Thursday, September 2, 2010

Abstract: DES and neurotrophic keratitis in children

[Dry eye syndrome and neurotrophic keratitis in childhood : Causes and therapy.]
Ophthalmologe. 2010 Aug 28. [Epub ahead of print]
[Article in German]
Dietrich T, Renner AB, Helbig H, Oberacher-Velten IM.
Klinik und Poliklinik für Augenheilkunde, Universitätsklinikum Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Deutschland,

PURPOSE: The purpose of this review is to enhance the physician's awareness of dry eye syndrome and neurotrophic keratitis in children, to describe the most frequently associated conditions and to discuss the diagnostic and therapeutic options available.

METHODS: A literature review of the pathogenesis of dry eye syndrome and neurotrophic keratitis in children was carried out, clinical cases from our pediatric ophthalmology office are presented as well as therapeutic strategies.

RESULTS: Diseases of the cornea and ocular surface such as dry eye syndrome, neurotrophic keratitis and corneal ulcers are infrequent in children compared to adults. However, they do occur and should be diagnosed and treated as soon as possible in order to prevent long-term complications and amblyopia.

CONCLUSIONS: Inflammatory diseases of the ocular surface can be easily overlooked in children due to the often unknown spectrum of differential diagnoses and the frequently reduced cooperation during examination of young children. Correct and early diagnosis is essential for prevention of long-term complications, e.g. corneal ulceration and scarring.

Abstract: Systane

For heaven's sakes, there must be as many studies of Systane by now as there are of Restasis.

Novel hydroxypropyl-guar gellable lubricant eye drops for treatment of dry eye.
Adv Ther. 2010 Aug 26. [Epub ahead of print]
Springs CL.
Department of Ophthalmology, Indiana University School of Medicine, 702 Rotary Circle, Indianapolis, IN, 46202-5175, USA,

OBJECTIVE|: The objective of this review is to evaluate the safety and efficacy of polyethylene glycol 400/propylene glycol/hydroxypropyl-guar (Systane(R) Ultra [PEG/PG with HP-guar], Alcon Laboratories, Inc., Fort Worth, TX, USA) lubricant eye drops in reducing the signs and symptoms of dry-eye disease.

METHODS|: A systematic literature search utilizing MEDLINE was conducted to identify peer-reviewed articles related to dry-eye disease and PEG/PG with HP-guar lubricant eye drops. The search covered the period prior to October 2009. Additionally, a manual search based on citations in the published literature was conducted.

RESULTS|: The PEG/PG with HP-guar artificial tears shows in-vitro viscoelastic properties with pH optimization. The pH of the solution adjusts to the pH of the ocular surface upon instillation, which results in tear film elasticity and viscosity similar to that of subjects without dry-eye disease. The reviewed literature demonstrated that this delivery system showed a reduction in corneal and conjunctival staining in dryeye disease, an improvement in tear film stability, a low coefficient of friction in an in-vitro model, and improved maintenance of best-corrected visual acuity over time.

CONCLUSION|: A few small-sized studies with short-term follow-up demonstrated that PEG/PG with HP-guar is a safe and effective lubricant eye drops for the treatment of dry-eye disease. Larger studies with longer duration are warranted to assess the long-term safety and efficacy of this formulation in patients with dry.eye disease.

Abstract: Demodex mites

Demodex mites: facts and controversies.
Clin Dermatol. 2010 Sep-Oct;28(5):502-4.
Elston DM.
Department of Dermatology, Geisinger Medical Center, Danville, PA 17822-5206, USA.

Because Demodex mites are ubiquitous, their potential as human pathogens has often been ignored. This contribution focuses on the growing body of evidence linking Demodex mites with various skin disorders. Histologically, spongiosis and lymphoid inflammation are regularly seen in follicles containing Demodex mites. In animals, they are well established as a cause of mange, and a human counterpart-demodectic alopecia-appears to exist. There is also a statistical association between Demodex mite density and rosacea, facial itching, and chronic blepharitis. Papulovesicular rosacealike lesions and spiny blepharitis often respond to agents that reduce Demodex numbers. Although these observations are not sufficient to fulfill Koch's postulates, Koch's postulates are also not fulfilled for the association between brown recluse spiders and dermal necrosis or the association between streptococci and guttate psoriasis. The evidence linking Demodex mites to human disease has implications regarding treatment.

Abstract: Thyroid orbitopathy and Restasis

Topical cyclosporine in thyroid orbitopathy-related dry eye: clinical findings, conjunctival epithelial apoptosis, and MMP-9 expression.
Curr Eye Res. 2010 Sep;35(9):771-7.
Gürdal C, Genç I, Saraç O, Gönül I, Takmaz T, Can I.
Ankara Atatürk Training and Research Hospital, 2nd Ophthalmology Department, Ankara, Turkey.

OBJECTIVES: To evaluate the effects of topical cyclosporine A (CsA) 0.05% (Restasis) on the signs and symptoms of dry eye, on apoptosis, and on MMP-9 expression in conjunctiva epithelial cells in thyroid orbitopathy (TO)-related dry eye patients.

METHODS: Prospective, clinical study. Twenty-four eyes of 12 consecutive TO patients with dry eye findings instilled CsA twice daily for 2 months. Ocular surface disease index, Schirmer tear test, tear breakup time (TBUT), conjunctival apoptosis index, and conjunctival MMP-9 expression were evaluated before and after 2 months treatment. Conjunctival biopsies were harvested from all eyes at baseline and after 2 months treatment. Apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling (TUNEL) assay. MMP-9 expression was determined by immunohistochemistry.

RESULTS: After 2 months of topical CsA treatment, the mean OSDI score was significantly decreased from 58.08 +/- 6.28 to 36.41 +/- 11.75 (P = 0.001). At baseline, the mean Schirmer tear test score was 8.92 +/- 5.52 mm. It was increased to 11.25 +/- 4.71 mm after treatment (P > 0.05). The mean TBUT increased significantly from 3.92 +/- 2.18 sec to 9.16 +/- 3.34 sec (P = 0.001). The mean percentage of apoptosis index at baseline was 72.10 +/- 35.82%. This was significantly decreased to 53.29 +/- 34.46% after treatment (P = 0.008). The mean percentage of MMP-9 expression of the conjunctival epithelial cells was significantly decreased from 48.12 +/- 28.58% to 26.66 +/- 25.13% following treatment (P = 0.005).

CONCLUSIONS: Topical CsA treatment appears to improve the signs and symptoms of dry eye and inhibits apoptosis and MMP-9 expression in conjunctival epithelial cells in TO-related dry eye patients after 2 months of treatment.

Newsblurb: Inspire finally calls it quits on Prolacria

Inspire shelves dry-eye drug, shifts focus with Allergan

After a decade of development and disappointment, Inspire Pharmaceuticals finally has put a stop to its efforts to win U.S. Food and Drug Administration approval of a dry eye drug now called Prolacria.
The Durham company on Wednesday unveiled a modified collaboration agreement with longtime partner Allergan (NYSE: AGN) that opens the way for Inspire to close the door on Prolacria and move its focus to pink eye treatment AzaSite and the company’s promising cystic fibrosis program.
Investors hailed the new agreement, pushing up Inspire shares by 3.88 percent, to $4.66, in mid-day trading Wednesday.
Inspire twice saw its dry eye drug fail to outperform a placebo in the last stage of human testing. The company tried changing the drug’s name and adjusted the end point of the phase III clinical trial but ended up with the same results.
After studying the potential of moving forward with Prolacria, Inspire and Allergan were ready to move on. But the complicated nature of their drug development deal – which involves another dry eye treatment, Restasis – left Inspire facing a significant and immediate revenue hit.
Inspire (Nasdaq; ISPH) receives royalties from Allergan on sales of Restasis and received payments from the Irish company for hitting development milestones on Prolacria. The previous terms called for a 30 percent reduction in Inspire’s Restasis royalty rate of 7.5 percent if the company dropped the Prolacria program and didn’t begin contributing to the marketing and promotion of Restasis.
The new terms keep Inspire’s Restasis royalty rate unchanged at 7.5 percent for 2010, before reducing it by 3 percentage points in 2011, a further 0.25 percentage point in 2013, and a final 0.50 percentage point in 2014. The rate will remain at 3.75 percent until 2020, when the contract runs out.
Restasis generated $11.2 million in royalty revenue for Inspire during the second quarter, which ended June 30. That was up from $8.9 million in the year-ago quarter.
For the quarter, Restasis accounted for more than 40 percent of Inspire’s total revenue of $27.3 million and topped AzaSite, which produced revenue of $9.6 million.
“This agreement provides clarity on the revenue stream and respective responsibilities of the parties in our ophthalmic collaboration,” said Adrian Adams, president and CEO of Inspire, which has 240 employees.

Abstract: MGD literature review

Good one for those who have access to the full article....

Meibomian Gland Dysfunction: The Past, The Present, and The Future.
Eye Contact Lens. 2010 Aug 10. [Epub ahead of print]
Foulks GN, Borchman D.
From the Department of Ophthalmology and Visual Sciences (G.N.F.), University of Louisville School of Medicine, Louisville, KY; Louisville Veterans Administration Medical Center (G.N.F.), Louisville, KY; and Department of Surgery (D.B.), University of Louisville, Louisville, KY.

OBJECTIVE: To recount the historic evaluation of meibomian gland dysfunction (MGD) and describe new techniques to monitor disease and therapy.

METHODS: A review of the literature regarding the description of MGD and the role of abnormalities of meibomian gland secretion in health and disease.

RESULTS: Meibomian gland dysfunction is a common clinical condition and is a major cause of evaporative dry eye with associated discomfort, visual disturbance, and contact lens intolerance. Despite the early description of the anatomy and physiology of the meibomian gland, recognition of the importance of the MGD and particularly therapeutic options to treat it has been limited.

CONCLUSIONS: Improved methods of spectroscopic and chemical analysis of the meibomian gland secretion in health and disease are providing a better understanding of the physical and chemical abnormalities of the meibomian gland secretions and are allowing better evaluation of medical therapies.

Abstract: That strange animal, LASIK dry eye

Post-LASIK tear dysfunction and dysesthesia.
Ocul Surf. 2010 Jul;8(3):135-45.
Nettune GR, Pflugfelder SC.
Ocular Surface Center, Cullen Eye Institute, Baylor College of Medicine, Houston, TX 77098, USA.

Symptoms of tear dysfunction after laser in situ keratomileusis (LASIK) occur in nearly all patients and resolve in the vast majority. Although dry eye complaints are a leading cause of patient discomfort and dissatisfaction after LASIK, the symptoms are not uniform, and the disease is not a single entity. Post-LASIK tear dysfunction syndrome or dry eye is a term used to describe a spectrum of disease encompassing transient or persistent post-operative neurotrophic disease, tear instability, true aqueous tear deficiency, and neuropathic pain states. Neural changes in the cornea and neuropathic causes of ocular surface discomfort may play a separate or synergistic role in the development of symptoms in some patients. Most cases of early post-operative dry eye symptoms resolve with appropriate management, which includes optimizing ocular surface health before and after surgery. Severe symptoms or symptoms persisting after 9 months rarely respond satisfactorily to traditional treatment modalities and require aggressive management. This review covers current theories of post-LASIK dry eye disease, pathophysiology, risk factors, and management options for this disease spectrum of post-LASIK tear dysfunction and neuropathic pain.

Abstract: Argon laser punctal stenosis in contact lens wear

These things make me grimace. Do we really have to be doing everything we possibly can to help people wear contacts as many years as possible when they're already symptomatic?

The use of argon laser punctal stenosis in patients with contact lens-induced dry eyes.
Eye Contact Lens. 2010 May;36(3):144-8.
Djalilian AR, Mali JO, Holland EJ.
Department of Ophthalmology, University of Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL 60612, USA.

OBJECTIVE: To determine the efficacy of argon laser punctal stenosis inpatients with contact lens-induced dry eyes.

METHODS: A retrospective review of 25 eyes of 13 patients who underwent argon laser punctal stenosis to improve their contact lens intolerance was performed. The mean age was 31 (range, 21-52) years and 11 patients (85%) were women. The mean Schirmer I test was 15.2 (range, 3-35).

RESULTS: All patients tolerated the procedure well. In 19 eyes, the treatment involved only the lower punctum, whereas in six eyes, it involved both the upper and lower puncta. Eight patients required more than one treatment session (range, 2-6). At follow-up after 6 months, 10 of the 13 (77%) patients reported a substantial improvement in their symptoms and contact lens wear time.

CONCLUSIONS: Argon laser punctual stenosis provides a useful and titratable treatment of contact lens intolerance due to dry eyes

Abstract: The battle between signs and symptoms

...and quality of life.

Association between clinical diagnostic tests and health-related quality of life surveys in patients with dry eye syndrome.
Jpn J Ophthalmol. 2010 Jul;54(4):259-65. Epub 2010 Aug 11.
Mizuno Y, Yamada M, Miyake Y; Dry Eye Survey Group of the National Hospital Organization of Japan.
Collaborators (36)
Division for Vision Research, National Institute of Sensory Organs, National Tokyo Medical Center, Meguro-ku, Tokyo, Japan.

PURPOSE: This study was performed to assess the impact of dry eye on patients' quality of life (QOL) and to analyze the association between subjective symptoms and ocular surface findings of dry eye.

METHODS: The study population consisted of 158 patients with dry eye aged 20 years or older who visited any of the 15 medical care facilities enrolled in the study. The backgrounds and ocular findings of the patients were investigated, and their QOL was evaluated with the Japanese version of the 25-item National Eye Institute Visual Functioning Questionnaire (VFQ-25) and of the Medical Outcomes Study (MOS) 8-item Short-Form Health Survey (SF-8) to examine the association between subjective symptoms and ocular surface findings.

RESULTS: Of the patients enrolled, 15 were men and 143 were women, and their average age was 62.5 +/- 12.6 years. Sixty patients (38.0%) had comorbid Sjögren syndrome (SS). The results of Schirmer testing, fluorescein staining, and rose bengal staining for SS patients were significantly worse than those for the non-SS patients, but the VFQ-25 and SF-8 scores were not significantly different between the SS and non-SS patients. In the ocular surface findings, a weak association between the fluorescein staining scores and general vision scores, a subscale of the VFQ-25, was found. However, the ocular surface findings and VFQ-25/SF-8 results in the simple correlation analysis as well as in the multiple linear regression analysis showed no significant associations.

CONCLUSIONS: Ocular surface findings and QOL scores of patients with dry eye appear to disagree. Therefore, it is necessary to address subjective symptoms and QOL scores in addition to examination findings when evaluating dry eye.

Abstract: Restasis in Chinese patients

A comparison of cyclosporine 0.05% ophthalmic emulsion versus vehicle in chinese patients with moderate to severe dry eye disease: an eight-week, multicenter, randomized, double-blind, parallel-group trial.
J Ocul Pharmacol Ther. 2010 Aug;26(4):361-6.
Chen M, Gong L, Sun X, Xie H, Zhang Y, Zou L, Qu J, Li Y, He J.
Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.

PURPOSE: The goals of this study were to compare the efficacy and safety profile of topical cyclosporine 0.05% versus vehicle in Chinese patients with moderate to severe dry eye disease.

METHODS: In this multicenter, randomized, double-blind, vehicle-controlled, parallel-group study, 233 dry eye patients were allocated to receive either cyclosporine 0.05% or vehicle twice daily for 8 weeks. Primary outcome was the difference between groups, in total score of 4 symptoms and 4 signs change from baseline at weeks 2, 4, and 8. Changes in symptoms (ocular dryness, foreign body sensation, photophobia and burning) and signs (conjunctival hyperemia, Schirmer test, tear Break-up time (BUT), and corneal punctate fluorescein staining) at weeks 2, 4, and 8 as well as frequency of administration of concomitant artificial tears, were considered as secondary outcomes. The safety profile was evaluated by examining adverse events, changes in visual acuity, and ocular tolerance.

RESULTS: Greater improvements of the total score were seen in cyclosporine 0.05% group than in the vehicle group at all follow-up times (P < 0.01). Improvements in ocular dryness at week 8 (P = 0.040) and foreign body sensation during weeks 4 and 8 (P < 0.020) were significantly greater with cyclosporine. In addition, compared with the vehicle, cyclosporine significantly improved 2 objective dry eye disease signs: corneal staining at weeks 4 (P = 0.025) and 8 (P = 0.050) and the Schirmer test at week 4 (P = 0.035). However, no between-group difference approached statistical significance in photophobia, burning, BUT value, conjunctival hyperemia and frequency of administration of concomitant artificial tears at any follow-up times (P > 0.05).The cumulative frequency of adverse events did not significantly differ between the groups (P = 0.519), which were 11.21% and 8.55%, respectively. There were no patients who experienced reduced visual acuity.

CONCLUSION: Cyclosporine 0.05% ophthalmic emulsion is an effective and safe treatment for Chinese patients with moderate to severe dry eye disease.

Abstract: Therapeutic ocular surface medium

Clinical Trials of Therapeutic Ocular Surface Medium for Moderate to Severe Dry Eye.
Cornea. 2010 Aug 5. [Epub ahead of print]
Watson SL, Daniels JT, Geerling G, Dart JK.
From the *Cornea and External Diseases, Moorfields Eye Hospital, London, United Kingdom; daggerOcular Repair and Regeneration Biology Unit, Department of Pathology, Institute of Ophthalmology, University College London, London, United Kingdom; double daggerDepartment of Ophthalmology, University of Würzburg, Würzburg, Germany; and section signDepartment of Pathology, Institute of Ophthalmology, University College London, London, United Kingdom.

PURPOSE: To investigate therapeutic ocular surface medium (TOSM), a potential physiological tear replacement therapy, for moderate to severe dry eye.

METHODS: Forty-six patients with symptoms of moderate to severe dry eye despite maximal standard therapy were enrolled in a prospective pilot study of TOSM over 1 month (n = 10) and a randomized, double-masked, controlled trial of TOSM versus saline (placebo) over 2 months (n = 36). The primary outcome measure was conjunctival rose bengal staining.

RESULTS: An improvement in conjunctival rose bengal staining by >/=3 points occurred in 7 of 10 patients receiving TOSM in the pilot study (P = 0.017) and in 8 of 18 patients (44%) in the randomized trial (P = 0.982). In the pilot study, subjective dry eye symptoms significantly improved (P = 0.005). TOSM significantly improved the blepharitis score (P = 0.002) and conjunctival impression cytology (P = 0.028) in the randomized controlled trial. There were no serious or irreversible side effects with TOSM.

CONCLUSIONS: TOSM is a physiological tear replacement for dry eye that, unlike autologous serum, can be easily manufactured, could be widely available, and may also be beneficial for blepharitis.

Abstract: Demodex and bleph

Curr Opin Allergy Clin Immunol. 2010 Oct;10(5):505-10.
Pathogenic role of Demodex mites in blepharitis.
Liu J, Sheha H, Tseng SC.
Ocular Surface Center, and Ocular Surface Research & Education Foundation, Miami, Florida 33173, USA.

PURPOSE OF REVIEW: To summarize the key literature and our research experience regarding Demodex infestation as a potential cause of ocular inflammatory diseases with a special emphasis on Demodex blepharitis.

RECENT FINDINGS: Two distinct Demodex species have been confirmed as a cause of blepharitis: Demodex folliculorum can cause anterior blepharitis associated with disorders of eyelashes, and D. brevis can cause posterior blepharitis with meibomian gland dysfunction and keratoconjunctivitis. Tea tree oil treatments with either 50% lid scrubs or 5% lid massages are effective in eradicating mites and reducing ocular surface inflammation.

SUMMARY: Demodex blepharitis is a common but overlooked external eye disease. The pathogenesis of Demodex blepharitis in eliciting ocular surface inflammation has been further clarified. The modified eyelash sampling and counting method makes it easier and more accurate to diagnose Demodex infestation. Tea tree oil shows promising potential to treat Demodex blepharitis by reducing Demodex counts with additional antibacterial, antifungal, and anti-inflammatory actions.

Abstract: Azasite in DuraSite for Bleph

Azithromycin in DuraSite for the treatment of blepharitis.
Clin Ophthalmol. 2010 Jul 30;4:681-8.
Luchs J.
Department of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, NY, USA.

Blepharitis is a common inflammatory disease of the eyelid. Posterior blepharitis affects the posterior lamella of the eyelid and involves inflammation of the meibomian glands, whereas anterior blepharitis affects the anterior lamella of the eyelid and the eyelashes; either version can be inflammatory or infectious in nature. Each of these conditions can incite or propagate the other; anterior blepharitis, if not treated, can lead to meibomian gland disease, and vice versa. Blepharitis is typically chronic, and can be associated with a variety of systemic diseases such as dermatitis, as well as ocular diseases such as dry eye, conjunctivitis, or keratitis. The standard treatment regimen historically consists of lid hygiene with warm compresses and eyelid scrubs, although these treatment modalities may have limited efficacy for many patients, especially those with more severe disease. Adjunctive treatment includes systemic and topical antibiotics, topical corticosteroids, and tear replacement therapy. Topical antibiotics are recommended to decrease the bacterial load, and topical corticosteroids may help in cases of severe inflammation. Azithromycin ophthalmic solution 1% in DuraSite((R)) (AzaSite((R)); Inspire Pharmaceuticals, Durham, North Carolina, USA) has been proposed as a novel treatment for posterior blepharitis, based on its well-known anti-infective profile, its anti-inflammatory properties, its excellent tissue penetration, and its regulatory approval for the treatment of bacterial conjunctivitis. This review focuses on an off-label indication for topical azithromycin 1% in DuraSite for the treatment of blepharitis.

Abstract: Restasis vs. 0.1% cyclosporine

0.1% pretty dramatically outperformed 0.5% (Restasis).

No word on adverse effects in the abstract.

Br J Ophthalmol. 2010 Aug 1. [Epub ahead of print]
A comparative clinical trial of the efficacy of two different aqueous solutions of cyclosporine for the treatment of moderate-to-severe dry eye syndrome.
Baiza-Durán L, Medrano-Palafox J, Hernández-Quintela E, Lozano-Alcazar J, Alaníz-de la O JF.

Laboratorios Sophia, S.A. de C.V. Guadalajara, Jalisco, México.
To evaluate the efficacy and safety of two different concentrations of cyclosporine A (CsA) in aqueous solution compared to vehicle in patients with dry eye syndrome.

Multicentre, randomised, double-masked, vehicle-controlled, clinical trial.

A total of 183 patients were enrolled and randomised to either CsA 1% (group A), CsA 0.05% (group B) or vehicle only (group C). The main objective was to evaluate the efficacy of CsA aqueous solution in the reduction of signs and symptoms in patients with moderate to severe dry eye disease.

An early (day 21) statistically significant improvement (p<0.05) was evident in four symptoms and three ocular signs in group A. An equivalent improvement in three symptoms and three ocular signs was demonstrated in group B. A significant improvement was identified in two symptoms and two ocular signs in group C. Comparing the three groups together, group A performed better in four symptoms than group B did with just one symptom. Group C did not show significant improvement. At day 42, group A showed improvement in four symptoms, while group B showed improvement in one symptom and one ocular sign.

Cyclosporine A reduced complaints and improved major ocular signs in patients with moderate-to-severe dry eye disease. The group treated with the 0.1% cyclosporine A aqueous solution outperformed the other groups.

Abstract: BAK on healthy eyes

This is an interesting one.

Basically, you expose healthy eyes to BAC (BAK) for 12 weeks. They don't show any signs of dry eye (no information on whether they experienced symptoms). Density of their corneal Langerhans cells increases during treatment but goes back down after they're taken off.

Not sure what the implications are for either the dry eye crowd or the non dry eye crowd other than that people without dry eye who use a BAK-preserved Rx drop for short term probably don't have to worry about BAK. People with healthy eyes who have to take BAK for longer than 12 weeks (everyone with glaucoma that doesn't already have dry eye) on the other hand... and people with existing dry eye on the other hand...

Influence of benzalkonium chloride on langerhans cells in corneal epithelium and development of dry eye in healthy volunteers.
Curr Eye Res. 2010 Aug;35(8):762-9.
Zhivov A, Kraak R, Bergter H, Kundt G, Beck R, Guthoff RF.
Department of Ophthalmology, University of Rostock, Rostock, Germany.

PURPOSE: To investigate the influence of benzalkonium chloride (BAC) on corneal Langerhans cells (LCs) and on the development of dry eye.

METHODS: A randomized double-blind clinical trial was performed in 20 healthy volunteers. One eye of each subject was treated with a 0.01% BAC solution (and the fellow eye with a placebo solution) three times daily for 12 weeks. The distribution and density of LCs in the central and peripheral corneal epithelium were evaluated by in-vivo confocal laser-scanning microscopy (CLSM). The subjects were monitored for dry eye (subjective discomfort, slit-lamp biomicroscopy, tear film break-up time, Schirmer's test).

RESULTS: In the BAC group, compared with placebo, a marked increase in LC density was found in the central cornea at Week 6 and in the central and peripheral cornea at Week 12. LC density then decreased again in both zones after the end of treatment, falling toward (or even below) baseline levels. Significant changes in the LC count relative to baseline were found at Week 12 in the central and peripheral cornea in the BAC group as well as in the peripheral cornea in the placebo group. LC density in the BAC group increased more rapidly in the central than in the peripheral cornea. During therapy the BAC group showed no signs of dry eye.

CONCLUSION: 12-week application of a 0.01% BAC solution in healthy volunteers induces a significant increase in LCs in the central cornea at Week 12 without dry-eye changes. The return of LC counts toward (or even below) baseline levels just four weeks after the end of BAC administration demonstrates the rapid normalization of the inflammatory environment.

Abstract: Systane (or a lookalike)

Efficacy in patients with dry eye after treatment with a new lubricant eye drop formulation.
J Ocul Pharmacol Ther. 2010 Aug;26(4):347-53.
Davitt WF, Bloomenstein M, Christensen M, Martin AE.
Corona Research Consultants, El Paso, Texas, USA.

PURPOSE: The effective management of dry eye must include a clinically meaningful reduction in ocular staining. Evaluations of corneal and conjunctival staining and other ocular symptoms of dry eye were conducted for a new formulation of polyethylene glycol 400/propylene glycol-based lubricant eye drops containing hydroxypropyl guar as a gelling agent (Test Product) in comparison to Optive Lubricant Eye Drops (Control Product) in adult patients with dry eye.

METHODS: One hundred thirteen patients, 18 years of age and older, with dry eye were enrolled in a prospective, double-masked, multisite, parallel-group study. After a 2-week run-in period during which patients administered aqueous saline eye drops 4 times daily (QID) in each eye, patients were randomized (1:1) to receive either Test Product or Control Product to be administered QID for 6 weeks. Efficacy and safety were evaluated by corneal and conjunctival staining scores, tear film breakup time, assessments of ocular symptoms, ocular surface disease index (OSDI) scores, dry eye treatment satisfaction, visual function-14 questionnaires, and adverse events.

RESULTS: The intent-to-treat data set included 105 patients randomized to Test Product (n = 52) or Control Product (n = 53). Patients primarily were between the ages of 18-64 years (70.5%), female (73.3%), white (93.3%), and not Hispanic (81.9%). Patients in the Test Product group exhibited significantly lower mean corneal staining scores than the Control Product group at day 14 (P = 0.0009) and day 42 (P = 0.0106), and significantly lower mean conjunctival staining scores at day 28 (P = 0.0475) and day 42 (P = 0.0009). Patients in both treatment groups reported significant reductions in the mean scores for the ocular symptoms of dryness, gritty/sandy feeling, and burning (P < or = 0.0021 for all comparisons to baseline). Lastly, a significantly lower OSDI score than baseline was reported at day 42 by patients in both the Test Product (P = 0.0013) and Control Product (P < 0.0001) groups.

CONCLUSIONS: The results of this study indicate that the Test Product significantly reduced corneal and conjunctival staining, indicating a reduction in disease severity. Evaluations of ocular staining scores provide clinically meaningful evidence of dry eye severity and are an important indicator of dry eye disease progression.

Abstract: Immune response in conjunctival epi of DES patients

Immune response in the conjunctival epithelium of patients with dry eye.
Exp Eye Res. 2010 Jul 21. [Epub ahead of print]
Barabino S, Montaldo E, Solignani F, Valente C, Mingari MC, Rolando M.
Ocular Surface Research Center, Department of Neurosciences, Ophthalmology, and Genetics, University of Genoa, viale Benedetto XV 5, 16132 Genoa, Italy.

The aim of our project was to test the hypothesis that patients with dry eye have a significant degree of inflammation and lymphocyte infiltration in conjunctival epithelium by using flow cytometry analysis of cells stored in cell culture medium. Impression cytology specimens were collected in 15 normal subjects and 15 dry eye patients. Samples collected from the right eye were placed in Phosphate Buffered Saline containing 0.05% paraformaldehyde (PFA), and samples from the left eye in cell culture medium containing 10% foetal calf serum (FCS). Phenotypic analysis was performed on cells derived from 21 dry eye patients and 16 healthy controls. The cells collected in FCS were stained for the expression of CK19, CD3, CD4, CD8, CD56, CD19, CD20, CD14 and HLA-DR, and analyzed by flow cytometry. FCS samples contained a statistically increased number of cells when compared to PFA samples. No statistically significant differences were present in the number of CD45+CK19- cells, CD3+ and CD4+T cells, B and NK cells in dry eye patients compared to healthy controls. In the dry eye group there was a significant difference in the CD4/CD8 ratio respect to what observed in normal subjects, and an increased number of CD14+ cells. HLA-DR expression was increased only in CK19+ conjunctival epithelial cells of dry eye patients. This study indicates that immune cells isolated from the superficial layer of the conjunctiva may play a pivotal role in the pathogenesis of dry eye, and that a new method of preservation of impression cytology samples can enhance flow cytometry analysis of epithelial and immune cells of the conjunctiva.

Wednesday, September 1, 2010

Abstract: High rate of dry eye in Mongolia

No seriously. And anyone in, let's see, Colorado or New Mexico can probably relate.

Prevalence of dry eye disease in Mongolians at high altitude in China: the Henan eye study.
Ophthalmic Epidemiol. 2010 Aug;17(4):234-41.
Guo B, Lu P, Chen X, Zhang W, Chen R.
West China Hospital, Sichuan University, Chengdu, China.

PURPOSE: To estimate the prevalence of dry eye disease, analyze the associations between dry eye symptoms and signs, and identify the risk factors in an elderly Mongolian population at high altitude in China. Methods: A population-based survey was conducted in 2006. A total of 2,486 Mongolians age 40 and older were selected. Symptoms of dry eye were assessed using a 6-item validated questionnaire. Dry eye disease was defined if participants reported one or more symptoms often or all the time. Positive signs included a tear-film breakup time of < or =10 seconds, a Schirmer test score of or= 1 in one or both eyes. Presence of dry eye symptoms and positive signs were analyzed. Correlations between symptoms and signs, and risk factors were evaluated in a multivariate model.

RESULTS: Of the 1,816 participants, 50.1% (95% confidence interval, 47.8-52.4) were symptomatic. Tear-film breakup time of < / = 10 seconds was 37.7% (95% confidence interval, 35.5-39.9). A Schirmer test score of or = 1 was 6.0% (95% confidence interval, 4.9-7.1). The correlation between dry eye symptoms and positive signs (tear-film breakup time of < or = 10 seconds[r = 0.414, P < 0.001], Schirmer test score of < or = 5 mm [r = 0.164, P = 0.001], and fluorescein staining score > or =1 [r = 0.361, P < 0.001]) were statistically significant. Independent risk factors included increased age, age-related cataract and pterygium.

CONCLUSION: This study demonstrates a high prevalence rate of dry eye disease in a Mongolian population. Dry eye signs were significantly associated with dry eye symptoms.

Abstract: Try sour gummy worms?

Salivation induced better lacrimal gland function in dry eyes.
Nepal Med Coll J. 2009 Dec;11(4):258-60.
Pramanik T, Ghising R.
Dept of Physiology, Nepal Medical College, Jorpati, Kathmandu, Nepal.

The dry eye syndrome is a common eye symptom causing blurry vision. To meet the demand of the modem world students and professionals are compelled to expose themselves to the computer screen for long stretch of time, which is one of the causes of dry eye. It is not always feasible to instil eyes with artificial tears time to time to protect them from dryness. Rather to adopt any simple physiological process associated with optimum lacrimation is a better option to keep eyes moist during computer works. Volunteers (n = 22) having mild dry eyes participated in this study. Tear production was assessed by Schirmer test by keeping Schirmer strip on ocular surface for 5 minutes and recording the length of the moistened area. Then the subject was allowed to keep a piece of lopsy candy (a sour fruit pulp mixed with sugar that is sweet and sour in taste) in mouth for 5 minutes that caused salivation. During salivation, again tear production was assessed. [It was standardized in such a way that, the length of the moistened strip will be 25 - 30 mm for normal eyes, 15 - 10 mm for dry eye, 06 - 10 mm for mild dry eye, 02 - 05 mm for moderate dryness and 00 - 01 mm for severe dry eye.] Tear production was found to be increased significantly (supported by increased length of moistened area of Schirmer strip) during salivation especially in dry eye in all volunteers. The lacrimal gland is the major contributor to the aqueous layer of the tear film which consists of water, electrolytes and proteins; secretion of which are under tight neural control. Anticholinergic agents play an important role in ocular dryness because of hypo-secretion. The sensory root of facial nucleus contains efferent preganglionic parasympathetic fibers for submandibular and sublingual salivary gland and lacrimal gland. The sensory root conveys gustatory fibers from the presulcul area (anterior two-third) of the tongue via the chorda tympani and via the palatine and greater petrosal nerve, taste fibers from the soft palate; it also carries preganglionic (secretomotor) innervations of the submandibular and sublingual salivary gland, lacrimal gland and gland of nasal and palatine mucosa. The taste sensation from the anterior two-third of the tongue, carried by the seventh cranial nerve, a nerve, parasympathetic in nature that contains efferent preganglionic fibers to lacrimal gland. Being stimulated, seventh cranial nerve helps in secretion of tear from the lacrimal glands and gives a sense of relief to the persons facing the problem of mild dryness of eyes.

Abstract: Surprisingly poor rate of retention of silicone punctal plugs

Retention Rate of Silicone Punctal Plugs Placed by Residents in a General Clinic Setting.
Ophthal Plast Reconstr Surg. 2010 Jul 15. [Epub ahead of print]
Parikh NB, Francis JH, Latkany RA.
New York Eye and Ear Infirmary, New York, New York, U.S.A.

PURPOSE: To evaluate the retention rate of silicone punctal plugs placed in patients with dry eye in a general clinic setting by ophthalmology residents.

METHODS: A cohort study reviewing charts of 88 patients who underwent punctal plug placement in the resident clinic at The New York Eye and Ear Infirmary from January 2007 to November 2008. Information recorded included age and sex of the patients, date of insertion, initial versus replacement plug, type and size of plug, location of insertion, and retention versus spontaneous extrusion versus removal of plugs at follow-up visits. Follow-up data were recorded at 30 and 60 days.

RESULTS: Follow-up data for 106 plug placements were available at 30 days. A total of 71.7% were retained, 23.6% were lost, and 4.7% were removed. At 60 days, data were available for 96 plug placements. A total of 50.0% were retained, 47.9% were lost, 5.2% had been removed prior to 60 days, and 2.1% had been replaced prior to 60 days.

CONCLUSION: Spontaneous extrusion is a common complication in punctal plug insertion, and the retention rate in a general clinic setting with ophthalmology residents is low. This may suggest that attention should be placed on improved instruction in placement techniques and sizing, better patient education on avoidance of rubbing, and importance of follow-up. It may also support the need for better designed plugs or considering alternatives to the silicone plugs, or the placement of such plugs in a dedicated punctal plug clinic under supervision of an experienced attending physician.

Abstract: Tear film osmolarity best measure of disease severity in all categories

An objective approach to dry eye disease severity.
Invest Ophthalmol Vis Sci. 2010 Jul 14. [Epub ahead of print]
Sullivan BD, Whitmer D, Nichols KK, Tomlinson A, Foulks GN, Geerling G, Pepose JS, Kosheleff V, Porreco A, Lemp MA.
TearLab, Corp., San Diego, United States.

Purpose: A prospective, multi-site clinical study (10 sites in the E.U. and U.S.) evaluated the clinical utility of commonly used tests and tear osmolarity for assessing dry eye disease severity.

Methods: 314 consecutive subjects between the ages of 18-82 years were recruited from the general patient population, 299 of which qualified with complete datasets. TearLab osmolarity, Schirmers without anesthesia, tear film breakup time (TBUT), corneal staining, meibomian dysfunction assessment, and conjunctival staining were performed bilaterally. A symptom questionnaire (OSDI), was also recorded for each patient. Distributions of clinical signs and symptoms against a continuous, composite severity index were evaluated.

Results: Osmolarity was found to have the highest correlation coefficient to disease severity (r2=0.55), followed by conjunctival staining (r2=0.47), corneal staining (r2=0.43), OSDI (r2=0.41), meibomian grading (r2=0.37), TBUT (r2=0.30), and Schirmers (r2=0.17). Comparison of standard threshold-based classification with the composite severity index revealed significant overlap between the disease severities of prospectively defined "Normal" and "Dry Eye" groups. Fully 63% of the subjects were found to be poorly classified by combinations of clinical thresholds.

Conclusions: Tear film osmolarity was found to be the single best marker of disease severity across normal, mild/moderate and severe categories. Other tests were found to be informative in more severe forms of disease, thus clinical judgment remains an important element in clinical assessment of severity. The study also indicates that the initiation and progression of dry eye is multifactorial, and supports the rationale for redefining severity of dry eye based on a continuum of clinical signs.

Abstract: High cholesterol and MGD

Association of dyslipidemia in moderate to severe meibomian gland dysfunction.
Am J Ophthalmol. 2010 Sep;150(3):371-375.e1. Epub 2010 Jul 8.
Dao AH, Spindle JD, Harp BA, Jacob A, Chuang AZ, Yee RW.
University of Texas Medical School at Houston, Department of Ophthalmology and Visual Sciences, Houston, TX 77030, USA.

PURPOSE: To determine whether meibomian gland disease, a major contributor to dry eye syndrome, is associated with dyslipidemia.

DESIGN: Retrospective case-control study.

METHODS: setting: Clinical practice. patient or study population: Sixty-six patients from January 2008 to July 2009 with moderate to severe meibomian gland disease whose serum lipid levels were obtained. We excluded patients who were already taking lipid-altering substances and patients with rheumatologic disease. We analyzed several parameters in prevalence of dyslipidemia (total cholesterol > 200 mg/dL, low-density lipoprotein [LDL] > 130 mg/dL, high-density lipoprotein [HDL] < 40 mg/dL, and triglycerides >150 mg/dL) in MGD patients and compared these patients to the general population as reported by data from the National Health and Nutrition Examination Survey (NHANES). main outcome measure: The prevalence of dyslipidemia (elevated total cholesterol, elevated LDL, decreased HDL, or elevated triglycerides) in patients with moderate to severe MGD.

RESULTS: Patients with moderate to severe MGD had a higher incidence of dyslipidemia with respect to elevated total cholesterol (>200 mg/dL), 67.4% to 45.1% (P = .0012) when compared to population controls. There was a smaller number of MGD patients with low HDL (HDL < 40 mg/dL), 6.5%, when compared to controls, 15.7% (P = .045). The incidence of increased LDL was not statistically significant (P = .184). There was a statistically smaller number of MGD patients with high triglycerides (TG > 150 mg/dL), 15.2%, when compared to controls, 33.1% (P = .0049).

CONCLUSIONS: Patients with moderate to severe MGD have a higher incidence of dyslipidemia with respect to elevated total cholesterol than the general population. Surprisingly, the component of total cholesterol that contributed most to this increase in total cholesterol came from elevated serum HDL levels. To our knowledge, elevated HDL has not been associated with any pathologic state. Patients with MGD had a statistically significant lower incidence of hypoalphalipoproteinemia (low HDL) than the general population. Patients with MGD also had a lower incidence of hypertriglyceridemia than the general population.

Abstract: Maskin intraductal probe for MGD

There's a fair amount of discussion about this on DryEyeTalk (search on Maskin Probe)

Intraductal Meibomian Gland Probing Relieves Symptoms of Obstructive Meibomian Gland Dysfunction.
Cornea. 2010 Jul 9. [Epub ahead of print]
Maskin SL.
From the The Dry Eye and Cornea Treatment Center, Tampa, FL. 33609.

PURPOSE: To perform a retrospective evaluation of a new treatment for obstructive meibomian gland dysfunction (O-MGD) using invasive orifice penetration and intraductal probing.

SETTING: Office-based ophthalmology private practice.

METHODS: Medical charts of 25 consecutive patients with O-MGD (based on presence of lid margin or tarsal hyperemia, lid margin telangiectasia, thickening or irregularity, and meiboman gland orifice metaplasia) plus lid tenderness or symptoms of lid margin congestion were reviewed to evaluate the effect of probing on tenderness and congestion.

RESULTS: Twenty-four of 25 patients (96%) had immediate postprobing relief, whereas all 25 patients (100%) had relief of symptoms by 4 weeks after procedure. Twenty patients (80%) only required 1 reatment and had an average of 11.5-month follow-up. Five patients (20%) had retreatment at an average of 4.6 months. All patients had symptom relief at time of last follow-up. Of 56 symptomatic and treated lids, 42 (75%) were upper lids. Patients frequently reported improvement in newly recognized but previously subclinical symptoms.

CONCLUSIONS: Invasive orifice penetration and intraductal probing seems to provide lasting rapid symptom relief for patients with O-MGD. Probing findings in this study frequently included (1) mild resistance upon orifice penetration, (2) proximal duct gritty tactile and aural sensation suggestive of keratinized cellular debris, and (3) focal variable resistance deeper within the duct, which may be relieved with the probe, suggestive of fibrovascular tissue. Taken together, these findings may offer probing characteristics that may allow for a grading system for duct obstruction. The postprobing improvement of symptoms not previously appreciated supports the notion that meibomian gland disease exists subclinically.

Abstract: Evidence of corneal lymphangiogenesis in dry eye disease

Evidence of corneal lymphangiogenesis in dry eye disease: a potential link to adaptive immunity?
Arch Ophthalmol. 2010 Jul;128(7):819-24.
Goyal S, Chauhan SK, El Annan J, Nallasamy N, Zhang Q, Dana R.
Schepens Eye Research Institute, 20 Staniford St., Boston, MA 02114, USA.

OBJECTIVE: To determine the effect of desiccating stress on corneal angiogenic responses in dry eye disease (DED) using a murine model.

METHODS: Dry eye was induced in murine eyes using high-flow desiccated air. Corneas were double stained with CD31 (panendothelial marker) and LYVE-1 (lymphatic endothelial marker). Real-time polymerase chain reaction was performed to quantify expression of vascular endothelial growth factors (VEGF-A, VEGF-C, and VEGF-D) and their receptors (VEGFR-2 and VEGFR-3) in the cornea on days 6, 10, and 14. Enumeration of CD11b(+)/LYVE-1(+) monocytic cells was performed in corneas with DED on day 14. Flow cytometric evaluation of the draining lymph nodes in normal mice and mice with DED was performed to determine whether DED is associated with homing of mature (major histocompatibility complex class II(hi)) antigen-presenting cells to the lymphoid compartment.

RESULTS: Lymphatic vessels unaccompanied by blood vessels were seen growing toward the center of corneas with DED. Significant increases in lymphatic area (P < .001) and lymphatic caliber (P < .02) were seen on day 14 of disease. Lymphangiogenic-specific VEGF-D and VEGFR-3 levels increased earliest on day 6 followed by increased VEGF-C, VEGF-A, and VEGFR-2 levels. Increased recruitment of CD11b(+)/LYVE-1(+) monocytic cells to the cornea and homing of mature CD11b(+) antigen-presenting cells to the draining lymph nodes were also associated with DED.

CONCLUSION: Low-grade inflammation associated with DED is an inducer of lymphangiogenesis without accompanying hemangiogenesis.

Abstract: And as we all know by now...

[The clinical and functional characteristics of the course of the dry eye syndrome associated with soft contact lens wear]
Vestn Oftalmol. 2010 May-Jun;126(3):31-4.
[Article in Russian]
Chuprov AD, Kudriavtseva IuV, Zhukovskaia IN.

The study deals with the clinical course of the dry eye syndrome (DES) associated with soft contact lens (SCL) wear. One hundred and two subjects (204 eyes) aged 18 to 38 years were examined for DES. The course of the disease was compared among men and women at Stage 1, among hydrogel and silicone hydrogel SCL wearers at Stage 2, among the patients who had worn SCL for a year or longer and SCL nonusers. The subjects who wear SCL from various materials develop DES significantly more frequently than do SCL nonusers. This pathology develops in both women and men. DES develops with equal frequencies in both hydrogel and silicone hydrogen SCL wearers. The individuals wearing SCL for a year or longer are much more likely to develop DES

Abstract: Visante OCT for tear meniscus height measurement

Application of Visante Optical Coherence Tomography Tear Meniscus Height Measurement in the Diagnosis of Dry Eye Disease.
Ophthalmology. 2010 Jun 2. [Epub ahead of print]
Ibrahim OM, Dogru M, Takano Y, Satake Y, Wakamatsu TH, Fukagawa K, Tsubota K, Fujishima H.
Keio University School of Medicine, Johnson & Johnson Ocular Surface and Visual Optics Department, Tokyo, Japan; Keio University School of Medicine, Department of Ophthalmology, Tokyo, Japan.

PURPOSE: To investigate the applicability of tear meniscus height (TMH) measurement using Visante optical coherence tomography (OCT) in the diagnosis of dry eye disease.

DESIGN: Prospective, controlled, single-center study.

PARTICIPANTS: Twenty-four right eyes of 24 patients (6 males, 18 females; mean age, 63.14+/-13.4 years) with definite dry eye according to the Japanese dry eye diagnostic criteria and 27 right eyes of 27 control subjects (12 males, 15 females; mean age, 56.04+/-14.22 years) were recruited.

METHODS: All subjects underwent slit-lamp TMH measurement, OCT upper and lower TMH measurements, tear film breakup time (BUT) measurements, vital stainings, and Schirmer test. The results were compared between the 2 groups by Mann-Whitney test.

MAIN OUTCOME MEASURES: The correlation between the clinical findings of slit-lamp TMH, strip meniscometry examination, tear functions, vital staining scores, and the OCT upper and lower TMH parameters were tested by Spearman's correlation test. Receiver operating characteristic (ROC) curve technique was used to evaluate the sensitivity, specificity and cutoff values of OCT TMH examination in the diagnosis of dry eye.

RESULTS: The OCT upper and lower TMH values, slit-lamp TMH, strip meniscometry, tear film BUT, and vital staining scores were significantly lower in the dry eye patients compared with controls (P<0.001). A significant correlation between the OCT upper and lower TMH measurements as well as slit-lamp TMH, strip meniscometry, tear functions, vital staining scores, and the Schirmer test was found. The ROC curve technique analysis of the OCT lower TMH showed that, when the cutoff value was set at <0.30 mm, the sensitivity and specificity of the testing were 67% and 81%, respectively.

CONCLUSIONS: The Visante OCT is a quick, noninvasive method for assessing the TMH, with acceptable sensitivity, specificity, and repeatability, and may have potential applications for the diagnosis and evaluation of dry eye disease.

FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Abstract: TearLab osmolarity test to determine dry eye disease severity

I'd really like to know how this correlated with the OSDI scores.

Performance of tear osmolarity compared to previous diagnostic tests for dry eye diseases.
Curr Eye Res. 2010 Jul;35(7):553-64.
Versura P, Profazio V, Campos EC.
Ophthalmology Unit, University of Bologna, Bologna, Italy.

PURPOSE: Tear osmolarity is considered a key point in dry eye disease (DED) and its measurement is the gold standard in dry eye diagnosis. Tear osmolarity was evaluated in dry eye (DE) patients vs. a control group to assess its diagnostic performance compared to clinical and laboratory tests performed in either clinical or research settings.

METHODS: Tear osmolarity was measured with the TearLab Osmolarity System (OcuSense) in 25 normal subjects and 105 DE patients (severity score 1-4, Dry Eye Workshop (DEWS)). The following tests were also performed: Ocular Surface Disease Index (OSDI) symptoms questionnaire, Schirmer I test, Tear Film Break Up Time (TFBUT), ferning test, lissamine green staining, tear clearance, corneal esthesiometry, and conjunctival cytology by scraping and imprint. Statistical evaluation was performed by unpaired Student's t and Mann-Whitney tests, the Spearman's rho and the Pearson's r correlation coefficients (significance p < 0.05); all variables were also analyzed for sensitivity, specificity, Receiver Operating Characteristics (ROC) curves, likelihood ratio LR+, and positive predictive value (PPV).

RESULTS: Tear osmolarity normal values were 296.5 +/- 9.8 mOsm/L, increasing values were shown stepwise DE severity (mild to moderate to severe dry eye, respectively: 298.1 +/- 10.6 vs. 306.7 +/- 9.5 vs. 314.4 +/- 10.1, p < 0.05). A progressive worsening occurred in all the parameters with DED severity increase. Tear osmolarity exhibited the larger correlation strength vs. tear clearance, TFBUT and clinical score, strength increased with DED severity, mainly to inflammatory score and corneal sensitivity. Tear osmolarity 305 mOsm/L was selected as cut-off value for dry eye, 309 mOsm/L for moderate dry eye, 318 mOsm/L for severe dry eye (Area-Under-the-Curve was 0.737, 0.759, and 0.711, respectively).

CONCLUSIONS: Tear osmolarity can now be considered a test suitable to be performed in a clinical setting. It showed a good performance in dry eye diagnosis, higher than the other tests considered, mainly in severe dry eye. Tear osmolarity values should be interpreted as an indicator of DED evolutionary process to severity.

Abstract: DR-1 for measuring tear meniscus volume

[Evaluation of tear meniscus volume using the DR-1 tear specular scope]
Nippon Ganka Gakkai Zasshi. 2010 Jun;114(6):512-9.
[Article in Japanese]
Sakane Y, Yamaguchi M, Shiraishi A, Kataoka H, Ohashi Y.
Department of Ophthalmology, Graduate School of Medicine, Ehime University, 454 Shitsukawa, Toon-shi, Ehime-ken 791-0295, Japan.

PURPOSE: To investigate whether images obtained using DR-1, a tear specular microscope, can be applied to the evaluation of tear meniscus volume.

METHODS: Of 94 eyes of 47 subjects examined, 66 eyes of 33 subjects were diagnosed with definite, suspected or absence of dry eye using the 2006 diagnostic criteria. Tear meniscus height values found using DR-1 meniscus height (DRMH, mm), slit lamp meniscus height (SLMH, low/medium/high), and fluorescein meniscus height (FLMH, mm) were compared. The reproducibility, sensitivity and specificity of DRMH values with regard to dry eye diagnosis were investigated. Changes in DRMH after insertion of lacrimal plugs and during soft contact lens (SCL) wear were also examined.

RESULTS: DRMH was significantly correlated with SLMH (r = 0.737, Spearman rank correlation coefficient) and FLMH (r = 0.06, Bland-Altman analysis). DRMH values (mm) in the normal (0.29 +/- 0.05), suspected dry eye (0.19 +/- 0.07), and definitely dry eye groups (0.17 +/- 0.06) were significantly different (p < 0.001), and showed good reproducibility. At a cut-off value of 0.22 mm, the sensitivity of dry eye diagnosis was 84.1% and specificity was 90.9%. DRMH increased significantly after insertion of lacrimal plugs (p < 0.0001) and decreased significantly during SCL use (before vs. 60 minutes after SCL insertion, p < 0.05, before vs. 120 minutes after insertion, p < 0.001).

CONCLUSION: DR-1 and specialized analysis software make simple and non-invasive evaluation of tear meniscus volume possible.

Abstract: Neurotrophic NGF in rats

Nerve Growth Factor in the Developing and Adult Lacrimal Glands of Rat With and Without Inherited Retinitis Pigmentosa.
Cornea. 2010 Jun 30. [Epub ahead of print]
Muzi S, Colafrancesco V, Sornelli F, Mantelli F, Lambiase A, Aloe L.
From the *Institute of Neurobiology and Molecular Medicine, National Research Council (CNR), Rome, Italy; daggerIRCCS-Bietti Foundation, Rome, Italy; and double daggerDepartment of Ophthalmology, University of Rome "Campus Bio-Medico," Rome, Italy.

PURPOSE: In the present study, we investigated lacrimal function and presence of the neurotrophin nerve growth factor (NGF) and its receptors in the lacrimal gland (LG) of normal rats and rats with inherited retinitis pigmentosa (IRP).

MATERIALS AND METHODS: After anesthesia, modified Schirmer tests were performed on IRP rats and Sprague Dawley (SD) rats to measure tear function. LGs of developing and adult IRP and SD rats were removed and used for histological, immunohistochemical, and biochemical analyses.

RESULTS: The results showed that basal tear secretion is reduced in IRP rats as compared with SD rats. NGF and NGF receptors are expressed in the LG of both rat strains. In SD rats, these NGF markers are low during early life and more elevated in adult life. Conversely in rats with IRP, NGF and its receptors decreased in adult life.

CONCLUSIONS: The role of NGF in maintaining ocular surface integrity is well known. The observations of this study further support the hypothesis that neurotrophins play a role in modulating tear secretion and probably in preventing the deleterious effects of dry eye. This hypothesis is presented and discussed.

Abstract: Acupuncture vs. OTC drops

[Observation on therapeutic effect of dry eye syndrome treated with acupuncture on the acupoints around the eyes]
Zhongguo Zhen Jiu. 2010 Jun;30(6):478-80.
[Article in Chinese]
Gao WP, Liu M, Zhang YB.
Eye Department, First Affiliated Clinical Medical College of Nanjing University of TCM, Nanjing 210029, China.

OBJECTIVE: To observed the clinical efficacy on dry eye syndrome treated with acupuncture on the acupoints around the eyes.

METHODS: Fifty-six cases of dry eye syndrome were divided into two groups, acupuncture group and western medicine group, 28 cases in each one. In acupuncture group, acupuncture was applied to Jingming (BL 1), Cuanzhu (BL 2), Sizhukong (TE 23), Tongziliao (GB 1), etc. In western medicine group, the topical artificial tear eye drops were administered. The corneal fluorescein staining, breaking-up time (BUT), tear volume and the symptom score were observed before and after treatment in two groups.

RESULTS: In comparison before and after treatment in acupuncture group, the statistical significant difference presented in BUT, tear volume and the symptom score (all P < 0.01). In comparison before and after treatment in western medicine group, the statistical significant difference presented in corneal staining, BUT and the symptom score (P < 0.01). The improvements in BUT, tear volume and the symptom score in acupuncture group were superior to those in western medicine group (P < 0.01).

CONCLUSION: Acupuncture on the acupoints around the eyes achieves a quite good efficacy on dry eye syndrome.

Abstract: Validating TearLab osmolarity measurement

Comparison of human tear film osmolarity measured by electrical impedance and freezing point depression techniques.
Cornea. 2010 Sep;29(9):1036-41.
Tomlinson A, McCann LC, Pearce EI.
From the Department of Vision Sciences, Glasgow Caledonian University, United Kingdom.

PURPOSE: Tear hyperosmolarity is diagnostic of dry eye disease (DED), yet difficulty in measurement has limited its utility; development of new instruments could facilitate its clinical application. This study compares the new OcuSense TearLab osmometer (OcuSense, Inc, San Diego, CA), based on electrical impedance "lab-on-a-chip" nanoliter technology, with the freezing point depression Clifton Osmometer (Clifton Technical Physics, Hartford, NY).

METHODS: Thirty-six subjects were recruited: 15 DED (9 women, 6 men age: 41 +/- 16 years) and 21 controls (12 women, 9 men age: 35 +/- 12 years); criteria for DED were noninvasive tear breakup time <10 seconds, Schirmer I test <5 mm, and positive symptoms. Samples were collected from the inferior tear meniscus for testing with both osmometers.

RESULTS: Osmolarity values measured with OcuSense TearLab were 308 +/- 6 and 321 +/- 16 mOsm/L for controls and dry eye, respectively, and those measured with Clifton were 310 +/- 7 and 323 +/- 14 mOsm/L for controls and dry eye, respectively; these values were significantly different. Significant correlation was found between OcuSense and Clifton measurements (r = 0.904; P = 0.006). Bland-Altman analysis revealed agreement between techniques; the majority of points fell within the 95% confidence limits, and actual values differed by less than 1%. A cutoff value of >316 mOsm/L, derived from the distribution of osmolarity values, was used to diagnose DED with an effectiveness of 73% sensitivity, 90% specificity, and 85% positive predictive value for the OcuSense and 73% sensitivity, 71% specificity, and 65% positive predictive value for the Clifton in the study samples.

CONCLUSIONS: Tear film osmolarity measured with the OcuSense TearLab system correlates well with the Clifton Osmometer. The new instrument has the potential to provide clinicians with a readily available clinically applicable measure, which could become the gold standard in DED.

Drug news: EGP-437 enters Phase III

June 24, Boston Business Journal

EyeGate launches dry eye trial
Eyegate Pharma has launched a phase 3 clinical trial for its drug target to treat dry eye syndrome, called EGP-437 . The drug candidate is a type of steroid, delivered using the company’s proprietary, non-invasive delivery system, known as Eyegate II.

The Waltham, Mass.-based privately-held biotechnology company said that its previous phase 2 study of the potential therapy found significant improvements in the signs and symptoms of dry eye during and after exposure to adverse environmental conditions.

Stephen From, President and Chief Executive Officer of EyeGate Pharma, said in a statement, “Based on clinical data, we recognize the potential value that EGP-437 may offer patients. Thus, we are excited to initiate this important pivotal study, which moves the Company one step closer to submitting a New Drug Application (NDA).”

Abstract: Hormone therapy & dry eye in postmenopausal women

Effectiveness of hormone therapy for treating dry eye syndrome in postmenopausal women: a randomized trial.
J Med Assoc Thai. 2010 Jun;93(6):647-52.
Piwkumsribonruang N, Somboonporn W, Luanratanakorn P, Kaewrudee S, Tharnprisan P, Soontrapa S.
Department of Obstetrics and Gynecology, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.

BACKGROUND: The efficacy of hormone therapy (HT) on dry eye syndrome remains debatable.

OBJECTIVE: To study the efficacy of HT on dry eye syndrome.

MATERIAL AND METHOD: A randomized controlled, double blind, parallel group, community-based study in 42 post-menopausal patients was conducted. The patients had dry eye syndrome and were not taking any medications. They were assigned to one of two groups. Group A comprised 21 patients given transdermal 17 beta-estradiol (50 mg/day) and medroxy progesterone acetate (2.5 mg/day) continuously for three months and group B comprised 21 patients given both transdermal and oral placebo. Participants in the study were included for final analysis. The improvement of dry eye symptoms were measured by visual analog scale, tear secretion, intraocular pressure, corneal thickness, and tear breakup time determined before treatment and at 6 and 12 weeks of treatment.

RESULTS: At 12 weeks, the number of patients who reported improvement of dry eye symptoms was greater in the HT group than that in the placebo group. However, the difference was not statistically significant (RR 0.25, 95% CI 0.04-2.80 and 0.60, 95% CI 0.33-2.03 in right and left eye, respectively). For other parameters, there was no significant difference between the two groups.

CONCLUSION: According to the present study, there is no strong evidence to support the use of HT for treating dry eye syndrome. The limited number of participants included in the present study may have contributed to the insignificant effects.

Abstract: Contact lenses: better doesn't necessarily mean better?

Objective clinical performance of 'comfort-enhanced' daily disposable soft contact lenses.
Cont Lens Anterior Eye. 2010 Apr;33(2):88-92. Epub 2010 Feb 9.
Wolffsohn JS, Hunt OA, Chowdhury A.
Aston University, Aston Triangle, Birmingham, United Kingdom.

PURPOSE: To examine the objective clinical performance of 'comfort-enhanced' daily disposable contact lenses over a 16-h day.

METHODS: Four contact lenses (Hilafilcon B, Etafilcon A Plus, Nelfilcon A and Nelfilcon A Plus) were evaluated in an investigator masked, open label trial at the end of a week's bilateral wear. Pre-lens non-invasive tear break-up time (PL-NITBUT), tear prism height, bulbar hyperaemia and ocular surface temperature (OST) were measured with the lens in situ at 8, 12 and 16h of wear.

RESULTS: There was no difference between how many hours the lenses types were worn each day (F=0.90, p=0.44). The PL-NITBUT decreased with the duration of daily lens wear (F=32.0, p<0.001) and was more stable with Nelfilcon A Plus (F=6.00, p=0.002) than with the other lenses evaluated. Bulbar blood vessels increased in coverage (F=11.5, p<0.001) but not overall redness (F=0.0, p=0.99) with the duration of daily lens wear, but there was no difference between the lenses (p>0.05). The tear prism height decreased with the duration of daily wear (F=27.0, p<0.001) and differed between lenses (F=2.9, p=0.04). The OST decreased with the duration of lens wear (F=119.7, p<0.001) and was reduced by daily disposable lens wear (F=7.88, p<0.001), but did not differ between lenses (F=0.88, p=0.45).

CONCLUSIONS: Objective measures of tear film indicated a difference between the lenses evaluated for PL-NITBUT and tear prism height, but not for wearing time or bulbar conjunctival hyperaemia. Therefore clinical benefits of daily disposable 'comfort enhancing' contact lenses can be measured, but challenges remain in producing contact lenses that do not compromise anterior eye physiology over the whole day.

Abstract: More on PF prostoglandin analogues for glaucoma

A review of preserved and preservative-free prostaglandin analogues for the treatment of open-angle glaucoma and ocular hypertension.
Drugs Today (Barc). 2010 Jun;46(6):409-16.
Hommer A.
Augenabteilung Hera Hospital, Vienna, Austria.
Glaucoma affects an increasing number of people worldwide and is the second leading cause of blindness. The aim of antiglaucoma therapy is to maintain a patient's visual function and quality of life. Prostaglandin analogues are first-line topical antiglaucoma therapy. They are effective at lowering intraocular pressure (IOP) and are generally well tolerated, with fewer systemic adverse events compared with the other classes. However, the use of prostaglandin analogues can be associated with ocular adverse effects, such as stinging/burning sensation, dry eyes, iris and periocular hyperpigmentation, and eye lash growth, which can affect patient compliance. Preservatives used in antiglaucoma preparations can have dose-dependent toxic effects, which contribute to adverse effects. The development of preservative-free preparations may reduce such adverse effects and therefore improve patient compliance. Tafluprost is a prostaglandin analogue in a preservative-free formulation that was recently approved for the reduction of elevated IOP in open-angle glaucoma and ocular hypertension.

Newblurb: BOS-P at Doheny

Nice to see some notice of this taken in local press.

Ocular Prosthesis Offers New View for Patients

DOWNTOWN LOS ANGELES - A special prosthesis that fits over the entire eye is bringing hope to patients suffering from corneal irregularities and severe dry eye.

The Boston Ocular Surface Prosthesis (BOS-P) is now available at the Perry Rosenthal Clinic at the USC Doheny Eye Institute. The prosthesis, about the size of a quarter, bathes the eye in saline solution and is thin enough that the patient can easily blink. The prostheses are custom designed and fitted to each patient, who is then trained on proper insertion and removal of the devices. The extra work is worth the trouble, patients say.

“One of our patients with dry eyes was almost forced to quit her job,” said Samuel Yiu, medical director of the clinic and a cornea specialist. “Now she is enjoying her work and her life again. Most of our patients feel the prosthesis gives them a new lease on their lives.”

The prosthesis, developed by Perry Rosenthal, and approved by the Food and Drug Administration in 1994, previously required patients to travel to the Boston Foundation for Sight in Massachusetts to be fitted for the lens. The lens has been available since last October at satellite clinics established at the Doheny Eye Institute, Baylor University and the Brooke Army Medical Center in Texas. The Doheny Eye Institute clinic has fitted 25 patients with the prosthesis and is working with many others from throughout the United States. The clinic is led by Yiu, executive director John Irvine and Gloria Chiu, the chief optometrist.

The device is designed for patients with keratoconus, a degenerative disease that affects the cornea, as well as other painful and potentially blinding diseases and conditions such as post-corneal transplant astigmatism and severe dry eye. The prosthesis fits on top of the sclera, which has few nerve endings.

Preservative-free saline solution is poured into a well in the center of the prosthesis. When the prosthesis is placed correctly, the patient can see through the saline solution. The solution serves as a kind of protective bandage on the eye.

The scleral footing of the prosthesis, along with the ability to bathe the cornea in fluid, allows a tremendous amount of improvement in selected patients’ vision, comfort and quality of life, said Irvine. Recognition of its potential for patient comfort and rehabilitation is growing. More physicians are weighing in on the device, which allows for positive feedback for further development.

After being fitted for and trained to use the prosthesis, patients return to the clinic for regular lens maintenance. The cost of the prosthesis is in the $7,000 range for patients without insurance. Irvine and Yiu are working to find a way to offer financial assistance to qualified patients once funding becomes available.

For information on the BOS-P, or to make an appointment, call (323) 442-6337 or visit

Newsblurb: Gee, I wish the solution were this simple for all of us

Not that it would hurt to try, of course!

McCann’s vision has improved since he cut out caffeine

Brian McCann has a noticeable new look – no glasses, and a hop in his step.

Going on a recommendation from his eye doctor to cut out caffeine, and hydrate with plenty of water, McCann said his problems with dry eye and blurry vision has improved.

“I’m real excited about it, real excited,” McCann said. “It’s the first time in a year and a half, two years that I’ve come to the baseball field and not had to worry about my eyes.”

McCann has undergone Lasik surgery twice, once in October of 2007 and then a tune-up procedure on one eye last October. He continued to have problems with dry eyes and blurry vision, though, and started wearing glasses last year during games.

McCann started this season without glasses or contacts but after struggling to see at the plate in night games, McCann resorted back to wearing glasses in May. He’s worn them on and off recently but since going on a recommendation from his ophthalmologist Dr. Alan Kozarsky last week, when the Braves were in Arizona, the glasses have been off.

“I see fine, way better than I did at the start of the season,” McCann said. “It’s hard to explain. I’ve been through a lot these last two years. I finally found a solution that works.”

McCann said he quit drinking Red Bull and 5-hour Energy drinks before games and now sticks to strictly water, and a lot of it, before games. He said he noticed a difference within about three days.

“I had chronic dry eye,” McCann said. “I was having to put drops in; now I don’t have to do the drops. My eye wouldn’t even hold a contact, they were so dry. And now that I’m hydrated and my eyes are fine, I can rub my eyes and tears will start forming. I couldn’t do that before.”

Since the Braves got to Arizona on June 7, McCann has hit .313 (10-for-32) in 10 games to raise his season average to .263 entering the weekend series with the Royals.

Abstract: Computer use causing lacrimal gland hypofunction?

Lacrimal hypofunction as a new mechanism of dry eye in visual display terminal users.
PLoS One. 2010 Jun 15;5(6):e11119.
Nakamura S, Kinoshita S, Yokoi N, Ogawa Y, Shibuya M, Nakashima H, Hisamura R, Imada T, Imagawa T, Uehara M, Shibuya I, Dogru M, Ward S, Tsubota K.
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
BACKGROUND: Dry eye has shown a marked increase due to visual display terminal (VDT) use. It remains unclear whether reduced blinking while focusing can have a direct deleterious impact on the lacrimal gland function. To address this issue that potentially affects the life quality, we conducted a large-scale epidemiological study of VDT users and an animal study.

METHODOLOGY/PRINCIPAL FINDINGS: Cross sectional survey carried out in Japan. A total of 1025 office workers who use VDT were enrolled. The association between VDT work duration and changes in tear film status, precorneal tear stability, lipid layer status and tear secretion were analyzed. For the animal model study, the rat VDT user model, placing rats onto a balance swing in combination with exposure to an evaporative environment was used to analyze lacrimal gland function. There was no positive relationship between VDT working duration and change in tear film stability and lipid layer status. The odds ratio for decrease in Schirmer score, index of tear secretion, were significantly increased with VDT working year (P = 0.012) and time (P = 0.005). The rat VDT user model, showed chronic reduction of tear secretion and was accompanied by an impairment of the lacrimal gland function and morphology. This dysfunction was recovered when rats were moved to resting conditions without the swing.

CONCLUSIONS/SIGNIFICANCE: These data suggest that lacrimal gland hypofunction is associated with VDT use and may be a critical mechanism for VDT-associated dry eye. We believe this to be the first mechanistic link to the pathogenesis of dry eye in office workers.

Tuesday, August 31, 2010

Abstract: [cringe]

It's gotten so I'm almost afraid to publish these abstracts lest patients swarm onto the internet looking for oral sea buckthorn oil. Don't believe me? Just look what happened in the wake of the (gentle sigh) honey thread.

Oral sea buckthorn oil attenuates tear film osmolarity and symptoms in individuals with dry eye.
J Nutr. 2010 Aug;140(8):1462-8. Epub 2010 Jun 16.
Larmo PS, Järvinen RL, Setälä NL, Yang B, Viitanen MH, Engblom JR, Tahvonen RL, Kallio HP.
Department of Biochemistry and Food Chemistry, University of Turku, Turku, Finland.
Dry eye is a common condition that can severely impair the quality of life. We aimed to find out whether oral sea buckthorn (SB) oil, containing (n-3) and (n-6) fatty acids and antioxidants, affects dry eye. In this double-blind, randomized, parallel trial, 20- to 75-y-old women and men experiencing dry eye symptoms consumed 2 g of SB or placebo oil daily for 3 mo from fall to winter. One hundred participants were recruited and 86 completed the study. Clinical dry eye tests and symptom follow-ups were performed. Tear film hyperosmolarity is a focal factor in dry eye. There was a general increase in the osmolarity from baseline to the end of the intervention. Compared with the placebo group, the increase was significantly less in the SB group when all participants were included [intention to treat (ITT), P = 0.04] and when only participants consuming the study products for at least 80% of the intervention days were included [per protocol (PP), P = 0.02]. The maximum intensities of redness and burning tended to be lower in the SB group. In the ITT participants, the group difference was significant for redness (P = 0.04) but not for burning (P = 0.05). In the PP participants, the group difference was significant for burning (P = 0.04) but not for redness (P = 0.11). In conclusion, SB oil attenuated the increase in tear film osmolarity during the cold season and positively affected the dry eye symptoms.

Abstract: Vision after warming eye area

Their, their, it's okay. Not everyone has to be a champion speller after all :-)

Very interesting study. Practical application? Sure, all you have to do is steam your eyes every 10 minutes during work hours.

[Comparison of effects of periocular region dry and wet warming on visual acuity and near reflex]
Nippon Ganka Gakkai Zasshi. 2010 May;114(5):444-53.
[Article in Japanese]
Takahashi Y, Igaki M, Sakamoto I, Suzuki A, Takahashi G, Dogru M, Tsubota K.
Doshisha University Anti-Aging Medical Research Center, Japan.
PURPOSE: To investigate the influence of warming the periocular region for 10 minutes after visual display terminal (VDT) work on the near reflex, and the differences in influence between lid closure, dry and wet warming, and the amounts of water vapor.

SUBJECTS AND METHODS: Subjects in the first trial were 10 healthy volunteers (10 eyes). Following VDT, subjects wore either a warming eye steamer (water vapor: 200 mg/10 min) or an eye mask with their eyelids closed for 10 minutes. Subjects in the second trial were 5 healthy volunteers (5 eyes). Following VDT, subjects applied either a dry-warming sheet (water vapor: 0 mg/10 min) or a wet-warming sheet (water vapor: 20, 35, 160 and 200 mg/10 min) to there eyelids and the periocular region for 10 minutes. In both experiments, subjective amplitude of accommodation, pupillary reaction, convergence reaction, near vision, and breakup time were measured before and immediately after VDT work and after 2 experimental settings.

RESULTS: The warming eye steamer significantly improved amplitude of accommodation (p<0.05), and near vision (p<0.05). Warming the periocular region with water vapor improved subjective amplitude of accommodation, and near vision, the effect of which depended on the amount of water vapor (p<0.05).

CONCLUSIONS: Warming the periocular region with water vapor improved subjective amplitude of accommodation, near vision and the effect depended on the amount of water vapor.

Abstract: Preserved vs. unpreserved glaucoma med

Switching from a preserved to a preservative-free prostaglandin preparation in topical glaucoma medication
Acta Ophthalmol. 2010 May;88(3):329-36.
Uusitalo H, Chen E, Pfeiffer N, Brignole-Baudouin F, Kaarniranta K, Leino M, Puska P, Palmgren E, Hamacher T, Hofmann G, Petzold G, Richter U, Riedel T, Winter M, Ropo A.
University of Tampere and Tampere University Hospital, Finland.

PURPOSE: The purpose of this study was to investigate the tolerability and intraocular pressure (IOP) reducing effect of the first preservative-free prostaglandin tafluprost (Taflotan) in patients exhibiting ocular surface side-effects during latanoprost (Xalatan) treatment.

METHODS: A total of 158 patients were enrolled in this open-label multicentre study. Eligible patients had to have at least two ocular symptoms, or one sign and one symptom, during treatment with latanoprost. At baseline, the patients were directly switched from latanoprost to preservative-free tafluprost for 12 weeks. The patients were queried for ocular symptoms, and ocular signs were assessed by using tear break-up time, Schirmer's test, fluorescein staining and evaluation of conjunctival hyperaemia and blepharitis. In addition, HLA-DR and MUC5AC in conjunctival impression cytology specimens were analyzed, and a drop discomfort/quality of life (QoL) questionnaire was employed. IOP was measured at all visits.

RESULTS: Preservative-free tafluprost maintained IOP at the same level after 12- weeks treatment (16.4 +/- 2.7 mmHg) as latanoprost at baseline (16.8 +/- 2.5 mmHg). During treatment with preservative-free tafluprost, the number of patients having irritation/burning/stinging (56.3%), itching (46.8%), foreign body sensation (49.4%), tearing (55.1%) and dry eye sensation (64.6%) decreased to 28.4%, 26.5%, 27.1%, 27.1% and 39.4% correspondingly. The number of the patients with abnormal fluorescein staining of cornea (81.6%) and conjunctiva (84.2%), blepharitis (60.1%), conjunctival hyperaemia (84.2%) and abnormal Schirmer's test (71.5%) was also reduced significantly to 40.6%, 43.2%, 40.6%, 60.0% and 59.4% correspondingly. The tear break-up time improved significantly from 4.5 +/- 2.5 seconds to 7.8 +/- 4.9 seconds. A reduction in the number of patients with abnormal conjunctival cells based on HLA-DR and MUC5AC was also detected.

CONCLUSIONS: Preservative-free tafluprost maintained IOP at the same level as latanoprost, but was better tolerated in patients having signs or symptoms while on preserved latanoprost. Preservative-free tafluprost treatment resulted in improved QoL, increased patient satisfaction and drop comfort.

Abstract: CCL-185 Cell Bioassay

Evaluation of the Transforming Growth Factor-beta Activity in Normal and Dry Eye Human Tears by CCL-185 Cell Bioassay.
Cornea. 2010 Sep;29(9):1048-54.
Zheng X, De Paiva CS, Rao K, Li DQ, Farley WJ, Stern M, Pflugfelder SC.

From the *Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX; daggerShanxi Eye Hospital, Taiyuan, Shanxi, China; and double daggerAllergan, Inc, Irvine, CA.
PURPOSE: To develop a new bioassay method using human lung epithelial cells (CCL-185) to assess activity of transforming growth factor beta (TGF-beta) in human tear fluid from normal subjects and patients with dry eye.

METHODS: Two epithelial cell lines, mink lung cells (CCL-64) and human lung cells (CCL-185), were compared to detect the active form of TGF-beta by BrdU incorporation (quantitation of cell DNA synthesis) and WST assay (metabolic activity of viable cells). The effect of TGF-beta on the growth of CCL-185 cells was observed microscopically. Human tears from normal control subjects and patients with dry eye (DE) with and without Sjögren syndrome were evaluated for TGF-beta concentration by Luminex microbead assay, and TGF-beta activity by the CCL-185 cell growth inhibition bioassay.

RESULTS: The metabolic activity of viable CCL-185 cells, measured by WST, was shown to be proportional to the TGF-beta1 concentration (R = 0.919) and confirmed by BrdU assay (R = 0.969). Compared with CCL-185, metabolic activity of viable cells and DNA synthesis, measured by WST and BrdU incorporation assays, were shown to be less proportional to the TGF-beta1 concentration in the CCL-64 line (R = 0.42 and 0.17, respectively). Coincubation with human anti-TGF-beta1 antibody (MAB-240) yielded a dose-dependent inhibition of TGF-beta1 (0.3 ng/mL) activity. CCL-185 cell growth observed microscopically was noted to decrease in response to increasing TGF-beta1 concentrations. Levels of immuodetectable TGF-beta1 and TGF-beta2 were similar in normal and DE tears. TGF-beta bioactivity in DE human tears measured by the CCL-185 cells assay was found to be higher (9777.5 +/- 10481.9 pg/mL) than those in normal controls (4129.3 +/- 1342.9 pg/mL) (P < 0.05). Among patients with DE, TGF-beta bioactivity was highest in those with Sjögren syndrome. Approximately, 79.1% of TGF-beta in DE tears and 37.6% TGF-beta in normal tears were found to be biologically active.

CONCLUSIONS: The CCL-185 cell assay was found to be a suitable tool for assessing TGF-beta activity in human tears. Tear TGF-beta bioactivity increases in DE, particularly in Sjögren syndrome, where elevated levels of TGF-beta1 transcripts in the conjunctival epithelium have been previously detected.

Abstract: Calorie restriction... in middle aged rats

I wonder how old a rat is when it's middle-aged?

I wonder how many doctors would not flinch at suggesting this therapeutic approach to their overweight dry eye patients?

I wonder whether those two numbers will be similar? ;-)

Calorie restriction: A new therapeutic intervention for age-related dry eye disease in rats.
Biochem Biophys Res Commun. 2010 Jul 9;397(4):724-8. Epub 2010 Jun 9.
Kawashima M, Kawakita T, Okada N, Ogawa Y, Murat D, Nakamura S, Nakashima H, Shimmura S, Shinmura K, Tsubota K.
Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan.
A decrease in lacrimal gland secretory function is closely related to aging and leads to an increased prevalence of dry eye syndrome. Since calorie restriction (CR) is considered to prevent functional decline of various organs due to aging, we hypothesized that CR could prevent age-related lacrimal dysfunction. Six-month-old male Fischer 344 rats were randomly divided into ad libitum (AL) and CR (-35%) groups. After 6months of CR, tear function was examined under conscious state. After euthanasia, lacrimal glands were subjected to histological examination, tear protein secretion stimulation test with Carbachol, and assessment of oxidative stress with 8-hydroxy-2 deoxyguanosine (8-OHdG) and 4-hydroxynonenal (HNE) antibodies. CR significantly improved tear volume and tended to increase tear protein secretion volume after stimulation with Carbachol compared to AL. The acinar unit density was significantly higher in the CR rats compared to AL rats. Lacrimal glands in the CR rats showed a lesser degree of interstitial fibrosis. CR reduced the concentration of 8-OHdG and the extent of staining with HNE in the lacrimal gland, compared to AL. Furthermore, our electron microscopic observations showed that mitochondrial structure of the lacrimal gland obtained from the middle-aged CR rats was preserved in comparison to the AL rats. Collectively, these results demonstrate for the first time that CR may attenuate oxidative stress related damage in the lacrimal gland with preservation of lacrimal gland functions. Although molecular mechanism(s) by which CR maintains lacrimal gland function remains to be resolved, CR might provide a novel therapeutic strategy for treating dry eye syndrome.

Abstract: Impact of tear break up on vision

Measurement of the time course of optical quality and visual deterioration during tear break-up.
Invest Ophthalmol Vis Sci. 2010 Jun;51(6):3318-26. Epub 2010 Jan 27.
Liu H, Thibos L, Begley CG, Bradley A.
School of Optometry, Indiana University, Bloomington, Indiana 47405, USA.

PURPOSE: To compare changes in optical quality and visual performance that accompany tear break-up (TBU) during blink suppression.

METHODS: A three-channel optical system was developed that simultaneously measured refractive aberrations (Shack-Hartmann aberrometer), 20/40 letter contrast sensitivity (CS), and TBU (retroillumination, RI). Ten wearers of silicone hydrogel contact lenses were asked to keep one eye open for approximately 18 seconds, while CS, wavefront aberrations, and RI images were collected. The wavefront was reconstructed by zonal methods, and image quality was quantified with a series of metrics including RMS fit error. Novel metrics for quantifying TBU over the contact lens surface were developed by quantifying the contrast of the RI image and by using Fourier descriptors of the first Purkinje (PJ) image shape.

RESULTS: There was a full range of TBU over the lens surface, with four subjects showing TBU across the corneal center and one subject with TBU in the inferior peripheral pupil. Among the four subjects with central corneal TBU, RMS fit error, RI contrast, and PJ Fourier descriptors showed high correlation with CS (r(2) range, 0.9187-0.9414, 0.6261-0.975, and 0.4917-0.8986, respectively). Some of the general optical-quality metrics such as blur strength, neural sharpness, and area of modulation transfer function (MTF) also showed that change correlated with CS loss.

CONCLUSIONS: Optical metrics of tear quality and retinal image quality are associated with the decline in vision that occurs with TBU. The evidence supports the hypothesis that blurry vision symptoms reported by contact lens wearers are caused by poor quality of the retinal image due to TBU.

Abstract: MGD thermodynamic treatment device

Restoration of meibomian gland functionality with novel thermodynamic treatment device-a case report.
Cornea. 2010 Aug;29(8):930-3.
Korb DR, Blackie CA.

Korb Associates, Boston, MA, USA.

A new and previously unpublished thermodynamic treatment device, which for the first time applies heat directly to both inner eyelid surfaces with a precision-controlled resistive heater while pulsating pressure is simultaneously applied to the outer eyelids using an inflatable air bladder, was used to restore meibomian gland functionality for a subject with severe evaporative dry eye. The subject, a 39-year-old white woman of light complexion with severe symptoms and corroborating objective signs of dry eye, had been unsuccessfully treated for 3 years by 7 practitioners. Using a new standardized meibomian gland expression device, a diagnosis of nonobvious meibomian gland dysfunction, where none of the approximately 24 meibomian glands of the right lower eyelid and 1 meibomian gland of the left lower eyelid were functional, was made. The patient underwent a single 12-minute treatment per eye with the treatment device. The treatment restored the functionality of 8 glands in each eye, doubled the fluorescein break-up time (FBUT) from 5 to 10 seconds, and decreased the symptom scores by approximately 80% for the entire follow-up period of 3 months.

Monday, August 30, 2010

Abstract: Plasma rich in growth factor for persistent epithelial defects

Plasma rich in growth factors as a therapeutic agent for persistent corneal epithelial defects.
Cornea. 2010 Aug;29(8):843-8.
López-Plandolit S, Morales MC, Freire V, Etxebarría J, Durán JA.
Instituto Clínico-Quirúrgico de Oftalmología, Bilbao, Vizcaya, Spain.

OBJECTIVE: To evaluate the efficacy of topically applied autologous plasma rich in growth factors (PRGF) as a treatment for persistent epithelial defects (PEDs) of the cornea.

METHODS: A series of prospective noncomparative cases.

PARTICIPANTS: Twenty eyes from 18 patients with PED with various underlying etiopathologies: neurogenic, iatrogenic, associated with burning or secondary to severe dry eye. Patients were treated with a PRGF eyedrop solution. Serial photographs of the cornea were taken until epithelialization was complete. We had previously characterized the levels of a panel of growth factors (platelet-derived growth factor, epithelial growth factor, vascular endothelial growth factor, hepatocyte growth factor, fibroblast growth factor, and nerve growth factor) in the PRGF of 11 of these patients. The following variables were additionally recorded: (1) duration of PED before treatment, (2) previous treatments, (3) time for complete epithelialization, and (4) treatments required concomitantly with PRGF.

RESULTS: Epithelial defects healed in 17 of 20 cases (85%), with a mean therapeutic time of 10.9 weeks (range 2-39 weeks). Mean progression time before treatment was 26.7 weeks (range 2-104 weeks). Growth factor concentrations were platelet-derived growth factor 12645.9 +/- 1690.0 pg/mL, epithelial growth factor 468.9 +/- 97.6 pg/mL, vascular endothelial growth factor 204.5 +/- 119.4 pg/mL, hepatocyte growth factor 149.5 +/- 173.5 pg/mL, fibroblast growth factor 82.6 +/- 95.9 pg/mL, and nerve growth factor 37.7 +/- 18.6 pg/mL.

CONCLUSION: PRGF, when applied as eyedrops, is a highly effective therapeutic agent for the treatment of a broad etiopathological spectrum of corneal PEDs.

Abstract: Azasite & bleph, multicenter study

This was published back in May but apparently I missed it when i was covering that period.

Multicenter open-label study evaluating the efficacy of azithromycin ophthalmic solution 1% on the signs and symptoms of subjects with blepharitis.
Cornea. 2010 Aug;29(8):871-7.
Haque RM, Torkildsen GL, Brubaker K, Zink RC, Kowalski RP, Mah FS, Pflugfelder SC.
Inspire Pharmaceuticals, Durham, NC, USA.

PURPOSE: To evaluate the effect of 4 weeks of treatment with azithromycin ophthalmic solution 1% on eyelid bacterial load, tear cytokines, and signs and symptoms of blepharitis.

METHODS: Twenty-six subjects (mean age 64.2 years; 65% female; 100% white) with moderate to severe blepharitis received azithromycin ophthalmic solution 1% in the absence of warm compresses or eyelid scrubs for 28 days (twice a day on days 1 and 2 and once a day on days 3-28). Blepharitis signs and symptoms were evaluated at baseline (day 1) and compared with end of treatment (day 29) and 2 follow-up visits (2 and 4 weeks posttreatment). Tear collection and eyelid margin bacterial cultures were performed at baseline and end of treatment. Tear cytokines were measured by a multiplex immunobead assay.

RESULTS: Four-week azithromycin treatment demonstrated significant decreases from baseline in investigator-rated signs of meibomian gland plugging, eyelid margin redness, palpebral conjunctival redness, and ocular discharge (P < or = 0.002) at day 29, which persisted 4 weeks posttreatment (P < or = 0.006). Subject-reported symptoms of eyelid itching, foreign body sensation/sandiness/grittiness, ocular dryness, ocular burning/pain, and swollen/heavy eyelids also demonstrated significant improvement from baseline (P < 0.001 for all symptoms and time points, except P = 0.037 for ocular dryness at visit 4). Eyelid margin culture exhibited significant decreases in coagulase-negative staphylococci and Corynebacterium xerosis bacteria. Changes in tear cytokine concentrations were not observed. Twelve subjects experienced 19 adverse events, 15 of which were ocular and none of which were serious.

CONCLUSIONS: Azithromycin provided significant improvement in signs and symptoms of blepharitis after 4 weeks of treatment compared with baseline and persisted in the 4-week follow-up period.