ABSTRACT: Currently, the Department of Ophthalmology of Toho University is engaging in various types of research with the aim of contributing to society. One of the areas of our research is DRY EYE. ...There are over an estimated 10 million patients with dry eye in Japan, and the number is believed to keep increasing, thus suggesting the extreme importance of research on dry eye treatments. Our research team has focused on mucins, one of the components of the tear film along with water and lipids. In Japan, diquafosol tetrasodium and rebamipide, two mucin secretagogue eye drops, are used as first-choice drugs to treat dry eye. When we compared these two drugs, we found that the secretion of tears promoted by these drugs had different characteristics. These studies made it possible to differentiate how these two drugs are used depending on the dry eye conditions. The author is one of the organizers of the Japan Dry Eye Society. The Japan Dry Eye Society revises the definition and diagnostic criteria of dry eye every 10 years, conducts academic activities as well as promotes awareness on the importance of tears and dry eye treatment to the people of Japan. Through the efforts of the Dry Eye Society, July 3rd was established as "Tears Day" in 2017. We have held various events associated with "Tears Day," and hope to continue to make social contributions through our work and involvement in the field of dry eye research and treatment.
Mucins, which play important roles on the ocular surface in wettability, lubrication, and barrier function, are classified into two categories: secreted mucins and membrane-associated mucins. The ...most important secreted mucin on the ocular surface is MUC5AC, which is secreted by the conjunctival goblet cells. In the human conjunctiva, goblet cells are present in higher concentrations in the fornix, inferior nasal bulbar, and the lid wiper on the lid margin. The number of conjunctival goblet cells and MUC5AC expression/secretion are decreased in a patient with dry eye. In Japan, drugs that stimulate mucin secretion or increase the number of conjunctival goblet cells are commercially available. A P2Y2 receptor, diquafosol, stimulates tear fluid secretion from conjunctival epithelial cells and promotes mucin secretion from conjunctival goblet cells. Rebamipide was marketed originally as an oral therapeutic drug to treat gastritis in Japan. Topical rebamipide increases numbers of goblet cells in the bulbar conjunctiva and the lid wiper area of palpebral conjunctiva. Many researchers have reported decreases in the ocular surface mucin expression including MUC5AC secreted by goblet cells in patients with dry eye. However, it is unknown whether changes in mucin expression on the ocular surface cause or result from dry eye. Further study is needed to determine the true mechanism of dry eye disease.
Purpose
To investigate the prevalence of myopia and high myopia and the risk factors for high myopia in infants at 3 years of age with retinopathy of prematurity (ROP).
Study design
Retrospective, ...observational.
Methods
We retrospectively analyzed all 89 preterm infants (178 eyes) with medical records of ROP between October 2008 and March 2018 at Toho University Medical Center Omori Hospital; these infants had a birth weight of less than 1,500 g and were followed up at least until 3 years of age. Cycloplegic autorefraction was performed to measure refractive outcomes. Multivariate analysis was performed to determine the risk factors for early-onset high myopia at 3 years of age.
Results
The prevalence of myopia and high myopia was significantly higher in the treated group (59.7% and 17.9%, respectively) than in the untreated group (19.7% and 0%, respectively) (
p
<0.001). Spherical equivalent (SE) at age 3 was more myopic in the treatment group (−1.72 ± 3.53 D) than in the untreated group (0.54 ± 1.08 D) (
p
<0.001). In the sub-analysis of the treatment group, there was a significant correlation between SE at age 3 and the number of laser shots (R
2
= 0.36,
p
<0.001). Multivariate logistic analysis showed that the number of laser shots was an independent risk factor for early onset high myopia (
p
<0.05).
Conclusion
The number of laser shots is an independent risk factor for early onset high myopia, and preterm infants who have undergone laser treatment for severe ROP should be considered for early optical correction with cycloplegic refractive examination.
Background:The electrophysiological characteristics of residual conduction gaps between the left atrium (LA) and pulmonary veins (PVs) after HotBalloon-based wide antral ablation (HBWA) of atrial ...fibrillation (AF) remain incompletely understood. This study aimed to characterize the residual gaps by means of ultra-high-resolution mapping.Methods and Results:A total of 55 AF patients underwent HBWA by a predetermined protocol (6-shot total-based antral approach). LA-PV maps were created using 64-electrode minibasket catheters. In total, 55 residual gaps were identified among 26 (47%) patients. Residual gaps included 33 left superior (LS: 60%), 10 left inferior (18%), 6 right superior (11%), and 6 right inferior (11%) PVs. Those gaps demonstrated both extremely lower bipolar amplitudes (0.11 interquartile range: 0.06–0.27 mV) and conduction velocities (0.75±0.27 m/s); however, the length was confined (10.3±4.1 mm) except for the LSPV anterior carina (12.2±2.4 mm) region. Among the carina regions, all gaps had far-field potentials consistently added to the PV potentials. Left atrial appendage pacing to split the far-field activity identified confined gap regions (6.7±1.9 mm). Touch-up ablation eliminated the residual PV potentials in all cases.Conclusions:HBWA resulted in a certain degree of residual gap conduction in particular antral regions. These gaps exhibited narrow lengths with lower amplitudes, and often had far-field recordings from the left atrial appendage. Combined with pacing maneuvers, ultra-high-resolution activation maps could both visualize all confined gaps and ensure a bare minimum of touch-up ablations in all patients with gap conduction.
To determine the risk of mask-associated dry eye (MADE), we investigated the fluorescein tear break-up time (FBUT), ocular surface temperature and blood flow, along with corneal sensitivity, in mask ...wearers. We enrolled 60 mask wearers (mean age, 27.1 ± 5.2 years) and then measured FBUT, corneal temperature and conjunctival blood flow without wearing masks (no mask), with masks, and with taped masks. We defined MADE as the condition in which dry eye symptoms appeared and the FBUT with mask was less than 5 s. The FBUT with a mask was significantly shorter compared to the no mask and taped mask groups (P < 0.01 and P < 0.05). The corneal temperature difference and conjunctival blood flow difference were significantly higher after wearing a mask than after wearing a taped mask (P < 0.01). Of the 60 subjects, 13 were diagnosed with MADE. Pain sensitivity and the Ocular Surface Disease Index (P < 0.05 and P < 0.01) were significantly higher in the MADE group, with the FBUT without masks (P < 0.05) significantly shorter than in the non-MADE group. MADE may be associated with corneal hypersensitivity. Wearing masks decreased FBUT and increased ocular surface temperature and blood flow. Taping the top edge of masks prevented these changes. Fitting masks properly may reduce MADE risk.
Potential differences in the nature of the influences of aging and gender on the optic nerve head (ONH) microcirculation, using laser speckle flowgraphy (LSFG) were evaluated. We studied 908 healthy ...subjects (men = 701, age: 50.0 ± 9.1 yrs, women = 208, 49.8 ± 9.5 yrs, p = 0.76). The average, maximum (Max), and minimum (Min) mean blur rate (MBR) in a heartbeat were evaluated. The parameters were analyzed separately for the tissue, vessels, and throughout the ONH (All). We investigated which MBR sections are correlated with gender and age by univariate and multivariate regression analyses. The Max MBR-All (r = -0.31) was most strongly correlated with gender (men = 1, women = 0). The Min MBR-All (r = -0.24) was most strongly correlated with age, followed by Min MBR-All (r = -0.20). The factors contributing independently to the Max MBR-All were gender (β = -0.15), pulse pressure, spherical refraction, ocular perfusion pressure, and red blood cell (RBC) count. The factors contributing independently to the Min MBR-Vessel were gender (β = -0.09), age (β = -0.25), body mass index, heart rate, and spherical refraction. The factors contributing independently to the Min-MBR-All were age (β = -0.22), heart rate, and RBC count. Our results revealed that gender differences influence the Max MBR, and aging influences the Min MBR. These correlations were stronger than that of average MBR.
In this paper, we propose a method for video reflection removal using a video restoration framework with enhanced deformable networks (EDVR). We examine the effect of each module in EDVR on video ...reflection removal and modify the models using 3D convolutions. The performance of each modified model is evaluated in terms of the RMSE between the structural similarity (SSIM) and the smoothed SSIM representing temporal consistency.
We investigated gender differences in the optic nerve head (ONH) microcirculation status in association with obstructive sleep apnea (OSA) by using laser speckle flowgraphy (LSFG). We evaluated 150 ...men (60.5 ± 11.0 yrs) and 45 women (63.0 ± 10.6 yrs) who underwent overnight polysomnography. The mean blur rate (MBR), maximum (Max) MBR, and minimum (Min) MBR were evaluated. The parameters were analyzed separately for the tissues, vessels, and throughout the ONH (All). The apnea hypopnea index (AHI: times/hr), the lowest SpO2%, and the mean SpO2% were calculated as indicators of OSA. We investigated which MBR sections are correlated with OSA parameters separately in the men and women. All MBR sections in the women were significantly positively correlated with the lowest SpO2. In the men, no MBR section was correlated with any OSA parameters. The factors contributing independently to MBR-Tissue were height (β = 0.31) and lowest SpO2 (β = 0.30). The lowest SpO2 in the women was significantly positively correlated with Max MBR-Tissue, Max MBR-All, and Min MBR-All. Our results confirmed a gender difference in characteristics of ONH microcirculation in association with OSA.
We aimed to perform superpixel segmentation of ocular blood flow maps obtained using laser speckle flowgraphy (LSFG) and investigate the effects of systemic parameters such as body weight, height, ...and sex on ocular blood flow resistivity. We studied 757 healthy participants (583 men, 174 women). We calculated the average beat strength over mean blur rate (BOM) as a LSFG resistivity index, as a function of age and sex using ordinary regions of interest (ROI) centered on the optic nerve head (ONH), the retinal vessels region and tissue around the ONH, and the choroid (CHD). We compared the ROI and superpixel-based methods, which are segmented based on image processing, for calculating the BOM. The sex differences in the BOM for the ONH, retinal-vessels region and tissue region of the ONH and CHD were significant for individuals aged ≤ 50 years (P < 0.01) but not those > 50 years old (P > 0.05). The average BOMs calculated using the ROI and superpixel methods were strongly correlated in the ONH (coefficient = 0.87, R
= 0.8, P < 0.0001, n = 5465). In summary, a superpixel-segmented BOM map is suitable for two-dimensional visualization of ocular blood flow resistivity.
Dry eye-induced chronic ocular pain is also called ocular neuropathic pain. However, details of the pathogenic mechanism remain unknown. The purpose of this study was to elucidate the pathogenic ...mechanism of dry eye-induced chronic pain in the anterior eye area and develop a pathophysiology-based therapeutic strategy.
We used a rat dry eye model with lacrimal gland excision (LGE) to elucidate the pathogenic mechanism of ocular neuropathic pain. Corneal epithelial damage, hypersensitivity, and hyperalgesia were evaluated on the LGE side and compared with the sham surgery side. We analyzed neuronal activity, microglial and astrocytic activity, α2δ-1 subunit expression, and inhibitory interneurons in the trigeminal nucleus. We also evaluated the therapeutic effects of ophthalmic treatment and chronic pregabalin administration on dry eye-induced ocular neuropathic pain.
Dry eye caused hypersensitivity and hyperalgesia on the LGE side. In the trigeminal nucleus of the LGE side, neuronal hyperactivation, transient activation of microglia, persistent activation of astrocytes, α2δ-1 subunit upregulation, and reduced numbers of inhibitory interneurons were observed. Ophthalmic treatment alone did not improve hyperalgesia. In contrast, continuous treatment with pregabalin effectively ameliorated hypersensitivity and hyperalgesia and normalized neural activity, α2δ-1 subunit upregulation, and astrocyte activation.
These results suggest that dry eye-induced hypersensitivity and hyperalgesia are caused by central sensitization in the trigeminal nucleus with upregulation of the α2δ-1 subunit. Here, we showed that pregabalin is effective for treating dry eye-induced ocular neuropathic pain even after chronic pain has been established.
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