Purpose: We present a rare case of acute visual acuity loss following intravitreal ganciclovir injection for the treatment of cytomegalovirus (CMV) retinitis.Case summary: A 35-year-old woman receiving immunosuppressive therapy for systemic lupus erythematosus developed CMV retinitis in the left eye. Oral valganciclovir was initiated but discontinued due to cytopenia and treatment was switched to intravitreal ganciclovir injections (2 mg/0.04 mL). One year later, CMV retinitis developed in the right eye and the same regimen was initiated. Although receiving bilateral injections at two-week intervals, the patient experienced a sudden decrease in visual acuity in the right eye one day after injection, 10 months after treatment initiation. Optical coherence tomography and fluorescein angiography revealed inner retinal edema and focal macular leakage. Treatment was switched to intravenous foscarnet resulting in resolution of macular edema; however, central retinal thinning persisted. Owing to recurrent retinitis, intravitreal ganciclovir injections are currently being continued at a reduced dose (1 mg/0.02 mL). Conclusions Acute visual acuity loss may rarely occur following intravitreal ganciclovir injection in patients with CMV retinitis. Careful consideration of potential mechanical injury and drug-induced retinal toxicity is needed during treatment.

Purpose: To investigate the impact of combined phacovitrectomy versus vitrectomy alone on perioperative concentrations of vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) in the aqueous humor (AH) of patients with proliferative diabetic retinopathy (PDR). Methods: This prospective, comparative case series included 15 patients with PDR indicated for vitreoretinal surgery. AH samples were collected at three time points: preoperatively (one week prior to surgery), intraoperatively, and postoperatively (one month after surgery).Twelve patients underwent phacovitrectomy, and three patients underwent vitrectomy alone. All patients received a preoperative intravitreal bevacizumab injection. Concentrations of VEGF and IL-8 were quantified using enzyme-linked immunosorbent assay. Results: In the overall cohort, AH VEGF concentrations followed a U-shaped pattern, decreasing from a preoperative mean of 322.26 pg/ mL to an intraoperative mean of 45.47 pg/mL (p = 0.002) before significantly rebounding to 205.16 pg/mL postoperatively (p = 0.005 vs.intraoperative). This trend was driven by the phacovitrectomy group, which showed a significant postoperative VEGF rebound (p = 0.002).Conversely, the vitrectomy-only group showed no significant change. IL-8 concentrations increased significantly from the intraoperative to the postoperative period in the phacovitrectomy group (p = 0.003), a change not observed in the vitrectomy-only group. Conclusions Phacovitrectomy induces a significant postoperative elevation of both VEGF and IL-8 in the anterior chamber, creating a pro-angiogenic and pro-inflammatory microenvironment. These findings provide a potential mechanistic explanation for increased risk of neovascular glaucoma observed clinically following combined phacovitrectomy.

Hormone receptor-positive (HR+) breast cancer is known for its potential to recur many years after initial treatment. Although most recurrences occur within the first 5–10 years, late recurrence, especially beyond 15 years of age, is rare and isolated cutaneous recurrence is even less frequently reported. However, awareness of the possibility of extremely late and subtle local recurrences in patients with HR+ breast cancer has gradually increased over time. Clinicians should remain vigilant for atypical cutaneous changes near previous surgical sites, even decades after the initial treatment, and consider biopsy in the absence of classic signs of recurrence. We report the case of a 56-year-old woman who experienced an isolated cutaneous recurrence nearly 20 years after mastectomy for HR+ breast cancer, presenting with only faint erythema.

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.