Purpose: We present an atypical case of cytomegalovirus corneal endotheliitis after intravitreal triamcinolone injection.Case summary: A 61-year-old man presented with decreased visual acuity after intravitreal triamcinolone (Maqaid®, Wakamoto Pharmaceutical Co., Ltd., Tokyo, Japan) injection for cystoid macular edema following cataract surgery. Ocular examination revealed elevated intraocular pressure, diffuse keratic precipitates with corneal edema, and anterior chamber inflammation. These findings were suggestive of viral corneal endotheliitis. Polymerase chain reaction analysis of the anterior chamber aqueous humor detected cytomegalovirus DNA. Consequently, the patient was diagnosed with cytomegalovirus corneal endotheliitis. He was treated with oral valganciclovir (Valcyte®, Roche, Basel, Switzerland) at a dose of 1,800 mg/day for 3 weeks as an induction phase, followed by 900 mg/day for 3 weeks as a remission phase. This treatment regimen led to significant improvement in corneal edema and anterior chamber inflammation with complete restoration of visual acuity. Conclusions It is important to note that cytomegalovirus endotheliitis can occur after intravitreal triamcinolone injection and can present in an atypical rather than a typical form.

Glucocorticoids suppress the vascular inflammation that occurs under hypercholesterolemia, as demonstrated in an animal model fed a high-cholesterol diet. However, the molecular mechanisms underlying these beneficial effects remain poorly understood. Because cholesterol is oxidized to form cholesterol oxides (oxysterols) that are capable of inducing inflammation, we investigated whether glucocorticoids affect the immune responses evoked by 7α-hydroxycholesterol (7αOHChol). The treatment of human THP-1 monocytic cells with dexamethasone (Dex) and prednisolone (Pdn) downregulated the expression of pattern recognition receptors (PRRs), such as TLR6 and CD14, and diminished 7αOHCholenhanced response to FSL-1, a TLR2/6 ligand, and lipopolysaccharide, which interacts with CD14 to initiate immune responses, as determined by the reduced secretion of IL-23 and CCL2, respectively. Glucocorticoids weakened the 7αOHChol-induced production of CCL2 and CCR5 ligands, which was accompanied by decreased migration of monocytic cells and CCR5-expressing Jurkat T cells. Treatment with Dex or Pdn also reduced the phosphorylation of the Akt-1 Src, ERK1/2, and p65 subunits. These results indicate that both Dex and Pdn impair the expression of PRRs and their downstream products, chemokine production, and phosphorylation of signaling molecules. Collectively, glucocorticoids suppress the innate immune response and activation of monocytic cells to an inflammatory phenotype enhanced or induced by 7αOHChol, which may contribute to the anti-inflammatory effects in hypercholesterolemic conditions.

Purpose: To evaluate the long-term effects of conventional corneal cross-linking in patients with progressive keratoconus. Methods: A total of 18 eyes of 9 patients diagnosed with keratoconus were analyzed retrospectively. One eye was diagnosed with progressive keratoconus and conventional corneal crosslinking was performed. The other eye was classified as non-progressive and remained untreated. All patients were assessed with best corrected visual acuity (BCVA), maximum keratometry (Kmax), mean keratometry (Kmean), corneal astigmatism, and corneal thickness. Clinical data were collected before the procedure and at 1, 3, 6 months and 1 to 10 years after the procedure. Results: The BCVA significantly improved from 0.63 ± 0.18 logarithm of the minimum angle of resolution (logMAR) to 0.46 ± 0.25 logMAR at 10 years after conventional corneal crosslinking (p = 0.027). The Kmax and Kmean decreased from 65.90 ± 9.43 D and 52.82 ± 5.16 D to 62.83 ± 8.16 D and 51.52 ± 5.18 D, respectively (p = 0.021, p = 0.028, respectively). Corneal astigmatism decreased from 6.97 ± 2.21 D to 5.53 ± 1.64 D (p = 0.008). The thinnest corneal thickness decreased from 435.11 ± 53.37 μm to 369.22 ± 64.00 μm 1 month after the procedure (p = 0.008), and gradually improved over time. At 10 years, the thinnest corneal thickness increased to 410.11 ± 61.32 μm (p = 0.097). In the untreated eyes, the mean keratometry significantly increased after 4 years of follow-up, but other factors did not change significantly. Although corneal opacity persisted for up to 10 years in 3 eyes of the treatment group, there was no significant difference of BCVA compared to the treated eyes without corneal opacity (p = 0.714). Conclusions In patients with progressive keratoconus, conventional corneal crosslinking is a safe and effective procedure that suppresses long-term progression.

Many of early findings regarding intestinal stem cells (ISCs) and their niche in the human intestine have relied on colorectal cancer cell lines and labor-intensive and time-consuming mouse models. However, these models cannot accurately recapitulate the physiologically relevant aspects of human ISCs. In this study, we demonstrate a reliable and robust culture method for 3D expanding intestinal spheroids (InSexp ) mainly comprising ISCs and progenitors, which can be derived from 3D human intestinal organoids (HIOs). We did functional chararcterization of InSexp derived from 3D HIOs, differentiated from human pluripotent stem cells, and optimization culture methods. Our results indicate that InSexp can be rapidly expanded and easily passaged, and show enhanced growth rates via WNT pathway activation. InSexp are capable of exponential cell expansion and cryopreservation. Furthermore, in vitro-matured HIO-derived InSexp proliferate faster than immature HIO-derived InSexp with preservation of the parental HIO characteristics. These findings may facilitate the development of scalable culture systems for the long-term maintenance of human ISCs and provide an alternative platform for studying ISC biology.

Purpose: To report a case of combination therapy with interferon β1b (IFN-β1b) and mitomycin-C (MMC) for recurrent ocular surface squamous neoplasia (OSSN).Case summary: A 72-year-old female presented with a white mass at the medial conjunctiva of the right eye. A gelatinous, nodular white lesion was observed near the medial limbus of the right eye. On histological examination, it was diagnosed as squamous cell carcinoma in situ. A white nodule was found at the resection site 1 year after the resection. IFN-β1b (1 mIU/mL) and 0.02% MMC were administered daily with a diagnosis of recurrent OSSN. IFN-β1b was instilled four times a day for 1 month, while MMC was instilled four times a day for 4 weeks. After 1 month of the combination treatment, the lesion disappeared. MMC was stopped, while IFN-β1b was reduced to twice daily instillation, maintained for 1 month, and then stopped. On examination 12 months after discontinuation of the combination treatment, there were no recurrences or drug-related complications. Conclusions Combination therapy with IFN-β1b and MMC for recurrent OSSN after surgical resection was relatively safe with no major complications.

BACKGROUND: To validate the clinical application of chromosomal microarray analysis (CMA) as a first-tier clinical diagnostic test and to determine the impact of CMA results on patient clinical management, we conducted a multicenter prospective study in Korean patients diagnosed as having developmental delay/intellectual disability (DD/ID), autism spectrum disorders (ASD), and multiple congenital anomalies (MCA). METHODS: We performed both CMA and G-banding cytogenetics as the first-tier tests in 617 patients. To determine whether the CMA results directly influenced treatment recommendations, the referring clinicians were asked to complete a 39-item questionnaire for each patient separately after receiving the CMA results. RESULTS: A total of 122 patients (19.8%) had abnormal CMA results, with either pathogenic variants (N=65) or variants of possible significance (VPS, N=57). Thirty-five well-known diseases were detected: 16p11.2 microdeletion syndrome was the most common, followed by Prader-Willi syndrome, 15q11-q13 duplication, Down syndrome, and Duchenne muscular dystrophy. Variants of unknown significance (VUS) were discovered in 51 patients (8.3%). VUS of genes putatively associated with developmental disorders were found in five patients: IMMP2L deletion, PTCH1 duplication, and ATRNL1 deletion. CMA results influenced clinical management, such as imaging studies, specialist referral, and laboratory testing in 71.4% of patients overall, and in 86.0%, 83.3%, 75.0%, and 67.3% of patients with VPS, pathogenic variants, VUS, and benign variants, respectively. CONCLUSIONS: Clinical application of CMA as a first-tier test improves diagnostic yields and the quality of clinical management in patients with DD/ID, ASD, and MCA.
Autism Spectrum Disorder ; Autistic Disorder ; Cytogenetics ; Diagnostic Tests, Routine ; Down Syndrome ; Humans ; Intellectual Disability ; Korea ; Microarray Analysis ; Muscular Dystrophy, Duchenne ; Prader-Willi Syndrome ; Prospective Studies ; Referral and Consultation ; Specialization

OBJECTIVE: To investigate the value of ultrasound (US) microflow assessment in distinguishing malignant from benign solid breast masses as well as the association between US parameters and histologic microvessel density (MVD). MATERIALS AND METHODS: Ninety-eight breast masses (57 benign and 41 malignant) were examined using Superb Microvascular Imaging (SMI) and contrast-enhanced US (CEUS) before biopsy. Two radiologists evaluated the quantitative and qualitative vascular parameters on SMI (vascular index, morphology, distribution, and penetration) and CEUS (time-intensity curve analysis and enhancement characteristics). US parameters were compared between benign and malignant masses and the diagnostic performance was compared between SMI and CEUS. Subgroup analysis was performed according to lesion size. The effect of vascular parameters on downgrading Breast Imaging Reporting and Data System (BI-RADS) category 4A masses was evaluated. The association between histologic MVD and US parameters was analyzed. RESULTS: Malignant masses were associated with a higher vascular index (15.1 ± 7.3 vs. 5.9 ± 5.6), complex vessel morphology (82.9% vs. 42.1%), central vascularity (95.1% vs. 59.6%), penetrating vessels (80.5% vs. 31.6%) on SMI (all, p < 0.001), as well as higher peak intensity (37.1 ± 25.7 vs. 17.0 ± 15.8, p < 0.001), slope (10.6 ± 11.2 vs. 3.9 ± 4.2, p = 0.001), area (1035.7 ± 726.9 vs. 458.2 ± 410.2, p < 0.001), hyperenhancement (95.1% vs. 70.2%, p = 0.005), centripetal enhancement (70.7% vs. 45.6%, p = 0.023), penetrating vessels (65.9% vs. 22.8%, p < 0.001), and perfusion defects (31.7% vs. 3.5%, p < 0.001) on CEUS (p ≤ 0.023). The areas under the receiver operating characteristic curve (AUCs) of SMI and CEUS were 0.853 and 0.841, respectively (p = 0.803). In 19 masses measuring < 10 mm, central vascularity on SMI was associated with malignancy (100% vs. 38.5%, p = 0.018). Considering all benign SMI parameters on the BI-RADS assessment, unnecessary biopsies could be avoided in 12 category 4A masses with improved AUCs (0.500 vs. 0.605, p < 0.001). US vascular parameters associated with malignancy showed higher MVD (p ≤ 0.016). MVD was higher in malignant masses than in benign masses, and malignant masses negative for estrogen receptor or positive for Ki67 had higher MVD (p < 0.05). CONCLUSION: US microflow assessment using SMI and CEUS is valuable in distinguishing malignant from benign solid breast masses, and US vascular parameters are associated with histologic MVD.
Area Under Curve ; Biopsy ; Breast Neoplasms ; Breast ; Estrogens ; Information Systems ; Microvessels ; Perfusion ; Prospective Studies ; ROC Curve ; Ultrasonography

PURPOSE: To evaluate the effect of periosteal fixation in patients with large-angle paralytic strabismus that was not corrected through conventional strabismus surgery. METHODS: Four eyes of three patients with large-angle paralytic strabismus who underwent periosteal fixation from June 2014 to August 2014 were examined. All patients presented with exotropia > 50 prism diopters (PD). Two of them showed exotropia caused by chronic complete oculomotor nerve palsy; the other two showed exotropia caused by medial rectus muscle injury during endoscopic sinus surgery. RESULTS: The mean preoperative exodeviation using the Krimsky test was 58 ± 29 PD. The postoperative values were 6.5 ± 9.4 PD at 1 week, and 11.25 ± 2.5 PD at 6 months. The mean surgical effect of exodeviation was 43.75 ± 21.36 PD. CONCLUSIONS: Periosteal fixation is an effective surgery for the management of paralytic strabismus that was not corrected through conventional strabismus surgery.
Exotropia ; Humans ; Oculomotor Nerve Diseases ; Strabismus