Ocular motility disorders following coronavirus disease-19 vaccination.

PURPOSE: To describe clinical manifestations and short-term prognosis of ocular motility disorders following coronavirus disease-2019 (COVID-19) vaccination. METHODS: Ocular motility disorders were diagnosed by clinical assessment, high-resolution magnetic resonance imaging, and laboratory testing. Clinical manifestations, short-term prognosis, and rate of complete recovery were analyzed. RESULTS: Sixty-three patients (37 males, 26 females) with a mean age of 61.6 ± 13.3 years (range, 22-81 years) were included in this study. Among 61 applicable patients with sufficient information regarding medical histories, 38 (62.3%) had one or more significant underlying past medical histories including vasculopathic risk factors. The interval between initial symptoms and vaccination was 8.6 ± 8.2 (range, 0-28) days. Forty-two (66.7%), 14 (22.2%), and 7 (11.1%) patients developed symptoms after the first, second, and third vaccinations, respectively. One case of internuclear ophthalmoplegia, 52 cases of cranial nerve palsy, two cases of myasthenia gravis, six cases of orbital diseases (such as myositis, thyroid eye disease, and IgG-related orbital myopathy), and two cases of comitant vertical strabismus with acute onset diplopia were found. Among 42 patients with follow-up data (duration: 62.1 ± 40.3 days), complete improvement, partial improvement, no improvement, and exacerbation were shown in 20, 15, 3, and 4 patients, respectively. CONCLUSION: This study provided various clinical features of ocular motility disorders following COVID-19 vaccination. The majority of cases had a mild clinical course while some cases showed a progressive nature. Close follow-up and further studies are needed to elucidate the underlying mechanisms and long-term prognosis.

Neuro-ophthalmologic symptoms after coronavirus disease 2019 vaccination: a retrospective study.

BACKGROUND: There have been several studies on inflammatory ophthalmic diseases; however, few studies have reported neuro-ophthalmological symptoms, such as diplopia and ocular motor nerve palsy, after coronavirus disease 2019 (COVID-19) vaccination. Therefore, this study aimed to report neuro-ophthalmological symptoms in patients after COVID-19 vaccination. METHODS: This was a retrospective study based on the medical records of 10 patients who visited our ophthalmology clinic in 2021 with symptoms, such as diplopia (nine patients) and decreased visual acuity (one patient), and showed findings, such as ocular motor nerve palsy, after vaccination against COVID-19. RESULTS: One patient had third nerve palsy, two had sixth nerve palsy, and five had fourth nerve palsy. One patient complained of subjective binocular diplopia but all test results were normal. One patient presented with decreased visual acuity accompanied by a sudden increase in intraocular pressure and orbital cellulitis in the other eye. The symptoms improved gradually in most patients. Compared with previous studies, this study reported three cases of antiplatelet therapy that was initiated due to the older age of the patients and underlying diseases. CONCLUSION: As COVID-19 vaccines can cause neuro-ophthalmological diseases, such as ocular motor nerve palsy, patients' age and underlying diseases should be considered while administering them.

Untargeted metabolomics-assisted comparative cytochrome P450-dependent metabolism of fenbendazole in human and dog liver microsomes.

Fenbendazole (FBZ), a benzimidazole carbamate anthelmintic, has attracted attention for its antitumor activity. This study examined the metabolic characteristics of FBZ in humans compared with those in dogs. The phase I metabolites were identified in liver microsomal incubates using liquid chromatography-mass spectrometry (MS)-based untargeted metabolomics approaches. Seven metabolites of FBZ were identified by principal component analysis and orthogonal partial least square-discriminant analysis based on the global ion variables of the FBZ incubation groups. The chemical structure of the FBZ metabolites was suggested by examining the MS/MS spectrum and isotope distribution pattern. Cytochrome P450 (CYP) 1A1, CYP2D6, and CYP2J2 were the major isozymes responsible for the FBZ metabolism. No differences in the types of metabolites produced by the two species were noted. Multivariate analysis of human and dog incubation groups showed that five metabolites were relatively abundant in humans and the other two were not. In summary, the phase I metabolic profile of FBZ and the comparative metabolism between humans and dogs were examined using an untargeted metabolomics approach. This study suggests a successful investigation of FBZ metabolism in humans for conducting safety assessments regarding drug repositioning.

Effect of concomitant oral administration of ethanol on the pharmacokinetics of nicardipine in rats.

Ethanol intake can alter pharmacokinetics by increasing the solubility or enhancing the absorption of concomitant drugs. Here, a selective, sensitive and reproducible high-performance liquid chromatography-tandem mass spectrometry method for the quantitative analysis of nicardipine in rat plasma was developed using simple protein precipitation. The calibration curve was linear over a concentration range of 1-2,000 ng/ml (r2 > 0.998). Accuracy ranged from 93.4 to 112.2% and precision was within 12.1% from three independent analytical batches. Stable conditions for the quantification of nicardipine in rat plasma were established in various conditions, including sample storage and handling. The matrix effect was negligible, and recovery was consistent at three different levels of quality control sample. The method was applied to assessment for the effect of ethanol on the pharmacokinetics of nicardipine in rats. The oral bioavailability of nicardipine was increased from 5.4 to 9.4% in Sprague-Dawley rats by concomitant oral administration of ethanol whereas the half-life was not altered. The findings indicated that concomitant ethanol intake can increase systemic drug exposure by increasing gastrointestinal absorption, especially poorly soluble drugs. This study provides an insight for further investigation of the alteration of the pharmacological effect of poorly soluble drugs owing to ethanol intake.

Effect of modified graded recession and anteriorization on unilateral superior oblique palsy: a retrospective study.

BACKGROUND: Several inferior oblique (IO) weakening methods exist for correction of superior oblique palsy (SOP). A previously reported method involved recession and anteriorization according to IO overaction (IOOA) grade, which might be subjective and cause upgaze limitation and opposite vertical strabismus. Therefore, this study attempted to examine the efficacy of modified graded recession and anteriorization of the IO muscle in correction of unilateral SOP without resulting in upgaze limitation or opposite vertical strabismus. METHODS: A total of 26 patients (male, 16; female, 10; age: 3-40 years) with SOP and head tilt or diplopia underwent modified graded recession and anteriorization. Patients were grouped by the position at which the IO muscle was attached inferior/temporal to the lateral border of the inferior rectus (IR) as follows: (1) 7.0/2.0 mm (4 patients), (2) 6.0/2.0 mm (3 patients), (3) 5.0/2.0 mm (3 patients), (4) 4.0/2.0 mm (11 patients), (5) 3.0/0.0 mm (2 patients), and (6) 2.0/0.0 mm (3 patients). Recession and anteriorization were matched to vertical deviation in the primary position at far distance. Remaining diplopia, head tilt, vertical deviation (≤3 prism diopter (PD), excellent; 4-7 PD, good; and ≥ 8 PD, poor), upgaze limitation, and opposite vertical strabismus were evaluated. RESULTS: The average pre and postoperative 1-year vertical deviation angles in the primary position at far distance were 15.0 ± 5.6 PD and 1.2 ± 2.0 PD, respectively. At 1 year post-surgery, the vertical deviation angles were reduced by 6.8-21.0 PD from those at baseline. Few patients exhibited remaining head tilt, diplopia, upgaze limitation, or opposite vertical strabismus. Correction of hypertropia was excellent in 22 and good in 4 patients. CONCLUSIONS: Modified graded recession and anteriorization of the IO muscle is an effective surgical method for treating unilateral SOP. It exhibits good results and reduces the incidence of opposite vertical strabismus.

Factors associated with myopia in 19-year-old adult men in Korea between 2014 and 2020.

Numerous environmental factors that influence myopia have been studied, but only few factors have been definitively identified. We examined factors influencing myopia using data from 2014 to 2020 physical examinations received from the Korean Military Manpower Administration. We used the Cochran-Armitage trend test to investigate the annual prevalence of myopia and high myopia. To determine risk factors for myopia, logistic regression was performed. The data of 2,215,126 19-year-old Korean men were examined. The myopia and high myopia prevalences showed significant annual increases; in 2020, these prevalences were 58.9% and 18.0%, respectively. The myopia prevalence was high when the birth season was spring, education level was high, height was small, weight and body mass index (BMI) were low (< 18.5 kg/m2), and color vision was normal (all, p < 0.05). The high myopia prevalence was high when the birth season was spring, education level was high, height was tall, weight and BMI were low (< 18.5 kg/m2), and color vision was normal (all, p < 0.05). The prevalence of myopia and high myopia in this population is increasing annually. The risk of both conditions increased when the birth season was spring, education level was high, BMI was low, color vision was normal, and diabetes was present.

Changes in Clinical Activity, Serum Autoantibody Levels, and Chorioretinal Vessels After Systemic Glucocorticoid Therapy in Thyroid Eye Disease.

INTRODUCTION: The aim of this study was to investigate changes in the Clinical Activity Score, serum thyroid-stimulating hormone receptor antibody and thyroid-stimulating immunoglobulin levels, chorioretinal blood vessels, and extraocular muscle thickness in patients with thyroid eye disease following systemic steroid treatment. METHODS: This prospective observational study enrolled 57 patients with active thyroid eye disease who received systemic intravenous glucocorticoids for 12 weeks. Demographics, clinical activity scores, optical coherence tomography images, and serum thyroid-stimulating immunoglobulin and thyroid-stimulating hormone receptor antibody levels were assessed at baseline, at 6 and 12 weeks after intravenous (IV) GC therapy initiation, and 2 months after IV GC therapy termination. The extraocular muscle thickness, choroidal thickness, and choroidal vascularity index were measured. RESULTS: The clinical activity scores showed a significant decrease. Serum thyroid-stimulating immunoglobulin levels dropped continuously for 2 months. The thyroid-stimulating hormone receptor antibody level decreased until 12 weeks after treatment but returned to within the normal range in 75% of patients after 77 and 126 days, respectively. The choroidal thickness decreased at all time points. The thickness of the medial and inferior rectus muscles decreased at 2 months after treatment. The clinical activity score decreased to < 3 points in 50% of patients after 78 days. CONCLUSION: Intravenous glucocorticoid therapy improved the clinical activity score, chorioretinal blood flow, and extraocular muscle thickness. The serum autoantibody levels were normalized in patients with active thyroid eye disease 2 months after IV GC termination. The serum thyroid-stimulating immunoglobulin and thyroid-stimulating hormone receptor antibody levels correlated with restoration of chorioretinal capillary perfusion and improved clinical symptoms and muscle thickness. Non-invasive optical coherence tomography findings and serologic factors predict the response to intravenous glucocorticoid therapy.

Comparison of Retinal and Choroidal Microvasculature Changes in Monocular Amblyopic and Non-amblyopic Eyes following Short-term Patch Occlusion Treatment.

PURPOSE: Our objective was to investigate whether there were differences in the short-term changes of retinal and choroidal microvasculature between amblyopic and non-amblyopic eyes after patch occlusion treatment in patients with monocular amblyopia. Additionally, we aimed to determine if these changes were associated with improvements in clinical parameters. METHODS: We conducted a retrospective, longitudinal paired-eye case-control study by analyzing the medical records of patients under the age of 12 who had monocular amblyopia and underwent patch occlusion treatment for a duration of 2 to 12 months. Using optical coherence tomography angiography images, we compared the foveal avascular zone width, retinal blood vessel density (VD), choroidal thickness (CT), and choroidal vascularity index (CVI) in amblyopic and non-amblyopic eyes before and after patch occlusion treatment. We analyzed the correlations between the aforementioned parameters and changes in best-corrected visual acuity (BCVA) and stereopsis. RESULTS: Overall, 114 eyes from 57 patients were enrolled. At baseline, parafoveal superficial plexus VD, foveal and parafoveal deep capillary plexus VD (DCPD) were lower by 0.994 ± 3.312% (p = .026), 2.403 ± 8.273% (p = .033), and 2.469 ± 4.095% (p < .001), respectively; CT was thicker by 30.6 ± 90.7 µm (p = .014); and CVI was higher by 1.920 ± 3.432% (p < 001) in the amblyopic eyes than in the non-amblyopic eyes. Following short-term patch occlusion treatment, foveal and parafoveal DCPD increased by 1.264 ± 3.829% (p = .017) and 1.028 ± 3.662% (p = .036), respectively, CT thinned by 15.5 ± 51.5 µm (p = .019), and CVI decreased by 1.296 ± 3.997% (p = .018) in the amblyopic eyes. Following patch occlusion treatment, as the foveal DCPD decreased and CVI increased, the BCVA improved (p = .017 and .035, respectively). CONCLUSION: Following patch occlusion treatment, increased foveal DCPD and decreased CVI were associated with improved BCVA.

Short-term effects of occlusion therapy and optical correction on microvasculature in monocular amblyopia: a retrospective case-control study.

This retrospective longitudinal case-control study investigated the short-term effects of patch occlusion treatment compared with optical correction on the microvasculature in monocular amblyopia. We included patients with monocular amblyopia treated for 2-12 months; they were classified into two groups according to the treatment regimen: patch occlusion or optical correction. Children aged < 12 years who presented to our clinic for examination without amblyopia diagnosis were enrolled as the control group. Changes in retinal and choroid microvasculature according to treatment were examined, and the correlation between changes in microvasculature and improvement in best-corrected visual acuity (BCVA) was evaluated. There were 57, 35, and 41 patients in the patch occlusion, optical correction, and control groups, respectively (mean age, 6.4 ± 2.0 years). Both amblyopic groups showed changes in the foveal and parafoveal deep capillary plexus vessel density (DCPD), choroidal thickness, and choroidal vascularity index (CVI) following short-term treatment (mean, 4.5 months). In the patch occlusion group, BCVA improved as the foveal DCPD increased (P = 0.013) and the CVI decreased (P = 0.037). In the optical correction group, BCVA improved as the foveal and parafoveal DCPD increased (P = 0.009). Increased foveal DCPD following amblyopia treatment and decreased CVI by patch occlusion were associated with improved BCVA.

Synergistic Induction of iNOS by IFN-γ and Glycoprotein Isolated from Dioscorea batatas.

Dioscorea species continue to be used in traditional Chinese medicine, and represent a major source of steroid precursors for conventional medicine. In the previous study, We isolated glycoprotein (GDB) from Dioscorea batatas, characterized, and demonstrated immunostimulating activity in C57BL/6 mice. The aim of this study was to investigate the mechanism whereby GDB activates macrophages. Macrophages activation by GDB was investigated by analyzing the effects of GDB on nitric oxide (NO) production, iNOS expression, mitogen activated protein kinase (MAPK) phosphorylation, and transcription factor activation. In the presence of IFN-γ, GDB strongly stimulated macrophages to express iNOS and produce NO. Furthermore, the activation of p38 was synergistically induced by GDB plus IFN-γ , but SB203580 (a p38 inhibitor) inhibited GDB plus IFN-γ-induced p38 activation. This study indicates that GDB is an important activator of macrophages. Furthermore, due to the critical role that macrophage activation plays in innate immune response, the activation effects of GDB on macrophages suggest that GDB may be a useful immunopotentiating agent.

Alterations of lower- and higher-order aberrations after unilateral horizontal rectus muscle surgery in children with intermittent exotropia: A retrospective cross-sectional study.

BACKGROUND: This retrospective, cross-sectional study investigated changes in corneal lower- and higher-order aberrations that cause visual disturbance after lateral rectus recession and medial rectus resection in children. METHODS: Eighty-five eyes of 85 patients (44 boys; 8.64±2.88 years) who underwent lateral rectus recession and medial rectus resection to correct intermittent exotropia were assessed. The Galilei G4 Dual Scheimpflug Analyzer was used for wavefront analysis. Risk factors (age, sex, amount of surgery, preoperative axial length, preoperative intraocular pressure) were determined. Outcome measures included simulated and ray-tracing mode keratometry with secondary defocus, oblique, and vertical astigmatism (for lower-order aberrations) and the root mean square, 3rd-order vertical and horizontal coma, oblique and horizontal trefoil, 4th-order spherical aberration, oblique and vertical secondary astigmatism, and oblique and vertical quadrafoil (2nd‒8th sums) (for higher-order aberrations). RESULTS: Myopic with-the-rule changes in low-order aberrations and increases in simulated and ray-tracing mode keratometry during the 3 months following lateral rectus recession and medial rectus resection were attributed to muscle healing and stability changes. High-order aberrations altered in the week following surgery almost returned to normal within 3 months. Axial length, the amount of surgery, age, and sex affected astigmatism due to differences in patients' scleral states. CONCLUSIONS: Clinicians should consider changes in high-order aberrations of young individuals who underwent lateral rectus recession and medial rectus resection and may not be able to verbalize changes in vision.

Simultaneous determination of perfluorooctanoic acid and perfluorooctanesulfonic acid in Korean sera using LC-MS/MS.

Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) are synthetic chemicals that have been used in various industries and household products. These can easily accumulate in the human body, causing adverse effects on human health. In this study, a high-performance liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous analysis of PFOA and linear PFOS in human serum. Owing to a lack of PFOA- and PFOS-free human serum, 13C8-PFOA and 13C8-PFOS were used as surrogate analytes for quantification. A sensitive and selective sample preparation method was developed and optimized by combining solid-phase extraction and protein precipitation method. The lower limit of quantification was 0.05 ng/mL, and the analytical response was linear up to 10 ng/mL for both PFOA and linear PFOS. Chromatographic separation of the linear PFOS from branched isomers was achieved within 5.5 min. The method was validated at various concentrations and afforded acceptable accuracy and precision values. After validation, the method was successfully applied to evaluate the exposure levels of PFOA and linear PFOS in the Korean population. The serum concentrations of PFOA and linear PFOS were 0.42-28.3 ng/mL and 0.81-57.6 ng/mL, respectively. The median concentration of linear PFOS was approximately 2.6-fold higher than that of PFOA. The concentration of PFOA was higher in women than men (p < 0.05) and that of linear PFOS was not significantly different between men and women. Therefore, a sensitive, selective, and reliable bioanalytical method was developed and validated. This method can potentially be applied to biomonitoring studies involving PFOA and linear PFOS.

Prolongation of graft survival via layer-by-layer assembly of collagen and immunosuppressive particles on pancreatic islets.

Pancreatic islet transplantation holds great potential as a curative therapy for treating type 1 diabetes. However, the need for lifelong systemic immunosuppression with inevitable side effects is an obstacle to clinical success. Here we devised a strategy for the site-specific delivery of an immunosuppressant (tacrolimus) using layer-by-layer assembly of polymeric particles and collagen on the islet surface. This approach aims to provide a continuous and sustained supply of tacrolimus in the vicinity of transplanted cells while avoiding systemic drug exposure. The dose and release rate of tacrolimus can be tunable to achieve therapeutic windows by varying layer-by-layer construction and chemistry of polymers. Transplanting 400 IEQ of pancreatic islets coated with particles containing ∼3 µg of TAC per recipient provided controlled drug release and rectified diabetes for up to 5 months in a xenogeneic rodent model of type 1 diabetes. We anticipate that the findings of this study will be found useful by those developing local immunomodulation strategies aimed at improving the outcomes and safety of cell therapies for curing type 1 diabetes.

Delayed unilateral pneumocephalus after bilateral endoscopic dacryocystorhinostomy in an elderly patient.

Dacryocystorhinostomy (DCR) is the 'gold standard' treatment for nasolacrimal duct obstruction (NLDO). However, despite its recent technical advancements, complications are possible. Herein, to the best of our knowledge, we present the first reported case of delayed unilateral pneumocephalus after bilateral endoscopic DCR. An 85-year-old man with bilateral NLDO underwent endoscopic DCR with silicone intubation. After 1 month, he became lethargic and was admitted to emergency room. Brain CT demonstrated left pneumocephalus and a suspected microfistula in left orbital wall. Intravenous antibiotic therapy was started, and cerebrospinal fluid studies showed no evidence of meningitis. After 13 days of antibiotic treatment, his mental state recovered with no signs of pneumocephalus. Although DCR has high success rate and is relatively safe, surgeons should be aware of the risk, although low, of pneumocephalus, especially in elderly patients who are vulnerable to fractures and who exhibit headache or mental status changes after endoscopic DCR.

An Overview of the Korean Intermittent Exotropia Multicenter Study by the Korean Association for Pediatric Ophthalmology and Strabismus.

The Korean Intermittent Exotropia Multicenter Study (KIEMS), which was initiated by the Korean Association of Pediatric Ophthalmology and Strabismus, is a collaborative multicenter study on intermittent exotropia in Korea. The KIEMS was designed to provide comprehensive information, including subjective and objective findings of intermittent exotropia in a large study population. A total of 65 strabismus specialists in 53 institutions contributed to this study, which, to date, is one of the largest clinical studies on intermittent exotropia. In this article, we provide a detailed methodology of the KIEMS to help future investigations that may use the KIEMS data.

Analysis of corneal real astigmatism and high order aberration changes that cause visual disturbances after lower eyelid epiblepharon repair surgery.

This retrospective, cross-sectional study investigated changes in corneal low and high order aberrations (LOAs and HOAs) after lower eyelid epiblepharon repair surgery. In total, 108 eyes from 54 patients were evaluated. Wavefront analyses for calibrated LOAs and HOAs were performed using a Galilei G4 Dual Scheimpflug Analyzer before surgery and during the first and second follow-ups (f/u), adjusting for several risk factors. Flat keratometry (K) and axis values decreased significantly from baseline at the first f/u. At the second f/u, mean K and axis values decreased. Coma and trefoil increased from baseline at the first f/u and normalized by the second f/u. Spherical aberrations (SA) only decreased at the second f/u. After correction for risk factors, cylinder, coma, trefoil, and SA significantly increased at the first f/u; axis and flat K values decreased. At the second f/u, cylinder increased while axis and mean K values significantly decreased. Epiblepharon repair surgery may result in a shift from 'with-the-rule' to 'against-the-rule' axis change. Flat K, coma, and trefoil may be affected by mechanical force changes immediately post-surgery, while mean K values and SA may also change with corneal state changes including corneal erosion healing after the second f/u during the postoperative period.

Analysis of astigmatism outcomes after horizontal rectus muscle surgery in patients with intermittent exotropia.

This study examined the factors affecting corneal curvature change after lateral rectus recession and medial rectus resection surgery in patients with intermittent exotropia. This was a retrospective cross-sectional study in intermittent exotropia patients who underwent rectus resection surgery. The study involved 41 male and 42 female patients (mean age: 9.55 ± 5.03 years, range: 3-28 years). Corneal astigmatism analysis was performed using the Galilei G4 Dual Scheimpflug Analyzer. The values of simulated and ray tracing corneal keratometry (K) of astigmatism, including axis changes, were determined preoperatively and at 1 week and 3 months postoperatively. The factors found to affect corneal curvature change were sex, extent of surgery, and axial length. Simulated and ray tracing changes were significant preoperatively and at 1 week and 3 months after rectus resection surgery (p < 0.05); however, there were no differences in astigmatism (D) at any time. The spherical equivalent had a myopic change after rectus resection surgery with cycloplegic refraction, and in ray tracing mode, flat K was decreased at 1 week from baseline and increased 3 months later. Steep, mean K, and axis increased continuously from baseline to 1 week and 3 months. Astigmatism, in contrast, was increased at 1 week, but decreased at 3 months, with no return to baseline. Univariable linear regression analyses showed that the extent of surgery had an effect on flat K change and that sex had an effect on steep K and axis. Additionally, axial length affected steep K and astigmatism, while age had no effect on any variable. Ray tracing values were significantly different from simulated values. In ray tracing mode, rectus resection surgery may result in astigmatism shifted toward with-the-rule, and myopic changes may be caused by differences in thickness and flexibility of the sclera. Notably, age did not affect any variable.

Course of upper eyelid retraction in thyroid eye disease.

AIMS: To evaluate the natural course of upper eyelid retraction (UER) in patients with thyroid eye disease (TED) and factors affecting its course. METHODS: Retrospective non-interventional cohort study in a single tertiary institution from March 2006 to March 2015 on patients with TED with (1) unilateral or bilateral UER within 6 months from initial presentation, and (2) no prior interventions nor surgical treatment for their UER. Main outcomes and measures were mean margin reflex distance 1 (MRD1) and factors associated with UER improvement. RESULTS: There were a total of 61 patients and 81 eyes (41 unilateral and 20 bilateral UER). Mean age was 42.3±15.1 years. Mean MRD1 decreased from 6.1 mm at presentation to 4.8 mm at 12 months, and 4.4 mm at 24 months. The proportion of eyes with normalisation of lid height increased from 0% at presentation to 22.2% at 6 months, 37.0% at 12 months and 49.4% at 24 months. Mean time to normalisation of MRD1 was 18.0±12.4 months. A positive family history of TED was found to be associated with a 6.2 times lower likelihood of normalisation. Change in exophthalmometry, clinical activity score and thyroid-stimulating immunoglobulin were significantly correlated to change in MRD1 (p<0.05). There was no correlation between change in MRD1 and thyroid-stimulating hormone receptor antibodies. CONCLUSION: An improved knowledge of the natural history of UER in TED will allow us to better decide and evaluate the optimal management for such patients.

Cyclosporine A eyedrops with self-nanoemulsifying drug delivery systems have improved physicochemical properties and efficacy against dry eye disease in a murine dry eye model.

PURPOSE: We aimed to compare the physicochemical properties and in vivo efficacy of commercially available nanoemulsion cyclosporine A (CsA) eyedrops in benzalkonium chloride (BAC)-induced dry eye disease (DED). METHODS: Particle size analysis was performed on conventional 0.05% CsA (Restasis, C-CsA) and two new types of 0.05% CsA eyedrops based on a self-nanoemulsifying drug delivery system (SNEDDS, SNEDDS-N and -T). Turbidometry, pH measurements and instability indices of each CsA solution were measured. DED was induced with BAC, and animals were treated with vehicle or CsA preparations. Tear volume and fluorescein staining scores were evaluated on days 7 and 14. Eyes were enucleated and subjected to IHC, TUNEL staining, periodic acid-Schiff (PAS) staining, real-time PCR and western blotting. RESULTS: Both SNEDDSs had lower and more uniform particle size distribution than C-CsA, and a similar optical density to phosphate-buffered saline and stable pH, in contrast to the high turbidity and unstable pH of C-CsA. Aqueous tear volume and fluorescein staining scores were improved in C-CsA- and SNEDDS-treated mice. Numbers of PAS-positive goblet cells and levels of inflammatory mediators were decreased by both C-CsA and SNEDDS, although SNEDDS resolved inflammation more effectively than C-CsA. CONCLUSIONS: Cyclosporine A eyedrops with SNEDDS have improved physicochemical properties and treatment efficacy in BAC-induced DED.