Diagnosis and Treatment of Central Serous Chorioretinopathy in Patients with Scleritis.

Central serous chorioretinopathy (CSCR) is characterized by central neurosensory retinal detachment from the retinal pigment epithelium. While the association between CSCR and steroid use is widely recognized, it is difficult to distinguish whether the subretinal fluid (SRF) in ocular inflammatory disease results from steroid use or an inflammation-related uveal effusion. We report the case of a 40-year-old man who presented to our department with intermittent redness and dull pain in both eyes that had persisted for three months. He was diagnosed with scleritis with SRF in both eyes and steroid therapy was started. Inflammation improved with steroid use, but SRF increased. This indicated that the fluid was not caused by the posterior scleritis-related uveal effusion but by steroid use. SRF and clinical symptoms subsided after steroids were discontinued completely and immunomodulatory therapy was initiated. Our study highlights that steroid-associated CSCR must be considered in the differential diagnosis of patients with scleritis, and prompt diagnosis with an immediate shift from steroids to immunomodulatory therapy can resolve SRF and clinical symptoms.

Podocalyxin-Like Protein 1 Regulates Pluripotency through the Cholesterol Biosynthesis Pathway.

Deciphering signaling mechanisms critical for the extended pluripotent stem cell (EPSC) state and primed pluripotency is necessary for understanding embryonic development. Here, a membrane protein, podocalyxin-like protein 1 (PODXL) as being essential for extended and primed pluripotency, is identified. Alteration of PODXL expression levels affects self-renewal, protein expression of c-MYC and telomerase, and induced pluripotent stem cell (iPSC) and EPSC colony formation. PODXL is the first membrane protein reported to regulate de novo cholesterol biosynthesis, and human pluripotent stem cells (hPSCs) are more sensitive to cholesterol depletion than fibroblasts. The addition of exogenous cholesterol fully restores PODXL knockdown-mediated loss of pluripotency. PODXL affects lipid raft dynamics via the regulation of cholesterol. PODXL recruits the RAC1/CDC42/actin network to regulate SREBP1 and SREBP2 maturation and lipid raft dynamics. Single-cell RNA sequencing reveals PODXL overexpression enhanced chimerism between human cells in mouse host embryos (hEPSCs 57%). Interestingly, in the human-mouse chimeras, laminin and collagen signaling-related pathways are dominant in PODXL overexpressing cells. It is concluded that cholesterol regulation via PODXL signaling is critical for ESC/EPSC.

Development of a Chemical Cocktail That Rescues Mouse Brain Demyelination in a Cuprizone-Induced Model.

Oligodendrocytes are glial cells located in the central nervous system (CNS) that play essential roles in the transmission of nerve signals and in the neuroprotection of myelinated neurons. The dysfunction or loss of oligodendrocytes leads to demyelinating diseases such as multiple sclerosis (MS). To treat demyelinating diseases, the development of a therapy that promotes remyelination is required. In the present study, we established an in vitro method to convert human fibroblasts into induced oligodendrocyte-like cells (iOLCs) in 3 days. The induced cells displayed morphologies and molecular signatures similar to oligodendrocytes after treatment with valproic acid and exposure to the small molecules Y27632, SU9516, and forskolin (FSK). To pursue the development of a cell-free remyelination therapy in vivo, we used a cuprizone-induced demyelinated mouse model. The small molecules (Y27632, SU9516, and FSK) were directly injected into the demyelinated corpus callosum of the mouse brain. This combination of small molecules rescued the demyelination phenotype within two weeks as observed by light and electron microscopy. These results provide a foundation for exploring the development of a treatment for demyelinating diseases via regenerative medicine.

Clinical Manifestations and Outcomes of Tubercular Uveitis in Taiwan-A Ten-Year Multicenter Retrospective Study.

Background andObjectives: This 10-year multicenter retrospective study reviewed the clinical manifestations, diagnostic tests, and treatment modalities of tubercular uveitis (TBU), including direct infection and indirect immune-mediated hypersensitivity to mycobacterial antigens in Taiwan. Materials and Methods: This retrospective chart review of patients with TBU was conducted at 11 centers from 1 January 2008 to 31 December 2017. We used a multiple regression model to analyze which factors influenced best-corrected visual acuity (BCVA) improvement. Results: A total of 79 eyes from 51 patients were included in the study. The mean age was 48.9 ± 16.4 years. The mean change of LogMAR BCVA at last visit was -0.21 ± 0.45. Diagnostic tools used include chest X-ray, chest computed tomography, Mantoux test, interferon gamma release test (QuantiFERON-TB Gold test), intraocular fluid tuberculosis polymerase chain reaction, and bronchial alveolar lavage. The clinical manifestations included 48% posterior uveitis and 37% panuveitis. In the sample, 55% of the cases were bilateral and 45% unilateral. There was 60.76% retinal vasculitis, 35.44% choroiditis, 21.52% serpiginous-like choroiditis, 17.72% vitreous hemorrhage, 12.66% posterior synechiae, 6.33% retinal detachment, and 3.80% choroidal granuloma. Treatment modalities included rifampicin, isoniazid, pyrazinamide, ethambutol, oral steroid, posterior triamcinolone, non-steroidal anti-inflammatory drugs, vitrectomy, and immunosuppressants. BCVA improved in 53.2% of eyes and remained stable in 32.9% of eyes. In the final model of multiple regression, worse initial BCVA, pyrazinamide, and receiving vitrectomy predicted better BCVA improvement. Ethambutol was associated with worse visual outcomes. Seven eyes experienced recurrence. Conclusions: This is the largest 10-year multicenter retrospective study of TBU in Taiwan to date, demonstrating the distribution of clinical manifestations and clinical associations with better treatment outcomes. The study provides a comprehensive description of TBU phenotypes in Taiwan and highlights considerations for the design of further prospective studies to reliably assess the role of ATT and vitrectomy in patients with TBU.

The Benefits and Hazards of Intravitreal Mesenchymal Stem Cell (MSC) Based-Therapies in the Experimental Ischemic Optic Neuropathy.

Mesenchymal stem cell (MSC) therapy has been investigated intensively for many years. However, there is a potential risk related to MSC applications in various cell niches. METHODS: The safety of intravitreal MSC application and the efficacy of MSC-derived conditioned medium (MDCM) were evaluated in the normal eye and the diseased eye, respectively. For safety evaluation, the fundus morphology, visual function, retinal function, and histological changes of the retina were examined. For efficacy evaluation, the MDCM was intravitreally administrated in a rodent model of anterior ischemic optic neuropathy (rAION). The visual function, retinal ganglion cell (RGC) density, and neuroinflammation were evaluated at day 28 post-optic nerve (ON) infarct. RESULTS: The fundus imaging showed that MSC transplantation induced retinal distortion and venous congestion. The visual function, retinal function, and RGC density were significantly decreased in MSC-treated eyes. MSC transplantation induced astrogliosis, microgliosis, and macrophage infiltration in the retina due to an increase in the HLA-DR-positive MSC proportion in vitreous. Treatment with the MDCM preserved the visual function and RGC density in rAION via inhibition of macrophage infiltration and RGC apoptosis. CONCLUSIONS: The vitreous induced the HLA-DR expression in the MSCs to cause retinal inflammation and retina injury. However, the MDCM provided the neuroprotective effects in rAION.

Effect of Orthokeratology on myopia progression: twelve-year results of a retrospective cohort study.

BACKGROUND: Several studies reported the efficacy of orthokeratology for myopia control. Somehow, there is limited publication with follow-up longer than 3 years. This study aims to research whether overnight orthokeratology influences the progression rate of the manifest refractive error of myopic children in a longer follow-up period (up to 12 years). And if changes in progression rate are found, to investigate the relationship between refractive changes and different baseline factors, including refraction error, wearing age and lens replacement frequency. In addition, this study collects long-term safety profile of overnight orthokeratology. METHODS: This is a retrospective study of sixty-six school-age children who received overnight orthokeratology correction between January 1998 and December 2013. Thirty-six subjects whose baseline age and refractive error matched with those in the orthokeratology group were selected to form control group. These subjects were followed up at least for 12 months. Manifest refractions, cycloplegic refractions, uncorrected and best-corrected visual acuities, power vector of astigmatism, corneal curvature, and lens replacement frequency were obtained for analysis. RESULTS: Data of 203 eyes were derived from 66 orthokeratology subjects (31 males and 35 females) and 36 control subjects (22 males and 14 females) enrolled in this study. Their wearing ages ranged from 7 years to 16 years (mean ± SE, 11.72 ± 0.18 years). The follow-up time ranged from 1 year to 13 years (mean ± SE, 6.32 ± 0.15 years). At baseline, their myopia ranged from -0.5 D to -8.0 D (mean ± SE, -3.70 ± 0.12 D), and astigmatism ranged from 0 D to -3.0 D (mean ± SE, -0.55 ± 0.05 D). Comparing with control group, orthokeratology group had a significantly (p < 0.001) lower trend of refractive error change during the follow-up periods. According to the analysis results of GEE model, greater power of astigmatism was found to be associated with increased change of refractive error during follow-up years. CONCLUSIONS: Overnight orthokeratology was effective in slowing myopia progression over a twelve-year follow-up period and demonstrated a clinically acceptable safety profile. Initial higher astigmatism power was found to be associated with increased change of refractive error during follow-up years.

Lymph Node Ratio-based Staging System Outperforms the Seventh AJCC System for Gastric Cancer: Validation Analysis With National Taiwan University Hospital Cancer Registry.

BACKGROUND: On the basis of SEER data, in which most gastric cancer patients had limited lymph node dissection, node ratio-based staging system (TNrM) has been shown to have better accuracy than the AJCC TNM system. This study is to validate the result with patients from Taiwan, where D2 lymphadenectomy is routinely performed. PATIENT AND METHOD: A total of 1405 consecutive gastric cancer patients treated at National Taiwan University Hospital between 1998 and 2010 were included. To evaluate the performance of the AJCC system, each TNM stage was stratified by TNrM stages. The homogeneity of patients' survival across TNrM strata was evaluated using the log-rank test. The performance of the TNrM system was evaluated with the same approach. RESULTS: Five of the 7 evaluable AJCC stages (IA, IIA, IIIA, IIIB, and IIIC) contained TNrM subgroups with statistically heterogenous survival (P=0.003, 0.04, 0.002, 0.04, and <0.001, respectively). Thirty-six percent of patients (506/1405) were misclassified by the AJCC TNM system. However, of the assessable 6 TNrM stages, none of the AJCC subgroups showed significantly heterogenous survivals (P>0.05). About 19% of patients (264/1405) were misclassified by using the TNrM system. CONCLUSIONS: Lymph node ratio significantly decreases the stage migration caused by inadequate examined lymph nodes. The advantage of TNrM was validated with a patient cohort from the Eastern medical center.

Increased Risk of Stroke in Patients With Nonarteritic Anterior Ischemic Optic Neuropathy: A Nationwide Retrospective Cohort Study.

PURPOSE: To investigate the incidence and prevalence of nonarteritic anterior ischemic optic neuropathy (NAION), and to extrapolate the risk of cerebrovascular events following NAION. DESIGN: Retrospective cohort study. METHODS: We identified NAION patients first, and then looked for the diagnosis of stroke after the diagnosis of NAION. SETTING: The study group was composed of patients diagnosed with NAION seeking ambulatory care from 2000 to 2011. The control group was extracted from a database by randomly selecting 2 patients for every NAION patient, matched by age and sex. MAIN OUTCOME MEASURES: Cox proportional hazards regression analysis was performed to calculate adjusted hazard ratio (aHR) of stroke for the 2 groups. Subgroup analysis of subjects with or without comorbidities was also investigated. RESULTS: Four hundred and fourteen patients were included in the study group and 789 in the control group. The mean follow-up period was 5.9 years. The incidence of NAION was 3.72/100 000 person-years in Taiwan, and the prevalence of NAION was 48.18/100 000 persons. The study group was more likely to have ischemic stroke (aHR = 2.03, P = .003), but not hemorrhagic stroke (aHR = 1.24, P = .696), than the control group. Among the subgroup with comorbidities, the risk of ischemic stroke among the subjects with NAION was 3.35 times higher than those without NAION (95% confidence interval: 1.67, 6.70). CONCLUSIONS: Patients with NAION have an increased risk of ischemic stroke. Physicians should refer all patients with NAION for systemic survey of vasculopathy and control of modifiable risk factors to prevent irreversible neurological sequelae.

Human adenovirus type 8 epidemic keratoconjunctivitis with large corneal epithelial full-layer detachment: an endemic outbreak with uncommon manifestations.

Epidemic viral conjunctivitis is a highly contagious disease that is encountered year-round. The causative agents are mainly adenoviruses and enteroviruses. It occurs most commonly upon infection with subgroup D adenoviruses of types 8, 19, or 37. For common corneal involvement of human adenovirus type 8 epidemic keratoconjunctivitis, full-layer epithelial detachment is rarely seen. Herein, we report three cases of epidemic keratoconjunctivitis during an outbreak which manifested as large corneal epithelial full-layer detachment within a few days. The lesions healed without severe sequelae under proper treatment. The unique manifestation of this outbreak may indicate the evolution of human adenovirus type 8.

Ocular leech infestation.

This case report describes a female toddler with manifestations of ocular leech infestation. A 2-year-old girl was brought to our outpatient clinic with a complaint of irritable crying after being taken to a stream in Hualien 1 day previous, where she played in the water. The parents noticed that she rubbed her right eye a lot. Upon examination, the girl had good fix and follow in either eye. Slit-lamp examination showed conjunctival injection with a moving dark black-brown foreign body partly attached in the lower conjunctiva. After applying topical anesthetics, the leech, measuring 1 cm in length, was extracted under a microscope. The patient began using topical antibiotic and corticosteroid agents. By 1 week after extraction, the patient had no obvious symptoms or signs, except for a limited subconjunctival hemorrhage, and no corneal/scleral involvement was observed.