Effectiveness of SCAR-Q for assessment of incisional SCAR after implant-based reconstruction in breast cancer patients: Can it be a tool for incision selection?

Incisional scarring is a factor of cosmetic appearance evaluated after breast reconstruction, along with the shape, position, and size of the breast. This study aimed to examine the effect of the incision scar location on patient satisfaction after breast reconstruction. Using the Japanese version of the SCAR-Q, we assessed the scar appearance, symptoms and psychosocial effects. Plastic surgeons performed assessments using the Manchester Scar Scale. The patients were divided into two groups: those with scars on the margins of the breast (MB group) and those with scars in the breast area (IB group). The results revealed that patients in the MB group reported significantly higher satisfaction with the scar appearance and psychological impact than those in the IB group. However, assessments using the Manchester Scar Scale did not reveal any significant differences between the two groups. In conclusion, this study underscores the importance of patient-reported outcomes in the evaluation of scar satisfaction after breast reconstruction. Patients tend to prefer and have higher satisfaction with scars along the breast margin, which offers valuable insights into surgical decisions. Further studies with larger and more diverse sample sizes are required for validation.

Identification of activity-based biomarkers for early-stage pancreatic tumors in blood using single-molecule enzyme activity screening.

Single-molecule enzyme activity-based enzyme profiling (SEAP) is a methodology to globally analyze protein functions in living samples at the single-molecule level. It has been previously applied to detect functional alterations in phosphatases and glycosidases. Here, we expand the potential for activity-based biomarker discovery by developing a semi-automated synthesis platform for fluorogenic probes that can detect various peptidases and protease activities at the single-molecule level. The peptidase/protease probes were prepared on the basis of a 7-amino-4-methylcoumarin fluorophore. The introduction of a phosphonic acid to the core scaffold made the probe suitable for use in a microdevice-based assay, while phosphonic acid served as the handle for the affinity separation of the probe using Phos-tag. Using this semi-automated scheme, 48 fluorogenic probes for the single-molecule peptidase/protease activity analysis were prepared. Activity-based screening using blood samples revealed altered single-molecule activity profiles of CD13 and DPP4 in blood samples of patients with early-stage pancreatic tumors. The study shows the power of single-molecule enzyme activity screening to discover biomarkers on the basis of the functional alterations of proteins.

Development of fluorogenic substrates for colorectal tumor-related neuropeptidases for activity-based diagnosis.

The M3 metalloproteases, neurolysin and THOP1, are neuropeptidases that are expressed in various tissues and metabolize neuropeptides, such as neurotensin. The biological roles of these enzymes are not well characterized, partially because the chemical tools to analyse their activities are not well developed. Here, we developed a fluorogenic substrate probe for neurolysin and thimet oligopeptidase 1 (THOP1), which enabled the analysis of enzymatic activity changes in tissue and plasma samples. In particular, the probe was useful for studying enzyme activities in a single-molecule enzyme assay platform, which can detect enzyme activity with high sensitivity. We detected the activity of neurolysin in plasma samples and revealed higher enzyme activity in the blood samples of patients with colorectal tumor. The result indicated that single-molecule neurolysin activity is a promising candidate for a blood biomarker for colorectal cancer diagnosis.

Characteristics of urine spraying and scraping the ground with hind paws as scent-marking of captive cheetahs (Acinonyx jubatus).

Olfactory communication is common in felids. We observed two scent-markings, urine spraying and scraping the ground with hind paws during excretion, of 25 captive cheetahs. We analyzed the association of sniffing with the timing of urine spraying and scraping, and differences in these behaviors based on sex, age, and captive environment to understand the olfactory communication among cheetahs. Both scent-markings were strongly associated with sniffing, especially scraping, and the presence or absence of scent was thought to be a trigger. Both behaviors were observed only in adults; scraping was observed only in males. To our knowledge, this study was first to confirm the discharge of secretions from the anal glands during scraping. The frequencies of both behaviors were significantly higher in males kept in shared enclosures containing other individuals than in males kept in monopolized enclosures, while there was no difference in the frequencies among females. Female cheetahs are solitary and have non-exclusive home range, whereas male cheetahs are either solitary or live in coalition groups and there are territorial and non-territorial males. Our results could be attributed to the differences in sociality between the sexes and effect of the living environment.

Assessment of Hypofluorescent Foci on Late-Phase Indocyanine Green Angiography in Central Serous Chorioretinopathy.

To assess the hypofluorescent foci (HFF) on late-phase indocyanine green angiography (ICGA) in central serous chorioretinopathy (CSC) using short-wavelength fundus autofluorescence (SW-FAF), near-infrared autofluorescence (NIR-AF), and fluorescein angiography (FA). The HFF area on late-phase ICGA for at least 20 min was compared with the area of abnormal foci on SW-FAF, NIR-AF, and FA. In 14 consecutive patients (12 men, including 1 with bilateral CSC; and 2 women with unilateral CSC), four kinds of images of 27 eyes were acquired. The mean age ± standard deviation (range) was 46 ± 9.2 years (31-69 years). The HFF on late-phase ICGA were found in 23 eyes (in all 15 CSC eyes and the contralateral 8 eyes). From the results of simple regression analysis, we obtained the following three formulas. The HFF area on ICGA = 1.058 × [abnormal SW-FAF area] + 0.135, the HFF area on ICGA = 1.001 × [abnormal NIR-AF area] + 0.015, and the HFF area on ICGA = 1.089 × [abnormal FA area] + 0.135. Compared to SW-FAF and FA, NIR-AF was found to be the easiest method to detect the HFF on late-phase ICGA, which may indicate melanin abnormalities, especially a decrease, in the retinal pigment epithelium.

Association between axial length and choroidal thickness in early age-related macular degeneration.

The clinical course of age-related macular degeneration (AMD) is related to choroidal conditions, and can be determined by the evaluation of the central choroidal thickness (CCT). The aim of this study was to determine the association between the axial length (AL) and choroidal thickness in AMD by measuring these parameters in patients with and without AMD. Seventy eyes of 70 patients (34 men and 36 women; age, 64-88 years; mean age, 77.0 ± 6.5 years) who underwent cataract surgery from February 2015 to March 2020 at the Department of Ophthalmology, Keio University School of Medicine were retrospectively analyzed. The AMD group (29 patients, 29 eyes) included eyes with early AMD, whereas the control group (41 patients, 41 eyes) included those without ocular diseases other than cataract. Optical coherence tomography images were used to measure the CCT and the choroidal vessel diameter (CVD). The IOL Master was used to measure the AL. The results revealed that mean CCT was greater in the AMD group (238.3 ± 108.3 µm) compared with the age-matched control group (187.2 ± 66.8 µm) (p = 0.03). The CCT was negatively correlated with AL in the overall sample (r = -0.42, p = 0.001), the AMD group (r = -0.42, p = 0.02), and the control group (r = -0.42, p = 0.006). Note that all eyes with CCT > 350 µm were included in the AMD group. CCT and CVD were positively correlated in the overall sample (r = 0.76, p < 0.001) as well as in the individual groups (AMD: r = 0.82, p < 0.001; control: r = 0.76, p = 0.004). Given that CCT is an important parameter for predicting the prognosis of subfoveal diseases, routine evaluation of AL may be valuable for a better understanding of the pathogenesis of AMD.

Hyperreflective Material in Optical Coherence Tomography Images of Eyes with Myopic Choroidal Neovascularization May Affect the Visual Outcome.

The visual outcome of myopic choroidal neovascularization (CNV) after anti-vascular endothelial growth factor (anti-VEGF) therapy varies among individuals. We retrospectively analyzed the data of 24 eyes (24 patients) with treatment-naïve myopic CNV who underwent anti-VEGF monotherapy following a pro-re-nata regimen at the Division of Medical Retina Clinic, Department of Ophthalmology, Keio University Hospital between May 2014 and December 2017. The mean age was 70.6 ± 2.1 years, and 16 (66.7%) patients were female. Overall, the mean best-corrected visual acuity (BCVA) improved (p = 0.034), and the mean height of the hyperreflective material (HRM), involving the CNV lesion recorded by optical coherence tomography, decreased (p < 0.01) 12 months after the initial treatment. Fifteen eyes (62.5%) achieved a BCVA of better than 0.10 in LogMAR at 12 months; they had a better BCVA (p = 0.015) and lower HRM intensity (p = 0.033) at baseline than the others. Remarkably, the BCVA improved (p < 0.05) and the HRM height (p < 0.01) decreased only in eyes with a final BCVA better than 0.10 as early as 1 month after the initial treatment, which was still present at 12 months. The HRM height and intensity, not only the BCVA, would be valuable in evaluating the prognosis of myopic CNV after anti-VEGF therapy, although further study is required.

Ocular and Systemic Effects of Antioxidative Supplement Use in Young and Healthy Adults: Real-World Cross-Sectional Data.

Randomized controlled studies have shown that antioxidative supplements are effective in suppressing the progression of age-related macular degeneration and visual display terminal syndrome. However, effects of their general use in the real-world and by young and healthy individuals have not been well documented. We analyzed 27 participants who were under 35 years of age and had no diagnosed diseases. Mean functional visual acuity (FVA) score and visual maintenance ratio, which represent quick recognition of a target, both measured using FVA system, were better (both p < 0.01) in subjects who had had regular antioxidative supplement intake for more than 2 months (11 participants) compared with those who had not. Systemic data, i.e., total cholesterol, hemoglobin A1c (HbA1c), and high-sensitivity C-reactive protein (hs-CRP) levels, which correspond to chronic low-grade inflammation, were lower (all p < 0.05) in the former. Overall, hs-CRP levels had a correlation with total cholesterol (p < 0.05) and a trend of correlation with HbA1c (p = 0.054) levels. Thus, current real-world data showed that young, healthy participants who had a regular intake of antioxidative supplements had better visual acuity and systemic levels of metabolic and low-grade inflammation markers. This study will help promote future research into the effects of general antioxidative supplement use.

The Area and Number of Intraretinal Cystoid Spaces Predict the Visual Outcome after Ranibizumab Monotherapy in Diabetic Macular Edema.

Visual outcomes in diabetic macular edema (DME) after anti-vascular endothelial growth factor therapy vary across individuals. We retrospectively reviewed the clinical records for 46 treatment-naive eyes of 46 patients with DME who underwent intravitreal ranibizumab (IVR) monotherapy with a pro re nata regimen for 12 months. Overall, mean best-corrected visual acuity (BCVA) improved. Multivariate analyses adjusted for age and baseline BCVA showed that the area ratio, compared with the retinal area, and the number of intraretinal cystoid spaces evaluated on OCT (optical coherence tomography) images at baseline positively correlated with LogMAR BCVA and the extents of ellipsoid zone and external limiting membrane disruption at 12 months, and negatively correlated with central retinal thickness at the time of edema resolution. Therefore, a high area ratio and large number of intraretinal cystoid spaces resulted in a disorganized outer retinal structure at 12 months, a thin and atrophic retina after edema resolution, and a worse visual outcome. The area ratio and number of intraretinal cystoid spaces on initial OCT images were predictors of the visual outcome after IVR therapy in DME irrespective of baseline age and BCVA. The factors were related to retinal neurodegenerative changes in DME and could help in obtaining proper informed consent before treatment.

Macular Pigment Optical Density and Photoreceptor Outer Segment Length as Predisease Biomarkers for Age-Related Macular Degeneration.

To explore predisease biomarkers, which may help screen for the risk of age-related macular degeneration (AMD) at very early stages, macular pigment optical density (MPOD) and photoreceptor outer segment (PROS) length were analyzed. Thirty late AMD fellow eyes, which are at high risk and represent the predisease condition of AMD, were evaluated and compared with 30 age-matched control eyes without retinal diseases; there was no early AMD involvement in the AMD fellow eyes. MPOD was measured using MPS2® (M.E. Technica Co. Ltd., Tokyo, Japan), and PROS length was measured based on optical coherence tomography images. MPOD levels and PROS length in the AMD fellow eyes were significantly lower and shorter, respectively, than in control eyes. MPOD and PROS length were positively correlated in control eyes (R = 0.386; p = 0.035) but not in AMD fellow eyes. Twenty (67%) AMD fellow eyes met the criteria of MPOD < 0.65 and/or PROS length < 35 µm, while only five (17%) control eyes did. After adjusting for age and sex, AMD fellow eyes more frequently satisfied the definition (p < 0.001; 95% confidence interval, 3.50-60.4; odds ratio, 14.6). The combination of MPOD and PROS length may be a useful biomarker for screening predisease AMD patients, although further studies are required in this regard.

Correlation between Macular Pigment Optical Density and Neural Thickness and Volume of the Retina.

Macular pigment (MP), which is composed of lutein/zeaxanthin/mezo-zeaxanthin, is concentrated in the central part of the retina, the macula. It protects the macula by absorbing short-wavelength light and suppressing oxidative stress. To evaluate whether MP levels are related to retinal neural protection and resulting health, we analyzed the association between the MP optical density (MPOD), and the macular thickness and volumes. Forty-three eyes of 43 healthy adult volunteers (21 men and 22 women; age: 22-48 (average 31.4 ± 1.1) years) were analyzed. Highly myopic eyes (<-6 diopters) were excluded. MPOD was measured using MPS2®, and the neural retinal thickness and volume were measured using optical coherence tomography. The mean MPOD was 0.589 ± 0.024, and it positively correlated with the central retinal thickness (P = 0.017, R = 0.360) and retinal volume of the fovea (1-mm diameter around the fovea; P = 0.029, R = 0.332), parafovea (1-3-mm diameter; P = 0.002, R = 0.458), and macula (6-mm diameter; P = 0.003, R = 0.447). In the macular area (diameter: 6 mm), MPOD was correlated with the retinal neural volume of the ganglion cell layer (P = 0.037, R = 0.320), inner plexiform layer (P = 0.029, R = 0.333), and outer nuclear layer (P = 0.020, R = 0.353). Thus, MPOD may help in estimating neural health. Further studies should determine the impact of MP levels on neuroprotection.

Predicting recurrences of macular edema due to branch retinal vein occlusion during anti-vascular endothelial growth factor therapy.

PURPOSE: To determine the predictive factors for recurrent macular edema due to branch retinal vein occlusion (BRVO) during intravitreal ranibizumab (IVR) monotherapy. METHODS: Clinical records were retrospectively reviewed for 65 patients (mean age 66.5 years, 65 eyes) who were diagnosed with macular edema due to BRVO and treated with IVR monotherapy for 12 months at the Medical Retina Division, Department of Ophthalmology, Keio University Hospital between October 2013 and August 2017. Best-corrected visual acuity (BCVA), fundus findings, and sectional optical coherence tomography (OCT) images were analyzed. RESULTS: Overall BCVA and central retinal thickness (CRT) improved (all p < 0.01). BCVA at 12 months was significantly worse in patients with recurrent macular edema (40 eyes [61.5%]) (p < 0.01) than in those without, while CRT decreased and was comparable in both groups at 12 months. Logistic regression analyses showed association of recurrence with disorganization of the retinal inner layer (DRIL) temporal to the fovea at baseline (odds ratio = 7.74; 95% confidence interval 1.62-37.08, p = 0.01), after adjusting for age, gender, and initial CRT. CONCLUSION: Recurrent macular edema due to BRVO affects visual outcome and is associated with initial DRIL temporal to the fovea, evaluated using OCT sectional images before treatments. DRIL may facilitate determination of follow-up schedules in clinical practice.

Comparative Evaluation of Selective Media for the Detection of Bacillus cereus.

The commercially available 3 types of selective media in Japan were compared for the detection of Bacillus cereus. When assessed inclusivity using 25 B. cereus strains, MYP agar, NGKG agar, and chromogenic X-BC agar demonstrated excellent inclusivity. For exclusivity study using 50 non-B. cereus strains, MYP, NGKG, and X-BC allowed to grow 11, 7, and 3 strains, respectively. Of the grown bacteria on each strains tested, only 2 strains of B. thuringiensis formed typical B. cereus colonies on all selective media tested. The NGKG and X-BC were compared with MYP as a reference using artificially contaminated food (fried rice, plain rice, fried noodle, and potato salad ), since MYP is recommended in ISO 7932: 2004. The both correlation coefficients between NGKG and MYP, and X-BC and MYP were 0.999. Therefore, we demonstrated that NGKG and X-BC can be adapted to ISO 7932: 2004 method for selected food as well as MYP.

Spatial-sweep steady-state pattern electroretinography can detect subtle differences in visual function among healthy adults.

We aimed to establish a highly sensitive method for measuring visual function using spatial-sweep steady-state pattern electroretinography (swpPERG). Overall, 35 eyes of 35 healthy adults (18 men; mean age, 32.3 years) were examined using swpPERG, and the data were recorded using spatial-patterned and contrast-reversed stimuli of size 1 (thickest) to 6. Data were converted into frequency-domain using a Fourier transform and expressed by signal-to-noise ratio (SNR). The number of participants who showed SNR ≥ 1 was significantly lesser at stimulus sizes 5 and 6 compared with those at greater stimulus sizes. Among the data with SNR ≥ 1, SNRs were negatively correlated with age at stimulus size 5 (r = -0.500, P = 0.029), and positively correlated with macular volume evaluated by optical coherence tomography (OCT) within a 6-mm circle diameter from the fovea of the retinal nerve fibre layer at size 4 (r = 0.409, P = 0.025) and of the ganglion cell layer at size 5 (r = 0.567, P = 0.011). We found that SNRs of swpPERG, recorded using the EvokeDx system, were correlated with age and macular morphology in participants without diagnosed eye diseases. The system detected subtle differences in retinal function, which may help in early disease diagnosis and visual evaluation in neuroprotective interventions in the future.

Ultra-Widefield Retinal Imaging for Analyzing the Association Between Types of Pathological Myopia and Posterior Staphyloma.

High myopia may develop to pathologic myopia, which brings severe visual impairment; however, the etiology is not fully understood. We, therefore, investigated the relationship between the presence of posterior staphyloma and posterior ocular disorders by assessing the patients with high myopia. A retrospective study was performed for the patients, who have more than 26 mm of the axial length and of whom fundus photography was taken with an ultra-widefield retinal imaging system. The objectives were 138 cases encompassing 229 eyes. In 138 cases, 91 were bilateral and 47 were unilateral. The averages ± SD of axial length of bilateral and unilateral were 28.8 ± 2.2 mm, 27.3 ± 1.2 mm, respectively, showing statistically significant difference. The number of eyes with and without posterior staphyloma were 107 (46.7%) and 122 (53.3%), respectively. Retinal detachment and retinal breaks are more observed in cases without posterior staphyloma (p = 0.017). Myopic choroidal neovascularization (mCNV) (p = 0.002), chorioretinal atrophy (p < 0.001), retinoschisis (p < 0.001), and optic neuropathy (p = 0.038) are more often seen in cases with posterior staphyloma. In conclusion, the prevalence rates of myopic choroidal neovascularization, retinal choroidal atrophy, and optic neuropathy were significantly higher with posterior staphyloma. The rate of periocular disorders such as retinal detachment was significantly higher without posterior staphyloma. These results indicate associations between types of pathological myopia and presence or absence of posterior staphyloma analyzed by ultra-widefield retinal imaging.

Dynamic changes in choroidal conditions during anti-vascular endothelial growth factor therapy in polypoidal choroidal vasculopathy.

We defined the relationships between initial choroidal conditions and their dynamics and exudative changes during anti-vascular endothelial growth factor (anti-VEGF) therapy in polypoidal choroidal vasculopathy (PCV). One hundred treatment-naïve eyes of 100 patients with PCV treated for 24 months at Keio University Hospital with intravitreal ranibizumab or aflibercept monotherapy (three injections and PRN thereafter) were retrospectively analyzed. Wet macula risk after three induction injections, which affected visual prognosis, was predicted by initial pachyvessels in the choroid (foveal greatest vertical choroidal vessel diameter [CVD] ≥180 µm) and pachychoroid (central choroidal thickness [CCT] ≥220 µm) recorded by optical coherence tomography. The risk for recurrent exudative change was greater in the pachyvessel groups irrespective of presence or absence of pachychoroid. Mean CVD and CCT decreased with anti-VEGF therapy when achieving a dry macula, suggesting that exudative changes are regulated by VEGF. Mean CVD and CCT at remission were greater in patients with initial pachyvessels and pachychoroid than in those without; the basal levels of CVD and CCT most likely represent VEGF-unrelated conditions. CVD increase preceded CCT increase and recurrent exudative changes, suggesting that the VEGF-related CVD increase may regulate CCT and exudative change; and that CVD may be a biomarker of exudative change.

Retinoblastoma Inactivation Induces a Protumoral Microenvironment via Enhanced CCL2 Secretion.

Cancer cell-intrinsic properties caused by oncogenic mutations have been well characterized; however, how specific oncogenes and tumor suppressors impact the tumor microenvironment (TME) is not well understood. Here, we present a novel non-cell-autonomous function of the retinoblastoma (RB) tumor suppressor in controlling the TME. RB inactivation stimulated tumor growth and neoangiogenesis in a syngeneic and orthotropic murine soft-tissue sarcoma model, which was associated with recruitment of tumor-associated macrophages (TAM) and immunosuppressive cells such as Gr1+CD11b+ myeloid-derived suppressor cells (MDSC) or Foxp3+ regulatory T cells (Treg). Gene expression profiling and analysis of genetically engineered mouse models revealed that RB inactivation increased secretion of the chemoattractant CCL2. Furthermore, activation of the CCL2-CCR2 axis in the TME promoted tumor angiogenesis and recruitment of TAMs and MDSCs into the TME in several tumor types including sarcoma and breast cancer. Loss of RB increased fatty acid oxidation (FAO) by activating AMP-activated protein kinase that led to inactivation of acetyl-CoA carboxylase, which suppresses FAO. This promoted mitochondrial superoxide production and JNK activation, which enhanced CCL2 expression. These findings indicate that the CCL2-CCR2 axis could be an effective therapeutic target in RB-deficient tumors. SIGNIFICANCE: These findings demonstrate the cell-nonautonomous role of the tumor suppressor retinoblastoma in the tumor microenvironment, linking retinoblastoma loss to immunosuppression.

QD laser eyewear as a visual field aid in a visual field defect model.

Visual field defects interfere with free actions and influence the quality of life of patients with retinitis pigmentosa; the prevalence of this disease is increasing in aging societies. Patients with progressive disease may require visual aids; however, no such devices are currently available. We utilized a retinal projection eyewear system, QD laser eyewear, which includes a projector inside the spectacle frame, to draw the image taken by a connected portable camera with a wide field lens. The images are projected onto the retina using a Maxwellian view optical system, which is not influenced by refractive error or the amount of incident light. Goldmann perimetry and figure recognition tests with the QD laser eyewear showed increased visual field areas and angles, and shortened the time for recognition of the number of figures in a sheet, in a limited visual field model that we developed by using a pin-hole system to simulate the tunnel vision of retinitis pigmentosa in 19 healthy adults. The device supported the quality of vision. Additionally, the visual field defect model used in healthy adults was useful for validating the device in the development stage of the study, to clarify both advantages and future goals for improving the device.

Benefits of aflibercept treatment for age-related macular degeneration patients with good best-corrected visual acuity at baseline.

Currently, age-related macular degeneration (AMD) is treated while patients exhibit good best-corrected visual acuity (BCVA). However, previous clinical trials only include patients with poor BCVA. We prospectively analyzed the benefits of intravitreal aflibercept (IVA) treatment for AMD patients exhibiting good BCVA at baseline. Twenty-nine treatment-naive AMD patients (29 eyes) with BCVA better than 0.6 (74 letters in ETDRS chart) were treated with IVA once a month for 3 months and every 2 months thereafter with no additional treatments. Improvement in mean BCVA, measured using the conventional Landolt C chart, contrast VA chart, and functional VA (FVA) system, and reductions in mean central retinal thickness (CRT), central choroidal thickness, macular volume (MV), and choroidal area on optical coherence tomography images were observed at 6 and 12 months. Improvements in contrast VA and FVA scores, in contrast to conventional BCVA, correlated with MV reduction; no VA scores correlated with a reduced CRT. The MV correlated with choroidal area after IVA. No severe adverse events occurred. IVA improved visual function, retinal condition, and quality of life evaluated by Visual Function Questionnaire, and was beneficial in these patients. The contrast VA and FVA scores and MVs, which detect subtle changes, helped demonstrate the benefits.