Purpose: Vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) have been the standard of care for advanced and metastatic clear cell renal cell carcinoma (ccRCC). However, the therapeutic effect of TKI monotherapy remains unsatisfactory given the high rates of acquired resistance to TKI therapy despite favorable initial tumor response. Materials and Methods: To define the TKI-resistance mechanism and identify new therapeutic target for TKI-resistant ccRCC, an integrative differential gene expression analysis was performed using acquired resistant cohort and a public dataset. Sunitinib-resistant RCC cell lines were established and used to test their malignant behaviors of TKI resistance through in vitro and in vivo studies. Immunohistochemistry was conducted to compare expression between the tumor and normal kidney and verify expression of pathway-related proteins. Results: Integrated differential gene expression analysis revealed increased interferon-induced transmembrane protein 3 (IFITM3) expression in post-TKI samples. IFITM3 expression was increased in ccRCC compared with the normal kidney. TKI-resistant RCC cells showed high expression of IFITM3 compared with TKI-sensitive cells and displayed aggressive biologic features such as higher proliferative ability, clonogenic survival, migration, and invasion while being treated with sunitinib. These aggressive features were suppressed by the inhibition of IFITM3 expression and promoted by IFITM3 overexpression, and these findings were confirmed in a xenograft model. IFITM3-mediated TKI resistance was associated with the activation of TRAF6 and MAPK/AP-1 pathways. Conclusions These results demonstrate IFITM3-mediated activation of the TRAF6/MAPK/AP-1 pathways as a mechanism of acquired TKI resistance, and suggest IFITM3 as a new target for TKI-resistant ccRCC.

Granular cell tumor is a rare disease, and it is even rarer in the male breast. Although it is typically a benign tumor, due to its features and image findings, it can be easily misdiagnosed and managed as a malignant tumor. Therefore, the extent of the surgery can inappropriately be expanded. To avoid misdiagnosis and overtreatment, surgeons must perform a careful evaluation. We describe a case of a granular cell tumor of the male breast treated with mastectomy.

Purpose: Tyrosine kinase inhibitors (TKI) targeting vascular endothelial growth factor receptor (VEGFR) signaling pathways have been used for metastatic clear cell renal cell carcinoma (mCCRCC), but resistance to the drug develops in most patients. We aimed to explore the underlying mechanism of the TKI resistance with regard to programmed death-ligand 1 (PD-L1) and to investigate signaling pathway associated with the resistant mechanism. Materials and Methods: To determine the mechanism of resistance, 10 mCCRCC patients from whom tumor tissues were harvested at both the pretreatment and the TKI-resistant post-treatment period were included as the discovery cohort, and their global gene expression profiles were compared. A TKI-resistant renal cancer cell line was established by long-term treatment with sunitinib. Results: Among differentially expressed genes in the discovery cohort, increased PD-L1 expression in post-treatment tissues was noted in four patients. Pathway analysis showed that PD-L1 expression was positively correlated with the mammalian target of rapamycin (mTOR) signaling pathway. The TKI-resistant renal cancer cells showed increased expression of PD-L1 and mTOR signaling proteins and demonstrated aggressive tumoral behaviour. Treatment with mTOR inhibitors down-regulated PD-L1 expression and suppressed aggressive tumoral behaviour, which was reversed with stimulation of the mTOR pathway. Conclusion These results showed that PD-L1 expression may be increased in a subset of VEGFR-TKI–resistant mCCRCC patients via the mTOR pathway.

Purpose: We assessed the extent of silicone oil (SO) emulsification using ultra-wide-field fundus photography (wFP) and the reflective ratios of swept-source optical coherence tomography (SS-OCT). Methods: We retrospectively enrolled 51 eyes of 51 patients who underwent intravitreal SO tamponade with vitrectomy. Two weeks after SO tamponade and immediately before SO removal, ultra-wide-field fundus photography and SS-OCT were performed. Based on the numbers of emulsified droplets in the ultra-wide-field fundus photographs, SO emulsification was qualitatively graded from 0 to 4. Reflective ratios were calculated by dividing the OCT reflectivity of the optic cup by the OCT reflectivity of SO near the retinal surface. We analyzed the changes in the SO emulsification grade and the reflective ratio over time (RR2/RR1). Results: The SO emulsification grade revealed by ultra-wide-field fundus photography was 2.12 ± 1.29, and the mean SS-OCT RR2/RR1 value was 1.14 ± 0.22. A longer duration of SO tamponade was associated with a higher emulsification grade on ultra-wide-field fundus photography and an increase in the RR2/RR1 value (both p < 0.01). We found a significant correlation between the SO emulsification grade on ultra-wide-field fundus photography and the SS-OCT RR2/RR1 (p = 0.028). Conclusions Ultra-wide-field fundus photography and SS-OCT can be used to determine objectively the extent of SO emulsification; this may indicate the appropriate SO removal time any complication.

Purpose: The purpose of this case was to report the inhibition of toxoplasma retinitis reactivation with long-term, low-dose antibiotics.Case summary: A 76-year-old woman complained of poor vision and floaters in her right eye. The corrected visual acuity (LogMAR) of the right eye was 0.5, and there was an area of yellow infiltration and dye leakage on the retinal fluorescein angiography images. Toxoplasma IgG were detected in the serum, the patient was diagnosed with toxoplasma retinitis, and the patient was advised oral trimethoprim-sulfamethoxazole, clindamycin, and steroids. Her visual acuity improved and the inflammation resolved. However, she again had decreased visual activity and retinal inflammation in her right eye after 5 months. The inflammation improved with oral steroids, but she was shifted to intravitreal dexamethasone because of the side effects of systemic steroids. Although the inflammation improved initially, there was worsening of inflammation (evidenced by vitreous opacity) after 2 months, which was treated with oral antibiotics. After vitrectomy for the removal of residual vitreous opacity, antibiotics were stopped because of the stable disease course. After discontinuation of the antibiotics, inflammation was noted again, and low-dose trimethoprim-sulfamethoxazole was administered. Low-dose antibiotics were continued for 5 months and the disease remained stable without any retinal inflammation. Conclusions Long-term, low-dose oral antibiotics may prevent reactivation of recurrent toxoplasma retinitis.

Purpose: To compare early changes in the macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (mGCIPL) thicknesses according to the severity of initial optic disc edema in optic neuritis patients using swept-source optical coherence tomography (SS-OCT). Methods: We retrospectively reviewed 18 eyes of patients diagnosed with naïve optic neuritis along with optic disc edema who underwent SS-OCT. The central thickness of the optic nerve head and the peripapillary retinal thickness were measured at the initial visit. To quantitate the degree of initial optic disc edema, we calculated the difference of each measurement between the affected eye and the normal fellow eye. The mRNFL and mGCIPL thicknesses were measured at the initial visit and at the 1 month follow-up. The association between changes in mRNFL and mGCIPL thicknesses at the 1 month follow-up and the severity of initial optic disc edema were evaluated. Results: In the affected eye, the mGCIPL thickness was reduced at 1 month. The central thickness of the optic nerve head at the initial visit correlated with the reduction in the temporal mGCIPL at 1 month (R = 0.648, p = 0.045). Furthermore, thicker nasal peripapillary retinal thickness at the initial visit correlated with a reduction in nasal (R = 0.659, p = 0.038) and temporal (R = 0.774, p = 0.009) mGCIPL at 1 month. Thicker temporal peripapillary retinal thickness at the initial visit correlated with reduction in the nasal (R = 0.646, p = 0.044) and temporal (R = 0.760, p = 0.011) mGCIPL at 1 month. Conclusions In optic neuritis patients with optic disc edema, severe optic disc edema, evaluated by peripapillary retinal thickness and central thickness of the optic nerve at the initial visit was associated with a reduced temporal mGCIPL thickness at 1 month. This study suggested that initially severe optic disc edema in optic neuritis patients can predict a rapid decline in the mGCIPL.

Purpose: To evaluate endothelial damage after cataract surgery in eyes affected by an angle-closure attack (ACA) and compare it to that in the unaffected fellow eyes (FEs) of patients with ACA and normal eyes (NEs). Methods: The medical data of eyes affected by ACA, FEs (with no history of acute glaucoma attack), and NEs of patients who underwent cataract surgery with simultaneous intraocular lens implantation were retrospectively reviewed. Endothelial cell density (ECD) and central corneal thickness (CCT) measured before surgery and at 1 week, 1 month, and 3 months after surgery were analyzed, and the percentages of loss in ECD and increase in CCT of the three groups were compared. Results: The study enrolled 140 eyes from 100 patients (50 eyes in the ACA group, 40 eyes in the FE group, and 50 eyes in the NE group). The mean ECD was significantly lower in the ACA group than in the other groups (p < 0.001). However, the percentage of ECD reduction was not significantly greater in the ACA group than in the other groups (p > 0.05). None of the eyes developed corneal edema at 3 months postoperatively. Moreover, the CCTs of the three groups were similar throughout the follow-up period (p > 0.05). Conclusions Phacoemulsification was not associated with greater endothelial cell loss in the ACA group than in the NE and FE groups. This finding shows that ACA history may not contribute to the exacerbation of corneal endothelial damage in cataract surgery.

Purpose: To evaluate endothelial damage after cataract surgery in eyes affected by an angle-closure attack (ACA) and compare it to that in the unaffected fellow eyes (FEs) of patients with ACA and normal eyes (NEs). Methods: The medical data of eyes affected by ACA, FEs (with no history of acute glaucoma attack), and NEs of patients who underwent cataract surgery with simultaneous intraocular lens implantation were retrospectively reviewed. Endothelial cell density (ECD) and central corneal thickness (CCT) measured before surgery and at 1 week, 1 month, and 3 months after surgery were analyzed, and the percentages of loss in ECD and increase in CCT of the three groups were compared. Results: The study enrolled 140 eyes from 100 patients (50 eyes in the ACA group, 40 eyes in the FE group, and 50 eyes in the NE group). The mean ECD was significantly lower in the ACA group than in the other groups (p < 0.001). However, the percentage of ECD reduction was not significantly greater in the ACA group than in the other groups (p > 0.05). None of the eyes developed corneal edema at 3 months postoperatively. Moreover, the CCTs of the three groups were similar throughout the follow-up period (p > 0.05). Conclusions Phacoemulsification was not associated with greater endothelial cell loss in the ACA group than in the NE and FE groups. This finding shows that ACA history may not contribute to the exacerbation of corneal endothelial damage in cataract surgery.