Subthreshold Photocoagulation Using Endpoint Management in the PASCAL® System for Diffuse Diabetic Macular Edema

We evaluated subthreshold photocoagulation using endpoint management (EPM) for the treatment of diabetic macular edema (DME). The study enrolled 10 eyes from 10 patients (6 men and 4 women) with DME. The entry criteria included central macular thickness (CMT) ≥ 300 μm and decimal visual acuity (VA) ≤ 0.5. The primary endpoints were VA (logMAR) and CMT at 6 months follow-up. Secondary endpoints included fundus autofluorescence, macular volume (MV), and macular sensitivity (MS). We used the PASCAL Streamline Yellow® (wavelength, 577 nm) system to perform grid pattern laser photocoagulation at 50% of the threshold (size, 100 μm; duration, 0.015 s; spacing, 0.5; and energy, 4.5–7.8 mJ). At 6 months posttreatment, CMT was significantly decreased, while there were no significant changes in macular sensitivity, mean BCVA (logMAR), or macular volume. Autofluorescence imaging revealed no changes after treatment in 6 of 10 eyes. No eyes exhibited subjective symptoms of scotoma after photocoagulation. Optical coherence tomography showed the complete resolution of macular edema in 4 eyes (40%) after a single treatment; MS was increased in all 4 of these eyes at 6 months posttreatment. In conclusion, subthreshold photocoagulation using EPM is safe and effective for DME treatment and preserves MS. This trial is registered with UMIN000012401

18F-fluorodeoxyglucose positron emission tomography and magnetic resonance imaging evaluation of chorea

Chorea is thought to be caused by deactivation of the indirect pathway in the basal ganglia circuit. However, few imaging studies have evaluated the basal ganglia circuit in actual patients with chorea. We investigated the lesions and mechanisms underlying chorea using brain magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). This retrospective case series included three patients with chorea caused by different diseases: hyperglycemic chorea, Huntington’s disease, and subarachnoid hemorrhage. All the patients showed dysfunction in the striatum detected by both MRI and FDG-PET. These neuroimaging findings confirm the theory that chorea is related to an impairment of the indirect pathway of basal ganglia circuit

Sublethal Photothermal Stimulation with a Micropulse Laser Induces Heat Shock Protein Expression in ARPE-19 Cells

Purpose/Aim of the Study. Subthreshold micropulse diode laser photocoagulation is an effective treatment for macular edema. The molecular mechanisms underlying treatment success are poorly understood. Therefore, we investigated the effects of sublethal laser energy doses on a single layer of densely cultured ARPE-19 cells as a model of the human retinal pigment epithelium (RPE). Materials and Methods. A single layer of densely cultured human ARPE-19 cells was perpendicularly irradiated with a micropulse diode laser. Nonirradiated cells served as controls. Sublethal laser energy was applied to form a photocoagulation-like area in the cultured cell layers. Hsp70 expression was evaluated using quantitative polymerase chain reaction and immunocytochemistry. Results. Photocoagulation-like areas were successfully created in cultured ARPE-19 cell layers using sublethal laser energy with our laser irradiation system. Hsp70 mRNA expression in cell layers was induced within 30 min of laser irradiation, peaking at 3 h after irradiation. This increase was dependent on the number of laser pulses. Hsp70 upregulation was not observed in untreated cell layers. Immunostaining indicated that Hsp70 expression occurred concentrically around laser irradiation sites and persisted for 24 h following irradiation. Conclusion. Sublethal photothermal stimulation with a micropulse laser may facilitate Hsp70 expression in the RPE without inducing cellular damage

Variants of C-C Motif Chemokine 22 (CCL22) Are Associated with Susceptibility to Atopic Dermatitis: Case-Control Studies

Atopic dermatitis (AD) is a common inflammatory skin disease caused by multiple genetic and environmental factors. AD is characterized by the local infiltration of T helper type 2 (Th2) cells. Recent clinical studies have shown important roles of the Th2 chemokines, CCL22 and CCL17 in the pathogenesis of AD. To investigate whether polymorphisms of the CCL22 gene affect the susceptibility to AD, we conducted association studies and functional studies of the related variants. We first resequenced the CCL22 gene and found a total of 39 SNPs. We selected seven tag SNPs in the CCL22 gene, and conducted association studies using two independent Japanese populations (1st population, 916 cases and 1,032 controls; 2nd population 1,034 cases and 1,004 controls). After the association results were combined by inverse variance method, we observed a significant association at rs4359426 (meta-analysis, combined P = 9.6×10−6; OR, 0.74; 95% CI, 0.65–0.85). Functional analysis revealed that the risk allele of rs4359426 contributed to higher expression levels of CCL22 mRNA. We further examined the allelic differences in the binding of nuclear proteins by electrophoretic mobility shift assay. The signal intensity of the DNA-protein complex derived from the G allele of rs223821, which was in absolute LD with rs4359426, was higher than that from the A allele. Although further functional analyses are needed, it is likely that related variants play a role in susceptibility to AD in a gain-of-function manner. Our findings provide a new insight into the etiology and pathogenesis of AD

Subfoveal Choroidal Thickness and Treatment Outcomes of Intravitreal Aflibercept for Branch Retinal Vein Occlusion

We aimed to investigate the relationship between subfoveal choroidal thickness (SCT) and treatment outcomes of intravitreal aflibercept (IVA) for macular edema (ME) due to branch retinal vein occlusion (BRVO). We retrospectively evaluated 46 patients with treatment-naive BRVO-ME who underwent IVA treatment between March 2016 and February 2017. There was no significant difference in visual acuity within 6 months (0.29 ± 0.20 vs. 0.27 ± 0.19, p = 0.338), the mean central foveal thickness improvement (332.0 ± 162.2 μm vs. 303.9 ± 166.6 μm, p = 0.492), and the mean number of IVA injections (1.7 ± 0.7 vs. 1.6 ± 0.7 times, p = 0.658) between the SCT thickened (n = 26 patients, 26 eyes) and SCT non-thickened groups (n = 20 patients, 20 eyes). The rate of ME recurrence was significantly lower in the SCT decreased group (6/17 eyes (35.2%) vs. 19/30 eyes (63.3%); p = 0.038). In conclusion, pretreatment choroidal thickening does not affect the therapeutic effect of IVA for BRVO, but ME recurrence was lower in cases of treatment-related choroidal thinning. Thus, changes in SCT may be a therapeutic indicator of IVA for acute BRVO

Biologics for allergy: therapeutic potential for ocular allergic diseases and adverse effects on the eye

Biologics applying antibodies against IgE, IL-5, IL-5 receptor α, IL-4 receptor α, and IL-13 have dramatically improved recent treatment outcomes in allergic diseases including asthma, rhinitis, and atopic dermatitis. However, these drugs have not been approved for ocular allergic diseases such as allergic conjunctivitis, vernal keratoconjunctivitis, and atopic keratoconjunctivitis. Although the putative mechanisms suggest that these drugs should have beneficial effects in patients with ocular allergies and some studies have reported such beneficial effects, various adverse ocular symptoms have also been observed in clinical trials and off-label use studies. Since ocular allergic diseases have distinct pathogeneses, each biologic drug must be examined regarding specific effects on each ocular allergy. For example, IgE-mediated type 1 hypersensitivity plays a critical role in allergic conjunctivitis. By contrast, T cells and eosinophilic and non-IgE-mediated type 2 inflammation play important roles in vernal keratoconjunctivitis. Allergists must fully understand the effects of each drug on the eye. This review outlines both potential therapeutic and adverse effects of various biologics on allergic diseases of the eye

A Case of Nephrotic Syndrome with Bilateral Serous Retinal Detachment and Shallow Anterior Chamber Associated with Ciliary Body Edema

Nephrotic syndrome is a disease that causes fluid retention in the body due to loss of protein in the blood, which can lead to serous retinal detachment (SRD) in the macula. We report a case of severe SRD in both eyes and angle closure due to ciliary body edema caused by nephrotic syndrome. A 57-year-old man was admitted to the Department of Nephrology in our hospital for a thorough examination of his generalized edema. He was diagnosed with nephrotic syndrome but proved to be refractory to steroid treatment. Due to distortion symptoms in both eyes on the 30th day of hospitalization, the patient was referred to our department. Best-corrected visual acuity (BCVA) was 0.8 in the right eye and 1.0 in the left eye. Slit lamp examination and anterior segmental optical coherence tomography (OCT) showed shallow anterior chambers in both eyes. Fundus and macular OCT demonstrated severe SRD in the posterior pole of both eyes. After observing the presence of hypoalbuminemia, we considered the possibility of SRD and angle closure due to ciliary edema that resulted from the leaks associated with the nephrotic syndrome. Thereafter, ocular findings improved in conjunction with systemic symptom improvements associated with ultrafiltration and low-density lipoprotein apheresis. On the 60th day of hospitalization, his BCVA improved to 1.2 in both eyes, SRD disappeared, and the anterior chamber depth normalized. This case demonstrates the importance of recognizing SRD and angle closure associated with ciliary body edema as complications linked with nephrotic syndrome

Upregulation of Mir-21 Levels in the Vitreous Humor Is Associated with Development of Proliferative Vitreoretinal Disease.

MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by post-transcriptional inhibition of mRNA translation. Dysregulation of miRNAs, including circulating miRNAs, has been reported to play an important role in the development of various diseases, including fibrotic diseases. Aberrant expression of miRNAs in the vitreous humor of vitreoretinal diseased eyes has been reported. However, the expression pattern of miRNAs present in the vitreous humor of proliferative vitreoretinal disease (PVD) patients, including proliferative diabetic retinopathy (PDR), and proliferative vitreoretinopathy (PVR), remains unknown. To investigate the factors important for the development of PVD, we characterized the miRNAs present in the vitreous humor of PVD patients and analyzed the expression profiles of 377 miRNAs using quantitative polymerase chain reaction-based miRNA arrays. The expression of a specific subset of miRNAs, previously reported to be associated with the development of angiogenesis and fibrosis, was significantly altered in the vitreous of PVD patients. Among these miRNAs, we identified miR-21 as a candidate fibrotic miRNA with an important role in the pathogenesis of PVD. Increased miR-21 levels in the vitreous were associated with retinal fibrosis, including PVR and PDR. Because epithelial-mesenchymal transition (EMT) of retinal pigment epithelial cells (RPECs) plays a critical role in retinal fibrosis, the expression of miR-21 in human RPECs was determined. Its expression in RPECs was induced by transforming growth factor-β, a key growth factor involved in fibrogenesis, and was enhanced by high glucose culture conditions, suggesting that miR-21 expression positively correlates with disease progression. Gain- and loss-of-function studies revealed that miR-21 promoted cell proliferation and migration of ARPE-19 cells without affecting EMT-related gene expression. Together, our studies have identified miR-21 as a potential disease-modifying miRNA in the vitreous humor that is involved in the development of retinal fibrosis and may be a novel marker of PVD