INCIDENCE AND CHARACTERISTICS OF NEOVASCULAR AGE-RELATED MACULAR WITH OVER A 12-MONTH REMISSION AFTER THREE MONTHLY AFLIBERCEPT ADMINISTRATION: 60 Months Results of a Pro Re Nata Regimen.

PURPOSE: To investigate the characteristics of patients with over a 12-month remission after 3 monthly intravitreal aflibercept injections followed by a pro re nata regimen for exudative age-related macular degeneration (AMD). METHODS: One hundred forty-four eyes with exudative AMD were included. All patients received 3 monthly intravitreal aflibercept injections as a loading dose, followed by an as-needed regimen for 60 months. Patients were classified into the remission and recurrence groups depending on the presence or absence of a 12-month remission. ARMS2 A69S and CFH I62V were genotyped in all cases. RESULTS: During the study, 82 eyes (56.9%) showed 12 months or more remission at least once. The cumulative incidence rate of a 12-month remission showed a plateau pattern and converged to 60% (y = -166.26x-2.172 + 0.6, R2 = 0.8168). Patients in the remission group were younger than those in the recurrence group (P < 0.001) and had less risk allele frequency of the ARMS2 gene than the recurrence group (P < 0.001). The longer the remission interval was prolonged, the better visual acuity was achieved at the 60-month visit (P < 0.001). CONCLUSION: Fifty-seven percent of patients showed a 12-month remission or more at least once during a 60-month follow-up, suggesting that patients with no reactivation can prolong the treatment interval.

DISTINCT CHARACTERISTICS OF SIMPLE VERSUS COMPLEX CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To compare the clinical and genetic characteristics of simple and complex central serous chorioretinopathy using central serous chorioretinopathy international group criteria. METHODS: Patients with idiopathic central serous chorioretinopathy were included. Depending on the presence or absence of retinal pigment alterations greater than 2-disc areas in either eye, patients were classified into complex or simple types. Demographic factors and clinical findings were compared between groups. CFH variants, including rs800292 and rs1329428, were genotyped using TaqMan technology. RESULTS: A total of 319 consecutive patients were evaluated at the initial presentation. Of them, 53 (16.6%) had the complex type. The complex type was exclusively seen in men (100% vs. 79.0%, P = 2.0 × 10 -4 ) and demonstrated a significantly higher proportion of bilateral involvement (75.5% vs. 17.7%, P = 6.2 × 10 -18 ) and descending tract(s) (83.0% vs. 0%, P = 1.2 × 10 -57 ) than the simple type. Increased choroidal thickness (425 ± 131 vs. 382 ± 110, P = 0.02) and decreased central retinal thickness (274 ± 151 vs. 337 ± 136, P = 2.9 × 10 -4 ) were observed for the complex versus simple type. The risk allele frequencies of both variants were significantly higher in the complex versus simple type (rs800292: 61.3% vs. 48.7%, P = 0.018; rs1329428: 65.1% vs. 54.3%, P = 0.04). CONCLUSION: In this new classification system, the complex type has distinct genetic and clinical characteristics compared with the simple type.

The Novel Arylamidine T-2307 Demonstrates In Vitro and In Vivo Activity against Candida auris.

The in vitro and in vivo activity of the arylamidine T-2307 against Candida auris was evaluated. T-2307 demonstrated in vitro activity (MIC ranges ≤ 0.008 to 0.015 µg/ml at 50% inhibition; 0.125 to >4 µg/ml at 100% inhibition). Treatment with T-2307 (3 mg/kg subcutaneous [SC] once daily) also significantly improved survival (70% at 21 days postinfection) and reduced kidney fungal burden (5.06 log10 CFU/g) compared to control (0% survival and 7.09 log10 CFU/g) (P < 0.01).

Association of CRP levels with ARMS2 and CFH variants in age-related macular degeneration.

PURPOSE: To investigate whether plasma high sensitivity C-reactive protein (hs-CRP) level is associated with exudative age-related macular degeneration (AMD) as well as variants of ARMS2 A69S and CFH I62V in patients with exudative AMD. METHODS: A case-control study was done comparing CRP among patients with exudative AMD including those with polypoidal choroidal vasculopathy, typical AMD and retinal angiomatous proliferation, and CRP were also compared between cases and controls. Plasma CRP was measured from peripheral blood using latex nepherometry for all participants. Genotyping of ARMS2 A69S and CFH I62V was performed for all patients with exudative AMD using TaqMan technology. RESULTS: Among 125 patients with exudative AMD, including 31 with typical neovascular AMD, 73 with PCV and 21 with RAP lesions and 150 controls, CRP levels were higher in exudative AMD than in controls. (P = 2.7 × 10-5) There was not a significant difference in hs-CRP levels among AMD subtypes. Neither variants of ARMS2 nor CFH was associated with hs-CRP level in patients with exudative AMD. A multiple regression analysis revealed that gender male, presence of exudative AMD and presence of cardiovascular diseases were associated with increased plasma hs-CRP. CONCLUSIONS: Plasma hs-CRP was elevated independent of variants of ARMS2 A69S and CFH I62V in patients with exudative AMD.

The Novel Arylamidine T-2307 Selectively Disrupts Yeast Mitochondrial Function by Inhibiting Respiratory Chain Complexes.

The novel arylamidine T-2307 exhibits broad-spectrum in vitro and in vivo antifungal activities against clinically significant pathogens. Previous studies have shown that T-2307 accumulates in yeast cells via a specific polyamine transporter and disrupts yeast mitochondrial membrane potential. Further, it has little effect on rat liver mitochondrial function. The mechanism by which T-2307 disrupts yeast mitochondrial function is poorly understood, and its elucidation may provide important information for developing novel antifungal agents. This study aimed to determine how T-2307 promotes yeast mitochondrial dysfunction and to investigate the selectivity of this mechanism between fungi and mammals. T-2307 inhibited the respiration of yeast whole cells and isolated yeast mitochondria in a dose-dependent manner. The similarity of the effects of T-2307 and respiratory chain inhibitors on mitochondrial respiration prompted us to investigate the effect of T-2307 on mitochondrial respiratory chain complexes. T-2307 particularly inhibited respiratory chain complexes III and IV not only in Saccharomyces cerevisiae but also in Candida albicans, indicating that T-2307 acts against pathogenic fungi in a manner similar to that of yeast. Conversely, T-2307 showed little effect on bovine respiratory chain complexes. Additionally, we demonstrated that the inhibition of respiratory chain complexes by T-2307 resulted in a decrease in the intracellular ATP levels in yeast cells. These results indicate that inhibition of respiratory chain complexes III and IV is a key factor for selective disruption of yeast mitochondrial function and antifungal activity.

Antifungal susceptibility trend and analysis of resistance mechanism for Candida species isolated from bloodstream at a Japanese university hospital.

We compared the susceptibility of six commercially available antifungal agents (fluconazole, itraconazole, voriconazole, caspofungin, micafungin, and amphotericin B) against 133 Candida bloodstream isolates between 2008 and 2013 at Aichi Medical University Hospital. C. albicans was the most common isolate, followed by C. parapsilosis, C. glabrata, and C. tropicalis. MIC90s of voriconazole against C. albicans, C. parapsilosis, and C. tropicalis were the lowest and that of micafungin against C. glabrata was the lowest among the agents tested. Of the 133 isolates, two strains were identified as drug-resistant. One was a fluconazole-resistant C. glabrata strain, in which the ATP-binding cassette (ABC) transporter gene expression was upregulated. The other was a micafungin-resistant C. glabrata strain, that had 13 amino acid substitutions in FKS1 and FKS2, including a novel substitution V1342I in FKS1 hotspot 2. We also evaluated the susceptibility of T-2307, a novel class of antifungal agents used in clinical trials, against the fluconazole- and micafungin-resistant C. glabrata strain; the MICs of T-2307 were 0.0039 and 0.0078 µg/mL, respectively. In conclusion, the incidence of bloodstream infection caused by drug-resistant Candida spp. was rare from 2008 to 2013 at our hospital. Of 133 isolates, only two strains of C. glabrata were resistant to azoles or echinocandins, that upregulated the ABC transporter genes or had novel FKS mutations, respectively.

In vitro and in vivo antifungal activities of T-2307, a novel arylamidine, against Cryptococcus gattii: an emerging fungal pathogen.

Objectives: T-2307, a novel arylamidine, exhibits potent broad-spectrum activities against the majority of fungal pathogens. In this study, the antifungal activity of T-2307 against Cryptococcus gattii was evaluated in comparison with those of amphotericin B, fluconazole and voriconazole in vitro and in vivo . Methods: The MICs for 15 clinical isolates were determined according to CLSI guidelines and time-kill studies were performed using C. gattii YF2784. In a murine model for intranasal pulmonary infection caused by C. gattii YF2784, the test compounds were administered once daily for 7 days from 2 h or 14 days post-infection. The viable counts in the lungs and brain were determined at 21 days post-infection. Results: The MIC range, MIC 50 , MIC 90 and geometric mean MIC of T-2307 were 0.0078-0.0625, 0.0313, 0.0625 and 0.0394 mg/L, respectively. The MIC of T-2307 was significantly lower than those of fluconazole, voriconazole and amphotericin B. T-2307 showed concentration-dependent fungicidal activity at 4 times the MIC or higher. Administration of T-2307 at 2 mg/kg/day, amphotericin B at 1 mg/kg/day and fluconazole at 160 mg/kg/day from 2 h post-infection significantly reduced viable counts in the lungs and brain. However, when the administration was started 14 days post-infection, only T-2307 significantly reduced the viable counts in both the lungs and the brain at 1 mg/kg/day. Conclusions: T-2307 shows excellent in vitro and in vivo antifungal activities against C. gattii and would be a promising new candidate for the treatment of cryptococcosis.

T-2307, a novel arylamidine, is transported into Candida albicans by a high-affinity spermine and spermidine carrier regulated by Agp2.

OBJECTIVES: T-2307, a novel arylamidine, exhibits potent broad-spectrum activities against pathogenic fungi, particularly Candida albicans. We previously reported that T-2307 uptake was mainly mediated by a saturable high-affinity carrier at the MIC for C. albicans. Since we hypothesized that the potent anticandidal activity arose from accumulation via the high-affinity carrier, we characterized the specificity and kinetic features of the carrier. METHODS: The MICs of T-2307 for C. albicans strains were evaluated in the presence and absence of potential competitive substrates. The cells were exposed to [(14)C]T-2307, [(14)C]spermine or [(14)C]spermidine in the presence of unlabelled T-2307, pentamidine, propamidine, or competitive substrates if necessary, and the radioactivity in the cells was measured. C. albicans gene deletion was performed using a one-step PCR-based technique. RESULTS: Coapplication with exogenous spermine or spermidine decreased the antifungal activity and uptake of T-2307 in C. albicans strains. T-2307 competitively inhibited spermine and spermidine uptake with inhibition constants similar to its Km for the high-affinity carrier. The comparison of MICs and kinetic values between T-2307 and other diamidine compounds suggested that the different antifungal properties could be partially attributable to the variations in their affinity with the carrier. Studies of gene deletion mutants revealed that T-2307 was transported into C. albicans by a high-affinity spermine and spermidine carrier regulated by Agp2. CONCLUSIONS: Uptake of T-2307 via the high-affinity spermine and spermidine carrier regulated by Agp2 could contribute to its potent antifungal activity. Further investigation is required to identify the high-affinity carrier for potential targeting with novel therapies.

The novel arylamidine T-2307 demonstrates in vitro and in vivo activity against echinocandin-resistant Candida glabrata.

OBJECTIVES: Candida species are major causes of invasive mycoses in immunocompetent and immunocompromised hosts. Treatment options are limited in the setting of antifungal resistance and increased rates of echinocandin-resistant Candida glabrata have been reported. The novel arylamidine T-2307 demonstrates potent in vitro antifungal activity against Candida species. Our objective was to evaluate the in vitro and in vivo activity of T-2307 against resistant C. glabrata. METHODS: In vitro activity was determined against 42 clinical C. glabrata isolates, including 17 echinocandin-resistant strains. Neutropenic ICR mice were inoculated intravenously with an echinocandin-resistant C. glabrata isolate (T-2307; caspofungin MICs ≤0.008 and 0.5 mg/L, respectively). Therapy with vehicle control, T-2307 (0.75, 1.5, 3 or 6 mg/kg subcutaneously once daily) or caspofungin (1 or 10 mg/kg intraperitoneally once daily) began 1 day post-challenge. Kidneys were collected on day 8 and fungal burden was assessed by counting cfu. RESULTS: T-2307 demonstrated potent in vitro activity against C. glabrata (geometric mean MIC 0.0135 mg/L), which was maintained against echinocandin-resistant isolates (geometric mean MIC 0.0083 mg/L). T-2307 also demonstrated in vivo efficacy in mice infected with echinocandin-resistant C. glabrata. Significant reductions in fungal burden were observed at each dosage level of T-2307 compared with control. Reductions in fungal burden were also observed with high-dose caspofungin. CONCLUSIONS: T-2307 demonstrated potent in vitro activity against C. glabrata, including echinocandin-resistant isolates, which translated into in vivo efficacy against invasive candidiasis caused by an echinocandin-resistant C. glabrata strain. These results demonstrate the potential for T-2307 as therapy against echinocandin-resistant Candida.

The novel arylamidine T-2307 maintains in vitro and in vivo activity against echinocandin-resistant Candida albicans.

We evaluated the in vitro and in vivo activities of the investigational arylamidine T-2307 against echinocandin-resistant Candida albicans. T-2307 demonstrated potent in vitro activity, and daily subcutaneous doses between 0.75 and 6 mg/kg of body weight significantly improved survival and reduced fungal burden compared to placebo control and caspofungin (10 mg/kg/day) in mice with invasive candidiasis caused by an echinocandin-resistant strain. Thus, T-2307 may have potential use in the treatment of echinocandin-resistant C. albicans infections.

[Sensitivity surveillance of Streptococcus pneumoniae isolates for several antibacterial agents in Gifu and Aichi prefectures (2011-2012)].

We investigated the susceptibility to antibacterial agents, genotype of penicillin-binding protein (PBP) genes and macrolide resistant genes, and the serotypes against 270 strains of Streptococcus pneumoniae isolated from medical facilities in Gifu and Aichi prefectures between October 2011 and April 2012. These results were compared with those against S. pneumoniae isolated in 2008-2009 and 2010-2011. The number of gPSSP with 3 normal PBP genes, gPISP with 1 or 2 normal PBP genes and gPRSP with 3 abnormal genes isolated in 2011-2012 was 15 (5.6%), 162 (60.0%) and 93 (34.4%) strains, respectively. Compared with those isolated in 2008-2009 and 2010-2011, the numbers of gPRSP were decreasing. On the other hand, the isolates with no macrolide-resistant gene, only mefA, only ermB, and both mefA and ermB were 16 (5.9%), 75 (27.8%), 153 (56.7%) and 26 (9.6%). Compared with those isolated in 2008-2009 and 2010-2011, the numbers of isolates with ermB, which was usually associated with high-level resistance, were increasing. The prevalent pneumococcal serotypes in children were type 3 (14.4%), following by type 15 and 19F (9.3%). The coverages of 7-valent pneumococcal conjugate vaccine (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) were calculated as 22.9% and 49.2%, respectively. The coverages of PCV7 and PCV13 in gPRSP isolated from children were 47.7% (21/44 strains) and 72.7% (32/44 strains). The MIC90 of each antibacterial agent was as follows; 0.125pg/mL for imipenem, panipenem and garenoxacin, 0.25 µg/mL for meropenem and doripenem, 0.5 µg/mL for cefditoren, moxifloxacin and tosufloxacin, 1 µg/mL for amoxicillin, clavulanic acid/amoxicillin, cefteram, cefcapene and ceftriaxone, 2 µg/mL for benzylpenicillin, ampicillin, sulbactam/ampicillin, piperacillin, tazobactam/piperacillin and levofloxacin, 4 µg/mL for cefdinir, flomoxef and pazufloxacin, 16 µg/mL for minocycline, > 64 µg/mL for clarithromycin and azithromycin, and these MIC90s were about the same as those in 2010-2011.

Association of Polyp Regression after Loading Phase with 12-Month Outcomes of Eyes with Polypoidal Choroidal Vasculopathy.

PURPOSE: We compared 12-month outcomes of eyes with polypoidal choroidal vasculopathy (PCV) with or without complete regression of polyps observed one month after three monthly intravitreal administrations (loading phase) of aflibercept (2.0 mg/0.05 mL) or brolucizumab (6.0 mg/0.05 mL). METHODS: All patients underwent indocyanine green angiography at both baseline and 3 months after initial injection and were followed up monthly with an as-needed regimen for up to 12 months. A total of 62 patients with PCV were included: 30 eyes were treated with brolucizumab, and 32 were treated with aflibercept. Eyes with complete regression of polyps (regression group) had significantly smaller maximum polyp diameter and were more frequently treated with brolucizumab than those without complete regression (non-regression) group. RESULTS: Best corrected visual acuity was comparable between the two groups at 12 months. Although the 12-month retreatment-free proportion was comparable between the two groups (33.0% versus 27.0%, p = 0.59), a retreatment-free period was significantly longer in the regression group than in the non-regression group (8.3 ± 3.3 versus 6.5 ± 3.6 months, p = 0.022), and the number of additional injections was significantly fewer in the regression group than in the non-regression group (1.2 ± 1.2 versus 3.0 ± 2.6, p = 0.007). CONCLUSIONS: Complete regression of polyps observed after the initial phase possibly prolongs the retreatment-free period and reduces the number of additional injections irrespective of aflibercept or brolucizumab.

Bactericidal activity of garenoxacin against in vitro biofilm formed by nontypeable Haemophilus influenzae.

Using ß-lactamase-negative ampicillin (ABPC)-susceptible (BLNAS) and ß-lactamase-negative ABPC-resistant (BLNAR) nontypeable Haemophilus influenzae (NTHi) strains isolated from otological patients, colony biofilm was prepared on membrane filter substrates. Bactericidal activities of garenoxacin (GRNX), levofloxacin (LVFX), cefditoren (CDTR), and clavulanic acid/amoxicillin (CVA/AMPC) were examined by counting viable cells after drug exposure to biofilm cells for 6 and 24 h and by observation under a scanning electron microscope (SEM). After exposure of biofilm to the 100-fold MIC of GRNX or LVFX for 24 h, GRNX and LVFX showed potent bactericidal activity (∆log10 CFU/ml, ≥5.1). In this case, the drug-exposure AUC, exposure concentration × 24 µg h/ml, was 64-128 % for GRNX and 121 % for LVFX of free AUC at the clinical dosage in humans, respectively. CDTR and CVA/AMPC at 100-fold MIC exhibited little bactericidal activity against biofilm cells. Under an SEM, after exposure of BLNAS and BLNAR biofilms to GRNX or LVFX, most of the biofilm matrices were transformed. Quinolones such as GRNX show potent bactericidal activity against biofilm-forming NTHi at the usual clinical dosage.

[Sensitivity surveillance of Streptococcus pneumoniae isolates for several antibacterial agents in Gifu and Aichi prefecture (2010-2011)].

We investigated genotype of penicillin-binding protein (PBP) genes and macrolide resistant genes, the serotypes and the susceptibility to antibacterial agents against 258 strains of Streptococcus pneumoniae isolated from medical facilities in Gifu and Aichi prefectures between January 2010 and March 2011. These results were compared with those against 377 strains of S. pneumoniae isolated in 2008-2009. The number of genotype penicillin-susceptible S. pneumoniae (gPSSP) with 3 normal PBP genes, genotype penicillin-intermediate S. pneumoniae (gPISP) with 1 or 2 normal PBP genes and genotype penicillin-resistant S. pneumoniae (gPRSP) with 3 abnormal genes was 11 (4.3%), 135 (52.3%) and 112 (43.4%) strains, respectively. The isolates with no macrolide-resistant gene, only mefA, only ermB, and both mefA and ermB were 17 (6.6%), 65 (25.2%), 143 (55.4%) and 33 (12.8%). The prevalent pneumococcal serotypes isolated from children were type 19F (18.2%), following by type 6A and 15 (11.7%). The potential coverage of pneumococcal conjugate vaccine (PCV7) was 43.8%. The prevalent pneumococcal serotypes isolated from adults were high in order of type 19F (12.8%), type 6A, 3 and 11 (10.3%), excepting non-typable strains (17.9%), and from elderly persons were type 6B (23.2%) and type 3 (13.4%). The MIC90 of each antibacterial agents was as follows; 0.0625 microg/mL for garenoxacin, 0.125 microg/mL for panipenem, 0.25 microg/mL for imipenem, doripenem, tosufloxacin, 0.5 microg/mL for cefditoren, meropenem, moxifloxacin, 1 microg/mL for amoxicillin, clavulanic acid/amoxicillin, cefteram, cefcapene, ceftriaxone, 2 microg/mL for benzylpenicillin, piperacillin, tazobactam/ piperacillin, pazufloxacin, levofloxacin, 4 microg/mL for cefdinir, flomoxef, 16 microg/mL for minocycline, > 64 microg/mL for clarithromycin, azithromycin and these MIC90s were about the same as those in 2008-2009.

Mid-Term Results of Ab Interno Trabeculectomy among Japanese Glaucoma Patients.

BACKGROUND: The evaluation of ab interno trabeculectomy, referred to as trabectome®, among Japanese patients is insufficient. SUBJECTS AND METHODS: Japanese patients who underwent trabectome® at the University of Yamanashi Hospital were included. The investigated parameters were intraocular pressure (IOP), best corrected visual acuity, glaucoma medications, visual field, and corneal endothelial cell density. The success rate and its associated factors were investigated. RESULTS: A total of 250 eyes from 197 patients were enrolled. The trabectome® significantly reduced IOP and glaucoma medications up to 48 months. Concomitant cataract extraction enhanced the reduction in IOP and glaucoma medications up to 42 months. At 36 months postoperatively, 40.8% satisfied IOP of the same or less than 18 mmHg or more than a 20% IOP reduction with the same or less use of glaucoma medications as preoperatively. Preoperative IOP and combined cataract extraction were significantly associated with the success rate. The trabectome® alone did not show a significant reduction in corneal endothelial cells. Eyes with postoperative transient IOP elevation and removal of anterior chamber hemorrhage were 11.2% and 1.2%, respectively. Twenty-four eyes (9.6%) underwent additional glaucoma surgeries. CONCLUSIONS: The trabectome® could be considered an effective and safe surgery. Compared to trabectome® alone, combined cataract surgery was superior in lowering IOP and reducing glaucoma medications.

Comparison of one-year outcomes between as-needed brolucizumab and aflibercept for polypoidal choroidal vasculopathy.

PURPOSE: To compare the one-year visual and anatomic outcomes of an as-needed regimen of brolucizumab and aflibercept for polypoidal choroidal vasculopathy (PCV). STUDY DESIGN: A retrospective comparative study. METHODS: A retrospective medical chart review was performed for consecutive 56 eyes from 56 patients with PCV initially treated with thee monthly intravitreal aflibercept (n = 33, 2.0 mg/0.05 ml) or brolucizumab (n = 23, 6.0 mg/0.05 ml) followed by as-needed administration, followed up for at least 12 months. All patients were followed up monthly, and fluorescein and indocyanine green angiography (ICGA) were performed at baseline, 3-month, and 12-month visits. RESULTS: At the 12-month visit, best-corrected visual acuity significantly improved from 0.30 ± 0.31 to 0.21 ± 0.29 (p = 0.042) in the brolucizumab-treated group and from 0.24 ± 0.25 to 0.14 ± 0.25 (p = 7.7×10-3) in the aflibercept-treated group, suggesting comparable visual improvement in both groups. Central retinal thickness and subfoveal choroidal thickness decreased by 38.4% and 14.2%, respectively, in the brolucizumab-treated group and by 34.8% and 13.9%, respectively, in the aflibercept-treated group at the 12-month visit. The mean number of additional injections was significantly higher in the aflibercept-treated group (2.9 ± 2.7) than in the brolucizumab-treated group (1.3 ± 1.2, p = 0.045). The complete resolution of polypoidal lesions on ICGA was higher in the brolucizumab-treated group than in the aflibercept-treated group (3-month visit: 56.5% vs 30.3%, 12-month visit: 56.5% vs 30.3%). CONCLUSIONS: In treatment-naïve eyes with PCV, the as-needed administration regimen of brolucizumab was comparable to aflibercept in terms of visual and anatomical outcomes, with fewer additional injections during the 12-month follow-up.

A Treat-and-Extend Regimen of Intravitreal Brolucizumab for Exudative Age-Related Macular Degeneration Refractory to Aflibercept: A 12-Month Result.

We aimed to investigate whether a treat-and-extend regimen of intravitreal brolucizumab (6.0 mg/0.05 mL) is effective for eyes with exudative age-related macular degeneration (AMD) refractory to aflibercept for 12 months. Sixty eyes from 56 patients receiving brolucizumab for exudative AMD refractory to aflibercept were included. Patients received a mean of 30.1 aflibercept administrations for a mean 67.9-month follow-up. All patients exhibited exudation on optical coherence tomography (OCT) despite regular 4-8 weeks of aflibercept administration. Visit 1 was scheduled at the same interval from the last aflibercept injection to the baseline. The treatment interval was extended or shortened by 1-2 weeks depending on the presence or absence of exudation on OCT. After switching to brolucizumab, the follow-up interval significantly extended at 12 months (before switching: 7.6 ± 3.8 weeks vs. at 12 months: 12.1 ± 6.2 weeks, p = 1.3 × 10-7). Forty-three percent of the eyes achieved a dry macula at 12 months after switching. However, the best-corrected visual acuity did not improve at any visit. Morphologically, the central retinal thickness and subfoveal choroidal thickness significantly decreased from baseline at 12 months (p = 3.6 × 10-3 and 1.0 × 10-3, respectively). Switching to brolucizumab can be considered to extend the treatment interval in eyes with exudative AMD refractory to aflibercept.

Repeated Measurements Are Necessary for Evaluating Accurate Diurnal Rhythm Using a Self-Intraocular Pressure Measurement Device.

PURPOSE: To investigate how many tests need to be performed to adequately assess intraocular pressure (IOP) diurnal change using a self-measuring rebound tonometer among glaucoma patients. SUBJECTS AND METHODS: Adult patients with primary open-angle glaucoma were included. IOP was measured in the morning (6 AM to 9 AM), afternoon (12 PM to 3 PM), and at night (6 PM to 9 PM) for seven consecutive days. Twenty-four (7 males and 17 females, mean age 59.5 ± 11.0 years) patients who successfully measured IOP at least three times per day during the correct time periods for four days were subjected to analysis. RESULTS: The IOP rhythm was significantly greater on the first day of measurement (6.6 ± 3.6 mmHg) than that averaged during subsequent days (4.4 ± 2.2 mmHg). The time of the highest and lowest IOP measurements on the first day of IOP measurement and during the entire measurement period coincided in 72.9% and 64.6% of cases, respectively. The concordance rate of the highest IOP time between the whole measurement period and each measurement day was less than 60%. CONCLUSION: The diurnal IOP rhythm measured by the patients themselves was not consistent, and multiple days of measurements may be necessary to correctly assess diurnal IOP rhythm.

[Antibacterial susceptibility surveillance of Haemophilus influenzae isolated from pediatric patients in Gifu and Aichi prefectures (2009-2010)].

We investigated the susceptibility to antibacterial agents of 197 strains of Haemophilus influenzae isolated from pediatric patients at medical facilities in Gifu and Aichi prefectures between 2009 and 2010. Those strains were also examined for the mutations of ftsI coding for penicillin-binding protein 3, presence of bla TEM-1, serotype and beta-lactamase producing ability. Among the 197 strains, the most prevalent serotype was non-typeable (89.8%), followed by serotype b (8.1%), e (1.5%) and f (0.5%). Based on the susceptibility among the 197 strains to antibacterial agents, beta-lactamase nonproducing ampicillin-susceptible H. influenzae (BLNAS) accounted for 27.4%, beta-lactamase nonproducing ampicillin-resistant H. influenzae (BLNAR) for 62.4%, beta-lactamase producing ampicillin-resistant H. influenzae (BLPAR) for 6.1% and beta-lactamase producing amoxicillin/ clavulanic acid-resistant H. influenzae (BLPACR) for 4.1%. According to PCR-based genotyping, the strains were classified into 6 categories: gBLNAS, gLow-BLNAR, gBLNAR, gBLPAR, gBLPACR-I and gBLPACR-II. The incidences of each resistant class were 17.3% for gBLNAS, 6.6% for gLow-BLNAR, 66.0% for gBLNAR, 5.6% for gBLPAR and 4.6% for gBLPACR-II. The combined incidence of gLow-BLNAR and gBLNAR was 72.6%, which was higher than that of BLNAR (62.4%). The MIC90s of antibacterial agents against the 197 strains were as follows; 0.0156 microg/mL for tosufloxacin and garenoxacin, 0.0313 microg/mL for levofloxacin and pazufloxacin, 0.0625 microg/mL for norfloxacin, 0.25 microg/mL for tazobactam/piperacillin (TAZ/PIPC) and ceftriaxone, 0.5 microg/mL for TAZ/PIPC (1:8) and cefditoren, 1 microg/mL for piperacillin, cefteram, cefotaxime, meropenem, tebipenem and minocycline, 2 microg/mL for doripenem, 4 microg/mL for cefcapene, imipenem and azithromycin, 8 microg/mL for sulbactam/ampicillin, clavulanic acid/amoxicillin (1:2, CVA/AMPC) and cefdinir, 16 microg/mL for CVA/AMPC (1:14), flomoxef and clarithromycin, 32 microg/mL for ampicillin. Although there was no rapid increase in the antibacterial resistance, the prevalence of BLNAR was still over 50%. In order to ensure the appropriate chemotherapy, it is important to continue the surveillance of susceptibility among H. influenzae.

[Sensitivity surveillance of Streptococcus pneumoniae isolates for several antibacterial agents in Gifu and Aichi prefecture (2008-2009)].

We investigated the susceptibility to antibacterials, genotype of penicillin-binding protein (PBP) genes and macrolide resistant genes, and the serotypes against 377 strains of Streptococcus pneumoniae isolated from medical facilities in Gifu and Aichi prefectures between June 2008 and April 2009. These results were compared with those against 160 strains of S. pneumoniae isolated in 2004. Referring to CLSI (M100-S17), the overall incidence of penicillin-susceptible (PSSP), penicillin-intermediate (PISP) and penicillin-resistant (PRSP) S. pneumoniae was 143 (38%), 185 (49%) and 49 (13%) strains, respectively. PISP and PRSP were isolated higher in the material of nasal cavity and throat, and PRSP was isolated higher in the area of Chuno district. The number of gPSSP with 3 normal PBP genes, gPISP with 1 or 2 normal PBP genes and gPRSP with 3 abnormal genes was 23 (6.1%), 173 (46%) and 181 (48%) strains, respectively. The isolates with no macrolide-resistant gene, only mefA, only ermB, and both mefA and ermB were 28 (7.4%), 138 (37%), 166 (44%) and 45 (12%). The prevalent pneumococcal serotypes were type 19 (92 strains; 24%), following by type 23 (60 strains; 16%) and type 6 (56 strains; 15%). The 80% of pneumococcal serotypes of PRSP were serotype 19 and 6. The MIC90 of each antibacterial was as follows; 0.1 microg/mL for imipenem, panipenem and garenoxacin, 0.2 microg/mL for moxifloxacin, 0.39 microg/mL for meropenem and tosufloxacin, 0.78 microg/ mL for amoxicillin, clavulanic acid/amoxicillin, cefditoren and cefcapene, 1.56 microg/mL for benzylpenicillin, piperacillin, cefteram and levofloxacin, 3.13 microg/mL for cefotiam, flomoxef and pazufloxacin, 6.25 microg/mL for cefdinir, 12.5 microg/mL for norfloxacin and minocycline, > 100 microg/mL for clarithromycin, and these MIC90s were about the same as those in 2004.