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Neuroptis Dry Eye Project with ML 7 (Myosin Light Chain Inhibitor)
1 juin 2015

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Invest Ophthalmol Vis Sci. 2015 May 1;56(5):3149-58. doi: 10.1167/iovs.14-16153.

Author information: 

  • 1Department of Ophthalmology and Research Institute of Medical Sciences Chonnam National University Medical School and Hospital, Gwangju, Korea.
  • 2Department of Ophthalmology and Research Institute of Medical Sciences Chonnam National University Medical School and Hospital, Gwangju, Korea 2Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiame.
  • 3College of Veterinary Medicine, Chonnam National University, Gwangju, Korea.

 

Abstract
PURPOSE: 

To investigate the efficacy of topical 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) in a mouse model of experimental dry eye (EDE).

METHODS: 

Eye drops consisting of 0.001% or 0.01% AICAR, 0.05% cyclosporine A (CsA), or balanced salt solution (BSS) were applied for the treatment of EDE. Tear volume, tear film break-up time (BUT), and corneal fluorescein staining scores were measured 10 days after treatment. Levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interferon gamma-induced protein 10 (IP-10), and monokine induced by interferon-γ (MIG) were measured in the conjunctiva. In addition, Western blot, periodic acid-Schiff staining for evaluating goblet cell density, flow cytometry for counting the number of CD4+CXCR3+ T cells, and immunohistochemistry for detection of 4-hydroxy-2-nonenal (4HNE) were performed.

RESULTS: 

Mice treated with 0.01% AICAR showed a significant improvement in all clinical parameters compared with the EDE control, vehicle control, and 0.001% AICAR groups (P < 0.001). A significant decrease in the levels of IL-1β, IL-6, TNF-α, IFN-γ, IP-10, and MIG, the number of CD4+CXCR3+ T cells, and the number of 4HNE-positive cells were also observed in the 0.01% AICAR group (P < 0.001). Although 0.05% CsA also led to an improvement in clinical parameters and inflammatory molecule levels, its therapeutic effects were comparable or inferior to those of 0.01% AICAR.

CONCLUSIONS: 

Topical application of 0.01% AICAR can markedly improve clinical signs and decrease inflammation in the ocular surface of EDE, suggesting that AICAR eye drops may be used as a therapeutic agent for dry eye disease.

  PMID: 26024098 [PubMed - in process]
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2. Cornea. 2015 May 26. [Epub ahead of print]

Author information: 

  • 1Department of Ophthalmology, University of Kitasato School of Medicine, Kanagawa, Japan.

 

Abstract
PURPOSE: 

To assess the changes in intraocular scattering before and after instillation of rebamipide ophthalmic suspension in patients with dry eye after corneal refractive surgery.

METHODS: 

This study enrolled 60 eyes of 30 dry eye patients undergoing corneal refractive surgery. Patients were randomly assigned to start topical administration of rebamipide ophthalmic suspension (rebamipide group) or artificial tears (control group) 4 times daily for 4 weeks. Tear secretion, tear break-up time (TBUT), and the fluorescein score were measured before and after treatment. Intraocular light scattering was also measured as the objective scattering index (OSI) at 0.5-second intervals over 10 seconds.

RESULTS: 

In the rebamipide group, the Schirmer I test, TBUT, and fluorescein score improved significantly, from 11.4 ± 9.0 mm, 2.2 ± 0.7 seconds, and 4.3 ± 1.3 to 14.9 ± 7.4 mm, 4.5 ± 1.7 seconds, and 1.9 ± 1.0, respectively (P = 0.006, P < 0.001, P < 0.001, Wilcoxon signed rank test). We found significant improvements in OSI at 5.0 to 10.0 seconds after blinking (5-8 seconds, P = 0.01; 9 seconds, P = 0.02; 10 seconds, P < 0.001). The mean OSI, the OSI change rate, and the OSI slope of the linear regression line improved significantly, from 2.73 ± 1.52, 74.7 ± 69.5%, and 0.10 ± 0.12 to 2.19 ± 1.19, 28.6 ± 48.7%, and 0.04 ± 0.08, respectively (P = 0.02, 0.003, and 0.03).

CONCLUSIONS: 

Rebamipide ophthalmic suspension was effective for improving both ocular surface parameters and optical quality in patients with dry eye undergoing corneal refractive surgery, suggesting that it may hold promise for the treatment of such patients.

  PMID: 26020821 [PubMed - as supplied by publisher]
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3. J Glaucoma. 2015 May 14. [Epub ahead of print]

Author information: 

  • 1*Devers Eye Institute at Legacy Health †RS Dow Neurobiology Laboratories, Legacy Research Institute ‡Oregon Health & Science University, Portland, OR.

 

Abstract
PURPOSE: 

To compare the effects of common pharmacy preparation and storage conditions on the stability of mitomycin C (MMC) in solution.

METHODS: 

We used C18 reversed-phase high-performance liquid chromatography to determine the stability of 0.4 mg/mL MMC solutions, and liquid chromatography-electrospray ionization-mass spectrometry to identify degradation products. Conditions compared were: compounding and storage by refrigeration (1 and 2 wk), freezing (23 d), shipment "on-ice" (1 mo frozen followed by 1-wk refrigeration), and immediately compounding dry powder (Mitosol; Mobius Therapeutics LLC). We tested 3 samples for each storage method when samples reached room temperature (time 0), and then 1, 4, and 24 hours later. We used MMC peak area as a percentage of total (MMC plus degradants) area detected with high-performance liquid chromatography as a measure of stability.

RESULTS: 

We assessed MMC stability for 5 preparation and storage methods at 4 timepoints (with n=3 per timepoint). At time 0, we found similar stabilities for MMC (F=0.72, P=0.599) between all 5 storage methods: 1-week refrigerated (97.9±0.2%), dry powder (97.5±0.3%), 2-week refrigerated (96.9±0.2%), 23-day frozen (96.7±3.1%), and shipment on-ice (96.0±1.2%). However, MMC demonstrated significant degradation over a 24-hour period with 2-week refrigeration (95.7±0.3%, β=-0.1%/h, P<0.001) and shipment on-ice (93.1±1.8%, β=-0.1%/h, P=0.013). We identified small amounts (<3.2%) of 2 degradants, cis-hydroxymitosene and trans-hydroxymitosene, across all samples.

CONCLUSIONS: 

The different preparation and storage methods of MMC showed similar stability when used immediately upon reaching room temperature. However, degradation of MMC occurred with further storage at room temperature. The clinical implication of small amounts of MMC degradants is unclear.

  PMID: 26020687 [PubMed - as supplied by publisher]
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4. Eye Sci. 2014 Dec;29(4):204-8.
Abstract
PURPOSE: 

To evaluate the effect of tear malate dehydrogenase 2 on monitoring ocular surface injury in mild dry eye (DE) disease.

METHODS: 

A total of 15 DE patients (30 eyes) with mild subjective symptoms but no ocular surface fluorescein staining signs were enrolled in this study (DE group). The control group was 15 healthy age- and sex-matched volunteers (30 eyes). All subjects were asked to fill out a DE symptoms questionnaire and take different tests including tear MDH and MDH2 activities evaluation, tear breakup time (TBUT), Schirmer I, and slit-lamp examination of the ocular surface. We investigated different changes in tear MDH and MDH2 activities in the DE group and control group, discussed the association between tear MDH2 activity and DE symptoms, and the relationship between tear MDH2 activity and diagnostic tests (Schirmer I and TBUT). We also analyzed the changes in tear MDH2 activities after the treatment with artificial tears.

RESULTS: 

Tear MDH activities in the DE group and control group were 288 ± 102 U/L and 259 ± 112 U/L, respectively, and this difference was not statistically significant (P > 0.05). The tear MDH2 activities in DE group were significantly increased compared with control group. Tear MDH2 was significantly and negatively correlated with the Schirmer's value (r = -0.733, P < 0.01) and the TBUT value (r = -0.841, P < 0.01). MDH2 also had a significant positive correlation with soreness symptoms (r = 0.687, P < 0.01). Treatment with artificial tears relieved or eliminated all discomfort symptoms, together with a considerable decrease in MDH2 activities (P < 0.01), but no significant changes in the Schirmer and the TBUT tests were observed.

CONCLUSION: 

Tear MDH2 activity can indicate ocular surface injury in mild DE patients and may be used to monitor the response to therapy.

  PMID: 26016071 [PubMed - in process]
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5. J Ophthalmic Vis Res. 2015 Jan-Mar;10(1):21-5. doi: 10.4103/2008-322X.156089.

Author information: 

  • 1Trauma Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
  • 2Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
  • 3Ocular Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • 4Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.

 

Abstract
PURPOSE: 

To evaluate the effectiveness of topical cyclosporine A 0.05% for treatment of mustard gas-induced ocular surface disorders with special attention to conjunctival goblet cell density in patients with severe dry eye.

METHODS: 

This prospective clinical study included 20 eyes of 20 patients previously exposed to mustard gas with dry eye syndrome unresponsive to artificial tears. Before and after treatment with topical cyclosporine A 0.05% twice daily for 3 months, subjects were evaluated for improvement in symptoms using the ocular surface disease index (OSDI) and signs by tear breakup time (TBUT), Schirmer test and measurement of superior bulbar conjunctival goblet cell density. Limbal stem cell deficiency (LSCD) and the degree of corneal squamous cell metaplasia were also assessed before and after treatment.

RESULTS: 

Before treatment, mean OSDI score, Schirmer test I value and mean TBUT were 42.8 ± 6.1, 4.2 ± 1.2 mm and 2.5 ± 1.3 s, respectively. After 3 months of treatment with topical cyclosporine A, these scores reached 36.4 ± 5.2, 5.8 ± 1.6 mm and 4.9 ± 2.1 s, respectively showing a statistically significant improvement (P < 0.001) in all parameters. Mean goblet cell density was 23.3 ± 17.1/high power field (hpf) at baseline which was significantly increased to 47.7 ± 16.1/hpf at the end of the study (P < 0.001). There was no improvement, however, in corneal conjunctivalization, LSCD and the degree of corneal squamous cell metaplasia based on impression cytology reports (P > 0.05).

CONCLUSION: 

Treatment with topical cyclosporine A 0.05% in patients with severe dry eye due to mustard gas injury increases goblet cell density in the bulbar conjunctiva and improves symptoms of the disease.

PMCID: PMC4424713 Free PMC Article 
  PMID: 26005548 [PubMed]
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6. Clin Exp Rheumatol. 2015 Mar-Apr;33(2):259-71. Epub 2015 Apr 10.

Author information: 

  • 1Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
  • 2Department of Rheumatology, University of Perugia, Perugia, Italy.
  • 3Department of Rheumatology, University of Florence, Florence, Italy.
  • 4Department of Rheumatology, Policlinico Le Scotte, University of Siena, Siena, Italy.

 

Abstract

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease mainly characterised by the inflammation of exocrine glands; however, a broad spectrum of systemic manifestations may characterise the disease. Recently, pSS has been the object of considerable immunologic and clinical research which has led to significant advances in the diagnosis, prognostic assessment and management of the disease. Herewith, we provide a critical digest of the recent literature on this topic. 

  PMID: 25896475 [PubMed - indexed for MEDLINE]
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7. Saudi J Kidney Dis Transpl. 2015 Mar;26(2):359-62.

Author information: 

  • 1Department of Internal Medicine, La Rabta Hospital, Tunis, Tunisia.

 

Abstract

The association between microscopic polyangiitis (MPA) and primary biliary cirrhosis (PBC) has seldom been reported. We describe here a patient who presented with sensorimotor neuropathy along with hypothyroidism, renal failure and liver dysfunction. Detection of antinuclear antibodies at a titer of 1/800, anti-SSA, anti-SSB, anti-GP210, anti-microsomial and p-ANCA anti-myeloperoxydase antibodies along with renal, salivary and liver biopsy led to a diagnosis of MPA associated with PBC, Sjogren's syndrome and Hashimoto's thyroiditis. 

Free Article 
  PMID: 25758890 [PubMed - indexed for MEDLINE]
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8. Saudi J Kidney Dis Transpl. 2015 Mar;26(2):344-8.

Author information: 

  • 1Department of Medicine, Olive-View UCLA Medical Center; Division of Nephrology, David Geffen School of Medicine, Ronald Regan UCLA Medical Center, Los Angeles, CA, USA.

 

Abstract

Calciphylaxis has seldom been reported in patients with acute renal failure or in pre-dialysis patients. It also has been reported at lower calcium phosphorous products and in patients with adynamic bone disease. We report a pre-hemodialysis (HD) patient with acute renal failure and biopsy-proven calciphylaxis involving multiple cutaneous sites with calcification of the perineal area resulting in dry gangrene of the penis that necessitated a partial penectomy. The patient had elevated serum calcium, phosphorous and parathyroid hormone level of 612 pg/mL. The same patient suffered subsequently from a calcium embolus that occluded his left ophthalmic artery and resulted in left eye blindness. Calciphylaxis is a devastating phenomenon and physicians should have a high clinical suspicion for it in HD patients as well as in patients with late stages of chronic kidney disease. 

Free Article 
  PMID: 25758887 [PubMed - indexed for MEDLINE]
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9. Intern Med. 2015;54(2):223-30. doi: 10.2169/internalmedicine.54.3094. Epub 2015 Jan 15.

Author information: 

  • 1Department of Internal Medicine, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Japan.

 

Abstract

Human immunodeficiency virus (HIV) infection disturbs the host's immune function and often coexists with various autoimmune and/or systemic rheumatic diseases with manifestations that sometimes overlap with each other. We herein present the case of a 43-year-old Japanese man infected with HIV who exhibited elevated serum creatine kinase and transaminases levels without any symptoms. He was diagnosed with autoimmune hepatitis, polymyositis and Sjögren's syndrome and received combined antiretroviral therapy (cART); however, the laboratory abnormalities persisted. We successfully administered cART with the addition of oral prednisolone, and the patient's condition recovered without side effects related to the metabolic or immunosuppressive effects of these drugs. 

Free Article 
  PMID: 25743017 [PubMed - indexed for MEDLINE]
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10. Nat Rev Rheumatol. 2015 Apr;11(4):202-3. doi: 10.1038/nrrheum.2015.10. Epub 2015 Feb 10.

Author information: 

  • 1Department of Pathophysiology, School of Medicine, National University of Athens, 75 Mikras Asias Street, Athens 11527, Greece.

 

Abstract

Examination of biopsy-obtained salivary gland tissue provides valuable insights for the diagnosis, classification and treatment of patients with primary Sjögren syndrome. Could the study of biomarkers present in saliva provide a noninvasive alternative?

  PMID: 25668140 [PubMed - indexed for MEDLINE]
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11. J Ocul Pharmacol Ther. 2014 Sep;30(7):525-6. doi: 10.1089/jop.2014.1509.

Author information: 

  • 1PharmaLogic Development, Inc. , San Rafael, California.

 

  PMID: 25188008 [PubMed - indexed for MEDLINE]
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12. Eye Sci. 2012 Mar;27(1):19-24. doi: 10.3969/j.issn.1000-4432.2012.01.004.

Author information: 

  • 1Wang Eye Clinic, Doraville, GA 30340, USA.

 

Abstract
PURPOSE: 

To compare the complications and the recurrence rate between fibrin glue (TISSEEL) and Vicryl 8-0 sutures in amniotic membrane transplant during pterygium surgery.

METHODS: 

Patients who underwent pterygium surgery with amniotic membrane transplant (AMT) in the Wang Eye Clinic (Doraville, USA) were randomly categorized into two groups: one group received TISSEEL and the other group received Vicryl 8-0 sutures. All procedures for both groups were performed by one ophthalmologist. Twenty-four patients (24 eyes) participated in the TISSEEL group (22 eyes with primary surgery and 2 eyes with surgery for recurrence) and 19 patients (19 eyes) took part in the suture group (18 primary eyes and 1 recurrence). The patients with recurrent pterygium in both groups had not received AMT previously. Post-operatively, patients were followed up for one week and then one year to check for any signs of complications and recurrence.

RESULTS: 

Conjunctival inflammation occurred in 3 eyes (12.5%) in the TISSEEL group, and 6 eyes (31.6%) in the suture group (P<0.05, Chi-square test). In the TISSEEL group, 1 eye (4.2%) showed recurrence, while there were no recurrences in the sutures group. There were 3 dry eyes (15.8%) in the suture group and 2 dry eyes (8.3%) in the TISSEEL group (P>0.05). No dislocated conjunctival grafts, Dellen, inflammation, infection, bleeding, pyogenic granuloma, or scleromalacia was observed in either group.

CONCLUSION: 

Pterygium surgery with AMT had less conjunctival inflammation and dry eye in patients receiving fibrin glue than those with Vicryl 8-0 sutures.

  PMID: 22447547 [PubMed - indexed for MEDLINE]
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13. Drug Dev Ind Pharm. 2012 Jul;38(7):893-8. doi: 10.3109/03639045.2011.633261. Epub 2011 Nov 16.

Author information: 

  • 1Department of Pharmaceutics, University of Minnesota, MN 55455, USA.

 

Abstract

The purpose of this study was to assess quantitatively the aerosol deposition in a model eye chamber to identify the mechanism(s) of deposition and delivery efficiency for application in retinal disease treated with vitrectomy. Dry aerosol particles were produced with mixtures of fluorescein and a variable concentration of cesium chloride, which ranged in aerodynamic size from 0.6 to 1.3 µm. The aerosol was injected through a small inlet tube into Teflon chambers that had a vented, spherical cavity (diameter ¾"). Two filling times of 60 s and 90 s were used. Although significant loss occurred in the syringe, the mass deposited within the chambers increased with aerosol concentration and ranged from 0.5 to nearly 15 µg. Between 60 and 90% of the mass was deposited on the lower surface of the chamber. The mechanism of deposition was consistent with diffusion through a boundary layer during filling followed by sedimentation of the remaining suspended aerosol particles. Based on these results, an aerosol with a median particle size of 1.3 µm was shown to provide a therapeutically effective dose of 5-fluorouracil. The approach is general and can be applied to the aerosol delivery of other drugs to the vitreous chamber.

  PMID: 22087844 [PubMed - indexed for MEDLINE]
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