Finding the Common Single-Nucleotide Polymorphisms in Three Autoimmune Diseases and Exploring Their Bio-Function by Using a Reporter Assay.

In clinical practice, it is found that autoimmune thyroid disease often additionally occurs with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In addition, several studies showed that eye-specific autoimmune diseases may have a strong relationship with systemic autoimmune diseases. We focused on Graves' disease (GD) with ocular conditions, also known as Graves' ophthalmopathy (GO), trying to find out the potential genetic background related to GO, RA, and SLE. There were 40 GO cases and 40 healthy controls enrolled in this study. The association between single-nucleotide polymorphisms (SNPs) of the co-stimulatory molecule genes and GO was analyzed using a chi-square test. It showed that rs11571315, rs733618, rs4553808, rs11571316, rs16840252, and rs11571319 of CTLA4, rs3181098 of CD28, rs36084323 and rs10204525 of PDCD1, and rs11889352 and rs4675379 of ICOS were significantly associated with GO based on genotype analysis and/or allele analysis (p < 0.05). After summarizing the GO data and the previously published SLE and RA data, it was found that rs11571315, rs733618, rs4553808, rs16840252, rs11571319, and rs36084323 were shared in these three diseases. Furthermore, the bio-function was confirmed by dual-luciferase reporter assay. It was shown that rs733618 T > C and rs4553808 A > G significantly decreased the transcriptional activity (both p < 0.001). This study is the first to confirm that these three diseases share genetically predisposing factors, and our results support the proposal that rs733618 T > C and rs4553808 A > G have bio-functional effects on the transcriptional activity of the CTLA4 gene.

Ocular circulation change in optic disc melanocytoma - a case report and a review of the literature.

BACKGROUND: Ocular circulation in optic disc melanocytoma (ODM) has not yet been well evaluated. We quantitatively evaluated longitudinal changes in the morphology and circulation hemodynamics of the disc and macula using optical coherence tomography angiography (OCTA) and laser speckle flowgraphy (LSFG) in a patient with optic disc melanocytoma. CASE PRESENTATION: A 50-year-old woman was referred to our hospital due to a dark pigmented tumor over the superior optic disc area of the left eye noted on physical examination. At the first visit, the patient's best-corrected visual acuity (BCVA) was 20/20 in both eyes, and the intraocular pressure (IOP) was 17 and 18 mmHg in the left and right eyes, respectively. Fluorescein angiography (FA) showed blockage of fluorescence in the topography of the lesion, and indocyanine green angiography (ICGA) showed hypofluorescence at all times. On LSFG, a low mean blur rate (MBR) was noted in the optic disc all area (MBRa) and tissue (MBRt) compared to the contralateral eye at the first visit and at the 3-month follow-up. A relatively low MBR was also detected in the macular area of the affected eye and the tumor itself. OCTA detected blood vessel networks in the deep retinal layer of the tumor. The visual field showed no specific defects. During follow-up, there was no tumor enlargement or vision decrease. CONCLUSIONS: We found that a lower MBR of the disc and macula area was noted on LSFG in this patient with optic disc melanocytoma, and it was continually observed at the 3-month follow-up. Although blood vessel networks in the deep retinal layer of the tumor were detected by OCTA, vascular compromise in the surrounding disc area and macula was found. Therefore, these results further increase our knowledge about the role that circulation impairment plays in the pathogenesis of the disease while vision is unaffected.

Using A modified quickert procedure combined with prolapsed fat and preseptal orbicularis muscle removal to correct involutional lower eyelid entropion in Asians.

PURPOSE: To propose a modified Quickert procedure combined with prolapsed fat and preseptal orbicularis muscle removal which corrects involutional lower eyelid entropion, and to validate the procedure as an adequate surgical management according to anatomical deformities and pathogenesis of Asian patients. METHODS: Ninety-five patients (45 men, 50 women; 108 eyelids [55 right eyes, 53 left eyes]) who underwent this modified surgical procedure with a minimum follow-up period of 2 months were examined. All pre- and post-operative evaluations and surgical procedure were performed exclusively from the same oculoplastic surgeon. Postoperative results, recurrence rate, and complications were assessed. RESULTS: The mean follow-up period was 13.33 months (range, 2-67 months). Of the 108 eyelids, 4 developed recurrent entropion with trichiasis, corresponding to an overall recurrence rate of 3.70%. No major complications, such as overcorrection (ectropion), symblepharon, infection, or wound dehiscence, occurred during the follow-up period after surgery. Of these 4 eyelids exhibiting recurrence, 3 occurred within 10 months and 1 occurred 49 months after surgery. Three recurrent patients received secondary surgery for re-correction with successful results. CONCLUSION: The modified Quickert procedure combined with prolapsed fat and preseptal orbicularis muscle removal not only demonstrated safety and effectiveness, but also led to low rate of recurrence and complications. It could be a strategy for correction of involutional entropion in Asian patients.

Evaluation of Microcirculation in Optic Nerve Head Using Laser Speckle Flowgraphy in Active Thyroid Eye Disease.

Background: Laser speckle flowgraphy (LSFG) can be used to estimate optic nerve blood flow. This study used LSFG to evaluate optic nerve microcirculation in patients with thyroid eye disease (TED). Methods: This was a retrospective review of patients with active TED who underwent LSFG between October 2020 and June 2021. The mean blur rate (MBR) for different severities of active TED was analyzed by one-way analysis of variance (ANOVA). Results: A total of 30 patients (60 eyes) with a diagnosis of active TED who underwent LSFG were included. The mean age was 49 (range, 33-74) years. Mean best-corrected visual acuity was the worst in the group with sight-threatening active TED (0.29 ± 0.33 logarithm of the minimum angle of resolution, p = 0.01). The MBR-overall was the highest in the group with mild active TED (28.5 ± 2.7), followed by that in the moderate to severe (23.6 ± 3.2), and in the sight-threatening (20.2 ± 4.3) active TED groups (p < 0.001). The MBR-vessel was 57.1, 47.0, and 39.3 in the mild, moderate to severe, and sight-threatening active TED groups, respectively (p < 0.001). The MBR-tissue was 16.9, 14.4, and 12.0 in the mild, moderate to severe, and sight-threatening active TED groups, respectively (p < 0.001). Conclusions: This study demonstrates that optic nerve blood flow is lower with more severe active TED. In addition, LSFG is an effective, objective, and noninvasive method for evaluating the severity of TED.

Efficacy of modified levator-muscle resection using Putterman ptosis clamp versus traditional levator-muscle resection for aponeurotic ptosis: A retrospective analysis.

BACKGROUND/OBJECTIVES: In recent years, a modified levator muscle resection using Putterman ptosis clamp was developed. We used a retrospective case-control study to compare the effects of the modified and traditional levator muscle resection methods. METHODS: Patients with moderate-to-severe ptosis who underwent the traditional or modified method for levator muscle resection were divided into two groups: Group I received the traditional method in 2013 and Group II received the modified method using Putterman clamp in 2015. During each postoperative visit, in addition to imaging, changes in the margin reflex distance 1 (MRD 1), and adverse events were recorded. Surgical time and final result in the last follow-up were recorded. RESULTS: Group I had 35 patients (54 eyes) and Group II had 33 patients (59 eyes). After the surgery, the MRD 1 in both groups was significantly improved at 1 week and at the final visit compared to baseline. Significant differences were observed in MRD 1 change at 1-week post-operation and the change at the final visit and the surgical time between Groups I and II (P < 0.05). Group II had a shorter surgical time than Group I. Compared with Group I (20.37%), the revision rate was lower in Group II (10.16%). CONCLUSIONS: The modified levator muscle resection using Putterman ptosis clamp and traditional levator muscle resection can both improve ptosis. Comparison results showed that using Putterman ptosis clamp assisted in levator muscle surgery had shorter operation time, faster postoperative recovery, and lower revision rate than the traditional method. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Conjunctival melanoma: A 20-year survey in a comprehensive medical center.

BACKGROUND: To better understand population-specific tumor characteristics and behavior of conjunctival melanoma in Asian. METHODS: A retrospective cohort enrolled patients with primary conjunctival melanoma treated and followed up at Chang Gung Memorial Hospital (CGMH) in Taiwan between 1995 and 2015. Basic characteristics such as age, gender, tumor size, cell type, location, and TNM stage were recorded. Prognostic parameters included disease free interval, local recurrence, distant metastasis, and survival were analyzed. RESULTS: There were 20 patients enrolled in the study hospital between 1995 and 2015. All were histological proved by pathologists. Their mean age at diagnosis was 57.8 ± 15.9 years. The mean follow-up time was 68.7 ± 55.8 months. Mean tumor thickness was 6.5 ± 5.9 mm. Six patients developed local recurrence. Twelve patients had distant metastasis. Ten patients died from conjunctival melanoma. The 10 patients had greater mean tumor thickness (8.4 ± 7.5 mm) and shorter mean survival time (40.2 ± 24.1 months). Tumor thickness was found as a prognostic factor for survival time (HR = 1.15, P = 0.01). Age, gender, T stage, and tumor location were not significantly associated with survival. CONCLUSION: Different tumor characteristics were found in this cohort. Higher metastasis and mortality rate could suggest a more aggressive disease pattern. Tumor thickness was indicated as a prognostic factor for survival time and was greater in size in cases with distant metastasis. Early and more invasive intervention with closely follow-up may be indicated in these cases.

Investigation of the Correlation between Graves' Ophthalmopathy and CTLA4 Gene Polymorphism.

Graves' disease (GD) is an autoimmune inflammatory disease, and Graves' ophthalmopathy (GO) occurs in 25-50% of patients with GD. Several susceptible genes were identified to be associated with GO in some genetic analysis studies, including the immune regulatory gene CTLA4. We aimed to find out the correlation of CTLA4 gene polymorphism and GO. A total of 42 participants were enrolled in this study, consisting of 22 patients with GO and 20 healthy controls. Chi-square or Fisher's exact test were used to appraise the association between Graves' ophthalmopathy and CTLA4 single nucleotide polymorphisms (SNPs). All regions of CTLA4 including promoter, exon and 3'UTR were investigated. There was no nucleotide substitution in exon 2 and exon 3 of CTLA4 region, and the allele frequencies of CTLA4 polymorphisms had no significant difference between patients with GO and controls. However, the genotype frequency of "TT" genotype in rs733618 significantly differed between patients with GO and healthy controls (OR = 0.421, 95%CI: 0.290-0.611, p = 0.043), and the "CC" and "CT" genotype in rs16840252 were nearly significantly differed in genotype frequency (p = 0.052). Haplotype analysis showed that CTLA4 Crs733618Crs16840252 might increase the risk of GO (OR = 2.375, 95%CI: 1.636-3.448, p = 0.043). In conclusion, CTLA4 Crs733618Crs16840252 was found to be a potential marker for GO, and these haplotypes would be ethnicity-specific. Clinical application of CTLA4 Crs733618Crs16840252 in predicting GO in GD patients may be beneficial.

IMPACT OF ETIOLOGY ON THE OUTCOME OF PEDIATRIC RHEGMATOGENOUS RETINAL DETACHMENT.

PURPOSE: To evaluate the clinical features and surgical outcomes of rhegmatogenous retinal detachment in pediatric patients and to identify the independent effect of each etiology on the outcome. METHODS: A review of patients younger than 18 years who underwent vitreoretinal surgery was conducted at Chang Gung Memorial Hospital, Taoyuan, between 2008 and 2013. Patients were classified according to etiology. Multivariate logistic regression analysis was performed to evaluate the association between outcomes and each etiologic factor. RESULTS: A total of 86 cases (mean age: 12.9 ± 4.8 years; 76.7% male) were included. The mean follow-up was 46.3 ± 23.9 months. In 90.7% of patients, at least one etiology could be identified, including myopia (55.8%), congenital or developmental disease (39.5%), trauma (27.9%), and previous intraocular surgery (17.4%). Among the risk factors examined in this study, congenital or developmental disease had the worst functional outcomes (P = 0.006). Myopia was a good prognostic factor for a better retinal reattachment rate (P = 0.030). Myopic rhegmatogenous retinal detachment had the lowest probability of surgical failure (8.08%), and idiopathic rhegmatogenous retinal detachment had the lowest likelihood of postoperative visual decline (4.65%). CONCLUSION: Myopia and congenital or developmental disease are the leading etiologies of pediatric rhegmatogenous retinal detachment. Different etiologies are associated with distinctive outcomes, and congenital and developmental diseases are independent prognostic factors of a poor response.

Early Versus Late Canalicular Laceration Repair Outcomes.

PURPOSE: To determine whether delayed repair of traumatic canalicular laceration affects the final outcome. DESIGN: Retrospective case series. METHODS: The medical records of 334 patients who underwent primary traumatic canalicular laceration repair were retrospectively reviewed. Patients were divided into 2 groups according to the surgical timing within 48 hours (early) or after 48 hours (delayed). The anatomic results were compared between these 2 groups. The causes of delayed repair and the mean operation time were also analyzed. RESULTS: There were 23 failed cases among 301 patients (7.6%) who had a repair within 48 hours and 3 failed cases among 33 patients (9.1%) who had a repair after 48 hours (P = .732). The mean operation time was 62 minutes in the early group and 66.3 minutes in the delayed group, which showed no significant difference (P = .371). The major cause of delayed surgery was traumatic brain injury, followed by facial or orbital fracture, long bone fracture, and chest injury. CONCLUSIONS: Delayed canalicular repair in unstable patients did not lead to poor results. An elective scheduling surgery, instead of an urgent repair, is feasible for an experienced surgeon.

Correction of involutional entropion with retractor redirection.

The study aims to report the surgical outcome of a retractor redirection procedure for involutional entropion repair for Asians. The study included all cases diagnosed with involutional entropion and significant ocular irritation who presented from 2008 to 2012. Sixty-seven eyelids in 54 patients were included in this study. All cases were operated on by one surgeon and had a minimum of 12-months follow-up. Success was defined as cases showing no recurrence of entropion with forceful eyelid squeezing postoperatively. A retrospective chart review was performed to assess the success rate, recurrences and complications of the procedure. During a mean follow-up period of 26.2 months (range, 12-53 months), 5 patients died during the study period. Two eyelids (3%) of one patient had a recurrence at 34 months postoperatively. One eyelid (1.5%) with a significant horizontal laxity developed postoperative ectropion and required a secondary horizontal shortening procedure. No other postoperative complications or dissatisfaction were reported. The retractor redirection procedure aims to repair the retractors and prevent orbicularis muscle overriding via inserting the retractors to the anterior lamellae. It yields a long-term success rate of 95.5% and is an effective technique for correcting involutional entropion.

Enteroscopic Diagnosis and Management of Small Bowel Diverticular Hemorrhage: A Multicenter Report from the Taiwan Association for the Study of Small Intestinal Diseases.

Small bowel diverticulum is a rare cause of gastrointestinal bleeding. The diagnosis and treatment of small bowel diverticular hemorrhage is clinically challenging before the development of deep enteroscopy. In this multicenter study from the Taiwan Association for the Study of Small Intestinal Diseases (TASSID), 608 patients underwent deep enteroscopy for obscure gastrointestinal bleeding during January 2004 and April 2010 from eight medical centers in Taiwan. Small bowel diverticular hemorrhage account for 7.89% of obscure gastrointestinal bleeding in this study. Most of the patients received endoscopic therapy with an initial hemostasis rate of 85.71% and rebleeding rate of 20%. In this large case series investigating the enteroscopic management of small intestinal diverticular hemorrhage, we found that, as to patients with peptic ulcer hemorrhage, most of these patients can be successfully managed by endoscopic therapy before surgery in the era of deep enteroscopy.

Use of extraocular muscle flaps in the correction of orbital implant exposure.

PURPOSES: The study is to describe a new surgical technique for correcting large orbital implant exposure with extraocular muscle flaps and to propose a treatment algorithm for orbital implant exposure. METHODS: In a retrospective study, seven patients with orbital implant exposure were treated with extraocular muscle flaps. All data were collected from patients in Chang Gung Memorial Hospital, Taiwan during 2007-2012. All surgeries were performed by one surgeon (Y.J.T). Patient demographics, the original etiology, details of surgical procedures, implant types, and follow-up interval were recorded. Small exposure, defined as exposure area smaller than 3 mm in diameter, was treated conservatively first with topical lubricant and prophylactic antibiotics. Larger defects were managed surgically. RESULTS: Seven patients consisting of two males and five females were successfully treated for orbital implant exposure with extraocular muscle flaps. The average age was 36.4 (range, 3-55) years old. Five patients were referred from other hospitals. One eye was enucleated for retinoblastoma. The other six eyes were eviscerated, including one for endophthalmitis and five for trauma. Mean follow-up time of all seven patients was 19.5 (range, 2-60) months. No patient developed recurrence of exposure during follow-up. All patients were fitted with an acceptable prosthesis and had satisfactory cosmetic and functional results. CONCLUSIONS: The most common complication of orbital implant is exposure, caused by breakdown of the covering layers, leading to extrusion. Several methods were reported to manage the exposed implants. We report our experience of treating implant exposure with extraocular muscle flaps to establish a well-vascularized environment that supplies both the wrapping material and the overlying ocular surface tissue. We believe it can work as a good strategy to manage or to prevent orbital implant exposure.

Orbital cellulitis caused by community-associated methicillin-resistant Staphylococcus aureus in a previously healthy neonate.

A 30-day-old, previously healthy, near-term neonate presented with fever and swelling of the left eye. Orbital cellulitis of the left eye was diagnosed by computed tomography. Both blood culture and pus that was drained from the orbital abscess were positive for methicillin-resistant Staphylococcus aureus (MRSA), which was found to be a strain indigenous to the local community by a molecular method. Using vancomycin therapy and surgical drainage, the infant recovered uneventfully. Orbital cellulitis in neonates may rapidly progress to abscess formation, even to sepsis, and S. aureus is the most common pathogen. With the increasing prevalence of community-associated MRSA, empiric antibiotics effective against MRSA should be first considered in endemic areas.

Comparing pericanalicular sutures with direct canalicular wall sutures for canalicular laceration.

PURPOSE: To determine whether a statistically significant difference exists between direct canalicular wall sutures (DCs) and pericanalicular sutures (PCs) in the repair of traumatic canalicular lacerations. METHODS: The medical records of 63 patients who underwent primary repairs for traumatic canalicular lacerations were retrospectively reviewed. Patients were divided in 2 groups according to the suturing techniques used: the DC group (n = 41) and the PC group (n = 22). Anatomic results were compared between these 2 groups. A successful result was determined by attempted irrigation and probing of the injured canaliculus at the last follow-up visit. RESULTS: There were 6 failed procedures among the patients who underwent pericanalicular repair and 1 failed procedure among the patients who underwent direct canalicular wall repair (p = 0.024). CONCLUSIONS: These data support the higher success rates in patients treated with direct canalicular repair compared with pericanalicular repair.

Analysis of bicanalicular nasal intubation in the repair of canalicular lacerations.

PURPOSE: To analyze the outcomes (success, failure) and complications of surgical repair of canalicular lacerations by bicanalicular nasal intubation in a series of patients treated over a 7-year period. METHODS: The case records of 98 patients undergoing surgical repair of canalicular lacerations were retrospectively reviewed. Patient characteristics and results of the surgical repair were analyzed to identify factors that may influence the outcomes. Two groups (success and failure) were statistically compared with the Mann-Whitney U test for scale variables and with Fisher's exact test for categorical variables. RESULTS: Of the 98 patients, 78 (79.6%) had patency after irrigation (anatomic success) and 83 (84.7%) were asymptomatic (functional success). Patients age, sex, injury location, anesthetic methods, and timing of surgical repair were not significantly associated with the postoperative patency of the lacerated canaliculus. Having a stent left for more than 90 days was significantly associated with restoration of the canalicular anatomy (P < 0.01). Patients with postoperative anatomic patency had a significantly lower rate of symptomatic epiphora than patients with anatomic obstruction (P < 0.001). Symptomatic epiphora was significantly more frequent in patients with combined upper and lower canalicular injuries (P < 0.01). CONCLUSION: Our results suggest that retaining bicanalicular silicone nasal intubation for more than 90 days can provide satisfactory results in restoring both canalicular anatomy and function. With an experienced operating team, repair of canalicular lacerations can be delayed for up to 11 days. However, patients with combined upper and lower canalicular lacerations are at an increased risk of developing postoperative symptomatic epiphora.

Double-balloon enteroscopy application in biliary tract disease-its therapeutic and diagnostic functions.

BACKGROUND: On occasion, it is impossible to perform ERCP with a traditional duodenoscope in patients who have had a Billroth II gastrectomy or hepatojejunostomy, and who now have biliary tract problems. Repeat surgery is not a suitable course of action in these patients. Therefore, finding alternative modalities to resolve these obstructions is of great importance. OBJECTIVE: To report successful endoscopic examination and treatment of difficult biliary obstructions by using double-balloon enteroscopy. PATIENTS: Five patients. DESIGN: Cases series. INTERVENTION: Double-balloon enteroscopy (DBE) for biliary tract examination and treatment. RESULTS: We report on 5 patients who underwent Billroth II gastrectomy or biliary tract Roux-en-Y surgery and who later had biliary tract obstruction from various causes. We were unable to perform ERCP with traditional duodenoscopy but successfully completed ERCP with DBE. DBE was originally designed to examine the small intestine. The successful biliary tract cannulation rate when using DBE is lower than with duodenoscope. We performed ERCP by using DBE a total of 5 times, with a successful biliary cannulation rate of 60%. We performed a special-method papillotomy in 2 patients. This method entailed inserting an electric sphincterotome through the percutaneous transhepatic cholangiography and drainage (PTCD) route after performing DBE intubation to the ampulla of Vater. We then successfully completed a papillotomy with an electric sphincterotome under DBE guidance. CONCLUSIONS: DBE appears to be a promising alternative in the examination and treatment of biliary tract disease in patients after GI operations such as Billroth II gastrectomy and choledochojejunostomy.

Pneumomediastinum after external dacryocystorhinostomy.

A 73-year-old man had right chronic epiphora for many years. After uneventful external dacryocystorhinostomy, he developed dyspnea and neck swelling after forcefully blowing his nose. CT showed diffuse cervicofacial subcutaneous emphysema and pneumomediastinum. He was admitted to prevent further cardiovascular complications. Pneumomediastinum is a rare complication of routine dacryocystorhinostomy. Supportive treatment to prevent additional air trapping is mandatory.

Medial canthal tophus associated with gout.

PURPOSE: To report a case with a gouty tophus at the medial canthus. DESIGN: Observational case report. METHODS: Review of the clinical, laboratory, photographic, and pathologic records of a patient with a gouty tophus at the medial canthus. RESULTS: A 27-year-old man had a 3-year history of gouty arthritis and poorly controlled hyperuricemia. A medial canthal mass without discomfort developed gradually over 3 months. An excisional biopsy was performed, and the tissue was fixed in formalin for pathology. Analysis of a routine hematoxylin-and-eosin-stained section disclosed a multilobulated pseudocyst filled with amorphous eosinophilic material. Further staining with nonaqueous alcoholic eosin and viewed under a polarizing microscope indicated the presence of birefringent urate crystals. CONCLUSIONS: Gouty tophus can develop progressively at the medial canthus, especially in people with uncontrolled hyperuricemia. A formalin-fixed specimen, stained with nonaqueous alcoholic eosin, demonstrates abundant birefringent urate crystals under a polarizing microscope.