Clinical and muscle MRI features in a family with tubular aggregate myopathy and novel STIM1 mutation.

Heterozygous mutations in the stromal interaction molecule-1-gene (STIM1) cause a clinical phenotype varying from tubular aggregate myopathy with single or multiple signs of Stormorken syndrome to the full Stormorken phenotype. We identified a novel heterozygous mutation c.325C > T (p.H109Y) in the EF-hand domain of STIM1 in six patients of a large Belgian family, and performed a detailed clinical (N = 6), histopathological (N = 2) and whole-body muscle MRI (N = 3) study. The clinical phenotype was characterized by a slowly progressive, predominant proximal muscle weakness in all patients (100%), and additional exercise-induced myalgia in three (60%). Patients experienced symptom onset between 10 and 20 years, remained ambulatory into late adulthood, showed elevated serum creatine kinase levels and tubular aggregates in type 1 and type 2 fibers on muscle biopsy. Interestingly, jaw contractures and hyperlaxity, as well as non-muscular multisystemic features such as menorrhagia, easy bruising and ichthyosis occurred in one patient, and miosis in another. Whole-body muscle MRI revealed predominant involvement of superficial neck extensors, subscapularis, obliquus abdominis externus, lumbar extensors, rectus femoris, biceps femoris longus, medial head of gastrocnemius and flexor hallucis longus. Our findings in patients with myopathy with tubular aggregates and a STIM1 mutation further support the concept of a continuous spectrum with Stormorken syndrome.

Pharmacological Strategies for Presbyopia Correction.

PURPOSE: To summarize the pharmacological strategies that are being explored for presbyopia correction. METHODS: The review concentrates on pharmacologically induced pupillary miosis to increase depth-of-focus and lens softening or other measures to restore active accommodation. RESULTS: Several studies suggest that near vision improves and distance vision is unaffected for many hours after either monocular or binocular instillation of any one of several drug combinations that cause miosis. Unfortunately, in most studies, measurements were limited to photopic visual acuity for near and distance vision, whereas it is anticipated that pupil constriction may have adverse effects on mesopic and scotopic vision. It is not clear whether improved near vision was due entirely to increased depth-of-focus, or whether, for example, a drug-induced myopic shift in refraction was also involved. Currently, no study has provided direct evidence for drug-induced restoration/enhancement of true accommodation involving an ocular power change. CONCLUSIONS: Although it is possible that, in the future, pharmacological drops may offer a safe and reliable solution for presbyopia correction, more evidence of their effectiveness and limitations is required. [J Refract Surg. 2019;35(12):803-814.].

Osteomielitis fúngica en niños quemados / Fungal osteomyelitis in burned children

Introducción: En pacientes pediátricos quemados la osteomielitis fúngica es una complicación infrecuente que conduce a una significativa morbilidad. La información en la literatura está limitada a unos escasos reportes de casos. Objetivo: Describir las características clínicas, epidemiológicas y de evolución de niños quemados con osteomielitis fúngica. Métodos: Se llevo a cabo un estudio retrospectivo y descriptivo de pacientes mayores de 1 mes y menores de 18 años quemados con osteomielitis fúngica internados en el hospital Juan P. Garrahan, un hospital terciario en Buenos Aires, Argentina. Resultados: entre enero del 2007 y enero del 2017, de 600 niños quemados, 9 pacientes presentaron diagnóstico confirmado de osteomielitis fúngica. La mediana de edad fue de 42.5 meses (RIC, 27-118 meses) y la mediana de superficie quemada fue de 33.5% (RIC, 18.5-58%). La osteomielitis fue diagnosticada con una mediana de 30 días luego de la quemadura. Las localizaciones más frecuentes de osteomielitis fueron los miembros superiores y a nivel de calota. Los microorganismos aislados a partir del cultivo de hueso fueron: Fusarium spp. en tres pacientes, Mucor spp. en un paciente; Trichosporon asahii en un paciente; Cándida albicans en dos pacientes y Candida parapsilosis en dos pacientes. En dos casos la infección fúngica fue asociada con aislamientos bacteriano concomitante. Todos los pacientes presentaron hallazgos histopatológicos compatibles con osteomielitis. La mediana de tiempo de tratamiento fue de 44.5 días (RIC, 34.5- 65.5 días). Seis pacientes (67%) presentaron secuela motora. Conclusión: La osteomielitis fúngica fue infrecuente Candida spp. y Fusarium spp. fueron los hongos más comúnmente identificados. La secuela funcional fue frecuente (AU)

Introduction: In pediatric burn patients fungal osteomyelitis is a rare complication that leads to significant morbidity. Data in the literature are limited to sporadic case reports. Objective: To describe the clinical and epidemiological features and outcome in burned children with fungal osteomyelitis. Methods: A retrospective descriptive study was conducted in burn patients older than 1 month and younger than 18 years admitted to Hospital Juan P. Garrahan, a tertiary hospital in Buenos Aires, Argentina. Results: Between January 2007 and January 2017, of 600 burned children, nine had a confirmed diagnosis of fungal osteomyelitis. Median age was 42.5 months (IQR, 27-118 months) and median burn surface was 33.5% (IQR, 18.5-58%). Osteomyelitis was diagnosed at a median of 30 days after the burn. The most common location of osteomyelitis were the upper limbs and skull. The microorganisms isolated form bone cultures were Fusarium spp. in three patients, Mucor spp. in one patient; Trichosporon asahii in one patient; Candida albicans in two patients; and Candida parapsilosis in two patients. In two cases the funal infection was associated with concomitant bacterial isolation. In all patients, the histopathological findings were compatible with osteomyelitis. Median duration of treatment was 44.5 days (IQR, 34.5-65.5 days). Six patients (67%) had motor sequelae. Conclusion: Fungal osteomyelitis is a rare disease. Candida spp. and Fusarium spp. were most frequently identified fungi. Functional sequelae were common (AU)

CRAC channels and disease - From human CRAC channelopathies and animal models to novel drugs.

Ca2+ release-activated Ca2+ (CRAC) channels are intimately linked with health and disease. The gene encoding the CRAC channel, ORAI1, was discovered in part by genetic analysis of patients with abolished CRAC channel function. And patients with autosomal recessive loss-of-function (LOF) mutations in ORAI1 and its activator stromal interaction molecule 1 (STIM1) that abolish CRAC channel function and store-operated Ca2+ entry (SOCE) define essential functions of CRAC channels in health and disease. Conversely, gain-of-function (GOF) mutations in ORAI1 and STIM1 are associated with tubular aggregate myopathy (TAM) and Stormorken syndrome due to constitutive CRAC channel activation. In addition, genetically engineered animal models of ORAI and STIM function have provided important insights into the physiological and pathophysiological roles of CRAC channels in cell types and organs beyond those affected in human patients. The picture emerging from this body of work shows CRAC channels as important regulators of cell function in many tissues, and as potential drug targets for the treatment of autoimmune and inflammatory disorders.

Efficacy of 0.015% intracameral epinephrine for significant miosis induced by photodisruption during femtosecond laser-assisted cataract surgery.

Despite the various advantages of femtosecond laser-assisted cataract surgery (FLACS), pupillary constriction during laser photodisruption is considered one of the most unfavorable events. This study aimed to investigate the efficacy of intracameral 0.015% epinephrine injection for miosis after laser pretreatment during FLACS.A total of 82 patients who underwent FLACS for age-related cataracts were investigated in this retrospective study. The epinephrine group included patients who received intracameral epinephrine injection for miosis after femtosecond laser pretreatment, while the no-epinephrine group included the patients who underwent FLACS without intracameral epinephrine due to minimal miosis. Quantitative pupil area measurements were performed through the analysis of captured images extracted from surgical videos of both femtosecond laser pretreatment and phacoemulsification.Laser photodisruption induced miosis in both groups, although the degree of miosis was greater in the epinephrine group (4.65 ±â€Š0.87 mm) than in the no-epinephrine group (6.30 ±â€Š0.65 mm; P < .001). The intracameral epinephrine injection significantly increased the pupil diameter from 4.65 ±â€Š0.87 to 5.49 ±â€Š0.76 mm (21.61 ±â€Š22.68%; P < .001) and the pupil area from 70.28 ±â€Š24.46 to 96.49 ±â€Š25.24 mm (52.89 ±â€Š63.54%; P < .001). After additional viscomydriasis, there was no difference between groups in pupil diameter (epinephrine vs no-epinephrine group; 6.10 ±â€Š0.77 vs 6.39 ±â€Š0.65 mm; P = .073).A single intracameral injection of 0.015% epinephrine provided immediate and appropriate redilation of pupil in patients with significant miosis after femtosecond laser photodisruption. Intracameral epinephrine is a simple and practical option for pupil redilation in case of miosis during FLACS.

Vinorelbine Potently Induces Placental Cell Death, Does Not Harm Fertility and is a Potential Treatment for Ectopic Pregnancy.

Ectopic pregnancies complicate 1-2 pregnancies and are a leading cause of maternal death. An effective oral drug therapy that replaces surgery might make its treatment safer, cheaper, simpler and therefore more widely accessible. The only current medical treatment offered to women is intramuscular methotrexate, but this only reliably resolves smaller ectopic pregnancies. As such, many ectopic pregnancies require surgical excision. We show that vinorelbine, an orally available chemotherapeutic agent, potently induced placental cell death but did not harm fertility in mice. Vinorelbine was 100-1000 times more potent than methotrexate in inducing placental cell death in vitro, and more potent than combination methotrexate and gefitinib (another proposed treatment for ectopic pregnancy being evaluated in phase III trials). Mechanistically, it caused microtubule condensation, blocked mitosis and activated the apoptosis cascade in placental cells. Vinorelbine was more efficacious than methotrexate±gefitinib in reducing the volume of placental cell tumors xenografted subcutaneously in SCID mice. Mice exposed to vinorelbine and allowed to breed, following a four week washout period, displayed normal fertility, however long-term fertility was not assessed. Human Fallopian tubes treated with vinorelbine did not exhibit up-regulation of apoptosis molecules. Our findings show that placental cells appear sensitive to vinorelbine and it has potential as a tablet-only approach to treat ectopic pregnancy.

Intracameral Use of Nepafenac: Safety and Efficacy Study.

PURPOSE: To test the intracameral safety of nepafenac and its efficacy in inhibiting prostaglandin synthesis during phacoemulsification surgery. METHODS: The safety evaluation was conducted in normal eyes of rabbits, 0.1ml of 0.3% and 1% nepafenac was injected intracamerally. Extensive studies to detect adverse response ranged from a gross examination of eyes under slit lamp biomicroscope, fluorescein dye test, Schirmer tear test, test for corneal sensitivity, intraocular pressure measurement (IOP), specular microscopy, electroretinography(ERG), and histopathological examination of intraocular tissues. Efficacy of nepafenac was studied by intracameral injection of 0.1%, 0.3% nepafenac, nepafenac 0.3%+1% lignocaine, and 1% lignocaine alone, before phacoemulsification surgery and intraoperative mydriasis along with PGE2(ProstaglandinE2) secretion were recorded. RESULTS: Single 0.1ml of 0.3% or 1% nepafenac did not significantly (p > 0.05) alter physiological parameters and histology of cornea, iris, and retina. Nepafenac 0.3% effectively inhibited PGE2 secretion. No significant (p > 0.05) prevention of miosis was recorded with 0.1% or 0.3% nepafenac. However, a combination of 0.3% nepafenac + 1% lignocaine and 1% lignocaine alone significantly (p < 0.05) arrested miosis during the intraoperative period. CONCLUSION: An intracameral concentration of up to 1% nepafenac does not adversely affect the rabbit eye. Nepafenac fails to prevent miosis but inhibits prostaglandin release during phacoemulsification surgery.

Lymphatic malformation with acquired Horner syndrome in an infant.

An infantpresented with right upper eyelid ptosis and was subsequently diagnosed with acquired Horner syndrome. Further evaluation revealed a right-sided cervicothoracic lymphatic malformation. At 13 weeks of age, the child underwent percutaneous intracystic sclerotherapy with a mixture of sodium tetradecyl sulphate and ethanol. Twenty-one weeks after initial treatment, ophthalmic examination showed complete resolution of the blepharoptosis and pupillary miosis. Percutaneous sclerotherapy not only effectively treated the space-occupying lymphatic malformation but also reversed the Horner syndrome that was presumably induced by neural tension (more likely) or compression.

Naphazoline as a confounder in the diagnosis of carotid artery dissection.

Diagnosing Horner Syndrome can be difficult in the setting of an incomplete triad. A 27-year-old man presented with unilateral eyelid droop and intermittent ipsilateral headaches, having already seen 7 physicians. Physical examination revealed unilateral ptosis but no pupillary miosis or facial anhidrosis. Inspection of his clinical photographs revealed elevation of the ipsilateral lower eyelid, suggesting sympathetic dysfunction. On further questioning, he admitted to naphazoline dependence. Reexamination after ceasing the naphazoline unveiled the anisocoria. Vascular imaging subsequently revealed carotid dissection, and the patient was started on anticoagulant and antiplatelet therapy. The ptosis persisted after conjunctival Müllerectomy. External levator resection was recommended, but patient declined. This case underscores the importance of clinical photography, meticulous medical record review, and complete medication history including over-the-counter preparations. Clinicians should meticulously inspect the lower eyelid in cases of atypical blepharoptosis and consider the effects of eye drops when inspecting pupils for miosis.

Ophthalmic utility of topical bromfenac, a twice-daily nonsteroidal anti-inflammatory agent.

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) act by inhibiting the formation of prostaglandin by cyclooxygenases. Several agents in this class have been approved for the treatment of postoperative pain and inflammation following cataract surgery. Bromfenac 0.09% (Xibrom, ISTA Pharmaceuticals, USA) is a relatively new topical NSAID that exhibits ocular penetration and duration of action sufficient to permit twice-daily dosing. Bromfenac dosed twice-daily was clearly superior to placebo for postoperative pain and inflammation in a large, controlled trial and compares favorably with other NSAIDs in smaller studies. Adverse events associated with use have been minimal in large studies, although there are reports of corneal compromise with bromfenac use in cases of preexisting corneal disease. The comfort and reduced frequency of use offered by bromfenac would be expected to improve patient compliance, which would in turn be expected to result in adoption of bromfenac over other NSAIDs by many physicians. However, head-to-head trials comparing bromfenac with other NSAIDs using a twice-daily dosing schedule have not been undertaken. Bromfenac and other NSAIDs are seeing expanded use for the treatment and prevention of cystoid macular edema, and could have clinical utility in other diseases of vascular permeability.

Redilatation with intracameral mydriatics in phacoemulsification surgery.

PURPOSE: To determine whether intracameral mydriatics can redilate pupils that contract during phacoemulsification cataract surgery. METHODS: A total of 80 patients were included in this prospective, randomized, double-blind study performed at Ornsköldsviks Hospital Eye Clinic. Of these, 60 patients had 0.6 microg/ml of epinephrine added to the balanced salt solution (BSS) used for irrigation and 20 patients did not. The patients in each group were randomized and given either an intracameral mydriatics (ICM) solution or placebo intracamerally after phacoemulsification and cortex cleaning. The pupil size was registered preoperatively, after cortex cleaning, 30 seconds after study injection, 2 mins after study injection and the day after surgery. RESULTS: No clinically relevant differences were found preoperatively. In the epinephrine material a significantly longer operation time (p = 0.023) and more procedures requiring Vision Blue and Kelman-type tip in the placebo group might indicate diversity in the grade of cataract. There was a greater degree of contraction in the absence of epinephrine in the irrigation solution (2.3 +/- 1.0 mm in the ICM group and 3.2 +/- 0.7 mm in the placebo group) compared to in the presence of epinephrine. With no epinephrine ICM significantly redilated the pupils at 30 seconds (p < or = 0.001) as well as at 2 mins (p = 0.015). CONCLUSION: We have shown that in cases with an intraoperative pupil contraction, ICM is effective in redilating the pupil. Insufficient adrenergic stimulation of the pupil dilator appears to be a major factor causing intraoperative pupil contraction during phacoemulsification cataract surgery.

Etanercept treatment in the endotoxin-induced uveitis of rats.

This study was conducted to investigate therapeutic value of a soluble tumor necrosis factor-alpha (TNF-alpha) receptor, etanercept, in a rat model of endotoxin-induced uveitis (EIU). Forty-two inbred male Lewis rats were divided into seven equal groups. 200 microg of Escherichia coli 055:B55 lipopolysaccharide (LPS) was injected in one hind footpad of the Groups 2, 3, 4, 5, 6, and 7 rats. Group 5, 6, and 7 rats also received subcutaneous etanercept 24 hr prior to LPS injection at a dose of 0.4 mg kg(-1). Group 1 rats were used as controls. Eight, 24, and 48 hr after treatment clinical uveitis scores (miosis, iris hyperemia, and hypopyon) were assessed by a masked observer and the rats were euthanized. Neutrophil leukocytes, CD8+, CD4+, and CD45RO+ cells in the anterior uveal tissue were counted either after hematoxylin-eosin or monoclonal antibody staining. TNF-alpha levels were also measured in the aqueous humor samples by an ELISA method. Etanercept treatment significantly improved clinical uveitis scores at all examination points compared to the LPS injected animals. The improvement was almost complete expect for the miosis score, since no significant difference was detected between the controls and LPS + Etanercept treated animals at all examination points. Cell counts were also at significantly lower levels in LPS + Etanercept treated animals at all examination points, except for CD8+ and CD45RO+ cell counts at 24 hr examination point. There was no significant difference between the controls and LPS + Etanercept treated animals at all examination points as with CD4+ and CD45RO+ cell counts at 48 hr. Our data showed that etanercept had a definite effect on the treatment of EIU. Further studies should clarify its efficacy on clinical uveitis conditions.

Comparison of diclofenac sodium and flurbiprofen for inhibition of surgically induced miosis.

PURPOSE: To compare the efficacy of two topical nonsteroidal anti-inflammatory drugs, diclofenac sodium and flurbiprofen, commonly used prior to cataract surgery to inhibit surgically induced miosis. SETTING: Department of Ophthalmology, Cornell University Medical College, The New York Hospital, New York, New York. METHODS: Fifty-one patients having phacoemulsification were randomly assigned to receive topical treatment with either diclofenac sodium 0.1% or flurbiprofen 0.03% every 15 minutes for four doses along with their dilating drops beginning 1 hour before surgery. All surgeries were videotaped, with the magnification calibrated. The videotapes were analyzed and the horizontal and vertical diameters of the pupil were measured just before the initial conjunctival incision (baseline) and then every 5 minutes during the procedure. Measurements were also made at the beginning of capsulorhexis, the beginning of phacoemulsification, the end of phacoemulsification, the end of cortical cleanup, and before and after implantation of an intraocular lens. RESULTS: There was no statistically significant difference between the two treatment groups in baseline pupil dilation; however, regardless of the drug received, the light irides were, on average, more dilated at baseline than the dark ones. After surgery began, there were no statistically significant differences between the two groups at any time or surgical interval except at the start of phacoemulsification, at which point the flurbiprofen-treated eyes were more dilated than the diclofenac-treated eyes. CONCLUSION: Diclofenac sodium and flurbiprofen were equally effective in maintaining intraoperative mydriasis during cataract surgery.

Characterization of the mechanism of acute ocular irritation to YAG laser capsulotomy in rabbits: effects of substance P antagonists, Met-enkephalin, tetracaine and tetrodotoxin.

This study was undertaken to characterize the mechanism of ocular irritation to YAG laser capsulotomy in rabbits. The blocking agents were administered intravitreally. (D-Arg1,D-Pro2,D-Trp7,9)-SP, a substance P antagonist, tended to reduce miosis but had no effect on intraocular pressure (IOP). It had less effect on miosis than (D-Arg1,D-Pro2,D-Trp7,9,Leu11)-SP another SP antagonist. Met-enkephalin and tetracaine had no effect on miosis or the increase in IOP after YAG laser capsulotomy, whereas tetrodotoxin reduced miosis, but had no clear-cut effect on IOP, or the increase in aqueous humor protein concentration. This indicates an involvement of sensory neurons with release of SP or a closely related peptide in the miotic component part while the increase in IOP and the barrier breakdown probably are dependent mainly on a release of prostaglandins.