Transcriptionally linked simultaneous overexpression of P450 genes for broad-spectrum herbicide resistance.

Broad-spectrum herbicide resistance (BSHR), often linked to weeds with metabolism-based herbicide resistance, poses a threat to food production. Past studies have revealed that overexpression of catalytically promiscuous enzymes explains BSHR in some weeds; however, the mechanism of BSHR expression remains poorly understood. Here, we investigated the molecular basis of high-level resistance to diclofop-methyl in BSHR late watergrass (Echinochloa phyllopogon) found in the United States, which cannot be solely explained by the overexpression of promiscuous cytochrome P450 monooxygenases CYP81A12/21. The BSHR late watergrass line rapidly produced 2 distinct hydroxylated diclofop acids, only 1 of which was the major metabolite produced by CYP81A12/21. RNA-seq and subsequent reverse transcription quantitative PCR (RT-qPCR)-based segregation screening identified the transcriptionally linked overexpression of a gene, CYP709C69, with CYP81A12/21 in the BSHR line. The gene conferred diclofop-methyl resistance in plants and produced another hydroxylated diclofop acid in yeast (Saccharomyces cerevisiae). Unlike CYP81A12/21, CYP709C69 showed no other herbicide-metabolizing function except for a presumed clomazone-activating function. The overexpression of the 3 herbicide-metabolizing genes was also identified in another BSHR late watergrass in Japan, suggesting a convergence of BSHR evolution at the molecular level. Synteny analysis of the P450 genes implied that they are located at mutually independent loci, which supports the idea that a single trans-element regulates the 3 genes. We propose that transcriptionally linked simultaneous overexpression of herbicide-metabolizing genes enhances and broadens the metabolic resistance in weeds. The convergence of the complex mechanism in BSHR late watergrass from 2 countries suggests that BSHR evolved through co-opting a conserved gene regulatory system in late watergrass.

Dioxotriazine derivatives as a new class of P2X3 receptor antagonists: Identification of a lead and initial SAR studies.

P2X3 receptor is an ATP-gated ion channel, mainly localized on peripheral sensory neurons. Currently, several clinical trials are being conducted with P2X3 receptor antagonists for the treatment of chronic pain or cough. To identify a P2X3 lead compound, we reexamined the HTS evaluation compounds and selected dioxotriazine derivatives from which we identified a hit compound. As a result of the hit-to-lead SAR, we obtained lead compound 1 which had a moderate inhibitory effect on P2X3 receptors (IC50, 128 nM). Further improvement of the potency and PK profiles of this lead compound finally led to the selected compound 74 (P2X3 IC50, 16.1 nM; P2X2/3 IC50, 2931 nM), which demonstrated a strong analgesic effect against allodynia on oral administration in the rat partial sciatic nerve ligation model of neuropathic pain (ED50, 3.1 mg/kg).

Anti-MOG antibody-associated disorders: differences in clinical profiles and prognosis in Japan and Germany.

BACKGROUND: Neurological disorders with IgG antibodies against myelin-oligodendrocyte glycoprotein (MOG-IgG) have been increasingly recognised as a new type of neuroinflammatory disorder. OBJECTIVE: The study aimed to identify regional and ethnic differences in clinical profiles of MOG-IgG-associated disorders between East Asian (Japanese) and Caucasian (German) patients. METHODS: Demographic, clinical and therapeutic data from 68 MOG-IgG-positive adults were collected (Japanese, n=44; German, n=24). RESULTS: Age and sex were similar between cohorts, with optic neuritis occurring most frequently at onset (Japanese: 61%; German: 58%). However, Japanese patients had a lower annualised relapse rate (0.4 vs 0.8, p=0.019; no relapse, 64% vs 25%, p=0.002) and lower Expanded Disability Status Scale score at the last visit (1.0 vs 2.0; p=0.008), despite similar follow-up periods (mean, 73.9 months vs 73.4 months), than those of German patients, respectively. Cerebral syndromes were more common (27% vs 4%; p=0.021) and myelitis less common (21% vs 50%; p=0.012) in Japanese than in German patients, respectively. Japanese patients were more commonly treated with long-term corticosteroids (73%), whereas German patients were more commonly treated with rituximab or other immunosuppressants (63%). CONCLUSIONS: Among patients with MOG-IgG, Japanese tended to have a monophasic milder disease, whereas the majority of German patients had a relapsing course and more frequent myelitis, findings compatible with neuromyelitis optica spectrum disorder. Although the attack-prevention treatment regimens were considerably different, genetic and environmental factors may be important to determine clinical phenotypes and disease activity.

Comparison of Mill Suss™-guided radial artery catheterization with the long-axis in-plane ultrasound-guided method under general anesthesia: a randomized controlled trial.

Continuous arterial blood pressure measurement is an effective perioperative monitoring method in patients with high-risk comorbidities. Recently, ultrasound guidance has been reported to facilitate radial artery catheterization. A new device, Mill Suss™, has also been developed for visualization of the radial artery and superficial veins using near-infrared laser light. In this study, we hypothesized that the Mill Suss-guided method might reduce the time and the number of attempts required for radial artery catheterization under general anesthesia, as compared to the long-axis in-plane ultrasound-guided method. Seventy-two adult patients aged 20-80 years, ASA physical status I or II, were randomly assigned to the Mill Suss-guided group (Group M: n = 36) or ultrasound-guided group (Group U: n = 36). Primary outcomes were the time required for successful radial artery catheterization and the number of cannulation attempts. There were no significant differences in the characteristics of patients between the two groups. The time required for successful radial artery catheterization was significantly shorter in Group M than in Group U. The number of attempts for successful cannulation was not statistically significantly different between the two groups. However, the results might be different among anesthesiologists well experienced in the ultrasound-guided method.

Coexistence of Two Types of Spin Splitting Originating from Different Symmetries.

The symmetry of a surface or interface plays an important role in determining the spin splitting and texture of a two-dimensional band. Spin-polarized bands of a triangular lattice atomic layer (TLAL) consisting of Sn on a SiC(0001) substrate is investigated by spin- and angle-resolved photoelectron spectroscopy. Surprisingly, both Zeeman- and Rashba-type spin-split bands, without and with spin degeneracy, respectively, coexist at a K point of the Sn TLAL. The K point has a threefold symmetry without inversion symmetry according to the crystal structure including the SiC periodicity, meaning that the Zeeman-type is consistent with the symmetry of the lattice while the Rashba-type is inconsistent. Our density functional calculations reveal that the charge density distribution of the Rashba-type (Zeeman-type) band shows (no) inversion symmetry at the K point. Therefore, the symmetry of the charge density distribution agrees with both types of the spin splitting.

CSF cytokine profile in MOG-IgG+ neurological disease is similar to AQP4-IgG+ NMOSD but distinct from MS: a cross-sectional study and potential therapeutic implications.

OBJECTIVE: To evaluate cerebrospinal fluid (CSF) cytokine profiles in myelin oligodendrocyte glycoprotein IgG-positive (MOG-IgG+) disease in adult and paediatric patients. METHODS: In this cross-sectional study, we measured 27 cytokines in the CSF of MOG-IgG+ disease in acute phase before treatment (n=29). The data were directly compared with those in aquaporin-4 antibody-positive (AQP4-IgG+) neuromyelitis optica spectrum disorder (NMOSD) (n=20), multiple sclerosis (MS) (n=20) and non-inflammatory controls (n=14). RESULTS: In MOG-IgG+ disease, there was no female preponderance and the ages were younger (mean 18 years, range 3-68; 15 were below 18 years) relative to AQP4-IgG+ NMOSD (41, 15-77) and MS (34, 17-48). CSF cell counts were higher and oligoclonal IgG bands were mostly negative in MOG-IgG+ disease and AQP4-IgG+ NMOSD compared with MS. MOG-IgG+ disease had significantly elevated levels of interleukin (IL)-6, IL-8, granulocyte-colony stimulating factor and granulocyte macrophage-colony stimulating factor, interferon-γ, IL-10, IL-1 receptor antagonist, monocyte chemotactic protein-1 and macrophage inflammatory protein-1α as compared with MS. No cytokine in MOG-IgG+ disease was significantly different from AQP4-IgG+ NMOSD. Moreover many elevated cytokines were correlated with each other in MOG-IgG+ disease and AQP4-IgG+ NMOSD but not in MS. No difference in the data was seen between adult and paediatric MOG-IgG+ cases. CONCLUSIONS: The CSF cytokine profile in the acute phase of MOG-IgG+ disease is characterised by coordinated upregulation of T helper 17 (Th17) and other cytokines including some Th1-related and regulatory T cells-related ones in adults and children, which is similar to AQP4-IgG+ NMOSD but clearly different from MS. The results suggest that as with AQP4-IgG+ NMOSD, some disease-modifying drugs for MS may be ineffective in MOG-IgG+ disease while they may provide potential therapeutic targets.

Modulation of Electron-Phonon Coupling in One-Dimensionally Nanorippled Graphene on a Macrofacet of 6H-SiC.

Local electron-phonon coupling of a one-dimensionally nanorippled graphene is studied on a SiC(0001) vicinal substrate. We have characterized local atomic and electronic structures of a periodically nanorippled graphene (3.4 nm period) prepared on a macrofacet of the 6H-SiC crystal using scanning tunneling microscopy/spectroscopy (STM/STS) and angle-resolved photoelectron spectroscopy (ARPES). The rippled graphene on the macrofacets distributes homogeneously over the 6H-SiC substrate in a millimeter scale, and thus replica bands are detected by the macroscopic ARPES. The STM/STS results indicate the strength of electron-phonon coupling to the out-of-plane phonon at the K̅ points of graphene is periodically modified in accordance with the ripple structure. We propose an interface carbon nanostructure with graphene nanoribbons between the surface rippled graphene and the substrate SiC that periodically modifies the electron-phonon coupling in the surface graphene.

Gemcitabine and Vinorelbine Combination Chemotherapy in Taxane-Pretreated Patients with Metastatic Breast Cancer: A Phase II Study of the Kinki Multidisciplinary Breast Oncology Group (KMBOG) 1015.

BACKGROUND: This phase II study was conducted to evaluate the efficacy and safety of the chemotherapy combination of gemcitabine and vinorelbine in taxane-pretreated Japanese metastatic breast cancer patients. METHODS: In this multicenter, phase II, single-arm study, patients with recurrent or metastatic HER2-negative breast cancer were administered gemcitabine (1,200 mg/m2) and vinorelbine (25 mg/m2) intravenously on days 1 and 8 every 3 weeks. The primary endpoint was the objective response rate, and other endpoints included progression-free survival, overall survival, and safety. RESULTS: A total of 42 patients were enrolled in this study. The objective response rate and clinical benefit rate were 24 and 43%, respectively. The median progression-free survival was 4.0 months. The median overall survival was 11.1 months. Grade 3/4 neutropenia was the most common hematologic toxicity, occurring in 22 patients (54%). Nonhematologic toxicity was moderate and transient, with fatigue (48%) being the most common condition and no severe adverse event reported. CONCLUSION: The combination of gemcitabine and vinorelbine is an effective and tolerable regimen for HER2-negative, taxane-pretreated, metastatic breast cancer patients in Japan.

Effects of Pb Intercalation on the Structural and Electronic Properties of Epitaxial Graphene on SiC.

The effects of Pb intercalation on the structural and electronic properties of epitaxial single-layer graphene grown on SiC(0001) substrate are investigated using scanning tunneling microscopy (STM), noncontact atomic force microscopy, Kelvin probe force microscopy (KPFM), X-ray photoelectron spectroscopy, and angle-resolved photoemission spectroscopy (ARPES) methods. The STM results show the formation of an ordered moiré superstructure pattern induced by Pb atom intercalation underneath the graphene layer. ARPES measurements reveal the presence of two additional linearly dispersing π-bands, providing evidence for the decoupling of the buffer layer from the underlying SiC substrate. Upon Pb intercalation, the Si 2p core level spectra show a signature for the existence of PbSi chemical bonds at the interface region, as manifested in a shift of 1.2 eV of the bulk SiC component toward lower binding energies. The Pb intercalation gives rise to hole-doping of graphene and results in a shift of the Dirac point energy by about 0.1 eV above the Fermi level, as revealed by the ARPES measurements. The KPFM experiments have shown that decoupling of the graphene layer by Pb intercalation is accompanied by a work function increase. The observed increase in the work function is attributed to the suppression of the electron transfer from the SiC substrate to the graphene layer. The Pb intercalated structure is found to be stable in ambient conditions and at high temperatures up to 1250 °C. These results demonstrate that the construction of a graphene-capped Pb/SiC system offers a possibility of tuning the graphene electronic properties and exploring intriguing physical properties such as superconductivity and spintronics.

[Maintenance of Long-Term Stable Disease(SD)in Metastatic Breast Cancer with Eribulin - A Case Report of Long-Term SD in Japan].

This case report discusses a 48-year-old woman with metastatic breast cancer: T4c(10.5 cm)N2bM1,(OSS, LYM), stage IV, estrogen receptor(ER)(+), progesterone receptor(PgR)(+), human epidermal growth factor receptor-2(HER2) (-), and Ki-67 17.2%. Administration of eribulin was initiated after treatment with anthracycline and taxane. Thereafter, 28 courses of eribulin maintained a SD state for over a year and improved the quality of life(QOL). Eribulin is effective for both prolonging life and improving QOL, which are the main goals in the treatment of metastatic or recurrent cancer. Therefore, this evidence suggests that eribulin can be effective in various clinical situations.

[A Case of Squamous Cell Carcinoma of the Breast].

Squamous cell carcinoma(SCC)of the breast is a rare disease. We encountered a case of SCC of the breast that relapsed in the early postoperative period and rapidly progressed thereafter. A 38-year-old woman visited our hospital presenting with a tumor in the left breast consisting of a 5-cm mass with an irregularly sharped wall. Fine needle biopsy examination showed squamous cell carcinoma. A modified radical mastectomy by Auchincloss's method was performed on the left breast. SCC was confirmed by histological examination. Two months later, local recurrence on the chest wall was found during adjuvant chemotherapy. Thereafter, the disease rapidly progressed, and finally, the patient died of respiratory failure caused by lung metastasis. The prognosis of SCC of the breast is recognized as being more unfavorable than that of invasive ductal carcinoma. We should develop an effective chemotherapeutic strategy for this disease.

[Ultrasound Analysis of the Anatomical Relationships between Vertebral Arteries and Internal Jugular Veins in Adults].

BACKGROUND: Accidental puncture of a vertebral artery can occur through the internal jugular vein during central venous catheterization. METHODS: We evaluated the anatomical relationships between vertebral arteries and internal jugular veins in one hundred adult patients under general anesthesia using echo image. RESULTS: The vertebral artery could be observed in all patients under the level of cricoid cartilage. Vertebral arteries ran in an outward direction toward the caudal side (3.9 mm lateral and 14.6 mm deep from the internal jugular vein : median). Mean width of vertebral artery was 4.2 mm. Because the width of central venous catheter guide wire is approx. 1 mm, accidental puncture of a vertebral artery can occur through the internal jugular vein during central venous catheterization. By the use of ultrasound analysis, the vertebral artery could be observed completely. CONCLUSIONS: It is important to identify the location of vertebral arteries under the level of cricoid cartilage and avoid the tap toward the lateral side. We can avoid accidental puncture of vertebral artery by taking care of these points.

[Is the LHRH Agonist Recommended for Fertility Preservation ?].

The POEMS reportedan effect of goserelin for fertility preservation. The Clinical Practice Guideline for Breast Cancer by The Japanese Breast Cancer Society indicates that the use of the LHRH agonist (LHRHa) for preventing chemotherapy-induced early menopause is a grade C-1 recommendation, and its use for fertility preservation is a grade C-2 recommendation. Results from previous studies on the effects of LHRHa for fertility preservation have varied owing to differences in chemotherapy regimens, definitions of ovarian failure, and dosages of tamoxifen. In the POEMS, the primary endpoint of ovarian failure at 2 years was significantly lower, and the secondary endpoint of pregnancy outcomes was better in the combination group; however, precise interpretation is difficult because many cases were excluded. Currently, it is not necessary to revise The Clinical Practice Guideline; however, desirable results from future studies may allow the recommendation of a specific dosage of LHRHa for fertility preservation.

Breast conserving surgery using volume replacement with oxidized regenerated cellulose: a cosmetic outcome analysis.

We evaluated the cosmetic outcome of volume replacement with oxidized regenerated cellulose (ORC) after breast-conserving surgery (BCS) and also examined factors that may have influenced the results. Ninety-four patients who underwent BCS with ORC replacement between January 2010 and August 2012 participated in this study. The cosmetic outcomes of these patients were evaluated using scores based on the criteria of the Japan Breast Cancer Society. We evaluated cosmetic scores with regards to several clinical factors and the occurrence of complications after this procedure. The mean score of the cosmetic outcome of all patients was 9.5 points of 12 points. Thirty-seven patients were categorized as "Excellent," 34 were "Good," 22 were "Fair," and 1 was "Poor." Patient age, body mass index, weight of the specimen, and ORC amount were not significantly different between patients with favorable cosmetic scores and those without. However, the weight of the removed specimen was slightly higher in patients with an unfavorable cosmetic score. Although acute dermatitis and eczema was observed in 15% and 3% of patients, all of them were improved with conservative treatment. Cosmetic scores were significantly higher in patients without complications than in patients with complications. In conclusion, ORC replacement after BCS is a simple and reliable procedure. The selection of indication and prevention of complications are important for obtaining a better cosmetic outcome. This is the first report to cosmetically evaluate a relatively large number of patients that have undergone ORC replacement after BCS.

Breast cancer subtype and distant recurrence after ipsilateral breast tumor recurrence.

BACKGROUND: There is little information about the impact of breast cancer subtype on prognosis after ipsilateral breast tumor recurrence (IBTR). METHODS: One hundred eighty-five patients were classified according to breast cancer subtype, as approximated by estrogen receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67, of IBTR, and we evaluated whether breast cancer subtype was associated with distant recurrence after IBTR. RESULTS: There was a significant difference in distant disease-free survival (DDFS) after IBTR according to breast cancer subtype defined by a cutoff of the Ki-67 index of 20 % (p = 0.0074, log-rank test). The 5-year DDFS rates for patients with luminal A, luminal B, triple-negative, and HER2 types were 86.3, 57.1, 56.6, and 65.9 %, respectively. In addition, breast cancer subtype was significantly associated with distant recurrence after IBTR on adjustment for various clinicopathologic factors (p = 0.0027, Cox proportional hazards model). CONCLUSIONS: Our study suggests that breast cancer subtype based on immunohistochemical staining predicts the outcomes of patients with IBTR. Further analyses are needed (UMIN-CTR number UMIN000008136).

Validation of online calculators to predict the non-sentinel lymph node status in sentinel lymph node-positive breast cancer patients.

PURPOSE: This study evaluated and compared the predictive values of the Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram and the Stanford nomogram for predicting non-sentinel lymph node (SLN) metastasis in patients with SLN metastasis, which were the only nomograms available online, and verified their usefulness in the macrometastasis or micrometastasis/isolated tumor cell (ITC) subgroups. METHODS: Eighty-nine patients with a positive SLN biopsy who underwent axillary lymph node dissection were analyzed. The predicted probability of non-SLN metastasis was calculated using a computerized model from the websites for each nomogram. The results were compared using the area under the curve (AUC) of the receiver operating characteristics curve for each model. The false-negative and false-positive rates were also calculated. RESULTS: The AUC for the entire population was 0.701 with the MSKCC nomogram and 0.756 with the Stanford nomogram. The AUCs of macrometastasis and micrometastasis/ITC groups were 0.680 and 0.469 with the MSKCC nomogram, and were 0.676 and 0.574 with the Stanford nomogram, respectively. Although false-negative cases were not identified, the false-positive rates were high in both subgroups when using these nomograms. CONCLUSIONS: This independent comparison found no significant difference between the two nomograms. In this study, these nomograms could not reliably predict positive non-SLN in patients with SLN micrometastasis/ITC.

Width-dependent band gap of arm-chair graphene nanoribbons formed on vicinal SiC substrates by MBE.

Formation and electronic states of graphene nanoribbons with arm-chair edges (AGNR) are studied on the SiC(0001) vicinal surfaces toward the [11-00] direction. The surface step and terrace structures of both 4H and 6H-SiC substrates are used as the growth templates of one-dimensional arrays of AGNRs, which are prepared using the carbon molecular beam epitaxy followed by hydrogen intercalation. A band gap is observed above theπ-band maximum by angle-resolved photoelectron spectroscopy (ARPES) for the both samples. The average widths of the AGNRs are 6 and 10 nm, and the estimated average band gaps are 0.40 and 0.28 eV for the 4H- and 6H- substrates, respectively. A simple and phenomenological inverse relation between the energy gap and AGNR width works in the analyses of the ARPES data.

Chemical evolution of primordial salts and organic sulfur molecules in the asteroid 162173 Ryugu.

Samples from the carbonaceous asteroid (162173) Ryugu provide information on the chemical evolution of organic molecules in the early solar system. Here we show the element partitioning of the major component ions by sequential extractions of salts, carbonates, and phyllosilicate-bearing fractions to reveal primordial brine composition of the primitive asteroid. Sodium is the dominant electrolyte of the salt fraction extract. Anions and NH4+ are more abundant in the salt fraction than in the carbonate and phyllosilicate fractions, with molar concentrations in the order SO42- > Cl- > S2O32- > NO3- > NH4+. The salt fraction extracts contain anionic soluble sulfur-bearing species such as Sn-polythionic acids (n < 6), Cn-alkylsulfonates, alkylthiosulfonates, hydroxyalkylsulfonates, and hydroxyalkylthiosulfonates (n < 7). The sulfur-bearing soluble compounds may have driven the molecular evolution of prebiotic organic material transforming simple organic molecules into hydrophilic, amphiphilic, and refractory S allotropes.

Systematic Literature Review of Clinical and Economic Evidence for Spinal Muscular Atrophy.

INTRODUCTION: The recent advent of disease-modifying therapies (DMTs) has dramatically changed the treatment landscape of spinal muscular atrophy (SMA), and the multifaceted impact of this advancement has not been assessed thoroughly in the growing body of literature. We sought to summarize the literature on the natural history of SMA and the impact of SMA DMTs, including health-related quality of life (HRQOL) and utilities, clinical efficacy and safety, and economic impact. METHODS: Systematic literature reviews were conducted following PRISMA guidelines with no inclusive dates. Relevant studies were identified by searching full-text databases on November 12-13, 2020, including MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and EconLit, conference proceedings, health technology assessment databases, and clinical trial registries. All searches used a combination of MeSH and key terms. Studies were screened according to criteria based upon population, intervention, outcomes, and study design structure. RESULTS: Findings from 17, 23, 32, and 42 studies were included for the evaluation of natural history of SMA, HRQOL and utilities, clinical efficacy and safety, and economic impact of DMTs, respectively. Currently available data indicate that untreated SMA is associated with considerable humanistic and economic burden, with estimates of costs varying by treatment. While a variety of interventions have been evaluated in SMA clinical trials, quantitative synthesis of safety and efficacy findings was not feasible because of inconsistencies in reported outcomes. Data assessing impacts of DMTs on HRQOL were also lacking. CONCLUSIONS: Overall, this systematic literature review highlights a clear need for up-to-date and methodologically rigorous clinical, HRQOL, and economic data to support unbiased assessments of the relative clinical and economic effectiveness of SMA treatments. More research is required to extend our understanding of the burden of SMA on HRQOL utility assessments and the impact of new DMTs on HRQOL and utilities for patients with SMA.

Effectiveness of Current Treatments for Wet Age-Related Macular Degeneration in Japan: A Systematic Review and Pooled Data Analysis.

PURPOSE: We conducted a systematic review to investigate the effectiveness of clinical treatments for wet age-related macular degeneration (wAMD) in Japanese patients in the decade since anti-vascular endothelial growth factor (VEGF) therapies were introduced. METHODS: PubMed was searched for articles published in English between 1 January 2008 and 30 September 2018 using a multistring search strategy. Reviews were scanned for additional relevant studies and select gray literature was evaluated. Mean and/or median for the logarithm of the minimum angle of resolution (logMAR) visual acuity (VA), central retinal thickness (CRT), and the number of injections after 12 months of treatment were calculated using extracted data. Data were stratified by disease type and treatment modality. RESULTS: Of 335 studies identified, 94 were selected for data extraction (147 treatment arms; typical AMD, n = 25; polypoidal choroidal vasculopathy [PCV], n = 85). Mean (median) logMAR VA was 0.44 (0.32) for typical AMD and 0.34 (0.31) for PCV; the respective mean number of anti-VEGF injections was 5.6 and 4.6. The mean CRT was approximately 220 µm for both groups. For typical AMD, anti-VEGF monotherapy resulted in better VA outcomes than photodynamic therapy (PDT) alone. For PCV, anti-VEGF monotherapy or anti-VEGF plus PDT combination therapy resulted in better VA and CRT outcomes than PDT monotherapy. Combination therapy required fewer injections than anti-VEGF monotherapy (PCV, 3.2 versus 5.3). CONCLUSION: wAMD treatment has advanced dramatically in the years since anti-VEGF drugs were introduced in Japan. Discrete patient populations may benefit from differing management regimens, including the fewer injections required with combination therapy.