Genetic Risk Stratification of Primary Open-Angle Glaucoma in Japanese Individuals.

PURPOSE: To assess the impact of genetic risk estimation for primary open-angle glaucoma (POAG) in Japanese individuals. DESIGN: Cross-sectional analysis. PARTICIPANTS: Genetic risk scores (GRSs) were constructed based on a genome-wide association study (GWAS) of POAG in Japanese people. A total of 3625 Japanese individuals, including 1191 patients and 2434 controls (Japanese Tohoku), were used for the model selection. We also evaluated the discriminative accuracy of constructed GRSs in a dataset comprising 1034 patients and 1147 controls (the Japan Glaucoma Society Omics Group [JGS-OG] and the Genomic Research Committee of the Japanese Ophthalmological Society [GRC-JOS]) and 1900 participants from a population-based study (Hisayama Study). METHODS: We evaluated 2 types of GRSs: polygenic risk scores using the pruning and thresholding procedure and a GRS using variants associated with POAG in the GWAS of the International Glaucoma Genetics Consortium (IGGC). We selected the model with the highest areas under the receiver operating characteristic curve (AUC). In the population-based study, we evaluated the correlations between GRS and ocular measurements. MAIN OUTCOME MEASURE: Proportion of patients with POAG after stratification according to the GRS. RESULTS: We found that a GRS using 98 variants, which showed genome-wide significance in the IGGC, showed the best discriminative accuracy (AUC, 0.65). In the Japanese Tohoku, the proportion of patients with POAG in the top 10% individuals was significantly higher than that in the lowest 10% (odds ratio [OR], 6.15; 95% confidence interval [CI], 4.35-8.71). In the JGS-OG and GRC-JOS, we confirmed similar impact of POAG GRS (AUC, 0.64; OR [top vs. bottom decile], 5.81; 95% CI, 3.79-9.01). In the population-based study, POAG prevalence was significantly higher in the top 20% individuals of the GRS compared with the bottom 20% (9.2% vs. 5.0%). However, the discriminative accuracy was low (AUC, 0.56). The POAG GRS was correlated positively with intraocular pressure (r = 0.08: P = 4.0 × 10-4) and vertical cup-to-disc ratio (r = 0.11; P = 4.0 × 10-6). CONCLUSIONS: The GRS showed moderate discriminative accuracy for POAG in the Japanese population. However, risk stratification in the general population showed relatively weak discriminative performance. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Successful spinal cord stimulation using fast-acting sub-perception therapy for postoperative neuropathic pain of syringomyelia with Chiari malformation type 1: a case report and literature review.

BACKGROUND: Central neuropathic pain after foramen magnum decompression (FMD) for Chiari malformation type 1 (CM-1) with syringomyelia can be residual and refractory. Here we present a case of refractory central neuropathic pain after FMD in a CM-1 patient with syringomyelia who achieved improvements in pain following spinal cord stimulation (SCS) using fast-acting sub-perception therapy (FAST™). CASE PRESENTATION: A 76-year-old woman presented with a history of several years of bilateral upper extremity and chest-back pain. CM-1 and syringomyelia were diagnosed. The pain proved drug resistant, so FMD was performed for pain relief. After FMD, magnetic resonance imaging showed shrinkage of the syrinx. Pain was relieved, but bilateral finger, upper arm and thoracic back pain flared-up 10 months later. Due to pharmacotherapy resistance, SCS was planned for the purpose of improving pain. A percutaneous trial of SCS showed no improvement of pain with conventional SCS alone or in combination with Contour™, but the combination of FAST™ and Contour™ did improve pain. Three years after FMD, percutaneous leads and an implantable pulse generator were implanted. The program was set to FAST™ and Contour™. After implantation, pain as assessed using the McGill Pain Questionnaire and visual analog scale was relieved even after reducing dosages of analgesic. No adverse events were encountered. CONCLUSION: Percutaneously implanted SCS using FAST™ may be effective for refractory pain after FMD for CM-1 with syringomyelia.

JACQLQ subjective symptom questionnaire score and clinical test results for patients with allergic conjunctival disease.

We investigated the relationship between subjective symptoms and objective findings in patients with allergic conjunctival diseases (ACD) and test results for tear total IgE (t-tIgE), conjunctival eosinophils (c-Eo), serum total IgE (s-tIgE), serum-antigen specific IgE (s-sIgE), and serum eosinophils (s-Eo). Subjective symptoms and objective findings of patients with ACD were evaluated using Japanese Allergic Conjunctival Disease Quality of Life Questionnaire (JACQLQ), which described disability score and emotional score written by patient and clinical findings score written by ophthalmologist. We investigated the relationship between questionnaire scores and laboratory data for t-tIgE, c-Eo, s-tIgE, s-sIgE, and s-Eo. Scores of impediments to life and of moods were highest in vernal keratoconjunctivitis among ACD. Cases with positive pollen-sIgE showed significantly more nasal symptom score than those with negative pollen-sIgE (P < 0.05). Cases with positive t-tIgE or c-Eo showed significantly more objective symptoms' JACQLQ score than those with negative t-tIgE or c-Eo (P < 0.05), respectively. Cases positive for house dust/mite-sIgE, showed significantly more objective symptoms' JACQLQ score than those without for house dust/mite-sIgE (P < 0.05). These results indicate that ACD could be analyzed more accurately by the combination of JACQLQ and laboratory data.

Functions of mucosal associated invariant T cells in eye diseases.

Mucosal-associated invariant T (MAIT) cells are a unique subset of T cells that recognizes metabolites derived from the vitamin B2 biosynthetic pathway. Since the identification of cognate antigens for MAIT cells, knowledge of the functions of MAIT cells in cancer, autoimmunity, and infectious diseases has been rapidly expanding. Recently, MAIT cells have been found to contribute to visual protection against autoimmunity in the eye. The protective functions of MAIT cells are induced by T-cell receptor (TCR)-mediated activation. However, the underlying mechanisms remain unclear. Thus, this mini-review aims to discuss our findings and the complexity of MAIT cell-mediated immune regulation in the eye.