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.

Role of Oncostatin M in the Pathogenesis of Vernal Keratoconjunctivitis: Focus on the Barrier Function of the Epithelium and Interleukin-33 Production by Fibroblasts.

Purpose: Vernal keratoconjunctivitis (VKC) is a severe, recurrent allergic conjunctivitis. Previously, we found high concentrations of oncostatin M (OSM) in the tears of patients with VKC. Here, we investigated the role of OSM in VKC by focusing on epithelial barrier function and IL-33 production. Methods: To assess the effect of OSM on the barrier function of human conjunctival epithelial cells (HConEpiCs), we measured transepithelial electrical resistance and dextran permeability. We also assessed expression of tight junction-related proteins such as E-cadherin and ZO-1 in HConEpiCs by Western blotting and immunofluorescence. Then we used immunohistochemistry to evaluate expression of Ki-67, E-cadherin, epithelial-mesenchymal transition-related proteins, and IL-33 in giant papillae (GPs) from patients with VKC. In addition, we used Western blotting, microarray, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay to examine whether OSM activates signal transducer and activator of transcription 1 (STAT1) or STAT3 and induces the expression of various genes in human conjunctival fibroblasts (HConFs). Results: OSM reduced expression of E-cadherin and ZO-1 in HConEpiCs, indicating barrier dysfunction. In immunohistochemistry, Ki-67 expression was present in the lower epithelial layer of the GPs, and E-cadherin expression was reduced in the superficial and lower layers; double staining revealed that GPs had a high number of fibroblasts expressing IL-33. In addition, in HConFs, OSM phosphorylated both STAT1 and STAT3 and induced IL-33. Conclusions: OSM has important roles in severe, prolonged allergic inflammation by inducing epithelial barrier dysfunction and IL-33 production by conjunctival fibroblasts.

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.

Factors Affecting a Short-Term Response to Anti-VEGF Therapy in Diabetic Macular Edema.

Diabetic macular edema (DME) is a common cause of visual impairment in patients with diabetes. Although intravitreal anti-vascular endothelial growth factor (VEGF) injections were efficacious in clinical trials, several patients exhibited a poor response. This study aimed to compare clinical features between patients who were susceptible to intravitreal anti-VEGF injections for DME and those who were not. A single-center, retrospective study of 102 such patients was conducted (123 eyes; mean ± standard deviation age, 63.4 ± 10.8 years; 57.8% males). Systemic and ocular data, assessed at baseline and after a month, were compared between good (>20% decrease in central macular thickness (CMT)) and poor (≤20% decrease in CMT) responders using the Mann-Whitney U test/Fisher's exact test. Eighty-one eyes (65.9%) were good responders. The glycosylated hemoglobin level was higher (p = 0.011) in poor (7.5% ± 0.94%) than in good (7.04% ± 1.19%) responders. The foveal avascular zone was larger (p = 0.0003) in poor (0.67 ± 0.33 µm2) than in good (0.47 ± 0.23 µm2) responders. The number of microaneurysms in the pericapillary network was higher (p = 0.0007) in poor (2.7 ± 2.2) than in good (1.4 ± 2.0) responders. Baseline glycemic control and macular ischemia may be associated with the short-term response to intravitreal anti-VEGF injections.

Role of oncostatin M in the pathogenesis of vernal keratoconjunctivitis: focus on tissue remodeling.

PURPOSE: Vernal keratoconjunctivitis (VKC) is a severe and recurrent allergic conjunctivitis, the mechanism of which is not well understood. In this study, we investigated the role of oncostatin M (OSM) in the pathogenesis of VKC, with a focus on tissue remodeling. STUDY DESIGN: Clinical and experimental. PATIENTS AND METHODS: The OSM concentrations in tear fluid samples obtained from VKC patients and healthy controls were measured using ELISA, and the expression of OSM mRNA and protein in giant papillae resected from VKC patients was investigated using RT-PCR and immunohistochemistry, respectively. In cultured human conjunctival epithelial cells (HconEpiCs), expression of OSM receptor ß (OSMRß) was detected using immunocytochemical and FACS analyses. Finally, we investigated whether recombinant OSM activated STAT1 and STAT3 to induce the expression of various genes related to tissue remodeling in HconEpiCs, by using Western blot analysis, microarray analysis, and RT-PCR. RESULTS: The OSM concentration was higher in the tear fluid of VKC patients than in that of the healthy controls, and strong expression of OSM mRNA was found in the giant papillae. We also detected T cells expressing OSM in the giant papillae. In addition, HconEpiCs showed surface expression of OSMRß. Recombinant human OSM strongly activated both STAT1 and STAT3 in HconEpiCs and induced various tissue remodeling-related genes, including MMP-1, MMP-3, IL-24, IL-20, serpinB3, S100A7, tenascin C, and SOCS3. CONCLUSION: Our results suggest that OSM is one of the key molecules involved in remodeling of giant papillae in VKC.

Relationship between Recurrence of Macular Edema Due to Branch Retinal Vein Occlusion and Changes in Choroidal Thickness.

INTRODUCTION: The role of vascular endothelial growth factor in macular edema (ME) due to branch retinal vein occlusion (BRVO) by enhancing vascular permeability has been well studied. ME due to BRVO often recurs; however, there has been no report on the relationship between this recurrence and choroidal thickness (CT), considering the high vascularity of the choroid. This study was designed to investigate this relationship. METHODS: In this retrospective consecutive case series, patients with recurrence of ME within 6 months of receiving intravitreal aflibercept injection treatment for naive ME due to BRVO at Juntendo University Urayasu Hospital were included. Retinal thickness (RT) and CT were measured in the fovea and on the occlusion, non-occlusion, nasal, and temporal sides at baseline, after the first intravitreal aflibercept administration, and before and after recurrence. We also examined the change for each side before and after reinjection. RESULTS: This study included 11 patients and 11 eyes. The subfoveal CT and RT at baseline were 261.9 ± 93.4 µm and 691.5 ± 254.4 µm, respectively, which significantly decreased to 208.5 ± 70.3 µm and 188.6 ± 33.8 µm, respectively, at 1 month after the first injection (p = 0.001 and p < 0.01, respectively). These values also significantly decreased at all the other sites after treatment. There were 14 recurrences within the 6 months following intravitreal aflibercept injection; RT significantly changed at all sites before and after recurrence and reinjection. CT significantly changed at the subfovea and on the occlusion and non-occlusion sides; however, there was no significant change on the nasal and temporal sides. CONCLUSION: In patients with BRVO, the CT around the macula after initial treatment was significantly reduced; however, at the time of ME recurrence and reinjection, there were site-dependent differences in the changes observed in the CT. These findings suggest that the pathologies of ME at initial occurrence and at the time of recurrence are different.

Twenty-four-month results of intravitreal aflibercept for macular edema due to branch retinal vein occlusion.

PURPOSE: To investigate 24-month results of intravitreal aflibercept (IVA) for macular edema due to branch retinal vein occlusion (BRVO-ME). STUDY DESIGN: Retrospective study. METHODS: Subjects were treatment-naïve BRVO-ME patients at the Ophthalmology Department of Juntendo University Urayasu Hospital from November 2015 to March 2017 who received IVA treatment for 24 months. After the first injection, reinjection was performed as needed when ME had recurred or was prolonged beyond 300 µm. Data included changes in best corrected visual acuity and central foveal thickness, total number of injections, and the case background factors that required reinjection after 12 months. ME remission was defined as patients without additional injections for 6 months. RESULTS: Forty eyes of 40 patients (64.5 ± 11.5 years), 21 men and 19 women, were included. Average best corrected visual acuity and central foveal thickness at baseline were logMAR 0.42 ± 0.21, 601.4 ± 181.3 µm, logMAR 0.08 ± 0.25, 214.6 ± 62.7 µm at 12 months, logMAR 0.02 ± 0.16, 216.6 ± 97.8 µm at 24 months, all significantly improved from baseline. The average number of injections was 2.2 ± 1.0 times in the first year and 0.4 ± 0.8 times in the second year. The rate of ME remission was 60.0% at 12 months and 87.5% at 24 months. Period between onset and injections was significantly associated with reinjection after 12 months (p =.030). CONCLUSIONS: IVA was effective over 24 months for ME due to BRVO in many cases. Early injection treatment may reduce the need for later injections.

Effects of Secreted Mast Cell Mediators on Retinal Pigment Epithelial Cells: Focus on Mast Cell Tryptase.

Numerous mast cells are present in the choroid, but the effects of mast cell mediators on retinal pigment epithelial (RPE) cells are not well understood. We investigated the influence of mast cell mediators on RPE cells in vitro, focusing on tryptase. Expression of receptors was examined by the reverse transcription polymerase chain reaction. We also assessed production of interleukin 8 and vascular endothelial growth factor (VEGF) after RPE cells were stimulated with mast cell mediators by using an antibody array and enzyme-linked immunosorbent assay. Furthermore, we investigated the influence of tryptase on RPE cell migration and integrity by the scratch assay and the transepithelial resistance. RPE cells expressed protease-activated receptor 2 (PAR2), histamine receptor 1, tumor necrosis factor-α (TNF-α) receptor 1, and CCR 1, 3, 4, 8, and 11. Tryptase, PAR2 agonists, histamine, and TNF-α all enhanced interleukin 8 production by RPE cells, while only tryptase enhanced VEGF production. Tryptase also enhanced expression of phosphorylated extracellular signal-regulated kinases 1/2, resulting in increased migration of RPE cells. However, tryptase did not alter epithelial integrity or the expression of zonula occludens-1 and junctional adhesion molecule-A by RPE cells. Mast cell mediators, especially tryptase, may influence RPE cell inflammation.

Short-term outcomes in patients with branch retinal vein occlusion who received intravitreal aflibercept with or without intravitreal ranibizumab.

PURPOSE: The purpose of this study was to determine the short-term outcomes for patients who received intravitreal aflibercept (IVA) with or without intravitreal ranibizumab (IVR) for macular edema (ME) due to branch retinal vein occlusion (BRVO). PATIENTS AND METHODS: Patients received IVA for ME due to BRVO. Patients who initially received IVA were defined as the treatment-naïve group and those who were switched from IVR to IVA after ME recurrence were defined as the switching group. Patient outcomes were examined at 1 week and 1 month postinjection. RESULTS: Both groups comprised 27 eyes from 27 patients. There was a significant decrease in central macular thickness (CMT) at 1 week and 1 month postinjection in both groups. There was also a significant improvement in best-corrected visual acuity (BCVA) at 1 week and 1 month postinjection in the treatment-naïve group and 1 month in the switching group. Younger age was associated with a good BCVA at 1 month postinjection in the switching group, and the absence of epiretinal membrane was associated with a reduction in CMT at 1 month postinjection in the switching group. CONCLUSION: IVA is temporarily effective for treating ME due to BRVO regardless of a history of IVR use.