An Appraisal of the Preventive Effect of Statins on the Development of Graves' Ophthalmopathy: A Hospital-Based Cohort Study.

INTRODUCTION: Graves' ophthalmopathy (GO) is an autoimmune inflammatory disorder observed in a substantial proportion of patients with Graves' disease (GD), with debilitating symptoms of disfiguring, periorbital pain, dry eyes, diplopia, and even visual disturbances. Previous studies involving Western populations have noted discrepancies in risk factors for GO. Therefore, this study aimed to determine the risk factors for GO development and the protective effect of statins in newly diagnosed patients with GD in Taiwan. METHODS: This retrospective case-control study was based on a tertiary center cohort involving patients with GD diagnosed between 2010 and 2019 at the National Taiwan University Hospital (n = 11,035). Patients who were diagnosed or treated elsewhere, had been followed up for less than 6 months or were with a diagnosis of orbital tumor were excluded. Overall, 3578 patients with GD met the inclusion criteria. Univariate and multivariate logistic regression analyses were used to ascertain the odds ratio (OR) of developing GO, with adjustment for sociodemographic factors, interventions for managing GD and thyroid hormone levels, to determine protective and risk factors for GO. RESULTS: In our multivariate model, the use of statins reduced the risk of GO development (OR 0.2; 95% confidence interval [CI] 0.08-0.50; p < 0.001). Thyroid dysfunction including hyperthyroidism (OR 4.2; 95% CI 2.97-5.88; p < 0.001) and hypothyroidism (OR 4.7; 95% CI 3.02-7.19; p < 0.001) was associated with an increased risk of developing GO. Smoking status and lipid profile were not risk factors in our cohort. CONCLUSION: In newly diagnosed patients with GD, the use of statins decreased the risk of developing GO by 80%, whereas serum lipid levels were not considered risk factors. Further nationwide population-based studies may help clarify the differences in risk factors between various ethnic groups. TRAIL REGISTRATION: This trial was approved by the Research Ethics Committee of National Taiwan University Hospital (202202066RINC), retrospectively registered from January 1, 2010 to December 31, 2019.

Supraperiosteal fat repositioning with midface lift in lower eyelid blepharoplasty: an 18-year experience.

PURPOSE: To assess the clinical outcomes of fat repositioning via supraperiosteal dissection with midface lift for correction of tear trough deformity in a large Asian patient population. METHODS: Retrospectively review 1152 Asian patients who underwent fat repositioning to the supraperiosteal plane with a midface lift between 2005 and 2022. Surgical technique, postoperative course, and complications were recorded. At the 6-month postoperative follow-up, the degree of patient satisfaction was assessed. RESULTS: A total of 2304 eyes from 1152 patients with an average follow-up of 10 months. These procedures were performed using a transforniceal approach in 185 patients (16%) or a transcutaneous skin excision approach in 967 patients (84%). Among the patients who underwent the transcutaneous technique, seven individuals (0.6%) experienced effective treatment of lower lid ectropion through lateral tarsal strip procedures. Nine patients (0.7%) required revision surgery to address the remaining lateral fat pad due to inadequate lateral orbital fat excision during the initial procedure. At the 6-month follow-up, most patients reported a high level of satisfaction, with 800 patients (78%) expressing extreme satisfaction and 196 patients (19.1%) reporting satisfaction with the improvement in their appearance. No one reported facial numbness, lower eyelid or cheek paralysis, newly developed diplopia or granuloma formation. CONCLUSION: The procedure of fat repositioning involving supraperiosteal dissection and a midface lift, whether performed using a transforniceal approach or a transcutaneous skin excision approach, in lower eyelid blepharoplasty proves to be a secure and auspicious surgical technique for rectifying tear trough deformity and attaining a pleasing aesthetic outcome.

Long-term outcomes of inferomedial orbital wall decompression in Graves' ophthalmopathy in an Asian population: A 30-year retrospective study.

PURPOSE: This study aims to evaluate the long-term outcomes of inferomedial orbital wall decompression (IMOD) in Graves' ophthalmopathy (GO). METHODS: A retrospective review of 422 eyes of 226 patients with GO-related cosmetically disfiguring proptosis (COS), dysthyroid optic neuropathy (DON), or exposure keratopathy (EXP) who received IMOD from 1989 to 2020 was conducted. Hertel value (HE) and corrected visual acuity (CVA) were evaluated at baseline and regularly thereafter. Proptosis recurrence, diplopia, and adjuvant surgeries were assessed. Complete success was defined as proptosis reduction over 2 mm without recurrence and improved diplopia. Partial success was defined as proptosis reduction without recurrence but with persistent or new-onset diplopia, and failure as proptosis recurrence. RESULTS: After follow-up for 40.1 ± 39.6 months (range, 6-239 months), 236 eyes (55.9%) achieved complete success, 175 eyes (41.5%) achieved partial success, and 11 eyes (2.6%) had failure. Significant CVA improvement was observed in both DON and COS groups (P < 0.001 and P = 0.045, respectively). Average proptosis reduction was 5.2 ± 2.2 mm, with a significant increase of 0.5 mm after long-term follow-up (P < 0.001). Incidence of proptosis recurrence was 2.6%. Surgical success rate of COS group was positively correlated with preoperative HE. CONCLUSION: IMOD demonstrated excellent success rate in all three subgroups with a low proptosis recurrence rate and improved visual outcome in both DON and COS groups. Delayed proptosis reduction effect of IMOD may result in delayed-onset asymmetry, especially in the unilateral group.

The Changes in Ocular Biomechanical Response Parameters and Intraocular Pressure After Surgical Treatment for Thyroid Eye Disease.

Purpose: To investigate changes in ocular biomechanical response parameters and intraocular pressure (IOP) in patients with thyroid eye disease (TED) undergoing orbital decompression or anterior blepharotomy. Methods: Eighty-three eyes from 46 patients receiving orbital decompression (the orbital decompression group) and 45 eyes from 28 patients receiving anterior blepharotomy (the anterior blepharotomy group) were retrospectively enrolled from a tertiary center. Corvis ST tonometry was used to assess ocular biomechanical response and biomechanically corrected IOP (bIOP) pre- and postoperatively. Non-contact tonometry (IOP-NCT) was also performed. Results: In the anterior blepharotomy group, the margin reflex distance decreased (P < 0001). The highest concavity radius (P = 0.026) and whole eye movement (P = 0.003) increased. Neither IOP-NCT nor bIOP had a significant change. In the orbital decompression group, the extent of exophthalmos decreased (P < 0.001). The A2 length (P = 0.009) decreased. The bIOP did not show a significant change (16.4 ± 2.7 vs. 16.7 ± 4.5; P = 0.415), but the IOP-NCT decreased significantly (17.5 ± 3.3 vs. 16.0 ± 3.3; P < 0.001). Higher baseline IOP-NCT (ß = -0.40, P < 0.001) and greater reduction in stiffness parameter A1 (SP-A1; ß = 0.05, P = 0.002) were associated with more significant IOP-NCT reduction after the orbital decompression. Conclusions: Ocular biomechanical response parameters may change after TED surgery, potentially affecting IOP measurements, particularly in patients receiving orbital decompression.

Execution of anticipatory guidance and the knowledge and practice gap among caregivers in Southern Taiwan: A retrospective study.

BACKGROUND/PURPOSE: This study examined the practice rate of Anticipatory Guidance (AG) and the gap between knowledge and practice among caregivers. METHODS: We retrospectively collected data from caregivers who brought their children for seven age-based well-child visits (birth to 7 years old) and seven corresponding AG checklists for practice (each ranged from 16 to 19 guidance items, 118 items in total) between 2015 and 2017. Practice rates of guidance items and their association with children's sex, age, residence, and body mass index were collected and analyzed. RESULTS: We enrolled 2310 caregivers (330 per well-child visit). Average practice rates of guidance items in the seven AG checklists were 77.6%-95.1%, generally without significant differences between urban/rural or male/female children. However, lower (<80%) rates were observed for 32 items, including dental check-ups (38.9%), use of fluoride toothpaste (44.6%), screen time (69.4%), and drinking less sugar-sweetened beverages (SSBs) (75.5%), with corresponding knowledge-to-practice gap rates of 55.5%, 47.9%, 30.3%, and 23.8%, respectively. "Drinking less SSBs" was the only item with a higher obesity rate in the non-achieved group versus the achieved group (16.7% vs. 7.4%, p = 0.036; odds ratio: 3.509, 95% CI: 1.153-10.677, p = 0.027). CONCLUSION: Caregivers in Taiwan practiced most AG recommendations. However, dental check-ups, fluoride toothpaste use, drinking less SSBs, and limiting screen time were less executed items. A higher obesity rate was found among 3-7-year-old children whose caregivers failed to practice the "Drink less SSBs" guidance. Strategies to overcome the gap between knowledge and practice are needed to improve these less-achieved guidance items.

Postoperative residual vertical deviation affects quality of life in Asian patients with thyroid-associated ophthalmopathy (Graves ophthalmopathy).

PURPOSE: To evaluate the treatment effect of strabismus surgery for Graves ophthalmopathy in an ethnic Chinese population. STUDY DESIGN: A prospective clinical study. METHODS: Thirty-one patients with Graves ophthalmopathy who had undergone strabismus surgery at National Taiwan University Hospital between 2012 and 2013 were consecutively recruited. The subjective outcome was evaluated using the Graves' Ophthalmopathy Quality-of-Life (GO-QoL) questionnaire, and the ocular deviation was measured preoperatively and postoperatively by use of a prism cover test. RESULTS: The GO-QoL scores for visual functioning and appearance improved significantly after surgery (preoperative scores 32.6 ± 19.9 and 43.8 ± 26.4, postoperative scores 55.2 ± 24.4 and 54.1 ± 27.6, respectively; P < .05). Motor success was achieved in 61.3% of the patients, and their postoperative visual scores were higher (61.5 ± 22.5) than the scores of those who experienced motor failure (45.3 ± 26.8, P = .048). The postoperative visual function scores showed a negative correlation with the residual vertical deviation (R2 = 0.546, P = .040). A higher increase in GO-QoL visual scores and a lower residual vertical deviation in downgaze were achieved among patients without previous decompression surgery. Our surgical methods resulted in a motor success rate of 76.5% for the correction of vertical deviation. CONCLUSION: GO-QoL scores and ocular deviation improved significantly after strabismus surgery. Precise correction of vertical deviation was of greater importance than horizontal deviation for visual function scores. Our surgical methods were effective for the correction of vertical deviation in Graves ophthalmopathy.

The Role of Interleukin-17A and NLRP3 Inflammasome in the Pathogenesis of Graves' Ophthalmopathy.

The development of Graves' ophthalmopathy (GO) is associated with autoimmune dysfunction. Recent studies have indicated that IL-17A, inflammasomes, and related cytokines may be involved in the etiology of GO. We sought to investigate the pathogenic role of IL-17A and NLRP3 inflammasomes in GO. Orbital fat specimens were collected from 30 patients with GO and 30 non-GO controls. Immunohistochemical staining and orbital fibroblast cultures were conducted for both groups. IL-17A was added to the cell cultures, and cytokine expression, signaling pathways, and inflammasome mechanisms were investigated using reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, Western blotting, and small interfering RNA (siRNA) methods. Immunohistochemical staining showed higher NLRP3 expression in GO orbital tissue than in non-GO controls. IL-17A upregulated pro-IL-1ß mRNA levels and IL-1ß protein levels in the GO group. Furthermore, IL-17A was confirmed to enhance caspase-1 and NLRP3 protein expression in orbital fibroblasts, suggesting NLRP3 inflammasome activation. Inhibiting caspase-1 activity could also decrease IL-1ß secretion. In siRNA-transfected orbital fibroblasts, significantly decreased NLRP3 expression was observed, and IL-17A-mediated pro-IL-1ß mRNA release was also downregulated. Our observations illustrate that IL-17A promotes IL-1ß production from orbital fibroblasts via the NLRP3 inflammasome in GO, and cytokines subsequently released may induce more inflammation and autoimmunity.

First-line antibiotic treatment in patients with localized extragastric mucosa-associated lymphoid tissue lymphoma.

Between January 2010 and December 2015, we enrolled 28 patients with stage IEI/IIE1 extragastric mucosa-associated lymphoid tissue (MALT) lymphoma who received first-line antibiotic treatment, after informing them about the pros and cons of alternative therapies. In addition, during the same period, 64 patients with stage IE/IIE1 disease who received conventional treatment were selected as the control group. The most common primary sites were the ocular adnexal area (17 cases), followed by the salivary glands (four cases), pulmonary (three cases), and thyroid, trachea, larynx, and colon region (one case each). First-line antibiotic treatment resulted in an overall response rate of 57.1%: 12 patients achieved complete remission (CR), while four achieved partial remission (antibiotic-responsive tumors). Monoclonal gammopathy was significantly prevalent in antibiotic-unresponsive tumors than in antibiotic-responsive tumors (50.0% [6/12] vs. 12.5% [2/16], p = 0.044). After a median follow-up of 7 years, all patients with CR remained lymphoma-free, with 7-year event-free survival (EFS) and overall survival (OS) rates of 62.7% and 96.4%, respectively. The 7-year EFS and OS rates of patients who received conventional treatments were 73.1% and 91.1%, respectively. Compared with that noted in patients who received conventional treatment, antibiotic treatment was effective in some patients with localized extragastric MALT lymphoma.

Personalized multidisciplinary approach of orbital apex foreign body: A case report and literature review.

Foreign bodies in the intraconal space are unusual, and lodgment at the orbital apex was even more unusual. High-velocity object injuries, such as gunshots or industrial accidents, are the common causes of intraorbital foreign bodies. It is difficult for surgeons to retrieve foreign bodies from the orbital apex as it is a deep, narrow space with critical surrounding structures. The use of an image-guided navigation system improves the accuracy of transnasal endoscopic surgery and causes less damage. We present a case in which a bullet became lodged in the orbital apex and was successfully removed using transnasal endoscopic surgery with the collaboration of otolaryngologists and ophthalmologists. To summarize, orbital apex foreign bodies are harmful, and prompt removal with a personalized multidisciplinary approach is critical.

The Changes in Optic Nerve after Orbital Decompression Surgery for Thyroid Eye Disease and Case Reports of Ischemic Optic Neuropathy.

Purpose: To demonstrate the changes in the retinal nerve fiber layer (RNFL) after orbital decompression for thyroid eye disease (TED). Methods: We retrospectively enrolled 52 surgical TED patients, 30 nonsurgical TED patients, and 30 control subjects. Five surgical TED eyes with disc edema were excluded. The surgical TED patients were classified into the "dysthyroid optic neuropathy (DON)" group (16 eyes) and the "non-DON" group (83 eyes). Optical coherence tomography (OCT) and visual field (VF) examinations were performed preoperatively and 6 months later. The control subjects and nonsurgical TED patients received two OCT examinations at 6-month intervals. The postoperative changes in the RNFL thickness were compared between groups. Three cases with severe postoperative vision loss were presented additionally. Results: The changes in the RNFL thickness of the controls (0.5 ± 3.4 µm) and the nonsurgical TED patients (0.3 ± 2.8 µm) were significantly smaller than the surgical TED patients (P < 0.001). The DON group (-9.2 ± 9.2 µm) had greater RNFL thickness reduction than the non-DON group (-3.9 ± 5.4 µm) (P = 0.002). Bone removal decompression was associated with decreased RNFL in the non-DON (P = 0.025; ß = -2.49) and DON (P = 0.042; ß = -9.43) groups. Three cases who were hard to operate due to extensive fibrosis experienced severe vision loss postoperatively due to anterior ischemic optic neuropathy, posterior ischemic optic neuropathy, and posterior ciliary artery occlusion, respectively. Conclusions: TED patients experienced subclinical optic nerve injury and significant RNFL loss after the orbital decompression surgery. Aggressive manipulation during decompression surgery may lead to dreadful vision loss. Tailored surgical plans and delicate manipulation are warranted.

Review, analysis, and education of antiseptic related ocular injury in the surgical settings.

Preoperative skin antiseptic preparation is the gold standard for prevention of surgical infection. However, improper use of antiseptics may lead to severe ocular damage. Currently, the most common surgical antiseptics can be divided into aqueous-based and alcohol-based disinfectants, with chlorhexidine and iodine/iodophors being the two major components. Chlorhexidine has a persistent antimicrobial effect and is resistant to neutralization by blood or organic products in surgical wounds. Nevertheless, due to its toxicity to the ears, meninges, and eyes, application of chlorhexidine should be prohibited in these surgical fields. Iodine/iodophor is better tolerated by the ocular surface and is the recommended antiseptic for ophthalmic or head and neck surgeries close to the periocular area. Alcohol is less pricey and has a rapid antiseptic effect, though its desiccating effect and flammability restrict the use in mucosal or laser surgeries. The single or combined use of these antiseptics may inadvertently induce severe ocular damage, especially during time-consuming head and neck surgeries with prone, hyperextension, or lateral tilt positions, or surgeries under general anesthesia. Apart from the choice of antiseptics, appropriate selection and attachment of bio-occlusive dressings are key to avoiding antiseptic-related ocular injuries. In this review, we provided a comprehensive summary of the characteristics of antiseptics used in surgical settings and the possible mechanisms and outcomes of antiseptic-related ocular injuries. The prevention, diagnosis, and acute management of these complications were also discussed.

Efficacy and predictability of Muller's muscle-conjunctival resection with different tarsectomy lengths for unilateral blepharoptosis treatment.

BACKGROUND: To investigate the efficacy and predictability of Muller's muscle-conjunctival resection (MMCR) with different lengths of tarsectomy for the treatment of unilateral mild-to-moderate blepharoptosis. METHODS: A retrospective study of patients who underwent MMCR with tarsectomy for unilateral mild-to-moderate blepharoptosis between January 2016 and December 2019 was performed. Individuals with adequate photographic documentation and good levator function were included. Data on age, gender, surgical designs, pre-operative and post-operative marginal reflex distance 1 (MRD1) and tarsal platform show (TPS), and complications were retrieved. RESULTS: Sixty patients underwent 8-mm MMCR with 1- or 2-mm tarsectomy; 53 patients (88.3%) showed postoperative symmetry of MRD1 within 1 mm. The average postoperative improvement in MRD1 was 2.15 ± 0.8 mm. Thirty-two patients received 8-mm MMCR with 1-mm tarsectomy (group 1), and 28 patients underwent 8-mm MMCR with 2-mm tarsectomy (group 2). In group 1, postoperative symmetry rate was 90.6%, and the mean elevation of MRD1 was 1.66 ± 0.6 mm. In group 2, postoperative symmetry rate was 85.7%, and the mean elevation of MRD1 was 2.72 ± 0.6 mm. Both groups showed postoperative symmetry of TPS and significant improvement in eyelid position (p < 0.0001). No postoperative complication was noted, and no secondary surgery was needed. CONCLUSIONS: MMCR with tarsectomy was proven to be a safe, rapid, and effective method for patients with mild-to-moderate ptosis. Predictability and symmetry of the outcome were statistically confirmed. We further suggest a 2.1-mm expected MRD1 elevation as a cut point for choosing between 1- or 2-mm tarsectomy.

Simvastatin Inhibits CYR61 Expression in Orbital Fibroblasts in Graves' Ophthalmopathy through the Regulation of FoxO3a Signaling.

Graves' ophthalmopathy (GO), which is characterized by orbital tissue inflammation, expansion, and fibrosis, is the ocular manifestation in 25% to 50% of patients with Graves' disease. As the pathology of GO is driven by autoimmune inflammation, many proinflammatory cytokines/chemokines, including TNF-α, IL-1ß, IL-6, and CCL20, are crucial in the pathogenesis of GO to activate the orbital fibroblasts. Cysteine-rich protein 61 (CYR61), which is known to regulate cell proliferation, adhesion, and migration, plays a proinflammatory role in the pathogenesis of many inflammatory diseases, such as rheumatoid arthritis. CYR61 was considered a potential biomarker of GO in recent studies. Statins, which are cholesterol-lowering drugs, were found to reduce the risk of GO, probably through their anti-inflammatory and immunomodulatory effects. In this study, we established a link between CYR61 and statins in the pathogenesis and potential treatment for GO. Firstly, our data showed the overexpression of CYR61 in the orbital tissue (n = 4) and serum specimens (n = 6) obtained from the patients with inactive GO. CYR61 could induce the production of IL-6 and CCL20 in cultured GO orbital fibroblasts. The expression of CYR61 in cultured GO orbital fibroblasts was upregulated via TNF-α stimulation. Secondly, we pretreated cultured GO orbital fibroblasts using simvastatin, a statin, followed by TNF-α stimulation. The data revealed that simvastatin could inhibit TNF-α-induced CYR61 expression by modulating the activity of transcription factor FoxO3a. Our results provided insights into some cellular mechanisms that may explain the possible protective effects of simvastatin against the development of GO.

Orbital and ocular adnexal lymphoma: a review of epidemiology and prognostic factors in Taiwan.

PURPOSE: To investigate the clinical features, prognostic outcomes of patients with orbital and ocular adnexal lymphoma (OALs) in Taiwanese cohort. METHODS: Total 112 patients with OALs were retrospectively reviewed. Demographic information such as age, gender, lymphoma subtype, tumor location and treatment modalities were recorded. The primary endpoints were disease-specific survival (DSS), and progression-free survival (PFS). RESULTS: The mean patient age was 59.0 ± 15.5 years (range, 23-92 years). The major histopathologic subtypes were mucosa-associated lymphoid tissue (MALT) lymphoma in 76 patients (67.9%), followed by diffuse large B-cell lymphoma (DLBCL) (9.8%), follicular cell lymphoma (FL) (8.0%), and small lymphocytic lymphoma (SLL) (5.4%). The anatomical locations for OALs were the orbit (44 patients, 39.3%), the conjunctiva (31 patients, 27.7%), the lacrimal gland (28 patients, 25.0%), and the eyelid (8 patients, 7.1%). With a mean follow-up time of 74.5 ± 59.8 months (range 6-342 months), the DSS for all patients were 93.1%, 87.7%, and 68.8% at 60, 120, and 180 months' follow-up, respectively. The PFS at 60, 120, and 180 months' follow-up were 86.2%, 61.2%, and 44.6%, respectively. Regarding the analysis of prognostic factors, patients with high grade lymphoma subtype and advanced stage exhibited a worse prognosis. CONCLUSIONS: MALT type lymphoma constitutes most of OALs in Taiwan and occurs more frequently than in Western countries. Patients with MALT lymphoma, FL, SLL and earlier stage have favorable outcomes compared with patients of high grade lymphoma and Ann Arbor stage IV lymphoma.

Fibroblast Growth Factor Receptor Inhibitors Reduce Adipogenesis of Orbital Fibroblasts and Enhance Myofibroblastic Differentiation in Graves' Orbitopathy.

Purpose: Orbital fibroblasts are involved in pathogenesis of Graves' orbitopathy (GO). Fibroblast growth factor (FGF) affects fibroblasts of GO. This study aims to investigate the roles of FGF and FGF receptor (FGFR) in GO.Methods: Serum FGF proteins and orbital fibroblast FGFR proteins and mRNAs were measured in GO patients and controls. Orbital fibroblasts of GO were cultured and accessed for changes in proliferation (by nuclei number and MTT), myofibroblastic differentiation (by α-SMA), and adipogenesis (by oil droplets using Oil Red O stain) under FGF1 with or without FGFR inhibitors (FGFRi).Results: Serum FGF1 and FGF2 were increased in GO patients. FGFR1 was the most abundantly expressed FGFR in GO orbital fibroblasts. FGF1 increased GO fibroblast proliferation/adipogenesis and suppressed myofibroblastic differentiation, while FGFRi reversed these effects.Conclusion: FGF signaling may be involved in GO pathogenesis. Manipulation of FGF-FGFR pathway for GO treatment is worthy of further investigation.Registration number on Clinicaltrials.gov: NCT03324022.

Orbital Compartment Syndrome and Irreversible Blindness Related to Orbital Varix Thrombosis: A Case Report.

BACKGROUND: Orbital compartment syndrome (OCS) is an ocular emergency that can severely threaten the visual potential. The most common etiologies include facial trauma-related orbital wall fractures and postoperative bleeding within the orbit. Nontraumatic cases were also reported sporadically, although they are rare. The orbital volume limits the compliance to expand when space-occupying lesions develop. Both direct compression of the optic nerve and depleted perfusion from elevated intraorbital pressure subsequently lead to ischemic optic neuropathy and vision loss. CASE REPORT: A 74-year-old man experienced headache, bulging left eye, dull pain, vision loss, nausea, and vomiting within 1 day. Computed tomography and magnetic resonance imaging revealed a heterogeneous mass extending from the orbital apex and connected with the ophthalmic vein. Lateral canthotomy and cantholysis were performed at bedside for emergent orbital decompression. The proptosis and pain relieved after surgery, but visual loss remained irreversible. Surgical exploration was conducted and pathology proved the diagnosis of varix of the ophthalmic vein with thrombosis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Clinicians should be aware of the presentation of OCS and perform timely orbital decompression, which could reverse visual impairment. These patients might also benefit from immediate consultants with ophthalmologists and radiologists.

Orbital exenteration: A 20-year experience from a tertiary center in Taiwan.

PURPOSE: To describe the prognostic factors and survival outcomes in patients who underwent orbital exenteration surgery at a tertiary center over a 20-year period. METHODS: This institutional retrospective study reviewed all patients who underwent orbital exenteration between January 1999 and January 2019 at Department of Ophthalmology, National Taiwan University Hospital. Patient demographics, tumor site, histopathology, status of surgical margins, additional resection, local recurrence, metastases, survival, and treatment data were recorded. Log-rank tests were used to verify the difference in survival curves among various potential prognostic factors. RESULTS: Thirty patients (27 with malignancy, 1 with hybrid neurofibroma/schwannoma, and 2 with mucormycosis) were included. Malignant melanoma (n = 11) and sebaceous gland carcinoma (n = 8) were the most common indications for exenteration. Survival rates were 83% at 1 year, 42% at 3 years, and 33% at 5 years. Among patients with malignancies, 71% patients had clear margins after exenteration. All the incidences of local recurrence developed in the first 2 years postoperatively. Postoperative survival was significantly related to lymphovascular invasion (p = 0.018), but was independent from surgical margins, presence of metastasis, local recurrence, or perineural invasion. CONCLUSION: We found worse prognosis with positive lymphovascular invasion. Although not significant, malignant melanoma showed poorer survival times compared to sebaceous gland carcinoma. Close follow-up, especially in the first 2 years after orbital exenteration, is crucial to identify disease recurrence.

A 45-year experience of uveal melanoma in Taiwan: Verification of American Joint Committee on Cancer staging system and prognostic factors.

BACKGROUND/PURPOSE: To verify the staging system of the American Joint Committee on Cancer (AJCC) 8th edition for uveal melanoma, and to propose the prognostic factors of uveal melanoma by a 45-year cohort study. METHODS: We collected patients who underwent operation with pathological proof from 1973 to 2017. The demographic data including gender, age, laterality, metastatic pattern, and histopathology type were recorded. The predictability for survival and monotonicity of gradients of the AJCC 8th edition were evaluated. The prognostic factors for survival were analyzed by univariate and multivariate analysis. RESULTS: A total of 72 patients were collected. The median age was 55 year-old (range 24-100). No specific gender predilection was revealed in our study. About 75.9% of metastases events happened in the first five-year of follow-up, and hepatic involvement was the most common. By the AJCC 8th edition, the distribution for stage I: II: III was 8 (11.1%), 37 (51.4%), and 27 (37.5%). The prognostic staging groups manifested fair predictability and monotonicity of gradients for survival outcome. The tumors with epithelioid cell type and ciliary body involvements had higher tumor-related mortality. CONCLUSION: The AJCC 8th edition prognostic staging groups for outcome prediction was validated. Periodic screening for metastases should be more frequent in the first five-year follow-up. The tumors with epithelioid cell pattern and ciliary body involvements were at risk of higher tumor-related mortality in Taiwanese patients.

Strategies in Surgical Decompression for Thyroid Eye Disease.

Surgical management of thyroid eye disease- (TED-) associated morbidity has been plagued by the complex interplay of different operative techniques. Orbital decompression is the well-recognized procedure for disfiguring exophthalmos and dysthyroid optic neuropathy (DON). There are numerous published techniques described for the removal of the orbital bone, fat, or a combination. The diverse studies are noncomparative as they include different indications, stages of disease, and methods of evaluation. Thus, it is difficult to conclude the most efficient decompression technique. To obtain effective and predictable results, it is therefore important to propose a logical and acceptable clinical guideline to customize patient treatment. Herein, we developed an algorithm based on the presence of DON, preoperative existing diplopia, and severity of proptosis which were defined by patient's disabling symptoms together with a set of ocular signs reflecting visual function or cosmesis. More specifically, we aimed to assess the minimal but effective surgical technique with acceptable potential complications to achieve therapeutic efficacy. Transcaruncular or inferomedial decompressions are indicated in restoring optic nerve function in patients with DON associated with mild or moderate to severe proptosis, respectively. Inferomedial or fatty decompressions are effective to treat patients with existing diplopia associated with mild or moderate to severe proptosis, respectively. Fatty or balanced decompressions can improve disfiguring exophthalmos in patients without existing diplopia associated with mild to moderate or severe proptosis, respectively. Inferomedial or 3-wall decompressions are preferred to address facial rehabilitation in patients associated with very severe proptosis but without preoperative diplopia.

Simvastatin and ROCK Inhibitor Y-27632 Inhibit Myofibroblast Differentiation of Graves' Ophthalmopathy-Derived Orbital Fibroblasts via RhoA-Mediated ERK and p38 Signaling Pathways.

Transforming growth factor-ß (TGF-ß)-induced differentiation of orbital fibroblasts into myofibroblasts is an important pathogenesis of Graves' ophthalmopathy (GO) and leads to orbital tissue fibrosis. In the present study, we explored the antifibrotic effects of simvastatin and ROCK inhibitor Y-27632 in primary cultured GO orbital fibroblasts and tried to explain the molecular mechanisms behind these effects. Both simvastatin and Y-27632 inhibited TGF-ß-induced α-smooth muscle actin (α-SMA) expression, which serves as a marker of fibrosis. The inhibitory effect of simvastatin on TGF-ß-induced RhoA, ROCK1, and α-SMA expression could be reversed by geranylgeranyl pyrophosphate, an intermediate in the biosynthesis of cholesterol. This suggested that the mechanism of simvastatin-mediated antifibrotic effects may involve RhoA/ROCK signaling. Furthermore, simvastatin and Y-27632 suppressed TGF-ß-induced phosphorylation of ERK and p38. The TGF-ß-mediated α-SMA expression was suppressed by pharmacological inhibitors of p38 and ERK. These results suggested that simvastatin inhibits TGF-ß-induced myofibroblast differentiation via suppression of the RhoA/ROCK/ERK and p38 MAPK signaling pathways. Thus, our study provides evidence that simvastatin and ROCK inhibitors may be potential therapeutic drugs for the prevention and treatment of orbital fibrosis in GO.