Abstract: Flaps & dry eye

Nothing particularly new here and I sure wish they'd make studies like this more useful by evaluating a longer interval than one month postop. Also would be helpful to know how they evaluated symptoms (why is it that the refractive surgery studies seem to be among the least likely to specify this in the methods in the abstract?). But I did think it was interesting that while intralase flaps seemed to create quite a bit less dry eye, amongst the keratome folks the thickness of the flap did not appear to matter (except, of course, for all the reasons other than dry eye why flap thickness matters).

Dry eye associated with laser in situ keratomileusis: Mechanical microkeratome versus femtosecond laser.
J Cataract Refract Surg. 2009 Oct;35(10):1756-60.
Salomão MQ, Ambrósio R Jr, Wilson SE.
Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.

PURPOSE: To compare the incidence of laser in situ keratomileusis (LASIK)-associated dry eye and the need for postoperative cyclosporine A treatment after flap creation with a femtosecond laser and a mechanical microkeratome.

SETTING: Cole Eye Institute, Cleveland, Ohio, USA.

METHODS: Eyes were randomized to flap creation with an IntraLase femtosecond laser (30 or 60 kHz) or a Hansatome microkeratome. No patient had signs, symptoms, or treatment of dry eye preoperatively. Flap thickness was determined by intraoperative ultrasonic pachymetry. Slitlamp assessments of the cornea and need for postoperative dry-eye treatment were evaluated preoperatively and 1 month postoperatively.

RESULTS: The flap was created with the femtosecond laser in 113 eyes and with the microkeratome in 70 eyes. The difference in mean central flap thickness between the femtosecond group (111 mum +/- 14 [SD]) and the microkeratome group (131 +/- 25 mum) was statistically significant (P<.001). The incidence of LASIK-associated dry eye was statistically significantly higher in the microkeratome group (46%) than in the femtosecond group (8%) (P<.0001), as was the need for postoperative cyclosporine A treatment (24% and 7%, respectively) (P<.01). In the microkeratome group, there was no correlation between thick flaps and a higher incidence of LASIK-induced dry eye.

CONCLUSIONS: Eyes with femtosecond flaps had a lower incidence of LASIK-associated dry eye and required less treatment for the disorder. In addition to neurotrophic effects from corneal nerve cutting, other factors may be important because no correlation was found between flap thickness (or ablation depth) and the incidence of LASIK-induced dry eye.

Abstract: New treatment for corneal neovascularization?

Mouse-stage and tested under pretty extreme conditions but interesting results and some of you with persistent issues of this type might want to be following developments on this one.

Inhibitory effects of polysaccharide extract from Spirulina platensis on corneal neovascularization.
Mol Vis. 2009 Sep 24;15:1951-61.
Yang L, Wang Y, Zhou Q, Chen P, Wang Y, Wang Y, Liu T, Xie L.
State Key Laboratory Cultivation Base, Shandong Provincial Key Lab of Ophthalmology, Shandong Eye Institute, Qingdao, China.

PURPOSE: To assess the effects of polysaccharide extract from Spirulina platensis (PSP) on corneal neovascularization (CNV) in vivo and in vitro.

METHODS: PSP was extracted from dry powder of Spirulina platensis. Its anti-angiogenic activity was evaluated in the mouse corneal alkali burn model after topical administration of PSP four times daily for up to seven days. Corneal samples were processed for histochemical, immunohistochemical, and gene expression analyses. The effects of PSP on proliferation, migration, tube formation, and serine threonine kinase (AKT) and extracellular regulated kinase1/2 (ERK1/2) signaling levels in vascular endothelial cells were determined using 3-(4,5)-dimethylthiahiazo (-z-y1)-3, 5-di-phenytetrazoliumromide (MTT) and carboxyfluorescein succinimidyl ester (CFSE) labeling assays, wound healing assay, Matrigel tube formation assay, and western blot.

RESULTS: Topical application of PSP significantly inhibited CNV caused by alkali burn. Corneas treated with PSP showed reduced levels of platelet endothelial cell adhesion molecule (CD31) and stromal cell-derived factor 1 (SDF1) proteins, reduced levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP2), matrix metalloproteinase-9 (MMP9), SDF1, and tumor necrosis factor-alpha (TNF-alpha) mRNAs, and an increased level of pigment epithelium-derived factor (PEDF) mRNA. These are parameters that have all been related to CNV and/or inflammation. In human vascular endothelial cells, PSP significantly inhibited proliferation, migration, and tube formation in a dose-dependent manner. Furthermore, PSP also decreased the levels of activated AKT and ERK 1/2.

CONCLUSIONS: These data suggest that polysaccharide extract from Spirulina platensis is a potent inhibitor of CNV and that it may be of benefit in the therapy of corneal diseases involving neovascularization and inflammation.

Drug news: Macusight's Perceiva (Sirolimus)

New to me. This drug is in four different Phase II studies looking at it for use in three different conditions, one of which is dry eye.

Here's a link to the clinical trial information (this is completely enrolled but in case you want to read about it)

And here's a news article from Sept 30th:

MacuSight(R) Provides Clinical Development Update for Perceiva(TM)

UNION CITY, Calif., Sept. 30 /PRNewswire/ -- MacuSight, a developer of innovative therapeutics for the treatment of severe ocular diseases and conditions, today provided a clinical development update for Perceiva, the company's proprietary ocular sirolimus product. The company has completed patient enrollment in four ongoing Phase 2 clinical trials of Perceiva and plans to announce data from these studies in the first half of 2010. All four studies are being conducted at investigational sites in the United States. These studies, which are evaluating Perceiva as a treatment for diabetic macular edema (DME), neovascular (wet) age-related macular degeneration (wet AMD) and dry eye syndrome, are part of MacuSight's broad Phase 2 Perceiva clinical program which spans five major ocular disease indications....

MacuSight's fourth Phase 2 trial, in which the company is using Perceiva to evaluate the potential role for sirolimus in the treatment of dry eye syndrome, has successfully enrolled 143 patients at four investigational sites. For this trial, MacuSight worked with Ora, Inc., a leading global clinical research organization located in Andover, MA. As part of this randomized, dose-ranging, placebo-controlled study, patients receive a single subconjunctival injection of Perceiva at baseline. Investigators will evaluate signs and symptoms of dry eye over a period of 28 days following a single injection.

Abstract: Corneal nerve regeneration

Zowie.

Seriously.

LASIK dry eye patients, don't get too excited yet, it's only at the bunny-trial stage but I'll definitely be following this one closely as it appears very promising. And looky, we are even mentioned in the conclusions.

Emphases mine.

PEDF plus DHA Induces Neuroprotectin D1 Synthesis and Corneal Nerve Regeneration after Experimental Surgery.
Invest Ophthalmol Vis Sci. 2009 Sep 24. [Epub ahead of print]
Cortina M, He J, Li N, Bazan N, Bazan H.
Ophthalmology, LSU, Chicago, United States.

Purpose: Define whether pigment epithelial-derive growth factor (PEDF) together with docosahexaenoic acid (DHA) enhances synthesis of neuroprotectin D1 (NPD1) and regeneration of corneal nerves damaged post-surgery.

Methods: A corneal stromal dissection was performed in the left eye of adult New Zealand rabbits treated with DHA+PEDF, PEDF, or DHA for 6 weeks. In vivo confocal images of the corneas were obtained at 2, 4 and 8 weeks and nerve areas quantified. At 8 weeks post-treatment, corneas were stained with tubulin betaIII antibody, and epithelial nerve area, sub-basal and stromal nerve plexus were quantified. At 1 and 2 weeks post-treatment, lipids were extracted from corneas and synthesis of NPD1 was analyzed by mass spectrometry. Epithelial cell density was quantified by confocal microscopy 8 weeks post-surgery.

Results: In vivo confocal images at 2 and 4 weeks post-surgery showed a 2.5-fold increase in corneal nerve area in PEDF+DHA-treated animals, compared with control animals. Increased nerve surface area in epithelia, sub-epithelial and stroma was observed in rabbits treated for 8 weeks with PEDF+DHA. PEDF or DHA alone did not produce a significant increase. NPD1 synthesis peaked at 1 week and was four times higher in PEDF+DHA-treated group, compared with controls.

Conclusions: PEDF+DHA promotes regeneration of corneal nerves. Neurotrophin-mediated NPD1 synthesis is suggested to precede nerve regeneration by demonstration of its accumulation upon addition of DHA and PEDF at earlier time points. Therefore, this signaling mechanism upregulates cornea nerve regeneration and may be targeted in neurotrophic keratitis, dry eye after refractive surgery, and other corneal diseases.

Abstract: Bleph & doxy

A common question for those trying Rx drug is, how long do I keep using it before I should expect to see improvement (if it IS going to help)? This one may answer that as regards doxycycline use for some patients.

In vivo characterization of doxycycline effects on tear metalloproteinases in patients with chronic blepharitis.
Eur J Ophthalmol. 2009 Sep-Oct;19(5):708-16.
Iovieno A, Lambiase A, Micera A, Stampachiacchiere B, Sgrulletta R, Bonini S.
Interdisciplinary Center for Biomedical Research (CIR), Laboratory of Ophthalmology, University of Roma Campus Bio-Medico, Roma - Italy.

PURPOSE: Matrix metalloproteinases (MMPs) have a role in the pathogenesis of rosacea-associated chronic blepharitis. Doxycycline is largely used as a treatment for recalcitrant chronic blepharitis. It has been shown in vitro that doxycycline inhibits MMPs activation. The aim of this study was to investigate in vivo the effect of doxycycline in modulating MMPs in patients with chronic idiopathic blepharitis.

METHODS: Eight patients (6 male, 2 female; mean age 45.7+/-17.5 years) were included in the study. Doxycycline (100 mg) was administered orally, twice a day, for 2 weeks and once a day for an additional 2 weeks. Clinical signs and symptoms were evaluated and scored (0-3) at baseline and after 4 weeks. Total sign (TSS) and total symptom (TSyS) scores were calculated. Tear samples and conjunctival impression cytologies were collected at baseline and after 4 weeks of treatment to evaluate MMP-9 and TIMP-1 expression and activity.

RESULTS: An improvement in TSS (4.5+/-1.1 vs 2.7+/-1.5) and TSyS (6.6+/-1.3 vs. 3.1+/-1.9) was observed after 4 weeks, with significant amelioration of hyperemia, marginal blepharitis, and superficial punctuate keratopathy. Zymography revealed a decrease of MMP-9 activity after 4 weeks. MMP-9 mRNA and protein levels did not change, while an upregulation of TIMP-1 expression was observed.

CONCLUSIONS: This study suggests that 4-week treatment with doxycycline significantly improved symptoms and signs in patients with chronic blepharitis in association with a decrease in MMP-9 activity. Upregulation of TIMP-1 is proposed as a possible mechanism of MMP-9 inactivation.

Abstract: Resistance to antibiotics.

Interesting one here about increase in resistance to antibiotics, implications in ocular infection (including blepharitis) and what can/should be done about it.

Impact of antibiotic resistance in the management of ocular infections: the role of current and future antibiotics.

Clin Ophthalmol. 2009;3:507-21. Epub 2009 Sep 24.
Bertino JS.
College of Physicians and Surgeons, Columbia University, New York, NY, USA;

PURPOSE: This article reviews the effects of the increase in bacterial resistance on the treatment of ocular infections.

DESIGN: Interpretive assessment.

METHODS: Literature review and interpretation.

RESULTS: Ocular bacterial infections include conjunctivitis, keratitis, endophthalmitis, blepharitis, orbital cellulitis, and dacryocystitis. Treatment for most ocular bacterial infections is primarily empiric with broad-spectrum antibiotics, which are effective against the most common bacteria associated with these ocular infections. However, the widespread use of broad-spectrum systemic antibiotics has resulted in a global increase in resistance among both Gram-positive and Gram-negative bacteria to a number of the older antibiotics as well as some of the newer fluoroquinolones used to treat ophthalmic infections. Strategies for the prevention of the increase in ocular pathogen resistance should be developed and implemented. In addition, new antimicrobial agents with optimized pharmacokinetic and pharmacodynamic properties that have low toxicity, high efficacy, and reduced potential for the development of resistance are needed.

CONCLUSIONS: New antimicrobial agents that treat ocular infections effectively and have a low potential for the development of resistance could be a part of strategies to prevent the global increase in ocular pathogen resistance.

Abstract: Antiinflammatory therapy for dry eye

Nothing new here - brief summary of a literature review. Emphasis (below) mine.

Advancements in anti-inflammatory therapy for dry eye syndrome.
Optometry. 2009 Oct;80(10):555-66.
McCabe E, Narayanan S.
Pennsylvania College of Optometry at Salus University, Elkins Park, Pennsylvania.

PURPOSE: The goal of this literature review is to discuss recent discoveries in the pathophysiology of dry eye and the subsequent evolution of diagnostic and management techniques. The mechanisms of various anti-inflammatory treatments are reviewed, and the efficacy of common pharmacologic agents is assessed. Anti-inflammatory therapy is evaluated in terms of its primary indications, target population, and utility within a clinical setting.

METHODS: The Medline PubMed database and the World Wide Web were searched for current information regarding dry eye prevalence, pathogenesis, diagnosis, and management. After an analysis of the literature, major concepts were integrated to generate an updated portrayal of the status of dry eye syndrome.

RESULTS: Inflammation appears to play a key role in perpetuating and sustaining dry eye. Discoveries of inflammatory markers found within the corneal and conjunctival epithelium of dry eye patients have triggered recent advancements in therapy. Pharmacologic anti-inflammatory therapy for dry eye includes 2 major categories: corticosteroids and immunomodulatory agents. Fatty acid and androgen supplementation and oral antibiotics have also shown promise in dry eye therapy because of their anti-inflammatory effects.

CONCLUSIONS: Anti-inflammatory pharmacologic agents have shown great success in patients with moderate to severe dry eye when compared with alternative treatment modalities. A deeper understanding of the link between inflammation and dry eye validates the utilization of anti-inflammatory therapy in everyday optometric practice.

Abstract: Systane, Optive, and visual acuity

For your reading ease...

PEG/PG = Systane

CMC/glycerin = Optive

(at least I'm assuming so as those are the only products I know with the indicated active ingredients)


The effects of lubricant eye drops on visual function as measured by the Inter-blink interval Visual Acuity Decay test.
Clin Ophthalmol. 2009;3:501-6. Epub 2009 Sep 24.
Torkildsen G.
Andover Eye Associates, Andover, MA, USA.

OBJECTIVE: The purpose of the current study was to evaluate the effects of two marketed ocular lubricants on the visual decay in dry eye patients using the Inter-blink interval Visual Acuity Decay (IVAD) test.

METHODS: This controlled, randomized, double-masked crossover study compared the effects of a polyethylene glycol/propylene glycol-based (PEG/PG) tear and a carboxymethylcellulose sodium (CMC)/glycerin tear on the visual acuity decay between blinks of dry eye patients. At visit 1 (Day 0), baseline IVAD measurements were recorded prior to instillation of a single drop of randomized study medication. IVAD testing was repeated at 15-, 45-, and 90-minutes post-instillation. Reading rate and functional blink rate were also evaluated. At the second visit (Day 7 +/- 3), study procedures were repeated using crossover treatment.

RESULTS: Forty-eight (48) subjects with dry eye (61.1 +/- 14.8 years old, 79.2% female, 95.8% white) completed the study. Treatment with the PEG/PG-based tear demonstrated statistically significantly longer time to one-line loss of best-corrected visual acuity (BCVA) as determined by the IVAD test at 90 minutes post-instillation compared to the CMC/glycerin tear (P = 0.0365). Measurements of median time at BCVA, reading rate, and functional blink rate were similar for both treatments. Both formulations were well tolerated in the population studied.

CONCLUSIONS: Treatment with the PEG/PG-based tear demonstrated statistically significant improved maintenance of visual acuity between blinks at 90 minutes post-instillation compared to the CMC/glycerin tear. This is the first study to demonstrate the ability of an artificial tear to extend visual acuity maintenance between blinks, as measured by the IVAD test.

Drug update: Prolacria chances declining?

Wedbush Morgan Securities has downgraded Inspire in part because of analyst concerns over whether Prolacria is producing good enough clinical data to ever get approved.

UPDATE 1-RESEARCH ALERT-Wedbush cuts Inspire Pharma to neutral
9/23/2009, Forbes

...'That key early-stage data won't be released until medical conferences in 2010, suggest to us that management will take their time to evaluate the next steps and may even choose a back-up compound to test in early stage again,' analyst Liana Moussatos said.

Moussatos, who maintained her $15 fair value target, sees upcoming late-stage data on the company's experimental dry-eye treatment Prolacria as a 'high-risk catalyst' as the drug has had mixed data in the past.

'We give Prolacria a 30 percent or less likelihood of success,' she said in a note to clients.

Abstract: Improved tear meniscus measurements via OCT

Reproducibility of tear meniscus measurement by fourier-domain optical coherence tomography: a pilot study.
Ophthalmic Surg Lasers Imaging. 2009 Sep-Oct;40(5):442-7. doi: 10.3928/15428877-20090901-01.
Zhou S, Li Y, Lu AT, Liu P, Tang M, Yiu SC, Huang D.

BACKGROUND AND OBJECTIVE:To study the reproducibility of tear meniscus measurement with high-speed high-resolution Fourier-domain optical coherence tomography (FD-OCT).

PATIENTS AND METHODS:Twenty normal participants were enrolled in this prospective study. The lower tear meniscus in the right eye of each subject was imaged by vertical scans centered on the inferior cornea and the lower eyelid using an FD-OCT system (RTVue; Optovue, Inc., Fremont, CA) with a corneal adaptor. The system performs 26,000 axial scans per second and has a 5-micron axial resolution. Each subject was examined at two visits 30 to 60 days apart. Each eye was scanned twice on each visit. The scans were taken 2 seconds after a blink. The lower meniscus height, depth, and cornea-meniscus angle were measured with a computer caliper. The cross-sectional area was calculated using a two-triangle approximation.

RESULTS:The between-visits coefficient of variation was 17.5%, 18.0%, 35.5%, and 12.2% for meniscus height, depth, area, and angle, respectively. The intraclass correlations for these parameters were 0.605, 0.558, 0.567, and 0.367, respectively.

CONCLUSION:FD-OCT measures lower tear meniscus dimensions and area with higher between-visits reproducibility than previous OCT instruments. FD-OCT may be a useful way to measure dry eye severity and treatment effectiveness.

Drug News: LX214 successful Phase I completion

Sept 23, 2009 - Business Wire
Lux Biosciences Reports Phase 1 Safety Results and Open Label Efficacy Results for LX214, a Potential Best-in-Class Treatment for Dry Eye

JERSEY CITY, N.J.--(BUSINESS WIRE)--Lux Biosciences, Inc. a privately held biotechnology company focused on the treatment of ophthalmic diseases, today announced results from a Phase 1 human safety and an open-label pilot efficacy study of the company’s potential best-in-class therapy for dry eye, LX214 (topical mixed nanomicellar formulation of voclosporin). Randomized, double-masked, placebo-controlled data from 30 healthy volunteers showed LX214 to be well tolerated at the two doses (0.02% and 0.2%) studied, with safety and tolerability measurements (pain, burning, reddening, photophobia, foreign body sensation and others) indistinguishable from placebo.

An additional cohort of five patients with severe dry eye syndrome was treated with LX214 in both eyes twice a day for 14 days at the target 0.2% concentration. Data from these patients confirmed that systemic exposure to voclosporin was very low and below the threshold level where measurement of voclosporin blood concentrations would be required in future studies. Signs and symptoms of disease were also assessed in this cohort of patients. Despite the small sample size and short duration of treatment, clinically meaningful improvements were noted in both signs (tear production) and symptoms (OSDI index) at both 7 and 14 days, a trend that bodes well for longer term, controlled studies to follow.

“The benign safety and tolerability results in humans demonstrated in both these trials confirm the positive profile exhibited by LX214 in preclinical studies, which showed this drug candidate to establish therapeutic levels in relevant ocular tissues and to be non-irritating when applied topically to the eye,” said Eddy Anglade, M.D., Lux Biosciences’ Chief Medical Officer. “Moreover, even though the 14 day results in severe dry eye patients were based on a small, uncontrolled sample, they presented quite encouraging indicators of efficacy.”

LX214, developed in cooperation with Ashim Mitra, Ph.D., University of Missouri Curator’s Professor of Pharmacy and Director of Translational Research at UMKC School of Medicine School of Pharmacy, University of Missouri-Kansas City, is a proprietary formulation of Lux Biosciences’ next generation calcineurin inhibitor, voclosporin. Utilizing voclosporin and Lux’s proprietary mixed nanomicellar formulation technology, LX214 establishes high levels of drug for 24 hours in relevant ocular tissues following a single administration, including the lacrimal gland and submandibular lymph nodes, suggesting that LX214 may be efficacious and suitable for once daily dosing.

Abstract: Aqueous deficient vs. evaporative dry eye (maybe, maybe not)

This study illustrates quite emphatically (if I understand it correctly) how these terms aqueous deficient dry eye and evaporative dry eye are too frequently used to distinguish between two conditions that really may NOT have any nice simple clear diagnostic distinctions.

Looks like we're graduating from "The tear film has three layers... blah blah blah" and going right back to "Golly the tear film and its diseases sure are complex."

The first thing that jumped out at me when I skimmed this abstract was the absence of any difference in meibomian gland dropout between the two types. What does it mean? That people with ADDE eventually lose their MGs so we're really not looking at ADDE vs EDE but rather ADDE+EDE vs EDE standalone? Or that the criteria for the initial classification was just plain wrong? Or that meibum doesn't really play all that big a role in retarding evaporation? Or, or, or... the possibilities are endless. I found only questions, not answers here.

Tear Physiology of Aqueous Deficiency and Evaporative Dry Eye.
Optom Vis Sci. 2009 Sep 17. [Epub ahead of print]
Khanal S, Tomlinson A, Diaper CJ.
*PhD daggerPhD, DSc, FAAO double daggerFRCS, FRC(Opth) School of Natural Sciences, University of Western Sydney, New South Wales, Australia (SK), Department of Vision Sciences, Glasgow Caledonian University, Glasgow, Scotland, United Kingdom (AT), and Southern General Hospital, South Glasgow University Hospitals NHS Trust, Glasgow, Scotland, United Kingdom (CJMD).

PURPOSE.: To determine the differences in tear physiology between aqueous deficiency dry eye (ADDE) and evaporative dry eye (EDE), and evaluate their utility in diagnosis.

METHODS.: Fifty-six dry eye patients were classified into 30 ADDE and 26 EDE according to the recently published Dry Eye Workshop criteria. A range of tear physiology measures comprising of tear evaporation, turnover rate (TTR), distribution, volume and osmolarity, and meibomian gland dropout were measured in these patients. The effectiveness of the tests, singly and in combinations, in differentiating between the dry eye subtypes was evaluated by retrospective allocation into groups and by Receiver Operative Characteristics (ROC) curve analysis.

RESULTS.: Statistically significant differences were seen for TTR and tear evaporation (with lower values for ADDE) between ADDE and EDE, but no significant differences were seen for tear osmolarity, volume, distribution, and meibomian gland dropout scores. Differentiation of ADDE and EDE by a cut-off value of 11%/min for TTR was found to have a sensitivity of 86%, specificity of 75%, positive predictive value 89%, negative predictive value 69%, and overall accuracy 83%. The area under the curve on the ROC curve was 0.83. For tear evaporation, a cut-off of 60 g/mh was found to have a sensitivity of 77%, specificity of 55%, positive predictive value 38%, negative predictive value 80%, and overall accuracy 58% in subtype differentiation. The area under the curve was 0.59 on the ROC curve. The distribution curve of the evaporation rates for ADDE and EDE, showed an overlap coefficient of 0.76 indicating that tear evaporation is within a similar range in these two dry eye subtypes.

CONCLUSIONS.: Tear turnover is significantly lower in ADDE than EDE, but there is considerable overlap of tear evaporation between the two dry eye subtypes. Tear osmolarity and turn over tests can be conducted sequentially to effectively diagnose dry eye and its subtypes.

Abstract: Protein biomarkers in contact lens dry eye

Very interesting.

I would like to better understand what they mean by "contact lens-related dry eye". It doesn't seem as though they're simply distinguishing between CTL wearers with and without dry eye, but at a practical level how could they distinguish those with ctl-related dry eye from dry eye independent of ctls?

Mass Spectrometry-Based Proteomic Analyses in Contact Lens-Related Dry Eye.
Cornea. 2009 Sep 16. [Epub ahead of print]
Nichols JJ, Green-Church KB.
From the Campus Chemical Instrumentation Center Mass Spectrometry and Proteomics Facility, College of Optometry, Ohio State University, Columbus, OH.

PURPOSE:: To identify potential protein biomarkers associated with dry eye in contact lens wearers.

METHODS:: Upon enrollment, current galyfilcon A contact lens wearers completed a previously described questionnaire used to classify dry eye status. Approximately 5 muL of aqueous tears were carefully sampled from the inferior-lateral tear prism of each eye using glass microcapillaries. A variety of proteomic approaches were used to compare samples including quantification by Bradford analyses, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) (alone in varying percentages and with MultiPlex analyses for posttranslational modifications), nano-liquid chromatography tandem mass spectometry (nano-LC-MS/MS), and differential gel electrophoresis.

RESULTS:: Twenty-one subjects were enrolled in the study (age 31.3 +/- 11.6 years). Eleven of the subjects were classified with contact lens-related dry eye, while the remaining 10 were normal contact lens wearers. Across all proteomic approaches, several proteins (including several glycoproteins) were identified as potential biomarkers associated with dry eye disease state. In summary across the approaches used, extracellular proteins identified to be altered included beta-2 microglobulin, proline rich 4, lacritin, and secretoglobin 1D1, which were found to be decreased in the dry eye state. Secretoglobin 2A2, serum albumin, glycoprotein 340, and prolactin-inducible protein were all found to be increased in the dry eye state.

CONCLUSIONS:: Dry eye in contact lens wearers is related to several changes in the tear film protein. While functional studies for these candidate proteins are ongoing, initial insights into the functions of these proteins suggest roles in altered tear secretion, in addition to possible increased susceptibility to infection.

Abstract: High frequency use of Restasis

High-frequency Topical Cyclosporine 0.05% in the Treatment of Severe Dry Eye Refractory to Twice-daily Regimen.
Cornea. 2009 Sep 15. [Epub ahead of print]
Dastjerdi MH, Hamrah P, Dana R.
From the Cornea and Refractive Surgery Service, Massachusetts Eye & Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA.

PURPOSE:: The purpose of this study was to report the efficacy of topical cyclosporine 0.05% at a frequency of 3 to 4 times daily in severe dry eye disease.

METHODS:: We retrospectively identified a cohort of patients with severe dry eye disease who had shown inadequate response to at least a 4-month course of treatment with twice-daily use of topical cyclosporine 0.05% but who showed significant improvement to more frequent dosing.

RESULTS:: Twenty-two patients, including 13 patients with ocular graft-versus-host disease and 9 patients with primary or secondary Sjögren's syndrome, were included. After a minimum of a 2-month course of treatment with more frequent dosing of cyclosporine 0.05% (3 times a day in 7 patients and 4 times a day in 15 patients), overall dry eye symptoms were improved in 15 (68.2%) patients (9 patients with ocular graft-versus-host disease and 6 patients with Sjögren's syndrome). Mean corneal fluorescein staining scores (National Eye Institute scale of 0-15) improved (decreased) from the baseline (precyclosporine use) by -3.5 (range, 0 to -7) in patients with ocular graft-versus-host disease (P < / = 0.0008) and -2.8 (range, 0 to -5) in patients with Sjögren's syndrome (P < / = 0.001). After treatment with high-frequency use of cyclosporine 0.05%, the global physician assessment of dry eye status was favorable (improved) in 16 (72.7%) patients. Three (13.6%) patients reported new-onset symptoms of burning or irritation with the use of high-frequency dosing of topical cyclosporine. No other associated adverse effect was reported.

CONCLUSION:: These data suggest that patients with severe dry eye may require more frequent dosing of topical cyclosporine 0.05% than twice daily.

Abstract: VisMed and Tears Again liposomal spray

Interesting study comparing a sodium hyaluronate drop with a popular eyelid spray, both for evaporative dry eye.

Klin Monatsbl Augenheilkd. 2009 Sep 15. [Epub ahead of print]
Comparative Investigation of Treatments for Evaporative Dry Eye.
Khaireddin R, Schmidt KG.
Klinik und Poliklinik für Augenheilkunde, Universitätsklinik Hamburg Eppendorf.

BACKGROUND: Evaporative dry eye is the most common form of tear film dysfunction. The present trial aims to evaluate the efficacy of two established treatment options with different modes of action by comparison.

PATIENTS/MATERIAL AND METHODS: 216 patients suffering from evaporative dry eye were included in this prospective, randomised two-centre trial. Divided into two treatment groups, patients either received treatment with hyaluronate artificial tears (Vismed light) or a phospholipid-liposome eye spray (Tears Again), each for three months. Tests (lid-parallel conjunctival folds [LIPCOF], non-invasive break-up time [NIBUT], Schirmer's test, inspection of lids and subjective assessment) were performed before as well as 4 and 12 weeks after initiation of this study.

RESULTS: In the patients of the eye spray group there was a significantly greater reduction of the LIPCOF grade (p < 0.02) and the grade of inflammation of the lid margin (p < 0.002). With respect to the tear film break-up time (NIBUT) there was a significant difference between the results of both groups (p < 0.003). The improvement of the break-up time in patients of the eye spray group turned out to be more than twice as high as that in the artificial tears group.

CONCLUSIONS: Both therapies improved evaporative dry eye, but patients on phospholipid-liposomal eye spray demonstrated greater clinical benefit from their therapy, particularly regarding the degree of inflammation of the lid margins as well as the grade of LIPCOF. When compared to hyaluronate artificial tears, NIBUT more than doubled in the phospholipid-liposome eye spray group. Clinical severity of dry eye is more pronounced when evaporative dry eye and aqueous tear deficiency coincide. A combination of the phospholipid-liposome eye spray and artificial tears appears to represent a considerable advancement in tear replacement therapy for severe cases of dry eye.