The Causes and Management of Asymmetrical Double Eyelids.

Blepharoplasty is a commonly performed aesthetic surgery, especially in Asians. Nevertheless, as in all surgeries, postoperative complications still occur. Asymmetry is the most common complication after double eyelid surgery. Preexisting asymmetries in patient appearance and technical faults during surgery are associated with postoperative asymmetrical double eyelids. In this review, we discuss how to prevent unfavorable outcomes after this procedure and how to manage asymmetrical double eyelids when they do occur.

Medial Epicanthoplasty: What Works and What Does Not.

Blepharoplasty is the most frequently performed cosmetic surgical procedure in Asia. The epicanthal fold, which is common in Asians, is characterized by a curved skin fold that partially hides the caruncle and lacrimal lake. The epicanthal fold may cause weakening of the esthetic appearance after blepharoplasty. It makes the palpebral fissure height narrower and the length shorter horizontally. Blepharoplasty with epicanthoplasty can enhance the esthetic appearance, but no gold standard surgical technique has been established for epicanthoplasty. Surgeons can choose the surgical technique according to their preference and the patient's characteristics. A carefully designed and fine surgical technique, especially with the use of loupes and tension-free skin closure with the thinnest needle, is required to avoid scarring.

Distribution of Adrenergic Receptor Subtypes and Responses to Topical 0.5% Apraclonidine in Patients With Blepharoptosis.

PURPOSE: To determine the relationship between the distribution of adrenergic receptors in the human eyelid and the eyelid elevation after topically instilling 0.5% apraclonidine in blepharoptosis patients. METHODS: A total of 26 blepharoptotic patients (30 eyelids) were included in the experimental study. Marginal reflex distance 1 was measured before and after topical instillation of 0.5% apraclonidine. Eyelids were divided into 2 groups according to the responses to topical 0.5% apraclonidine. Patients who positively responded to apraclonidine were classified as group A and those that negatively responded to it were classified as group B. Müller's muscle was obtained during the blepharoptotic surgery, followed by immunohistochemical staining and scoring. This study was approved by the Institutional Review Board of Kim's Eye Hospital and the study protocol adhered to the tenets of the Declaration of Helsinki. RESULTS: α-1D staining intensity was significantly higher in group A than in B (p < 0.001) and α-2C and ß-1 staining intensities were significantly higher in group B than in A (p < 0.001 and p < 0.05, respectively). The difference in ß-2 staining intensity between groups A and B was not statistically significant. CONCLUSIONS: α-1D adrenoceptor was predominant in patients showing a positive response to topical 0.5% apraclonidine. Because apraclonidine has an α-1 agonistic effect, α-1D adrenoceptor may contribute to apraclonidine's elevating effect in patients with blepharoptosis.

Asymmetry of Preoperative Incision Design Markings for Upper Blepharoplasty.

PURPOSE: To compare preoperative incision design markings between both eyelids in upper blepharoplasty. METHODS: This retrospective study examined 22 patients who underwent bilateral upper blepharoplasty surgery resulting from senile dermatochalasis and/or blepharoptosis. The initial preoperative incision design markings were drawn with the patient sitting upright. Then, with the patient in a supine position, preoperative design photographs were taken. The authors measured medial canthal excision angle, maximal lid excision height, maximal lid excision width, peak point angle, and peak point distance and compared measurements between both upper eyelids designs using Image J software. RESULTS: The mean medial canthal excision angle, maximal lid excision height, and maximal lid excision width for the right side (30.68°â€Š±â€Š10.16°, 1.17 ±â€Š0.24 cm, and 0.72 ±â€Š0.19 cm) were significantly different from those for the left side (35.39°â€Š±â€Š13.82°; P < 0.001, 1.24 ±â€Š0.25 cm; P = 0.002, and 0.77 ±â€Š0.21 cm; P = 0.011). The mean peak point angle and peak point distance for the right side (15.67°â€Š±â€Š5.09°, 2.41°â€Š±â€Š0.31°) were significantly different from those for the left side (18.11°â€Š±â€Š5.49°; P = 0.001, 2.22 ±â€Š0.28 cm; P = 0.001). CONCLUSIONS: In upper blepharoplasty, the preoperative incision marking design measurements of the left side were significantly greater than those of the right side. The symmetry can therefore be maximized by including the asymmetries in the preoperative design.

Fbxo25 controls Tbx5 and Nkx2-5 transcriptional activity to regulate cardiomyocyte development.

The ubiquitin-proteasome system (UPS) plays an important role in protein quality control, cellular signalings, and cell differentiation through the regulated turnover of key transcription factors in cardiac tissue. However, the molecular mechanism underlying Fbxo25-mediated ubiquitination of cardiac transcription factors remains elusive. We report that an Fbxo25-mediated SCF ubiquitination pathway regulates the protein levels and activities of Tbx5 and Nkx2-5 based on our studies using MG132, proteasome inhibitor, and the temperature sensitive ubiquitin system in ts20 cells. Our data indicate that Fbxo25 directly interacts with Tbx5 and Nkx2-5 in vitro and in vivo. In support of our findings, a dominant-negative mutant of Fbxo25, Fbxo251-236, prevents Tbx5 degradation and increases Tbx5 transcriptional activity in a Tbx5 responsive luciferase assay. Therefore, Fbxo25 facilitates Tbx5 degradation in an SCF-dependent manner. In addition, the silencing of endogenous Fbxo25 increases Tbx5 and Nkx2-5 mRNA levels and suppresses mESC-derived cardiomyocyte differentiation. Likewise, the exogenous expression of FBXO25 downregulates NKX2-5 level in human ESC-derived cardiomyocytes. In myocardial infarction model, Fbxo25 mRNA decreases, whereas the mRNA and protein levels of Tbx5 and Nkx2-5 increase. The protein levels of Tbx5 and Nkx2-5 are regulated negatively by Fbxo25-mediated SCF ubiquitination pathway. Thus, our findings reveal a novel mechanism for regulation of SCFFbox25-dependent Nkx2-5 and Tbx5 ubiquitination in cardiac development and provide a new insight into the regulatory mechanism of Nkx2-5 and Tbx5 transcriptional activity.

Hepatocellular carcinoma-targeted drug discovery through image-based phenotypic screening in co-cultures of HCC cells with hepatocytes.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignant cancers worldwide and is associated with substantial mortality. Because HCCs have strong resistance to conventional chemotherapeutic agents, novel therapeutic strategies are needed to improve survival in HCC patients. METHODS: Here, we developed a fluorescence image-based phenotypic screening system in vitro to identify HCC-specific drugs in co-cultures of HCC cells with hepatocytes. To this end, we identified two distinctive markers of HCC, CHALV1 and AFP, which are highly expressed in HCC cell lines and liver cancer patient-derived materials. We applied these markers to an HCC-specific drug screening system. RESULTS: Through pilot screening, we identified three anti-folate compounds that had HCC-specific cytotoxicity. Among them, pyrimethamine exhibited the greatest HCC-specific cytotoxicity. Interestingly, pyrimethamine significantly increased the size and number of lysosomes and subsequently induced the release of cathepsin B from the lysosome to the cytosol, which triggered caspase-3-dependent apoptosis in Huh7 (HCC) but not Fa2N-4 cells (immortalized hepatocytes). Importantly, Fa2N-4 cells had strong resistance to pyrimethamine relative to Huh7 cells in 2D and 3D culture systems. CONCLUSION: These results demonstrate that this in vitro image-based phenotypic screening platform has the potential to be widely adopted in drug discovery research, since we promptly estimated anticancer activity and hepatotoxicity and elucidated functional roles of pyrimethamine during the apoptosis process in HCC.

Patients With Lower Eyelid Orbital Fat Hyperplasia.

PURPOSE: Lower eyelid orbital fat hyperplasia has not been described in young age patients. METHODS: A fourteen-year-old girl, a 29-year-old man, and 42-year-old man had visited our hospital complaining of a lower eyelid bulge. In orbital computed tomography examination, there was excess fat tissue compared with the opposite side, but no mass lesion matched with the area of lower eyelid bulge in our patients. The authors planned surgery for the removal of excess fat through the conjunctival incision. Intraoperatively, there was no real fat herniation through the septum. Septum continuity was maintained and thinning or distention of the orbital septum was not observed in our patients. The authors opened the orbital septum and removed the excess fat to make symmetry bilaterally. In the pathologic examination, removed fat tissue is not different with normal fat tissue. CONCLUSIONS: The authors reported these findings at the first time. So they proposed the patient's condition as "lower eyelid orbital fat hyperplasia."

Comparison Between Continuous Buried Suture and Interrupted Buried Suture Methods for Double Eyelid Blepharoplasty.

PURPOSE: The objective of this study was to compare the surgical outcomes between interrupted and continuous buried suture methods in double eyelid blepharoplasty in Koreans. METHODS: Medical records of 204 patients (392 eyes) who underwent double eyelid operation by buried suture method and who were followed up for at least more than 3 months were reviewed. Patients were divided into 2 groups according to the buried suture method; an interrupted group (88 patients) and a continuous group (116 patients). RESULTS: The rate of loss of formed double eyelid is 19.3 % (17 of 88 patients) in interrupted buried method and 8.6 % (10 of 116 patients) in continuous group (P = 0.026). One patient experienced an exposure of suture knot in a continuous group, whereas 5 patients experienced an exposure of suture knot and 1 patient suffered from granuloma in an interrupted group (P = 0.021). CONCLUSIONS: The continuous buried suture method has a lower rate of the loss of double folds and less complication than the interrupted buried suture method for double fold formation in Koreans.

Loss of reflex tearing after maxillary orthognathic surgery: a report of two cases.

BACKGROUND: Few reports have described the ophthalmic complications that occur after maxillary orthognathic surgery. Since cases of decreased reflex tearing after maxillary orthognathic surgery are extremely rare, we describe 2 cases of loss of reflex tearing after maxillary orthognathic surgery. CASE PRESENTATION: Two Asian women, an 18-year-old and a 32-year-old, suffered from unilateral dryness and irritation caused by maxillary orthognathic surgery. In both patients, Schirmer test (II) showed reduced reflex tearing in 1 eye. Computed tomography showed that the pterygoid plate had been fractured in both patients. CONCLUSIONS: The pterygopalatine ganglion and its associated fibers in the pterygopalatine fossa may be injured during Le Fort osteotomy.

Nasolacrimal duct obstruction after maxillary orthognathic surgery.

PURPOSE: To report cases of nasolacrimal duct obstruction (NLDO) after maxillary orthognathic surgery. MATERIALS AND METHODS: The authors reviewed the clinical manifestations, dacryocystographic images, and orbital computed tomographic scans of 10 patients who were diagnosed with NLDO after undergoing maxillary orthognathic surgery. RESULTS: Six of the 10 patients (60%) complained of epiphora immediately after the surgery. Bilateral (n = 2, 20%) or unilateral (n = 8, 80%) NLDO occurred in all patients involved in the study. Twelve eyes of 10 patients were examined, and dacryocystography showed that the obstruction was present in the distal ostium in 7 eyes (58.3%), the junction between the sac and duct in 3 eyes (25%), and the common canaliculus in 2 eyes (16.7%). Computed tomographic scans of all subjects showed that mucosal swelling and congestion around the distal NLD opening narrowed the space between the lateral nasal wall and the inferior turbinate of the affected side. Dacryocystorhinostomy was performed in 9 eyes (8 patients), with a success rate of 100%. CONCLUSIONS: The distal to proximal portion of the NLD can become obstructed after maxillary orthognathic surgery. This obstruction seems to be caused by secondary inflammatory changes associated with an indirect injury of the NLD. Therefore, clinicians should be aware of the possibility of NLDO after orthognathic surgery, which can be treated successfully with dacryocystorhinostomy.

A novel Fbxo25 acts as an E3 ligase for destructing cardiac specific transcription factors.

Alterations in ubiquitin-proteasome system (UPS) have been implicated in the etiology of human cardiovascular diseases. Skp1/Cul1/F-box (SCF) ubiquitin E3 ligase complex plays a pivotal role in ubiquitination of cardiac proteins. However, a specific ubiquitin E3 ligase responsible for the destruction of cardiac transcription factors such as Nkx2-5, Isl1, Mef2C, and Tbx5 remains elusive to date. Here, we show that a novel F-box containing Fbxo25 is cardiac-specific and acts as an ubiquitin E3 ligase for cardiac transcription factors. Fbxo25 expression was nuclei-specific in vitro and cardiomyocytes. Expression level of Fbxo25 was higher in a fetal heart than an adult. Moreover, Fbxo25 expression was increased along with those of cardiac-specific genes during cardiomyocyte development from ESCs. Fbxo25 expression facilitated protein degradation of Nkx2-5, Isl1, Hand1, and Mef2C. Especially, Fbxo25 ubiquitinated Nkx2-5, Isl1, and Hand1. Altogether, Fbxo25 acts as an ubiquitin E3 ligase to target cardiac transcription factors including Nkx2-5, Isl1, and Hand1, indicating that cardiac protein homeostasis through Fbxo25 has a pivotal impact on cardiac development.

Nonincisional Blepharoplasty for Asians.

Various nonincisional techniques for double eyelid surgery have been introduced in the past. They are simple, noninvasive, and efficient techniques to create a double eyelid. The authors prefer the full-thickness single continuous method using the 7-0 nylon, round long needle. Appropriate choice of the patients and surgical method results in a natural, esthetically pleasing eyelid and decreases the loss of eyelid crease.

Nonmuscle myosin IIB regulates Parkin-mediated mitophagy associated with amyotrophic lateral sclerosis-linked TDP-43.

C-terminal fragments of Tar DNA-binding protein 43 (TDP-43) have been identified as the major pathological protein in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). However, how they affect cellular toxicity and neurodegeneration, including the modulation process remains unknown. This study revealed that the C-terminal fragment of TDP-43 (TDP-25) was localized primarily to mitochondria and caused abnormal mitochondrial morphology, inducing Parkin-mediated mitophagy. Also, we discovered that the knockdown of selective autophagy receptors, such as TAX1BP, Optineurin, or NDP52 caused TDP-25 accumulation, indicating that TDP-25 was degraded by mitophagy. Interestingly, myosin IIB, a nonmuscle type of myosin and actin-based motor protein, is mostly colocalized to TDP-25 associated with abnormal mitochondria. In addition, myosin IIB inhibition by siRNA or blebbistatin induced mitochondrial accumulation of insoluble TDP-25 and Tom20, and reduced neuronal cell viability. Our results suggest a novel role of myosin IIB in mitochondrial degradation of toxic TDP-25. Therefore, we proposed that regulating myosin IIB activity might be a potential therapeutic target for neurodegenerative diseases associated with TDP-43 pathology.

A case of congenital orbital malignant rhabdoid tumor: systemic metastasis following exenteration.

A newborn girl presented with massive proptosis of the right eye. Physical and radiologic examination disclosed that the primary orbital mass was confined to the site. A diagnosis of malignant rhabdoid tumor was made by histopathologic examination of an incisional biopsy specimen. Exenteration was performed, and the resection margins were free from tumor cells. However, distant metastasis developed in the liver 1 month after surgery. Despite chemotherapy, the patient died 2 months later due to tumor invasion into the central nervous system, which was confirmed by autopsy. To the best of our knowledge, this is the first case of congenital orbital malignant rhabdoid tumor showing systemic metastasis after exenteration, which suggests the need for aggressive systemic treatment rather than exenteration, even in a case of locally confined tumor.

Metabolic Engineering of Saccharomyces cerevisiae for Production of Shinorine, a Sunscreen Material, from Xylose.

Shinorine, a mycosporine-like amino acid (MAA), is a small molecule sunscreen produced in some bacteria. In this study, by introducing shinorine biosynthetic genes from cyanobacteria Nostoc punctiform into Saccharomyces cerevisiae, we successfully constructed yeast strains capable of producing shinorine. Sedoheptulose 7-phosphate (S7P), an intermediate of the pentose phosphate pathway, is a key substrate for shinorine biosynthesis. To increase the S7P pool, xylose, which is assimilated via the pentose phosphate pathway, was used as a carbon source after introducing xylose assimilation genes from Scheffersomyces stipitis into the shinorine-producing strain. The resulting xylose-fermenting strain produced a trace amount of shinorine when cells were grown in glucose, but shinorine production was dramatically increased by adding xylose in the medium. Shinorine production was further improved by modulating the pentose phosphate pathway through deleting TAL1 and overexpressing STB5 and TKL1. The final engineered strain JHYS17-4 produced 31.0 mg/L (9.62 mg/g DCW) of shinorine in the optimized medium containing 8 g/L of xylose and 12 g/L of glucose, demonstrating that S. cerevisiae is a promising host to produce this natural sunscreen material.

Clinical Features of Benign Essential Blepharospasm in Korean Patients.

PURPOSE: To analyze the clinical features of benign essential blepharospasm in Korean patients. METHODS: Patients diagnosed with benign essential blepharospasm in Kim's Eye Hospital from November 2014 to December 2016 were evaluated using a clinical examination and questionnaire. The questionnaire reviewed personal medical history, demographic factors, risk factors for blepharospasm development, and relieving and aggravating factors. RESULTS: Of the 101 patients enrolled, 78 (77.2%) were women. The mean age was 64.9 years old. Hypertension was the most common medical disorder (42.6%), followed by diabetes mellitus. The majority of the patients were non-smokers (83.2%) and drank less than a cup of a caffeinated beverage a day (30.7%). Fifty-seven percent of patients reported no stressful events immediately prior to symptom development. Fatigue and stress were aggravating factors in more than 55% of patients; rest was the most common relieving factor (35.6%). CONCLUSIONS: Here, we report the clinical features of benign essential blepharospasm in Korean patients for the first time. The results were consistent with previous reports showing that the majority of benign essential blepharospasm patients are women and non-smokers. In contrast to previous reports though, fatigue and stress were aggravating factors, and the most common relieving factor was rest. No stressful events had immediately preceded the development of blepharospasm in 57.4% of patients. This report may aid in treating and counseling patients with benign essential blepharospasm.

Comparison of the Efficacies of 0.94 mm and Double Silicone Tubes for Treatment of Canalicular Obstruction.

PURPOSE: To compare the clinical effects of the single wide-diameter bicanalicular silicone tube and the double bicanalicular silicone tube in endonasal dacryocystorhinostomy (DCR) with canalicular trephinization for canalicular obstruction. METHODS: We retrospectively reviewed the records of 121 patients with monocanalicular or common canalicular obstruction who had undergone endonasal DCR with random bicanalicular insertion of either double silicone tubes (insertion of two tubes into each canaliculus) or a single wide-diameter (0.94 mm) silicone tube. The tubes were removed at around 3 months after surgery. RESULTS: This study included 79 eyes of 61 patients in the double-tube intubation group and 68 eyes of 60 patients in the single wide-diameter tube intubation group. Anatomical success, evaluated by syringing, was achieved in 72 of the 79 eyes (91.1%) in the double-tube intubation group and 60 of the 68 eyes (88.2%) in the single wide-diameter tube intubation group. Functional success was achieved in 65 of the 79 eyes (82.3%) in the double-tube intubation group and 61 of the 68 (89.7%) eyes in the single wide-diameter tube intubation group. There were no significant differences in the success rates of surgery between the two groups. One patient in the double-tube intubation group underwent conjunctivodacryocystorhinostomy (CDCR) and two in the wide-diameter tube intubation group underwent CDCR or reintubation to treat recurrence. CONCLUSIONS: Intubation using a single wide-diameter tube during endonasal DCR is as effective as double-tube intubation for the treatment of canalicular obstruction, with a lower rate of complications such as inflammation or patient discomfort.

Potential mechanisms of CD133 in cancer stem cells.

Cancer stem cells (CSCs) have emerged as an underlying cause of cancer relapse and resistance to treatment. Initially, biomarkers were used to identify and isolate distinct cell populations. Several CSC markers have been identified from many types of tumors, and these markers are also being used for isolation and enrichment of CSCs. Cluster of differentiation CD133 is a well-characterized CSC marker, and it is involved in tumor cell proliferation, metastasis, tumorigenesis, and recurrence, as well as chemo- and radio-resistance. However, the mechanisms involved in CD133-mediated induction of CSC properties have not yet been elucidated. Here, we introduce and summarize the functions of CD133 in CSCs and suggest new mechanisms that may be of note in our approach to developing novel cancer therapies.

Cause and Management of Patients With Failed Endonasal Dacryocystorhinostomy.

OBJECTIVES: Endonasal dacryocystorhinostomy (DCR) is a well-established treatment method in patients with nasolacrimal duct obstruction. However, there are a few reports about the overall management of failed endonasal DCR. We investigated the causes and management strategies of failed endonasal DCR. METHODS: This retrospective review included 61 patients (61 eyes) who had undergone revision surgery by the same surgeon after failed endonasal DCR between January 2008 and December 2012. The appropriate revision method was determined after analysis of the etiology of failure by the fluorescein dye disappearance test, nasal endoscopy, lacrimal irrigation, and probing. The criteria for success of the revision surgery were defined by the passage of fluid without resistance upon lacrimal irrigation and normalization of the tear meniscus height. RESULTS: The mean duration between the primary endonasal DCR and revision surgery was 15.3 months. The average follow-up period after revision surgery was 12.2 months. The most common cause of endoscopic revision surgery was membranous obstruction. Endoscopic revision surgery was performed in 48 patients, while lacrimal silicone tube intubation under endoscopy was performed in 13 patients. The most common indication for lacrimal silicone tube intubation was functional epiphora. The overall success rate of the revision surgery was 89%. CONCLUSION: The most common cause of failed endonasal DCR was membranous obstruction. When patients with failed endonasal DCR presented at the clinic, it is important to identify the cause of the failure. Revision surgery could increase the final success rate of endonasal DCR.