during months 19–24 (P=0.002). No serious AEs were observed, with the exception of urinary tract infection and cataract progression. Two patients exhibited transient elevation of the serum creatinine level, which was normalized following a reduction in the dose of CsA. Conclusion: For refractory Behçet’s uveoretinitis, IFX+CsA combination therapy offers a promising treatment option as it appears to have an acceptable safety profile and can reduce the frequency and severity of ocular inflammatory attacks over a long period of time. Keywords: Behçet’s disease, uveitis, infliximab, cyclosporine, efficacy, safety

Satoshi Igawa,1 Noriko Nishinarita,1 Akira Takakura,1 Takahiro Ozawa,1 Shinya Harada,1 Seiichiro Kusuhara,1 Hideyuki Niwa,2 Shinji Hosotani,1 Hideyuki Sone,1 Yoshiro Nakahara,1,3 Tomoya Fukui,1 Hisashi Mitsufuji,4 Masanori Yokoba,5 Masaru Kubota,1 Masato Katagiri,5 Jiichiro Sasaki,6 Katsuhiko Naoki1 1Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara 252-0374, Kanagawa, Japan; 2Department of Respiratory Medicine, National Hospital Organization Nagoya Medical Center, Nagoya 460-0001, Aichi, Japan; 3Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama 241-8515, Kanagawa, Japan; 4Kitasato University School of Nursing, Sagamihara 252-0329, Kanagawa, Japan; 5School of Allied Health Sciences, Kitasato University, Sagamihara 252-0373, Kanagawa, Japan; 6Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Sagamihara 252-0374, Kanagawa, Japan Background: The optimal chemotherapy regimen for non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) remains unknown. Therefore, in this study, we investigated the real-world efficacy and safety of carboplatin (CBDCA) plus nab-paclitaxel (nab-PTX) as a first-line regimen for NSCLC patients with ILD. Patients and methods: We retrospectively reviewed advanced NSCLC patients with ILD who had received CBDCA plus nab-PTX as a first-line chemotherapy regimen between April 2013 and March 2018. Patients were diagnosed with ILD based on the findings of a pretreatment high-resolution computed tomography of the chest. Results: The 34 patients enrolled in this study were included in the efficacy and safety analysis. Collagen vascular disease or a history of exposure to dust or asbestos was not reported for any patients. The median age of patients was 71 years (range, 59–83 years), and 32 patients had a performance status of 0 or 1. The overall response rate was 38.2%. The median progression-free survival and overall survival were 5.8 months and 12.7 months, respectively. Chemotherapy-related acute exacerbation of ILD was observed in two patients (5.7%). Other toxicities were feasible, and no treatment-related deaths occurred. Conclusion: CBDCA plus nab-PTX, as a first-line chemotherapy regimen for NSCLC, showed favorable efficacy and safety in patients with preexisting ILD. Keywords: interstitial lung disease, non-small-cell lung cancer, carboplatin, nab-paclitaxel

Masayuki Shirasawa,1,* Tomoya Fukui,1,* Seiichiro Kusuhara,1 Yasuhiro Hiyoshi,1 Mikiko Ishihara,1 Masashi Kasajima,1 Yoshiro Nakahara,1 Sakiko Otani,1 Satoshi Igawa,1 Masanori Yokoba,2 Hisashi Mitsufuji,3 Masaru Kubota,1 Masato Katagiri,1 Jiichiro Sasaki,4 Katsuhiko Naoki1 1Department of Respiratory Medicine, Kitasato University School of Medicine, Kanagawa, Japan; 2Department of Medical Laboratory, Kitasato University School of Allied Health Sciences, Kanagawa, Japan; 3Fundamental Nursing, Kitasato University School of Nursing, Kanagawa, Japan; 4Research and Development Center for New Medical Frontiers, Kitasato University School of Medicine, Kanagawa, Japan *These authors contributed equally to this work Background: Small cell lung cancer (SCLC) is typically categorized according to disease extent as limited or extensive, and utility of the 8th TNM classification, recommended for lung cancer staging, which demonstrates a strong association with non-small-cell lung cancer (NSCLC) management, remains unclear.Methods: This retrospective study included 277 consecutive SCLC patients treated at a single institution between 2008 and 2016.Results: According to the currently used two-stage system, 186 (65.7%) of the patients were classified as having extensive disease (ED)-SCLC. Among the ED-SCLC patients, ten (5.3%), 38 (20.4%), 32 (17.2%), and 106 (57.0%) were categorized into stages M0, M1a, M1b, and M1c, respectively, according to the 8th TNM classification. There was a significant difference in overall survival based on the M descriptors: 15.8 (95% CI 9.4–22.2) months in the M1b group vs 7.3 (95% CI 5.7–8.9) months in the M1c group (P

PurposeTo test whether Heidelberg Retina Tomograph (HRT) is applicable to assess the optic nerve head (ONH) configuration of the atrophic phase of non-glaucomatous optic neuropathy when a default set of the reference plane is used.MethodsTen eyes with non-arteritic anterior ischaemic optic neuropathy (NAION), 17 eyes with Leber's hereditary optic neuropathy (LHON), 40 eyes with compressive optic neuropathy (CON) owing to chiasmal tumour, and 241 eyes of control individuals were examined with HRT using the default reference plane. The global values of HRT parameters were evaluated among the groups of patients and controls. The sectoral measurements of the eyes with LHON and CON were compared with controls. To eliminate the influence of disc size and age on HRT measurements, eyes with disc area- and age-matched normal controls were used for comparison with eyes with NAION and LHON.ResultsCup parameters in eyes with NAION were similar to those in controls. The retinal nerve fibre layer (RNFL) thickness was significantly thinner in eyes with NAION than that of controls. The eyes with LHON had significantly larger cup parameters, smaller rim volume, and thinner mean RNFL thickness than controls. Eyes with CON had significantly larger rim area and smaller cup parameters but similar RNFL thickness compared with controls.ConclusionsWhen the default reference plane is used, HRT can measure the ONH configuration in eyes with NAION and LHON as expected. However, caution must be made to interpret the parameters obtained from the eyes with CON.Eye (2008) 22, 1154–1160; doi:10.1038/sj.eye.6702871; published online 25 May 2007 [ABSTRACT FROM AUTHOR]

AimsTo assess the changes in macular and peripapillary retinal nerve fibre layer (RNFL) thickness in eyes with unilateral optic atrophy and to evaluate the relationship between retinal thickness and visual function.MethodsEnrolled were 22 patients with unilateral optic atrophy. Macular thickness at the divided nine areas and peripapillary RNFL thickness in quadrantic sections were measured by optical coherence tomography. Thickness values in the affected eyes were compared with those in the contralateral unaffected eyes. The correlation of foveal thickness with best-corrected visual acuity (BCVA) was evaluated. The correlation between retinal thickness and the remaining visual field area circumscribed with I-4-e isopter in superior and inferior hemifield was assessed.ResultsMacular thinning was observed in all areas (P<0.001 in each area) other than the fovea (P=0.068). Peripapillary RNFL thickness decreased in all quadrantic sections (P<0.001 in each section). The affected to unaffected eye ratio of retinal thickness was more than 0.6 in each area. BCVA did not correlate with foveal thickness (correlation coefficient=0.094, P=0.668). Although not statistically significant (P=0.281, superior hemifield; P=0.053, inferior hemifield), there was a tendency that eyes with severe visual field loss show more marked retinal thinning.ConclusionsMacular thinning with the preserved foveal thickness is a hallmark of eyes with optic atrophy. Together with no correlation between foveal thickness and BCVA, this finding would help in differential diagnosis of macular and optic nerve diseases.Eye (2006) 20, 882–887. doi:10.1038/sj.eye.6702013; published online 15 July 2005 [ABSTRACT FROM AUTHOR]

The localization of estrogen receptors (ER) in osteogenic cells during the early stage of medullary bone osteogenesis was studied immunohistochemically in the femurs of estrogen-treated male Japanese quail. Alkaline phosphatase (ALP) activity was used as a marker for osteogenic cells. ER immunostaining was observed in the nuclei of weak ALP-positive bone lining cells on the endosteal bone surface of nontreated birds. After 24 hours of estrogen treatment, nuclear immunostaining was detected in ALP-positive preosteoblasts on the endosteal bone surface. After 48 hours, the medullary bone appeared to some degree along the endosteal surface. ER immunostaining was observed in the nuclei of ALP-positive osteoblasts on the medullary bone surface. This study demonstrates that ER are present in osteogenic cells, and suggests that estrogen directly acts on medullary bone osteogenesis. [ABSTRACT FROM AUTHOR]