Risk of Autoimmune Diseases Following Optic Neuritis: A Nationwide Population-Based Cohort Study.

Objectives: Optic neuritis is (ON) is believed to be an immune-mediated disease; however, the association between optic neuritis and autoimmune diseases remains unclear. This study aimed to identify the incidence rate and adjusted hazard ratio (aHR) of autoimmune diseases in patients with optic neuritis. Methods: This nationwide, population-based, retrospective cohort study collected patients' data between 1999 and 2013 from the National Health Insurance Research Database in Taiwan. A total of 9,235 patients were included. Using 1:4 propensity scoring, 1,847 patients were enrolled in the optic neuritis group and 7,388 in the non-optic neuritis group according to age, sex, comorbidities, and corticosteroid use. Follow-up was started from the index date and the endpoint was a diagnosis of new-onset autoimmune diseases including, myasthenia gravis (MG), psoriatic arthritis (PsA), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Results: The Kaplan-Meier curves depicted that patients with optic neuritis had a higher cumulative incidence of autoimmune diseases than patients without optic neuritis. Cox proportional hazard regression showed that patients with optic neuritis were at a high risk of autoimmune diseases (aHR: 1.40; 95% C.I., 1.05-1.87), including MG (aHR: 4.16, 95% C.I.: 1.33-12.94), SLE (aHR: 3.33, 95% C.I.: 1.24-8.97), and AS (aHR: 2.86, 95% C.I.: 1.54-5.31). Subgroup analysis provided that patients with optic neuritis aged below 65 years (aHR: 1.42, 95% C.I.: 1.03-1.96) or who were females (aHR: 1.59, 95% C.I.: 1.11-2.27) had a significantly increased risk of autoimmune diseases compared to respective controls. The use of corticosteroids reduced the risk of autoimmune diseases in patients with optic neuritis (aHR for corticosteroids non-users: 1.46, 95% C.I.: 1.03-2.07). Conclusion: Patients with optic neuritis presented with a high risk of autoimmune diseases such as MG, SLE, and AS, especially patients with optic neuritis who were young or females. Corticosteroids attenuated the link between optic neuritis and subsequent autoimmune diseases.

Association of Long Non-Coding RNA Growth Arrest-Specific 5 Genetic Variants with Diabetic Retinopathy.

The aim of this work was to appraise the potential associations of single nucleotide polymorphisms (SNPs) of long non-coding RNA growth arrest-specific 5 (GAS5) with diabetic retinopathy (DR) in a diabetes mellitus (DM) population. Two loci of the GAS5 SNPs (rs55829688 and rs145204276) were genotyped via TaqMan allelic discrimination in 449 non-DR patients and 273 DR subjects. The SNP rs145204276 Del/Del showed a significantly higher distribution in the DR group compared to the non-DR group (AOR: 2.487, 95% CI: 1.424-4.344, p = 0.001). During subgroup analyses, the non-proliferative diabetic retinopathy (NPDR) subgroup demonstrated a significantly higher ratio of the SNP rs145204276 Del/Del (AOR: 2.917, 95% CI: 1.574-5.406, p = 0.001) and Ins/Del + Del/Del (AOR: 1.242, 95% CI: 1.016-1.519, p = 0.034) compared to the non-DR population, while the proliferative diabetic retinopathy (PDR) subgroup did not reveal significant differences in either SNP rs145204276 or rs55829688 distributions compared to the non-DR group. Furthermore, patients with a GAS5 SNP rs145204276 Del/Del showed a significantly shorter DM duration than the wild type (Ins/Ins) (p = 0.021). In conclusion, our findings demonstrate that the GAS5 SNP rs145204276 Del/Del variant is associated with an increased susceptibility to DR in DM patients, particularly in those patients with NPDR.

Differences in the Quantity and Composition of Extracellular Vesicles in the Aqueous Humor of Patients with Retinal Neovascular Diseases.

Extracellular vesicles (EVs) are secreted by various cells in the body fluid system and have been found to influence vessel formation and inflammatory responses in a variety of diseases. However, which EVs and their subtypes are involved in vascular retinal diseases is still unclear. Therefore, the aim of this study was to explore the particle distribution of EVs in retinal neovascular diseases, including age-related macular degeneration, polypoidal choroidal vasculopathy, and central retinal vein occlusion. The aqueous humor was harvested from 20 patients with different retinal neovascular diseases and six patients with cataracts as the control group. The particle distribution was analyzed using nanoparticle tracking analysis (NTA) and transmitting electron microscopy (TEM). The results revealed that the disease groups had large amounts of EVs and their subtypes compared to the control group. After isolating exosomes, a higher expression of CD81+ exosomes was shown in the disease groups using flow cytometry. The exosomes were then further classified into three subtypes of exomeres, small exosomes, and large exosomes, and their amounts were shown to differ depending on the disease type. To the best of our knowledge, this is the first study to elucidate the dynamics of EVs in retinal neovascular diseases using clinical cases. Our findings demonstrated the possible functionality of microvesicles and exosomes, indicating the potential of exosomes in the diagnosis and therapy of retinal neovascular diseases.

The Association of Diabetic Retinopathy and Cardiovascular Disease: A 13-Year Nationwide Population-Based Cohort Study.

OBJECTIVES: Previous studies have demonstrated that patients with diabetic retinopathy (DR) have a higher prevalence of risk factors known to be associated with cardiovascular disease (CVD). We hypothesized that patients with more severe DR could have a higher relative risk of CVD. METHODS: To test this hypothesis, we used the National Health Insurance Research Database (NHIRD) to evaluate whether associations exist between DR and CVD. The data for this nationwide population-based retrospective cohort study were obtained from the NHIRD in Taiwan from 2001 to 2013. The assessed study outcome used was the incidence and other statistical analyses of CVD in patients with DR during a 13-year follow-up period. RESULTS: Our findings obtained from 2001 to 2013 suggest that the incidence rates of CVD are 2.026 times that of diabetes mellitus (DM) without DR (95% C.I. = 1.876-2.187) and 2.75 times that of DM with DR (95% C.I. = 2.487-3.04) compared with the Non-DM group. CONCLUSION: The relative risk of CVD in DR was greater than that in the Non-DM group for both men and women. Targeted monitoring of DM, especially the co-existence of diabetic retinopathy, is of utmost importance in the clinical care of the DM population.

Quercetin Alleviates the Accumulation of Superoxide in Sodium Iodate-Induced Retinal Autophagy by Regulating Mitochondrial Reactive Oxygen Species Homeostasis through Enhanced Deacetyl-SOD2 via the Nrf2-PGC-1α-Sirt1 Pathway.

Oxidative damage of retinal pigment epithelium (RPE) cells plays an important role in the pathogenesis of blindness-related diseases, such as age-related macular degeneration (AMD). Quercetin, a bioactive flavonoid compound, has been shown to have a protective effect against oxidative stress-induced cell apoptosis and inflammation in RPE cells; however, the detailed mechanism underlying this protective effect is unclear. Therefore, the aim of this study was to investigate the regulatory mechanism of quercetin in a sodium iodate (NaIO3)-induced retinal damage. The clinical features of the mice, the production of oxidative stress, and the activity of autophagy and mitochondrial biogenesis were examined. In the mouse model, NaIO3 treatment caused changes in the retinal structure and reduced pupil constriction, and quercetin treatment reversed the oxidative stress-related pathology by decreasing the level of superoxide dismutase 2 (SOD2) while enhancing the serum levels of catalase and glutathione. The increased level of reactive oxygen species in the NaIO3-treated ARPE19 cells was improved by treatment with quercetin, accompanied by a reduction in autophagy and mitochondrial biogenesis. Our findings indicated that the effects of quercetin on regulating the generation of mtROS were dependent on increased levels of deacetyl-SOD2 through the Nrf2-PGC-1α-Sirt1 signaling pathway. These results demonstrated that quercetin may have potential therapeutic efficacy for the treatment of AMD through the regulation of mtROS homeostasis.

Deep Learning for Automated Diabetic Retinopathy Screening Fused With Heterogeneous Data From EHRs Can Lead to Earlier Referral Decisions.

Purpose: Fundus images are typically used as the sole training input for automated diabetic retinopathy (DR) classification. In this study, we considered several well-known DR risk factors and attempted to improve the accuracy of DR screening. Metphods: Fusing nonimage data (e.g., age, gender, smoking status, International Classification of Disease code, and laboratory tests) with data from fundus images can enable an end-to-end deep learning architecture for DR screening. We propose a neural network that simultaneously trains heterogeneous data and increases the performance of DR classification in terms of sensitivity and specificity. In the current retrospective study, 13,410 fundus images and their corresponding nonimage data were collected from the Chung Shan Medical University Hospital in Taiwan. The images were classified as either nonreferable or referable for DR by a panel of ophthalmologists. Cross-validation was used for the training models and to evaluate the classification performance. Results: The proposed fusion model achieved 97.96% area under the curve with 96.84% sensitivity and 89.44% specificity for determining referable DR from multimodal data, and significantly outperformed the models that used image or nonimage information separately. Conclusions: The fusion model with heterogeneous data has the potential to improve referable DR screening performance for earlier referral decisions. Translational Relevance: Artificial intelligence fused with heterogeneous data from electronic health records could provide earlier referral decisions from DR screening.

Factors affecting surgical outcome of intermittent exotropia.

PURPOSE: The purpose of this study was to investigate the factors affecting surgical outcome in intermittent exotropia. DESIGNS: This was a retrospective interventional study. METHODS: Intermittent exotropic patients who had undergone surgical correction with a postoperative follow-up period of 1 month or more were included in the study. Surgical success was defined as an alignment between 10 prism diopters (PD) of exotropia or 5 PD of esotropia at 1 month. After data collection, data were analyzed in SPSS version 23 software. The main outcome measures were the factors affecting surgical outcome. RESULTS: We included 101 patients, including 52 (51.5%) male and 49 (48.5%) female. Among them, 62 (61.4%) patients achieved surgical success. Undercorrection was the primary reason of surgical failure. Multivariate regression analysis showed that a larger preoperative angle of deviation was associated with unfavorable surgical outcome (P = 0.053, odds ratio [OR] =0.97, 95% confidence interval [CI] = 0.94-1.00), and the presence of postoperative day 1 (POD 1) diplopia correlated significantly with higher surgical success (P = 0.001, OR = 4.54, 95% CI = 1.80-11.43). The presence of POD 1 diplopia was highly associated with POD 1 esotropia (P = 0.005, OR = 7.26, 95% CI = 1.84-28.58). CONCLUSION: In intermittent exotropia, larger preoperative angle of deviation may predict a lower surgical success rate. Despite a worrisome issue, the presence of diplopia on first POD is associated with immediate postoperative alignment of esotropia and predicts a higher surgical success.