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Neuroptis Dry Eye Project with ML 7 (Myosin Light Chain Inhibitor)
24 septembre 2015

NEW PUBLICATIONS UPTO SEPTEMBER 18TH 2015

ChinMedJ_2015_128_18_2444_164927_u3

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NEW PUBLICATIONS UPTO SEPTEMBER 18TH 2015

 

 

 

The effects of long-term topical glaucoma medication on conjunctival i

Long-term use of topical drugs can induce changes in theconjunctiva and ocular surface. To determine theconjunctival changes resulting from topical glaucomamedication, patients with glaucoma were selected andclassified into seven groups, according to the medicationreceived: 24 eyes were treated with betaxolol, 20 eyes withlevobunolol, 32 eyes with timolol maleate, 22 eyes withpilocarpine, 52 eyes with beta-blocker and pilocarpine, 34eyes with beta-blocker and dipivefrin, and 32 eyes withmaximum therapy.

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1. Br J Ophthalmol. 2015 Sep 16. pii: bjophthalmol-2015-307094. doi: 10.1136/bjophthalmol-2015-307094. [Epub ahead of print]

Author information: 

  • 1Department of Ophthalmology, Miami Veterans Administration Medical Center, Miami, Florida, USA Bascom Palmer Eye Institute, University of Miami, Miami, Florida, USA.
  • 2Department of Ophthalmology, Miami Veterans Administration Medical Center, Miami, Florida, USA Department of Physical Medicine and Rehabilitation, University of Miami Miller School of Medicine, Miami, Florida, USA.
  • 3Departement of Ophthalmology, Washington University School of Medicine, St Louis, Missouri, USA.
  • 4Department of Ophthalmology, Miami Veterans Administration Medical Center, Miami, Florida, USA Department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami Miller School of Medicine, Miami, Florida, USA.
  • 5John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA.
  • 6Department of Ophthalmology, Miami Veterans Administration Medical Center, Miami, Florida, USA Department of Anesthesiology, Perioperative Medicine and Pain Management, University of Miami Miller School of Medicine, Miami, Florida, USA John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA John T Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, USA.

 

Abstract
AIMS: 

Artificial tears are first-line therapy for patients with dry eye symptoms. It is not known, however, which patient factors associate with a positive response to therapy. The purpose of this study was to evaluate whether certain ocular and systemic findings are associated with a differential subjective response to artificial tears.

METHODS: 

Cross-sectional study of 118 individuals reporting artificial tears use (hypromellose 0.4%) to treat dry eye-associated ocular pain. An evaluation was performed to assess dry eye symptoms (via the dry eye questionnaire 5 and ocular surface disease index), ocular and systemic (non-ocular) pain complaints and ocular signs (tear osmolarity, tear breakup time, corneal staining, Schirmer testing with anaesthesia, and eyelid and meibomian gland assessment). The main outcome measures were factors associated with differential subjective response to artificial tears.

RESULTS: 

By self-report, 23 patients reported no improvement, 73 partial improvement and 22 complete improvement in ocular pain with artificial tears. Patients who reported no or partial improvement in pain with artificial tears reported higher levels of hot-burning ocular pain and sensitivity to wind compared with those with complete improvement. Patients were also asked to rate the intensity of systemic pain elsewhere in the body (other than the eye). Patients who reported no or incomplete improvement with artificial tears had higher systemic pain scores compared with those with complete improvement.

CONCLUSIONS: 

Both ocular and systemic (non-ocular) pain complaints are associated with a differential subjective response to artificial tears.

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: 26377416 [PubMed - as supplied by publisher]
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2. Eye Contact Lens. 2015 Sep 14. [Epub ahead of print]

Author information: 

  • 1Department of Biochemistry and Molecular Biology IV (A.G.-A., B.F., A.M.-G., A.M.-A., J.P.), Faculty of Optic and Optometry, Universidad Complutense de Madrid, Madrid, Spain; and Department of Optics II (Optometry and Vision) (G.C.), Faculty of Optic and Optometry, Universidad Complutense de Madrid, Madrid, Spain.

 

Abstract

Dry eye disease affects a substantial segment of the word population with increasing frequency. It is a multifactorial disease of the ocular surface and tear film, which causes ocular discomfort, visual disturbances, and tear instability with potential damage to the cornea and conjunctiva. Because of its multifactorial etiology, the use of different pharmacological treatment for dry eye treatment has been proposed, which include anti-inflammatory molecules, lubricants or comfort agents, and secretagogues. However, in some cases these pharmacological approaches only relieve symptoms temporarily, and consequently, eye care professionals continue to have difficulties managing dry eye. To improve pharmacological therapy that allows a more efficient and long-term action, effective ocular drug delivery of the currently available drugs for dry eye treatment is required. Contact lenses are emerging as alternative ophthalmic drugs delivery systems that provide an increased residence time of the drug at the eye, thus leading to enhanced bioavailability and more convenient and efficacious therapy. In this article, we reviewed the different techniques used to prepare contact lens-based drug delivery systems and focused on articles that describe the delivery of compounds for dry eye treatment through contact lenses.

  PMID: 26372476 [PubMed - as supplied by publisher]
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3. J Fr Ophtalmol. 2015 Sep 11. pii: S0181-5512(15)00249-1. doi: 10.1016/j.jfo.2015.02.008. [Epub ahead of print]
[Article in French]

Author information: 

  • 1Service de pharmacie clinique, hôpitaux universitaires Paris Centre, site Hôtel-Dieu, 2, rue d'Arcole, 75004 Paris, France.
  • 2Service de pharmacie clinique, hôpitaux universitaires Paris Centre, site Hôtel-Dieu, 2, rue d'Arcole, 75004 Paris, France. Electronic address: stephanie.charles-weber@htd.aphp.fr.

 

Abstract
INTRODUCTION: 

The University Hospitals Paris Centre Pharmacy compounds three concentrations of cyclosporine eye drops: 20mg/mL (=2%); 5mg/mL (=0.5%) and 0.5mg/mL (=0.05%). Cyclosporine A 2% drops were developed in 1995 to prevent the rejection of high-risk cornea transplants after failure of topical steroids. The other concentrations of eye drops were developed for the treatment of various immune or inflammatory diseases of the cornea, conjunctiva and uvea. These eye drops are dispensed with a physician's prescription to hospitalized or ambulatory patients. A retrospective study over 4 years (2009-2013) was conducted to analyze the details of prescription and possible adverse events.

MATERIALS AND METHODS: 

Dispensations made from January 1st, 2009 through December 31st, 2013 were studied, including patient age, dose of cyclosporine and practice location of prescribing physician. We also recorded the indications for cyclosporine eye drops in a sample of ambulatory patients. The analysis of local tolerability and the effect on visual comfort was based on questionnaires sent to the patients on cyclosporine 2% over a period of 2 months.

RESULTS: 

Cyclosporine eye drops prescription grew continuously from 2009 through 2013 for all concentrations. In 2013, 5859patients were treated, among which 3616patients with topical cyclosporine 2%, 1681patients with 0.5%, and 562 patients with 0.05%. In total, this represents 62,621 eye drops. Treated patients ranged from 1 week to 100 years old. Topical 2% cyclosporine is indicated in 61% of cases to prevent high-risk corneal graft rejection. Other indications are corneal ulcer (6%), atopic keratoconjunctivitis (5%), vernal keratoconjunctivitis (5%) and herpetic keratitis (4%). Topical 0.5% cyclosporine is prescribed primarily for dry eye syndrome (20%) and to prevent rejection of high-risk corneal transplantation (11%), to treat ocular rosacea (10%), vernal keratoconjunctivitis (10%), atopic keratoconjunctivitis (8%) and Sjögren's syndrome (7%). Topical 0.05% cyclosporine is prescribed primarily for dry eye syndrome resistant to conventional treatment (47%) and Sjögren's syndrome (21%). Local tolerability of topical cyclosporine was evaluated in 388 patients. The majority of patients (63%) did not experience any adverse effects. The main side effects are redness, burning sensation and itching.

CONCLUSION: 

Prescription of various formulations of topical cyclosporine is current practice for surgical indications: rejection of high-risk corneal transplantation; or medical indications: vernal or atopic keratoconjunctivitis and dry eye syndrome. Further prospective randomized studies would be necessary to validate formulations, doses and indications of cyclosporine eye drops.

Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  PMID: 26371985 [PubMed - as supplied by publisher]
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4. Ophthalmologica. 2015 Sep 15. [Epub ahead of print]

Author information: 

  • 1University Eye Hospital, Medical School Hannover, Hannover, Germany.

 

Abstract
PURPOSE: 

Selective retina therapy (SRT), the confined laser heating and destruction of retinal pigment epithelial cells, has been shown to treat acute types of central serous chorioretinopathy (CSC) successfully without damaging the photoreceptors and thus avoiding laser-induced scotoma. However, a benefit of laser treatment for chronic forms of CSC is questionable. In this study, the efficacy of SRT by means of the previously used 1.7-µs and shorter 300-ns pulse duration was evaluated for both types of CSC, also considering re-treatment for nonresponders.

MATERIAL AND METHODS: 

In a two-center trial, 26 patients were treated with SRT for acute (n = 10) and chronic-recurrent CSC (n = 16). All patients presented with subretinal fluid (SRF) in OCT and leakage in fluorescein angiography (FA). SRT was performed using a prototype SRT laser system (frequency-doubled Q-switched Nd:YLF-laser, wavelength 527 nm) with adjustable pulse duration. The following irradiation settings were used: a train of 30 laser pulses with a repetition rate of 100 Hz and pulse durations of 300 ns and 1.7 µs, pulse energy 120-200 µJ, retinal spot size 200 µm. Because SRT lesions are invisible, FA was always performed 1 h after treatment to demonstrate laser outcome (5-8 single spots in the area of leakage). In cases where energy was too low, as indicated by missing FA leakage, energy was adjusted and the patient re-treated immediately. Observation intervals were after 4 weeks and 3 months. In case of nonimprovement of the disease after 3 months, re-treatment was considered.

RESULTS: 

Of 10 patients with active CSC that presents focal leakage in FA, 5 had completely resolved fluid after 4 weeks and all 10 after 3 months. Mean visual acuity increased from 76.6 ETDRS letters to 85.0 ETDRS letters 3 months after SRT. Chronic-recurrent CSC was characterized by less severe SRF at baseline in OCT and weaker leakage in FA than in acute types. Visual acuity changed from baseline 71.6 to 72.8 ETDRS letters after 3 months. At this time, SRF was absent in 3 out of 16 patients (19%), FA leakage had come to a complete stop in 6 out of 16 patients (38%). In 6 of the remaining chronic CSC patients, repeated SRT with higher pulse energy was considered because of persistent leakage activity. After the re-treatment, SRF resolved completely in 5 patients (83.3%) after only 25 days.

CONCLUSION: 

SRT showed promising results in treating acute CSC, but was less effective in chronic cases. Interestingly, re-treatment resulted in enhanced fluid resolution and dry conditions after a considerably shorter time in most patients. Therefore, SRT including re-treatment if necessary might be a valuable CSC treatment alternative even in chronic-recurrent cases.

© 2015 S. Karger AG, Basel.

  PMID: 26368551 [PubMed - as supplied by publisher]
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5. Chin Med J (Engl). 2015 20th Sep;128(18):2444-2449. doi: 10.4103/0366-6999.164927.

Author information: 

  • 1Department of Glaucoma, The State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong 510060, China.

 

Abstract
BACKGROUND: 

Long-term use of benzalkonium chloride (BAC)-preserved drugs is often associated with ocular surface toxicity. Ocular surface symptoms had a substantial impact on the glaucoma patients' quality of life and compliance. This study aimed to investigate the effects of sodium hyaluronate (SH) on ocular surface toxicity induced by BAC-preserved anti-glaucoma medications treatment.

METHODS: 

Fifty-eight patients (101 eyes), who received topical BAC-preserved anti-glaucoma medications treatment and met the severe dry eye criteria, were included in the analysis. All patients were maintained the original topical anti-glaucoma treatment. In the SH-treated group (56 eyes), unpreserved 0.3% SH eye drops were administered with 3 times daily for 90 days. In the control group (55 eyes), phosphate-buffered saline were administered with 3 times daily for 90 days. Ocular Surface Disease Index (OSDI) questionnaire, break-up time (BUT) test, corneal fluorescein staining, corneal and conjunctival rose Bengal staining, Schirmer test, and conjunctiva impression cytology were performed sequentially on days 0 and 91.

RESULTS: 

Compared with the control group, SH-treated group showed decrease in OSDI scores (Kruskal-Wallis test: H = 38.668, P < 0.001), fluorescein and rose Bengal scores (Wilcoxon signed-ranks test: z = -3.843, P < 0.001, and z = -3.508, P < 0.001, respectively), increase in tear film BUT (t-test: t = -10.994, P < 0.001) and aqueous tear production (t-test: t = -10.328, P < 0.001) on day 91. The goblet cell density was increased (t-test: t = -9.981, P < 0.001), and the morphology of the conjunctival epithelium were also improved after SH treatment.

CONCLUSIONS: 

SH significantly improved both symptoms and signs of ocular surface damage in patients with BAC-preserved anti-glaucoma medications treatment. SH could be proposed as a new attempt to reduce ocular surface toxicity, and alleviate symptoms of ocular surface damage in BAC-preserved anti-glaucoma medications treatment.

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  PMID: 26365960 [PubMed - as supplied by publisher]
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6. Ophthalmology. 2015 Sep 10. pii: S0161-6420(15)00777-0. doi: 10.1016/j.ophtha.2015.08.001. [Epub ahead of print]

Author information: 

  • 1Tauber Eye Center, Kansas City, Missouri. Electronic address: jt@taubereye.com.
  • 2Koffler Vision Group, Lexington, Kentucky.
  • 3Physician Eye Care of New York, New York, New York.
  • 4South Shore Eye Care, Wantagh, New York.
  • 5Martel Eye Medical Group, Rancho Cordova, California.
  • 6Sall Research Medical Center, Inc., Artesia, California.
  • 7Shire, Wayne, Pennsylvania.

 

Abstract
PURPOSE: 

Lifitegrast is an integrin antagonist that decreases T-cell-mediated inflammation associated with dry eye disease (DED). We report the results of OPUS-2, a phase III study evaluating the efficacy and safety of lifitegrast compared with placebo for the treatment of DED.

DESIGN: 

A 12-week, multicenter, randomized, prospective, double-masked, placebo-controlled clinical trial.

PARTICIPANTS: 

Adults aged ≥18 years with use of artificial tears within 30 days, inferior corneal staining score ≥0.5 (0-4 scale), Schirmer tear test (without anesthesia) ≥1 and ≤10 mm, and eye dryness score ≥40 (0-100 visual analogue scale [VAS]).

METHODS: 

Subjects were randomized 1:1 after 14-day placebo run-in to lifitegrast ophthalmic solution 5.0% or placebo twice daily for 84 days.

MAIN OUTCOME MEASURES: 

Co-primary efficacy end points were change, from baseline to day 84, in eye dryness score (VAS, both eyes) and inferior corneal fluorescein staining score in the designated study eye. Secondary end points were change, from baseline to day 84, in ocular discomfort score (0-4 scale) in study eye, eye discomfort score (VAS), total corneal staining score in study eye, and nasal conjunctival lissamine green staining score (0-4 scale) in study eye. Treatment-emergent adverse events (TEAEs) were recorded.

RESULTS: 

A total of 718 subjects were randomized: placebo, n = 360; lifitegrast, n = 358 (intent-to-treat population). Lifitegrast-treated subjects experienced greater improvement in eye dryness than placebo-treated subjects (treatment effect, 12.61; 95% confidence interval [CI], 8.51-16.70; P < 0.0001). There was no between-group difference in inferior corneal staining (treatment effect, 0.03; 95% CI, -0.10 to 0.17; P = 0.6186). There was nominally significant improvement of secondary symptom end points among lifitegrast-treated subjects: ocular discomfort (nominal P = 0.0005) and eye discomfort (nominal, P < 0.0001). There were no between-group differences on secondary signs: total corneal staining and nasal lissamine staining. More lifitegrast-treated subjects (33.7%) than placebo-treated subjects (16.4%) experienced ocular TEAEs; no ocular TEAEs were serious.

CONCLUSIONS: 

Lifitegrast met the co-primary symptom end point (eye dryness) but not the co-primary sign end point (inferior corneal staining). Secondary end point findings were consistent with this pattern. Most ocular TEAEs were mild to moderate; there were no unexpected TEAEs. Lifitegrast warrants further consideration as a treatment for DED.

Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

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  PMID: 26365210 [PubMed - as supplied by publisher]
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7. Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4336-49. doi: 10.1167/iovs.15-17088.
Ma Y1Zhao S1Wang X1Shen S1Ma M2Xu W1Hong A1.

Author information: 

  • 1Institute of Biomedicine and Department of Cellular Biology National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou, Guangdong Province, China.
  • 2School of Medicine of Jinan University, Guangzhou, Guangdong Province, China.

 

Abstract
PURPOSE: 

A new recombinant pituitary adenylate cyclase-activating polypeptide (PACAP)-derived peptide, MPAPO, which has higher stability and PAC1-specific potency, was generated. The actions of MPAPO on corneal wound repairing and lacrimal secretion were examined.

METHODS: 

MPAPO was prepared and identified by gene recombination, high-performance liquid chromatography (HPLC), and electrospray ionization mass spectrometry (ESI-MS). Stability assay was performed by HPLC-ESI-MS. PAC1-specific binding and potency assays were performed using PAC1-CHO cells. C57BL/6 mice and Japanese white rabbits were respectively used to analyze the effects of MPAPO on corneal wound repairing and lacrimal fluid secretion. Tetrazolium-based colorimetric assay (MTT), immunofluorescence, gene microarrays, and Western blot assay were performed to measure the effects of MPAPO on corneal epithelial cell proliferation, synapse growth, and gene differential expression of trigeminal ganglion cells.

RESULTS: 

As compared with the wild PACAP, the in vitro stability and PAC1-specific potency of MPAPO with four mutations (M17L, L27K and M, K, respectively, added to the N- and C-terminus) were increased approximately 31- and 2-fold, respectively. MPAPO can significantly promote the proliferation of mouse corneal epithelium cells and the synapse growth of trigeminal ganglion cells. In experimental animals, MPAPO performed a complete corneal epithelial wound closure in 30 hours and significantly inhibited corneal neovascularization, and the effects were obviously stronger than for wild PACAP and recombinant bovine (rb)-bFGF (an anti-corneal wound drug). Furthermore, MPAPO can increase the lacrimal secretion, which may efficiently improve dry eye.

CONCLUSIONS: 

MPAPO may represent a promising external therapeutic peptide for corneal wound repairing or dry eye.

  PMID: 26176871 [PubMed - indexed for MEDLINE]
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8. Invest Ophthalmol Vis Sci. 2015 Jul;56(8):4186-97. doi: 10.1167/iovs.14-15496.

Author information: 

  • 1Department of Ophthalmology and the Ocular Surface Center Baylor College of Medicine, Houston, Texas, United States.
  • 2Departments of Medicine and Pathology & Immunology and the Biology of Inflammation Center, Baylor College of Medicine, Houston, Texas, United States.

 

Abstract
PURPOSE: 

To investigate the effects of IL-13 on goblet cell proliferation, differentiation, and expression of mucin and immunomodulatory genes.

METHODS: 

Explants were excised from the conjunctiva of young C57BL/6 mice. Cultures received 200 μL per week of either Keratinocyte media (KSFM) or KSFM supplemented with 10 ng/mL IL-13 and were incubated for 3 (D3), 7 (D7), or 14 (D14) days. Subsequently, cell proliferation was assessed or cultures were immunostained, collected for dot blot, or for reverse transcription (RT) and quantitative real-time PCR (qPCR) or for RT-PCR gene array.

RESULTS: 

The cultured conjunctival epithelium expressed goblet cell associated keratin 7 and mucins MUC5AC and MUC2 and when stimulated with IL-13 showed increased proliferation at D3 and D7 (P < 0.05) compared with control. MUC5AC expression was increased in the IL-13-treated group at D3 and D14 (P < 0.05). IL-13-treated cultures showed increased chemokine ligand 26 (CCL26), chloride channel calcium activated channel 3 (CLCA3), fas ligand (FasL), and Relm-β at D7. All conjunctival cultures expressed MUC2, and its expression was decreased at D3 (P < 0.05) and increased at D14 (P < 0.05) with IL-13 treatment.

CONCLUSIONS: 

This study demonstrated that conjunctival goblet cells are IL-13 responsive cells that produce factors known to maintain epithelial barrier, stimulate mucin production, and modulate immune response in nonocular mucosa when treated with IL-13. The functional significance of IL-13-stimulated factors remains to be determined.

PMCID: PMC4495812 [Available on 2016-01-01]
  PMID: 26132778 [PubMed - indexed for MEDLINE]
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9. Respir Care. 2015 Apr;60(4):e90-1. doi: 10.4187/respcare.03972.

Author information: 

  • 1Department of Pneumology Centro Hospitalar de São João Porto, Portugal and Life and Health Sciences Research Institute (ICVS) School of Health Sciences University of Minho Braga, Portugal and ICVS/3B's-PT Government Associate Laboratory Braga/Guimarães, Portugal.
  • 2Department of Pneumology Centro Hospitalar de São João Porto, Portugal.
  • 3Department of Pneumology Centro Hospitalar de São João Porto, Portugal and Faculty of Medicine University of Porto Porto, Portugal.

 

  PMID: 25841047 [PubMed - indexed for MEDLINE]
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10. J Cataract Refract Surg. 2015 Mar;41(3):652-65. doi: 10.1016/j.jcrs.2015.02.006.

Author information: 

  • 1From the Francis I. Proctor Foundation (Moshirfar), University of California San Francisco, San Francisco, California, the University of New Mexico School of Medicine (McCaughey), Albuquerque, New Mexico, and the John A. Moran Eye Center (Fenzl), University of Utah, Salt Lake City, Utah, USA; the London Vision Clinic (Reinstein), London, United Kingdom; the New Vision Laser Centers (Shah), Vadodara, India; the Ophthalmology Department (Santiago-Caban), University of Puerto Rico School of Medicine Ophthalmology Department, San Juan, Puerto Rico. Electronic address: majid.moshirfar@ucsf.edu.
  • 2From the Francis I. Proctor Foundation (Moshirfar), University of California San Francisco, San Francisco, California, the University of New Mexico School of Medicine (McCaughey), Albuquerque, New Mexico, and the John A. Moran Eye Center (Fenzl), University of Utah, Salt Lake City, Utah, USA; the London Vision Clinic (Reinstein), London, United Kingdom; the New Vision Laser Centers (Shah), Vadodara, India; the Ophthalmology Department (Santiago-Caban), University of Puerto Rico School of Medicine Ophthalmology Department, San Juan, Puerto Rico.

 

Abstract

This review looks at the benefits, limitations, complications, and future applications of the small-incision lenticule extraction procedure. Using the search terms small incision lenticule extraction and femtosecond lenticule extraction, we obtained data from 56 articles (omitting German and Chinese articles) from the PubMed database. Small-incision lenticule extraction has shown efficacy, predictability, and safety that are proportionate to those of laser in situ keratomileusis (LASIK), with the additional benefit that it eliminates flap creation and the attendant risks. The potential advantages of the procedure related to improved biomechanical stability, postoperative inflammation, and dry-eye symptoms have not been fully established. Small-incision lenticule extraction-treated eyes have shown a reduced degree of postoperative corneal denervation and higher-order aberrations and an accelerated rate of corneal nerve convalescence relative to LASIK. Future possibilities related to long-term cryogenic storage of extracted lenticules with eventual reimplantation or donation have been investigated with encouraging preliminary results.

FINANCIAL DISCLOSURE: 

Drs. Reinstein and Shah are consultants to Carl Zeiss Meditec AG. No author has a financial or proprietary interest in any material or method mentioned.

Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

  PMID: 25804585 [PubMed - indexed for MEDLINE]
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11. J Clin Rheumatol. 2015 Jan;21(1):31-2. doi: 10.1097/RHU.0000000000000210.

Author information: 

  • 1From the *Department of Immunology and Rheumatology and †Medical Direction, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico.

 

Abstract

Primary Sjögren syndrome (PSS) is a chronic autoimmune disease characterized by sicca complex and various systemic manifestations. Although it is well accepted to use corticosteroids for the treatment of systemic manifestations, there is scarce information available regarding the use of targeted therapy for refractory cases. We describe a case of a severe PSS patient refractory to conventional treatment with a response to bortezomib, a proteasome inhibitor commonly used for the treatment of multiple myeloma. Bortezomib administration resulted in a notable improvement of the general symptoms, particularly fatigue, and a decrease in serum globulin levels as well as in serum viscosity. Hyperglobulinemic purpura disappeared, and prednisone tapering succeeded. Because of chronicity, no clinical changes were observed in sicca symptoms. As far as we know, this is the first report on the use of bortezomib in a refractory case of PSS. 

  PMID: 25539431 [PubMed - indexed for MEDLINE]
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12. Arthritis Res Ther. 2014 Feb 11;16(1):R51. doi: 10.1186/ar4481.
Abstract
INTRODUCTION: 

Subjects with primary Sjögren's syndrome (SjS) have an increased risk of developing B-cell lymphoma and may harbor monoclonal B-cell expansions in the peripheral blood. Expanded B-cell clones could be pathogenic, and their persistence could exacerbate disease or predispose toward the development of lymphoma. Therapy with anti-CD20 (rituximab) has the potential to eliminate expanded B-cell clones and thereby potentially ameliorate disease. This study was undertaken to identify and track expanded B-cell clones in the blood of subjects with primary SjS who were treated with rituximab.

METHODS: 

To determine whether circulating B-cell clones in subjects with primary SjS emerge or remain after B cell-depleting therapy with rituximab, we studied the antibody heavy-chain repertoire. We performed single-memory B-cell and plasmablast sorting and antibody heavy-chain sequencing in six rituximab-treated SjS subjects over the course of a 1-year follow-up period.

RESULTS: 

Expanded B-cell clones were identified in four out of the six rituximab-treated SjS subjects, based upon the independent amplification of sequences with identical or highly similar VH, DH, and JH gene segments. We identified one SjS subject with a large expanded B-cell clone that was present prior to therapy and persisted after therapy. Somatic mutations in the clone were numerous but did not increase in frequency over the course of the 1-year follow-up, suggesting that the clone had been present for a long period of time. Intriguingly, a majority of the somatic mutations in the clone were silent, suggesting that the clone was under chronic negative selection.

CONCLUSIONS: 

For some subjects with primary SjS, these data show that (a) expanded B-cell clones are readily identified in the peripheral blood, (b) some clones are not eliminated by rituximab, and (c) persistent clones may be under chronic negative selection or may not be antigen-driven. The analysis of sequence variation among members of an expanded clone may provide a novel means of measuring the chronicity and selection of expanded B-cell populations in humans.

PMCID: PMC3978607 Free PMC Article 
  PMID: 24517398 [PubMed - indexed for MEDLINE]
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13. Arthritis Res Ther. 2014 Feb 6;16(1):R46. doi: 10.1186/ar4475.
Abstract
INTRODUCTION: 

Faecal calprotectin (FC) has been proposed to be a biomarker of gastrointestinal (GI) disease in systemic sclerosis (SSc). The purpose of this study was to extend cross-sectional observations and prospectively assess the variability of FC over time in SSc patients. We also aimed to examine FC in relation to immunosuppressive therapy. Finally we wanted to analyse FC in other rheumatic diseases to evaluate the specificity of FC for SSc GI disease.

METHODS: 

FC was measured in consecutive patients with SSc, primary Sjögren's syndrome (pSS), rheumatoid arthritis (RA) and in healthy hospital workers. The intraindividual variability of FC in SSc was assessed with intra class correlation (ICC) and κ statistics. Associations between FC and objective markers of GI disease and immunosuppressive medication were investigated.

RESULTS: 

FC was associated with micronutrient deficiency and GI pathology as assessed by cineradiography confirming our previous results. FC showed only a limited intra-individual variation in SSc, ICC = 0.69 (95% confidence interval, CI: 0.57-0.78) and κ = 0.64 (95% CI: 0.56-0.73). Generalised immunosuppression did not have any significant impact on FC. FC was significantly higher in SSc patients compared to patients with pSS or RA as well as compared to healthy subjects.

CONCLUSIONS: 

FC is a promising non-invasive biomarker for GI disease in SSc. In view of stable levels over time, FC could be a useful marker when novel, more specific drugs targeting the GI tract in SSc will be introduced.

PMCID: PMC3978565 Free PMC Article 
  PMID: 24499541 [PubMed - indexed for MEDLINE]
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14. Respir Care. 2014 Oct;59(10):e156-9. doi: 10.4187/respcare.02929. Epub 2013 Dec 31.

Author information: 

  • 1Service de Réanimation Médicale, Hôpital Européen Georges Pompidou, Assistance Publique-Hopitaux de Paris.
  • 2Service de Pneumologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hopitaux de Paris.
  • 3Service de Radiologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hopitaux de Paris, 20 rue Leblanc.
  • 4Service de Réanimation Médicale, Hôpital Européen Georges Pompidou, Assistance Publique-Hopitaux de Paris Institut National de la Santé et de la Recherche Médicale U765, Faculté de Pharmacie and Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. jldiehl@invivo.edu.

 

Abstract

Airway and cystic lung diseases can be observed in patients with Sjögren's syndrome. We report a case of such a patient suffering from respiratory failure due to recurrent episodes of right pneumothorax, requiring invasive mechanical ventilation. Despite thoracic drainage and adequate pneumothorax management, the patient could not be weaned from the ventilator. Fiberoptic bronchoscopy revealed severe central excessive dynamic airway collapse of the lower part of the trachea and proximal bronchi. The severity of airway collapse was maximal at the intermediate bronchus level, with a near-complete obstruction during expiration. Inspiratory and expiratory computed tomography studies confirmed the fiberoptic findings and suggested a possible expiratory posterior compression of the intermediate bronchus by parenchymal lung cysts. Stenting was considered, but the patient died from ventilator-associated pneumonia before the procedure could be performed. This case is the first description of severe central excessive dynamic airway collapse in a patient with primary Sjögren's syndrome complicated by diffuse airway and cystic lung disease. 

Copyright © 2014 by Daedalus Enterprises.

  PMID: 24381188 [PubMed - indexed for MEDLINE]
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