Fatal outcome of severe fever with thrombocytopenia syndrome (SFTS) and severe and critical COVID-19 is associated with the hyperproduction of IL-10 and IL-6 and the low production of TGF-ß.

Severe fever with thrombocytopenia syndrome virus (SFTSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause the hyperproduction of inflammatory cytokines, which have pathological effects in patient including severe or fatal cytokine storms. To characterize the effect of SFTSV and SARS-CoV-2 infection on the production of cytokines in severe fever with thrombocytopenia syndrome (SFTS) and COVID-19 patients, we performed an analysis of cytokines in SFTS and COVID-19 patients and also investigated the role of interleukin-10 (IL-10) in vitro studies: lipopolysaccharide-induced THP-1-derived macrophages, SFTSV infection of THP-1 cells, and SARS-CoV-2 infection of THP-1 cells. In this study, we found that levels of both IL-10 and IL-6 were significantly elevated, the level of transforming growth factor-ß (TGF-ß) was significantly decreased and IL-10 was elevated earlier than IL-6 in severe and critical COVID-19 and fatal SFTS patients, and inhibition of IL-10 signaling decreased the production of IL-6 and elevated that of TGF-ß. Therefore, the hyperproduction of IL-10 and IL-6 and the low production of TGF-ß have been linked to cytokine storm-induced mortality in fatal SFTS and severe and critically ill COVID-19 patients and that IL-10 can play an important role in the host immune response to severe and critical SARS-CoV-2 and fatal SFTSV infection.

Design of a Novel Theranostic Nanomedicine (III): Synthesis and Physicochemical Properties of Tumor-Targeting Cisplatin Conjugated to a Hydrophilic Polyphosphazene.

PURPOSE: A new theranostic nanomedicine involving anticancer-active cisplatin moiety was designed to study its tumor-targeting properties as well as its drug efficacy and toxicity. METHODS: A cisplatin carrier polymer was prepared by grafting equimolar polyethylene glycol of a molecular weight of 550 (PEG550) and aminoethanol to the poly(dichlorophosphazene) backbone. Cisplatin was conjugated to the carrier polymer using cis-aconitic acid as a linker. RESULTS: The cisplatin-loaded polyphosphazene, named "Polycisplatin" was found to be amphiphilic in aqueous solution and self-assembled into nanoparticles with an average particle size of 18.6 nm in diameter. The time-dependent organ distribution study of Cy5.5-labeled Polycisplatin in the A549-tumor-bearing mice exhibited a high tumor selectivity of Polycisplatin by EPR effect despite the relatively small particle size. In order to compare the in vivo efficacy of Polycisplatin and cisplatin, their xenograft trials were performed using nude mice against the human gastric cell line MKN-28. Polycisplatin exhibited slightly less tumor suppression effect compared with cisplatin at the same dose of 1.95 mg Pt/kg, which is the maximum tolerate dose of cisplatin, but at the higher double dose of 3.9 mg Pt/kg, Polycisplatin exhibited a little better efficacy than cisplatin. Furthermore, mice treated with cisplatin at the dose of 1.95 mg Pt/kg exhibited severe body weight decrease by about 25%, while mice treated with Polycisplatin did not show serious body weight decrease even at its double dose of 3.9 mg Pt/kg. Furthermore, kidney indicators including kidney index, BUN, and creatinine values measured displayed that Polycisplatin is much less nephrotoxic than cisplatin. CONCLUSION: Nanoparticular Polycisplatin was successfully prepared by conjugating cisplatin to a hydrophilic polyphosphazene carrier polymer using the acid-cleavable cis-aconitic acid. Polycisplatin nanoparticles exhibit excellent tumor-targeting properties by EPR effect. The xenograft trials exhibited excellent antitumor efficacy and reduced systemic toxicity of Polycisplatin.

Glistening Formation on a Single-Piece Prehydrated Hydrophobic Acrylic Intraocular Lens in a Diabetic Patient.

PURPOSE: To report a case of intraocular lens (IOL) glistening after uneventful cataract surgery and in-the-bag implantation of an enVista MX60 IOL (Bausch & Lomb, Rochester, NY) in a patient with uncontrolled diabetes mellitus. METHODS: Case report. RESULTS: A 76-year-old woman with non-insulin-dependent diabetes mellitus underwent uncomplicated phacoemulsification with in-the-bag implantation of an enVista MX60 IOL. After 6 months, glistening formation within the IOL optic was observed. In the fellow pseudophakic eye, an acrylic hydrophilic Akreos Adapt AO IOL (Bausch & Lomb) was implanted without complications. CONCLUSIONS: IOL glistening can develop with the enVista MX60 IOL, even after uneventful cataract surgeries in certain situations (eg, uncontrolled diabetes mellitus). Increased vascular permeability due to uncontrolled diabetes mellitus might have been responsible for the postoperative IOL glistening formation. [J Refract Surg. 2016;32(10):710-712.].

The effects of proinflammatory cytokines on the apoptosis of corneal endothelial cells following argon laser iridotomy.

The aim of this study was to evaluate the relationship between the expression of proinflammatory cytokines and the apoptosis of corneal endothelial cells after argon laser iridotomy (ALI). ALI was performed on each quadrant of the iris in the right eye of mice (ALI1 group). Left eyes were used as control group. The levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß, and interferon (IFN)-γ in mice eyes were measured, and TUNEL staining was performed 12 h after ALI. Mice in the ALI-Dexa group were pretreated daily with an intraperitoneal injection of dexamethasone for 4 days before undergoing ALI and compared with mice without dexamethasone pretreatment (ALI2 group). Twelve corneas from six rabbits were incubated ex vivo with (n = 6) or without (n = 6) IL-1ß. TUNEL staining was performed 24 h after ex vivo incubation. In the mice experiment, the levels of IL-1ß, TNF-α, TGF-ß, and IFN-γ were increased in the ALI1 group compared to the control group. Although many TUNEL-positive cells were observed in the ALI1 group, those were not detected in the control group. Dexamethasone pretreatment inhibited the increase in the levels of all four proinflammatory cytokines and reduced TUNEL-positive cells. In the rabbit experiment, TUNEL-positive cells were increased in the incubated corneas with IL-1ß compared to those without IL-1ß. Expression of proinflammatory cytokines following ALI seems to play a role in the apoptosis of corneal endothelial cells after ALI. Dexamethasone pretreatment inhibited increases in proinflammatory cytokines and reduced the apoptosis of corneal endothelial cells.

Comparison of the actual amount of axial movement of 3 aspheric intraocular lenses using anterior segment optical coherence tomography.

PURPOSE: To compare the mean effective lens position (ELP) and actual amount of axial movement of 3 aspheric intraocular lenses (IOLs) using anterior segment optical coherence tomography (AS-OCT). SETTING: Department of Ophthalmology, Korea University College of Medicine, Seoul, South Korea. DESIGN: Retrospective comparative study. METHODS: Consecutive patients had phacoemulsification with aspheric IOL implantation. The ELP measurements by AS-OCT were taken 1 week and 1, 3, and 6 months postoperatively. The ELPRMS was defined as the root mean square (RMS) of the change in ELP at each follow-up timepoint. RESULTS: An XL Stabi ZO 3-plate IOL was implanted in 30 eyes, an Acrysof IQ C-loop IOL in 22 eyes, and an Akreos MI-60 4-plate IOL in 17 eyes. The 4-plate IOL showed significant changes in the mean ELP from 1 week to 1 month and from 3 to 6 months postoperatively (P=.005 and P=.028, respectively). The changes of the other 2 IOLs were insignificant during the 3 postoperative visits. However, the mean ELPRMS of the C-loop IOL (0.06 mm ± 0.31 [SD]) was smaller than that of the 3-plate IOL (0.14 ± 0.28 mm) and the 4-plate IOL (0.20 ± 0.35 mm) (P=.014 and P=.023, respectively) during the 3 timepoints. CONCLUSION: An appropriate method based on the actual amount of axial IOL movement, such as the ELPRMS, is needed to assess the axial positional stability of IOLs. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Axis difference between corneal and internal astigmatism to consider for toric intraocular lenses.

PURPOSE: To evaluate the axis difference between corneal and internal astigmatism in patients with cataract, because if the axis of corneal astigmatism is opposite to the axis of internal astigmatism, the amount of refractive astigmatism will increase after cataract surgery owing to disappearance of the neutralizing effect of the crystalline lens on corneal astigmatism. DESIGN: Retrospective cross-sectional study. METHODS: One hundred eighty patients (180 eyes) who underwent cataract surgery were enrolled. Preoperative refractive, corneal, and internal astigmatism were measured using a wavefront analyzer and retrospectively analyzed. On-axis was defined as an axis difference between corneal and internal astigmatism of 180 ± 10 degrees. Opposite-axis was defined as an axis difference between corneal and internal astigmatism of 90 ± 10 degrees. The remaining cases were defined as oblique-axis. RESULTS: Corneal and internal astigmatic vectors showed a tendency to have the opposite direction. An on-axis difference was seen in 10.0% of patients (18 eyes), oblique-axis in 69.4% of patients (125 eyes), and opposite-axis in 20.6% of patients (37 eyes). Of all eyes, 10.0% had an opposite-axis difference with more than 1.00 diopter (D) of both corneal and internal astigmatism. The percentage of eyes with an opposite-axis difference between corneal and internal astigmatism had a tendency to increase as corneal and internal astigmatism increased (P = .030 and P = .003, respectively). CONCLUSIONS: A total of 10.0% of all eyes with cataract had an opposite-axis difference with more than 1.00 D of both corneal and internal astigmatism. In these cases, surgical techniques to reduce corneal astigmatism, such as a toric intraocular lens, should be recommended to increase patient satisfaction.

Calcium hydroxyapatite crystals in the anterior chamber of the eye in a patient with renal hyperparathyroidism.

PURPOSE: To report a case of calcium hydroxyapatite crystals in the anterior chamber of a patient with renal hyperparathyroidism. METHODS: Case report. RESULTS: A 54-year-old man visited our clinic with mild ocular pain and decreased visual acuity in his left eye. A slit-lamp examination showed peripheral corneal band keratopathy and multiple white crystals in the anterior chamber. The patient had chronic renal failure and was on regular hemodialysis treatment for 12 years. He had previously undergone total parathyroidectomy because of secondary renal hyperparathyroidism. Aqueous humor analysis showed elevated phosphate levels. Multiple crystals were removed using a manual irrigation and aspiration cannula and were found to be calcium hydroxyapatite crystals on elemental analysis using energy dispersive x-ray spectroscopy. Ocular pain and visual acuity improved and corneal edema and ocular inflammation decreased after the surgery. CONCLUSIONS: Calcium hydroxyapatite crystals can form in the anterior chamber of the eye in a patient with renal hyperparathyroidism.

Traumatic aniridia through opposite clear corneal incision in a pseudophakic eye.

A 56-year-old man complaining of decreased visual acuity in his left eye visited the emergency room 1 hour after blunt trauma. Slitlamp examination showed no visible iris tissue. The corneal wound at 5 o'clock was sharp, and Seidel was negative. In the right eye, there was a main clear corneal incision (CCI) at 11 o'clock and an opposite CCI (OCCI) to correct corneal astigmatism at 5 o'clock in the left eye. Anterior chamber inflammation and hyphema resolved 4 weeks after the trauma. The intraocular lens and capsular bag were intact, and the corrected distance visual acuity returned to 20/25. To our knowledge, this is the first report of traumatic iris expulsion through a 3.0 mm OCCI. An OCCI may seal better than a main CCI, which is used in cataract surgery, because the OCCI is not used during the cataract procedure. However, surgeons should be aware of the risk for postoperative wound dehiscence associated with the OCCI.

Which keratometer is most reliable for correcting astigmatism with toric intraocular lenses?

PURPOSE: To evaluate the accuracy of preoperative keratometers used in cataract surgery with toric intraocular lens (IOL). METHODS: Twenty-five eyes received an AcrySof toric IOL implantation. Four different keratometric methods, a manual keratometer, an IOL master, a Pentacam and an auto keratometer, were performed preoperatively in order to evaluate preexisting corneal astigmatism. Differences between the true residual astigmatism and the anticipated residual astigmatism (keratometric error) were compared at one and three months after surgery by using a separate vector analysis to identify the keratometric method that provided the highest accuracy for astigmatism control. RESULTS: The mean keratomeric error was 0.52 diopters (0.17-1.17) for the manual keratometer, 0.62 (0-1.31) for the IOL master, 0.69 (0.08-1.92) for the Pentacam, and 0.59 (0.08-0.94) for the auto keratometer. The manual keratometer was the most accurate, although there was no significant difference between the keratometers (p > 0.05). All of the keratometers achieved an average keratometric error of less than one diopter. CONCLUSIONS: Manual keratometry was the most accurate of the four methods evaluated, although the other techniques were equally satisfactory in determining corneal astigmatism.

Differences in corneal astigmatism between partial coherence interferometry biometry and automated keratometry and relation to topographic pattern.

PURPOSE: To compare the corneal astigmatism values obtained with a partial coherence interferometry (PCI) biometer and an automated keratometer and to evaluate the association between these differences and corneal topographic patterns. SETTING: Department of Ophthalmology, Guro Hospital, Korea University College of Medicine, Seoul, Korea. DESIGN: Comparative case series. METHODS: Corneal astigmatism was measured by PCI biometry (IOLMaster) and automated keratometry (RK-F1 autorefractor). Eyes were divided into 3 groups based on the difference in absolute astigmatism values between PCI biometry and automated keratometry (ie, PCI biometry - automated keratometry) as follows: Group 1, more than 0.25 diopter (D); Group 2, within ±0.25 D; Group 3, less than -0.25 D. The topographic maps were grouped into patterns of round, oval, symmetric bow tie, asymmetric bow tie, and irregular. Distributions of topographic patterns according to group and astigmatism values by topographic patterns were evaluated. RESULTS: The study enrolled 312 eyes. The most common pattern was the asymmetric bow tie (34.6%) followed by symmetric bow tie (20.5%), round (18.9%), irregular (16.3%), and oval (9.6%). The asymmetric bow-tie pattern was the most common in Group 1 and Group 2 (36.1% and 50.0%, respectively); however, in Group 3, the symmetric bow-tie pattern was the most common (32.8%). The distribution of topographic patterns by groups was statistically significantly different (P=.015, Pearson chi-square test). CONCLUSION: The difference in corneal astigmatism between the PCI biometer and automated keratometer may depend on the corneal topography pattern.

New axis-marking method for a toric intraocular lens: mapping method.

PURPOSE: A new axis-marking method, the mapping method, for toric intraocular lens (IOL) implantation is described, and its accuracy is compared with that of conventional methods. METHODS: For toric IOL implantation, the steepest corneal axis was determined by IOLMaster optical biometer measurement (Carl Zeiss Meditec). Three marking methods for accurate alignment of the IOL astigmatism axis to the steepest corneal axis were evaluated and compared. For method 1, the patient was seated at the surgical table and instructed to gaze at a distant target. Using a toric reference marker, the corneal limbus was marked at the 3-, 6-, and 9-o'clock positions. The goal axis was also marked using a toric axis marker. Method 2 used a horizontal slit beam for reference marking points at 3 and 9 o'clock. Method 3 was the new mapping method, in which an anterior segment photograph was used to identify several reference vessel points and axis marking points and to calculate actual lengths from the reference vessel points to the axis marking points. During surgery, the axis marking points were marked on the limbus of the eye using calipers. The accuracy of the three axis-marking methods was evaluated using anterior segment photographs. RESULTS: With method 1, the average axis-marking error was 3.69±1.49°. With method 2, the average axis-marking error was 3.14±1.64°. With method 3, the new mapping method, the average axis-marking error was 2.29±1.06°. The new mapping method was more accurate than methods 1 and 2 (P<.01 and P=.016, respectively, paired t test). Axis-marking errors of the two conventional methods were not significantly different (P=.061). CONCLUSIONS: The new axis-marking method, which uses distinct conjunctival vessels as a reference point, showed less axis-marking error compared to the conventional methods examined in this study.