Effect of spectacle correction on hyperopic children.

Background: Hyperopia is a significant refractive error in children, often leading to vision impairment. This study aimed to investigate whether partial or full spectacle correction is benefit for hyperopia in preschool-aged children. Methods: A retrospective study was conducted on hyperopic children visited to teaching medical center outpatient clinic between October 2011 and October 2018, and were categorized into three groups: full correction, overcorrection, and undercorrection. The study was approved by the institutional ethical committee of Tri-Service General Hospital. Results: Following a minimum of one-year follow-up period, no statistically significant differences were observed in best-corrected visual acuity (BCVA) among children receiving full, over, or under spectacle correction. Notably, the overcorrection group exhibited a significant reduction in spherical equivalent (SE) compared to both the full and under correction groups, indicating a better SE with spectacle overcorrection. Conclusions: Spectacle overcorrection may offer potential benefits for enhancing SE in preschool children with hyperopia. Nevertheless, further investigation through randomized controlled trials is warranted to establish the validity of this approach and its impact on visual outcomes in this hyperopic pediatric population.

Baseline characteristics and treatment response predictive of nAMD outcomes with ranibizumab therapy in treatment-naive patients: the RACER subgroup analysis.

BACKGROUND: The Ranibizumab AMD Clinical Efficacy Study (RACER) conducted in treatment-naive adult Taiwanese patients with neovascular age-related macular degeneration (nAMD) suggested the importance of early and intensive dosing of ranibizumab for optimal treatment outcomes. This subgroup analysis aims to provide clinical information on treatment response that can potentially guide on maintaining the treatment or switching anti-VEGF agents in the real-world setting. METHODS: Visual acuity (VA) and central retinal thickness (CRT) were assessed in the RACER subgroup population. Subgroup analysis sets were categorised based on: (1) baseline best-corrected VA (BCVA; ≤ 48 and > 48 letters); (2) baseline CRT (≤ 325 or > 325 µm); and (3) treatment response after three monthly initial injections: < or ≥ 5-letter gain in BCVA and reduction of < or ≥ 50 µm in CRT. RESULTS: Patient age, sex, nAMD duration and number of ranibizumab injections did not differ significantly between the treatment subgroups. Poor baseline BCVA (≤ 48 letters) and baseline CRT severity (> 325 µm) were predictors of maximum BCVA gains (9.6 ± 12.9 letters [95%CI: 6.3 to 12.9] and 5.1 ± 18.3 letters [95%CI: - 0.5 to 10.8] at Months 3 and 12, respectively) and better CRT reductions (- 127.6 ± 104.2 µm and - 104.2 ± 107.4 µm at Months 3 and 12, respectively; both P < 0.001). For the subgroup showing favourable treatment improvement with BCVA gains ≥ 5 letters after three monthly initial injections, 75.6% of patients maintained follow-up at Month 12 with a mean of 6.5 ± 14.3 letter gains (95% CI: 1.2 to 11.7). The BCVA gains < 5-letter subgroup nevertheless had stable BCVA (0.4 ± 12.1 letter gains) and CRT (- 41.9 ± 61.2 µm) at Month 12, respectively. In the subgroup with ≥ 50 µm CRT reduction after three monthly initial injections, there are significantly higher BCVA improvements vs. the < 50 µm CRT reduction subgroup at Month 3 (5.0 ± 8.6 letter gains vs. 1.5 ± 11.6 letter gains, respectively; intergroup P = 0.005). CONCLUSION: Lower baseline BCVA and higher baseline CRT were associated with BCVA gains and CRT reductions throughout the 12-month study period. Early CRT improvements after three monthly initial injections were associated with BCVA gains as early as Month 3.

Optimal approaches and criteria to treat-and-extend regimen implementation for Neovascular age-related macular degeneration: experts consensus in Taiwan.

The management of neovascular age-related macular degeneration (nAMD) has taken a major stride forward with the advent of anti-VEGF agents. The treat-and-extend (T&E) approach is a refined management strategy, tailoring to the individual patient's disease course and treatment outcome. To provide guidance to implementing anti-VEGF T&E regimens for nAMD in resource-limited health care systems, an advisory board was held to discuss and generate expert consensus, based on local and international guidelines, current evidence, as well as local experience and reimbursement policies. In the experts' opinion, treatment of nAMD should aim to maximize and maintain visual acuity benefits while minimizing treatment burden. Based on current evidence, treatment could be initiated with 3 consecutive monthly injections. After the initial period, treatment interval may be extended by 2 or 4 weeks each time for the qualified patients (i.e. no BCVA loss ≥5 ETDRS letters and dry retina), and a maximum interval of 16 weeks is permitted. For patients meeting the shortening criteria (i.e. any increased fluid with BCVA loss ≥5 ETDRS letters, or presence of new macular hemorrhage or new neovascularization), the treatment interval should be reduced by 2 or 4 weeks each time, with a minimal interval of 4 weeks. Discontinuation of anti-VEGF may be considered for those who have received 2-3 consecutive injections spaced 16 weeks apart and present with stable disease. For these individuals, regular monitoring (e.g. 3-4 months) is recommended and monthly injections should be reinstated upon signs of disease recurrence.

Dental caries and periodontitis and the risk of myopia in young adults: CHIEF oral health study.

AIM: Oral health and ocular diseases may be associated with collagen defects and inflammation status. However, the results from prior studies are conflicting. The aim of this study was to explore the association of dental caries and periodontitis with myopia in young adults. MATERIALS AND METHODS: A total of 938 military personnel aged 19-39 years receiving both oral and eye examinations from 2018 through 2020 were included in this study in Taiwan. The severity of myopia was graded as no myopia (diopters > - 0.5, N = 459), low myopia (diopters: - 0.5 to -5.9, N = 225) and high myopia (diopters ≤ - 6.0, N = 254). A multiple logistic regression analysis with adjustments for age, body mass index, systolic blood pressure, smoking, alcohol consumption, missing teeth numbers, blood leucocyte counts, triglycerides, high-density lipoprotein, and uric acid were used to determine the associations of actively dental caries, filled teeth and stage II/III periodontitis with myopia. RESULTS: The presence of any actively dental caries was significantly associated with a higher risk of any myopia (low or high) (odds ratio [OR] and 95% confidence intervals [95% CI] 1.42 [1.04-1.94]), whereas there was no association for filled teeth. Moreover, the association for stage II/III periodontitis was only observed with high myopia (OR: 1.52 [1.07-2.15]) and was not observed with low myopia. CONCLUSIONS: Our findings suggest that only actively dental caries and a higher severity of periodontitis were associated with myopia among young adults, thus highlighting the dental inflammation status in the oral cavity as a potential link to ocular diseases.

A Pulmonary Pleomorphic Carcinoma Patient with Exudative Retinal Detachment Secondary to Choroid Metastasis as Initial Presentation-A Case Report.

Choroid metastasis is the initial presentation of pleomorphic carcinoma (PC) of the lung. PC is classified as poorly differentiated non-small cell lung carcinoma. It has a tendency to metastasize early and has a poor response to chemotherapy, which often results in poor prognosis. We report the case of a 63-year-old woman with a one-month history of deteriorating vision in the left eye. Fundus examination, fluorescein angiography, indocyanine green angiography, and B-scan sonography demonstrated choroidal metastasis of the left eye. Positron emission tomography/computed tomography (PET/CT) revealed a tumor with increased uptake in the left upper lung. Subsequent bronchoscopic biopsy confirmed a pleomorphic carcinoma of the lungs. Choroid metastasis as an initial presentation of PC in the lung is rare. Usually, it represents the late course of disseminated disease with hematogenous spread. Prompt diagnosis is imperative for patients to immediately initiate treatment.

A 12-month, prospective, observational study of ranibizumab in treatment-naïve Taiwanese patients with neovascular age-related macular degeneration: the RACER study.

BACKGROUND: The current National Health Insurance scheme in Taiwan reimburses 3 initial plus 4 additional injections of ranibizumab 0.5 mg for eligible patients with neovascular age-related macular degeneration (nAMD). The Ranibizumab AMD Clinical Efficacy in Real-world practice (RACER) study aimed to observe the effectiveness of ranibizumab injections under this reimbursement system. METHODS: RACER was a 12-month, prospective, observational study conducted in treatment-naïve, adult Taiwanese patients with nAMD. Patients received intravitreal ranibizumab 0.5 mg injections in adherence with local prescribing information. RESULTS: Of 161 patients enrolled, 114 (70.8%) completed the 12-month study. Overall, patients received a mean (standard deviation [SD]) of 4.3 (1.7) ranibizumab injections. The mean (SD, [95% confidence interval], P value) gain in best-corrected visual acuity (BCVA) from baseline at Month 3 was 5.2 (12.2, [3.1, 7.3] letters, P < 0.0001) and at Month 12 was 3.4 (15.4, [0.2-6.6] letters, P = 0.0352). Mean central retinal thickness also decreased from baseline at Months 3 and 12 (both P < 0.001). In subgroup analyses, better treatment outcomes at Months 3 and 12 were observed among patients who received a loading dose and those who had a shorter duration of nAMD at baseline. Adverse events were reported in 58.4% of patients; most (94.4%) were mild-to-moderate in severity and 98.8% were deemed unrelated to study treatment. CONCLUSIONS: Treatment with ranibizumab 0.5 mg resulted in significant improvements in visual outcomes among treatment-naïve Taiwanese patients with nAMD. Early treatment and frequent dosing in the real-world setting may be the key to achieving better outcomes.

AR12286 Alleviates TGF-ß-Related Myofibroblast Transdifferentiation and Reduces Fibrosis after Glaucoma Filtration Surgery.

Scar formation can cause the failure of glaucoma filtration surgery. We investigated the effect of AR12286, a selective Rho-associated kinase inhibitor, on myofibroblast transdifferentiation and intraocular pressure assessment in rabbit glaucoma filtration surgery models. Cell migration and collagen contraction were used to demonstrate the functionality of AR12286-modulated human conjunctival fibroblasts (HConFs). Polymerase chain reaction quantitative analysis was used to determine the effect of AR12286 on the production of collagen Type 1A1 and fibronectin 1. Cell migration and collagen contraction in HConFs were activated by TGF-ß1. However, compared with the control group, rabbit models treated with AR12286 exhibited higher reduction in intraocular pressure after filtration surgery, and decreased collagen levels at the wound site in vivo. Therefore, increased α-SMA expression in HConFs induced by TGF-ß1 could be inhibited by AR12286, and the production of Type 1A1 collagen and fibronectin 1 in TGF-ß1-treated HConFs was inhibited by AR12286. Overall, the stimulation of HConFs by TGF-ß1 was alleviated by AR12286, and this effect was mediated by the downregulation of TGF-ß receptor-related SMAD signaling pathways. In vivo results indicated that AR12286 thus improves the outcome of filtration surgery as a result of its antifibrotic action in the bleb tissue because AR12286 inhibited the TGF-ß receptor-related signaling pathway, suppressing several downstream reactions in myofibroblast transdifferentiation.

Glucosamine impedes transforming growth factor ß1-mediated corneal fibroblast differentiation by targeting Krüppel-like factor 4.

BACKGROUND: Transforming growth factor (TGF) family members play important roles in the regulation of corneal integrity, and the pathogenesis of corneal fibrosis. Currently, there are no effective agents targeting TGF-ß signaling to diminish corneal fibrosis. Glucosamine (GlcN), which is widely used in the treatment of osteoarthritis, abrogates the morphologic effects of TGF-ß2 on retinal pigmented epithelial cells in a mouse disease model. Here, we sought to determine whether GlcN would exert beneficial effects against TGF-ß1-induced corneal fibrosis. METHODS: In human corneal fibroblasts (HCFs) treated with GlcN, the expression of Krüppel-like factor 4 (KLF4) and its downstream signaling effects were determined in the presence and absence of TGF-ß1 using immunoblot analysis. We further explored GlcN inhibition of fibroblast-to-myofibroblast differentiation via KLF4 siRNA. The effect of cycloheximide on KLF4 protein levels with or without GlcN administration was assessed to determine whether GlcN affects the stability of the KLF4 protein. RESULTS: In HCFs, GlcN induced the expression of KLF4, which regulated the maturation and maintenance of the ocular surface. GlcN partially suppressed the TGF-ß1-induced expression of alpha-smooth muscle actin (α-SMA) and reduced the collagen contraction capacity in HCFs, suggesting a decrease in fibroblast-to-myofibroblast differentiation. This effect appeared to be mediated through suppression of Smad2 phosphorylation and ERK-dependent signaling. The levels of KLF4 mRNA were increased by GlcN and decreased by TGF-ß1 and the TGF-ß1-induced α-SMA mRNA expression was upregulated when the KLF4 gene was silenced. GlcN also appeared to stabilize the KLF4 protein, reducing its turnover in corneal fibroblasts. CONCLUSION: These findings shed light on a novel mechanism by which GlcN suppresses TGF-ß1-induced fibroblast-to-myofibroblast differentiation through the upregulation of KLF4 expression. Current strategies for treating corneal fibrosis were not effective. Elevating KLF4 levels through the use of GlcN might provide an effective alternative to alleviate the development and progression of corneal fibrosis.

Glucosamine-Induced Autophagy through AMPK⁻mTOR Pathway Attenuates Lipofuscin-Like Autofluorescence in Human Retinal Pigment Epithelial Cells In Vitro.

Age-related macular degeneration (AMD) is a vision-threatening age-associated disease. The retinal pigment epithelial (RPE) cells phagocytose and digest photoreceptor outer segment (POS). Incomplete digestion of POS leads to lipofuscin accumulation, which contributes to the pathology of the AMD. Autophagy could help reduce the amount of lipofuscin accumulation. In the present study, we evaluated the effects of glucosamine (GlcN), a natural supplement, on the induction of autophagy and POS-derived lipofuscin-like autofluorescence (LLAF) in ARPE-19 cells in vitro, and investigated the potential molecular pathway involved. Our results revealed that GlcN had no effect on phagocytosis of POS at the lower doses. GlcN treatment induced autophagy in cells. GlcN decreased the LLAF in native POS-treated cells, whereas malondialdehyde or 4-hydroxynonenal-modified POS attenuated this effect. 3-Methyladenine inhibited GlcN-induced autophagy and attenuated the effect of GlcN on the decrease of the native POS-derived LLAF. Furthermore, GlcN induced the phosphorylation of AMP-activated protein kinase (AMPK) and inhibited the phosphorylation of mammalian target of rapamycin (mTOR), whereas Compound C inhibited these effects of GlcN. Altogether, these results suggest that GlcN decreased the native POS-derived LLAF through induction of autophagy, at least in part, by the AMPK⁻mTOR pathway. This mechanism has potential for the preventive treatment of lipofuscin-related retinal degeneration such as AMD.

Glucosamine Modulates T Cell Differentiation through Down-regulating N-Linked Glycosylation of CD25.

Glucosamine has immunomodulatory effects on autoimmune diseases. However, the mechanism(s) through which glucosamine modulates different T cell subsets and diseases remain unclear. We demonstrate that glucosamine impedes Th1, Th2, and iTreg but promotes Th17 differentiation through down-regulating N-linked glycosylation of CD25 and subsequently inhibiting its downstream Stat5 signaling in a dose-dependent manner. The effect of glucosamine on T helper cell differentiation was similar to that induced by anti-IL-2 treatment, further supporting an IL-2 signaling-dependent modulation. Interestingly, excess glucose rescued this glucosamine-mediated regulation, suggesting a functional competition between glucose and glucosamine. High-dose glucosamine significantly decreased Glut1 N-glycosylation in Th1-polarized cells. This finding suggests that both down-regulated IL-2 signaling and Glut1-dependent glycolytic metabolism contribute to the inhibition of Th1 differentiation by glucosamine. Finally, glucosamine treatment inhibited Th1 cells in vivo, prolonged the survival of islet grafts in diabetic recipients, and exacerbated the severity of EAE. Taken together, our results indicate that glucosamine interferes with N-glycosylation of CD25, and thereby attenuates IL-2 downstream signaling. These effects suggest that glucosamine may be an important modulator of T cell differentiation and immune homeostasis.

Neurotrophic and neuroprotective potential of human limbus-derived mesenchymal stromal cells.

BACKGROUND AIMS: The purpose of this study was to examine neurotrophic and neuroprotective effects of limbus stroma-derived mesenchymal stromal cells (L-MSCs) on cortical neurons in vitro and in vivo. METHODS: Cultured L-MSCs were characterized by flow cytometry and immunofluorescence through the use of specific MSC marker antibodies. Conditioned media were collected from normoxia- and hypoxia-treated L-MSCs to assess neurotrophic effects. Neuroprotective potentials were evaluated through the use of in vitro hypoxic cortical neuron culture and in vivo rat focal cerebral ischemia models. Neuronal morphology was confirmed by immunofluorescence with the use of anti-MAP2 antibody. Post-ischemic infarct volume and motor behavior were assayed by means of triphenyltetrazolium chloride staining and open-field testing, respectively. Human growth antibody arrays and enzyme-linked immunoassays were used to analyze trophic/growth factors contained in conditioned media. RESULTS: Isolated human L-MSCs highly expressed CD29, CD90 and CD105 but not CD34 and CD45. Mesenchymal lineage cell surface expression pattern and differentiation capacity were identical to MSCs derived form human bone marrow and adipose tissue. The L-MSC normoxic and hypoxic conditioned media both promoted neurite outgrowth in cultured cortical neurons. Hypoxic conditioned medium showed superior neurotrophic function and neuroprotective potential with reduced ischemic brain injury and improved functional recovery in rat focal cerebral ischemia models. Human growth factor arrays and enzyme-linked immunoassays measurements showed neuroprotective and growth-associated cytokines (vascular endothelial growth factor [VEGF], VEGFR3, brain-derived neurotrophic factor, insulin-like growth factor -2 and hepatocyte growth factor) contained in conditioned media. Hypoxic exposure caused VEGF and brain-derived neurotrophic factor upregulation, possibly contributing to neurotrophic and neuroprotective effects. CONCLUSIONS: L-MSCs can secrete various neurotrophic factors stimulating neurite outgrowth and protecting neurons against brain ischemic injury through paracrine mechanism.

Investigation of corneal epithelial thickness and irregularity by optical coherence tomography after transepithelial photorefractive keratectomy.

CLINICAL RELEVANCE: Corneal epithelial healing after refractive surgery is a clinically significant issue, especially for surface ablation procedures, and this can be monitored using optical coherence tomography (OCT). BACKGROUND: The aim of this work is to investigate the corneal epithelial thickness and irregularity by OCT after transepithelial photorefractive keratectomy (t-PRK) and analyse its correlation with visual and refractive outcomes. METHODS: Patients aged ≥18 years with myopia, with or without astigmatism, who underwent t-PRK between May 2020 and August 2021 were included. All participants were subjected to complete ophthalmic examinations and OCT pachymetry at every follow-up visit. Patients were followed up at 1 week and 1, 3, and 6 months postoperatively. RESULTS: A total of 67 patients (126 eyes) were enrolled in this study. One month postoperatively, spherical equivalent refraction and visual acuity achieved preliminary stability. However, central corneal epithelial thickness (CCET) and standard deviation of the corneal epithelial thickness (SDcet) took 3-6 months to progressive recovery. Patients with higher baseline spherical equivalent refraction were associated with slower epithelial recovery. At every follow-up time point, a significant superior-inferior difference in the minimum corneal epithelial thickness area was observed. Higher stromal haze was correlated with higher spherical equivalent refraction (both baseline and residual) but had no relation with visual outcomes. There was a significant correlation between higher CCET with a better uncorrected distance visual acuity and lower corneal epithelial thickness irregularity. CONCLUSIONS: CCET and SDcet measured by OCT seem to be a good auxiliary indicator for reflecting the status of corneal wound recovery after t-PRK surgery. However, a well-designed randomised control study is needed to confirm the study results.

The Association between Diabetic Retinopathy and Macular Degeneration: A Nationwide Population-Based Study.

OBJECTIVE: Age-related macular degeneration (AMD), particularly its exudative form, is a primary cause of vision impairment in older adults. As diabetes becomes increasingly prevalent in aging, it is crucial to explore the potential relationship between diabetic retinopathy (DR) and AMD. This study aimed to assess the risk of developing overall, non-exudative, and exudative AMD in individuals with DR compared to those without retinopathy (non-DR) based on a nationwide population study in Taiwan. METHODS: A retrospective cohort study was conducted using the Taiwan National Health Insurance Database (NHIRD) (2000-2013). A total of 3413 patients were placed in the study group (DR) and 13,652 in the control group (non-DR) for analysis. Kaplan-Meier analysis and the Cox proportional hazards model were used to calculate the hazard ratios (HRs) and adjusted hazard ratios (aHRs) for the development of AMD, adjusting for confounding factors, such as age, sex, and comorbid conditions. RESULTS: Kaplan-Meier survival analysis indicated a significantly higher cumulative incidence of AMD in the DR group compared to the non-DR group (log-rank test, p < 0.001). Adjusted analyses revealed that individuals with DR faced a greater risk of overall AMD, with an aHR of 3.50 (95% CI = 3.10-3.95). For senile (unspecified) AMD, the aHR was 3.45 (95% CI = 3.04-3.92); for non-exudative senile AMD, it was 2.92 (95% CI = 2.08-4.09); and for exudative AMD, the aHR was 3.92 (95% CI = 2.51-6.14). CONCLUSION: DR is a significant risk factor for both overall, senile, exudative, and non-exudative AMD, even after adjusting for demographic and comorbid conditions. DR patients tend to have a higher prevalence of vascular comorbidities; however, our findings indicate that the ocular pathologies inherent to DR might have a more significant impact on the progression to AMD. Early detection and appropriate treatment of AMD is critically important among DR patients.

Anterior chamber paracentesis and pH values in patients with acute primary angle closure.

BACKGROUND: To assess the efficacy and safety of anterior chamber paracentesis (ACP) and the changes in pH values in eyes with acute primary angle closure (APAC). METHODS: This retrospective case-control study involved 22 patients with APAC who underwent ACP (study group) and 21 patients with APAC who did not undergo ACP (control group). Intraocular pressure (IOP) and visual acuity were measured before treatment and 15 min and 24 h after treatment in both groups. The pH of aqueous humor was measured immediately after ACP in the study group. RESULTS: A total of 43 eyes in 43 patients were reviewed. The IOP 15 min after ACP (23.3 ± 9.6 mmHg) and 24 h after ACP (21.6 ± 12.0 mmHg) were significantly lower than that before ACP (58.6 ± 12.9 mmHg). The IOP 15 min after ACP was significantly lower than the IOP 15 min after conventional treatment (55.4 ± 10.3 mmHg). Visual acuity recovery was achieved earlier after ACP than after conventional treatment. Hyphema after ACP was noted in one eye. The mean pH of the aqueous humor in APAC was 6.99 ± 0.35. The pH of the aqueous humor significantly correlated with the duration of acute IOP elevation and the IOP before ACP. CONCLUSIONS: ACP is an effective and safe procedure. The pH of aqueous humor is lower in eyes with APAC of longer duration and in eyes with higher IOP at presentation.

Correlation of microRNA-145 levels and clinical severity of pterygia.

PURPOSE: MicroRNA-145 (miR-145) has known anti-tumor properties and has been reported to be involved in regulating corneal epithelium differentiation. The exact role of miR-145 in ocular tissue remains unclear. In this study, we evaluate the effect of miR-145 expression levels on pterygium properties. SETTING: Ophthalmology department of a tertiary medical center. DESIGN: : Case series study. METHODS: Information regarding patient age, pterygium recurrence and pterygium severity (extension [E], vascularity [V] and thickness [T]) were gathered from records. Expression levels of miR-145 were obtained through examination of excised pterygium tissue. Correlations between age, pterygium classification, and miR-145 levels were evaluated. RESULTS: This study evaluated 253 patients (mean age 54.1±10.8 years). As pterygium severity increased, miR-145 levels decreased. Negative correlations were also found between miR-145 expression levels and pterygium extension (E) and vascularity (V). Thickness (T) had a weak negative correlation. There was only a mild negative correlation between patient age and miR-145 levels, which was only seen in patients with primary pterygium (not recurrent ones). Additionally, miR-145 expression was significantly higher in primary samples than in recurrent ones. CONCLUSIONS: We demonstrated an association between miR-145 and pterygium characteristics, consistent with its known tumor suppression effect. Because the management of pterygium is often difficult, we suggest that miR-145 should be further studied as a potential treatment.

Impact of Endophthalmitis on the Risk of Acute Myocardial Infarction in Ankylosing Spondylitis Patients: A Population-Based Retrospective Cohort Study.

Many studies have demonstrated an increased cardiovascular (CV) risk in ankylosing spondylitis (AS) patients. Nevertheless, the influence of an endophthalmitis episode toward the future risks of acute myocardial infarction (AMI) in AS patients has been unclear. The objective of this study was to explore the impact of endophthalmitis on AMI risk in this particular patient population by a population-based retrospective cohort study with a follow-up period up to 16 years. Univariate and multivariate Cox regression analyses were used for the risk evaluation and the results were presented as crude and adjusted hazard ratios (HRs). Overall, we enrolled 557 AS patients with endophthalmitis as the study cohort and selected another 2228 matched AS patients without endophthalmitis as the comparison cohort. Comparing the comparison cohort, the study cohort showed a significantly higher overall AMI incidence rate with an adjusted HR of 1.631 (p < 0.001). In conclusion, endophthalmitis increased the risk of AMI in AS patients after adjusting for possible clinical confounders. Special attention and work-up are required for physicians when encountering a history of endophthalmitis in these special patient populations, especially when they are comorbid with other potential CV risk factors.

MicroRNA-4516 suppresses proliferative vitreoretinopathy development via negatively regulating OTX1.

Proliferative vitreoretinopathy (PVR) progression is associated with TGF-ß2-induced epithelial-mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells. In cancer cells, miR-4516 downregulates orthodenticle homeobox 1 (OTX1)-mediated cell invasion. Moreover, OTX1 is shown to be involved in invasion and EMT. The purpose of this study was to assess whether microRNA (miR-4516) suppresses EMT in RPE cells. EMT features were assessed using Western blotting, immunocytochemical staining, scratch-wound healing, modified Boyden chamber assay, and collagen gel contraction assay. For in vivo testing, a rabbit model was used, which involved induction of PVR by injection of transfected spontaneously arising RPE (ARPE) cells into the vitreous chamber. The putative target of miR-4516 was identified by luciferase reporter assay. Results showed that TGF-ß2-induced transdifferentiation and migration of RPE cells was inhibited by miR-4516 delivery. Overexpression of miR-4516 led to upregulation of zonula occludens-1, downregulation of α-smooth muscle actin and vimentin, and cell contractility-all EMT features-in the TGF-ß2-treated ARPE-19 cells. MiR-4516 regulated OTX1 expression negatively by binding to its 3'-UTR. TGF-ß2-induced phosphorylated ERK was inhibited in miR-4516-overexpressing ARPE-19 cells. MiR-4516 suppressed experimental PVR in vitro and in vivo. In conclusion, the overexpression of miR-4516 suppresses TGF-ß2-induced EMT in a PVR model, and its role in PVR depends on OTX1/ERK. Further research is needed to develop a feasible treatment method to prevent and treat PVR.

Increased Risk of Acute Coronary Syndrome in Ankylosing Spondylitis Patients With Uveitis: A Population-Based Cohort Study.

Background: Uveitis, a sight-threatening ocular inflammatory state, is associated with autoimmune diseases and systemic inflammation. This prolonged systemic inflammation may cause plaque formation in coronary arteries, subsequently resulting in acute coronary syndrome (ACS). Methods: This retrospective, population-based study (15-year period) used the Longitudinal Health Insurance Database based on the National Health Insurance Research Database in Taiwan. Chi-square and Student's t-tests were used to examine differences between the study and comparison cohorts for categorical and continuous variables, respectively. Fine and Gray's competing risk model was used to determine the hazard ratio of the risk of ACS. Furthermore, the cumulative risk of ACS was determined using Kaplan-Meier analysis. Results: A total of 1,111 patients with AS and uveitis were enrolled in this study cohort, and 4,444 patients with AS without uveitis were enrolled in the comparison cohort. After adjustment for age, sex, and comorbidities, patients with AS and uveitis demonstrated an increased risk of ACS compared to those without uveitis (adjusted hazard ratio: 1.675, p<0.001). In addition, Kaplan-Meier analysis revealed that patients with AS and uveitis had a significantly higher risk of ACS than those without uveitis (p<0.001). Age, diabetes mellitus, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, asthma, and systemic steroids were significant risk factors for ACS. Both anterior uveitis and posterior segment involvement were associated with an increased risk of ACS in patients with AS. All-cause mortality was higher in the uveitis group (9.81%) than in the non-uveitis group (8.10%) (p=0.015). Conclusion: Our analysis revealed that uveitis could potentially be a predictor of ACS in patients with AS. However, further prospective controlled studies are required to assess the association between uveitis and ACS in patients with AS.

Correlation between Endophthalmitis and Stroke Development in Ankylosing Spondylitis Patients: A Population-Based Cohort Study.

BACKGROUND: This cohort study aimed to research the correlation between endophthalmitis and stroke development in ankylosing spondylitis (AS) patients by reviewing National Health Insurance Research Database (NHIRD) data. METHODS: This study obtained data from the NHIRD over a sixteen-year period. The primary outcome was stroke development. We used Fisher's exact test and Pearson's chi-squared test to analyze the variables. We investigated the risk factors for disease development using Cox regression analyses. We compared the cumulative incidence of stroke using Kaplan-Meier analysis. RESULTS: The study cohort included 549 patients with AS and endophthalmitis, while the comparison cohort included 2196 patients with AS but without endophthalmitis. The stroke development was increased in the study cohort (adjusted hazard ratio, 1.873; p ≤ 0.001). The total stroke development in the study cohort and the comparison cohort was 1724.44 per 100,000 person-years and 1085.11 per 100,000 person-years, respectively (adjusted hazard ratio, 1.873; 95% confidence interval, 1.776-2.022; p < 0.001). Our study cohort showed an increased stroke rate. CONCLUSIONS: Our studies showed that endophthalmitis increases the risk of stroke in AS patients and endophthalmitis is an independent risk factor for stroke in AS patients. Nonetheless, advanced studies that thoroughly investigate the correlation between endophthalmitis and stroke in AS patients are needed to validate our findings.

Diabetic Macular Edema Detection Using End-to-End Deep Fusion Model and Anatomical Landmark Visualization on an Edge Computing Device.

Purpose: Diabetic macular edema (DME) is a common cause of vision impairment and blindness in patients with diabetes. However, vision loss can be prevented by regular eye examinations during primary care. This study aimed to design an artificial intelligence (AI) system to facilitate ophthalmology referrals by physicians. Methods: We developed an end-to-end deep fusion model for DME classification and hard exudate (HE) detection. Based on the architecture of fusion model, we also applied a dual model which included an independent classifier and object detector to perform these two tasks separately. We used 35,001 annotated fundus images from three hospitals between 2007 and 2018 in Taiwan to create a private dataset. The Private dataset, Messidor-1 and Messidor-2 were used to assess the performance of the fusion model for DME classification and HE detection. A second object detector was trained to identify anatomical landmarks (optic disc and macula). We integrated the fusion model and the anatomical landmark detector, and evaluated their performance on an edge device, a device with limited compute resources. Results: For DME classification of our private testing dataset, Messidor-1 and Messidor-2, the area under the receiver operating characteristic curve (AUC) for the fusion model had values of 98.1, 95.2, and 95.8%, the sensitivities were 96.4, 88.7, and 87.4%, the specificities were 90.1, 90.2, and 90.2%, and the accuracies were 90.8, 90.0, and 89.9%, respectively. In addition, the AUC was not significantly different for the fusion and dual models for the three datasets (p = 0.743, 0.942, and 0.114, respectively). For HE detection, the fusion model achieved a sensitivity of 79.5%, a specificity of 87.7%, and an accuracy of 86.3% using our private testing dataset. The sensitivity of the fusion model was higher than that of the dual model (p = 0.048). For optic disc and macula detection, the second object detector achieved accuracies of 98.4% (optic disc) and 99.3% (macula). The fusion model and the anatomical landmark detector can be deployed on a portable edge device. Conclusion: This portable AI system exhibited excellent performance for the classification of DME, and the visualization of HE and anatomical locations. It facilitates interpretability and can serve as a clinical reference for physicians. Clinically, this system could be applied to diabetic eye screening to improve the interpretation of fundus imaging in patients with DME.