We aimed to investigate the risks of Alzheimer’s (AD) and Parkinson’s disease (PD) in the 10 years following diagnosis of open-angle glaucoma (OAG) using a nationwide cohort. This propensity score-matched retrospective cohort study included 1,025,340 subjects from the Korean National Health Insurance Service National Sample Cohort database. The OAG group (n = 1,469) included patients who were initially diagnosed with OAG between 2004 and 2007, and the subjects in the comparison group were matched in a 1:5 ratio using propensity scores. Cox regression analyses were performed to investigate the risks of developing AD or PD. The diagnosis of OAG was significantly associated with an increased incidence of AD (hazard ratio [HR] = 1.403, 95% confidence interval [CI] 1.180–1.669, p < 0.001), but not PD (HR = 0.995, 95% CI 0.620–1.595, p = 0.983) after adjusting for possible confounding factors. In subgroup analyses, participants with OAG aged ≥65 years were more likely to develop AD compared with those aged <65 years, and female OAG patients had a greater risk of developing AD than males. Patients diagnosed with OAG have a higher risk of developing AD, but not PD, and the risk differed according to age and sex.

Purpose. To determine the incidence of keratoconus and to determine its possible association with common systemic diseases using a nationwide cohort. Methods. This retrospective nationwide cohort study included 1,025,340 subjects from the Korean National Health Insurance Service-National Sample Cohort database from 2004 to 2013. Estimates for incidence rates of keratoconus were identified. After 1 : 5 matching using propensity scores, associations between keratoconus and certain systemic comorbidities were determined using multivariate logistic regression analysis. Results. The incidence during the same period was 15.1 cases per 100,000 person-years. Adjusted logistic regression analysis after propensity score matching revealed significant associations between keratoconus and allergic rhinitis (odds ratio (OR): 1.86; 95% confidence interval (CI): 1.63–2.13; p<0.001), asthma (OR: 1.20; 95% CI: 1.06–1.36; p<0.001), atopic dermatitis (OR: 1.33; 95% CI: 1.13–1.56; p<0.001), and diabetes mellitus (DM) (OR: 1.35; 95% CI: 1.15–1.58; p<0.001). Conclusion. Estimates of the incidence of keratoconus may help in the planning of eye-care policies, and the results of this study determined the associations between allergic diseases and keratoconus. Conflicting results regarding the association between keratoconus and DM should be further evaluated.

Increasing evidence suggests that exosomes are involved in retinal cell degeneration, including their insufficient release; hence, they have become important indicators of retinopathies. The exosomal microRNA (miRNA), in particular, play important roles in regulating ocular and retinal cell functions, including photoreceptor maturation, maintenance, and visual function. Here, we generated retinal organoids (ROs) from human induced pluripotent stem cells that differentiated in a conditioned medium for 60 days, after which exosomes were extracted from ROs (Exo-ROs). Subsequently, we intravitreally injected the Exo-RO solution into the eyes of the Royal College of Surgeons (RCS) rats. Intravitreal Exo-RO administration reduced photoreceptor apoptosis, prevented outer nuclear layer thinning, and preserved visual function in RCS rats. RNA sequencing and miRNA profiling showed that exosomal miRNAs are mainly involved in the mitogen-activated protein kinase (MAPK) signaling pathway. In addition, the expression of MAPK-related genes and proteins was significantly decreased in the Exo-RO-treated group. These results suggest that Exo-ROs may be a potentially novel strategy for delaying retinal degeneration by targeting the MAPK signaling pathway.

This study investigated the therapeutic effects of exosomes derived from human-induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs) on corneal epithelial wound healing. Exosomes were isolated from the culture medium of the hiPSC-derived ROs (Exo-ROs) using ultracentrifugation, and then they were characterized by a nanoparticle tracking analysis and transmission electron microscopy. In a murine model of corneal epithelial wounds, these exosomes were topically applied to evaluate their healing efficacy. The results demonstrated that the exosome-treated eyes showed significantly enhanced wound closures compared with the controls at 24 h post-injury. The 5-ethyl-2′-deoxyuridine assay and quantitative reverse transcription polymerase chain reaction revealed a substantial increase in cell proliferation and a decrease in inflammatory marker contents in the exosome-treated group. The RNA sequencing and exosomal microRNA analysis revealed that the Exo-RO treatment targeted various pathways related to inflammation and cell proliferation, including the PI3K-Akt, TNF, MAPK, and IL-17 signaling pathways. Moreover, the upregulation of genes related to retinoic acid and eicosanoid metabolism may have enhanced corneal epithelial healing in the eyes treated with the Exo-ROs. These findings suggest that hiPSC-derived RO exosomes could be novel therapeutic agents for promoting corneal epithelial wound healing.

Jung SJ, et al. Korean J Ophthalmol. 2018 Dec;33:e4. https://doi.org/10.3341/kjo.2018.0065

Various non-intraocular pressure factors have been identified as possible risk factors for open-angle glaucoma (OAG). However, there is still controversy around the association between OAG and chronic kidney disease (CKD). In this study, we used a nationwide cohort to investigate the risk of OAG in the 12 years following a diagnosis of CKD. This retrospective cohort study included 1,103,302 subjects from the Korean National Health Insurance Service National Sample Cohort database. The CKD group (n = 1318) included patients who were initially diagnosed with CKD between 2003 and 2008. The subjects in the comparison group were matched at a 1:5 ratio using propensity scores. In multivariate Cox regression analysis, a diagnosis of CKD was significantly associated with an increased incidence of OAG (hazard ratio [HR] = 1.546, 95% confidence interval [CI] 1.363–1.754, p < 0.001). Further analysis revealed that the risk of OAG increased with the severity of CKD (mild to moderate CKD [CKD stage 1–3]: HR = 1.280, 95% CI 1.077–1.521, p = 0.005; advanced CKD [CKD stage 4–5]: HR = 1.861, 95% CI 1.589–2.180, p < 0.001). In subgroup analysis, female CKD patients had a greater risk of developing OAG than males, and subjects with CKD aged ≥ 40 years were more likely to develop OAG compared with those aged < 40 years. Our study demonstrates that CKD is a significant risk factor for OAG and that severe CKD is associated with an increased risk of developing OAG.