Aqueous Flare Changes in Ex-PRESS Glaucoma Shunt Eyes After 4.7 Tesla High-Field Magnetic Resonance Imaging.

Purpose: Ex-PRESS glaucoma shunt stainless steel devices have been used worldwide for glaucoma treatment. The purpose of this study was to evaluate the safety of high-field magnetic resonance imaging (MRI) for Ex-PRESS-inserted eyes. Methods: Using rabbits, we performed Ex-PRESS shunt surgery in one eye in each rabbit and divided the rabbits into MRI and non-MRI groups. In the MRI group, 1 week after Ex-PRESS shunt surgery under low specific absorption rate (SAR) conditions and 1 week later under high SAR conditions, high-field 4.7-Tesla MRI was performed. Aqueous flare counts were measured before and after the Ex-PRESS shunt surgery and each MRI examination. The rabbits in the non-MRI group received only general anesthesia, and aqueous flare counts were measured as for those of the MRI group. Aqueous flare counts were expressed in photon counts per millisecond. Results: No dislocation of the Ex-PRESS shunt device was observed after MRI. The flare count ratio (MRI/non-MRI) in Ex-PRESS-inserted eyes 2 hours after high SAR MRI increased significantly compared with that before MRI (0.8 ± 0.3 vs 2.7 ± 0.8; pre-high SAR MRI vs 2 hours after high SAR MRI, respectively; P = 0.01). The day after MRI, the flare count improved spontaneously to the same level as that before MRI. Conclusions: Our results indicate that high-field MRI can be performed relatively safely after Ex-PRESS shunt surgery. Translational Relevance: This study demonstrates the safety of high-field MRI for Ex-PRESS-inserted eyes using a rabbit model.

Dietary Vitamins A, C, and Potassium Intake Is Associated With Narrower Retinal Venular Caliber.

INTRODUCTION: The retinal vasculature, a surrogate for the systemic microvasculature, can be observed non-invasively, providing an opportunity to examine the effects of modifiable factors, such as nutrient intake, on microcirculation. We aimed to investigate the possible associations of dietary nutrient intake with the retinal vessel caliber. METHODS: In this cross-sectional study, a total of 584 participants in a medical survey of Japanese descendants living in Los Angeles in 2015 underwent a dietary assessment, fundus photographic examination, and comprehensive physical and blood examinations. Retinal vessel caliber was measured using fundus photographs with a semi-automated computer system and summarized as central retinal artery and vein equivalents (CRAE and CRVE). The association between dietary nutrient intake and retinal vessel caliber was analyzed using a multivariate linear regression model adjusted for two models including potential confounders. The first model was adjusted for age and sex. The second model was adjusted for age, sex, smoking status, body mass index, hypertension, diabetes, dyslipidemia, history of coronary heart disease, and history of stroke. RESULTS: After adjustment of potential confounders, compared to the quartile with the lowest intake, the difference in CRVE for the highest quartile was -5.33 µm [95% confidence interval (CI): -9.91 to -0.76, P for trend = 0.02] for vitamin A, -4.93 µm (95% CI: -9.54 to -0.32, P for trend = 0.02) for vitamin C and -3.90 µm (95% CI: -8.48 to 0.69, P for trend = 0.04) for potassium. CONCLUSIONS: A significant association was observed between higher vitamins A, C and potassium intakes and narrower retinal venular caliber.

Association of Dietary Nutrient Intake with Early Age-Related Macular Degeneration in Japanese-Americans.

Lifestyle factors may be associated with the development of age-related macular degeneration (AMD), in addition to demographic and genetic factors. The purpose of this cross-sectional study is to elucidate the association between nutrient intake and AMD in the Japanese-American population living in Los Angeles. We conducted a medical survey of Japanese immigrants and their descendants living in Los Angeles, including interviews on dietary habits, fundus photography, and physical examinations. Participants were classified into early AMD and control groups on the basis of fundus photographic findings. Consequently, among the 555 participants, 111 (20.0%) were diagnosed with early AMD. There were no late-stage AMD participants. Multivariate logistic regression analysis showed that the intake of animal fat and saturated fatty acids (SFA) was positively associated with early AMD (p for trend = 0.01 for animal fat, p for trend = 0.02 for SFA), and the intake of vegetable fat, total carbohydrate, simple carbohydrate, sugar, and fructose was inversely associated with early AMD (p for trend = 0.04 for vegetable fat, p for trend = 0.046 for carbohydrate, p for trend = 0.03 for simple carbohydrate, p for trend = 0.046 for sugar, p for trend = 0.02). Our findings suggest that excessive animal fat and SFA intake increases the risk for early AMD in Japanese-Americans whose lifestyles have been westernized.

Capacity of Retinal Ganglion Cells Derived from Human Induced Pluripotent Stem Cells to Suppress T-Cells.

Retinal ganglion cells (RGCs) are impaired in patients such as those with glaucoma and optic neuritis, resulting in permanent vision loss. To restore visual function, development of RGC transplantation therapy is now underway. Induced pluripotent stem cells (iPSCs) are an important source of RGCs for human allogeneic transplantation. We therefore analyzed the immunological characteristics of iPSC-derived RGCs (iPSC-RGCs) to evaluate the possibility of rejection after RGC transplantation. We first assessed the expression of human leukocyte antigen (HLA) molecules on iPSC-RGCs using immunostaining, and then evaluated the effects of iPSC-RGCs to activate lymphocytes using the mixed lymphocyte reaction (MLR) and iPSC-RGC co-cultures. We observed low expression of HLA class I and no expression of HLA class II molecules on iPSC-RGCs. We also found that iPSC-RGCs strongly suppressed various inflammatory immune cells including activated T-cells in the MLR assay and that transforming growth factor-ß2 produced by iPSC-RGCs played a critical role in suppression of inflammatory cells in vitro. Our data suggest that iPSC-RGCs have low immunogenicity, and immunosuppressive capacity on lymphocytes. Our study will contribute to predicting immune attacks after RGC transplantation.

Risk factors for exposure of Baerveldt glaucoma drainage implants: a case-control study.

BACKGROUND: Glaucoma drainage implant exposure is one of the serious complications after glaucoma drainage implant surgery. The purpose of this study is to evaluate the risk factors for exposure of the device after implantation of a Baerveldt glaucoma drainage implant. METHODS: This is a retrospective review of the medical records of all patients who underwent Baerveldt glaucoma drainage implant surgery at the Hiroshima University Hospital between April 1, 2012 and October 31, 2016, and who were followed for at least 6 months after surgery. We examined the risk factors for implant exposure based on data obtained from the medical records, with a particular focus on the differences in implant models. RESULTS: A total of 80 eyes from 80 patients were identified; all patients were Japanese. In this study, the rate of Baerveldt glaucoma drainage implant exposure was 15.0% (12 of 80 eyes). The exposure rate for the BG 102-350 tended to be higher than that for the BG 101-350 and BG 103-250 (p = 0.092; adjusted odds ratio = 3.34; 95% confidence interval, 0.82-13.58). In the patients who had diabetic mellitus, the BG 102-350 showed a significant risk of implant exposure (p = 0.038; adjusted odds ratio = 15.36; 95% confidence interval, 1.17-202.59). CONCLUSIONS: In Baerveldt glaucoma drainage implant surgery in patients with diabetes, using the BG 102-350 was associated with greater risk of implant exposure compared with using the BG 101-350 or BG 103-250.

Retinal Pigment Epithelial Cells Derived from Induced Pluripotent Stem (iPS) Cells Suppress or Activate T Cells via Costimulatory Signals.

Human retinal pigment epithelial (RPE) cells derived from induced pluripotent stem (iPS) cells have immunosuppressive properties. However, RPE cells are also known as immunogenic cells, and they have major histocompatibility complex expression and produce inflammatory proteins, and thus experience immune rejection after transplantation. In this study, to confirm the immunological properties of IPS-RPE cells, we examined whether human RPE cells derived from iPS cells could suppress or stimulate inflammatory T cells from uveitis patients via costimulatory signals. We established T cells from patients with active uveitis as target cells and used iPS-RPE cells as effector cells. As a result, cultured iPS-RPE cells inhibited cell proliferation and the production of IFN-γ by activated uveitis CD4+ T cells, especially Th1-type T cells. In contrast, iPS-RPE cells stimulated T cells of uveitis patients. The iPS-RPE cells constitutively expressed B7-H1/CD274 and B7-DC/CD273, and suppressed the activation of T cells via the PD-1 receptor. iPS-RPE expressed these negative costimulatory molecules, especially when RPE cells were pretreated with recombinant IFN-γ. In addition, iPS-RPE cells also expressed B7-H3/CD276 costimulatory molecules and activated uveitis T cells through the B7-H3-TLT-2 receptor. Thus, cultured iPS-derived retinal cells can suppress or activate inflammatory T cells in vitro through costimulatory interactions.

A Strategy for Personalized Treatment of iPS-Retinal Immune Rejections Assessed in Cynomolgus Monkey Models.

Recently, we successfully transplanted an autograft, or major histocompatibility complex (MHC)-matched allografts, from induced-pluripotent-stem-cell-derived retinal pigment epithelial (iPSC-RPE) cells in patients with age-related macular degeneration. However, there was an issue regarding immune rejection after transplantation. In this study, we established a preoperational in vitro "drug-lymphocytes-grafts immune reaction (Drug-LGIR)" test to determine the medication for immune rejection using host immunocompetent cells (lymphocytes) and transplant cells (target iPSC-RPE cells) together with different medications. The adequacy of the test was assessed by in vivo transplantation in monkey models together with medication based on in vitro data. In the results of Drug-LGIR tests, some drugs exhibited significant suppression of RPE cell-related allogeneic reactions, while other drugs did not, and the efficacy of each drug differed among the recipient monkeys. Based on the results of Drug-LGIR, we applied cyclosporine A or local steroid (triamcinolone) therapy to two monkeys, and successfully suppressed RPE-related immune rejections with RPE grafts, which survived without any signs of rejection under drug administration. We propose that our new preoperational in vitro Drug-LGIR test, which specifies the most efficacious medication for each recipient, is useful for controlling immune attacks with personalized treatment for each patient after retinal transplantation.

Usefulness of B-scan ocular ultrasound images for diagnosis of optic perineuritis.

PURPOSE: This study was performed to examine the usefulness of B-scan ocular ultrasound images for the diagnosis of optic perineuritis. OBSERVATIONS: A 72-year-old woman developed nonpainful blurred vision in her left eye. At the first ophthalmological consultation, she had optic disc swelling and choroidal folds in both eyes and subretinal fluid in the left eye. She was referred to our clinic 1 month after symptom onset. At the first visit to our clinic, she still complained of blurred vision. She was found to have mild vitreous cells in the left eye and optic disc swelling in both eyes. However, the choroidal folds had already resolved in both eyes. B-scan ultrasound images displayed the optic nerve sheath as a highly reflective circle with shadowing around the optic disc in both eyes and scleral thickening in the left eye with fluid in sub-Tenon's space. Bilateral optic perineuritis with posterior scleritis seemed highly plausible. Magnetic resonance imaging with intravenous contrast revealed increased signal intensity around the optic nerve (i.e., the "tram track sign") in both eyes, which was consistent with optic perineuritis. CONCLUSION AND IMPORTANCE: Optic perineuritis is a rare inflammatory disorder involving the optic nerve sheath. Although magnetic resonance imaging is reportedly useful for diagnosis of this disease, no previous reports have described B-scan ultrasound imaging for this purpose. We herein provide the first report of a patient suspected to have optic perineuritis based on B-scan images. B-scan ultrasound may be useful for diagnosis of optic perineuritis, especially with inflammation surrounding the optic nerve.