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Naja species bite is the commonest cause for consultation to Remote Envenomation Consultancy Services in Malaysia. Envenomation by Naja species may result in neuroparalysis and cardiotoxic effects including arrhythmias, hypertension, tachycardia, atrioventricular blocks, ventricular tachycardia, and ventricular fibrillation. We report a case of cardiotoxicity as an early manifestation following an equatorial spitting cobra, Naja sumatrana bite, preceding early paralytic envenomation manifestation. A 14-year-old boy presented to an emergency department with mild local envenomation. ECG showed multiple ventricular premature complexes. Subsequently patient developed ptosis. Complete resolution of ptosis and resumption of normal sinus rhythm occurred following administration of the appropriate antivenom. The patient was discharged well after two days of hospitalization. The patient's ECG findings and neurotoxic manifestation suggested acute systemic envenomation. High index of suspicion for cardiotoxicity with close serial monitoring is recommended to ensure timely administration of antivenom., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To determine the incidence of blepharoptosis after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections and compare the rates of blepharoptosis between patients injected with an eyelid speculum and those injected without a speculum., Design: Retrospective cohort study., Methods: International Classification of Diseases, Tenth Revision (ICD-10), codes were used to identify patients with exudative age-related macular degeneration (AMD) and those who developed ptosis after intravitreal injections. Patients with nonexudative AMD who did not receive intravitreal injections served as controls. The outcomes were the incidence of ptosis in the injection group compared to the noninjection group and incidence of ptosis in patients whose injections were performed with an eyelid speculum as compared to those whose injections were performed without a speculum., Results: We recruited 1100 exudative AMD patients who received at least 1 intravitreal anti-VEGF injection and 2258 nonexudative AMD patients who had not received an injection. In the injection group, 18 of 1100 patients (1.6%) developed ptosis, compared with 52 of 2258 patients (2.3%) in the noninjection group (P = .25). Within the injection group, ptosis was mostly bilateral, diagnosed on average 22.4 months after the initial injection, and after more than a 1-year injection-free period. Eleven of 537 patients (2.0%) injected without a speculum developed ptosis, compared with 8 of 444 patients (1.8%) injected with a speculum (P = .82)., Conclusions: No statistically significant differences in incidence rates of ptosis were observed. In this analysis, neither intravitreal anti-VEGF injections nor speculum use during injections appears to increase the risk of ptosis., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Oculomotor nerve palsy (ONP) is often discovered in the ophthalmology department, manifested as ptosis with the same side, eyeball in the fixed external booth, or accompanied by limited inward, upward, and downward movements. The present case report described the effect of electroacupuncture (EA) on a breast cancer patient with ONP after chemotherapy., Patient Concerns: A 56-year-old breast cancer patient presented with severe ptosis and fixed right eye exotropia. Besides, it is challenging to perform the movement inward, upward, and downward, and with obvious diplopia., Diagnoses: The breast cancer patient was diagnosed with ONP, chemotherapy history., Interventions: The patient was introduced to acupuncture department to receiving EA treatment., Outcomes: After 12 times of EA treatments, the symptom of ptosis was significantly improved, and the right upper eyelid can lift autonomously as same as the left eye. Besides, the patient's right lateral eye could move freely, and the symptoms of double vision disappeared., Conclusion: The case suggests that EA may be an effective alternative treatment for ONP., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To evaluate the efficacy and safety of peribulbar triamcinolone acetonide injection for treating ocular myasthenia gravis (OMG), with a comparison of traditional oral drug therapy., Methods: A total of 22 patients with OMG who received periocular triamcinolone acetonide injection (initially 20 mg weekly, then once per month later if symptoms were improved) from July 2019 to July 2022 were evaluated by a comparison of symptom degree before and after treatment. Adverse reactions were also monitored during the period of treatment. The period of follow-up was more than 6 months. Additionally, a comparison of the treatment efficacy between this periocular injection and traditional oral administration was performed in OMG patients., Results: After 4 weeks of treatment, the degree of ptosis in OMG patients decreased to -3.00 ± 0.69, compared to the value (-0.86 ± 1.32) before treatment. The degree of ophthalmoplegia also decreased from 3.12 ± 0.72 to 0.86 ± 0.88 (P < 0.001) after treatment. The achievement rates of minimal manifestations status (MMS)for ptosis and ophthalmoplegia after 4 week-treatment were 86.3% and 75%, respectively, while they were 50% and 30% in patients with traditional oral administration. There was statistically significant difference only in MMS (rather than symptom relief rate and generalization conversion rate) between two groups. No serious complications (except for intraorbital hematoma) were found in OMG patients during the treatment period., Conclusion: Repeated peribulbar injection of triamcinolone acetonide can effectively alleviate the initial symptoms of OMG patients. However, the evaluation of its long-term efficacy is still needed., Clinical Trial Registry: This study has been clinically registered by Chinese Clinical Trial Registry (ChiCTR), first trial registration date:05/07/2019, registration number: ChiCTR1900024285., (© 2024. The Author(s).)

Background: Eyelid ptosis following periocular onabotulinumtoxinA (BoNT-A) treatment is a known complication that can be frustrating for both patients and practitioners. Iatrogenic blepharoptosis occurs due to local spread of the BoNT-A from the periocular region into the levator palpebrae superioris muscle. Although injectors should have a thorough understanding of the relevant anatomy in order to prevent it, BoNT-A induced ptosis can occur even in the most experienced hands., Objectives: The aim of this study was to describe a case series of patients treated effectively with topical oxymetazoline HCl 0.1% and pretarsal BoNT-A injections in the setting of botox-induced ptosis., Methods: The study group consisted of 8 patients who had undergone recent cosmetic BoNT-A treatment preceding the sudden onset of unilateral upper eyelid ptosis., Results: A diagnosis of severe ptosis (>3 mm) was made in all the cases in this series. Pretarsal BoNT-A injections alone or in association with topical administration of Upneeq eyedrops (Upneeq, Osmotica Pharmaceuticals, Marietta, GA) significantly reversed the ptosis in all treated cases., Conclusions: This is the first documented case series of patients treated effectively with topical oxymetazoline HCl 0.1% and pretarsal BoNT-A injections in the setting of botox-induced ptosis. This treatment combination is a safe and effective option in these cases., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Blepharoptosis, commonly referred to as ptosis or eyelid sagging, is a condition where the upper eyelid droops over the eye. It can be congenital or acquired and is caused by the weakening of the eyelid muscles., Case Report: We present a case of a 3-year-old boy with T-cell acute lymphoblastic leukemia who developed bilateral ptosis while on treatment with Berlin-Frankfurt Munster-98 protocol., Management & Outcome: The patient was diagnosed with bilateral ptosis due to vincristine, the primary agent in the induction phase of the protocol. The addition of the neuroregenerative agents and supportive measures led to marked improvement, followed by complete resolution within 3 weeks., Discussion: Vincristine is an anticancer agent with known neurotoxicity, which has a significant role in treating hematological malignancies and sarcoma. In many studies, the addition of neuroregenerative agents such as pyridoxine and pyridostigmine has been noted to hasten recovery without any documented side effects. Similar findings were also drawn from our research due to India's higher incidence of vincristine-induced neurotoxicity. It is essential to promptly diagnose and manage symptoms at the earliest to prevent the risk of permanent nerve damage and inferior quality of life for the patient.

Purpose: This study assesses the effects of topical oxymetazoline 0.1% on eyelid position, eye redness, and patient-perceived eye appearance in patients without severe ptosis., Methods: This is a randomized double-blinded controlled trial conducted at a single institute. Patients aged 18-100 years were randomized to receive one drop of oxymetazoline hydrochloride 0.1% or placebo bilaterally. Marginal reflex distance (MRD) 1 and 2, palpebral fissure height, eye redness, and patient-perceived eye appearance were assessed at baseline and two hours after drop instillation. Primary outcome measures included the change in MRD1, MRD2, and palpebral fissure height. Secondary outcome measures included changes in eye redness and patient-perceived eye appearance after drop instillation., Results: In total, 114 patients were included, 57 treatment patients (mean age 36.4 ± 12.7 years, 31.6% male) and 57 controls (mean age 31.3 ± 10.1 years, 33.3% male). Baseline mean MRD1, MRD2, and palpebral fissure were similar between groups (p = 0.24, 0.45, and 0.23, respectively). Changes in MRD1 and eye redness in the treatment group were significantly greater than those in the control group (0.9 ± 0.9 mm vs. - 0.3 ± 0.4 mm, p < 0.001; - 2.6 ± 4.4 vs. - 0.5 ± 2.3, p = 0.002, respectively). Patient-perceived eye appearance was significantly improved in the treatment group compared to the controls (p = 0.002), with more treatment group patients also reporting increased eye size and decreased eye redness (p = 0.008, p = 0.003, respectively). There were 9 treatment-emergent adverse events (TEAEs) in 7 treatment group patients and 5 TEAEs in 5 control patients (p = 0.25), all of which were mild in severity., Conclusions: Topical oxymetazoline 0.1% increases MRD1 and palpebral fissure height, decreases eye redness, and improves patient-perceived eye appearance., Competing Interests: Conflicts of Interest WWL is a consultant for Allergan, Galderma, Revance, Evolus, RVL, Horizon Therapeutics, Mallinckrodt, Tarsus and Solta. The following authors have no relevant financial disclosures or conflicts of interest: MKS, ZM, KA, EB, KDC, and SU., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Botulinum toxin type A is an effective preventive therapy for chronic migraine. Although the guidelines suggest a 50U/ml dilution of OnabotulinumtoxinA (BoNT/A), many clinicians use more concentrated solutions. However, there are no studies regarding the effect and safety of 100U/ml BoNT/A dilution with the saline solution following the PREEMPT paradigm. Our primary goal was to evaluate the efficacy, in reducing migraine frequency, and safety of two different BoNT/A dilutions (100U/ml vs 50U/ml) in the treatment of Chronic migraine. Our secondary goal was to determine the predictors of BoNT/A response. We retrospectively collected data from 113 chronic migraine patients treated with 3 rounds of BoNT/A according to the PREEMPT protocol as a preventive therapy. Patients were divided into two groups, based on BoNT/A dilution: 50U/ml (49 patients) vs. 100U/ml (64 patients) of sodium chloride 0.9%. We compared the migraine days/month, intensity, and intake of symptomatic medications at the baseline with the data obtained after the treatment; moreover, we evaluated the occurrence of adverse effects observed in the two groups. There was no difference regarding efficacy and safety between the two groups except for eyelid ptosis, which was more common in the 50U/ml BoNT/A group (p 0.018). Unilateral localization of migraine was associated with a more favorable outcome (OR 5.593, C.I. 2.358-13.268; p < 0.001) while Major Depressive Disorder predicted a less favorable response (OR 0.213, C.I. 0.087-0.523; p < 0.001). In our study, BoNT/A dilution did not influence the response to the therapy, but 100U/ml dilution could reduce the risk of eyelid ptosis. Unilateral localization of migraine pain might predict a more favorable response to the therapy, while the presence of a Major Depressive Disorder might predict a less favorable response., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objective: We present a case of a patient who developed myasthenia gravis (MG)-like symptoms during erenumab treatment., Case Report: The patient had a years-long history of chronic migraine with visual and sensory aura. Two months after the beginning of erenumab therapy, she reported intermittent bilateral weakness of the eyelids, with ptosis. The eyelid ptosis was severe enough to block the patient's vision. The symptoms would usually last between 5 and 10 minutes and resolve completely spontaneously, but they repeated on a daily basis. Antibodies against acetylcholine receptors and muscle-specific kinase were all negative, and other work-up excluded the usual etiology of ptosis. Since the cause of symptoms was not detected, we suspected they were induced by erenumab. The treatment was discontinued, and after 7 weeks from the last dose of erenumab, ocular symptoms resolved completely. In the presented case, other possible causes of MG-like symptoms were excluded by diagnostic tests and clinical course of the disease. The temporal relationship between the administration of erenumab and occurrence of ptosis, with regression of the symptoms after the drug discontinuation supports the hypothesis of causal relationship with erenumab. According to the Naranjo's Adverse Drug Reaction Probability Scale, erenumab-related MG-like symptoms were rated 'probable'. Reviewing the literature, we identified no similar case reports., Conclusion: Drug-induced MG-like symptoms might be life threatening. Therefore, clinicians should be aware of these adverse reactions during the use of erenumab.

Nivolumab blocks inhibitors of T-cell activation and restores antitumor immunity but promotes T-cell activity in host tissues by blocking inhibition of the T-cell function, resulting in immune-related adverse effects. We herein report an 80-year-old man presenting with nivolumab-related myasthenia gravis with anti-muscular voltage-gated potassium channel-complex (Kv1.4) antibodies. On day 29 after nivolumab administration, he simultaneously developed rapidly progressing right ptosis and left facial paralysis. Nivolumab administration was discontinued. He subsequently presented with bulbar paralysis, dyspnea, and muscle weakness and received intravenous immunoglobulin, methylprednisolone, and plasma exchange. The severity of nivolumab-related myasthenia gravis with anti-Kv1.4 antibodies presented with diverse clinical findings.

Purpose: To evaluate the effects of discontinuing anticoagulants (ACs)/antiplatelets (APs) preoperatively on surgery for blepharoptosis., Method: A retrospective analysis included patients with acquired blepharoptosis who underwent surgical correction, and were followed for more than 1 month. Patients were classified into 2 groups depending on AC/AP treatment or otherwise. All patients taking AC/AP discontinued with the treatment 1 week prior to surgery in accordance with our clinical guidelines. Preoperative and postoperative marginal reflex distance 1 (MRD1) and ecchymosis grade were evaluated and compared., Results: Group 1 (AC/AP treatment cessation) included 47 patients with 93 eyelids, and group 2 (control) included 51 patients with 98 eyelids. The preoperative MRD1 showed no significant difference between groups. Group 1 showed a significantly higher rate of severe ecchymosis (41.8 versus 22.4%, P = 0.004) at 1 week of surgery as well as persistent ecchymosis (58.8 versus 7.3%, P = 0.000) compared with group 2 postoperatively at 1 month. Postoperative MRD1 was significantly lower in group 1 at 1 week (P = 0.019). However, the MRD1 and degree of improvement in lid height (postoperative MRD1 "preoperative MRD1) was not significantly different between the 2 groups (P = 0.499, P = 0.058) at 1 month postoperatively., Conclusions: Postoperative ecchymosis was more severe in group 1 at 1 month after ptosis surgery even though the ACs/APs were discontinued. Surgeons should be careful about this before operation., The Synopsis: Significant ecchymosis could occur even after discontinuation of antithrombotic agents in patients with a history of taking medication in ptosis surgery. Surgeons should be careful about this before operation., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Background: Botulinum toxin A (BoNT-A) has grown tremendously in aesthetic dermatology since 2002 when the United States Food and Drug Administration (FDA) first approved its use for treating moderate-to-severe glabellar lines. Blepharoptosis, due to local spread of toxin, is a reported side effect of BoNT-A which, although rare, more frequently occurs among inexperienced practitioners., Objectives: The purpose of this review is to highlight the causes and management of eyelid ptosis secondary to BoNT-A administration including new anatomic pathways for BoNT-A spread from the brow area to the levator palpebrae superioris muscle., Methods: A literature search was conducted using electronic databases (PubMed, Science Direct, MEDLINE, Embase, CINAHL, EBSCO) regarding eyelid anatomy and the underlying pathogenesis, presentation, prevention, and treatment of eyelid ptosis secondary to BoNT-A. Anatomic dissection has been performed to assess the role of neurovascular pedicles and supraorbital foramen anatomic variations., Results: Blepharoptosis occurs due to weakness of the levator palpebrae superioris muscle. Mean onset is 3-14 days after injection and eventually self-resolves after the paralytic effect of BoNT-A wanes. Administration of medications, such as oxymetazoline hydrochloride or apraclonidine hydrochloride eye drops, anticholinesterase agents, or transdermal BoNT-A injections to the pre-tarsal orbicularis, can at least partially reverse eyelid ptosis. Anatomic study shows that a supraorbital foramen may be present in some patients and constitutes a shortcut from the brow area directly into the orbital roof, following the supraorbital neurovascular pedicle., Conclusion: Providers should understand the anatomy and be aware of the causes and treatment for blepharoptosis when injecting BoNT-A for the reduction of facial wrinkles. Thorough anatomic knowledge of the supraorbital area and orbital roof is paramount to preventing incorrect injection into "danger zones," which increase the risk of eyelid ptosis., (© 2021 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: An increasing number of people are undergoing non-surgical aesthetic procedures, especially injections of botulinum toxin and dermal fillers. While toxin injections have lower rates of complications, profound and serious consequences can arise with the use of dermal fillers., Case: A 29-year-old woman presented to the eye casualty department with sudden visual loss, ptosis and ophthalmoplegia after having had non-surgical rhinoplasty in a beauty salon in West London. The filler was administered by a healthcare professional not registered with the General Medical Council (GMC) or similar governing body., Discussion: Despite prompt measures on arrival at our service, the symptoms of visual loss, ptosis and ophthalmoplegia persisted. Attempts from the patient and medical services to report the incident (to trading standards and the police) were to no avail., Conclusion: This case highlights the poor treatment response to filler-related ophthalmic complications. It is also evident that in the United Kingdom, there appears to be poor regulation in the use of these products, a lack of clear guidelines for the management of their complications and finally no recourse for patients to challenge practitioners who lack medical registration and are not held accountable.

Background: At present, patients with ocular myasthenia gravis (OMG) are typically treated with systemic drugs. We investigated the use of dexamethasone injected in the peribulbar region or extraocular muscle to treat patients with OMG., Methods: Patients with OMG were given dexamethasone via peribulbar injection or direct injection into the main paralyzed extraocular muscles, once a week, for 4-6 weeks. The severity of diplopia, blepharoptosis, eye position, and eye movement were evaluated before and after treatment. The duration of follow-up time was ≥6 months., Results: Among the 14 patients with OMG who received this treatment, mean age was 38.7 ± 29.7 years. After treatment, symptoms were relieved in 12 patients (85.7%), 1 patient (7.1%) had partial response to treatment, and 1 patient (7.1%) had no response. Two patients (14.2%) experienced symptom recurrence during the follow-up period., Conclusions: Dexamethasone peribulbar or extraocular muscle injection is effective in the treatment of patients with OMG and may replace systemic drug therapy., Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000038863 , October 7, 2020.Retrospectively registered.

Purpose: The purpose of the study is to analyze the incidence, manifestations, and treatment of blepharoptosis caused by long-term use of corticosteroid eyedrops., Methods: Retrospective case series include 46 patients with a history of using corticosteroid eyedrops unilaterally for at least 2 months. The palpebral fissure, MRD1, and levator function were evaluated., Results: Among 46 patients, the differences of mean MRD1 (p < 0.0005), palpebral fissure height (p < 0.0005), and levator function (p = 0.003) between eyes with and without corticosteroid eyedrops application were significant. Ptosis existed in 40 out of 46 eyes with corticosteroid; the differences of the mean MRD1 (p < 0.0005) and palpebral fissure height (p = 0.001) between eyes with and without ptosis were significant. Nine patients underwent levator aponeurosis repair surgeries. Pathological examinations revealed mainly vascular fibers and few muscle fibers, as well as apoptosis of levator palpebrae muscle and Muller muscle., Conclusion: Blepharoptosis is frequently observed after chronic corticosteroid eyedrops use in Chinese population.

Cannabis is the most consumed illicit drug worldwide. As more countries consider bills that would legalize adult use of cannabis, health care providers, including eye care professionals (ophthalmologists, optometrists), will need to recognize ocular effects of cannabis consumption in patients. There are only 20 studies on the eyelid effects of cannabis usage as a medical treatment or a recreational drug. These include ptosis induction, an "eyelid tremor" appearance and blepharospasm attenuation. Six articles describe how adequately dosed cannabis regimens could be promising medical treatments for blepharospasm induced by psychogenic factors. Fourteen articles report eyelid tremors in intoxicated drivers and ptosis as a secondary effect in cannabinoid animal experimental models. The exact mechanism of cannabinoids connecting cannabis to the eyelids is unclear. Further studies should be conducted to better understand the cannabinoid system in relation to the eyelid and eventually develop new, effective and safe therapeutic targets derived from cannabis., (© 2019 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: To investigate the prevalence and frequency of patients with blepharoptosis who take anticholesterol therapies. To our knowledge, this is the first large single-center series to evaluate this association., Methods: A retrospective chart review of adult patients presenting with ptosis on concomitant anticholesterol medications., Results: Two hundred ninety-three adult patients with ptosis taking anticholesterol therapy were identified from October 2011 to October 2016. Forty-seven patients (16.0%) reported muscle weakness. Laboratory markers including creatine kinase (CK) and myoglobin levels were obtained. Of the 47 patients, 13 patients (4.4%) were identified to have ptosis and laboratory confirmed anticholesterol therapy-induced myopathy. Two additional patients with statin-induced myositis and rhabdomyolysis were identified from the period 2008-2011. All patients had measurably elevated CK and/or myoglobin levels. All patients experienced improvement in ptosis or systemic symptoms after discontinuation or changing medications. Nine patients (60%) demonstrated statistically significant improvement in the ptosis., Conclusions: Many patients with involutional ptosis also have both cardiovascular disease and hyperlipidemia and thus take cholesterol-lowering medication. Our study demonstrates a World Health Organization-defined probable association between ptosis and anticholesterol-induced myopathy. The frequency of anticholesterol-induced myopathy in adult ptosis was 4.4%, which is substantially higher than previously predicted. Anticholesterol-induced myositis can cause a reversible ptosis, and thus, a thorough evaluation of adult patients presenting with involutional ptosis includes inquiry into the use of anticholesterol drugs and associated muscle weakness.Anticholesterol medication may induce or exacerbate myogenic ptosis in some individuals.

A 73-year-old man developed diplopia after the administration of pembrolizumab for lung adenocarcinoma. He had ptosis and external ophthalmoplegia without general muscle weakness. Serum CK levels were elevated. Although autoantibodies to acetylcholine receptor and muscle-specific kinase, the edrophonium test, and the repetitive nerve stimulation test were all negative, anti-titin autoantibody was positive, leading to the diagnosis of myasthenia gravis (MG). Muscle pathology showed necrotizing myopathy with tubular aggregates. Unlike previously reported cases of pembrolizumab-associated MG, the present case showed ocular MG. This is the first case of pembrolizumab-associated MG with anti-titin antibody, as well as the first case with tubular aggregates.

Hyaluronic acid injection can lead to skin necrosis, visual loss, and other complications. The blindness with ophthalmoplegia and ptosis is a rare, but terrible and devastating complication. The disfigured appearance usually has significant impact on patient's social life. There is no standard treatment. A patient with hyaluronic acid induced blindness, ophthalmoplegia, and ptosis is reported. Six days after the onset, peribulbar/retrobulbar injections of high dosage hyaluronidase were performed. The orbital edema and ptosis immediately improved. The ophthalmoplegia and ptosis improved significantly within a month and resolved completely within 3 months, although the right vision remained blind. Peribulbar/retrobulbar injection of hyaluronidase is a potential rescue therapy for the hyaluronic acid induced ophthalmoplegia and ptosis.

Functional somatic syndromes (FSS), a clinical condition manifesting a variety of unexplained somatic symptoms, has been proposed as an inclusive nosology encompassing individual syndromes such as fibromyalgia syndrome and irritable bowel syndrome. Accumulating evidence suggests that disturbance of the endogenous monoamine system could be involved in the aetiology of FSS. Therefore, the purpose of present study was to investigate whether the disturbance of the monoamine system would cause FSS-associated symptomatology in mice. The optimal dose of reserpine, an inducer of endogenous monoamines reduction, was first explored in mice. General body condition (body weight, rectal temperature, and ptosis) and FSS-associated symptomatology (paw withdrawal threshold, small intestinal transit, and locomotor activity) were measured. The concentration of monoamines was measured in central and peripheral tissues. Mice dosed with reserpine (0.25 mg/kg s.c., once daily for 3 consecutive days) exhibited a decrease in paw withdrawal threshold, delay in small intestinal transit, and reduction of locomotor activity without deterioration of general body condition on day 5 after the first reserpine injection. The concentration of monoamines was decreased in the central nervous system and skeletal muscle, but not in the small intestine. A reserpine dose of 0.5 mg/kg or more caused deterioration of general body condition. In conclusion, the optimal protocol of reserpine treatment for inducing pain symptom without deterioration of general physical condition is 0.25 mg/kg s.c., once daily for 3 consecutive days in mice. This protocol causes not only pain but also FSS-associated symptomatology which are associated with disruption of the endogenous monoamine system. The reserpine-treated animal may be useful for the research of not only fibromyalgia syndrome but also FSS, especially for the research focusing on the hypothesis that FSS is associated with the disturbance of endogenous monoamine system., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The non-vitamin K antagonist oral anticoagulant rivaroxaban is indicated in prevention and treatment of venous thromboembolism (VTE). A 60-year-old male patient complained of bilateral ptosis after administration of rivaroxaban for deep vein thrombosis (DVT). Myasthenia gravis (MG) was confirmed by positive serum antiacetylcholine receptor antibody test. No mediastinal thymoma was found. The ocular myasthenia reversed after discontinuing rivaroxaban treatment. Nevertheless, ptosis recurred and chronic oral pyridostigmine bromide treatment was necessary. The mechanism of MG development by rivaroxaban therapy is not completely understood. The development of rivaroxaban-induced autoimmune disease could be based on cross-reactivity between antibodies against rivaroxaban-derived antigens or by T-cell activation. To our knowledge, this report of ocular myasthenia by rivaroxaban administration is the first in the literature. Despite the benefits of rivaroxaban, it is important to recognize unexpected immune-related adverse events., (Copyright © 2018 Elsevier Inc. All rights reserved.)

FK506 (tacrolimus) is an immunosuppressive drug and more potent than cyclosporine. FK506 is widely used for immunosuppression in the prevention and treatment of graft-versus-host disease after allogeneic bone marrow transplantation and solid organ transplantation. Neurotoxicity is a recognized complication of FK506 therapy, but ptosis and weakness of eye abduction unilaterally has not been reported in association with FK506 administration to date. We discuss a 13-year-old male patient who developed ptosis and weakness of eye abduction unilaterally 90 days after transplantation with bone marrow from an unrelated donor, for acute lymphoblastic leukemia in this case report. FK506 therapy was administered for graft-versus-host disease prophylaxis and CMV infection was treated with ganciclovir. The physical examination findings completely resolved 72 to 96 hours after concomitant FK506 and ganciclovir treatment were terminated.

Objective To examine treatment utilization patterns and safety of onabotulinumtoxinA for the prophylactic treatment of chronic migraine in routine clinical practice. Background Clinical trials support onabotulinumtoxinA for the prophylaxis of headache in patients with chronic migraine, but real-world data are limited. Design/methods A prospective, observational, post-authorization study in adult patients with chronic migraine treated with onabotulinumtoxinA. Data were collected at the first study injection and approximately every three months for ≤52 weeks for utilization and ≤64 weeks for safety data, and summarized using descriptive statistics. Results Eighty-five physicians (81% neurologists) at 58 practices in the United Kingdom, Germany, Spain, and Sweden participated and recruited 1160 patients (84.2% female, median age 46.6 years). At baseline, 85.8% of patients had physician diagnoses of chronic migraine/transformed migraine and reported an average of 11.3 (SD = 6.9) severe headache days per 28 days; 50.6% had previously used onabotulinumtoxinA for chronic migraine. A total of 4017 study treatments were observed. The median number of injection sites (n = 31) and total dose (155 U) were consistent across all treatment sessions, with a median 13.7 weeks observed between sessions. At least one treatment-related adverse event was reported by 291 patients (25.1%); the most frequently reported treatment-related adverse event was neck pain (4.4%). Most patients (74.4%) were satisfied/extremely satisfied with onabotulinumtoxinA treatment. Conclusions Patient demographics/characteristics are consistent with published data on the chronic migraine population. Utilization of onabotulinumtoxinA treatment for chronic migraine appears to be consistent with the Summary of Product Characteristics and published PREEMPT injection paradigm. No new safety signals were identified.

Rationale: Ptosis is a rare complication of periocular steroid use. Studies report that local injections of steroids produce ptosis. We describe the first 2 cases of ptosis because of long-term treatment with topical steroid eye drops., Patient Concerns: Two cases admitted to our hospital because of ptosis of their right eye after long-term treatment with topical steroid eye drops. Both of them had uncontrolled Posner-Schlossman syndrome., Diagnosis: Two cases were diagnosed as steroid-related ptosis., Interventions: Regulatory anti-inflammation therapy was prescribed for case 1, and after inflammation control, phacoemulsification was done for her. Six months after steroid withdrawal, the levator resection of the right eye was performed. Case 2 refused our advice of steroid reduction and ptosis surgery., Outcomes: After surgery, case 1 retained a symmetrical appearance during a 1-year follow-up. In the surgery, we found thin levator muscles and slack levator palpebrae superioris aponeurosis (LPSA) in the affected eye. Postoperative transmission electron microscopy revealed typical signs of apoptosis in levator muscle cells., Lessons: We suggest topical application of steroids induces levator muscle apoptosis and LPSA weakness, and results in ptosis., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The first symptoms of myasthenia gravis (MG) usually involve weakness of the ocular muscles, making it relevant that ophthalmologists have updated information on studies as regards its relationship with the consumption of drugs, such as statins., Materials and Methods: A bibliometric analysis was performed using the Scopus database and by a search strategy in the selection of documents containing descriptors related to statins in the «Title» («TI») field and the descriptors «ophthalm *', «myast *', «visual *' in other fields of the document (period 1986-2015)., Results: The results showed that, while the number of scientific publications on ocular effects of statins has grown lineally (n=838; y=2.267x-4507.1; r=0.7221; time of duplication: 4.66 years, and rate of annual growth: 50.06%), the specific publications about MG have experienced an exponential growth (n=38; y=2E-262e 0.3001x ; r=0.3892; time of duplication: 2.95 years, and rate of annual growth: 46.25%) without reaching the saturation postulated in Price theory of the expansion of the scientific literature. The majority of publications relating to MG are reports of cases linked to a worsening of the MG symptoms, and simvastatin and atorvastatin are the agents mentioned in most of the publications., Conclusions: These results should enable ophthalmologists to expand their knowledge concerning the evolution of studies on statins and MG, pointing out the relevance of such causal relationships., (Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.)

In this article, a case of recurrent epithelial defects in neurotrophic keratopathy is described. Multiple abrasions of the corneal epithelium with a therapeutic contact lens, corneal stitches, and amniotic membrane transplantation in combination with artificial tears brought only short-term success. However, a botulinum toxin A induced protective ptosis could finally achieve permanent epithelial closure. As this case shows, protective ptosis can be a promising approach in spite of multiple previous ineffective therapeutic efforts.

Transient ptosis is a known complication of botulinum toxin (BoNT) injection due to inadvertent migration of toxin into the levator palpebrae superioris muscle. Currently there is no treatment available for BoNT induced ptosis. Apraclonidine hydrochloride is a topical ophthalmic solution with selective alpha-2 and weak alpha-1 receptor agonist activity that has the ability to elevate the eye lid. Apraclonidine has been used as a diagnostic test in Horner's syndrome. We evaluated the effects apraclonidine in a cohort of BoNT induced ptosis and a patient with Horner syndrome. Each patient was administered 2 drops of apraclonidine 0.5% solution to the eye with the ptosis and was re-examined 20-30min later. All 6 patients showed improvement in ptosis. There was also improvement in ptosis in a patient with Horner's syndrome. Apraclonidine is not only useful as a diagnostic test in Horner's syndrome, but may be an effective and safe treatment for BoNT-induced ptosis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Immune checkpoint inhibitors have changed the landscape of the treatment of multiple solid malignancies, and have been used increasingly in the recent years. Although usually well tolerated, given the relative inexperience of using immune checkpoint inhibitors, we are still learning of new side effects from the treatment. We report on two cases of ocular myasthenia gravis that occurred after treatment with pembrolizumab, an antiprogrammed-death (anti-PD1) monoclonal antibody for advanced melanoma in responding patients. One case is in an 81-year-old man and the second case in an 86-year-old woman, both with BRAF-negative metastatic melanoma receiving pembrolizumab. These two cases of ocular only associated myasthenic syndrome appeared 7 and 11 weeks after the initiation of pembrolizumab. We conclude that the condition is most likely associated with pembrolizumab as symptoms started after treatment with pembrolizumab, neither patient had other evidence of neurological cause for presentation, and symptoms also improved rapidly with administration of steroids. Both patients showed good oncological response to anti-PD1 treatment and one patient successfully continued to receive ongoing treatment with no further complications.

Background: Ptosis after botulinum toxin injection is a disturbing complication. Decongestant and antiglaucoma eyedrops are frequently prescribed for temporary improvement of eyelid ptosis. Although frequently cited on informal communications, the effect of these drugs on eyelid position has never been compared in a formal study., Objective: To measure the effect of low-concentration, nonmydriatic selective alpha agonist eyedrops on upper eyelid position., Methods and Materials: This nonrandomized clinical trial enrolled 20 healthy subjects aged 18 to 50 years. The upper margin-reflex distance (MRD1) was measured before, 30, 60, and 120 minutes after administration of 1 drop of brimonidine 0.2%, phenylephrine 0.12%, or naphazoline 0.05% to the left eye., Results: There was no statistically significant difference in mean MRD1 between the brimonidine and phenylephrine groups when comparing baseline to all other study time points. After administration of naphazoline 0.05%, MRD1 had a mean increase of 0.56 ± 0.11 mm (p < 0.001) after 30 minutes, 0.47 ± 0.12 mm (p = 0.001) after 60 minutes, and 0.26 ± 0.09 mm (p = 0.028) after 120 minutes when compared with baseline., Conclusion: Brimonidine 0.2% and phenylephrine 0.12% have no effect on eyelid aperture, but naphazoline 0.05% eyedrops could be useful for temporary relief of upper eyelid ptosis in selected patients.

The Radix Bupleuri and Radix Paeoniae Alba drug pair plays a pivotal role in Xiaoyaosan, a famous Chinese herbal preparation that is popular in clinical medicine. To investigate the antidepressant-like effects and potential mechanism of action of the Radix Bupleuri and Radix Paeoniae Alba drug pair, we carried out the forced swim test (FST) and tail suspension test (TST), as the mouse models of depression; and the open field test (OFT) to exclude false-positive results. Subsequently, ptosis and hypothermia induced by reserpine were assessed. Finally, the concentrations of monoamine neurotransmitters and their metabolites, namely epinephrine (NE), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampal and cortical tissues of mice were detected with HPLC with electrochemical detector. The Radix Bupleuri and Radix Paeoniae Alba (1:1) drug pair at low, medium, and high doses decreased immobility time in both the FST and TST, and counteracted hypothermia induced by reserpine in mice. After the administration of reserpine, the concentrations of 5-HT and NE in the hippocampal and cortical tissues were decreased; however, pre-treatment with the Radix Bupleuri and Radix Paeoniae Alba drug pair significantly elevated the concentrations of 5-HT and NE in the hippocampal and cortical tissues. The results suggested that, compared with single dose of fluoxetine and the drugs used individually, the Radix Bupleuri and Radix Paeoniae Alba drug pair had an excellent antidepressant-like effect. These data revealed a possible mechanism of action, as the regulation of the central monoaminergic neurotransmitter system in the hippocampal and cortical tissues., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Through its conversion to dopamine by aromatic l-amino acid decarboxylase (AADC), l-3,4-dihydroxyphenylalanine (l-DOPA) replenishes depleted brain dopamine in Parkinson's disease patients. We recently identified GPR143 as a candidate receptor for l-DOPA. In this study, we investigated the behavioral actions of l-DOPA in wild type (wt) and Gpr143-deficient mice. l-DOPA dose-dependently (10-100 mg/kg, i.p.) induced ptosis under treatment with 3-hydroxybenzylhydrazine, a centrally acting AADC inhibitor. This effect was not mimicked by 3-O-methyldopa. l-DOPA-induced ptosis in Gpr143-deficient mice to a similar extent as in wt mice. These results suggest that l-DOPA induces ptosis in a GPR143-independent fashion in mice., (Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

This column highlights some of the potential complications that have been associated with cosmetic procedures. Tips for how dermatology residents may prevent, identify, and manage complications from cosmetic procedures for optimal patient outcomes is provided. In part 1 of this series, soft-tissue augmentation and botulinum toxin injections are discussed. Part 2 will focus on chemical peels and laser therapy.

A 70-year-old woman presented to our practice with profound ptosis of the left upper eyelid and notable asymmetry of the periocular area. On examination, she was noted to have significant atrophy of the periocular tissues on the left side, with lower eyelid retraction. These features were present but less severe on the right side. Upon further questioning, she stated that she had cataract surgery on the left side that was complicated by a high intraocular pressure and required subsequent secondary surgery. She had taken a prostaglandin eyedrop for many months after her cataract surgery to keep the eye pressure low. Recently, a newly recognized adverse effect of prostaglandin eyedrops has been described in the ophthalmic literature in which patients develop periorbital lipodystrophy. This case emphasizes that this may occur unilaterally in patients taking the eyedrop in only one eye, and should be recognized prior to considering functional and aesthetic surgery of the periocular area., (© 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)