Intravitreal anti-vascular endothelial growth factor and combined photodynamic therapy for pachychoroid neovasculopathy: long-term treatment outcomes.

PURPOSE: To examine the long-term visual outcomes after initial treatment with combined photodynamic therapy (PDT) or aflibercept treat-and-extend (TAE) monotherapy in patients with pachychoroid neovasculopathy (PNV). METHODS: Patients diagnosed with PNV, initially treated with PDT combined with anti-vascular endothelial growth factor (VEGF) or intravitreal aflibercept (IVA) monotherapy in the TAE protocol and followed up for at least 6 months, were included in the study. Medical records were retrospectively reviewed. Survival analysis was performed, in which deterioration in logMAR visual acuity by 0.1 or 0.3 is defined as "death." The annual number of treatments was also analyzed. Sub-analysis was performed on 33 patients diagnosed with PNV without polypoidal lesions. RESULTS: This study included 46 patients (23 in the initial combined PDT group and 23 in the IVA TAE group). Mean age, sex, mean baseline logMAR visual acuity, or duration of observation (3.6 ± 3.2 years vs. 3.1 ± 1.9 years) in both groups were comparable. As for visual outcome, no significant differences were found in survival analysis based on worsening of 0.1 or 0.3 logMAR (3-year survival; 26% vs. 26%, 91% vs. 90%, respectively). Meanwhile, the additional number of anti-VEGF injections per year was significantly lower in the initial combined PDT group than in the IVA TAE group (1.0 ± 1.3 vs. 4.1 ± 1.5, p < 0.0001). No significant differences were found in the number of additional PDTs per year (0.07 ± 0.20 vs. 0.02 ± 0.09, p = 0.27). Similar results were found in a sub-analysis of 33 patients without polyps. CONCLUSION: In the treatment of PNV, regardless of the presence of polyps, the long-term visual outcomes were similar between the initial combined PDT and IVA TAE monotherapy. However, the annual number of anti-VEGF injections was lower in the initial combined PDT group than in the aflibercept TAE group, whereas that of PDT was comparable.

Long-term visual outcomes in pachychoroid spectrum diseases and its associating factors of eyes with chronic central serous chorioretinopathy.

To analyze the long-term visual outcomes of pachychoroid spectrum diseases (PSD). Retrospective study. We reviewed the medical charts of consecutive patients with PSD, including focal choroidal excavation (FCE), pachychoroid pigment epitheliopathy (PPE), central serous chorioretinopathy (CSC), and pachychoroid neovasculopathy (PNV). The patients initially visited the Tokyo University Hospital from January 2008 to March 2021. Survival analyses were performed, in which loss of vision was defined as visual acuity (VA) of 0.2 logarithm of minimal angle of resolution (logMAR) or worse, 0.5 logMAR or worse, or VA worsening by 0.3 logMAR or greater. Moreover, we further investigated factors associated with visual prognosis, particularly in the CSC group. A total of 741 eyes of 638 patients were included in this analysis. The CSC or PNV group showed significantly worse visual prognosis than the FCE&PPE group for VA to 0.2 logMAR or worse (P = 0.0117 or 0.0001, respectively) and for VA worsening by 0.3 logMAR or greater (P = 0.0283 or 0.0037, respectively). In the CSC group, unlike age, sex, or treatment history, the accumulative duration of subfoveal fluid existence ≥ 12 months (continuous or intermittent) was significantly associated with visual prognosis (P < 0.0001). Among PSD, CSC and PNV were associated with a higher risk of vision loss in the long term than FCE and PPE. The duration of subretinal fluid existence was identified as a significant factor affecting long-term visual outcomes in CSC.

Assessment of Office-Based Probing with Dacryoendoscopy for Treatment of Congenital Nasolacrimal Duct Obstruction: A Retrospective Study.

We aimed to evaluate the safety and efficacy of office-based probing with dacryoendoscopy under local anesthesia for congenital nasolacrimal duct obstruction (CNLDO). This single-institution study retrospectively reviewed data on 72 eyes of 64 consecutive children (38 boys, 43 eyes; 26 girls, 29 eyes), aged between 6 and 17 (mean age: 10.0 ± 2.7) months with suspected CNLDO, from July 2016 to February 2022. These patients underwent probing with dacryoendoscopy under local anesthesia. CNLDO was diagnosed clinically based on the presence of epiphora and sticky eyes due to mucous discharge commencing within the first 3 months of life, increased tear meniscus height, and fluorescein dye disappearance test results. A total of 63 of the 72 eyes had narrowly defined CNLDO, and 9 eyes had other types of obstructions. The intervention success rate was 100% (63/63 eyes) for patients with typical CNLDO and 97.2% (70/72 eyes) for the entire study cohort. Moreover, CNLDO was classified into five types based on the features of the distal end of the nasolacrimal duct. Probing with dacryoendoscopy is safe and yields a high success rate in pediatric patients with CNLDO. This is the first study to assess the safety and efficacy of probing with dacryoendoscopy under local anesthesia in pediatric patients with CNLDO.

Marked Choroidal Thinning Observed after Intravitreal Brolucizumab Injection.

Introduction: Here, we report a case of severe intraocular inflammation (IOI) and prominent choroidal thinning following the initial intravitreal brolucizumab injection (IVBr). Case Presentation: The patient was a 75-year-old Japanese man with type 2 age-related macular degeneration of both eyes. Until 2015, he had undergone two intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections and two photodynamic therapies in his right eye. His decimal best-corrected visual acuity (BCVA) was 0.1 in the right eye and 0.1 in the left eye. Central choroidal thickness (CCT) measured 240 µm in his right eye. IVBr was administered to the right eye. The patient reported pain in the right eye 23 days after the injection. On day 26, panuveitis and retinal vasculitis were observed in the right eye. CCT measured 436 µm. On the same day, a sub-tenon triamcinolone injection was administered. On day 42, retinal inflammation remained at a similar level. The CCT decreased to 164 µm. On day 68, the intraocular pressure (IOP) in the right eye increased to 39 mm Hg, and IOI persisted. On day 89, the patient's eye pain disappeared, and the IOP decreased to 13 mm Hg. On day 225, the IOI and symptoms were completely resolved. The decimal BCVA was 0.04 in the right eye, and CCT measured 84 µm. Conclusion: Brolucizumab is a highly effective anti-VEGF drug; however, it has the potential to induce inflammation in tissues adjacent to the retina and may occasionally cause irreversible sequelae.

Pleuritis associated with immunoglobulin G4-related disease under normal thoracoscopic findings: a case report.

BACKGROUND: Immunoglobulin G4 (IgG4)-related disease is a chronic inflammatory disease that was recognized in 2011. Pleuritis associated with IgG4-related disease is rare and can be difficult to diagnose. Although there have been previous reports on pleuritis associated with IgG4-related disease by thoracoscopic findings, this is the first to observe pleuritis with IgG4-related disease from normal pleural thoracoscopic findings. CASE PRESENTATION: A 70-year-old Japanese female treated for breast cancer 33 years ago was referred to our hospital complaining of dyspnea on exertion. Chest computed tomography (CT) revealed left pleural effusion that was exudative and predominant with lymphocytes, elevated adenosine deaminase (ADA) and Class III cytology (malignancy suspected). Subsequently, thoracoscopic pleural biopsy was performed for definitive diagnosis. Although pleural macroscopic findings appeared normal, we performed pleural biopsy at random sites. This patient was negative for mycobacterium tuberculosis, and neither granulomas nor malignant cells were found in the collected specimens. An infiltration of inflammatory cells, mainly plasma cells and lymphocytes, was observed. Immunostaining revealed the number of IgG4-positive plasma cells was 102/high power field (HPF), and the percentage of IgG4 positive/immunoglobulin G (IgG)-positive cells was 41.4%. Since IgG4 serum levels were high and IgG4-related submandibular sialadenitis was also observed, a definitive diagnose of pleuritis associated with IgG4-related disease was confirmed. CONCLUSIONS: We diagnosed pleuritis associated with IgG4-related disease by thoracoscopic pleural biopsy samples taken from a visually normal pleura. Although exudative pleural effusion with high ADA and lymphocyte predominance is a characteristic of tuberculous pleuritis, other diseases might be present. Since thoracoscopy can increase the diagnostic yield, pleural biopsy should be considered even if thoracoscopic pleural findings are deemed normal.

Refractory secondary pneumothorax complicated with lung cancer treated by bronchial occlusion: a case report.

BACKGROUND: Pneumothorax is defined as the presence of air or gas in the pleural cavity. Secondary pneumothorax usually occurs in patients with overt underlying lung disease, most commonly chronic obstructive pulmonary disease (COPD). Patients with poor lung function often suffer from pneumothorax with a persistent air leak. Various strategies have been employed in the treatment of such refractory pneumothorax. Bronchial occlusion with an Endobronchial Watanabe Spigot (EWS) (Novatech, Grasse, France) has been shown to be useful in treating prolonged bronchopleural fistulas. Although the effects of bronchial occlusion with EWS are known, refractory pneumothorax often involves multiple affected bronchi, and in some cases the affected bronchi cannot be easily identified. In addition, secondary pneumothorax associated with advanced lung cancer often prolongs the treatment of pneumothorax, which can significantly reduce patients' quality of life and prognosis. CASE PRESENTATION: We report a case of refractory pneumothorax where collateral ventilation was successfully treated by bronchial occlusion of the affected bronchi using multiple methods. In August 2019, an 80-year-old Japanese man with asthma and COPD overlap was admitted for exacerbation triggered by respiratory tract infection. During hospitalization, he presented with chest pain due to pneumothorax. Subsequently, a chest drain tube was inserted and pleurodesis was performed; however, the lung could not be sufficiently expanded and an air leak remained. Further investigation revealed a tumor suspicious for lung cancer at the entrance of the left upper lobe bronchus. Due to poor lung function, surgical treatments were deemed high risk. Therefore, we performed bronchial occlusion using the Endobronchial Watanabe Spigot (EWS). Because we could not determine the affected bronchi by computed tomography (CT), we located the affected bronchi by balloon occlusion test and bronchography with iopamidol. After occlusion, the air leak decreased but still persisted. Thus, we performed pleurodesis twice, and the air leak ceased completely. CONCLUSIONS: Refractory secondary pneumothorax, which affected multiple bronchi and developed into collateral ventilation due to lung cancer, was treated successfully with bronchial occlusion and EWS. In cases where the affected bronchi cannot be determined by the balloon occlusion test, bronchography with iopamidol might be an effective treatment.

Evaluation by various methods of the physiological mechanism of a high-flow nasal cannula (HFNC) in healthy volunteers.

INTRODUCTION: Several reports have described the usefulness of a high-flow nasal cannula (HFNC). However, the physiological mechanisms of this system are unclear. In the current study, various methods were used to investigate the physiological mechanisms of an HFNC in healthy volunteers. METHODS: The physiological mechanisms of the constant-flow and constant-pressure models of HFNC were studied in 10 healthy volunteers by the oesophageal balloon method, the electrical impedance method and the forced oscillation technique (FOT). RESULTS: The tidal volume (TV) increased markedly during HFNC (off, 30 L/min, 50 L/min: 685.6±236.5 mL, 929.8±434.7 mL, 968.8±451.1 mL). The end-inspiratory oesophageal pressure (EIOP) was not significantly different, but there was a tendency for it to decrease. HFNC 30 L/min and 50 L/min, the increment in TV and the difference in EIOP showed strong negative correlations (p=0.0025, 0.003). The end-expiratory oesophageal pressure (EEOP) increased. The respiratory system reactance at 5 Hz (X5) by FOT decreased significantly. There was a flow rate-dependent EEOP increase, and the positive end-expiratory pressure (PEEP) effect of HFNC was confirmed. There was a correlation between the difference in X5 and the difference in EEOP during HFNC 30 L/min and 50 L/min, with correlation coefficients of 0.534 and 0.404 (p=0.112, 0.281). The amount of change in EEOP and the fluctuation in X5 were positively correlated. CONCLUSIONS: The PEEP effect of HFNC was confirmed by the electrical impedance method and FOT. The increment in TV and the difference in EIOP of HFNC showed strong negative correlations.

Sclerosing thymoma-like thymic amyloidoma with nephrotic syndrome: a case report.

BACKGROUND: Primary localized amyloidosis presenting as an isolated mediastinal mass is extremely rare, especially in the thymus. Sclerosing thymoma is also an extremely rare anterior mediastinal tumor, pathologically characterized by extensive sclerotic lesions with hyalinization and calcification. Only 14 cases of sclerosing thymoma and five cases of thymic amyloidosis have been reported to date. CASE PRESENTATION: A 78-year-old Japanese woman was diagnosed as having sclerosing thymoma (Masaoka stage IVa pericardial dissemination)-like thymic amyloidoma. She was diagnosed as having either lung cancer or mediastinal tumor with pericardial dissemination, and received palliative treatment. Three years later, she was readmitted with a complaint of general malaise. Since minimal change nephrotic syndrome was suspected based on the disease onset and selectivity index of urinary protein, steroid pulse therapy was started. Subsequently, because a marked reduction in tumor size was observed during maintenance treatment with prednisolone, a thoracoscopic needle biopsy was performed for a definitive diagnosis. According to the pathological findings and clinical investigations, a final diagnosis of sclerosing thymoma (Masaoka stage IVa pericardial dissemination)-like thymic amyloidoma was made. CONCLUSIONS: This is a case report of sclerosing thymoma-like thymic amyloidoma. Both sclerosing thymoma and thymic amyloidoma are extremely rare diseases: only 14 cases of sclerosing thymoma and five cases of thymic amyloidosis have been reported to date. In either diagnosis, our case is the first case in which marked reduction in tumor size was observed with steroid therapy. All reported cases of sclerosing thymomas underwent surgical resection, but steroid therapy to sclerosing thymoma has not been reported. It is still unknown whether steroid therapy is effective or not. The hyalinized components of sclerosing thymoma possibly contain amyloid deposits. The marked reduction in tumor size with steroid therapy may result in amyloid deposits. The association between sclerosing thymoma and thymic amyloidoma remains uncertain. Sclerosing thymoma should be stained with Congo red.

Nasal high-flow oxygen therapy system for improving sleep-related hypoventilation in chronic obstructive pulmonary disease: a case report.

INTRODUCTION: Sleep-related hypoventilation should be considered in patients with chronic obstructive pulmonary disease, because appropriate respiratory management during sleep is important for preventing elevation of PaCO2 levels. A nasal high-flow oxygen therapy system using a special nasal cannula can deliver suitably heated and humidified oxygen at up to 60 L/min. Since the oxygen concentration remains a constant independent of minute ventilation, this system is particularly useful in patients with chronic obstructive pulmonary disease who have hypercapnia. This is the first report of sleep-related hypoventilation with chronic obstructive pulmonary disease improving using a nasal high-flow oxygen therapy system. CASE PRESENTATION: We report the case of a 73-year-old Japanese female who started noninvasive positive-pressure ventilation for acute exacerbation of chronic obstructive pulmonary disease and CO2 narcosis due to respiratory infection. Since she became agitated as her level of consciousness improved, she was switched to a nasal high-flow oxygen therapy system. When a repeat polysomnography was performed while using the nasal high-flow oxygen therapy system, the Apnea Hypopnea Index was 3.7 times/h, her mean SpO2 had increased from 89 to 93%, percentage time with SpO2 ≤ 90% had decreased dramatically from 30.8 to 2.5%, and sleep stage 4 was now detected for 38.5 minutes. As these findings indicated marked improvements in sleep-related hypoventilation, nasal high-flow oxygen therapy was continued at home. She has since experienced no recurrences of CO2 narcosis and has been able to continue home treatment. CONCLUSIONS: Use of a nasal high-flow oxygen therapy system proved effective in delivering a prescribed concentration of oxygen from the time of acute exacerbation until returning home in a patient with chronic obstructive pulmonary disease, dementia and sleep-related hypoventilation. The nasal high-flow oxygen therapy system is currently used as a device to administer high concentrations of oxygen in many patients with type I respiratory failure, but may also be useful instead of a Venturi mask in patients like ours with type II respiratory failure, additionally providing some positive end-expiratory pressure.

Positive outcome of average volume-assured pressure support mode of a Respironics V60 Ventilator in acute exacerbation of chronic obstructive pulmonary disease: a case report.

INTRODUCTION: We were able to treat a patient with acute exacerbation of chronic obstructive pulmonary disease who also suffered from sleep-disordered breathing by using the average volume-assured pressure support mode of a Respironics V60 Ventilator (Philips Respironics: United States). This allows a target tidal volume to be set based on automatic changes in inspiratory positive airway pressure. This removed the need to change the noninvasive positive pressure ventilation settings during the day and during sleep. The Respironics V60 Ventilator, in the average volume-assured pressure support mode, was attached to our patient and improved and stabilized his sleep-related hypoventilation by automatically adjusting force to within an acceptable range. CASE PRESENTATION: Our patient was a 74-year-old Japanese man who was hospitalized for treatment due to worsening of dyspnea and hypoxemia. He was diagnosed with acute exacerbation of chronic obstructive pulmonary disease and full-time biphasic positive airway pressure support ventilation was initiated. Our patient was temporarily provided with portable noninvasive positive pressure ventilation at night-time following an improvement in his condition, but his chronic obstructive pulmonary disease again worsened due to the recurrence of a respiratory infection. During the initial exacerbation, his tidal volume was significantly lower during sleep (378.9 ± 72.9mL) than while awake (446.5 ± 63.3mL). A ventilator that allows ventilation to be maintained by automatically adjusting the inspiratory force to within an acceptable range was attached in average volume-assured pressure support mode, improving his sleep-related hypoventilation, which is often associated with the use of the Respironics V60 Ventilator. Polysomnography performed while our patient was on noninvasive positive pressure ventilation revealed obstructive sleep apnea syndrome (apnea-hypopnea index = 14), suggesting that his chronic obstructive pulmonary disease was complicated by obstructive sleep apnea syndrome. CONCLUSION: In cases such as this, in which patients with severe acute respiratory failure requiring full-time noninvasive positive pressure ventilation therapy also show sleep-disordered breathing, different ventilator settings must be used for waking and sleeping. On such occasions, the Respironics V60 Ventilator, which is equipped with an average volume-assured pressure support mode, may be useful in improving gas exchange and may achieve good patient compliance, because that mode allows ventilation to be maintained by automatically adjusting the inspiratory force to within an acceptable range whenever ventilation falls below target levels.

SIMCOMP/SUBCOMP: chemical structure search servers for network analyses.

One of the greatest challenges in bioinformatics is to shed light on the relationship between genomic and chemical significances of metabolic pathways. Here, we demonstrate two types of chemical structure search servers: SIMCOMP (http://www.genome.jp/tools/simcomp/) for the chemical similarity search and SUBCOMP (http://www.genome.jp/tools/subcomp/) for the chemical substructure search, where both servers provide links to the KEGG PATHWAY and BRITE databases. The SIMCOMP is a graph-based method for searching the maximal common subgraph isomorphism by finding the maximal cliques in the association graph. In contrast, the SUBCOMP is an extended method for solving the subgraph isomorphism problem. The obtained links to PATHWAY or BRITE databases can be used to interpret as the biological meanings of chemical structures from the viewpoint of the various biological functions including metabolic networks.

[A case of interstitial pneumonia complicating RS3PE syndrome in which soluble interleukin-2 receptor (sIL-2R) proved useful for assessing symptoms].

The patient was a 70-year-old man who had been given a diagnosis of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome and had been placed on low-dose steroid therapy in the Department of Orthopedics. During treatment, sudden fever, hypoxemia and chest radiography-confirmed interstitial shadows throughout the lung fields were noted, and the patient was referred to the Department of Internal Medicine. RS3PE complicated by interstitial pneumonia was diagnosed, and steroid pulse therapy and immunosuppressant therapy were initiated. In the present case, soluble interleukin-2 receptor (sIL-2R) proved useful for assessing symptoms. To the best of our knowledge, RS3PE syndrome complicated by pulmonary lesions and accompanied by severe acute respiratory failure requiring noninvasive positive-pressure ventilation has not previously been reported, and this rare case is discussed with reference to the literature.

Rapid improvement of massive bloody pleural effusion after splenectomy for splenic marginal zone lymphoma.

Splenic marginal zone lymphoma (SMZL) is a rare malignant lymphoma involving marginal zone B cells, accounting for only 1% of non-Hodgkin lymphomas. No previous reports have documented SMZL accompanied by massive bloody pleural effusion. Herein, the case of a patient with SMZL that was only diagnosed after splenectomy and thoracoscopic pleural biopsy is presented. SMZL in this patient was accompanied by massive bloody pleural effusion. The characteristics of the patient's pleural effusion changed from bloody to transudative after splenectomy, and rapid improvement was observed. It was considered that the splenectomy was valid for treatment of unidentified pleural effusion with enlarged spleen.

[A case of non-tuberculous mycobacteriosis with pleurisy with a past history of dense exposure to environmental asbestos].

We report a case of non-tuberculous mycobacteriosis (NTM) with pleurisy in a 75-year-old man. The patient was admitted with a diagnosis of pneumonia. Chest radiography and CT scans revealed a tumorous shadow that increased rapidly in size despite treatment with antibiotics. Bronchoalveolar lavage fluid (BALF) disclosed numerous asbestos bodies, suggesting dense exposure and pulmonary silicosis. The tumorous chest shadow remained undiagnosed. Repeated microscopic examination of sputum and BALF revealed no acidophilic-bacilli. Diagnostic pneumonectomy was performed to further explore the nature of the tumorous shadow on chest radiography. Ziehl-Neelsen staining of excised lung tissue disclosed no acid-bacilli; however, the washed fluid of the tissue specimen showed acid-fast bacilli that were subsequently verified as M. avium by in vitro culture. The X-ray findings in our case were not consistent with NTM or specific for disease due to asbestos inhalation. A final diagnosis of NTM was confirmed via open biopsy of the lung. Our case suggests that in addition to tuberculosis, NTM should be taken into consideration as a complication of silicosis.

Identification of endocrine disruptor biodegradation by integration of structure-activity relationship with pathway analysis.

We present a SAR method that can predict estrogen-like endocrine disrupting chemical (EDC) activity as well as key biodegradation steps for detoxification. This method is based on a recent graph-mining algorithm developed by Kudo et al., which generates a set of descriptors from all potent chemical fragments (including rings). This method is novel in that it achieves chemical diversity in the training data set by sampling another data set of larger diversity. The model achieved an 83% accuracy prediction rate, and identified 1291 EDC candidates from the KEGG database. From this set of candidate compounds, bisphenol A was chosen for assay validation and biodegradation pathway analysis. Results showed that bisphenol A exhibited estrogen-like activity and was degraded in three distinct reactions. The prediction model provided information on the mechanism of the ligand-target binding, such as key functional groups involved. We focused on the enzyme commission number, which is useful for analyses of biodegradation pathways. Results identified oxygenases, ether hydrolases, and carbon-halide lyases as being important in the biodegradation pathway. This combined approach provided new information regarding the biodegradation of EDCs, and can potentially be extended to applications with transcriptomic, proteomic, and metabolomic data to provide a quick screen of biological activity and biodegradation pathway(s).