Profiling miRNAs in tear extracellular vesicles: a pilot study with implications for diagnosis of ocular diseases.

PURPOSE: To estimate the roles of extracellular vesicles (EVs) in tears and to determine whether their profiles are associated with the type of ocular disease. STUDY DESIGN: Cross-sectional study. METHODS: Tear EVs were extracted from 14 healthy participants and from 21 patients with retinal diseases (age-related macular degeneration [AMD] or diabetic macular edema [DME]). The surface marker expression of tear EVs was examined, and microRNAs (miRNAs) were extracted and profiled by use of real-time PCR array. The stability of the expression of the miRNAs was determined, and their functions were assessed by network analyses. Classification accuracy was evaluated by use of a random forest classifier and k-fold cross-validation. RESULTS: The miRNAs that were highly expressed in tear EVs were miR-323-3p, miR-548a-3p, and miR-516a-5p. The most stably expressed miRNAs independent of diseases were miR-520h and miR-146b-3p. The primary networks of the highly stably expressed endogenous miRNAs were annotated as regulation of organismal injury and abnormalities. The highly expressed miRNAs for severe retinal disease were miR-151-5p for AMD and miR-422a for DME, suggesting potential roles of tear EVs in liquid biopsy. Nine miRNAs (miR-25, miR-30d, miR-125b, miR-132, miR-150, miR-184, miR-342-3p, miR-378, and miR-518b) were identified as distinguishing individuals with AMD from healthy individuals with a classification accuracy of 91.9%. CONCLUSIONS: The finding that tear EVs contain characteristic miRNA species indicates that they may help in maintaining homeostasis and serve as a potential tool for disease diagnosis.

Intraoperative Measurement of Crystalline Lens Diameter in Living Humans.

BACKGROUND: There are no reports on accurate measurement of lens equatorial diameter of the living human eye. This study aimed to measure lens equatorial diameter with a special measurement device during cataract surgery and examine the relationships with preoperative parameters. METHODS: From April 7 to December 1, 2019, the equatorial diameters of 24 eyes from 24 patients who underwent cataract surgery at Kushimoto Arita Hospital were measured with a loop shaped measurement device during cataract surgery. Correlations between the value of the diameters and various preoperative parameters measured by CASIA2® were evaluated. RESULTS: The average value of the measured equatorial diameter using the device was 10.5 ± 0.4 mm and the value estimated by circular approximation using the CASIA2®ï¸ was 10.1 ± 0.7 mm. A significant difference was observed between these two groups (P = 0.016), and only a weak correlation was observed (γ = 0.31). A positive correlation was observed between equatorial diameter and anterior chamber depth (ACD) or anterior chamber width (ACW) (γ = 0.57 and 0.47, respectively). No significant correlation was found between other parameters and the value measured by the device. CONCLUSION: Our method is a completely new approach to measuring the living human lens equatorial region of the eye. No complications were observed in any of the cases. One new finding was the values of the lens equatorial diameters are actually longer than those reported previously. The results suggest that the values of the equatorial diameter measured by the loop device and those estimated by CASIA2® measurement were closer than those reported previously by other methods, although both were slightly different. We conclude that it is still difficult to estimate the equatorial diameter of the living human lens using preoperative examination parameters. This research will greatly contribute to the development of accommodative intraocular lenses in the future.

Perioperative Bypassing Agent Therapy for Pulmonary Pleomorphic Carcinoma with Acquired Hemophilia.

A 74-year-old man was admitted with lung cancer, and preoperative blood test showed abnormal activated partial thromboplastin time (APTT). Coagulation factor screening and APTT mixing test achieved a diagnosis of acquired hemophilia A (AHA). Bypassing agent therapy was indicated and lobectomy was successfully performed without bleeding complications. APTT returned to normal after the operation without any additional treatment for AHA. The pathogenesis of AHA is still unknown and there is no evidence for hemostatic strategy for AHA patients requiring surgery. This study supports the importance of hemostatic therapy and suggests that malignancy might cause AHA.

High interleukin-8 level in aqueous humor is associated with poor prognosis in eyes with open angle glaucoma and neovascular glaucoma.

Glaucoma is a leading cause of blindness worldwide. Purpose of this study was to identify molecular markers that were significantly correlated with presence of glaucoma and outcome of glaucoma surgery. To accomplish this, we determined the profiles of pro-inflammatory cytokines in the aqueous humor of 101 glaucoma patients; 31 primary open angle glaucoma (POAG), 38 pseudoexfoliation glaucoma (PEG), and 32 neovascular glaucoma (NVG). We also studied 100 normal subjects as controls. In eyes with POAG or PEG, the level of interleukin (IL)-1α, IL-2, IL-4, IL-8, IL-23, and CCL2 were significantly elevated. In the NVG eyes, many inflammatory cytokines were also highly elevated. IL-8 had the highest odds ratio, and levels of IL-8 and CCL2 were significantly correlated with preoperative IOP or visual field defects in PEG eyes. Principal component analysis showed that IL-8 had the highest association to the IOP-cytokine component, and Cox proportional hazard model indicated that an elevation of IL-8 was a significant risk of filtering surgery failure. Together with modeling of their interactions and prognosis, IL-8 elevation is a significant risk factor both for detecting and managing glaucoma and may serve as a therapeutic target candidate to improve the prognosis of glaucoma surgery.

Large Plasmacytoma Occupying the Upper Limb in a Myeloma Patient.

Extramedullary disease (EMD) is an issue for patients with multiple myeloma (MM), since extramedullary spread of MM is associated with an aggressive course and a poor prognosis. Moreover, the mechanism of EMD development is uncertain. Here, we present extensive extramedullary plasmacytoma occupying the left upper limb of a 66-year-old female patient with MM with an extremely aggressive course and multiple visceral organ involvement without bone marrow infiltration or plasma cell leukemia. EMD of this large size is extremely rare and this case may provide a clue for better understanding of clinical features of EMD in MM.

[Four cases of therapy-related leukemia in multiple myeloma].

We have experienced 4 cases of therapy-related leukemia (TRL) in 119 patients with multiple myeloma (MM) who had received combination chemotherapy including alkylating agents between 1988 and 1998. All 4 cases were acute myelogenous leukemia, 3 were males and 1 was female. Median age at diagnosis of MM was 60 years, and median time to TRL from diagnosis of MM was 5.5 years. The chromosome abnormalities were found in 3 of those cases. All 4 cases were resistant to antileukemic chemotherapy, and median survival time from TRL was only 5.5 months. The TRL in MM is thought to be a more important problem, because recently the treatment for this disease has become more intensive, including high-dose chemotherapy supported by autologous stem cell transplantation.

Prognostic significance of the serum phosphorus level and its relationship with other prognostic factors in multiple myeloma.

We studied the serum phosphorus (P) level of 110 patients with multiple myeloma (MM) (age range 42-83 years, median 62 years) and evaluated the relationship between that and other prognostic factors. Serum P level significantly correlated with the prognostic factors that are relevant to renal dysfunction: serum creatinine (P<0.00000001), serum beta2-microglobulin (P=0.00000088), serum uric acid (P=0.0000014), and corrected serum calcium (cCa P=0.000067). Although it also correlated with the percentage of plasma cells in bone marrow nucleated cells (BMPC%) and the hemoglobin (Hb) and leukocyte counts, the significance was less than for the other four prognostic factors. Serum creatinine, BMPC%, leukocyte count, serum uric acid, bone lesions, beta2-microglobulin, and serum cCa were all significantly higher and Hb significantly was lower in the MM patients with hyperphosphatemia (serum P>3.8 mg/dl). The survival time was significantly shorter in these patients (P=0.000087). Multivariate analysis (Cox's proportional hazards regression model) showed that the serum P level is a significant negative prognostic factor in MM patients.