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Disease staging involves the assessment of disease severity or progression and is used for treatment selection. In diabetic retinopathy, disease staging using a wide area is more desirable than that using a limited area. We investigated if deep learning artificial intelligence (AI) could be used to grade diabetic retinopathy and determine treatment and prognosis. The retrospective study analyzed 9,939 posterior pole photographs of 2,740 patients with diabetes. Nonmydriatic 45° field color fundus photographs were taken of four fields in each eye annually at Jichi Medical University between May 2011 and June 2015. A modified fully randomly initialized GoogLeNet deep learning neural network was trained on 95% of the photographs using manual modified Davis grading of three additional adjacent photographs. We graded 4,709 of the 9,939 posterior pole fundus photographs using real prognoses. In addition, 95% of the photographs were learned by the modified GoogLeNet. Main outcome measures were prevalence and bias-adjusted Fleiss' kappa (PABAK) of AI staging of the remaining 5% of the photographs. The PABAK to modified Davis grading was 0.64 (accuracy, 81%; correct answer in 402 of 496 photographs). The PABAK to real prognosis grading was 0.37 (accuracy, 96%). We propose a novel AI disease-staging system for grading diabetic retinopathy that involves a retinal area not typically visualized on fundoscopy and another AI that directly suggests treatments and determines prognoses.

PurposeTo classify macular neovascularization (MNV) based on pachychoroid and drusen features and to examine the aqueous humor cytokine signatures of each group.MethodsIn total, 106 consecutive eyes with treatment-naïve MNV and 104 control eyes were examined. The aqueous humor concentrations of 15 cytokines were compared among the MNV groups classified based on the presence of drusen and/or pachychoroid features. Multidimensional scaling analysis was used to visualize the similarity level of the MNV subtypes according to their cytokine profiles.ResultsThirty-one, 18, 43, and 10 eyes were classified into the pachychoroid-associated, drusen-associated, pachychoroid/drusen-associated, and non-drusen/non-pachychoroid MNV groups, respectively. Compared with the control group, cytokines were differently upregulated among the MNV groups. CRP and CXCL12 were significantly upregulated in all MNV groups, whereas CXCL13 and IL-8 were significantly upregulated in three MNV groups, excluding the non-pachychoroid/non-drusen-associated MNV group. Ang-2 was significantly upregulated in three MNV groups except the drusen-associated MNV group. PlGF was significantly upregulated in the pachychoroid-associated and drusen-associated MNV groups. CCL-2 was significantly upregulated in the pachychoroid-associated and pachychoroid/drusen-associated MNV groups. VEGF was downregulated in the pachychoroid-associated and drusen-associated MNV groups, respectively. Multidimensional scaling analysis showed a distinct cytokine profile for each MNV group.ConclusionAll MNV groups showed distinct cytokine profiles. Eyes with “neovascular age-related macular degeneration with drusen and concomitant pachychoroid” may share a similar etiology to those with “pachychoroid neovasculopathy” and “choroidal neovascularization with drusen,” but have a distinct etiology to those without these. These findings suggest the importance of evaluating drusen and the choroid during the diagnosis of neovascular age-related macular degeneration.

Constructing colloidal particles into functional nanostructures, materials, and devices is a promising yet challenging direction. Many optical techniques have been developed to trap, manipulate, assemble, and print colloidal particles from aqueous solutions into desired configurations on solid substrates. However, these techniques operated in liquid environments generally suffer from pattern collapses, Brownian motion, and challenges that come with reconfigurable assembly. Here, we develop an all-optical technique, termed optothermally-gated photon nudging (OPN), for the versatile manipulation and dynamic patterning of a variety of colloidal particles on a solid substrate at nanoscale accuracy. OPN takes advantage of a thin surfactant layer to optothermally modulate the particle-substrate interaction, which enables the manipulation of colloidal particles on solid substrates with optical scattering force. Along with in situ optical spectroscopy, our non-invasive and contactless nanomanipulation technique will find various applications in nanofabrication, nanophotonics, nanoelectronics, and colloidal sciences. Particle manipulation is still challenging even with the many tools available, especially manipulating particles on a surface. Here, the authors report a technique for nanomanipulation of various objects on solid substrates by modulating particle-substrate interactions through laser-induced opto-thermal dynamics.

Conventional endoscopic resection (CER) is a widely accepted treatment for early colorectal neoplasia; however, large colorectal neoplasias remain problematic, as they necessitate piecemeal resection, increasing the risk of local recurrence. Endoscopic submucosal dissection (ESD) can improve the en bloc resection rate. This study aimed to evaluate local recurrence and its associated risk factors after endoscopic resection (ER) for colorectal neoplasias ≥20 mm. A multicenter prospective study at 18 medium- and high-volume specialized institutions was conducted in Japan. Follow-up colonoscopy was performed after 12 months in cases of complete resection and after 3-6 months in cases of incomplete resection. Local recurrence was confirmed by endoscopic findings and/or pathological analysis. Follow-up colonoscopy was performed in 1,524 of 1,845 enrolled colorectal neoplasias (mean age, 65 years; 885 men; median tumor size, 32.8 mm). The local recurrence rates were 4.3% (65/1,524), 6.8% (55/808), and 1.4% (10/716) for the entire cohort, for CER, and for ESD, respectively. The relative risks of local recurrence were 0.21 (95% confidence interval, 0.11-0.39) with ESD compared with CER, 0.32 (95% confidence interval, 0.11-0.92) with en bloc ESD compared with en bloc CER, and 0.90 (95% confidence interval, 0.39-2.12) with piecemeal ESD compared with piecemeal CER. Significant factors associated with local recurrence were piecemeal resection, laterally spreading tumors of granular type, tumor size ≥40 mm, no pre-treatment magnification, and ≤10 years of experience in CER, and piecemeal resection only in ESD. En bloc ESD reduces the local recurrence rate for large colorectal neoplasias. Piecemeal resection is the most important risk factor for local recurrence regardless of the ER method used.

Background Conventional endoscopic resection (CER) for early colorectal neoplasia (CRN) is widely accepted as a minimally invasive treatment. Endoscopic submucosal dissection (ESD) was developed in Japan to resect larger lesions, but ESD was not covered by the Japanese national health insurance until April 2012. In addition, treatment strategies vary considerably among medical facilities. To evaluate the current situation in Japan regarding endoscopic treatment of CRNs measuring ≥20 mm, we conducted a prospective multicenter study at 18 medium-volume and high-volume specialized facilities in cooperation with the Japan Society for Cancer of the Colon and Rectum (JSCCR). Methods The JSCCR conducted a multicenter, observational study of all patients treated by CER and ESD of CRNs measuring ≥20 mm. Results From October 2007 to December 2010, CERs and ESDs were performed on 1,845 CRNs (CERs 1,029; ESDs 816). Lesions diagnosed as protruded, flat, and depressed totaled 541, 1224, and 48, respectively. En bloc resection rates and mean procedure times for CER/ESD were 56.9 %/94.5 % ( P  < 0.01) and 18 ± 23 min/96 ± 69 min, respectively. The average ESD procedure time was 129 ± 83 min in the ≥40-mm group. As lesion size increased, the CER en bloc resection rate decreased significantly (trend P  < 0.01), but the ESD en bloc resection rate remained over 93 %. Perforation and delayed bleeding rates of CER/ESD were 0.8 %/1.6 % ( P  < 0.05) and 2 %/2.2 % ( P  = 0.3), respectively. Conclusions The en bloc resection rate for ESD was significantly higher than for CER, although complication rates were fairly low. Despite a longer procedure time, safety of colorectal ESD has improved in various facilities in Japan. However, ESD for lesions measuring ≥40 mm must be performed by experienced endoscopists due to the longer procedure time.

Purpose Air pollutants, such as Asian sand and particulate matter (PM) 2.5, have become a global concern for causing ocular inflammation and allergic symptoms. This study, as part of an international investigation, examined the effects of eyewashes for ocular damage caused by air pollution in Indonesia. Methods This was a single-center, patient- and-evaluator-blinded, parallel two-arm, nonrandomized trial. In Jakarta, Indonesia, 30 eyes of 15 car commuters and 30 eyes of 15 motorcycle commuters were recruited from healthy volunteers. After commuting to work, both eyes were washed with a commercial eyewash. Before and after eyewashing, eight items of ocular surface symptoms and four items of rhinitis subjective symptoms were scored using a modified Japanese Allergic Conjunctival Disease Quality-of-Life Questionnaire. Results Five of the 12 subjective symptom scores before eyewashing were higher in motorcycle commuters than in car commuters ( p < 0.05). Motorcycle commuters showed improvement in the five symptom scores of “itchy eyes, foreign body sensation, eye mucus, dryness, and eye strain” after eyewashing compared to before eyewashing ( p < 0.05). In all patients, sootlike particles and ocular mucus were found in the solutions collected after eyewashing. Conclusion These findings indicate that eyewashing for ocular symptoms caused by airborne particles may be effective in removing foreign particles from the ocular surface and relieving subjective symptoms.

Background The use of laparoscopic surgery has become widespread, and many surgeons are striving to acquire the necessary techniques for it. The Endoscopic Surgical Skill Qualification System (ESSQS), established by the Japan Society for Endoscopic Surgery, serves to maintain and improve the quality of laparoscopic surgery in Japan. In this study, we aimed to determine whether ESSQS certification is useful in maintaining and improving the quality of surgical techniques and in standardization of laparoscopic surgery in Japan. Methods This retrospective study used data from the Institute for Integrated Medical Sciences, Tokyo Women’s Medical University , Japan. From January 2016 to October 2017, 241 patients with colorectal cancer underwent laparoscopic surgery. Of them, 220 patients were selected and divided into two groups on the basis of surgery performed by an ESSQS-qualified surgeon (QS group) ( n  = 170) and a non-ESSQS-QS (NQS) ( n  = 50). We compared the short-term results in the two groups and examined those before and after propensity score matching (PSM). Results Mean operation time was longer in the NQS group than in the QS group. Furthermore, mean blood loss was significantly less in the QS group. These were similar before and after PSM. The rate of conversion to open surgery was significantly higher in the NQS group before PSM. However, the rate of postoperative complications was not different between the two groups. Conclusions A laparoscopic procedure performed by ESSQS-QS often leads to good short-term outcomes. Thus, the ESSQS system works and is potentially useful in maintaining and improving the quality of surgical techniques and in standardization of laparoscopic surgery in Japan.

Objective Rapid eye movement (REM) obstructive sleep apnea (OSA) is associated with the risk of cardiovascular events. Arterial stiffness and carotid artery intima-media thickness (IMT) predict these events, but few relevant studies have been conducted. We compared long-term changes in arterial stiffness and IMT between patients with REM OSA and non-REM (NREM) OSA receiving continuous positive airway pressure (CPAP) or oral appliance (OA) therapy. Methods Newly diagnosed female patients with OSA received CPAP (n = 6) or OA (n = 7). Pulse wave velocity (PWV) and carotid artery ultrasound were performed before and 60 months after treatment. Results There were no differences in baseline characteristics (mean age: 56.0 vs. 61.3 years; mean body mass index: 22.6 vs. 21.7 kg/m2) between the REM OSA and non-REM OSA groups. The median apnea-hypopnea index was lower in the REM OSA group than in the non-REM OSA group. Increased PWV (12.92 ± 1.64 to 14.56 ± 2.73 m/s) and deteriorated glucose metabolism were observed in the REM OSA group after treatment. PWV, IMT, and cardiovascular risk factors were unaffected in the non-REM OSA group. Conclusion Arterial stiffness and glucose metabolism are deteriorated in patients with REM OSA compared with these parameters in patients with non-REM OSA after CPAP or OA treatment.

PurposeTo develop a cloud-based software for analysing the disc–fovea angle (DFA) in fundus images using the stacking ensemble model and to evaluate the accuracy of the objective DFA assessment between automatic and manual analyses.MethodsA total of 682 fundus images (573 and 109 images of healthy individuals and patients with cyclotropia, respectively) were included in this retrospective study. For manual DFA analysis, two examiners analysed the DFA using web-based analysis software for the DFA, which was defined as the average value between the two examiners. For automatic DFA analysis, the stacking ensemble model on the cloud web integrated a single-shot multi-box detector to identify the fovea and centre of the optic nerve head, along with a single convolutional neural network combined with five machine learning algorithms.ResultsThe DFA did not significantly vary between the automatic (7.25° ± 4.93°) and manual analyses (7.27° ± 5.07°) (p=0.52). The time required to analyse the DFA in a single fundus image was significantly shorter with the automatic analysis (0.430±0.240 s) than with the manual analysis (15.794±1.558 s) (p<0.001).ConclusionThese findings suggest that automatic analysis using the stacking ensemble model is useful for determining the DFA in clinical settings.

We aimed to construct a better model for predicting treatment outcomes of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD) using the concentrations of aqueous humour proteins at baseline and during treatment. From the data of 48 treatment-naïve nAMD eyes that received intravitreal ranibizumab pro re nata for up to 12 months, we used the aqueous humour concentrations of C-X-C motif chemokine ligand 1 (CXCL1), CXCL12, CXCL13, interferon-γ-induced protein 10, monocyte chemoattractant protein 1 (MCP-1), C-C motif chemokine ligand 11, interleukin 6 (IL-6), IL-10, and matrix metalloproteinase 9 (MMP-9). After stepwise regression, multivariate analysis was performed to identify which predictors were significantly associated with best-corrected visual acuity (BCVA) changes and the number of injections. The results demonstrated that besides male sex (β coefficient = -0.088, P = 0.040) and central retinal thickness (β coefficient = 0.00051 per μm, P = 0.027), MCP-1 (β coefficient = 0.44, P < 0.001) and IL-10 (β coefficient = -0.16, P = 0.033) were significantly correlated with baseline BCVA. Additionally, high MCP-1 at baseline (β coefficient = -0.20, P = 0.015) and low CXCL13 at baseline (β coefficient = 0.10, P = 0.0054) were independently associated with better BCVA change at 12 months. High MMP-9 at the first injection (β coefficient = 0.56, P = 0.01), CXCL12 at the third injection (β coefficient = 0.10, P = 0.0002), and IL-10 at the third injection (β coefficient = 1.3, P = 0.001) were predictor variables associated with the increased number of injections. In conclusion, aqueous humour protein concentrations may have predictive abilities of BCVA change over 12 months and the number of injections in pro re nata treatment of exudative nAMD.