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Neuroptis Dry Eye Project with ML 7 (Myosin Light Chain Inhibitor)
27 avril 2015

Dry Eye Publications up to Apr. 27th 2015

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1. Optom Vis Sci. 2015 Apr 23. 

Author information: 

  • 1*MD Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy (all authors); Eye Clinic San Giuseppe Hospital of Milan, Milan, Italy (EV, VT, FP, PN); and Eye Clinic Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico of Milan, Milan, Italy (EG, RR).

 

Abstract
PURPOSE: 

To evaluate, by in vivo laser scanning confocal microscopy (LSCM), the corneal findings in moderate-to-severe dry eye patients before and after treatment with topical corticosteroid and to associate the confocal findings to the clinical response.

METHODS: 

Fifty eyes of 50 patients with moderate-to-severe dry eye were included in this open-label, masked study. Exclusion criteria were any systemic or ocular condition (other than dry eye) and any systemic or topical treatment (except artificial tears), ongoing or performed in the previous 3 months, with known effect on the ocular surface. All patients were treated with loteprednol etabonate ophthalmic suspension 0.5% qid for 4 weeks. Baseline and follow-up (day 30 ± 2) visits included Ocular Surface Disease Index (OSDI) questionnaire, full eye examination, and central cornea LSCM. We compared data obtained before and after treatment and looked for associations between baseline data and steroid-induced changes. Based on the previously validated OSDI Minimal Clinically Important Difference, we reanalyzed the baseline findings comparing those patients clinically improved after steroids to patients not clinically improved after steroids.

RESULTS: 

Ocular Surface Disease Index score and LSCM dendritic cell density (DCD) significantly decreased after treatment. Baseline DCD correlated with both OSDI and DCD steroid-related changes (r = -0.44, p < 0.05 and r = -0.70, p < 0.01, respectively; Spearman) and was significantly higher in patients clinically improved after steroids than in patients not clinically improved after steroids (164.1 ± 109.2 vs. 72.4 ± 45.5 cells/mm, p < 0.01; independent samples t test).

CONCLUSIONS: 

Laser scanning confocal microscopy examination of DCD allows detection of treatment-related inflammation changes and shows previously unknown associations between confocal finding and symptoms improvement after treatment. These promising preliminary data suggest the need for future studies testing the predictive value of DCD for a clinical response to topical corticosteroids.

  PMID: 25909241 [PubMed - as supplied by publisher]
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2. Cornea. 2015 Apr 23. [Epub ahead of print]

Author information: 

  • 1*Tianjin Medical University, Tianjin, China; †Tianjin Eye Hospital & Eye Institute, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Medical University, Tianjin, China; ‡University of California, Berkeley, College of Chemistry, Berkeley, CA; and §University of Toronto, Faculty of Arts and Science, Sidney Smith Hall, Toronto, Ontario, Canada.

 

Abstract
PURPOSE: 

To evaluate the efficacy and safety of topical diquafosol ophthalmic solution for treatment of dry eye.

METHODS: 

Randomized clinical trials (RCTs) from MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were identified to evaluate the efficacy and safety of topical administration of diquafosol to patients with dry eyes. Data evaluation was based on endpoints including Schirmer test, tear film break-up time, ocular surface staining score, subjective symptom score, and adverse events.

RESULTS: 

A total of 8 RCTs involving 1516 patients were selected based on the prespecified criteria. Significant improvement of Schirmer test values and tear film break-up time were reported in 40% (2 of 5) and 80% (4 of 5) studies, respectively. Ocular surface staining scores significantly decreased in 100% (fluorescein corneal staining, 6 of 6; Rose Bengal corneal and conjunctival staining, 4 of 4) RCTs. Symptoms significantly improved in 75% (6 of 8) RCTs in patients with dry eyes. No severe adverse events were reported with the concentration of diquafosol from 0.5% to 5%. Heterogeneity in study design prevented meta-analysis from statistical integration and summarization.

CONCLUSIONS: 

Topical diquafosol seems to be a safe therapeutic option for the treatment of dry eye. The high variability of the selected RCTs compromised the strength of evidence and limits the determination of efficacy. However, the topical administration of diquafosol seems to be beneficial in improving the integrity of the epithelial cell layer of the ocular surface and mucin secretion in patients with dry eyes. This review indicates a need for standardized criteria and methods for evaluation to assess the efficacy of diquafosol in the future clinical trials.

  PMID: 25909234 [PubMed - as supplied by publisher]
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3. Br J Ophthalmol. 2015 Apr 22. pii: bjophthalmol-2015-306629. doi: 10.1136/bjophthalmol-2015-306629. [Epub ahead of print]

Author information: 

  • 1Massachusetts Eye Research and Surgery Institution, Cambridge, Massachusetts, USA Ocular Immunology & Uveitis Foundation, Cambridge, Massachusetts, USA Faculty of Medicine, Department of Ophthalmology, Rajavithi Hospital, College of Medicine, Rangsit University, Bangkok, Thailand.
  • 2Massachusetts Eye Research and Surgery Institution, Cambridge, Massachusetts, USA Ocular Immunology & Uveitis Foundation, Cambridge, Massachusetts, USA.
  • 3Massachusetts Eye Research and Surgery Institution, Cambridge, Massachusetts, USA Ocular Immunology & Uveitis Foundation, Cambridge, Massachusetts, USA Harvard Medical School, Boston, Massachusetts, USA.

 

Abstract

Systemic lupus erythematosus (SLE) can involve many parts of the eye, including the eyelid, ocular adnexa, sclera, cornea, uvea, retina and optic nerve. Ocular manifestations of SLE are common and may lead to permanent blindness from the underlying disease or therapeutic side effects. Keratoconjunctivitis sicca is the most common manifestation. However, vision loss may result from involvement of the retina, choroid and optic nerve. Ocular symptoms are correlated to systemic disease activity and can present as an initial manifestation of SLE. The established treatment includes prompt systemic corticosteroids, steroid-sparing immunosuppressive drugs and biological agents. Local ocular therapies are options with promising efficacy. The early recognition of disease and treatment provides reduction of visual morbidity and mortality.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  PMID: 25904124 [PubMed - as supplied by publisher]
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4. Eur J Nucl Med Mol Imaging. 2015 Apr 22. [Epub ahead of print]

Author information: 

  • 1Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan.

 

Abstract
OBJECTIVE: 

The aim of this study was to determine the prevalence of salivary and lacrimal gland dysfunction and a second primary malignancy in patients from Taiwan with thyroid cancer after radioiodine therapy.

METHODS: 

This nationwide population-based cohort study was based on data obtained from the Taiwan National Health Insurance Database from 2000 to 2011. A total of 1,834 thyroid cancer patients treated with 131I therapy and 1,834 controls (thyroid cancer without 131I therapy) selected by 1:1 matching on a propensity score were enrolled. The cumulative 131I dose in each patient was calculated. A Cox proportional hazards model was applied to estimate the effect of radiation from the 131I therapy on the risk of salivary and lacrimal gland impairment as well as second primary malignancies in terms of hazard ratios (HRs) and 95 % confidence intervals (CIs).

RESULTS: 

In patients treated with 131I therapy and in controls, the incidence rates of salivary gland dysfunction were 6.76 and 1.01 per 10,000 person-years, respectively (HR 6.81, 95 % CI 0.74 - 55.3), the incidence rates of keratoconjunctivitis sicca (KCS) were 13.6 and 16.3 per 10,000 person-years, respectively (HR 0.84, 95 % CI 0.41 - 1.73), and the incidence rates of second primary malignancy were 76.7 and 62.4 per 10,000 person-years, respectively (HR 1.23, 95 % CI 0.88 - 1.72). The risk of salivary secretion impairment significantly increased with increasing administered doses (HR 14.3, 95 % CI 1.73 - 119.0). However, there was no increase in the incidence of KCS or secondary cancer in patients treated with higher doses.

CONCLUSION: 

131I therapy insignificantly increased the risk of salivary gland dysfunction and second primary malignancy. In patients with higher cumulative doses, an increase in the incidence of salivary gland dysfunction was observed. By contrast, we did not find an association between 131I treatment and KCS development.

  PMID: 25900274 [PubMed - as supplied by publisher]
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5. Cont Lens Anterior Eye. 2015 Apr 18. pii: S1367-0484(15)00044-2. doi: 10.1016/j.clae.2015.03.005. [Epub ahead of print]

Author information: 

  • 1Hogeschool Utrecht, Utrecht, The Netherlands; Cardiff University, School of Optometry and Vision Sciences, Cardiff, UK. Electronic address: Mirjam.vantilborg@hu.nl.
  • 2University of Waterloo, School of Optometry and Vision Science, Waterloo, ON, Canada.
  • 3Cardiff University, School of Optometry and Vision Sciences, Cardiff, UK.

 

Abstract
PURPOSE: 

To investigate the agreement in dry eye care management between general practitioners (GPs) and optometrists in the Netherlands.

METHODS: 

A web-based survey was used to investigate the agreement in symptoms associated with dry eye, causes of developing dry eye, and investigative techniques used in practice, between GPs and optometrists. Additional questions surveyed knowledge of the latest research, and co-management of dry eye disease in primary healthcare. The anonymised questionnaire contained 16 forced-choice questions with Likert scales, and was sent to 1471 general medical practitioners and 870 registered optometrists. The response data was stored on an online database, and was converted directly to text format for analysis using SPSS 21 statistical analysis software.

RESULTS: 

138 optometrists and 93 GPs responded to the survey (Cronbach α=0.885, optometrists, and 0.833, GPs). Almost no agreement was found for all the questions: a statistically significant difference (Chi-square p<0.0001) was found between the optometrists and GPs in the use of investigative techniques, associating symptoms, causes of dry eye (p>0.0001), and dry eye symptoms, except for 'burning sensation of the eye' and 'irritation of the eye' as agreed symptoms, and agreement that dry eye is an age-related disease.

CONCLUSIONS: 

As the optometrist and the GP are the gatekeepers for secondary healthcare, the fundamental differences in the methods of investigation and interpretation of dry eye-related symptoms, the possible cause of developing dry eye disease, and the therapy given by GPs and optometrists in the Netherlands, may have a significant impact on consistency of patient care.

Copyright © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  PMID: 25899636 [PubMed - as supplied by publisher]
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6. Drug Des Devel Ther. 2015 Apr 1;9:1913-1926.

Author information: 

  • 1Department of Neurology, University of Freiburg, Freiburg, Germany.
  • 2Clinic and Policlinic for Neurology, University of Rostock, Rostock, Germany.
  • 3Institute of Medical Biometry and Medical Informatics, University of Freiburg, Freiburg, Germany.
  • 4Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
  • 5Department of Neurology, Palacky University Olomouc, Faculty of Medicine and Dentistry and University Hospital, Olomouc, Czech Republic.
  • 6University Eye Clinic of Bonn, Bonn, Germany.
  • 7Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 8Rush University Medical Center, Chicago, IL, USA.

 

Abstract
BACKGROUND: 

IncobotulinumtoxinA (Xeomin®) is a purified botulinum neurotoxin type A formulation, free from complexing proteins, with proven efficacy and good tolerability for the treatment of neurological conditions such as blepharospasm, cervical dystonia (CD), and post-stroke spasticity of the upper limb. This article provides a comprehensive overview of incobotulinumtoxinA based on randomized controlled trials and prospective clinical studies.

SUMMARY: 

IncobotulinumtoxinA provides clinical efficacy in treating blepharospasm, CD, and upper-limb post-stroke spasticity based on randomized, double-blind, placebo-controlled trials with open-label extension periods (total study duration up to 89 weeks). Adverse events were generally mild or moderate. The most frequent adverse events, probably related to the injections, included eyelid ptosis and dry eye in the treatment of blepharospasm, dysphagia, neck pain, and muscular weakness in patients with CD, and injection site pain and muscular weakness when used for treating spasticity. In blepharospasm and CD, incobotulinumtoxinA was investigated in clinical trials permitting flexible intertreatment intervals based on the individual patient's clinical need; the safety profile of intervals shorter than 12 weeks was comparable to intervals of 12 weeks and longer. There were no cases of newly formed neutralizing antibodies during the Phase III and IV incobotulinumtoxinA trials. Phase III head-to-head trials of incobotulinumtoxinA versus onabotulinumtoxinA for the treatment of blepharospasm and CD have demonstrated therapeutic equivalence of both formulations. Additional Phase III trials of incobotulinumtoxinA in conditions such as lower-limb spasticity, spasticity in children with cerebral palsy, and sialorrhea in various neurological disorders are ongoing.

CONCLUSION: 

IncobotulinumtoxinA is an effective, well-tolerated botulinum neurotoxin type A formulation. Data from randomized clinical trials and further observational studies are expected to help physicians to optimize treatment by tailoring the choice of formulation, dose, and treatment intervals to the patient's clinical needs.

PMCID: PMC4389813 Free PMC Article 
  PMID: 25897202 [PubMed - as supplied by publisher]
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7. Mol Pain. 2015 Apr 21;11(1):21. [Epub ahead of print]

Author information: 

  • 1Bascom Palmer Eye Institute, University of Miami, 900 NW 17th Street, Miami, FL, 33136, USA. alevitt@med.miami.edu.
  • 2Bascom Palmer Eye Institute, University of Miami, 900 NW 17th Street, Miami, FL, 33136, USA. agalor@med.miami.edu.
  • 3Miami Veterans Administration Medical Center, 1201 NW 16th St, Miami, FL, 33125, USA. agalor@med.miami.edu.
  • 4Departments of Ophthalmology, Pathology and Pharmacology, Louisiana State University Health Sciences Center, Louisiana State University Eye Center, New Orleans, LA, USA. jweiss@lsuhsc.edu.
  • 5Miami Veterans Administration Medical Center, 1201 NW 16th St, Miami, FL, 33125, USA. EFelix@med.miami.edu.
  • 6Department of Physical Medicine and Rehabilitation, University of Miami Miller School of Medicine, Miami, FL, USA. EFelix@med.miami.edu.
  • 7John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA. EMartin1@med.miami.edu.
  • 8John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA. EMartin1@med.miami.edu.
  • 9Department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami Miller School of Medicine, Miami, FL, USA. dpatin@med.miami.edu.
  • 10Department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami Miller School of Medicine, Miami, FL, USA. KSarantopoulos@med.miami.edu.
  • 11Miami Veterans Administration Medical Center, 1201 NW 16th St, Miami, FL, 33125, USA. RLevitt@med.miami.edu.
  • 12John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA. RLevitt@med.miami.edu.
  • 13John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA. RLevitt@med.miami.edu.
  • 14Department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami Miller School of Medicine, Miami, FL, USA. RLevitt@med.miami.edu.

 

Abstract

Laser in-situ keratomileusis (LASIK) is a commonly performed surgical procedure used to correct refractive error. LASIK surgery involves cutting a corneal flap and ablating the stroma underneath, with known damage to corneal nerves. Despite this, the epidemiology of persistent pain and other long-term outcomes after LASIK surgery are not well understood. Available data suggest that approximately 20-55% of patients report persistent eye symptoms (generally regarded as at least 6 months post-operation) after LASIK surgery. While it was initially believed that these symptoms were caused by ocular surface dryness, and referred to as "dry eye," it is now increasingly understood that corneal nerve damage produced by LASIK surgery resembles the pathologic neuroplasticity associated with other forms of persistent post-operative pain. In susceptible patients, these neuropathological changes, including peripheral sensitization, central sensitization, and altered descending modulation, may underlie certain persistent dry eye symptoms after LASIK surgery. This review will focus on the known epidemiology of symptoms after LASIK and discuss mechanisms of persistent post-op pain due to nerve injury that may be relevant to these patients. Potential preventative and treatment options based on approaches used for other forms of persistent post-op pain and their application to LASIK patients are also discussed. Finally, the concept of genetic susceptibility to post-LASIK ocular surface pain is presented.

Free Article 
  PMID: 25896684 [PubMed - as supplied by publisher]
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8. Retina. 2014 Dec;34(12):2367-75. doi: 10.1097/IAE.0000000000000258.

Author information: 

  • 1Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Australia.

 

Abstract
BACKGROUND: 

Previous reports suggest that the outcome of age-related macular degeneration treatment is dependent on variants in the apolipoprotein E (APOE) gene. We wish to establish if variants in this gene are associated with anatomical location of fluid within the macula on optical coherence tomography imaging before and after three anti-vascular endothelial growth factor treatments.

METHODS: 

Patients with subfoveal choroidal neovascularization secondary to age-related macular degeneration were prospectively enrolled and monitored over a 12-month period. Main outcome measures were logMAR best-corrected visual acuity and correlation of qualitative optical coherence tomography features (intraretinal fluid [IRF] and/or subretinal fluid) at baseline and after three anti-vascular endothelial growth factor injections with genetic variants of the APOE gene.

RESULTS: 

One hundred and eighty-six eyes of 186 patients aged 79.4 years (range, 58-103 years). Subjects with an ε2 allele were more likely to have IRF at baseline compared with the eyes without (odds ratio: 2.98, 95% confidence interval: 1.22-7.29, P = 0.02). After 3 injections, 184 eyes remained. Of these, 114 of eyes (62.0%) were classified as "dry" on optical coherence tomography, whereas 48 eyes (26.1%) still had a component of IRF, and 22 (12.0%) had subretinal fluid alone. There was no statistically significant association between APOE variants and presence of persistent IRF, although there were almost double the number of subjects with ε2 (40%) who had persistent fluid compared with those with ε3/ε4 (23%) (P = 0.06).

CONCLUSION: 

In patients with neovascular age-related macular degeneration, the presence of the ε2 allele of the APOE gene was associated with having IRF at baseline. Larger studies are required to determine if a greater proportion of those with the ε2 allele retain this fluid after three initial injections.

  PMID: 25077528 [PubMed - indexed for MEDLINE]
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9. Ren Fail. 2014 Aug;36(7):1162-5. doi: 10.3109/0886022X.2014.917764. Epub 2014 May 15.

Author information: 

  • 1Department of Rehabilitation, Tao Yuan General Hospital , Tao Yuan, Taiwan , Republic of China .

 

Abstract

Thrombotic microangiopathy (TMA) is rarely associated with Sjögren's syndrome (SS). This is the first documented case of a patient undergoing chronic hemodialysis with SS who developed TMA. TMA is an infrequent, life-threatening multisystem disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia, accompanied by microvascular thrombosis that causes variable degrees of tissue ischemia and infarction. It is important to make a quick diagnosis of TMA to cure the reported case as early as possible. The patients with TMA should be diagnosed quickly, and in this case plasma exchange and corticosteroids in combination with cyclophosphamide have been associated with a recurrence free period. Cyclophosphamide has led to the development of treatment protocols using alternative immunosuppressive agents in patients with SS showing a poor response to plasmapheresis and potentially life-threatening manifestations. Further research is required to ascertain the sensitivity, specificity, efficacy, timing, cost-benefit ratio, and necessity of cyclophosphamide in the setting of TMA complicating SS.

  PMID: 24828887 [PubMed - indexed for MEDLINE]
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10. Wiad Lek. 2013;66(2 Pt 2):164-70.
[Article in Polish]

Author information: 

  • 1Oddział Neurologii Szpitala Specialistyczneqo w Końskich. wbrola@wp.pl

 

Abstract

Multiple sclerosis (MS) is a progressive demyelinating-inflammatory disease of the central nervous system, probably of autoimmune etiology. Characteristic qualities include multifocal demyelination, which result in varied clinical pictures of the disease. MS must be differentiated from chronic or recurring diseases, as well as from those with multifocal neurological manifestations and multifocal lesions revealed in a MR scan. Particular signs may precede the development of the full-blown MS, but they may be initial manifestations of autoimmune disease such as systemic lupus, antiphospholipid syndrome, Behçet's disease or Sjögren's syndrome as well. Diagnosis is easier in the later stages due to appearance of characteristic manifestations, absent in the course of MS. Nevertheless, the mildly symptomatic nature of those diseases may lead to misdiagnosis, putting the patient at risk of an expensive and inefficient treatment, which may only exacerbate the symptoms. In many cases a long-term follow-up is necessary to confirm the diagnosis.

  PMID: 25775811 [PubMed - indexed for MEDLINE]
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