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.

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.

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.

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.

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.

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.

Causes and Surgical Outcomes of Lower Eyelid Retraction.

PURPOSE: To investigate the causes of lower eyelid retraction and evaluate the outcomes of various surgical procedures. METHODS: We conducted a retrospective medical record review of patients who underwent lower eyelid retraction surgery performed by a single surgeon at Kim's Eye Hospital between 2006 and 2013. We investigated the causes of lower eyelid retraction, clinical history, characteristics, treatment, and surgical outcomes. Preoperative and postoperative margin reflex distance 2 and inferior scleral show were measured for each eyelid. Success was defined as a positive eyelid elevation and a decrease in inferior scleral show. RESULTS: A total of 19 lower eyelids were treated in 14 patients with lower eyelid retraction. For cosmetic reasons, surgical correction for congenital lower eyelid retraction was performed on seven eyelids (36.8%). Ten eyelids (52.6%) exhibited secondary lower eyelid retraction after surgery. One eyelid (5.3%) was affected by facial palsy and one eyelid (5.3%) exhibited exophthalmos of an unknown origin. We adopted a selective approach based on lower eyelid retraction severity. Spacer grafting via a subconjunctival approach was the most commonly performed surgical technique (13 eyelids, 68.4%). The lateral tarsal strip procedure was used to horizontally tighten three eyelids (15.8%). At the time of the procedure, one of these eyelids (5.3%) also received an adjuvant suborbicularis oculi fat lift. Autogenous dermis fat grafting was performed on two lower eyelids (10.5%), whose retraction was caused by fat and soft tissue loss. Cosmetic outcomes were satisfactory in all cases. CONCLUSIONS: To achieve satisfactory surgical outcomes, surgeons should adopt an approach based on the severity of lower eyelid retraction. Mild lower eyelid retraction can be corrected without grafts. When retraction is severe and exceeds 2 mm, spacer grafts that push the lower eyelid margin upwards and support it from below are required.

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.

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.

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.

Differences in interpalpebral fissure measurement in patients with unilateral enophthalmos resulting from orbital wall fractures.

PURPOSE: To determine the correlation between the degree of enophthalmos and interpalpebral fissure (IPF) measurements in a group of patients with unilateral orbital wall fractures. MATERIALS AND METHODS: The medical charts of 45 patients diagnosed with unilateral enophthalmos resulting from an orbital wall fracture were reviewed. Demographic characteristics were investigated, including patient age, sex, medical history, and type of orbital wall fracture. The correlation between the degree of enophthalmos and IPF was determined, adjusting for confounding demographic factors. RESULTS: In the group with orbital wall fractures, the correlation between the degree of enophthalmos and the IPF measurements was positive and significant (R = 0.299, p = 0.046, Pearson's correlation). The correlation coefficient increased after adjusting for age, sex, medical history, and type of orbital wall fracture (R = 0.316, p = 0.044). CONCLUSION: The patient group with more severe enophthalmos tended to have lower IPF values.

CD133 confers cancer stem-like cell properties by stabilizing EGFR-AKT signaling in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the seventh most common malignant tumor and the third leading cause of cancer-related death in the world. Cancer stem cells (CSCs) are small subpopulation of cells within tumors that drive chemoresistance and tumor recurrence in various cancers. We characterized CSCs in primary HCC and identified CD133 as a CSC surface marker. CD133+ HCC cells displayed more stem cell-like properties, tumor spheroid-forming ability, chemoresistance, migration ability, and tumorigenic capacity than CD133- HCC cells. The biological function and molecular mechanism of CD133 remain unclear. HCC cell lines with a high level of CD133 expression overexpressed EGFR, which is overexpressed in approximately 70% of conventional HCCs. CD133 depletion destabilized EGFR by augmenting EGFR internalization and thus inhibited EGFR-AKT signaling. CD133 would therefore serve to sustain aberrant EGFR-mediated oncogenic signaling. Furthermore, EGFR-deficient CD133+ HCC cells manifested greater sensitivity to anticancer drugs and less spheroid-formation capacity than control CD133+ HCC cells. Our results strongly indicate that CD133 facilitates CSC-like properties by stabilizing EGFR-AKT signaling in HCC. It might therefore be feasible to use CD133 as a novel target to sensitize HCC cells that manifest resistance to EGFR-targeted therapy.

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.

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.

Preoperative Computed Tomography Findings for Patients with Nasolacrimal Duct Obstruction or Stenosis.

PURPOSE: To identify and analyze the role of preoperative computed tomography (CT) in patients with tearing symptoms with nasolacrimal duct obstruction (NLDO). METHODS: We retrospectively reviewed the medical records and CT results on 218 patients who complained of tearing symptoms with NLDO between January 2014 and December 2014. All patients were recruited from Kim's Eye Hospital's outpatient clinic and assessed by clinical history, examination, and CT to evaluate periocular pathology and nasolacrimal drainage system. Patients with abnormal findings assessed by preoperative CT were further reviewed. RESULTS: CT was performed on 218 patients (average age, 58.2 ± 11.9 years). Of these, 196 (89.9%) had endonasal dacryocystorhinostomy, 14 (6.4%) declined surgery, and 8 (3.7%) were inoperable due to abnormal CT findings. Soft tissue opacity was the most common finding which 243 cases (85.9%) of 283 obstructed nasolacrimal duct and 89 cases (81.7%) of 109 non-obstructed nasolacrimal duct showed it. Thirty-nine (17.8%) of 218 patients showed either maxillary sinusitis or ethmoidal sinusitis and 32 (14.7%) of 218 patients presented with periocular inflammation. Other abnormal CT findings included septal deviations, previous fractures, masses, and structural abnormalities of nasal cavity. CONCLUSIONS: Preoperative CT imaging is useful in the assessment of both nasolacrimal drainage and nearby anatomical structures. This information will be helpful in planning surgical interventions and management of NLDO.

Predictors of Silicone Tube Intubation Success in Patients with Lacrimal Drainage System Stenosis.

PURPOSE: To evaluate prognostic factors affecting silicone tube intubation outcomes in Asian patients with lacrimal drainage system stenosis. METHODS: A retrospective review was conducted on the medical records of 822 patients (1,118 eyes) who had undergone silicone tube intubation to treat lacrimal drainage system stenosis between January 2011 and December 2012. Patients were divided into two groups: a success group and a failure group. Success was defined as the disappearance of epiphora symptoms, normalization of tear meniscus height, and the easy passage of fluid without resistance on the postoperative syringing test. Patient and ocular parameters were compared between the success and failure groups. RESULTS: A total of 994 eyes of 727 patients were included in analyses. Patients had a mean follow-up period of 34.11 ± 18.70 weeks. Silicone tube intubation was successful in 67.2% of participants. Significant differences between the success and failure groups were found for age (p < 0.001), history of ipsilateral facial palsy (p = 0.028), follow-up period (p < 0.001), and degree of passage on the preoperative syringing test (p = 0.001). Only age (p < 0.001) and degree of passage on the preoperative syringing test (p = 0.002) remained significantly associated with silicone tube intubation success in multivariate analysis. CONCLUSIONS: Age was negatively associated with silicone tube intubation success in patients with lacrimal drainage system stenosis. The success rate was higher in patients who showed easy passage of fluid without resistance on the preoperative syringing test. These factors should be considered by surgeons planning silicone tube intubation in patients with lacrimal drainage system stenosis.

Surgical Outcomes of Canalicular Trephination Combined with Endoscopic Dacryocystorhinostomy in Patients with Distal or Common Canalicular Obstruction.

PURPOSE: This study investigated the surgical outcomes of canalicular trephination combined with endoscopic dacryocystorhinostomy (DCR) in patients with a distal or common canalicular obstruction. It also identified the factors affecting surgical success rates associated with this technique. METHODS: We retrospectively reviewed the medical records of 57 patients (59 eyes) in whom a canalicular obstruction was encountered during endoscopic DCR. All patients were treated with endoscopic DCR, followed by canalicular trephination and silicone tube placement. The surgical outcome was categorized as a functional success according to the patient's subjective assessment of symptoms, including epiphora, and as an anatomical success according to a postoperative nasolacrimal duct irrigation test. Surgical success rates were compared based on age, sex, location of the obstruction, number of silicone tubes, and experience of the surgeon. RESULTS: Functional success was achieved in 55 of 59 eyes (93%) at one month, 50 eyes (84%) at three months, and 46 eyes (78%) at six months. Anatomical success was achieved in 58 of 59 eyes (98%) at one month, 52 eyes (88%) at three months, and 50 eyes (84%) at six months. There was a statistically significant difference in surgical outcome according to the experience of the surgeon. The anatomical success rate at the six-month follow-up exam was 95.4% in the >5 years of experience group, and 53.3% in the <5 years of experience group (p = 0.008, Pearson chi-square test). CONCLUSIONS: The success rate of canalicular trephination combined with endoscopic DCR in patients with a distal or common canalicular obstruction decreased gradually during the six-month follow-up period. In particular, patients undergoing procedures with experienced surgeons tended to show excellent surgical outcomes at the six-month follow-up exam.

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.