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Neuroptis Dry Eye Project with ML 7 (Myosin Light Chain Inhibitor)
20 juillet 2015

NEW PUBLICATIONS UPTO JULY 18TH 2015

 

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NEW PUBLICATIONS UPTO JULY 18TH 2015 

 

 

 

A Pragmatic Approach to the Management of Dry Eye Disease:... : Optometry & Vision Science

Dry eye disease (DED) is a highly prevalent chronic ocular disorder that can lead to significant discomfort and visual disturbance. It is a potentially debilitating condition that can have significant negative impact on quality of life. A diverse range of management options exists for DED, incl...

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1. Exp Eye Res. 2015 Jul 14. pii: S0014-4835(15)00227-4. doi: 10.1016/j.exer.2015.06.032. [Epub ahead of print]

Author information: 

  • 1Department of Ophthalmology, Huashan Hospital Affiliated to Fudan University, 12 Middle Wulumuqi Road, Buiding 3, Room 802, Shanghai 200040, China.
  • 2Tongji Eye Institute and Department of Regenerative Medicine, Tongji University School of Medicine, 1239 Siping Road, Medical School Building, Room 521, Shanghai 200092, China.
  • 3Department of Ophthalmology, Huashan Hospital Affiliated to Fudan University, 12 Middle Wulumuqi Road, Buiding 3, Room 802, Shanghai 200040, China. Electronic address: yewen0412@hotmail.com.

 

Abstract

FTY720 is a promising drug in attenuating multiple sclerosis, prolonging survival of organ allograft, and many other protective effects. Its mechanism of action is considered to be mediated by the internalization of sphingosine 1-phosphate receptors (S1PRs). In the current study, we investigated the efficacy of FTY720 in Non-Obese Diabetic (NOD) mice, serving as a model of Dry Eye Disease (DED). NOD mice were divided into six study groups, i.e., FTY720-treated groups with 3 concentrations of FTY720 (0.05%, 0.005%, and 0.001%), 0.05% Cyclosporin A (CsA) treated group, normal saline treated group, and no treatment control group. FTY720 was reconstituted with normal saline and prepared as eye drop. The stability and production of tear film was measured by Tear Break up Time test (TBUT) and phenol red cotton thread test (PRCTT), respectively. Tear fluid washings were collected and assessed by ELISA. Cytokines were detected in lacrimal glands by RT-PCR. Inflammation in conjunctiva was assessed by immunohistochemistry, goblet cells and conjunctival epithelia were examined and evaluated by impression cytology. Our results indicated that FTY720 had a significantly therapeutic effect in NOD mice. After FTY720 intervention, TBUT and PRCTT data were greatly improved (p < 0.01), the interleukin 1β (IL-1β) level was markedly decreased in tear fluid washings compared to control and normal saline groups after 2 weeks (Control: 1.06 ± 0.12, Normal saline:0.97 ± 0.09 pg/ml, CsA:0.22 ± 0.02 pg/ml, 0.001% FTY720:0.23 ± 0.02 pg/ml, 0.005% FTY720:0.14 ± 0.03 pg/ml, 0.05% FTY720: 0.18 ± 0.03 pg/ml. CsA group and 3 FTY720 groups VS. control group and normal saline groups: p < 0.01). Proinflammatory factors were greatly decreased in lacrimal glands (p < 0.01). Leukocytes were identified and markedly decreased in conujnctiva (p < 0.01), inflammatory reaction of DED was greatly relieved. More importantly, the goblet cells were largely restored and ocular surface lesions were significantly ameliorated (p < 0.01). Thus, we observed FTY720 alleviated DED in NOD mice by inhibiting leukocytes, the function of ocular surface tissue in NOD mice was partially restored via inhibiting ocular surface inflammation and increasing the density of goblet cells and conjunctival epithelia. FTY720 may offer a novel strategy for the treatment of inflammatory disorders in the ocular surface.

Copyright © 2015. Published by Elsevier Ltd.

  PMID: 26187517 [PubMed - as supplied by publisher]
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2. J Control Release. 2015 Jul 13. pii: S0168-3659(15)30022-5. doi: 10.1016/j.jconrel.2015.07.007. [Epub ahead of print]

Author information: 

  • 1Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030.
  • 2 Ocular Surface Center, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030. Electronic address: gacharya@bcm.edu.

 

Abstract

Dry eye disease is a major public health problem that affects millions of people worldwide. It is presently treated with artificial tear and anti-inflammatory eye drops that are generally administered several times a day and may have limited therapeutic efficacy. To improve convenience and efficacy, a dexamethasone (Dex) loaded nanowafer (Dex-NW) has been developed that can release the drug on the ocular surface for a longer duration of time than drops, during which it slowly dissolves. The Dex-NW was fabricated using carboxymethyl cellulose polymer and contains arrays of 500nm square drug reservoirs filled with Dex. The in vivo efficacy of the Dex-NW was evaluated using an experimental mouse dry eye model. These studies demonstrated that once a day Dex-NW treatment on alternate days during a five-day treatment period was able to restore a healthy ocular surface and corneal barrier function with comparable efficacy to twice a day topically applied dexamethasone eye drop treatment. The Dex-NW was also very effective in down regulating expression of inflammatory cytokines (TNF-α, and IFN-γ), chemokines (CXCL-10 and CCL-5), and MMP-3, that are stimulated by dry eye. Despite less frequent dosing, the Dex-NW has comparable therapeutic efficacy to topically applied Dex eye drops in experimental mouse dry eye model, and these results provide a strong rationale for translation to human clinical trials for dry eye.

Copyright © 2015. Published by Elsevier B.V.

  PMID: 26184051 [PubMed - as supplied by publisher]
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3. Br J Ophthalmol. 2015 Jul 15. pii: bjophthalmol-2015-306842. doi: 10.1136/bjophthalmol-2015-306842. [Epub ahead of print]

Author information: 

  • 1Department of Ophthalmology and Visual Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.

 

Abstract

Human serum-derived and plasma-derived therapies have become increasingly popular in the treatment of ocular surface disorders, with mounting clinical and scientific evidence suggesting good safety and efficacy profiles. These therapies may be considered for various ocular surface conditions, such as dry eye syndrome and persistent epithelial defect, when conservative management does not suffice. The costly and inconvenient process of obtaining the blood-derived products is the barrier to their more widespread use. Some blood-derived therapies, such as umbilical cord serum-derived and platelet-derived plasma preparations, may be more viable options since these therapies can be made readily available to patients. In this review, the existing literature on the safety and efficacy of blood-derived products, such as autologous serum tears, in the treatment of ocular surface diseases is discussed. Issues relevant to the production of autologous serum tears are also described.

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: 26178904 [PubMed - as supplied by publisher]
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4. Invest Ophthalmol Vis Sci. 2015 Jul 1;56(8):4350-63. doi: 10.1167/iovs.15-16475.

Author information: 

  • 1Department of Anatomy and Cell Biology, Martin Luther University, Halle-Wittenberg, Halle (Saale), Germany 2Department of Ophthalmology, University of Düsseldorf, Düsseldorf, Germany 3Department of Anatomy II, Friedrich Alexander University Erlangen-Nürnb.
  • 2Department of Anatomy and Cell Biology, Martin Luther University, Halle-Wittenberg, Halle (Saale), Germany.
  • 3Department of Anatomy II, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany.
  • 4Fraunhofer Institution for Marine Biotechnology, Fraunhofer Institution, Lübeck, Germany.
  • 5Department of Anatomy and Cell Biology, Martin Luther University, Halle-Wittenberg, Halle (Saale), Germany 3Department of Anatomy II, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany.

 

Abstract
PURPOSE: 

Aqueous tear deficiency due to lacrimal gland insufficiency is one of the major causes of dry eye disease. In severe cases, such as Sjogren's syndrome, Stevens-Johnson syndrome, or ocular cicatricial pemphigoid, therapy with artificial tears is often insufficient to relieve severe discomfort, prevent progressive ocular surface disease, or enable visual rehabilitation by corneal transplantation. Cell or organ generation from stem cells, resulting in tear-like secretion, presents an option as a suitable alternative treatment. To obtain deeper insights into lacrimal gland stem cells we analyzed murine lacrimal glands for markers of pluripotency, self-renewal, and differentiation.

METHODS: 

A special, patented technique with mechanical and enzymatic digestion was used to generate high numbers of cells in vitro from murine lacrimal glands. These presumptive "murine lacrimal gland stem cells" ("mLGSCs") can be propagated as monolayer cultures over multiple passages. By means of RT-PCR, Western blot, and immunohistochemistry, markers of pluripotency and differentiation were demonstrated. Hanging drop culture was used to build organoid bodies from mLGSCs to investigate their spontaneous differentiation in three-dimensional culture with histology, immunohistochemistry, and transmission electron microscopy methods.

RESULTS: 

Isolated mLGSCs were cultured over more than 65 passages. Murine lacrimal gland stem cells expressed markers of pluripotency such as Nanog, Sox2, Kruppel-like factor 4 (Klf4), as well as early-lineage markers of all three germ layers. Three-dimensional culture of these cells revealed their ability to differentiate into various cell types.

CONCLUSIONS: 

Our results suggest that mLGSCs were isolated and cultured successfully. These cells have the ability to differentiate into all three germ layers. The results provide further insights into lacrimal gland stem cell physiology for engineering of a lacrimal gland construct to treat severe cases of tear deficiency in the future.

  PMID: 26176872 [PubMed - in process]
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5. J Biomater Sci Polym Ed. 2015 Jul 15:1-26. [Epub ahead of print]

Author information: 

  • 1a Maliba Pharmacy College, Uka Tarsadia University , Surat 394350 , Gujarat , India , Tel.: +91 8238651055.

 

Abstract

Current dry eye treatment includes delivering comfort enhancing agents to the eye via eye drops, but low residence time of eye drops leads to low bioavailability. Frequent administration leads to incompliance in patients, so there is a great need for medical device such as contact lenses to treat dry eye. Studies in the past have demonstrated the efficacy of hyaluronic acid in the treatment of dry eyes using eye drops. In this paper, we present two methods to load hyaluronic acid in hydrogel contact lenses, soaking method and direct entrapment. The contact lenses were characterized by studying their optical and physical properties to determine their suitability as extended wear contact lenses. Hyaluronic acid laden hydrogel contact lenses prepared by soaking method showed release up to 48 hours with acceptable physical and optical property. Hydrogel contact lenses prepared by direct entrapment method showed significant sustained release in comparison to soaking method. Hyaluronic acid entrapped in hydrogels resulted in reduction in % transmittance, sodium ion permeability, and surface contact angle, while increase in % swelling. The impact on each of these properties was proportional to hyaluronic acid loading. The batch with 200 μg hyaluronic acid loading showed all acceptable values (parameters) for contact lens use. Results of cytotoxicity study indicated the safety of hydrogel contact lenses. In vivo pharmacokinetics studies in rabbit tear fluid showed dramatic increase in HA mean residence time and area under curve with lenses in comparison to eye drop treatment. The study demonstrates the promising potential of delivering hyaluronic acid through contact lenses for treatment of dry eye syndrome.

  PMID: 26176811 [PubMed - as supplied by publisher]
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6. Optom Vis Sci. 2015 Jul 13. [Epub ahead of print]

Author information: 

  • 1*OD, PhD, FAAO †OD, MS, FAAO School of Optometry (both authors), and Clinical Research Center (MCL), University of California, Berkeley, Berkeley, California; and Vision Science Program, University of California, San Francisco, San Francisco, California (both authors).

 

Abstract

: A panel of experts was invited to discuss the following questions: Why does the prevalence of dry eye disease (DED) appear to be increasing? Are you satisfied with the current definition and classification of DED-aqueous deficiency versus evaporative dry eye? Beyond the innate human factors (e.g., genetics), what external factors might contribute to DED? What areas related to DED need to be more fully understood? In examining a patient complaining of dry eye, what is your strategy (e.g., tests, questionnaire)? What is your strategy in unraveling the root cause of a patient's dry eye symptoms that may be shared by many anterior segment diseases? What are the two or three most common errors made by clinicians in diagnosing DED? Why do contact lens (CL) patients complain of dry eye while wearing lenses but not when not wearing lenses? What areas related to CL discomfort need to be more fully understood? What is your most effective strategy for minimizing CL discomfort? With current advances in biotechnology in dry eye diagnostics and management tools, do you think our clinicians are better prepared to diagnose and treat this chronic condition than they were 5 or 10 years ago? Do you foresee any of these new point-of-care tests becoming standard clinical tests in ocular surface evaluation? What treatments are effective for obstructed Meibomian glands secondary to lid margin keratinization? What level of DED would prevent you from recommending an elected ophthalmic surgery? What strategy do you use to help your patients comply with the recommended home therapies? How do you best manage patients whose severity of dry eye symptoms does not necessarily match clinical test results, especially in cases of ocular surface neuropathy? Where do you see dry eye diagnosis and treatment in 10 years or more?

  PMID: 26176354 [PubMed - as supplied by publisher]
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7. Optom Vis Sci. 2015 Jul 13. [Epub ahead of print]

Author information: 

  • 1*PhD, BOptom, PGCertOcTher †PhD, BAppSc(Optom), PGCertOcTher Department of Optometry and Vision Sciences, University of Melbourne, Parkville, Victoria, Australia (LED, PRK); and Macular Research Unit, Centre for Eye Research Australia, East Melbourne, Victoria, Australia (PRK).

 

Abstract

: Dry eye disease (DED) is a highly prevalent chronic ocular disorder that can lead to significant discomfort and visual disturbance. It is a potentially debilitating condition that can have significant negative impact on quality of life. A diverse range of management options exists for DED, including tear supplement products, anti-inflammatory agents, immunomodulators, punctal occlusive devices, and environmental modifiers. Although the availability of a variety of treatment approaches provides clinical flexibility and can enable individualized care, it can also complicate clinical management decisions and lead to variability in the nature of the clinical care provided to patients. By considering two dry eye case scenarios, this review evaluates the currently available evidence relating to DED therapy to describe a pragmatic clinical approach to best-practice management of dry eye patients.

  PMID: 26176353 [PubMed - as supplied by publisher]
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8. Clin Ophthalmol. 2015 Jul 3;9:1209-13. doi: 10.2147/OPTH.S84704. eCollection 2015.

Author information: 

  • 1Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

 

Abstract
PURPOSE: 

To evaluate the ocular presentation, treatment, and clinical course of graft-versus-host disease (GVHD).

DESIGN: 

Retrospective case series.

PARTICIPANTS: 

Two hundred and forty-nine patients with systemic GVHD were included in the study.

METHODS: 

Ocular and systemic data were collected from 2003 to 2013.

MAIN OUTCOME MEASURES: 

Mortality, visual acuity, and response of ocular symptoms.

RESULTS: 

Sixty-four patients had ocular manifestations (25.7%). At presentation, the mean age was 44.5 years and mean latency was 16.4 months. The most common presentations were keratoconjunctivitis sicca, cataract, blepharitis, ocular hypertension, and filamentary keratitis. Visual acuity at presentation was 20/49; at the worst point in the disease was 20/115; and at most recent visit was 20/63. When topical anti-inflammatory drops were used in addition to tears, 54.3% of patients' ocular symptoms stabilized. When autologous serum was used in addition, 80% stabilized. The overall 10-year mortality of GVHD was 29.7%. For those with ocular involvement, it was 21.9%.

CONCLUSION: 

Systemic GVHD has a high mortality rate, but ocular involvement does not suggest a worse prognosis. The main ocular presentations were keratoconjunctivitis sicca, cataracts, and ocular hypertension. Dry eyes in this population were very severe with overall worsening in visual acuity. However, with a step-wise approach involving topical anti-inflammatory medications and autologous serum tears, ocular symptoms do improve. It is important to monitor these patients closely, as they are prone to serious ocular complications such as corneal perforation and endophthalmitis.

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  PMID: 26170614 [PubMed]
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9. Clin Ophthalmol. 2015 Jun 24;9:1137-45. doi: 10.2147/OPTH.S81355. eCollection 2015.

Author information: 

  • 1Department of Ophthalmology, Mount Sinai School of Medicine, New York, NY, USA.

 

Abstract
PURPOSE: 

To determine the changes in dry eye disease (DED) severity and the percentage of cells expressing HLA-DR on the ocular surface following treatment with lubricant eyedrops containing polyethylene glycol and propylene glycol (PEG/PG) and the gelling agent hydroxypropyl guar (HP-Guar).

PATIENTS AND METHODS: 

Nineteen patients with DED used PEG/PG + HP-Guar eyedrops four times per day for 30 days. Assessments included DED severity (Ocular Surface Disease Index [OSDI], corneal staining, conjunctival staining, tear film break-up time [TFBUT], and Schirmer testing) and impression cytology of the conjunctiva with masked flow cytometry at baseline and at 30 days.

RESULTS: 

There was a significant decrease in corneal staining (P<0.01), OSDI (P=0.02), and TFBUT (P<0.01) following treatment with PEG/PG + HP-Guar. Results from flow cytometry revealed a significant decrease in cells expressing HLA-DR (P=0.02).

CONCLUSION: 

Treatment with PEG/PG + HP-Guar eyedrops showed improvement in dry eye severity and reduction in surface inflammation as indicated by a reduction in HLA-DR expression.

Free Article 
  PMID: 26170605 [PubMed]
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10. Optom Vis Sci. 2015 Jul 8. [Epub ahead of print]

Author information: 

  • 1*OD, MPH, FAAO †OD, PHD, FAAO ‡OD, FAAO TearScience Inc, Morrisville, North Carolina (all authors); and Korb Associates, Boston, Massachusetts (all authors).

 

Abstract
PURPOSE:

To investigate which warm compress (WC) methods used in a small case series are the most effective in providing heat to the inner eyelids for the supplemental treatment of meibomian gland dysfunction.

METHODS: 

Inclusion criteria included the following: 18 years or older and willingness to participate in the study, no current ocular inflammation/disease, and no ocular surgery within the last 6 months. Five patients were fully consented and enrolled. Various forms of contact and noncontact WC heating methods (dry, wet/moist, and chemically activated dry heat) were tested. A paired contralateral design was used; each subject had a heated test eye and an unheated control eye. For both test and control eyes, the temperature of the external upper, external lower, and internal lower lids was measured at baseline and every 2 minutes for 10 minutes during application. Each participant underwent each of the eight treatments under study. Microwaved compresses were heated to 47 ± 1.0°C; two compresses were self-heating and thus not under investigator control.

RESULTS: 

The mean (±SD) age of the patients was 42.2 (±20.3) years. Out of the eight methods tested, the bundled wet/moist towel method was the only compress that elevated the temperature of all three lid surfaces (external upper, external lower, and internal lower lids) to 40°C or higher. The chemically activated EyeGiene, MGDRx EyeBag, and MediBeads compresses resulted in the lowest temperature increase at the inner palpebral surface.

CONCLUSIONS: 

The Bundle method, although the most labor intensive, increased lid temperatures above therapeutic levels, as reported in the literature, for all measured sections during the WC application. As such, this method of WC application can be recommended for supplemental at-home therapy for meibomian gland dysfunction and any condition requiring that therapeutic heat of 40°C be administered to the meibomian glands.

  PMID: 26164316 [PubMed - as supplied by publisher]
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11. Optom Vis Sci. 2015 Jul 8. [Epub ahead of print]

Author information: 

  • 1*OD, BSc, FAAO †OD, PhD, FAAO ‡PhD, BSOptom, FAAO §PhD, FCOptom, FAAO Centre for Contact Lens Research, School of Optometry and Vision Science, University of Waterloo, Waterloo, Ontario, Canada (WN, SS, LWJ); and Toronto Eye Care, Toronto, Ontario, Canada (BC).

 

Abstract
PURPOSE: 

To evaluate the effect of lid debridement-scaling (LDS) on dry eye signs and symptoms in subjects with Sjögren syndrome (SS).

METHODS: 

This prospective randomized controlled study enrolled 14 female subjects with SS. Seven subjects were randomized into the treatment group where they were selected to receive LDS; the remainder did not receive LDS and served as control subjects. Lid debridement-scaling was conducted using a stainless steel golf club spud (Hilco Wilson Ophthalmics, Plainville, MA) on both the upper and lower eyelids of both eyes. Outcome variables were assessed before LDS and again 1 month later. The outcome variables were the Ocular Surface Disease Index (OSDI), Symptom Assessment iN Dry Eye (SANDE) visual analog scores, ocular staining (SICCA OSS [Sjögren's International Collaborative Clinical Alliance Ocular Staining Score]), fluorescein tear breakup time (FLBUT), meibomian gland score (MGS), meibomian gland yielding liquid secretions (MGYLS) score, and line of Marx's (LOM) position.

RESULTS: 

Thirteen subjects completed the study. Data from only the right eye were analyzed. For the control group (n = 6; mean [±SD] age, 62.3 [±11.6] years), the pre-LDS, post-LDS, and significance level (pre-LDS mean [±SD] vs. post-LDS mean [±SD]; p value) were as follows: OSDI (58.3 [±22.1] vs. 48.3 [±29.0]; p = 0.051), SANDE (77.4 [±22.1] vs. 89.6 [±32.6]; p = 0.20), SICCA OSS (7.0 [±4.5] vs. 8.2 [±3.5]; p = 0.25), MGS (1.3 [±1.5] vs. 1.0 [±0.9]; p = 0.75), MGYLS (0.3 [±0.5] vs. 0.0 [±0.0]; p = 0.50), FLBUT (2.99 [±1.54] vs. 2.85 [±1.79]; p = 0.63), and LOM (2.0 [±0.0] vs. 2.0 [±0.0]; p = n/a). For the treatment group (n = 7; mean [±SD] age, 58.0 [±8.1] years), the pre-LDS, post-LDS, and significance level were as follows: OSDI (63.2 [±13.3] vs. 46.9 [±19.4]; p = 0.04), SANDE (72.6 [±17.1] vs. 77.0 [±28.0]; p = 0.54), SICCA OSS (6.6 [±2.9] vs. 5.0 [±3.9]; p = 0.02), MGS (1.0 [±1.2] vs. 3.1 [±1.7]; p = 0.01), MGYLS (0.0 [±0.0] vs. 0.6 [±1.0]; p = 0.50), FLBUT (3.13 [±0.81] vs. 3.45 [±1.03]; p = 0.53), and LOM (0.9 [±0.9] vs. 1.0 [±1.0]; p = 1.00).

CONCLUSIONS: 

This pilot study showed that LDS improved symptoms, ocular staining, and meibomian gland function for the group that received LDS. This indicates that LDS can aid in the management of SS dry eye.

  PMID: 26164314 [PubMed - as supplied by publisher]
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12. Optom Vis Sci. 2015 Jul 8. [Epub ahead of print]

Author information: 

  • 1*MD †OD, FAAO Department of Ophthalmology, School of Medicine, Texas Tech University, Lubbock, Texas (AHB); and Department of Optometry, School of Optometry, The University of Alabama at Birmingham, Birmingham, Alabama (JDB).

 

Abstract

: Dry eye disease and other ocular surface diseases are complex multifactorial disorders often characterized by ocular surface inflammatory changes, instability of the tear film, and functional vision impairment. Recent research has led to new concepts regarding diagnosis and management, and therapeutic interventions now include ocular lubricants, secretagogues, topical and systemic anti-inflammatory and immunosuppressive agents, tear preservation, and, for advanced cases, a variety of surgical approaches. This review considers contemporary procedures for treatment of advanced ocular surface diseases, including thermal and electrocautery of the lacrimal puncta, lid surgeries such as tarsorrhaphy, and multiple procedures to protect the exposed or compromised ocular surface.

  PMID: 26164312 [PubMed - as supplied by publisher]
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13. Optom Vis Sci. 2015 Jul 8. [Epub ahead of print]

Author information: 

  • 1*OD, FAAO †MD, MBA ‡BA Private Practice, Azusa, California (MMH); and Icahn School of Medicine at Mount Sinai, New York, New York (PA, BB).

 

Abstract

The omega-3 (ω3) and omega-6 (ω6) essential fatty acid knowledge base has been exploding. In the last 5 years, at least 12 clinical trials on ω3 and ω6 supplementation and dry eye disease (DED) were published in the peer-reviewed literature (2010 to 2015), about double the amount published in the 5 years prior. Although there is increasing scientific evidence that supports the potential use of ω3 and ω6 supplementation for DED, there are limited randomized controlled trials to properly inform evidence-based medicine. Dry eye disease is one of the most common eye conditions that patients seek care for and cannot be disregarded as a trivial condition. The roles of ω3 and ω6 polyunsaturated fatty acids (PUFAs) in the treatment of DED are still not completely understood. There are distinct and sometimes opposite effects of ω3 and ω6 PUFAs, both of which are essential and cannot be synthesized de novo in the body. These fatty acids must be obtained from the diet, which varies widely by region, even within the United States. Omega-3 PUFAs have anti-inflammatory effects; a proper ratio of ω6:ω3 in the diet must be established. Objectively correlating changes in dry eye syndrome with blood levels of ω3 PUFAs has not been done in a large-scale multisite study. Just as Wilder's law of initial value states that "the direction of response of a body function to any agent depends to a large degree on the initial level of that function," the baseline status needs to be taken into account. There is also no consensus on the dose, composition, length of treatment, and so on with ω3 or ω6 PUFAs. Increased quality evidence on the usefulness of over-the-counter supplements is needed to enable eye care providers to confidently outline specific treatment recommendations for using ω3 PUFAs in DED.

  PMID: 26164311 [PubMed - as supplied by publisher]
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14. Eye (Lond). 2015 Jul 10. doi: 10.1038/eye.2015.125. [Epub ahead of print]

Author information: 

  • 1Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

 

Abstract

PurposeTo investigate the long-term results of 3% diquafosol ophthalmic solution as an alternative therapy to existing ophthalmic solutions, including topical immunosuppression, for the treatment of dry eye in patients with Sjögren's syndrome.MethodsThis study involved 14 female dry-eye patients (mean age: 62.4 years) with Sjögren's syndrome who insufficiently responded to their current therapy. In all patients, 3% diquafosol ophthalmic solution was administered six times daily for 12 months in substitution for artificial tears and sodium hyaluronate ophthalmic solution. Their use of corticosteroid eye drops remained unchanged from that prior to the treatment with diquafosol sodium. The subjective symptoms assessed, and ocular signs including tear meniscus radius and the tear film breakup time, and ocular-surface epithelial damage score were examined at 1, 2, 3, 4, 5, 6, 9, and 12 months after initiating treatment.ResultsAmong the subjective symptoms, significant improvement was obtained in dryness at 2 months post treatment, in eye fatigue at 1, 2, 3, 4, and 12 months post treatment, and in pain at 1, 2, 6, and 12 months post treatment. Difficulty in opening the eye, foreign body sensation, and redness were also significantly ameliorated at various time-points. The tear meniscus radius and the tear film breakup time were significantly improved throughout the observation period, and the corneal epithelial staining scores were significantly decreased at 3 months post treatment.ConclusionsIn dry-eye patients with Sjögren's syndrome, treatment with 3% diquafosol ophthalmic solution improved both symptoms and signs, and that effectiveness was maintained for 12 months.Eye advance online publication, 10 July 2015; doi:10.1038/eye.2015.125.

  PMID: 26160526 [PubMed - as supplied by publisher]
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15. J Ocul Pharmacol Ther. 2015 Jul 8. [Epub ahead of print]

Author information: 

  • 1Department of Ophthalmology, University of Cologne , Cologne, Germany .

 

Abstract

Thrombospondin-1 (TSP-1) is a matricellular glycoprotein that belongs to a family of evolutionary highly conserved calcium-binding proteins consisting of 5 members (TSP-1-TSP-5). In the eye, TSP-1 is expressed by several ocular cell types and is also detectable in the aqueous humor and the vitreous body. So far, TSP-1 is one of the major activators of TGFβ, suggesting a strong influence on various important cellular functions and interactions such as differentiation, migration, and wound healing. TSP-1 is also a key endogenous inhibitor of hem- and lymphangiogenesis. Several lines of evidence indicate a crucial role of TSP-1 in maintaining the ocular immune and angiogenic privilege, for example, by regulating T lymphocytes and the tolerance-promoting properties of ocular antigen-presenting cells. This review discusses the role of TSP-1 in dry eye disease and corneal graft rejection through its effects on hem- and lymphangiogenesis, as well as on the underlying immune responses. Recent work will be reviewed showing by which molecular mechanism TSP-1 modulates inflammatory processes during ocular diseases. This opens potential new treatment avenues in inflammatory and (lymph)angiogenic ocular diseases.

  PMID: 26154823 [PubMed - as supplied by publisher]
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16. Optom Vis Sci. 2015 Jul 3. [Epub ahead of print]

Author information: 

  • 1*OD †OD, PhD ‡OD, PhD, FAAO School of Optometry (all authors), Vision Science Program (NAMc, MCL), University of California, Berkeley, Berkeley, California; Proctor Foundation, University of California, San Francisco, San Francisco, California (NAMc); and Clinical Research Center, University of California, Berkeley, Berkeley, California (MCL).

 

Abstract

: The authors have reviewed the potential etiology and long-standing consequences of isotretinoin use in the development of dry eye symptoms in the absence of significant clinical findings. Despite the normal appearance of meibomian gland structure on meibography and minimal signs of eyelid margin inflammation, the secretory function of these glands is reduced and symptoms of dryness can greatly impact a patient's quality of life. The available literature indicates that isotretinoin's effect on the meibomian glands likely mimics its effects on the sebaceous glands of the skin in the treatment of acne. Several representative cases seen at the University of California Berkeley School of Optometry Dry Eye Clinic provide a clinical paradigm with the goal of raising awareness of the potential prevalence of this disease in patients who experience symptoms of dry eye. These cases highlight the importance of meibomian gland expression in determining whether there is poor quality and/or quantity of meibum secondary to reduced gland function. Currently, there is no definitive method to restore the structure and function of damaged meibomian glands; thus, treatment options for isotretinoin-associated meibomian gland dysfunction are primarily palliative to manage patient symptoms.

  PMID: 26154692 [PubMed - as supplied by publisher]
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17. Optom Vis Sci. 2015 Jul 3. [Epub ahead of print]

Author information: 

  • 1*BA †MD Keck School of Medicine, University of Southern California, Los Angeles, California (CT); Boston Foundation for Sight, Needham, Massachusetts (DSJ); and Cornea & Refractive Surgery Service, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts (DSJ, PH).This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

 

Abstract
PURPOSE: 

To illustrate that corneal neuralgia may be the basis for refractory dry eye syndrome after laser-assisted in situ keratomileusis (LASIK).

METHODS: 

The methodology used is that of a retrospective medical record review of a small case series.

RESULTS: 

Three male patients, aged 30 to 48 years, referred in 2012 for dry eye syndrome refractory to treatment within 1 year of LASIK or LASIK enhancement are reported. Each patient gave history of eye pain, light sensitivity, and difficulty with visual activities beginning within 2 months of LASIK or LASIK enhancement. Best-corrected visual acuity was 20/15 or 20/20 in each of the six eyes. Tear-centered models and metrics did not explain persistent symptoms, which was consistent with inadequate response to standard dry eye treatments used before referral and reported here. In vivo confocal microscopy was abnormal at presentation in each case and was followed over time. Treatments undertaken subsequent to referral included autologous serum tears (three cases), PROSE (Prosthetic Replacement of the Ocular Surface Ecosystem) treatment (two cases), and systemic agents for pain, anxiety, or depression (three cases). By the end of 2013, at a mean of 23 months after LASIK or LASIK enhancement, symptoms improved in all three patients.

CONCLUSIONS: 

Patients with persistent dry eye symptoms out of proportion to clinical signs after LASIK have a syndrome that may best be classified as corneal neuralgia. In vivo confocal microscopy can be informative as to the neuropathic basis of this condition. In keeping with current understanding of complex regional pain syndrome, early multimodal treatment directed toward reducing peripheral nociceptive signaling is warranted to avoid subsequent centralization and persistence of pain. Distinguishing this syndrome from typical post-LASIK dry eye remains a challenge.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

  PMID: 26154691 [PubMed - as supplied by publisher]
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18. Optom Vis Sci. 2015 Apr;92(4):393. doi: 10.1097/OPX.0000000000000577.

Author information: 

  • 1Editor in Chief Optometry and Vision Science.

 

  PMID: 25946096 [PubMed - indexed for MEDLINE]
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19. Immunology. 2015 Jun;145(2):232-41. doi: 10.1111/imm.12439.

Author information: 

  • 1Stead Family Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.

 

Abstract

CD4(+) CD25(+) Foxp3(+) regulatory T (Treg) cells are required to maintain immunological tolerance; however, defects in specific organ-protective Treg cell functions have not been demonstrated in organ-specific autoimmunity. Non-obese diabetic (NOD) mice spontaneously develop lacrimal and salivary gland autoimmunity and are a well-characterized model of Sjögren syndrome. Lacrimal gland disease in NOD mice is male-specific, but the role of Treg cells in this sex-specificity is not known. This study aimed to determine if male-specific autoimmune dacryoadenitis in the NOD mouse model of Sjögren syndrome is the result of lacrimal gland-protective Treg cell dysfunction. An adoptive transfer model of Sjögren syndrome was developed by transferring cells from the lacrimal gland-draining cervical lymph nodes of NOD mice to lymphocyte-deficient NOD-SCID mice. Transfer of bulk cervical lymph node cells modelled the male-specific dacryoadenitis that spontaneously develops in NOD mice. Female to female transfers resulted in dacryoadenitis if the CD4(+) CD25(+) Treg-enriched population was depleted before transfer; however, male to male transfers resulted in comparable dacryoadenitis regardless of the presence or absence of Treg cells within the donor cell population. Hormone manipulation studies suggested that this Treg cell dysfunction was mediated at least in part by androgens. Surprisingly, male Treg cells were capable of preventing the transfer of dacryoadenitis to female recipients. These data suggest that male-specific factors promote reversible dysfunction of lacrimal gland-protective Treg cells and, to our knowledge, form the first evidence for reversible organ-protective Treg cell dysfunction in organ-specific autoimmunity.

© 2015 John Wiley & Sons Ltd.

PMCID: PMC4427388 [Available on 2016-06-01]
  PMID: 25581706 [PubMed - indexed for MEDLINE]
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20. Clin Plast Surg. 2015 Jan;42(1):79-86. doi: 10.1016/j.cps.2014.08.005. Epub 2014 Oct 11.

Author information: 

  • 1Oculo-Facial Plastic Surgery, London, UK; Centre for London Facial Cosmetic & Plastic Surgery, London, UK.
  • 2Prasad Cosmetic Surgery, New York, NY, USA; Division of Oculofacial Plastic & Reconstructive Surgery, Winthrop University Hospital, State University of New York College of Medicine, NY, USA. Electronic address: Amiya1Prasad@hotmail.com.

 

Abstract

Support of the lower eyelid with canthal suspension is a useful tool in the prevention of complications of lower blepharoplasty with particular relevance to eyelids with increased lower lid laxity, relatively prominent globes, and negative vector configuration of the eyelid-cheek junction. Caution is required in surgical management of this highly delicate anatomic area, as relatively small adjustments can result in relatively large changes that can alter the shape and appearance of the lower eyelids. Management options include canthopexy, orbicularis sling, and modified canthoplasty. The most conservative surgical management option is canthopexy, which supports the lower eyelid over either the short or long term. The use of the orbicularis sling technique avoids surgery around the relatively complex lateral canthus, but may not be suitable for cases without a need for a skin incision or a history of dry eye. Canthoplasty is generally reserved for more marked laxity, which is less common in the group of patients seeking aesthetic blepharoplasty.

Copyright © 2015 Elsevier Inc. All rights reserved.

  PMID: 25440744 [PubMed - indexed for MEDLINE]
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21. Clin Plast Surg. 2015 Jan;42(1):63-71. doi: 10.1016/j.cps.2014.08.008.

Author information: 

  • 1Ophthalmology, Montefiore Medical Center, Albert Einstein College of Medicine, 135 East 71st Street, New York, NY 10021, USA. Electronic address: rschwarcz@gmail.com.
  • 2Private Practice, New York, NY, USA.

 

Abstract

Lower eyelid blepharoplasty and midface lifting share a complex anatomy, which should be mastered before attempting these types of surgeries. In recent years, there have been significant contributions to rejuvenating this area. A thorough understanding of the rejuvenative approaches and their outcomes is imperative. Thus, the problem must be preoperatively evaluated to offer the appropriate technique and minimize complications.

Published by Elsevier Inc.

  PMID: 25440742 [PubMed - indexed for MEDLINE]
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22. Immunol Invest. 2014;43(8):888-901. doi: 10.3109/08820139.2014.910024.

Author information: 

  • 1Department of Microbiology and Immunology; Department of Ophthalmology, VA Western New York Healthcare System , Buffalo, New York , USA.

 

Abstract

Corneal transplant is the most common solid tissue transplant in humans. Advances in microsurgical techniques, eye banking and the use of corticosteroids have improved the success of corneal transplants. Over 65,000 corneal transplants are being performed worldwide annually. Most of these transplants are performed in developed countries. Cornea is considered an immune privileged site. Despite this, immune mediated graft rejection is the most single cause of cornea graft failure and is one of the major postoperative complications. Incidences from as low as 2% to as high as 50% have been reported depending upon the degree of vascularization. Rejection involves donor tissue recognition and various factors may influence this rejection. Major factors include the antigenic load of the donor tissue; other factors include death to enucleation time, methods and temperature of preserving the tissue. Host factors that may impact the graft include ocular surface diseases such as dry eye, chemical burns and autoimmune diseases such as mucous membrane pemphigoid. Following infection, surgery or trauma, cells of the innate immune system invade the cornea as a result of up-regulation of cytokines, cellular adhesion molecules and growth and angiogenic factors. These factors results in neoangiogenesis and lymphoangiogenesis, leading to immune activation and graft rejection. The various immunological mechanisms that may play a role in the corneal transplant are discussed. 

  PMID: 25296240 [PubMed - indexed for MEDLINE]
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23. J Coll Physicians Surg Pak. 2014 Jun;24(6):441-3. doi: 06.2014/JCPSP.441443.

Author information: 

  • 1Department of Medicine, University Malaya Medical Centre, 50603, Kuala Lumpur, Malaysia.

 

Abstract

Pulmonary hypertension is frequently associated with atrial septal defect and various connective tissue disorders. This case describes a 74-year-old woman who presented with symptoms of heart failure and concomitant involvement of salivary glands and keratoconjunctivitis. An echocardiogram demonstrated ostium secundum atrial septal defect with left to right shunt and severe pulmonary hypertension. Laboratory investigations confirmed the diagnosis of Sjögren's syndrome (SS) with positive anti-nuclear factor and centromere SS-A/Ro pattern. Anti-Ro (SS-A) was found positive. Atrial septal defect was closed through transcatheter route with significant improvement in clinical outcome. This case report suggests a possible association of atrial septal defect with primary Sjögren's syndrome in an adult patient.

  PMID: 24953923 [PubMed - indexed for MEDLINE]
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24. J Craniofac Surg. 2014 May;25(3):898-901. doi: 10.1097/SCS.0000000000000559.

Author information: 

  • 1From the Department of Ophthalmology, College of Medicine, Chung-Ang University Hospital, Seoul, Republic of Korea.

 

Abstract
OBJECTIVE: 

The aim of this study was to investigate the clinical outcomes of conjunctiva-Müller muscle resection (CMMR) in patients with mild to moderate ptosis, the factors related to successful procedures, and the influence of CMMR on dry eye symptoms and signs.

METHODS: 

In a tertiary university hospital, the medical records of 30 patients who had CMMR were retrospectively reviewed, including the detailed preoperative and postoperative eyelid measurements, surgical outcomes, and dry eye evaluations. Inclusion criteria included older than 18 years, acquired ptosis, and no previous eyelid surgery or trauma.

RESULTS: 

The surgery had a success rate of 86.7%. In the patients who responded to phenylephrine application with a marginal reflex distance 1 (MRD1) increase of more than 2 mm, the postoperative MRD1 correction was 2.41 ± 0.84 mm, whereas the postoperative MRD1 correction was 1.19 ± 0.78 mm in the group with responses of less than 2 mm. The postoperative MRD1 correction was 1.21 ± 0.80 mm in the group with a negative response. Seven patients complained of dry eye symptoms and showed a transiently significant aggravation in the Schirmer test and ocular surface disease index score after the procedure, which normalized within 2 months postoperatively.

CONCLUSIONS: 

Responsiveness to phenylephrine is directly correlated with the postoperative results. Nevertheless, even in the patients with negative phenylephrine response, some degree of eyelid elevation can be expected. Damage to goblet cells after the procedure may result in defective tear production, leading to transient aggravation of dry eye symptoms.

  PMID: 24670280 [PubMed - indexed for MEDLINE]
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